ALNYLAM PHARMACEUTICALS, INC. (Form: 10-Q, Received: 05/09/2014 16:36:21)

Large accelerated filer

Accelerated filer

Non-accelerated filer

¨ (do not check if a smaller reporting company)

Smaller reporting company

UNITED STATES

SECURITIES AND EXCHANGE COMMISSION

Washington, D.C. 20549

FORM 10-Q

x	QUARTERLY REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934

For the quarterly period ended March 31, 2014

¨	TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934

For the transition period from to

Commission File Number 001-36407

ALNYLAM PHARMACEUTICALS, INC.

(Exact Name of Registrant as Specified in Its Charter)


Delaware		77-0602661
(State or Other Jurisdiction of Incorporation or Organization)		(I.R.S. Employer Identification No.)

300 Third Street, Cambridge, MA		02142
(Address of Principal Executive Offices)		(Zip Code)

(617) 551-8200

(Registrant’s Telephone Number, Including Area Code)

Indicate by check mark whether the registrant (1) has filed all reports required to be filed by Section 13 or 15(d) of the Securities Exchange Act of 1934 during the preceding 12 months (or for such shorter period that the registrant was required to file such reports), and (2) has been subject to such filing requirements for the past 90 days. Yes x No ¨

Indicate by check mark whether the registrant has submitted electronically and posted on its corporate Web site, if any, every Interactive Data File required to be submitted and posted pursuant to Rule 405 of Regulation S-T (§232.405 of this chapter) during the preceding 12 months (or for such shorter period that the registrant was required to submit and post such files). Yes x No ¨

Indicate by check mark whether the registrant is a large accelerated filer, an accelerated filer, a non-accelerated filer, or a smaller reporting company. See the definitions of “large accelerated filer,” “accelerated filer” and “smaller reporting company” in Rule 12b-2 of the Exchange Act. (Check one):

Indicate by check mark whether the registrant is a shell company (as defined in Rule 12b-2 of the Exchange Act). Yes ¨ No x

At April 30, 2014, the registrant had 75,553,391 shares of Common Stock, $0.01 par value per share, outstanding.

INDEX


	PAGE NUMBER
PART I. FINANCIAL INFORMATION

ITEM 1. FINANCIAL STATEMENTS (Unaudited)
CONDENSED CONSOLIDATED BALANCE SHEETS AS OF MARCH 31, 2014 AND DECEMBER 31, 2013		2
CONDENSED CONSOLIDATED STATEMENTS OF COMPREHENSIVE LOSS FOR THE THREE MONTHS ENDED MARCH 31, 2014 AND 2013		3
CONDENSED CONSOLIDATED STATEMENTS OF CASH FLOWS FOR THE THREE MONTHS ENDED MARCH 31, 2014 AND 2013		4
NOTES TO CONDENSED CONSOLIDATED FINANCIAL STATEMENTS		5

ITEM 2. MANAGEMENT’S DISCUSSION AND ANALYSIS OF FINANCIAL CONDITION AND RESULTS OF OPERATIONS		13

ITEM 3. QUANTITATIVE AND QUALITATIVE DISCLOSURES ABOUT MARKET RISK		24

ITEM 4. CONTROLS AND PROCEDURES		24

PART II. OTHER INFORMATION

ITEM 1. LEGAL PROCEEDINGS		25

ITEM 1A. RISK FACTORS		26

ITEM 2. UNREGISTERED SALES OF EQUITY SECURITIES AND USE OF PROCEEDS		46

ITEM 6. EXHIBITS		46

SIGNATURES		48

ALNYLAM PHARMACEUTICALS, INC.

CONDENSED CONSOLIDATED BALANCE SHEETS

(In thousands, except share and per share amounts)

(Unaudited)


	March 31, 2014			December 31, 2013
ASSETS
Current assets:
Cash and cash equivalents	$	350,589		$	53,169
Marketable securities		314,901			192,701
Billed and unbilled collaboration receivables		164			4,248
Prepaid expenses and other current assets		8,409			3,910

Total current assets		674,063			254,028
Marketable securities		335,025			104,602
Investment in equity securities of Regulus Therapeutics Inc.		55,478			45,452
Property and equipment, net		15,731			16,448

Total assets	$	1,080,297		$	420,530

LIABILITIES AND STOCKHOLDERS’ EQUITY
Current liabilities:
Accounts payable	$	5,037		$	5,896
Accrued expenses		16,600			14,160
Liability for stock issuance		25,379			—
Accrued intraperiod tax allocation		6,825			—
Deferred rent		869			1,112
Deferred revenue		29,121			32,696

Total current liabilities		83,831			53,864
Deferred rent, net of current portion		2,819			2,925
Deferred revenue, net of current portion		37,674			93,394
Other liabilities		1,000			—

Total liabilities		125,324			150,183

Commitments and contingencies (Note 3)
Stockholders’ equity:
Preferred stock, $0.01 par value, 5,000,000 shares authorized and no shares issued and outstanding at March 31, 2014 and December 31, 2013		—			—
Common stock, $0.01 par value, 125,000,000 shares authorized; 75,484,782 shares issued and outstanding at March 31, 2014; 63,741,573 shares issued and outstanding at December 31, 2013		755			637
Additional paid-in capital		1,776,366			846,228
Accumulated other comprehensive income		25,030			19,717
Accumulated deficit		(847,178	)		(596,235	)

Total stockholders’ equity		954,973			270,347

Total liabilities and stockholders’ equity	$	1,080,297		$	420,530

The accompanying notes are an integral part of these condensed consolidated financial statements.

ALNYLAM PHARMACEUTICALS, INC.

CONDENSED CONSOLIDATED STATEMENTS OF COMPREHENSIVE LOSS

(In thousands, except per share amounts)

(Unaudited)


	Three Months Ended March 31,
	2014			2013
Net revenues from collaborators	$	8,275		$	18,642

Operating expenses:
Research and development ⁽¹⁾		43,758			22,179
In-process research and development		224,656			—
General and administrative ⁽¹⁾		8,925			6,267

Total operating expenses		277,339			28,446

Loss from operations		(269,064	)		(9,804	)

Other income (expense):
Interest income		333			224
Other (expense) income		(82	)		5

Total other income		251			229

Loss before income taxes		(268,813	)		(9,575	)

Benefit from income taxes		17,870			562

Net loss	$	(250,943	)	$	(9,013	)

Net loss per common share - basic and diluted	$	(3.70	)	$	(0.15	)

Weighted average common shares used to compute basic and diluted net loss per common share		67,786			59,173

Comprehensive loss:
Net loss	$	(250,943	)	$	(9,013	)
Unrealized gain on marketable securities, net of tax		5,313			5,159

Comprehensive loss	$	(245,630	)	$	(3,854	)


(1) Non-cash stock-based compensation expenses included in operating expenses are as follows:
Research and development	$	3,681		$	2,087
General and administrative		1,910			988

The accompanying notes are an integral part of these condensed consolidated financial statements.

ALNYLAM PHARMACEUTICALS, INC.

CONDENSED CONSOLIDATED STATEMENTS OF CASH FLOWS

(In thousands)

(Unaudited)


	Three Months Ended March 31,
	2014			2013
Cash flows from operating activities:
Net loss	$	(250,943	)	$	(9,013	)
Adjustments to reconcile net loss to net cash used in operating activities:
Depreciation and amortization		2,600			2,127
Non-cash stock-based compensation		5,591			3,075
Charge for 401(k) company stock match		157			120
Benefit from intraperiod tax allocation		(17,870	)		(562	)
In-process research and development		224,656			—
Changes in operating assets and liabilities:
Proceeds from landlord tenant improvements		—			192
Billed and unbilled collaboration receivables		4,084			(454	)
Prepaid expenses and other assets		(4,499	)		(944	)
Accounts payable		(1,379	)		(959	)
Accrued expenses and other		3,773			(1,790	)
Deferred revenue		(7,845	)		7,237

Net cash used in operating activities		(41,675	)		(971	)

Cash flows from investing activities:
Purchases of property and equipment		(388	)		(1,799	)
Purchases of marketable securities		(487,598	)		(187,077	)
Sales and maturities of marketable securities		133,206			58,036
Payment for asset acquisition		(25,000	)		—

Net cash used in investing activities		(379,780	)		(130,840	)

Cash flows from financing activities:
Proceeds from exercise of stock options and other types of equity		11,541			4,638
Proceeds from issuance of common stock, net of offering costs		—			173,572
Proceeds from issuance of common stock to Genzyme		723,037			—
Payments for repurchase of common stock for employee tax withholding		(15,703	)		—

Net cash provided by financing activities		718,875			178,210

Net increase in cash and cash equivalents		297,420			46,399
Cash and cash equivalents, beginning of period		53,169			51,405

Cash and cash equivalents, end of period	$	350,589		$	97,804

The accompanying notes are an integral part of these condensed consolidated financial statements.

ALNYLAM PHARMACEUTICALS, INC.

NOTES TO CONDENSED CONSOLIDATED FINANCIAL STATEMENTS

(Unaudited)

1. SUMMARY OF SIGNIFICANT ACCOUNTING POLICIES

Basis of Presentation and Principles of Consolidation

The accompanying condensed consolidated financial statements of Alnylam Pharmaceuticals, Inc. are unaudited and have been prepared in accordance with accounting principles generally accepted in the United States of America, or GAAP, applicable to interim periods and, in the opinion of management, include all normal and recurring adjustments that are necessary to state fairly the results of operations for the reported periods. Our condensed consolidated financial statements have also been prepared on a basis substantially consistent with, and should be read in conjunction with, our audited consolidated financial statements for the year ended December 31, 2013, which were included in our Annual Report on Form 10-K that was filed with the Securities and Exchange Commission, or SEC, on February 20, 2014. The year-end condensed consolidated balance sheet data was derived from our audited financial statements, but does not include all disclosures required by GAAP. The results of our operations for any interim period are not necessarily indicative of the results of our operations for any other interim period or for a full fiscal year.

The accompanying condensed consolidated financial statements reflect the operations of Alnylam and our wholly-owned subsidiaries. All significant intercompany accounts and transactions have been eliminated.

Use of Estimates

The preparation of financial statements in conformity with GAAP requires management to make estimates and assumptions that affect the reported amounts of assets and liabilities and the disclosure of contingent assets and liabilities at the date of the condensed consolidated financial statements and the reported amounts of revenues and expenses during the reporting period. Actual results could differ from those estimates.

Net Loss Per Common Share

We compute basic net loss per common share by dividing net loss by the weighted average number of common shares outstanding. We compute diluted net loss per common share by dividing net loss by the weighted average number of common shares and dilutive potential common share equivalents then outstanding. Potential common shares consist of shares issuable upon the exercise of stock options (using the treasury stock method) and unvested restricted stock awards. Because the inclusion of potential common shares would be anti-dilutive for all periods presented, diluted net loss per common share is the same as basic net loss per common share.

The following table sets forth for the period presented the potential common shares (prior to consideration of the treasury stock method) excluded from the calculation of net loss per common share because their inclusion would be anti-dilutive, in thousands:


	At March 31,
	2014		2013
Options to purchase common stock		8,185		8,568
Unvested restricted common stock		10		604
Other		378		—

		8,573		9,172

Public Offering

In January 2013, we sold an aggregate of 9,200,000 shares of our common stock through an underwritten public offering at a price to the public of $20.13 per share. As a result of this offering, we received aggregate net proceeds of $173.6 million, after deducting underwriting discounts and commissions and other offering expenses of $11.6 million.

Fair Value Measurements

The fair value is the price that would be received to sell an asset or paid to transfer a liability in an orderly transaction between market participants at the measurement date. The following tables present information about our assets that are measured at fair value on a recurring basis at March 31, 2014 and December 31, 2013, and indicate the fair value hierarchy of the valuation techniques we utilized to determine such fair value. In general, fair values determined by Level 1 inputs utilize quoted prices (unadjusted) in active markets for identical assets or liabilities. Fair values determined by Level 2 inputs utilize data points that are observable, such as quoted prices (adjusted), interest rates and yield curves. Fair values determined by Level 3 inputs utilize unobservable data points for the asset or liability, and include situations where there is little, if any, market activity for the asset or liability. The fair value hierarchy level is determined by the lowest level of significant input. Financial assets measured at fair value on a recurring basis are summarized as follows, in thousands:


Description	At March 31, 2014		Quoted Prices in Active Markets (Level 1)		Significant Observable Inputs (Level 2)		Significant Unobservable Inputs (Level 3)
Cash equivalents	$	344,211	$	342,208	$	2,003	$	—
Marketable securities (fixed income):
Corporate notes		512,081		—		512,081		—
U.S. Government obligations		65,930		—		65,930		—
Commercial paper		71,915		—		71,915		—
Marketable securities (Regulus equity holdings)		55,478		55,478		—		—

Total	$	1,049,615	$	397,686	$	651,929	$	—


Description	At December 31, 2013		Quoted Prices in Active Markets (Level 1)		Significant Observable Inputs (Level 2)		Significant Unobservable Inputs (Level 3)
Cash equivalents	$	32,571	$	32,571	$	—	$	—
Marketable securities (fixed income):
Corporate notes		228,462		—		228,462		—
U.S. Government obligations		56,863		—		56,863		—
Commercial paper		11,978		—		11,978		—
Marketable securities (Regulus equity holdings)		45,452		45,452		—		—

Total	$	375,326	$	78,023	$	297,303	$	—

During the three months ended March 31, 2014, there were no transfers between Level 1 and Level 2 financial assets. The carrying amounts reflected in our condensed consolidated balance sheets for cash, billed and unbilled collaboration receivables, other current assets, accounts payable, liability for stock issuance and accrued expenses approximate fair value due to their short-term maturities.

Investments in Marketable Securities

We invest our excess cash balances in short-term and long-term marketable debt and equity securities. We classify our investments in marketable debt securities as either held-to-maturity or available-for-sale based on facts and circumstances present at the time we purchased the securities. At each balance sheet date presented, we classified all of our investments in debt and equity securities as available-for-sale. We report available-for-sale investments at fair value at each balance sheet date and include any unrealized holding gains and losses (the adjustment to fair value) in accumulated other comprehensive income (loss), a component of stockholders’ equity. Realized gains and losses are determined using the specific identification method and are included in other income. We did not recognize any realized gains or losses from sales of our available-for-sale securities during the three months ended March 31, 2014, and as a result, did not reclassify any amount out of accumulated other comprehensive income for the same period. If any adjustment to fair value reflects a decline in the value of the investment, we consider all available evidence to evaluate the extent to which the decline is “other than temporary” and, if so, mark the investment to market through a charge to our condensed consolidated statements of comprehensive income (loss). We did not record any impairment charges related to our fixed income marketable securities during the current period. Our marketable securities are classified as cash equivalents if the original maturity, from the date of purchase, is 90 days or less, and as marketable securities if the original maturity, from the date of purchase, is in excess of 90 days. Our cash equivalents are composed of money market funds and corporate notes.

In the fourth quarter of 2012, we began accounting for our investment in Regulus Therapeutics Inc., or Regulus, as an available-for-sale marketable security. Intraperiod tax allocation rules require us to allocate our provision for income taxes between continuing operations and other categories of earnings, such as other comprehensive income. In periods in which we have a year-to-date pre-tax loss from continuing operations and pre-tax income in other categories of earnings, such as other comprehensive income, we must allocate the tax provision to the other categories of earnings. We then record a related tax benefit in continuing operations. The following table summarizes the fair value, accumulated other comprehensive income and intraperiod tax allocation regarding our investment in Regulus available-for-sale marketable securities at March 31, 2014 and 2013 and the activity for the three months ended March 31, 2014 and 2013, in thousands:


Description	At December 31, 2013			Three Months Ended March 31, 2014			Balance at March 31, 2014
Carrying value	$	12,449		$	—		$	12,449
Accumulated other comprehensive income, before tax		33,003			10,026			43,029

Investment in equity securities of Regulus, as reported	$	45,452		$	10,026		$	55,478

Accumulated other comprehensive income, before tax	$	33,003		$	10,026		$	43,029
Intraperiod tax allocation recorded as a benefit from income taxes		(13,267	)		(2,699	)		(15,966	)
Intraperiod tax allocation recorded as an accrued liability		—			(1,380	)		(1,380	)

Accumulated other comprehensive income, net of tax	$	19,736		$	5,947		$	25,683


Description	At December 31, 2012			Three Months Ended March 31, 2013			Balance at March 31, 2013
Carrying value	$	12,449		$	—		$	12,449
Accumulated other comprehensive income, before tax		26,299			8,918			35,217

Investment in equity securities of Regulus, as reported	$	38,748		$	8,918		$	47,666

Accumulated other comprehensive income, before tax	$	26,299		$	8,918		$	35,217
Intraperiod tax allocation recorded as a benefit from income taxes		(10,572	)		(562	)		(11,134	)
Intraperiod tax allocation recorded as an accrued liability		—			(3,023	)		(3,023	)

Accumulated other comprehensive income, net of tax	$	15,727		$	5,333		$	21,060

We obtain fair value measurement data for our marketable securities from independent pricing services. We perform validation procedures to ensure the reasonableness of this data. This includes meeting with the independent pricing services to understand the methods and data sources used. Additionally, we perform our own review of prices received from the independent pricing services by comparing these prices to other sources and confirming those securities are trading in active markets.

The following tables summarize our marketable securities, other than our holdings in Regulus noted above, at March 31, 2014 and December 31, 2013, in thousands:


	At March 31, 2014
Description	Amortized Cost		Gross Unrealized Gains		Gross Unrealized Losses			Fair Value
Commercial paper (Due within 1 year)	$	71,940	$	—	$	(25	)	$	71,915
Corporate notes (Due within 1 year)		223,039		49		(137	)		222,951
Corporate notes (Due after 1 year through 2 years)		289,659		32		(561	)		289,130
U.S. Government obligations (Due within 1 year)		20,024		11		—			20,035
U.S. Government obligations (Due after 1 year through 2 years)		45,916		7		(28	)		45,895

Total	$	650,578	$	99	$	(751	)	$	649,926


	At December 31, 2013
Description	Amortized Cost		Gross Unrealized Gains		Gross Unrealized Losses			Fair Value
Commercial paper (Due within 1 year)	$	11,983	$	—	$	(5	)	$	11,978
Corporate notes (Due within 1 year)		154,175		33		(46	)		154,162
Corporate notes (Due after 1 year through 2 years)		74,312		23		(35	)		74,300
U.S. Government obligations (Due within 1 year)		26,553		8		—			26,561
U.S. Government obligations (Due after 1 year through 2 years)		30,300		2		—			30,302

Total	$	297,323	$	66	$	(86	)	$	297,303

2. SIGNIFICANT AGREEMENTS

The following table summarizes our total consolidated net revenues from collaborators, for the periods indicated, in thousands:


	Three Months Ended March 31,
	2014		2013
Description
Takeda	$	5,493	$	5,493
Monsanto		1,410		1,410
The Medicines Company		1,266		834
Cubist		—		9,721
Other		106		1,184

Total net revenues from collaborators	$	8,275	$	18,642

Product Alliances

Genzyme Collaboration

In January 2014, we entered into a global, strategic collaboration with Genzyme Corporation, a Sanofi company, or Genzyme, to discover, develop and commercialize RNA interference, or RNAi, therapeutics as genetic medicines to treat orphan diseases. The 2014 Genzyme collaboration is governed by a master collaboration agreement, dated January 11, 2014, by and between us and Genzyme, which became effective in February 2014 upon the closing of the equity transaction, described below. The master agreement superseded and replaced the previous collaboration between us and Genzyme entered into in October 2012 to develop and commercialize RNAi therapeutics targeting transthyretin, or TTR, for the treatment of transthyretin-mediated amyloidosis, or ATTR, including patisiran (ALN-TTR02) and ALN-TTRsc.

2012 Genzyme Agreement

In consideration for the rights granted to Genzyme under the 2012 Genzyme agreement, Genzyme paid us an upfront cash payment of $22.5 million. We were also entitled to receive certain milestone payments under the 2012 Genzyme agreement. In the fourth quarter of 2013, we earned a milestone of $7.0 million based upon the completion of a successful patisiran Phase 2 clinical trial and a milestone of $4.0 million based upon the initiation of the Phase 3 clinical trial for patisiran.

Under the 2012 Genzyme agreement, the parties agreed to collaborate in the development of licensed products, with Genzyme assuming primary responsibility for the development and commercialization of licensed products in the Genzyme territory, which included Japan and the Asia-Pacific region, and us retaining primary responsibility for the development and commercialization of licensed products in the rest of the world. The collaboration between Genzyme and us was governed by a joint steering committee comprised of an equal number of representatives from each party. Genzyme was responsible, at its expense, for all development activities under the development plan reasonably necessary for the regulatory approval and commercialization of an RNAi therapeutic for the treatment of ATTR in the Genzyme territory.

We determined that the deliverables under the 2012 Genzyme agreement included the license, the joint steering committee and any additional TTR-specific RNAi therapeutic compounds that comprised the ALN-TTR program. We also determined that, pursuant to the accounting guidance governing revenue recognition on multiple element arrangements, the license and undelivered joint steering committee and any additional TTR-specific RNAi therapeutic compounds did not have standalone value due to the specialized nature of the services to be provided by us. In addition, while Genzyme had the ability to grant sublicenses, it could not sublicense all or substantially all of its rights under the 2012 Genzyme agreement. The uniqueness of our services and the limited sublicense right were indicators that standalone value was not present in the arrangement. Therefore the deliverables were not separable and, accordingly, the license and undelivered services were treated as a single unit of account. We were unable to reasonably estimate the period of performance under the 2012 Genzyme agreement, as we were unable to estimate the timeline of our deliverables related to the deliverable for any additional TTR-specific RNAi therapeutic compounds. Through December 31, 2013, we had deferred all revenue, or $33.5 million, under the 2012 Genzyme agreement.

2014 Genzyme Collaboration

In January 2014, we entered into the 2014 Genzyme collaboration. As noted above, the 2014 Genzyme collaboration is governed by a master agreement, which became effective upon the closing of the equity transaction in February 2014 and superseded and replaced the 2012 Genzyme agreement.

The 2014 Genzyme collaboration is structured as an exclusive relationship for the worldwide development and commercialization of RNAi therapeutics in the field of genetic medicines, which includes our current and future genetic medicine programs that reach human proof-of-principal study completion, or Human POP, by the end of 2019, subject to extension to the end of 2021 in various circumstances. We will retain product rights in North America and Western Europe, referred to as the Alnylam Territory, while Genzyme will obtain exclusive rights to develop and commercialize collaboration products in the rest of the world, referred to as the Genzyme Territory, together with certain broader co-development/co-promote or worldwide rights for certain products. Genzyme’s rights are structured as an opt-in that is triggered upon achievement of Human POP. We maintain development control for all programs prior to Genzyme’s opt-in and maintain development and commercialization control after Genzyme’s opt-in for all programs in the Alnylam Territory.

In addition to its regional rights for our current and future genetic medicine programs in the Genzyme Territory, Genzyme will have the right to either (i) co-develop and co-promote ALN-AT3 for the treatment of hemophilia and other rare bleeding disorders in the Alnylam Territory, with us maintaining development and commercialization control, or (ii) obtain a global license to ALN-AS1 for the treatment of hepatic porphyrias. Genzyme will exercise this selection right upon the completion of Human POP for both the ALN-AT3 and ALN-AS1 programs. Finally, Genzyme will have the right for a global license to a single, future genetic medicine program that is not one of our currently defined genetic medicine programs. We will retain global rights to any RNAi therapeutic genetic medicine program that does not reach Human POP by the end of 2019, subject to certain limited exceptions. Under the terms of the master agreement, we retain full rights to all current and future RNAi therapeutic programs outside of the field of genetic medicines, including the right to form new collaborations.

Under the 2014 Genzyme collaboration, Genzyme’s specific license rights include the following:

•

Regional license terms – Upon opt-in, Alnylam will retain product rights in the Alnylam Territory, while Genzyme will obtain exclusive rights to develop and commercialize the product in the Genzyme Territory. Genzyme can elect this license for any of Alnylam’s current and future genetic medicine programs that complete Human POP by the end of 2019, subject to limited extension. Development costs for products once Genzyme exercises an option will be shared between Genzyme and us, with Genzyme responsible for twenty percent of the global development costs. Upon the effective date of the 2014 Genzyme collaboration, Genzyme opted-in to a regional license and collaboration for patisiran, an RNAi therapeutic currently in a Phase 3 clinical trial for the treatment of ATTR patients with familial amyloidotic polyneuropathy, or FAP. In consideration for the rights granted to Genzyme under the regional license and collaboration terms for patisiran, Genzyme will be required to make payments totaling up to $50.0 million upon the achievement of certain development milestones. In addition, Genzyme will be required to make payments totaling up to $75.0 million per product other than patisiran, including up to $55.0 million in development milestones and $20.0 million in commercial milestones. Genzyme will also be required to pay tiered double-digit royalties up to twenty percent for each regional product based on annual net sales, if any, of such regional product by Genzyme, its affiliates and sublicensees.

•

Co-development/co-promote license terms - Upon opt-in, Alnylam will retain product rights in the Alnylam Territory, while Genzyme will obtain exclusive rights to develop and commercialize the product in the Genzyme Territory, and will co-promote the product in the Alnylam Territory. Upon the effective date of the 2014 Genzyme collaboration, Genzyme opted-in to a co-development/co-promote license and collaboration for ALN-TTRsc, an RNAi therapeutic currently in a Phase 2 clinical trial for the treatment of ATTR patients with TTR amyloid cardiomyopathy. Genzyme also has the right to elect a co-development/co-promote license and collaboration for ALN-AT3, if they do not elect a global license and collaboration for ALN-AS1. Development costs for co-development/co-promote products, once Genzyme exercises an option, will be shared between Genzyme and us, with Genzyme responsible for fifty percent of the global development costs. In consideration for the rights granted to Genzyme under the co-development/co-promote license terms, Genzyme will be required to make payments totaling up to $75.0 million in development milestones for each of ALN-TTRsc and ALN-AT3, if selected. We could potentially earn the next development milestone payment of $25.0 million under the 2014 Genzyme collaboration based upon the initiation of the first global Phase 3 clinical trial for ALN-TTRsc. Genzyme will also be required to pay tiered double-digit royalties up to twenty percent for

each co-development/co-promote product based on annual net sales, if any, in the Genzyme Territory for such co-development/co-promote product by Genzyme, its affiliates and sublicensees. The parties will share profits equally and we will book product sales in the Alnylam Territory.

•

Global license terms – Upon opt-in, Genzyme will obtain a worldwide license to develop and commercialize the product. Genzyme can elect a global license for ALN-AS1, if they do not elect a co-development/co-promote license for ALN-AT3. Genzyme will also have one right to a global license through 2019, subject to limited extension, for a future genetic medicine program that is not one of our currently defined genetic medicine programs. Genzyme shall be responsible for one hundred percent of global development costs. In consideration for the rights granted to Genzyme under the global license terms, Genzyme will be required to make payments totaling up to $200.0 million per product, including up to $60.0 million in development milestones and $140.0 million in commercial milestones. Genzyme will also be required to pay tiered double-digit royalties up to twenty percent for each global product based on annual net sales, if any, of each global product by Genzyme, its affiliates and sublicensees.

Under the master agreement, the parties will collaborate in the development of option products, with us leading development for all programs prior to Genzyme’s opt-in and also leading development and commercialization for all programs in the Alnylam Territory after Genzyme’s opt-in. If Genzyme does not exercise its option to license rights to a particular program, we will retain the exclusive right to develop and commercialize such program throughout the world, including the right to sublicense to third parties.

The 2014 Genzyme collaboration is governed by an alliance joint steering committee that is comprised of an equal number of representatives from each party. There will also be additional committees to manage various aspects of each regional, co-developed/co-promoted and global program. We and Genzyme intend to enter into supply agreements to provide for supply of collaboration products to Genzyme for clinical studies, and, at Genzyme’s request, commercial sales. Genzyme also has certain rights to manufacture collaboration products. Additionally, Genzyme has certain limited opt-out rights, as specified in the master agreement, upon which products revert fully back to us with no further obligations to Genzyme.

In consideration for the rights granted to Genzyme under the master agreement and pursuant to the terms of a stock purchase agreement dated January 11, 2014, upon the closing of the equity transaction in February 2014, we sold to Genzyme 8,766,338 shares of our common stock and Genzyme paid $700.0 million in aggregate cash consideration to us. We recorded this issuance using the price of our common stock on the date the shares were issued to Genzyme. Based on the common stock price of $85.72, the fair value of the shares issued was $751.5 million, which was $51.5 million in excess of the proceeds received from Genzyme for the issuance of our common stock. This $51.5 million will be amortized on a straight line basis over the performance period, which is currently five years as described below. In addition, due to intraperiod tax allocation rules, we recorded a benefit from income taxes of $15.2 million for the three months ended March 31, 2014 due to the Genzyme equity purchase being recorded in additional paid-in capital, net of tax.

As a condition to the closing of the equity transaction, Genzyme entered into an investor agreement with us. Under the investor agreement, until the earlier of the fifth anniversary of the expiration or earlier termination of the 2014 Genzyme collaboration and the date on which Genzyme and its affiliates cease to beneficially own at least 5% of our outstanding common stock, Genzyme and its affiliates are bound by certain “standstill” provisions. The standstill provisions include agreements not to acquire more than 30% of our outstanding common stock, call stockholder meetings, nominate directors other than those approved by our board of directors, subject to certain limited exceptions, or propose or support a proposal to acquire us.

Further, Genzyme has agreed to vote, and cause its affiliates to vote, all shares of our voting securities they are entitled to vote, up to a maximum of 20% of our outstanding common stock, in a manner either as recommended by our board of directors or proportionally with the votes cast by our other stockholders, except with respect to certain change of control transactions or our liquidation or dissolution. Until Genzyme owns less than 7.5% of our outstanding common stock, subject to Genzyme’s limited right to maintain its ownership percentage as described below, if we issue common stock or securities convertible into or exercisable for common stock to a third party that holds at least 30% of our outstanding common stock or, in connection with a collaboration or license transaction, to a third party that will initially hold at least the percentage of our outstanding common stock represented by the shares purchased by Genzyme at the closing of the equity transaction, we will offer Genzyme an opportunity to amend the standstill and voting provisions in the investor agreement to be consistent with the terms provided to such third party.

In accordance with the investor agreement, as a result of our issuance of shares in connection with our acquisition of Sirna Therapeutics, Inc., or Sirna, described below, in March 2014, Genzyme exercised its right to purchase an additional 344,448 shares of our common stock for $23.0 million, allowing Genzyme to maintain its ownership level of our common stock of approximately 12%.

We determined that the deliverables for the programs Genzyme has opted-in to include the licenses to our patisiran and ALN-TTRsc clinical programs, which licenses were delivered to Genzyme upon their immediate opt-in on the closing date of the transaction, and the associated development activities, joint steering committee participation and information exchange for these clinical programs. We also determined that, pursuant to the accounting guidance governing revenue recognition on multiple element arrangements, the license and associated undelivered development activities, joint steering committee participation and information exchange activities did not have standalone value due to the specialized nature of the services to be provided by us. In addition, while Genzyme has the ability to grant sublicenses, it cannot sublicense all or substantially all of its rights under the 2014 Genzyme collaboration. The uniqueness of our services and the limited sublicense rights are indicators that standalone value is not present in the arrangement. Therefore the deliverables are not separable and, accordingly, the license and undelivered services were treated as a single unit of account. When multiple deliverables are accounted for as a single unit of account, we base our revenue recognition model on the final deliverable. Under the 2014 Genzyme collaboration, the last deliverables for patisiran and ALN-TTRsc are expected to be completed within five years.

We determined that the total cash received from Genzyme under the now superseded 2012 Genzyme agreement reflects consideration for certain of the performance obligations for ALN-TTR programs included in the 2014 Genzyme collaboration. Therefore we are recognizing the $33.5 million of deferred revenue under the 2012 Genzyme agreement on a straight-line basis over the period of performance of the ALN-TTR programs, which is currently five years. As future consideration, including any milestones or reimbursement for research and development services, is achieved, we will recognize as revenue a portion of these payments equal to the percentage of the performance period completed when the milestone or service has been satisfied, multiplied by the amount of the payment. We will recognize the remaining portion of consideration received over the remaining performance period on a straight-line basis.

We determined that the opt-in rights that Genzyme has for future genetic medicine programs represent separate and additional deliverables that Genzyme may receive from us in future periods. Upon each opt-in by Genzyme, we have determined that each program and the related activities will represent a single unit of account and, consistent with our accounting policies, we will base our revenue recognition period on the final deliverable associated with each future opt-in, if any.

Asset acquisition

In-process research and development

In January 2014, we entered into a stock purchase agreement with Sirna, Merck Sharp & Dohme Corp., or Merck, and, for limited purposes, Merck & Co., Inc., pursuant to which we purchased from Merck all of Merck’s right, title and interest in and to all of the outstanding shares of common stock of Sirna. The Merck transaction closed on March 5, 2014. Sirna possesses intellectual property and RNAi assets including early-stage pre-clinical therapeutic candidates, chemistry, and siRNA-conjugate and other delivery technologies that we intend to integrate into our platform for delivery of RNAi therapeutics.

At the closing of the transaction, we paid Merck $25.0 million in cash and issued 2,142,037 shares of our common stock. We recorded this issuance using the price of our common stock on March 5, 2014, the date that these shares were issued to Merck. Based on the common stock price of $81.36, the fair value of the shares issued was $174.3 million. As a result of the cash payment and issuance of shares to Merck, we recorded a total of $199.3 million to in-process research and development expense. We will issue an additional 378,007 shares of common stock to Merck upon the completion of certain technology transfer activities, which are expected to be completed in the second quarter of 2014. We have recorded a liability of $25.4 million associated with this future obligation to issue shares, which was also charged to in-process research and development expense. We recorded a total of $224.7 million to in-process research and development expense for the three months ended March 31, 2014 as a result of this asset acquisition. Upon completion of these technology transfer activities, we will re-measure the expense recorded in connection with these shares using the then current price of our common stock.

We accounted for this transaction as an acquisition of in-process research and development assets and recorded the entire amount to in-process research and development expense as we did not acquire any employees, manufacturing or other facilities, developed processes or clinical-stage assets as part of our acquisition of Sirna.

Pursuant to the Sirna agreement, Merck is also eligible to receive the following consideration from us: (i) up to an aggregate of $10.0 million upon the achievement by us or our related parties of specified regulatory milestones for RNAi products covered by Sirna intellectual property, and (ii) up to an aggregate of $105.0 million upon the achievement by us or our related parties of specified development and regulatory ($40.0 million) and commercial ($65.0 million) milestones associated with the clinical development progress of certain pre-clinical candidates discovered by Sirna, together with low single-digit royalties for our products and single-digit royalties for Sirna products, in each case based on annual worldwide net sales, if any, by us and our related parties of any such products.

Under the Sirna agreement, Merck also agreed not to dispose of (i) any shares of our common stock beneficially owned for a period of six months following the closing date, subject to certain limited exceptions, and (ii) 50% of the shares of our common stock beneficially owned for a period of six additional months following the termination of the initial lock-up, referred to as the Subsequent Lock-Up. During and following the expiration of the Subsequent Lock-Up, Merck will be permitted to sell such shares of our common stock subject to certain limitations, including certain volume and manner of sale restrictions.

3. COMMITMENTS AND CONTINGENCIES

Operating Lease

We lease office and laboratory space located at 300 Third Street, Cambridge, Massachusetts for our corporate headquarters under a non-cancelable real property lease agreement by and between us and ARE-MA Region No. 28, LLC, or the Landlord, dated as of September 26, 2003, as amended by a First Amendment to Lease dated March 16, 2006, a Second Amendment to Lease dated June 26, 2009, a Third Amendment to Lease dated May 11, 2010 and a Fourth Amendment to Lease dated November 4, 2011, referred to collectively as the Lease. Pursuant to the Lease, we lease a total of approximately 129,000 square feet of office and laboratory space. The term of the Lease was set to expire in September 2016.

In March 2014, we and the Landlord entered into a Fifth Amendment to Lease, pursuant to which we exercised our option to extend the Lease for an additional five years, through September 30, 2021. Under the Fifth Amendment to Lease, we have the option to extend the Lease, as amended, for one additional five-year term. As a result of the Fifth Amendment to Lease, our operating lease obligations through 2021 increased by $37.8 million.

Litigation

University of Utah Litigation

On March 22, 2011, The University of Utah, or Utah, filed a civil complaint in the United States District Court for the District of Massachusetts against us, Max Planck Gesellschaft Zur Foerderung Der Wissenschaften e.V. and Max Planck Innovation GmbH, together, Max Planck, the Whitehead Institute for Biomedical Research, or Whitehead, the Massachusetts Institute of Technology, or MIT, and the University of Massachusetts, or UMass, claiming a professor at Utah is the sole inventor or, in the alternative, a joint inventor, of the Tuschl patents. Utah did not serve the original complaint on us or the other defendants. On July 6, 2011, Utah filed an amended complaint alleging substantially the same claims against us, Max Planck, Whitehead, MIT and UMass. The amended complaint was served on us on July 14, 2011. Utah is seeking changes to the inventorship of the Tuschl patents, unspecified damages and other relief. On October 31, 2011, we, Max Planck, Whitehead, MIT and UMass filed a motion to dismiss. Also on October 31, 2011, UMass filed a motion to dismiss on separate grounds, which we, Max Planck, Whitehead and MIT have joined. On December 31, 2011, Utah filed a second amended complaint dropping UMass as a defendant and adding as defendants several UMass officials. In June 2012, the Court denied both motions to dismiss. We, Max Planck, Whitehead, MIT and UMass filed an appeal of the Court’s ruling on the motion to dismiss for lack of jurisdiction and a motion requesting that the Court stay the case pending the outcome of the appeal. In July 2012, the Court stayed discovery in the case pending the outcome of the defendants’ appeal. Oral arguments in the appeal were heard in early March 2013 in the United States Court of Appeals for the Federal Circuit, or CAFC. In August 2013, the CAFC affirmed the lower Court’s ruling, in a split decision. We believe the majority made an error in law when affirming the lower Court’s decision, and in September 2013, we filed a petition with the CAFC for rehearing or rehearing en banc. In October 2013, the CAFC invited Utah to file an answer to the petition. In November 2013, the CAFC denied our petition for rehearing or rehearing en banc and remanded the case back to the lower Court. In February 2014, we filed a petition for writ of certiorari from the Supreme Court and a motion to stay the lower Court proceedings pending a decision from the Supreme Court on our petition. We are awaiting the Courts’ decisions.

Although we believe we have meritorious defenses and intend to vigorously defend ourselves in this matter, litigation is subject to inherent uncertainty and a court could ultimately rule against us. In addition, the defense of litigation and related matters are costly and may divert the attention of our management and other resources that would otherwise be engaged in other activities. We have not recorded an estimate of the possible loss associated with this legal proceeding due to the uncertainties related to both the likelihood and the amount of any possible loss or range of loss.

Our accounting policy for accrual of legal costs is to recognize such expenses as incurred.

ITEM 2. MANAGEMENT’S DISCUSSION AND ANALYSIS OF FINANCIAL CONDITION AND RESULTS OF OPERATIONS.

This Quarterly Report on Form 10-Q contains forward-looking statements that involve risks and uncertainties. The statements contained in this Quarterly Report on Form 10-Q that are not purely historical are forward-looking statements within the meaning of Section 27A of the Securities Act of 1933, as amended and Section 21E of the Securities Exchange Act of 1934, as amended. Without limiting the foregoing, the words “may,” “will,” “should,” “could,” “expects,” “plans,” “intends,” “anticipates,” “believes,” “estimates,” “predicts,” “potential,” “continue,” “target,” “goal” and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these words. All forward-looking statements included in this Quarterly Report on Form 10-Q are based on information available to us up to, and including, the date of this document, and we expressly disclaim any obligation to update any such forward-looking statements to reflect events or circumstances that arise after the date hereof. Our actual results could differ materially from those anticipated in these forward-looking statements as a result of certain important factors, including those set forth in this Item 2 — “Management’s Discussion and Analysis of Financial Condition and Results of Operations,” as well as under Part II, Item 1A — “Risk Factors” and elsewhere in this Quarterly Report on Form 10-Q. You should carefully review those factors and also carefully review the risks outlined in other documents that we file from time to time with the Securities and Exchange Commission, or SEC.

Overview

We are a biopharmaceutical company developing novel therapeutics based on RNA interference, or RNAi. RNAi is a naturally occurring biological pathway within cells for selectively silencing and regulating the expression of specific genes. Since many diseases are caused by the inappropriate activity of specific genes, the ability to silence genes selectively through RNAi could provide a new way to treat a wide range of human diseases. We believe that drugs that work through RNAi have the potential to become a broad new class of drugs, like small molecule, protein and antibody drugs. Using our intellectual property and the expertise we have built in RNAi, we are developing a set of biological and chemical methods and know-how that we apply in a systematic way to develop RNAi therapeutics for a variety of diseases.

Our core product strategy, which we refer to as “Alnylam 5x15,” was launched in January 2011 and is focused on the development and commercialization of novel RNAi therapeutics as genetic medicines. Our genetic medicine programs are RNAi therapeutics directed towards genetically defined targets for the treatment of diseases with high unmet medical need. Under our core product strategy, we expect to have six to seven genetic medicine product candidates in clinical development, including at least two programs in Phase 3 and five to six programs with human proof of concept, by the end of 2015. We are currently advancing the following programs in clinical or pre-clinical development: patisiran (ALN-TTR02), an intravenously delivered RNAi therapeutic targeting transthyretin, or TTR, in development for the treatment of TTR-mediated amyloidosis, or ATTR, in patients with familial amyloidotic polyneuropathy, or FAP; ALN-TTRsc, a subcutaneously delivered RNAi therapeutic targeting TTR in development for the treatment of ATTR in patients with TTR cardiac amyloidosis, including familial amyloidotic cardiomyopathy, or FAC, and senile systemic amyloidosis, or SSA; ALN-AT3, an RNAi therapeutic targeting antithrombin, or AT, in development for the treatment of hemophilia and rare bleeding disorders, or RBD; ALN-CC5, an RNAi therapeutic targeting complement component C5 in development for the treatment of complement-mediated diseases; ALN-AS1, an RNAi therapeutic targeting aminolevulinate synthase-1, or ALAS-1, in development for the treatment of hepatic porphyrias, including acute intermittent porphyria, or AIP; ALN-PCSsc, an RNAi therapeutic targeting proprotein convertase subtilisin/kexin type 9, or PCSK9, in development for the treatment of hypercholesterolemia; ALN-AAT, an RNAi therapeutic targeting alpha-1-antitrypsin, or AAT, in development for the treatment of AAT deficiency liver disease; ALN-TMP, an RNAi therapeutic targeting transmembrane protease, serine 6, or TMPRSS6, in development for the treatment of beta-thalassemia and iron-overload disorders; ALN-ANG, an RNAi therapeutic targeting angioprotein-like 3, or ANGPTL3, in development for the treatment of genetic forms of mixed hyperlipidemia and severe hypertriglyceridemia; ALN-AC3, an RNAi therapeutic targeting apolipoprotein C-III, or apoCIII, for the treatment of hypertriglyceridemia; and other yet to be disclosed programs. Our strategy is to retain development and commercial rights for our current and future genetic medicine pipeline in North America and Western Europe, while forming alliances with leading, innovative companies for the development and commercialization of these products in the rest of world. In early 2014, we formed an alliance with Genzyme Corporation, a Sanofi company, or Genzyme, to develop and commercialize our current “Alnylam 5x15” and future genetic medicine pipeline principally in territories outside of North America and Western Europe, subject to certain broader rights. The 2014 Genzyme collaboration is described in more detail below under the heading “Strategic Alliances.”

We believe that the strength of our intellectual property portfolio relating to the development and commercialization of small interfering RNAs, or siRNAs, as therapeutics provides us a leading position with respect to this therapeutic modality. Our intellectual property portfolio includes ownership of, or exclusive rights to, issued patents and pending patent applications claiming fundamental

features of siRNAs and RNAi therapeutics as well as those claiming crucial chemical modifications and promising delivery technologies. We believe that no other company possesses a portfolio of such broad and exclusive rights to the patents and patent applications required for the commercialization of RNAi therapeutics. Given the importance of our intellectual property portfolio to our business operations, we intend to vigorously enforce our rights and defend against challenges that have arisen or may arise in this area.

In addition, our expertise in RNAi therapeutics and broad intellectual property estate have allowed us to form alliances with leading pharmaceutical and life sciences companies, including Isis Pharmaceuticals, Inc., or Isis, Medtronic, Inc., or Medtronic, Novartis Pharma AG, or Novartis, Biogen Idec Inc., or Biogen Idec, F. Hoffmann-La Roche Ltd, or Roche (which assigned its rights and obligations to Arrowhead Research Corporation, or Arrowhead, during 2011), Takeda Pharmaceutical Company Limited, or Takeda, Kyowa Hakko Kirin Co., Ltd., or Kyowa Hakko Kirin, Cubist Pharmaceuticals, Inc., or Cubist, Ascletis BioScience Co., Ltd., or Ascletis, Monsanto Company, or Monsanto, Genzyme and The Medicines Company, or MDCO. We also have established collaborations with and, in some instances, received funding from major medical and disease associations. Finally, to further enable the field and monetize our intellectual property rights, we also grant licenses to biotechnology companies for the development and commercialization of RNAi therapeutics for specified targets in which we have no direct strategic interest under our InterfeRx™ program, and to research companies that commercialize RNAi reagents or services under our research product licenses.

We also seek to form or advance new ventures and opportunities in areas outside our primary focus on RNAi therapeutics. In 2007, we and Isis established Regulus Therapeutics Inc., or Regulus, a company focused on the discovery, development and commercialization of microRNA therapeutics. In October 2012, Regulus completed its initial public offering and currently, we own approximately 14% of Regulus’ outstanding common stock. Through an internal effort we refer to as Alnylam Biotherapeutics, we have evaluated the application of RNAi technology to improve the manufacturing processes for biologics. We have also evaluated the utility of our VaxiRNA™ platform, an RNAi technology developed under our Alnylam Biotherapeutics initiative, for the enhanced production of viruses used in the manufacture of vaccine products.

In January 2014, we entered into a stock purchase agreement with Sirna Therapeutics, Inc., or Sirna, Merck Sharp & Dohme Corp., or Merck, and, for limited purposes, Merck & Co., Inc., pursuant to which we purchased from Merck all of Merck’s right, title and interest in and to all of the outstanding shares of common stock of Sirna. The Merck transaction closed in March 2014. Sirna possesses intellectual property and RNAi assets including pre-clinical therapeutic candidates, chemistry, and siRNA-conjugate and other delivery technologies that we intend to integrate into our platform for delivery of RNAi therapeutics. We did not acquire any employees, manufacturing or other facilities, developed processes or clinical-stage assets as part of the acquisition of Sirna. In consideration for the Sirna common stock, we (i) paid Merck $25.0 million in cash and (ii) agreed to issue to Merck 2,520,044 shares of our common stock, having a value of $150.0 million as calculated under the terms of the stock purchase agreement on the date of execution. At the closing in March 2014, we issued to Merck 2,142,037 shares of our common stock. We will issue the remaining 378,007 shares to Merck upon the completion of certain technology transfer activities, which are expected to be completed in the second quarter of 2014. Merck beneficially owns approximately 3% of our outstanding common stock.

In addition, Merck is eligible to receive the following consideration from us: (i) up to an aggregate of $10.0 million upon the achievement by us or our related parties of specified regulatory milestones for RNAi products covered by Sirna intellectual property, and (ii) up to an aggregate of $105.0 million upon the achievement by us or our related parties of specified development and regulatory ($40.0 million) and commercial ($65.0 million) milestones associated with the clinical development progress of certain pre-clinical candidates discovered by Sirna, together with low single-digit royalties for our products and single-digit royalties for Sirna products, in each case based on annual worldwide net sales, if any, by us and our related parties of any such products.

We have incurred significant losses since we commenced operations in 2002 and expect such losses to continue for the foreseeable future. At March 31, 2014, we had an accumulated deficit of $847.2 million. Historically, we have generated losses principally from costs associated with research and development activities, acquiring, filing and expanding intellectual property rights and general administrative costs. As a result of planned expenditures for research and development activities relating to our drug development programs, including the development and optimization of drug delivery technologies and clinical trial costs, extension of the capabilities of our technology platform, including through business initiatives, continued management and growth of our patent portfolio, collaborations and general corporate activities, we expect to incur additional operating losses for the foreseeable future. We anticipate that our operating results will fluctuate for the foreseeable future. Therefore, period-to-period comparisons should not be relied upon as predictive of the results in future periods.

Although we currently have programs focused on a number of therapeutic areas, we are unable to predict when, if ever, we will successfully develop or be able to commence sales of any product. To date, a substantial portion of our total net revenues has

been derived from collaboration revenues from strategic alliances with Roche/Arrowhead, Takeda, Cubist and Novartis, and from the United States government in connection with our development of treatments for hemorrhagic fever viruses, including Ebola. We expect our sources of potential funding for the next several years to be derived primarily from new and existing strategic alliances, which may include license and other fees, funded research and development and milestone payments, and proceeds from the sale of equity or debt.

In January 2013, we sold an aggregate of 9,200,000 shares of our common stock through an underwritten public offering at a price to the public of $20.13 per share. As a result of the offering, we received aggregate net proceeds of $173.6 million, after deducting underwriting discounts and commissions and other offering expenses of $11.6 million.

Research and Development

Since our inception, we have focused on drug discovery and development programs. Research and development expenses represent a substantial percentage of our total operating expenses. Under our core product strategy, we expect to have six to seven genetic medicine product candidates in clinical development, including at least two programs in Phase 3 and five to six programs with human proof of concept, by the end of 2015. While focusing our efforts on our core product strategy, we also intend to continue to advance additional partner-based development programs through existing or future alliances. In addition, we continue to work internally and with third-party collaborators to develop and optimize new technologies to deliver our RNAi therapeutics both directly to specific sites of disease, and systemically by intravenous or subcutaneous administration.

Our most advanced core product development program, ALN-TTR, targets the TTR gene for the treatment of ATTR. ATTR is an inherited, progressively debilitating and fatal disease caused by a mutation in the TTR gene. We are advancing patisiran as our lead product candidate in our ALN-TTR program. In November 2013, we announced the initiation of our APOLLO Phase 3 clinical trial of patisiran. The APOLLO Phase 3 clinical trial is a randomized, double-blind, placebo-controlled, global study designed to evaluate the efficacy and safety of patisiran in ATTR patients with FAP. We are also conducting an open-label extension, or OLE, study of patisiran for patients treated in our Phase 2 clinical trial. The Phase 2 OLE study is designed to evaluate the long-term safety and tolerability of patisiran administration. Of the 29 patients eligible for enrollment, 25 had been enrolled as of the end of April 2014 and an additional two patients are expected to be enrolled by the end of May. In April 2014, we reported preliminary results from 23 patients that were evaluable for analysis based on a data cut-off as of April 3, 2014. These results showed that the TTR knockdown observed following the first dose in the OLE study closely matched TTR knockdown shown in the Phase 2 study, with essentially superimposable pharmacodynamic effects. Moreover, repeat dosing of patisiran led to a sustained TTR knockdown of approximately 80% through up to day 168, equivalent to up to eight doses of drug, as measured in pre-dose blood samples. Repeat dosing of patisiran was found to be well tolerated, with minimal adverse events. Importantly, the incidence of infusion-related reactions was found to be significantly reduced to 2% in patients from the Phase 2 and Phase 2 OLE studies receiving study drug with a proprietary micro-dosing regimen, as compared with an incidence of 15% in patients receiving a standard infusion (p=0.03). All other reported adverse events were mild to moderate, and there were no changes in liver function tests, renal function or hematological parameters.

In addition to ALN-TTR02, we are advancing ALN-TTRsc, a subcutaneously delivered RNAi therapeutic targeting TTR for the treatment of ATTR in patients with TTR cardiac amyloidosis. ALN-TTRsc is in a Phase 2 clinical trial in patients with FAC and SSA. We are also evaluating additional cohorts in an ongoing Phase 1 study of ALN-TTRsc to confirm a fixed-dose regimen for further development. We plan to initiate a Phase 3 trial for ALN-TTRsc in patients with TTR cardiac amyloidosis by the end of 2014.

Under the 2014 Genzyme collaboration, we will lead development and commercialization of patisiran in North America and Western Europe, referred to as the Alnylam Territory, while Genzyme will develop and commercialize the product in the rest of the world, referred to as the Genzyme Territory. In addition, under this new collaboration, we and Genzyme have agreed to co-develop and co-commercialize ALN-TTRsc in the Alnylam Territory, with Genzyme developing and commercializing the product in the Genzyme Territory. This broadened relationship on ALN-TTRsc is aimed at expanding and accelerating the product’s potential global value.

We are also developing ALN-AT3, an RNAi therapeutic targeting AT, a genetically defined target, for the treatment of hemophilia and RBD. ALN-AT3 is a novel therapeutic approach aimed at re-balancing the coagulation cascade and normalizing hemostasis in severe hemophilia A and B patients, including patients with inhibitors against their replacement factor. ALN-AT3 also

has potential as a treatment for RBD patients and patients with other bleeding disorders. In January 2014, we initiated a Phase 1 clinical trial with ALN-AT3. The Phase 1 clinical trial is being conducted in the U.K. as a single- and multi-dose, dose-escalation study consisting of two parts. Under the 2014 Genzyme collaboration, Genzyme will have the right to opt-in to the ALN-AT3 program after completion of human proof-of-principal study completion, or Human POP, to either co-develop and co-promote ALN-AT3 with us in the Alnylam Territory, with Genzyme developing and commercializing in the Genzyme Territory (subject to its development decision regarding ALN-AS1), or to develop and commercialize the product in the Genzyme Territory. In both circumstances, we will lead and control development and commercialization in the Alnylam Territory.

We are also advancing several additional programs through pre-clinical development and expect to file two investigational drug, or IND, applications, or IND equivalents, with respect to these programs in late 2014 and one IND or IND equivalent in early 2015. These programs include:

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ALN-CC5, an RNAi therapeutic targeting the C5 component of the complement pathway for the treatment of complement-mediated diseases. We expect to file an IND or IND equivalent for ALN-CC5 in late 2014. Under the 2014 Genzyme collaboration, Genzyme will have the right to opt-in to the ALN-CC5 program after completion of Human POP to develop and commercialize the product in the Genzyme Territory. We will lead and control development and commercialization in the Alnylam Territory.

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ALN-AS1, an RNAi therapeutic targeting ALAS-1 for the treatment of AIP. We expect to file an IND or IND equivalent for ALN-AS1 in late 2014 or early 2015. Under the 2014 Genzyme collaboration, Genzyme will have the right to opt-in to the ALN-AS1 program after completion of Human POP to either obtain a global license to ALN-AS1 for the treatment of hepatic porphyrias (subject to its development decision regarding ALN-AT3), or to develop and commercialize the product in the Genzyme Territory. In the latter case, we will lead and control development and commercialization in the Alnylam Territory.

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ALN-PCSsc, an RNAi therapeutic targeting PCSK9, in development for the treatment of hypercholesterolemia. We expect to file an IND or IND equivalent for ALN-PCS SC in late 2014 or early 2015. In February 2013, we and MDCO entered into a license and collaboration agreement pursuant to which we granted to MDCO an exclusive, worldwide license to develop, manufacture and commercialize RNAi therapeutics targeting PCSK9, including ALN-PCSsc.

In addition to the programs described above, we are also advancing other early-stage genetic medicine programs. These programs include: ALN-AAT, an RNAi therapeutic targeting AAT in development for the treatment of AAT deficiency liver disease; ALN-TMP, an RNAi therapeutic targeting TMPRSS6 in development for the treatment of beta-thalassemia and iron-overload disorders; ALN-ANG, an RNAi therapeutic targeting ANGPTL3 in development for the treatment of genetic forms of mixed hyperlipidemia and severe hypertriglyceridemia; ALN-AC3, an RNAi therapeutic targeting apoCIII for the treatment of hypertriglyceridemia; and other yet to be disclosed programs. In the case of ALN-AAT, we have recently selected our development candidate and expect to file an IND or IND equivalent for this program in mid-2015.

There is a risk that any drug discovery or development program may not produce revenue for a variety of reasons, including the possibility that we will not be able to adequately demonstrate the safety and efficacy of the product candidate. Moreover, there are uncertainties specific to any new field of drug discovery, including RNAi. The successful development of any product candidate we develop is highly uncertain. Due to the numerous risks associated with developing drugs, we cannot reasonably estimate or know the nature, timing and estimated costs of the efforts necessary to complete the development of, or the period, if any, in which material net cash inflows will commence from, any potential product candidate. These risks include the uncertainty of:

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our ability to discover new product candidates;

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our ability to progress product candidates into pre-clinical and clinical trials;

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the scope, rate of progress and cost of our pre-clinical trials and other research and development activities, including those related to developing safe and effective ways of delivering siRNAs into cells and tissues;

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the scope, rate of progress and cost of any clinical trials we commence;

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clinical trial results;

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the cost of filing, prosecuting, defending and enforcing any patent claims and other intellectual property rights;

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the terms, timing and success of any collaboration, licensing and other arrangements that we may establish;

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the cost, timing and success of regulatory filings and approvals or potential changes in regulations that govern our industry or the way in which they are interpreted or enforced;

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the cost and timing of establishing sufficient sales, marketing and distribution capabilities;

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the cost and timing of establishing sufficient clinical and commercial supplies for any product candidates and products that we may develop;

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limits on our ability to research, develop, or manufacture our product candidates as a result of contractual obligations to third parties or intellectual property held by third parties;

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the costs associated with legal activities, including litigation, arising in the course of our business activities and our ability to prevail in any such legal disputes; and

•

the effect of competing technological and market developments.

Any failure to complete any stage of the development of any potential products in a timely manner could have a material adverse effect on our operations, financial position and liquidity. A discussion of some of the risks and uncertainties associated with completing our development projects on schedule, or at all, and the potential consequences of failing to do so, are set forth in Part II, Item 1A below under the heading “Risk Factors.”

Strategic Alliances

A significant component of our business plan is to enter into strategic alliances and collaborations with leading pharmaceutical and life sciences companies, academic institutions, research foundations and others, as appropriate, to gain access to funding, capabilities, technical resources and intellectual property to further our development efforts and to generate revenues. We also seek to form or advance new ventures and opportunities in areas outside our primary focus on RNAi therapeutics.

Since delivery of RNAi therapeutics remains an important objective of our research activities, we also look to form collaboration and licensing arrangements with other companies and academic institutions to gain access to delivery technologies. For example, we have entered into agreements with Arrowhead, Tekmira Pharmaceuticals Corporation, or TPC, Protiva Biotherapeutics, Inc., or Protiva, a wholly-owned subsidiary of TPC, and together with TPC, referred to as Tekmira, the Massachusetts Institute of Technology, or MIT, The University of British Columbia, or UBC, and Acuitas Therapeutics Inc. (formerly AlCana Technologies, Inc.), or Acuitas, among others, to focus on various delivery strategies. We have also entered into license agreements with Isis, Max Planck Innovation GmbH (formerly known as Garching Innovation GmbH), or Max Planck Innovation, Tekmira, MIT, Cancer Research Technology Limited, or CRT, and Whitehead Institute for Biomedical Research, or Whitehead, as well as a number of other entities, to obtain rights to intellectual property in the field of RNAi.

To generate revenues from our intellectual property rights, we grant licenses to biotechnology companies under our InterfeRx program for the development and commercialization of RNAi therapeutics for specified targets in which we have no direct strategic interest. We also license key aspects of our intellectual property to companies active in the research products and services market, which includes the manufacture and sale of reagents. We expect our InterfeRx and research product licenses to generate modest near-term revenues that we can re-invest in the development of our proprietary RNAi therapeutics pipeline. At March 31, 2014, we had granted such licenses, on both an exclusive and non-exclusive basis, to approximately 20 companies.

The 2014 Genzyme Collaboration. In January 2014, we entered into a global, strategic collaboration with Genzyme to discover, develop and commercialize RNAi therapeutics as genetic medicines to treat orphan diseases. The 2014 Genzyme collaboration is governed by a master collaboration agreement, including the license terms appended thereto, which became effective upon closing of the equity transaction, described below. As of the closing of the equity transaction in February 2014, the master agreement superseded and replaced the 2012 Genzyme agreement, which original Genzyme agreement is described under the heading “Strategic Alliances” in our annual report on Form 10-K for the year ended December 31, 2012.

product rights in the Alnylam Territory, while Genzyme will obtain exclusive rights to develop and commercialize collaboration products in the Genzyme Territory, together with certain broader co-development/co-promote or worldwide rights for certain products. Genzyme’s rights are structured as an opt-in that is triggered upon achievement of Human POP. We will maintain development control for all programs prior to Genzyme’s opt-in and maintain development and commercialization control after Genzyme’s opt-in for all programs in our territory.

Upon the effective date of the 2014 Genzyme collaboration, Genzyme opted-in to patisiran for the Genzyme Territory. We retain full product rights in the Alnylam Territory. We and Genzyme have also expanded our current collaboration on ALN-TTRsc, so that we and Genzyme will co-develop and co-promote ALN-TTRsc in the Alnylam Territory. We will maintain development and commercialization control with ALN-TTRsc in the Alnylam Territory. Genzyme will develop and commercialize the product in the Genzyme Territory.

In addition to its regional rights for our current and future genetic medicine programs in the Genzyme Territory, Genzyme will have the right to either (i) co-develop and co-promote ALN-AT3 for the treatment of hemophilia and other RBDs in our territory, with us maintaining development and commercialization control, or (ii) obtain a global license to ALN-AS1 for the treatment of hepatic porphyrias. Genzyme will exercise this selection right upon completion of Human POP for both the ALN-AT3 and ALN-AS1 programs. Finally, Genzyme will have the right for a global license to a single, future genetic medicine program that is not one of our currently defined genetic medicine programs. We will retain global rights to any RNAi therapeutic genetic medicine program that does not reach Human POP by the end of 2019, subject to certain limited exceptions. Under the terms of the master agreement, we will retain full rights to all current and future RNAi therapeutic programs outside of the field of genetic medicines, including the right to form new collaborations.

In consideration for the rights granted to Genzyme under the master agreement and pursuant to the terms of a stock purchase agreement, we sold to Genzyme 8,766,338 shares of our common stock and Genzyme paid us $700.0 million in aggregate cash consideration. At the closing, we also entered into an investor agreement with Genzyme. Our investor agreement with Genzyme provides Genzyme with the right, subject to certain exceptions, generally to maintain its ownership position in us until Genzyme owns less than 7.5% of our outstanding common stock, subject to certain additional limited rights of Genzyme to maintain its ownership percentage. In accordance with the investor rights agreement, as a result of our issuance of shares in connection with our acquisition of Sirna in March 2014, on March 25, 2014, Genzyme exercised its right to purchase an additional 344,448 shares of our common stock, at a purchase price of $66.88, the price of our common stock that day, and paid us $23.0 million. This purchase allowed Genzyme to maintain its ownership level of our outstanding common stock of approximately 12%.

A more detailed description of our 2014 Genzyme collaboration and the related stock purchase agreement is set forth in Note 2 to our condensed consolidated financial statements included in Part I, Item 1, “Financial Statements,” of this quarterly report on Form 10-Q.

microRNA Therapeutics

Regulus. In September 2007, we and Isis established Regulus, a company focused on the discovery, development and commercialization of microRNA therapeutics. Regulus leverages our and Isis’ technologies, know-how and intellectual property relating to microRNA therapeutics.

Regulus, which initially was established as a limited liability company, converted to a C corporation as of January 2, 2009 and changed its name to Regulus Therapeutics Inc. In consideration for our and Isis’ initial interests in Regulus, we and Isis each granted Regulus exclusive licenses to our intellectual property for certain microRNA therapeutics as well as certain patents in the microRNA field. Regulus operates as an independent company with a separate board of directors, scientific advisory board and management team, some of whom have options to purchase common stock of Regulus. Members of the board of directors of Regulus who are our employees or Isis’ employees have not been eligible to receive options to purchase Regulus common stock. In October 2012, Regulus completed an underwritten initial public offering, raising $45.0 million in net proceeds, including proceeds from the exercise by the underwriters of the over-allotment option. In July 2013, Regulus completed an additional underwritten public offering, raising an additional $45.8 million in net proceeds, including proceeds from the exercise of the over-allotment option. Currently, we own approximately 14% of Regulus’ outstanding common stock.

Regulus is exploring therapeutic opportunities that arise from microRNA dysregulation. Since microRNAs are believed to regulate broad networks of genes and biological pathways, microRNA therapeutics define a new and potentially high-impact strategy to target multiple nodes on disease pathways. microRNAs are small non-coding RNAs that regulate the expression of other genes. More than 500 microRNAs have been identified to date in humans, each of which is believed to interact with a specific set of genes

that control key aspects of cell biology. Since microRNAs may act as master regulators of the genome and are often found to be dysregulated in disease, microRNAs potentially represent an exciting new platform for drug discovery and development. Regulus is advancing microRNA therapeutics in several areas including oncology, fibrosis, hepatitis C virus and metabolic diseases.

Regulus has entered into a number of strategic alliances with leading pharmaceutical companies, including GSK, sanofi, Biogen Idec and AstraZeneca PLC. Each of Alnylam and Isis is entitled to receive specified sublicense income in connection with certain collaborative agreements entered into by Regulus, as well as royalties on net sales, if any, of certain products developed by Regulus or its collaborators, in each case subject to the terms and conditions of the license and collaboration agreement among Regulus, Isis and Alnylam.

Intellectual Property

The strength of our intellectual property portfolio relating to the development and commercialization of siRNAs as therapeutics is essential to our business strategy. We own or license issued patents and pending patent applications in the United States and in key markets around the world claiming fundamental features of siRNAs and RNAi therapeutics as well as those claiming crucial chemical modifications and promising delivery technologies. Specifically, we have a portfolio of patents, patent applications and other intellectual property covering: fundamental aspects of the structure and uses of siRNAs, including their use as therapeutics, and RNAi-related mechanisms; chemical modifications to siRNAs that improve their suitability for therapeutic uses; siRNAs directed to specific targets as treatments for particular diseases; delivery technologies, such as in the field of cationic liposomes and conjugates; and all aspects of our specific development candidates.

We believe that no other company possesses a portfolio of such broad and exclusive rights to the patents and patent applications required for the commercialization of RNAi therapeutics. Our intellectual property portfolio for RNAi therapeutics includes over 1,800 active cases and over 700 granted or issued patents, of which over 300 are issued or granted in the United States, the European Union and Japan. We continue to seek to grow our portfolio through the creation of new technology in this field. In addition, we are very active in our evaluation of third-party technologies. To that end, we recently acquired Sirna’s RNAi assets, including an extensive patent estate. The granted patents, applications and know-how obtained through this acquisition further strengthens the breadth and depth of our intellectual property portfolio.

Our expertise in RNAi therapeutics and broad intellectual property portfolio have allowed us to form alliances with leading companies, including Isis, Medtronic, Novartis, Biogen Idec, Roche/Arrowhead, Takeda, Kyowa Hakko Kirin, Cubist, Ascletis, Monsanto, Genzyme and MDCO, as well as enter into license agreements with other biotechnology companies interested in developing RNAi therapeutic products and research companies that commercialize RNAi reagents or services.

Given the importance of our intellectual property portfolio to our business operations, we intend to vigorously enforce our rights and defend against challenges that have arisen or may arise in this area.

Critical Accounting Policies and Estimates

There have been no significant changes to our critical accounting policies since the beginning of this fiscal year. Our critical accounting policies are described in the “Management’s Discussion and Analysis of Financial Condition and Results of Operations” section of our Annual Report on Form 10-K for the year ended December 31, 2013, which we filed with the SEC on February 20, 2014.

Results of Operations

The following data summarizes the results of our operations for the periods indicated, in thousands:


	Three Months Ended March 31,
	2014			2013
Net revenues from collaborators	$	8,275		$	18,642
Operating expenses		277,339			28,446
Loss from operations		(269,064	)		(9,804	)
Net loss	$	(250,943	)	$	(9,013	)

The increase in operating expenses for the three months ended March 31, 2014 resulted from a $224.7 million charge to in-process research and development expense in connection with the purchase of the Sirna RNAi assets from Merck, which is described below under the heading “In-process research and development.”

Net revenues from collaborators

We generate revenues through research and development collaborations. The following table summarizes our total consolidated net revenues from collaborators, for the periods indicated, in thousands:


	Three Months Ended March 31,
	2014		2013
Description
Takeda	$	5,493	$	5,493
Monsanto		1,410		1,410
The Medicines Company		1,266		834
Cubist		—		9,721
Other		106		1,184

Total net revenues from collaborators	$	8,275	$	18,642

Net revenues from collaborators decreased during the three months ended March 31, 2014 as compared to the three months ended March 31, 2013 due primarily to the recognition of the remaining deferred revenue under the Cubist agreement of $9.7 million, due to the termination of the Cubist agreement in February 2013 and the end of our performance obligations thereunder.

We also had $66.8 million of deferred revenue at March 31, 2014, which primarily consists of payments we have received from collaborators, but have not yet recognized pursuant to our revenue recognition policies.

For the foreseeable future, we expect our revenues to continue to be derived primarily from our alliances with Takeda, Monsanto, MDCO and Genzyme, and other strategic alliances, as well as any new collaborations and licensing activities.

Operating expenses

The following table summarizes our operating expenses for the periods indicated, in thousands and as a percentage of total operating expenses, together with the changes, in thousands and percentages:


	Three Months Ended March 31,		% of Total Operating			Three Months Ended March 31,		% of Total Operating			Increase (Decrease)
	2014		Expenses			2013		Expenses			$		%
Research and development	$	43,758		16	%	$	22,179		78	%	$	21,579		97	%
In-process research and development		224,656		81	%		—		0	%		224,656		N/A
General and administrative		8,925		3	%		6,267		22	%		2,658		42	%

Total operating expenses	$	277,339		100	%	$	28,446		100	%	$	248,893		875	%

Research and development. The following table summarizes the components of our research and development expenses for the periods indicated, in thousands and as a percentage of total research and development expenses, together with the changes, in thousands and percentages:


	Three Months Ended		% of Expense			Three Months Ended		% of Expense			Increase (Decrease)
	March 31, 2014		Category			March 31, 2013		Category			$			%
Research and development
Clinical trial and manufacturing	$	12,752		29	%	$	4,018		18	%	$	8,734			217	%
Compensation and related		9,276		21	%		5,908		27	%		3,368			57	%
License fees		8,384		19	%		585		3	%		7,799			1,333	%
Facilities-related		4,354		10	%		3,540		16	%		814			23	%
Non-cash stock-based compensation		3,681		8	%		2,087		9	%		1,594			76	%
External services		3,299		8	%		4,024		18	%		(725	)		(18	)%
Lab supplies and materials		1,333		3	%		1,307		6	%		26			2	%
Other		679		2	%		710		3	%		(31	)		(4	)%

Total research and development expenses	$	43,758		100	%	$	22,179		100	%	$	21,579			97	%

Research and development expenses increased during the three months ended March 31, 2014 as compared to the three months ended March 31, 2013 due primarily to additional expenses related to the advancement of our patisiran and ALN-TTRsc programs. In addition, license fees increased during the three months ended March 31, 2014 as compared to the three months ended March 31, 2013 due to payments to certain entities, primarily fees due to Isis as a result of the 2014 Genzyme collaboration.

We expect to continue to devote a substantial portion of our resources to research and development expenses as we continue development of our and our collaborators’ product candidates and focus on continuing to develop drug delivery-related technologies. Excluding a one-time license fee in the first quarter due to Isis as a result of the 2014 Genzyme collaboration, we expect that research and development expenses will increase for the remainder of 2014 on a quarterly basis.

A significant portion of our research and development expenses are not tracked by project as they benefit multiple projects or our technology platform. Our collaboration agreements may contain cost-sharing arrangements pursuant to which certain costs incurred under the project are reimbursed by the counterparty to such agreement. Costs reimbursed under these agreements could include certain direct external costs and a negotiated full-time equivalent labor rate for the actual time worked on the project. However, while we may track direct external costs attributable to, and the actual time our employees worked on certain of our collaborations agreements, we do not track or manage total research and development expenses by product area or development phase.

In-process research and development. For the three months ended March 31, 2014, we incurred a $224.7 million charge to in-process research and development expense in connection with the purchase of the Sirna RNAi assets from Merck. Specifically, at the closing of the transaction, we paid Merck $25.0 million in cash and issued 2,142,037 shares of our common stock, resulting in a charge to in-process research and development expense of $199.3 million. We will issue an additional 378,007 shares of common stock to Merck upon the completion of certain technology transfer activities, which are expected to be completed in the second quarter of 2014. We have recorded a liability of $25.4 million associated with this future obligation to issue shares, which was charged to in-process research and development expense. Upon completion of these technology transfer activities, we will re-measure the expense recorded in connection with these shares using the then current price of our common stock.

General and administrative. The following table summarizes the components of our general and administrative expenses for the periods indicated, in thousands and as a percentage of total general and administrative expenses, together with the changes, in thousands and percentages:


	Three Months Ended March 31, 2014		% of Expense Category			Three Months Ended March 31, 2013		% of Expense Category			Increase (Decrease)
	Three Months Ended March 31, 2014		% of Expense Category			Three Months Ended March 31, 2013		% of Expense Category			$			%
General and administrative
Consulting and professional services	$	3,772		42	%	$	2,519		40	%	$	1,253			50	%
Compensation and related		2,182		25	%		1,657		26	%		525			32	%
Non-cash stock-based compensation		1,910		21	%		988		16	%		922			93	%
Facilities-related		444		5	%		468		8	%		(24	)		(5	)%
Other		617		7	%		635		10	%		(18	)		(3	)%

Total general and administrative expenses	$	8,925		100	%	$	6,267		100	%	$	2,658			42	%

General and administrative expenses increased during the three months ended March 31, 2014 as compared to the three months ended March 31, 2013 due primarily to an increase in consulting and professional services related to business development activities. In addition, compensation and related and non-cash stock-based compensation expenses increased during the three months ended March 31, 2014 as compared to the three months ended March 31, 2013 due primarily to an increase in the valuation of the stock awards granted. For the remainder of 2014, we expect that general and administrative expenses on a quarterly basis will remain consistent with the first quarter of 2014.

Benefit from income taxes

Our benefit from income taxes was $17.9 million for the three months ended March 31, 2014 as compared to $0.6 million for the three months ended March 31, 2013. The increase was due to the corresponding income tax benefit associated with the sale of common stock to Genzyme under the 2014 Genzyme collaboration being recorded net of tax to additional paid-in capital. In addition, we also recorded an income tax benefit for the increase in the value of our investment in Regulus that we carried at fair market value during the same respective period.

Liquidity and Capital Resources

The following table summarizes our cash flow activities for the periods indicated, in thousands:


	Three Months Ended March 31,
	2014			2013
Net loss	$	(250,943	)	$	(9,013	)
Adjustments to reconcile net loss to net cash used in operating activities		215,134			4,760
Changes in operating assets and liabilities		(5,866	)		3,282

Net cash used in operating activities		(41,675	)		(971	)
Net cash used in investing activities		(379,780	)		(130,840	)
Net cash provided by financing activities		718,875			178,210

Net increase in cash and cash equivalents		297,420			46,399
Cash and cash equivalents, beginning of period		53,169			51,405

Cash and cash equivalents, end of period	$	350,589		$	97,804

Since we commenced operations in 2002, we have generated significant losses. At March 31, 2014, we had an accumulated deficit of $847.2 million. At March 31, 2014, we had cash, cash equivalents and fixed income marketable securities of $1.0 billion, compared to cash, cash equivalents and fixed income marketable securities of $350.5 million at December 31, 2013, in each period excluding our investment in equity securities of Regulus.

We invest primarily in cash equivalents, U.S. government obligations, high-grade corporate notes and commercial paper. Our investment objectives are, primarily, to assure liquidity and preservation of capital and, secondarily, to obtain investment income. All of our investments in debt securities are recorded at fair value and are available-for-sale. Fair value is determined based on quoted market prices and models using observable data inputs. We have not recorded any impairment charges related to our fixed income marketable securities at March 31, 2014.

Operating activities

We have required significant amounts of cash to fund our operating activities as a result of net losses since our inception. For the three months ended March 31, 2014, net cash used in operating activities of $41.7 million was due primarily to our net loss. For the three months ended March 31, 2013, net cash used in operating activities of $1.0 million was due primarily to our net loss partially offset by an increase in deferred revenue of $7.2 million. In addition, net cash used in operating activities is adjusted for non-cash items to reconcile net loss to net cash used in or provided by operating activities. These non-cash adjustments consist primarily of in-process research and development, stock-based compensation, depreciation and amortization.

We expect that we will require significant amounts of cash to fund our operating activities for the foreseeable future as we continue to develop and advance our research and development initiatives. The actual amount of overall expenditures will depend on numerous factors, including the timing of expenses, the timing and terms of collaboration agreements or other strategic transactions, if any, and the timing and progress of our research and development efforts.

Investing activities

For the three months ended March 31, 2014, net cash used in investing activities of $379.8 million was due primarily to $354.4 million of net purchases of fixed income marketable securities. For the three months ended March 31, 2013, net cash used in investing activities of $130.8 million was due primarily to $129.0 million of net purchases of fixed income marketable securities.

Financing activities

For the three months ended March 31, 2014, net cash of $718.9 million provided by financing activities was due primarily to proceeds of $723.0 million received from our issuance of common stock to Genzyme, as well as proceeds of $11.5 million from the issuance of common stock in connection with stock option exercises, partially offset by $15.7 million of payments for the repurchase of common stock for employee tax withholding. For the three months ended March 31, 2013, net cash of $178.2 million provided by financing activities was due primarily to proceeds of $173.6 million received from our January 2013 underwritten public offering, as well as proceeds of $4.6 million from the issuance of common stock in connection with stock option exercises.

Operating Capital Requirements

We do not know when, if ever, we will successfully develop or be able to commence sales of any product. Therefore, we anticipate that we will continue to generate significant losses for the foreseeable future as a result of planned expenditures for research and development activities relating to our drug development programs, including the development and optimization of drug delivery technologies and clinical trial costs, extension of the capabilities of our technology platform, including through business initiatives, continued management and growth of our patent portfolio, collaborations and general corporate activities. Based on our current operating plan, we believe that our existing cash, cash equivalents and fixed income marketable securities, will be sufficient to fund our planned operations through the launch of our first commercial product. For reasons discussed below, we may require significant additional funds earlier than we currently expect in order to develop, conduct clinical trials for and commercialize any product candidates.

In the future, we may seek additional funding through additional collaborative arrangements and public or private financings. In December 2012, we filed an automatically effective shelf registration statement with the SEC for an indeterminate number of shares. Additional funding may not be available to us on acceptable terms or at all. In addition, the terms of any additional financing may further adversely affect the holdings or the rights of our stockholders. For example, if we raise additional funds by issuing equity securities, further dilution to our existing stockholders may result. In addition, as a condition to providing additional funds to us, future investors may demand, and may be granted, rights superior to those of existing stockholders. If we are unable to obtain funding on a timely basis, we may be required to significantly delay or curtail one or more of our research or development programs. We also could be required to seek funds through arrangements with collaborators or others that may require us to relinquish rights to some of our technologies or product candidates that we would otherwise pursue.

Even if we are able to raise additional funds in a timely manner, our future capital requirements may vary from what we expect and will depend on many factors, including:

•

our progress in demonstrating that siRNAs can be active as drugs;

•

our ability to develop relatively standard procedures for selecting and modifying siRNA product candidates;

•

progress in our research and development programs, as well as the magnitude of these programs;

•

the timing, receipt and amount of milestone and other payments, if any, from present and future collaborators, if any;

•

our ability to maintain and establish additional collaborative arrangements and/or new business initiatives;

•

the resources, time and costs required to successfully initiate and complete our pre-clinical and clinical trials, obtain regulatory approvals, and obtain and maintain licenses to third-party intellectual property;

•

our ability to manufacture, or contract with third-parties for the manufacture of, our product candidates for clinical testing and commercial sale;

•

the resources, time and cost required for the preparation, filing, prosecution, maintenance and enforcement of patent claims;

•

the costs associated with legal activities, including litigation, arising in the course of our business activities and our ability to prevail in any such legal disputes;

•

progress in the research and development programs of Regulus; and

•

the timing, receipt and amount of sales and royalties, if any, from our potential products.

Contractual Obligations and Commitments

The disclosure of our contractual obligations and commitments is set forth under the heading “Management’s Discussion and Analysis of Financial Condition and Results of Operations—Contractual Obligations and Commitments” in our Annual Report on Form 10-K for the year ended December 31, 2013. In March 2014, we amended the lease for our Cambridge, Massachusetts facility to exercise our option to extend the lease for an additional five years, through September 30, 2021. As a result, our operating lease obligations through 2021 increased by $37.8 million.

Recent Accounting Pronouncements

For a discussion of recent accounting pronouncements see Note 2 to our audited consolidated financial statements included in our Annual Report on Form 10-K for the year ended December 31, 2013. We did not adopt any new accounting pronouncements during the three months ended March 31, 2014 that had a material effect on our condensed consolidated financial statements.

ITEM 3. QUANTITATIVE AND QUALITATIVE DISCLOSURES ABOUT MARKET RISK.

As part of our investment portfolio, we own financial instruments that are sensitive to market risks. The investment portfolio is used to preserve our capital until it is required to fund operations, including our research and development activities. Our marketable securities consist of U.S. government and municipal obligations, high-grade corporate notes and commercial paper. All of our investments in debt securities are classified as available-for-sale and are recorded at fair value. Our available-for-sale investments in debt securities are sensitive to changes in interest rates and changes in the credit ratings of the issuers. Interest rate changes would result in a change in the net fair value of these financial instruments due to the difference between the market interest rate and the market interest rate at the date of purchase of the financial instrument. If market interest rates were to increase immediately and uniformly by 50 basis points, or one-half of a percentage point, from levels at March 31, 2014, the net fair value of our interest-sensitive financial instruments would have resulted in a hypothetical decline of $3.5 million. We currently do not seek to hedge this exposure to fluctuations in interest rates. A downgrade in the credit rating of an issuer of a debt security or further deterioration of the credit markets could result in a decline in the fair value of the debt instruments. Our investment guidelines prohibit investment in auction rate securities and we do not believe we have any direct exposure to losses relating from mortgage-based securities or derivatives related thereto such as credit-default swaps. We have not recorded any impairment charges to our fixed income marketable securities at March 31, 2014.

ITEM 4. CONTROLS AND PROCEDURES.

Our management, with the participation of our chief executive officer (principal executive officer) and vice president of finance and treasurer (principal financial officer), evaluated the effectiveness of our disclosure controls and procedures as of March 31, 2014. The term “disclosure controls and procedures,” as defined in Rules 13a-15(e) and 15d-15(e) under the Securities Exchange Act of 1934, as amended, or the Exchange Act, means controls and other procedures of a company that are designed to ensure that information required to be disclosed by a company in the reports that it files or submits under the Exchange Act is recorded, processed, summarized and reported within the time periods specified in the SEC’s rules and forms. Disclosure controls and procedures include, without limitation, controls and procedures designed to ensure that information required to be disclosed by a company in the reports that it files or submits under the Exchange Act is accumulated and communicated to the company’s management, including its principal executive and principal financial officers, as appropriate to allow timely decisions regarding required disclosure. Management recognizes that any controls and procedures, no matter how well designed and operated, can provide only reasonable assurance of achieving their objectives and management necessarily applies its judgment in evaluating the cost-benefit relationship of possible controls and procedures. Based on the evaluation of our disclosure controls and procedures as of March 31, 2014, our chief executive officer and vice president of finance and treasurer concluded that, as of such date, our disclosure controls and procedures were effective at the reasonable assurance level.

No change in our internal control over financial reporting (as defined in Rules 13a–15(f) and 15d–15(f) under the Exchange Act) occurred during the three months ended March 31, 2014 that has materially affected, or is reasonably likely to materially affect, our internal control over financial reporting.

PART II. OTHER INFORMATION

ITEM 1. LEGAL PROCEEDINGS.

University of Utah Litigation

On March 22, 2011, The University of Utah, or Utah, filed a civil complaint in the United States District Court for the District of Massachusetts against us, Max Planck, Whitehead, MIT and University of Massachusetts, or UMass, claiming a professor at Utah is the sole inventor or, in the alternative, a joint inventor, of the Tuschl patents. Utah did not serve the original complaint on us or the other defendants. On July 6, 2011, Utah filed an amended complaint alleging substantially the same claims against us, Max Planck, Whitehead, MIT and UMass. The amended complaint was served on us on July 14, 2011. Utah is seeking changes to the inventorship of the Tuschl patents, unspecified damages and other relief. On October 31, 2011, we, Max Planck, Whitehead, MIT and UMass filed a motion to dismiss. Also on October 31, 2011, UMass filed a motion to dismiss on separate grounds, which we, Max Planck, Whitehead and MIT joined. On December 31, 2011, Utah filed a second amended complaint dropping UMass as a defendant and adding as defendants several UMass officials. In June 2012, the Court denied both motions to dismiss. We, Max Planck, Whitehead, MIT and UMass filed an appeal of the Court’s ruling on the motion to dismiss for lack of jurisdiction and a motion requesting that the Court stay the case pending the outcome of the appeal. In July 2012, the Court stayed discovery in the case pending the outcome of the defendants’ appeal. Oral arguments in the appeal were heard in early March 2013 in the United States Court of Appeals for the Federal Circuit, or CAFC. In August 2013, the CAFC affirmed the lower Court’s ruling, in a split decision. We believe the majority made an error in law when affirming the lower Court’s decision, and in September 2013, we filed a petition with the CAFC for rehearing or rehearing en banc. In October 2013, the CAFC invited Utah to file an answer to the petition. In November 2013, the CAFC denied our petition for rehearing or rehearing en banc and remanded the case back to the lower Court. In February 2014, we filed a petition for writ of certiorari from the Supreme Court and a motion to stay the lower Court proceedings pending a decision from the Supreme Court on our petition. We are awaiting the Courts’ decisions.

ITEM 1A.

RISK FACTORS

Our business is subject to numerous risks. We caution you that the following important factors, among others, could cause our actual results to differ materially from those expressed in forward-looking statements made by us or on our behalf in filings with the SEC, press releases, communications with investors and oral statements. All statements other than statements relating to historical matters should be considered forward-looking statements. When used in this report, the words “believe,” “expect,” “plan,” “anticipate,” “estimate,” “predict, “may,” “could,” “should,” “intend,” “will,” “target,” “goal” and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these words. Any or all of our forward-looking statements in this Quarterly Report on Form 10-Q and in any other public statements we make may turn out to be wrong. They can be affected by inaccurate assumptions we might make or by known or unknown risks and uncertainties. Many factors mentioned in the discussion below will be important in determining future results. Consequently, no forward-looking statement can be guaranteed. Actual future results may vary materially from those anticipated in forward-looking statements. We explicitly disclaim any obligation to update any forward-looking statements to reflect events or circumstances that arise after the date hereof. You are advised, however, to consult any further disclosure we make in our reports filed with the SEC.

Risks Related to Our Business

Risks Related to Being a Clinical Stage Company

Because we are in clinical development, there is limited information about our ability to successfully overcome many of the risks and uncertainties encountered by companies in the biopharmaceutical industry.

As a company in clinical development, we have limited experience and have not yet demonstrated an ability to successfully overcome many of the risks and uncertainties frequently encountered by companies in new and rapidly evolving fields, particularly in the biopharmaceutical area. For example, to execute our business plan, we will need to successfully:

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execute product development activities using unproven technologies related to both RNAi and to the delivery of siRNAs to the relevant tissues and cells;

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build and maintain a strong intellectual property portfolio;

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gain regulatory acceptance for the development of our product candidates and market success for any products we commercialize;

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develop and maintain successful strategic alliances; and

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manage our spending as costs and expenses increase due to clinical trials, regulatory approvals and commercialization.

If we are unsuccessful in accomplishing these objectives, we may not be able to develop product candidates, commercialize products, raise capital, expand our business or continue our operations.

The approach we are taking to discover and develop novel RNAi therapeutics is unproven and may never lead to marketable products.

We have concentrated our efforts and therapeutic product research on RNAi technology and our future success depends on the successful development of this technology and products based on it. Neither we nor any other company has received regulatory approval to market therapeutics utilizing siRNAs, the class of molecule we are trying to develop into drugs. The scientific discoveries that form the basis for our efforts to discover and develop new drugs are relatively new. The scientific evidence to support the feasibility of developing drugs based on these discoveries is both preliminary and limited. Skepticism as to the feasibility of developing RNAi therapeutics has been expressed in scientific literature. For example, there are potential challenges to achieving safe RNAi therapeutics based on the so-called off-target effects and activation of the interferon response. In addition, decisions by other companies with respect to their RNAi development efforts may increase skepticism in the marketplace regarding the potential for RNAi therapeutics.

Relatively few product candidates based on these discoveries have ever been tested in animals or humans. siRNAs may not naturally possess the inherent properties typically required of drugs, such as the ability to be stable in the body long enough to reach the tissues in which their effects are required, nor the ability to enter cells within these tissues in order to exert their effects. We currently have only limited data, and no conclusive evidence, to suggest that we can introduce these drug-like properties into siRNAs. We may spend large amounts of money trying to introduce these properties, and may never succeed in doing so. In addition, these compounds may not demonstrate in patients the chemical and pharmacological properties ascribed to them in laboratory studies, and they may interact with human biological systems in unforeseen, ineffective or harmful ways. As a result, we may never succeed in developing a marketable product, we may not become profitable and the value of our common stock will decline.

Further, our focus solely on RNAi technology for developing drugs, as opposed to multiple, more proven technologies for drug development, increases the risks associated with the ownership of our common stock. If we are not successful in developing a product candidate using RNAi technology, we may be required to change the scope and direction of our product development activities. In that case, we may not be able to identify and implement successfully an alternative product development strategy.

Risks Related to Our Financial Results and Need for Financing

We have a history of losses and may never become and remain consistently profitable.

We have experienced significant operating losses since our inception. At March 31, 2014, we had an accumulated deficit of $847.2 million. To date, we have not developed any products nor generated any revenues from the sale of products. Further, we do not expect to generate any product revenues in the foreseeable future. We expect to continue to incur annual net operating losses over the next several years and will require substantial resources over the next several years as we expand our efforts to discover, develop and commercialize RNAi therapeutics. We anticipate that the majority of any revenues we generate over the next several years will be from alliances with pharmaceutical and biotechnology companies, but cannot be certain that we will be able to secure or maintain these alliances, or meet the obligations or achieve any milestones that we may be required to meet or achieve to receive payments. We anticipate that revenues derived from such sources will not be sufficient to make us consistently profitable.

We believe that to become and remain consistently profitable, we must succeed in discovering, developing and commercializing novel drugs with significant market potential. This will require us to be successful in a range of challenging activities, including pre-clinical testing and clinical trial stages of development, obtaining regulatory approval for these novel drugs and manufacturing, marketing and selling them. We may never succeed in these activities, and may never generate revenues that are significant enough to achieve profitability. Even if we do achieve profitability, we may not be able to sustain or increase profitability on a quarterly or annual basis. If we cannot become and remain consistently profitable, the market price of our common stock could decline. In addition, we may be unable to raise capital, expand our business, develop additional product candidates or continue our operations.

We will require substantial additional funds to complete our research and development activities and if additional funds are not available, we may need to critically limit, significantly scale back or cease our operations.

We have used substantial funds to develop our RNAi technologies and will require substantial funds to conduct further research and development, including pre-clinical testing and clinical trials of our product candidates, and to manufacture and market any products that are approved for commercial sale. Because we cannot be certain of the length of time or activities associated with successful development of our product candidates, we are unable to estimate the actual funds we will require to develop and commercialize them.

Our future capital requirements and the period for which we expect our existing resources to support our operations may vary from what we expect. We have based our expectations on a number of factors, many of which are difficult to predict or are outside of our control, including:

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our progress in demonstrating that siRNAs can be active as drugs;

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our ability to develop relatively standard procedures for selecting and modifying siRNA product candidates;

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progress in our research and development programs, as well as the magnitude of these programs;

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the timing, receipt and amount of milestone and other payments, if any, from present and future collaborators, if any;

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our ability to maintain and establish additional collaborative arrangements and/or new business initiatives;

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the resources, time and costs required to initiate and complete our pre-clinical and clinical trials, obtain regulatory approvals, and obtain and maintain licenses to third-party intellectual property;

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our ability to manufacture, or contract with third-parties for the manufacture of, our product candidates for clinical testing and commercial sale;

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the resources, time and cost required for the preparation, filing, prosecution, maintenance and enforcement of patent claims;

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the costs associated with legal activities, including litigation, arising in the course of our business activities and our ability to prevail in any such legal disputes;

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progress in the research and development programs of Regulus; and

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the timing, receipt and amount of sales and royalties, if any, from our potential products.

If our estimates and predictions relating to these factors are incorrect, we may need to modify our operating plan.

Even if our estimates are correct, we will be required to seek additional funding in the future and intend to do so through either collaborative arrangements, public or private equity offerings or debt financings, or a combination of one or more of these funding sources. Additional funds may not be available to us on acceptable terms or at all.

In addition, the terms of any financing may adversely affect the holdings or the rights of our stockholders. For example, if we raise additional funds by issuing equity securities, under our shelf registration statement or otherwise, further dilution to our stockholders will result. In addition, as a condition to providing additional funds to us, future investors may demand, and may be granted, rights superior to those of existing stockholders. Moreover, our investor agreement with Genzyme provides Genzyme with the right, subject to certain exceptions, generally to maintain its ownership position in us until Genzyme owns less than 7.5% of our outstanding common stock, subject to certain additional limited rights of Genzyme to maintain its ownership percentage. In accordance with the investor agreement, as a result of our issuance of shares in connection with our acquisition of Sirna in March 2014, Genzyme exercised its right to purchase an additional 344,448 shares of our common stock, and paid us $23.0 million. This purchase allowed Genzyme to maintain its ownership level of approximately 12% of our outstanding common stock. While the exercise of these rights by Genzyme has provided us with an additional $23.0 million in cash, and the exercise in the future by Genzyme may provide us with additional funding under some circumstances, these exercises have caused, and any future exercise of these rights by Genzyme will also cause further, dilution to our stockholders. Debt financing, if available, may involve restrictive covenants that could limit our flexibility in conducting future business activities and, in the event of insolvency, would be paid before holders of equity securities received any distribution of corporate assets.

If we are unable to obtain funding on a timely basis, we may be required to significantly delay or curtail one or more of our research or development programs or undergo future reductions in our workforce or other corporate restructuring activities. We also could be required to seek funds through arrangements with collaborators or others that may require us to relinquish rights to some of our technologies, product candidates or products that we would otherwise pursue on our own.

If the estimates we make, or the assumptions on which we rely, in preparing our condensed consolidated financial statements prove inaccurate, our actual results may vary from those reflected in our projections and accruals.

Our condensed consolidated financial statements have been prepared in accordance with accounting principles generally accepted in the United States of America. The preparation of these condensed consolidated financial statements requires us to make estimates and judgments that affect the reported amounts of our assets, liabilities, revenues and expenses, the amounts of charges accrued by us and related disclosure of contingent assets and liabilities. We base our estimates on historical experience and on various other assumptions that we believe to be reasonable under the circumstances. We cannot assure you, however, that our estimates, or the assumptions underlying them, will be correct.

The investment of our cash, cash equivalents and fixed income marketable securities is subject to risks which may cause losses and affect the liquidity of these investments.

At March 31, 2014, we had $1.0 billion in cash, cash equivalents and fixed income marketable securities. We historically have invested these amounts in corporate bonds, commercial paper, securities issued or sponsored by the U.S. government, certificates of deposit and money market funds meeting the criteria of our investment policy, which is focused on the preservation of our capital. These investments are subject to general credit, liquidity, market and interest rate risks. We may realize losses in the fair value of these investments or a complete loss of these investments, which would have a negative effect on our condensed consolidated financial statements. In addition, should our investments cease paying or reduce the amount of interest paid to us, our interest income would suffer. The market risks associated with our investment portfolio may have an adverse effect on our results of operations, liquidity and financial condition.

Risks Related to Our Dependence on Third Parties

Our license and collaboration agreements with pharmaceutical companies are important to our business. If these pharmaceutical companies do not successfully develop drugs pursuant to these agreements or we develop drugs targeting the same diseases as our non-exclusive licensees, our business could be adversely affected.

In July 2007, we entered into a license and collaboration agreement with Roche. Under the license and collaboration agreement we granted Roche a non-exclusive license to our intellectual property to develop and commercialize therapeutic products that function through RNAi, subject to our existing contractual obligations to third parties. In November 2010, Roche announced the discontinuation of certain activities in research and early development, including their RNAi research efforts. In October 2011, Arrowhead announced its acquisition of RNA therapeutics assets from Roche, including our license and collaboration agreement with Roche. As a result of the assignment, Arrowhead now has all of the rights and obligations of Roche under that agreement. The license is limited to four therapeutic areas and may be expanded to include additional therapeutic areas, upon payment to us by Arrowhead of

an additional $50.0 million for each additional therapeutic area, if any. In addition, for each RNAi therapeutic product developed by Arrowhead, its affiliates, or sublicensees under the collaboration agreement, we are entitled to receive milestone payments upon achievement of specified development and sales events, totaling up to an aggregate of $100.0 million per therapeutic target, together with royalty payments based on worldwide annual net sales, if any. Our receipt of milestone payments under this agreement is dependent upon Arrowhead’s ability to successfully develop and commercialize RNAi therapeutic products.

In May 2008, we entered into a similar license and collaboration agreement with Takeda, which is limited to two therapeutic areas, and which may be expanded to include additional therapeutic areas, upon payment to us by Takeda of an additional $50.0 million for each additional therapeutic area, if any. For each RNAi therapeutic product developed by Takeda, its affiliates and sublicensees, we are entitled to receive specified development and commercialization milestone payments, totaling up to $171.0 million per product, together with royalty payments based on worldwide annual net sales, if any.

In September 2010, Novartis exercised its right under our collaboration and license agreement to select 31 designated gene targets, for which Novartis has exclusive rights to discover, develop and commercialize RNAi therapeutic products using our intellectual property and technology. Under the terms of the collaboration and license agreement, for any RNAi therapeutic products Novartis develops against these targets, we are entitled to receive milestone payments upon achievement of certain specified development and annual net sales events, up to an aggregate of $75.0 million per therapeutic product, as well as royalties on annual net sales of any such product, if any.

If Takeda, Novartis or Arrowhead fails to successfully develop products using our technology, we may not receive any milestone or royalty payments under our agreements with them. Finally, Takeda or Arrowhead could become a competitor of ours in the development of RNAi-based drugs targeting the same diseases that we choose to target. Takeda has significantly greater financial resources than we do and far more experience in developing and marketing drugs, which could put us at a competitive disadvantage if we were to compete with them in the development of RNAi-based drugs targeting the same disease.

We may not be able to execute our business strategy if we are unable to enter into alliances with other companies that can provide business and scientific capabilities and funds for the development and commercialization of our product candidates. If we are unsuccessful in forming or maintaining these alliances on terms favorable to us, our business may not succeed.

We do not have any capability for sales, marketing or distribution and have limited capabilities for drug development. Accordingly, we have entered into alliances with other companies and collaborators that we believe can provide such capabilities, and we intend to enter into additional such alliances in the future. Our collaboration strategy is to form alliances that create significant value for ourselves and our collaborators in the advancement of RNAi therapeutics as a new class of innovative medicines. Specifically, our goal is to retain development and commercial rights for our current and future genetic medicine pipeline in North America and Western Europe, while forming alliances with leading, innovative companies for the development and commercialization of these products in the rest of the world. In early 2014, we formed an alliance with Genzyme to develop and commercialize our current and future genetic medicine pipeline principally in territories outside of North America and Western Europe, subject to certain broader rights. This broad collaboration replaced our 2012 alliance with Genzyme. With respect to programs that are outside of our core focus on genetic medicines (for example, in the fields of metabolic and infectious disease and in oncology), we intend to seek regional or global alliances. For example, in February 2013, we entered into a global alliance with MDCO to advance our ALN-PCS program.

In such alliances, we expect our current, and may expect our future, collaborators to provide substantial capabilities in clinical development, regulatory affairs, and/or marketing, sales and distribution. Under certain of our alliances, we also may expect our collaborators to develop, market and/or sell certain of our product candidates. We may have limited or no control over the development, sales, marketing and distribution activities of these third parties. Our future revenues may depend heavily on the success of the efforts of these third parties. For example, we will rely entirely on (i) Genzyme for the development and commercialization of patisiran, ALN-TTRsc and potentially other of our genetic medicine programs in territories outside of North America and Western Europe under the 2014 Genzyme collaboration, and (ii) MDCO for later stage development and commercialization of ALN-PCSsc worldwide. If Genzyme and/or MDCO are not successful in their commercialization efforts, our future revenues from RNAi therapeutics for these indications may be adversely affected.

We may not be successful in entering into such alliances on terms favorable to us due to various factors, including our ability to successfully demonstrate proof of concept for our technology in humans, our ability to demonstrate the safety and efficacy of our specific drug candidates, our ability to manufacture or have third parties manufacture RNAi therapeutics, the strength of our intellectual property and/or concerns around challenges to our intellectual property. Even if we do succeed in securing any such alliances, we may not be able to maintain them if, for example, development or approval of a product candidate is delayed, challenges are raised as to the validity or scope of our intellectual property or sales of an approved drug are lower than we expected. In the case of the Monsanto agreement, if we cease to own or otherwise exclusively control certain licensed patent rights in the agriculture field, resulting in the loss of exclusivity with respect to Monsanto’s rights to such patent rights, and such loss of exclusivity has a material adverse effect on the licensed products (as defined in the agreement), we would be required to pay Monsanto up to $5.0 million in liquidated damages, and Monsanto’s royalty obligations to us would be reduced or, under certain circumstances, terminated.

Furthermore, any delay in entering into collaboration agreements would likely either delay the development and commercialization of certain of our product candidates and reduce their competitiveness even if they reach the market, or prevent the development of certain product candidates. Any such delay related to our collaborations could adversely affect our business.

For certain product candidates that we may develop, we have formed collaborations to fund all or part of the costs of drug development and commercialization, such as our collaboration with MDCO. We may not, however, be able to enter into additional collaborations for certain other programs, and the terms of any collaboration agreement we do secure may not be favorable to us. If we are not successful in our efforts to enter into future collaboration arrangements with respect to one or more of our product candidates, we may not have sufficient funds to develop that or any other product candidate internally, or to bring any product candidates to market. If we do not have sufficient funds to develop and bring our product candidates to market, we will not be able to generate sales revenues from these product candidates, and this will substantially harm our business.

If any collaborator terminates or fails to perform its obligations under agreements with us, the development and commercialization of our product candidates could be delayed or terminated.

Our dependence on collaborators for capabilities and funding means that our business could be adversely affected if any collaborator terminates its collaboration agreement with us or fails to perform its obligations under that agreement. Our current or future collaborations, if any, may not be scientifically or commercially successful. Disputes may arise in the future with respect to the ownership of rights to technology or products developed with collaborators, which could have an adverse effect on our ability to develop and commercialize any affected product candidate.

Our current collaborations allow, and we expect that any future collaborations will allow, either party to terminate the collaboration for a material breach by the other party. In addition, our collaborators may have additional termination rights for convenience under certain circumstances. For example, our agreement with MDCO relating to the development and commercialization of ALN-PCS worldwide may be terminated by MDCO at any time upon four months’ prior written notice. If we were to lose a commercialization collaborator, we would have to attract a new collaborator or develop internal sales, distribution and marketing capabilities, which would require us to invest significant amounts of financial and management resources.

In addition, if we have a dispute with a collaborator over the ownership of technology or other matters, or if a collaborator terminates its collaboration with us, for breach or otherwise, or determines not to pursue the research and development of RNAi therapeutics, it could delay our development of product candidates, result in the need for additional company resources to develop product candidates, make it more difficult for us to attract new collaborators and could adversely affect how we are perceived in the business and financial communities. For example, in March 2011, Tekmira filed a civil complaint against us claiming, among other things, misappropriation of its confidential and proprietary information and trade secrets. As a result of the litigation, which was settled in November 2012, we were required to expend resources and management attention that would otherwise have been engaged in other activities. In addition, in August 2013, we initiated binding arbitration proceedings to resolve a disagreement with Tekmira regarding the achievement by Tekmira of a $5.0 million milestone payment under our cross-license agreement relating to the manufacture of ALN-VSP clinical trial material for use in China.

Moreover, a collaborator, or in the event of a change in control of a collaborator or the assignment of a collaboration agreement to a third-party, the successor entity or assignee, could determine that it is in its interests to:

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pursue alternative technologies or develop alternative products, either on its own or jointly with others, that may be competitive with the products on which it is collaborating with us or which could affect its commitment to the collaboration with us;

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pursue higher-priority programs or change the focus of its development programs, which could affect the collaborator’s commitment to us; or

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if it has marketing rights, choose to devote fewer resources to the marketing of our product candidates, if any are approved for marketing, than it does for product candidates developed without us.

If any of these occur, the development and commercialization of one or more product candidates could be delayed, curtailed or terminated because we may not have sufficient financial resources or capabilities to continue such development and commercialization on our own.

We rely on third parties to conduct our clinical trials, and if they fail to fulfill their obligations, our development plans may be adversely affected.

We rely on independent clinical investigators, contract research organizations and other third-party service providers to assist us in managing, monitoring and otherwise carrying out our clinical trials. We have contracted, and we plan to continue to contract with, certain third-parties to provide certain services, including site selection, enrollment, monitoring and data management services. Although we depend heavily on these parties, we do not control them and therefore, we cannot be assured that these third-parties will adequately perform all of their contractual obligations to us. If our third-party service providers cannot adequately and timely fulfill their obligations to us, or if the quality and accuracy of our clinical trial data is compromised due to failure by such third-party to adhere to our protocols or regulatory requirements or if such third-parties otherwise fail to meet deadlines, our development plans may be delayed or terminated.

We have very limited manufacturing experience or resources and we must incur significant costs to develop this expertise and/or rely on third parties to manufacture our products.

We have very limited manufacturing experience. Some of our product candidates utilize specialized formulations, such as lipid nanoparticle, or LNP-based formulations, whose scale-up and manufacturing could be very difficult. We also have very limited experience in such scale-up and manufacturing, requiring us to depend on a limited number of third parties, who might not be able to deliver in a timely manner, or at all. In order to develop products, apply for regulatory approvals and commercialize our products, we will need to develop, contract for, or otherwise arrange for the necessary manufacturing capabilities. Our internal manufacturing capabilities have been limited to small-scale production of material for use in in vitro and in vivo experiments that is not required to be produced under current good manufacturing practice, or cGMP, standards. During 2012, we developed cGMP capabilities and processes for the manufacture of patisiran for late-stage clinical trial use and early commercial supply.

We may manufacture clinical trial materials ourselves or we may rely on others to manufacture the materials we will require for any clinical trials that we initiate. There are a limited number of manufacturers that supply synthetic siRNAs. We currently rely on several contract manufacturers for our supply of synthetic siRNAs. There are risks inherent in pharmaceutical manufacturing that could affect the ability of our contract manufacturers to meet our delivery time requirements or provide adequate amounts of material to meet our needs. Included in these risks are synthesis and purification failures and contamination during the manufacturing process, which could result in unusable product and cause delays in our development process, as well as additional expense to us. To fulfill our siRNA requirements, we may also need to secure alternative suppliers of synthetic siRNAs and such alternative suppliers may not be available, or we may be unable to enter into agreements with them on reasonable terms and in a timely manner.

In addition to the manufacture of the synthetic siRNAs, we may have additional manufacturing requirements related to the technology required to deliver the siRNA to the relevant cell or tissue type, such as LNPs or conjugates. In some cases, the delivery technology we utilize is highly specialized or proprietary, and for technical and legal reasons, we may have access to only one or a limited number of potential manufacturers for such delivery technology. Failure by manufacturers to properly formulate our siRNAs for delivery could result in unusable product. Furthermore, a breach by such manufacturers of their contractual obligations or a dispute with such manufacturers would cause delays in our discovery and development efforts, as well as additional expense to us. Given the limited number of suppliers for our delivery technology and other materials, we have developed cGMP capabilities and processes for the manufacture of patisiran formulated bulk drug product for late-stage clinical use and early commercial supply, and in the future, we may also develop our own capabilities to manufacture drug substance, including siRNAs and siRNA conjugates for human clinical use. In developing these manufacturing capabilities by building our own manufacturing facility, we have incurred substantial expenditures. Also, we have had to, and will likely need to continue to, hire and train qualified employees to staff our new facility. We do not currently have a second source of supply for patisiran formulated bulk drug product. If we are unable to manufacture sufficient quantities of material or if we encounter problems with our facility in the future, we may also need to secure alternative suppliers of for patisiran formulated bulk drug product and such alternative suppliers may not be available, or we may be unable to enter into agreements with them on reasonable terms and in a timely manner.

The manufacturing process for any products that we may develop is subject to the United States Food and Drug Administration, or FDA, and foreign regulatory authority approval process and we will need to meet, and will need to contract with manufacturers who can meet, all applicable FDA and foreign regulatory authority requirements on an ongoing basis. In addition, if we receive the necessary regulatory approval for any product candidate, we also expect to rely on third parties, including our commercial collaborators, to produce materials required for commercial supply. We may experience difficulty in obtaining adequate manufacturing capacity for our needs. If we are unable to obtain or maintain contract manufacturing for these product candidates, or to do so on commercially reasonable terms, we may not be able to successfully develop and commercialize our products.

To the extent that we have existing, or enter into future, manufacturing arrangements with third parties, we depend, and will depend in the future, on these third parties to perform their obligations in a timely manner and consistent with contractual and regulatory requirements, including those related to quality control and quality assurance. The failure of a third-party manufacturer to perform its obligations as expected, or, to the extent we manufacture all or a portion of our product candidates ourselves, our failure to execute on our manufacturing requirements could adversely affect our business in a number of ways, including:

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we or our current or future collaborators may not be able to initiate or continue clinical trials of products that are under development;

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we or our current or future collaborators may be delayed in submitting regulatory applications, or receiving regulatory approvals, for our product candidates;

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we may lose the cooperation of our collaborators;

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our facilities and products could be the subject of inspections by regulatory authorities;

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we may be required to cease distribution or recall some or all batches of our products; and

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ultimately, we may not be able to meet commercial demands for our products.

If any third-party manufacturer with whom we contract fails to perform its obligations, we may be forced to manufacture the materials ourselves, for which we may not have the capabilities or resources, or enter into an agreement with a different third-party manufacturer, which we may not be able to do on reasonable terms, if at all. In some cases, the technical skills required to manufacture our products or product candidates may be unique or proprietary to the original manufacturer and we may have difficulty, or there may be contractual restrictions prohibiting us from, transferring such skills to a back-up or alternate supplier, or we may be unable to transfer such skills at all. In addition, if we are required to change manufacturers for any reason, we will be required to verify that the new manufacturer maintains facilities and procedures that comply with quality standards and with all applicable regulations and guidelines. We will also need to verify, such as through a manufacturing comparability study, that any new manufacturing process will produce our product according to the specifications approved by FDA. The delays associated with the verification of a new manufacturer could negatively affect our ability to develop product candidates in a timely manner or within budget. Furthermore, a manufacturer may possess technology related to the manufacture of our product candidate that such manufacturer owns independently. This would increase our reliance on such manufacturer or require us to obtain a license from such manufacturer in order to have another third-party manufacture our products or product candidates.

We have no sales, marketing or distribution experience and would have to invest significant financial and management resources to establish these capabilities.

We have no sales, marketing or distribution experience. We currently expect to rely heavily on third parties to launch and market certain of our product candidates in certain geographies, if approved. However, we intend to commercialize the majority of our genetic medicine programs on our own in North America and Western Europe, and accordingly, we will need to develop internal sales, distribution and marketing capabilities as part of our core product strategy, which will require significant financial and management resources. For our genetic medicine programs where we will perform sales, marketing and distribution functions ourselves, we could face a number of additional risks, including:

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we may not be able to attract and build a significant marketing or sales force;

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the cost of establishing a marketing or sales force may not be justifiable in light of the revenues generated by any particular product; and

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our direct sales and marketing efforts may not be successful.

If we are unable to develop our own sales, marketing and distribution capabilities, we will not be able to successfully commercialize our genetic medicine programs without reliance on third parties.

The current credit and financial market conditions may exacerbate certain risks affecting our business.

Due to the tightening of global credit, there may be a disruption or delay in the performance of our third-party contractors, suppliers or collaborators. We rely on third parties for several important aspects of our business, including significant portions of our manufacturing needs, development of product candidates and conduct of clinical trials. If such third parties are unable to satisfy their commitments to us, our business could be adversely affected.

Risks Related to Managing Our Operations

If we are unable to attract and retain qualified key management and scientists, staff, consultants and advisors, our ability to implement our business plan may be adversely affected.

We are highly dependent upon our senior management and scientific staff. The loss of the service of any of the members of our senior management, including Dr. John Maraganore, our Chief Executive Officer, may significantly delay or prevent the achievement of product development and other business objectives. Our employment agreements with our key personnel are terminable without notice. We do not carry key man life insurance on any of our employees.

We face intense competition for qualified individuals from numerous pharmaceutical and biotechnology companies, universities, governmental entities and other research institutions, many of which have substantially greater resources with which to reward qualified individuals than we do. We may be unable to attract and retain suitably qualified individuals, and our failure to do so could have an adverse effect on our ability to implement our future business plan.

We may have difficulty expanding our operations successfully as we evolve from a company primarily involved in discovery and pre-clinical testing into one that develops and commercializes drugs.

We expect that as we increase the number of product candidates we are developing we will also need to expand our operations. This expected growth may place a strain on our administrative and operational infrastructure. As product candidates we develop enter and advance through clinical trials, we will need to expand our development, regulatory, manufacturing, marketing and sales capabilities or contract with other organizations to provide these capabilities for us. As our operations expand due to our development progress, we expect that we will need to manage additional relationships with various collaborators, suppliers and other organizations. Our ability to manage our operations and future growth will require us to continue to improve our operational, financial and management controls, reporting systems and procedures. We may not be able to implement improvements to our management information and control systems in an efficient or timely manner and may discover deficiencies in existing systems and controls.

Our business and operations could suffer in the event of system failures.

Despite the implementation of security measures, our internal computer systems and those of our contractors and consultants are vulnerable to damage from computer viruses, unauthorized access, natural disasters, terrorism, war, and telecommunication and electrical failures. Such events could cause interruption of our operations. For example, the loss of pre-clinical trial data or data from completed or ongoing clinical trials for our product candidates could result in delays in our regulatory filings and development efforts and significantly increase our costs. To the extent that any disruption or security breach were to result in a loss of or damage to our data, or inappropriate disclosure of confidential or proprietary information, we could incur liability and the development of our product candidates could be delayed.

Risks Related to Our Industry

Risks Related to Development, Clinical Testing and Regulatory Approval of Our Product Candidates

Any product candidates we develop may fail in development or be delayed to a point where they do not become commercially viable.

Before obtaining regulatory approval for the commercial distribution of our product candidates, we must conduct, at our own expense, extensive pre-clinical tests and clinical trials to demonstrate the safety and efficacy in humans of our product candidates. Pre-clinical and clinical testing is expensive, difficult to design and implement, can take many years to complete and is uncertain as to outcome, and the historical failure rate for product candidates is high. We currently have several programs in clinical development, including patisiran in a Phase 3 clinical trial, ALN-TTRsc in a Phase 2 clinical trial and ALN-AT3 in a Phase 1 clinical trial. We have also conducted Phase 1 clinical trials for ALN-PCS02 and ALN-VSP, and Phase 1 and 2 clinical trials for ALN-RSV. However, we may not be able to further advance these or any other product candidate through clinical trials.

If we enter into clinical trials, the results from pre-clinical testing or early clinical trials of a product candidate may not predict the results that will be obtained in subsequent human clinical trials of that product candidate or any other product candidate. For example, patisiran and ALN-TTRsc employ novel delivery formulations that have yet to be extensively evaluated in human clinical trials and proven safe and effective. We, the FDA or other applicable regulatory authorities, or an institutional review board, or IRB, or similar foreign review board or committee, may suspend clinical trials of a product candidate at any time for various reasons, including if we or they believe the subjects or patients participating in such trials are being exposed to unacceptable health risks. Among other reasons, adverse side effects of a product candidate on subjects or patients in a clinical trial could result in the FDA or foreign regulatory authorities suspending or terminating the trial and refusing to approve a particular product candidate for any or all indications of use.

Clinical trials of a new product candidate require the enrollment of a sufficient number of patients, including patients who are suffering from the disease the product candidate is intended to treat and who meet other eligibility criteria. Rates of patient enrollment are affected by many factors, including the size of the patient population, the age and condition of the patients, the stage and severity of disease, the nature of the protocol, the proximity of patients to clinical sites, the availability of effective treatments for the relevant disease, and the eligibility criteria for the clinical trial. For example, we may experience difficulty enrolling our clinical trials, including, but not limited to, our clinical trials for patisiran, due to the small population of ATTR patients suffering from FAP and the availability of existing approved treatments, as well as other investigational treatments in development. Although our RNAi therapeutics have been generally well tolerated in our clinical trials to date, in our ALN-VSP clinical trial, one patient with advanced pancreatic neuroendocrine cancer with extensive involvement of the liver developed hepatic failure five days following the second

dose of ALN-VSP and subsequently died; this was deemed possibly related to the study drug. In addition, in our ALN-VSP and ALN-TTR01 Phase 1 clinical trials, we have reported an incidence of acute infusion reactions occurring in 15-20% of patients. These were graded as mild or moderate in severity and readily responded to slowing of the infusion rate; all patients completed dosing without further incident. The frequency of acute infusion reactions in our ALN-PCS02 and patisiran Phase 1 clinical trials has been less than three percent. In our ALN-PCS02 Phase 1 clinical trial, we reported the occurrence of a mild, transient rash that was observed in sixteen subjects, including four who received placebo; the incidence of this finding was the same in both placebo and drug treatment arms. In our ALN-TTRsc clinical trial, we observed injection site reactions in a minority of subjects receiving ALN-TTRsc or placebo. These were reported as being clinically mild and consisted of transient erythema associated in a minority of cases with edema and/or pain. In all cases, these reactions were self-limiting and resolved within approximately two hours of onset. Delays or difficulties in patient enrollment or difficulties retaining trial participants, including as a result of the availability of existing or other investigational treatments or the occurrence of adverse events, can result in increased costs, longer development times or termination of a clinical trial.

Clinical trials also require the review, oversight and approval of IRBs, which continually review clinical investigations and protect the rights and welfare of human subjects. Inability to obtain or delay in obtaining IRB approval can prevent or delay the initiation and completion of clinical trials, and the FDA or foreign regulatory authorities may decide not to consider any data or information derived from a clinical investigation not subject to initial and continuing IRB review and approval in support of a marketing application.

Our product candidates that we develop may encounter problems during clinical trials that will cause us, an IRB or regulatory authorities to delay, suspend or terminate these trials, or that will delay or confound the analysis of data from these trials. If we experience any such problems, we may not have the financial resources to continue development of the product candidate that is affected, or development of any of our other product candidates. We may also lose, or be unable to enter into, collaborative arrangements for the affected product candidate and for other product candidates we are developing.

A failure of one or more of our clinical trials can occur at any stage of testing. We may experience numerous unforeseen events during, or as a result of, pre-clinical testing and the clinical trial process that could delay or prevent regulatory approval or our ability to commercialize our product candidates, including:

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our pre-clinical tests or clinical trials may produce negative or inconclusive results, and we may decide, or regulators may require us, to conduct additional pre-clinical testing or clinical trials, or we may abandon projects that we expect to be promising;

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delays in filing INDs or comparable foreign applications or delays or failure in obtaining the necessary approvals from regulators or IRBs in order to commence a clinical trial at a prospective trial site, or their suspension or termination of a clinical trial once commenced;

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conditions imposed on us by the FDA or comparable foreign authorities regarding the scope or design of our clinical trials;

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problems in engaging IRBs to oversee clinical trials or problems in obtaining or maintaining IRB approval of trials;

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delays in enrolling patients and volunteers into clinical trials, and variability in the number and types of patients and volunteers available for clinical trials;

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high drop-out rates for patients and volunteers in clinical trials;

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negative or inconclusive results from our clinical trials or the clinical trials of others for product candidates similar to ours;

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inadequate supply or quality of product candidate materials or other materials necessary for the conduct of our clinical trials;

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greater than anticipated clinical trial costs;

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serious and unexpected drug-related side effects experienced by participants in our clinical trials or by individuals using drugs similar to our product candidates;

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poor effectiveness of our product candidates during clinical trials;

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unfavorable FDA or other regulatory agency inspection and review of a clinical trial site or records of any clinical or pre-clinical investigation;

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failure of our third-party contractors or investigators to comply with regulatory requirements or otherwise meet their contractual obligations in a timely manner, or at all;

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governmental or regulatory delays and changes in regulatory requirements, policy and guidelines, including the imposition of additional regulatory oversight around clinical testing generally or with respect to our technology in particular; or

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varying interpretations of data by the FDA and similar foreign regulatory agencies.

Even if we successfully complete clinical trials of our product candidates, any given product candidate may not prove to be a safe and effective treatment for the diseases for which it was being tested.

We may be unable to obtain United States or foreign regulatory approval and, as a result, unable to commercialize our product candidates.

Our product candidates are subject to extensive governmental regulations relating to, among other things, research, testing, development, manufacturing, safety, efficacy, approval, recordkeeping, reporting, labeling, storage, packaging, advertising and promotion, pricing, marketing and distribution of drugs. Rigorous pre-clinical testing and clinical trials and an extensive regulatory approval process are required to be successfully completed in the United States and in many foreign jurisdictions before a new drug can be marketed. Satisfaction of these and other regulatory requirements is costly, time consuming, uncertain and subject to unanticipated delays. It is possible that none of the product candidates we may develop will obtain the regulatory approvals necessary for us or our collaborators to begin selling them.

We have limited experience in conducting and managing the clinical trials necessary to obtain regulatory approvals, including approval by the FDA. The time required to obtain FDA and other approvals is unpredictable but typically takes many years following the commencement of clinical trials, depending upon the type, complexity and novelty of the product candidate. The standards that the FDA and its foreign counterparts use when regulating us are not always applied predictably or uniformly and can change. Any analysis we perform of data from pre-clinical and clinical activities is subject to confirmation and interpretation by regulatory authorities, which could delay, limit or prevent regulatory approval. We may also encounter unexpected delays or increased costs due to new government regulations, for example, from future legislation or administrative action, or from changes in FDA policy during the period of product development, clinical trials and FDA regulatory review. It is impossible to predict whether legislative changes will be enacted, or whether FDA or foreign regulations, guidance or interpretations will be changed, or what the impact of such changes, if any, may be.

Because the drugs we are developing may represent a new class of drug, the FDA and its foreign counterparts have not yet established any definitive policies, practices or guidelines in relation to these drugs. While we believe the product candidates that we are currently developing are regulated as new drugs under the Federal Food, Drug, and Cosmetic Act, the FDA could decide to regulate them or other products we may develop as biologics under the Public Health Service Act. The lack of policies, practices or guidelines may hinder or slow review by the FDA of any regulatory filings that we may submit. Moreover, the FDA may respond to these submissions by defining requirements we may not have anticipated. Such responses could lead to significant delays in the clinical development of our product candidates. In addition, because there may be approved treatments for some of the diseases for which we may seek approval, in order to receive regulatory approval, we may need to demonstrate through clinical trials that the product candidates we develop to treat these diseases, if any, are not only safe and effective, but safer or more effective than existing products. Furthermore, in recent years, there has been increased public and political pressure on the FDA with respect to the approval process for new drugs, and the FDA’s standards, especially regarding drug safety, appear to have become more stringent.

Any delay or failure in obtaining required approvals could have a material adverse effect on our ability to generate revenues from the particular product candidate for which we are seeking approval. Furthermore, any regulatory approval to market a product may be subject to limitations on the approved uses for which we may market the product or the labeling or other restrictions. In addition, the FDA has the authority to require a Risk Evaluation and Mitigation Strategy, or REMS, plan as part of a new drug application, or NDA, or biologics license application, or BLA, or after approval, which may impose further requirements or restrictions on the distribution or use of an approved drug or biologic, such as limiting prescribing to certain physicians or medical centers that have undergone specialized training, limiting treatment to patients who meet certain safe-use criteria and requiring treated patients to enroll in a registry. These limitations and restrictions may limit the size of the market for the product and affect reimbursement by third-party payors.

We are also subject to numerous foreign regulatory requirements governing, among other things, the conduct of clinical trials, manufacturing and marketing authorization, pricing and third-party reimbursement. The foreign regulatory approval process varies among countries and includes all of the risks associated with FDA approval described above as well as risks attributable to the satisfaction of local regulations in foreign jurisdictions. Approval by the FDA does not ensure approval by regulatory authorities outside the United States and vice versa.

Even if we obtain regulatory approvals, our marketed drugs will be subject to ongoing regulatory review. If we fail to comply with continuing U.S. and foreign requirements, our approvals could be limited or withdrawn, we could be subject to other penalties, and our business would be seriously harmed.

Following any initial regulatory approval of any drugs we may develop, we will also be subject to continuing regulatory review, including the review of adverse drug experiences and clinical results that are reported after our drug products are made commercially available. This would include results from any post-marketing tests or surveillance to monitor the safety and efficacy of the drug product required as a condition of approval or agreed to by us. Any regulatory approvals that we receive for our product candidates may also be subject to limitations on the approved uses for which the product may be marketed. Other ongoing regulatory requirements include, among other things, submissions of safety and other post-marketing information and reports, registration and listing, as well as continued compliance with cGMP requirements and good clinical practices for any clinical trials that we conduct post-approval. In addition, we are conducting, and intend to continue to conduct, clinical trials for our product candidates, and we intend to seek approval to market our product candidates, in jurisdictions outside of the United States, and therefore will be subject to, and must comply with, regulatory requirements in those jurisdictions.

The FDA has significant post-market authority, including, for example, the authority to require labeling changes based on new safety information and to require post-market studies or clinical trials to evaluate serious safety risks related to the use of a drug and to require withdrawal of the product from the market. The FDA also has the authority to require a REMS plan after approval, which may impose further requirements or restrictions on the distribution or use of an approved drug.

The manufacturer and manufacturing facilities we use to make any of our product candidates, including our Cambridge facility, will also be subject to periodic review and inspection by the FDA and other regulatory agencies. To date, our manufacturing facility has not been subject to an inspection by any regulatory authority. The discovery of any new or previously unknown problems with us or our third-party manufacturers, or our or their manufacturing processes or facilities, may result in restrictions on the drug or manufacturer or facility, including withdrawal of the drug from the market. We have recently developed cGMP capabilities and processes for the manufacture of patisiran for Phase 3 clinical and early commercial use. We may not have the ability to manufacture material for a broader commercial scale in the future. We may manufacture clinical trial materials or we may contract a third party to manufacture these materials for us. Reliance on third-party manufacturers entails risks to which we would not be subject if we manufactured products ourselves, including reliance on the third-party manufacturer for regulatory compliance. We will not have control over our third-party manufacturers’ compliance with applicable rules and regulations. Our product promotion and advertising will also be subject to regulatory requirements and continuing regulatory review.

If we or our collaborators, manufacturers or service providers fail to comply with applicable continuing regulatory requirements in the United States or foreign jurisdictions in which we may seek to market our products, we or they may be subject to, among other things, fines, warning letters, holds on clinical trials, refusal by the FDA to approve pending applications or supplements to approved applications, suspension or withdrawal of regulatory approval, product recalls and seizures, refusal to permit the import or export of products, operating restrictions, injunction, civil penalties and criminal prosecution.

Even if we receive regulatory approval to market our product candidates, the market may not be receptive to our product candidates upon their commercial introduction, which will prevent us from becoming profitable.

The product candidates that we are developing are based upon new technologies or therapeutic approaches. Key participants in pharmaceutical marketplaces, such as physicians, third-party payors and consumers, may not accept a product intended to improve therapeutic results based on RNAi technology. As a result, it may be more difficult for us to convince the medical community and third-party payors to accept and use our product, or to provide favorable reimbursement.

Other factors that we believe will materially affect market acceptance of our product candidates include:

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the timing of our receipt of any marketing approvals, the terms of any approvals and the countries in which approvals are obtained;

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the safety and efficacy of our product candidates, as demonstrated in clinical trials;

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relative convenience and ease of administration of our product candidates;

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the willingness of patients to accept potentially new routes of administration;

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the success of our physician education programs;

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the availability of adequate government and third-party payor reimbursement;

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the pricing of our products, particularly as compared to alternative treatments; and

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availability of alternative effective treatments for the diseases that product candidates we develop are intended to treat and the relative risks, benefits and costs of the treatments.

In addition, our estimates regarding the potential market size may be materially different from what we currently expect at the time we commence commercialization, which could result in significant changes in our business plan and may have a material adverse effect on our results of operations and financial condition.

If we or our collaborators, manufacturers or service providers fail to comply with healthcare laws and regulations, we or they could be subject to enforcement actions, which could affect our ability to develop, market and sell our products and may harm our reputation.

As a manufacturer of pharmaceuticals, we are subject to federal, state, and foreign healthcare laws and regulations pertaining to fraud and abuse and patients’ rights. These laws and regulations include:

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the U.S. federal healthcare program anti-kickback law, which prohibits, among other things, persons from soliciting, receiving or providing remuneration, directly or indirectly, to induce either the referral of an individual for a healthcare item or service, or the purchasing or ordering of an item or service, for which payment may be made under a federal healthcare program such as Medicare or Medicaid;

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the U.S. federal false claims law, which prohibits, among other things, individuals or entities from knowingly presenting or causing to be presented, claims for payment by government funded programs such as Medicare or Medicaid that are false or fraudulent, and which may apply to us by virtue of statements and representations made to customers or third parties;

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the U.S. federal Health Insurance Portability and Accountability Act, or HIPAA, and Health Information Technology for Economic and Clinical Health, or HITECH, Act, which impose requirements relating to the privacy, security, and transmission of individually identifiable health information; and require notification to affected individuals and regulatory authorities of certain breaches of security of individually identifiable health information;

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the U.S. federal Open Payments requirements under the National Physician Payment Transparency Program require that manufacturers of pharmaceutical and biological drugs covered by Medicare, Medicaid and Children’s Health Insurance Programs report all consulting fees, travel reimbursements, research grants, and other payments or gifts with values over $10 made to physicians and teaching hospitals;

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pharmaceutical manufacturers are required to track certain financial arrangements with physicians and teaching hospitals, including any “transfer of value” made or distributed to such entities, as well as any investment interests held by physicians and their immediate family members. Manufacturers were required by the Patient Protection and Affordable Care Act, or PPACA, to begin tracking this information in 2013 and to report this information to The Centers for Medicare and Medicaid Services, or CMS, beginning in 2014; and

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state laws comparable to each of the above federal laws, such as, for example, anti-kickback and false claims laws applicable to commercial insurers and other non-federal payors, requirements for mandatory corporate regulatory compliance programs, and laws relating to patient data privacy and security.

If our operations are found to be in violation of any such requirements, we may be subject to penalties, including civil or criminal penalties, monetary damages, the curtailment or restructuring of our operations, loss of eligibility to obtain approvals from the FDA, or exclusion from participation in government contracting, healthcare reimbursement or other government programs, including Medicare and Medicaid, any of which could adversely our financial results. Although effective compliance programs can mitigate the risk of investigation and prosecution for violations of these laws, these risks cannot be entirely eliminated. Any action against us for an alleged or suspected violation could cause us to incur significant legal expenses and could divert our management’s attention from the operation of our business, even if our defense is successful. In addition, achieving and sustaining compliance with applicable laws and regulations may be costly to us in terms of money, time and resources.

If we or our collaborators, manufacturers or service providers fail to comply with applicable federal, state or foreign laws or regulations, we could be subject to enforcement actions, which could affect our ability to develop, market and sell our products successfully and could harm our reputation and lead to reduced acceptance of our products by the market. These enforcement actions include, among others:

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adverse regulatory inspection findings;

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warning letters;

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voluntary or mandatory product recalls or public notification or medical product safety alerts to healthcare professionals;

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restrictions on, or prohibitions against, marketing our products;

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restrictions on, or prohibitions against, importation or exportation of our products;

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suspension of review or refusal to approve pending applications or supplements to approved applications;

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exclusion from participation in government-funded healthcare programs;

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exclusion from eligibility for the award of government contracts for our products;

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suspension or withdrawal of product approvals;

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product seizures;

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injunctions; and

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civil and criminal penalties and fines.

Moreover, federal, state or foreign laws or regulations are subject to change, and while we, our collaborators, manufacturers and/or service providers currently may be compliant, that could change due to changes in interpretation, prevailing industry standards or the legal structure.

Any drugs we develop may become subject to unfavorable pricing regulations, third-party reimbursement practices or healthcare reform initiatives, thereby harming our business.

The regulations that govern marketing approvals, pricing and reimbursement for new drugs vary widely from country to country. Some countries require approval of the sale price of a drug before it can be marketed. In many countries, the pricing review period begins after marketing or product licensing approval is granted. In some foreign markets, prescription pharmaceutical pricing remains subject to continuing governmental control even after initial approval is granted. Although we intend to monitor these regulations, most of our programs are currently in the earlier stages of development and we will not be able to assess the impact of price regulations for a number of years. As a result, we might obtain regulatory approval for a product in a particular country, but then be subject to price regulations that delay our commercial launch of the product and negatively impact the revenues we are able to generate from the sale of the product in that country.

Our ability to commercialize any products successfully also will depend in part on the extent to which reimbursement for these products and related treatments will be available from government health administration authorities, private health insurers and other organizations. Even if we succeed in bringing one or more products to the market, these products may not be considered cost-effective, and the amount reimbursed for any products may be insufficient to allow us to sell our products on a competitive basis. Because most of our programs are in the earlier stages of development, we are unable at this time to determine their cost effectiveness or the likely level or method of reimbursement. Increasingly, the third-party payors who reimburse patients or healthcare providers, such as government and private insurance plans, are requiring that drug companies provide them with predetermined discounts from list prices, and are seeking to reduce the prices charged or the amounts reimbursed for pharmaceutical products. If the price we are able to charge for any products we develop, or the reimbursement provided for such products, is inadequate in light of our development and other costs, our return on investment could be adversely affected.

We currently expect that any drugs we develop may need to be administered under the supervision of a physician on an outpatient basis. Under currently applicable U.S. law, certain drugs that are not usually self-administered (including injectable drugs) may be eligible for coverage under the Medicare Part B program if:

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they are incident to a physician’s services;

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they are reasonable and necessary for the diagnosis or treatment of the illness or injury for which they are administered according to accepted standards of medical practice; and

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they have been approved by the FDA and meet other requirements of the statute.

There may be significant delays in obtaining coverage for newly-approved drugs, and coverage may be more limited than the purposes for which the drug is approved by the FDA. Moreover, eligibility for coverage does not imply that any drug will be reimbursed in all cases or at a rate that covers our costs, including research, development, manufacture, sale and distribution. Interim payments for new drugs, if applicable, may also not be sufficient to cover our costs and may not be made permanent. Reimbursement may be based on payments allowed for lower-cost drugs that are already reimbursed, may be incorporated into existing payments for other services and may reflect budgetary constraints or imperfections in Medicare data. Net prices for drugs may be reduced by mandatory discounts or rebates required by government healthcare programs or private payors and by any future relaxation of laws

that presently restrict imports of drugs from countries where they may be sold at lower prices than in the United States. Third-party payors often rely upon Medicare coverage policy and payment limitations in setting their own reimbursement rates. Our inability to promptly obtain coverage and adequate reimbursement rates from both government-funded and private payors for new drugs that we develop and for which we obtain regulatory approval could have a material adverse effect on our operating results, our ability to raise capital needed to commercialize products, and our overall financial condition.

We believe that the efforts of governments and third-party payors to contain or reduce the cost of healthcare and legislative and regulatory proposals to broaden the availability of healthcare will continue to affect the business and financial condition of pharmaceutical and biopharmaceutical companies. A number of legislative and regulatory changes in the healthcare system in the United States and other major healthcare markets have been proposed in recent years, and such efforts have expanded substantially in recent years. These developments have included prescription drug benefit legislation that was enacted and took effect in January 2006, healthcare reform legislation enacted by certain states, and major healthcare reform legislation that was passed by Congress and enacted into law in the United States in 2010. These developments could, directly or indirectly, affect our ability to sell our products, if approved, at a favorable price.

In particular, in March 2010, the PPACA was signed into law. This new legislation changes the current system of healthcare insurance and benefits intended to broaden coverage and control costs. The new law also contains provisions that will affect companies in the pharmaceutical industry and other healthcare related industries by imposing additional costs and changes to business practices. Provisions affecting pharmaceutical companies include the following:

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Mandatory rebates for drugs sold into the Medicaid program have been increased, and the rebate requirement has been extended to drugs used in risk-based Medicaid managed care plans.

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The 340B Drug Pricing Program under the Public Health Services Act has been extended to require mandatory discounts for drug products sold to certain critical access hospitals, cancer hospitals and other covered entities.

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Pharmaceutical companies are required to offer discounts on brand-name drugs to patients who fall within the Medicare Part D coverage gap, commonly referred to as the “Donut Hole.”

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Pharmaceutical companies are required to pay an annual non-tax deductible fee to the federal government based on each company’s market share of prior year total sales of branded products to certain federal healthcare programs, such as Medicare, Medicaid, Department of Veterans Affairs and Department of Defense. Since we expect our branded pharmaceutical sales to constitute a small portion of the total federal health program pharmaceutical market, we do not expect this annual assessment to have a material impact on our financial condition.

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The new law provides that approval of an application for a follow-on biologic product may not become effective until 12 years after the date on which the reference innovator biologic product was first licensed by the FDA, with a possible six-month extension for pediatric products. After this exclusivity ends, it will be easier for generic manufacturers to enter the market, which is likely to reduce the pricing for such products and could affect our profitability.

The full effects of the U.S. healthcare reform legislation cannot be known until the new law is fully implemented through regulations or guidance issued by the CMS and other federal and state healthcare agencies. The financial impact of the U.S. healthcare reform legislation over the next few years will depend on a number of factors, including but not limited, to the policies reflected in implementing regulations and guidance, and changes in sales volumes for products affected by the new system of rebates, discounts and fees. The new legislation may also have a positive impact on our future net sales, if any, by increasing the aggregate number of persons with healthcare coverage in the United States.

Moreover, we cannot predict what healthcare reform initiatives may be adopted in the future. Further federal and state legislative and regulatory developments are likely, and we expect ongoing initiatives in the United States to increase pressure on drug pricing. Such reforms could have an adverse effect on anticipated revenues from product candidates that we may successfully develop and for which we may obtain regulatory approval and may affect our overall financial condition and ability to develop drug candidates.

Our ability to obtain services, reimbursement or funding from the federal government may be impacted by possible reductions in federal spending.

Under the Budget Control Act of 2011, the failure of Congress to enact deficit reduction measures of at least $1.2 trillion for the years 2013 through 2021 triggered automatic cuts to most federal programs. These cuts included aggregate reductions to Medicare payments to providers of up to 2% per fiscal year, starting in 2013. Under the American Taxpayer Relief Act of 2012, which was enacted on January 1, 2013, the imposition of these automatic cuts was delayed until March 1, 2013. As required by law, President Obama issued a sequestration order on March 1, 2013. Certain of these automatic cuts have been implemented resulting in reductions in Medicare payments to physicians, hospitals, and other healthcare providers, among other things. The full impact on our business of these automatic cuts is uncertain.

If other federal spending is reduced, any budgetary shortfalls may also impact the ability of relevant agencies, such as the FDA or NIH to continue to function. Amounts allocated to federal grants and contracts may be reduced or eliminated. These reductions may also impact the ability of relevant agencies to timely review and approve drug research and development, manufacturing, and marketing activities, which may delay our ability to develop, market and sell any products we may develop.

There is a substantial risk of product liability claims in our business. If we are unable to obtain sufficient insurance, a product liability claim against us could adversely affect our business.

Our business exposes us to significant potential product liability risks that are inherent in the development, testing, manufacturing and marketing of human therapeutic products. Product liability claims could delay or prevent completion of our clinical development programs. If we succeed in marketing products, such claims could result in an FDA investigation of the safety and effectiveness of our products, our manufacturing processes and facilities or our marketing programs, and potentially a recall of our products or more serious enforcement action, limitations on the approved indications for which they may be used, or suspension or withdrawal of approvals. Regardless of the merits or eventual outcome, liability claims may also result in decreased demand for our products, injury to our reputation, costs to defend the related litigation, a diversion of management’s time and our resources, substantial monetary awards to trial participants or patients and a decline in our stock price. We currently have product liability insurance that we believe is appropriate for our stage of development and may need to obtain higher levels prior to marketing any of our product candidates. Any insurance we have or may obtain may not provide sufficient coverage against potential liabilities. Furthermore, clinical trial and product liability insurance is becoming increasingly expensive. As a result, we may be unable to obtain sufficient insurance at a reasonable cost to protect us against losses caused by product liability claims that could have a material adverse effect on our business.

If we do not comply with laws regulating the protection of the environment and health and human safety, our business could be adversely affected.

Our research, development and manufacturing involves the use of hazardous materials, chemicals and various radioactive compounds. We maintain quantities of various flammable and toxic chemicals in our facilities in Cambridge that are required for our research, development and manufacturing activities. We are subject to federal, state and local laws and regulations governing the use, manufacture, storage, handling and disposal of these hazardous materials. We believe our procedures for storing, handling and disposing these materials in our Cambridge facilities comply with the relevant guidelines of the City of Cambridge, the Commonwealth of Massachusetts and the Occupational Safety and Health Administration of the U.S. Department of Labor. Although we believe that our safety procedures for handling and disposing of these materials comply with the standards mandated by applicable regulations, the risk of accidental contamination or injury from these materials cannot be eliminated. If an accident occurs, we could be held liable for resulting damages, which could be substantial. We are also subject to numerous environmental, health and workplace safety laws and regulations, including those governing laboratory procedures, exposure to blood-borne pathogens and the handling of biohazardous materials.

Although we maintain workers’ compensation insurance to cover us for costs and expenses we may incur due to injuries to our employees resulting from the use of these materials, this insurance may not provide adequate coverage against potential liabilities. We do not maintain insurance for environmental liability or toxic tort claims that may be asserted against us in connection with our storage or disposal of biological, hazardous or radioactive materials. Additional federal, state and local laws and regulations affecting our operations may be adopted in the future. We may incur substantial costs to comply with, and substantial fines or penalties if we violate, any of these laws or regulations.

Risks Related to Patents, Licenses and Trade Secrets

If we are not able to obtain and enforce patent protection for our discoveries, our ability to develop and commercialize our product candidates will be harmed.

Our success depends, in part, on our ability to protect proprietary methods and technologies that we develop under the patent and other intellectual property laws of the United States and other countries, so that we can prevent others from unlawfully using our inventions and proprietary information. However, we may not hold proprietary rights to some patents required for us to commercialize our proposed products. Because certain U.S. patent applications are confidential until the patents issue, such as applications filed prior to November 29, 2000, or applications filed after such date which will not be filed in foreign countries, third parties may have filed patent applications for technology covered by our pending patent applications without our being aware of those applications, and our patent applications may not have priority over those applications. For this and other reasons, we may be unable to secure desired patent rights, thereby losing desired exclusivity. Further, we may be required to obtain licenses under third-party patents to market our proposed products or conduct our research and development or other activities. If licenses are not available to us on acceptable terms, we will not be able to market the affected products or conduct the desired activities.

Our strategy depends on our ability to rapidly identify and seek patent protection for our discoveries. In addition, we may rely on third-party collaborators to file patent applications relating to proprietary technology that we develop jointly during certain collaborations. The process of obtaining patent protection is expensive and time-consuming. If our present or future collaborators fail to file and prosecute all necessary and desirable patent applications at a reasonable cost and in a timely manner, our business will be adversely affected. Despite our efforts and the efforts of our collaborators to protect our proprietary rights, unauthorized parties may be able to obtain and use information that we regard as proprietary. While issued patents are presumed valid, this does not guarantee that the patent will survive a validity challenge or be held enforceable. Any patents we have obtained, or obtain in the future, may be challenged, invalidated, adjudged unenforceable or circumvented by parties attempting to design around our intellectual property. Moreover, third parties or the United States Patent and Trademark Office, or USPTO, may commence interference proceedings involving our patents or patent applications. Any challenge to, finding of unenforceability or invalidation or circumvention of, our patents or patent applications, would be costly, would require significant time and attention of our management and could have a material adverse effect on our business.

Our pending patent applications may not result in issued patents. The patent position of pharmaceutical or biotechnology companies, including ours, is generally uncertain and involves complex legal and factual considerations. The standards that the USPTO and its foreign counterparts use to grant patents are not always applied predictably or uniformly and can change. Similarly, the ultimate degree of protection that will be afforded to biotechnology inventions, including ours, in the United States and foreign countries, remains uncertain and is dependent upon the scope of the protection decided upon by patent offices, courts and lawmakers. Moreover, there are periodic discussions in the Congress of the United States and in international jurisdictions about modifying various aspects of patent law. For example, the America Invents Act includes a number of changes to the patent laws of the United States. If any of the enacted changes do not provide adequate protection for discoveries, including our ability to pursue infringers of our patents for substantial damages, our business could be adversely affected. One major provision of the America Invents Act, which took effect in March 2013, changed United States patent practice from a first-to-invent to a first-to-file system. If we fail to file an invention before a competitor files on the same invention, we no longer have the ability to provide proof that we were in possession of the invention prior to the competitor’s filing date, and thus would not be able to obtain patent protection for our invention. There is also no uniform, worldwide policy regarding the subject matter and scope of claims granted or allowable in pharmaceutical or biotechnology patents.

Accordingly, we do not know the degree of future protection for our proprietary rights or the breadth of claims that will be allowed in any patents issued to us or to others. We also rely to a certain extent on trade secrets, know-how and technology, which are not protected by patents, to maintain our competitive position. If any trade secret, know-how or other technology not protected by a patent were to be disclosed to or independently developed by a competitor, our business and financial condition could be materially adversely affected.

We license patent rights from third-party owners. If such owners do not properly or successfully obtain, maintain or enforce the patents underlying such licenses, our competitive position and business prospects will be harmed.

We are a party to a number of licenses that give us rights to third-party intellectual property that is necessary or useful for our business. In particular, we have obtained licenses from, among others, CRT, Isis, MIT, Whitehead, Max Planck Innovation, Tekmira and Arrowhead. We also intend to enter into additional licenses to third-party intellectual property in the future.

Our success will depend in part on the ability of our licensors to obtain, maintain and enforce patent protection for our licensed intellectual property, in particular, those patents to which we have secured exclusive rights. Our licensors may not successfully prosecute the patent applications to which we are licensed. Even if patents issue in respect of these patent applications, our licensors may fail to maintain these patents, may determine not to pursue litigation against other companies that are infringing these patents, or may pursue such litigation less aggressively than we would. Without protection for the intellectual property we license, other companies might be able to offer substantially identical products for sale, which could adversely affect our competitive business position and harm our business prospects. In addition, we sublicense our rights under various third-party licenses to our collaborators. Any impairment of these sublicensed rights could result in reduced revenues under our collaboration agreements or result in termination of an agreement by one or more of our collaborators.

Other companies or organizations may challenge our patent rights or may assert patent rights that prevent us from developing and commercializing our products.

RNAi is a relatively new scientific field, the commercial exploitation of which has resulted in many different patents and patent applications from organizations and individuals seeking to obtain patent protection in the field. We have obtained grants and issuances of RNAi patents and have licensed many of these patents from third parties on an exclusive basis. The issued patents and pending patent applications in the United States and in key markets around the world that we own or license claim many different methods, compositions and processes relating to the discovery, development, manufacture and commercialization of RNAi therapeutics.

Specifically, we have a portfolio of patents, patent applications and other intellectual property covering: fundamental aspects of the structure and uses of siRNAs, including their manufacture and use as therapeutics, and RNAi-related mechanisms; chemical modifications to siRNAs that improve their suitability for therapeutic uses; siRNAs directed to specific targets as treatments for particular diseases; and delivery technologies, such as in the field of cationic liposomes.

As the field of RNAi therapeutics is maturing, patent applications are being fully processed by national patent offices around the world. There is uncertainty about which patents will issue, and, if they do, as to when, to whom, and with what claims. It is likely that there will be significant litigation and other proceedings, such as interference, reexamination and opposition proceedings, in various patent offices relating to patent rights in the RNAi field. For example, various third parties have initiated oppositions to patents in our Kreutzer-Limmer and Tuschl II series in the European Patent Office, or EPO, and in other jurisdictions. We expect that additional oppositions will be filed in the EPO and elsewhere, and other challenges will be raised relating to other patents and patent applications in our portfolio. In many cases, the possibility of appeal exists for either us or our opponents, and it may be years before final, unappealable rulings are made with respect to these patents in certain jurisdictions. The timing and outcome of these and other proceedings is uncertain and may adversely affect our business if we are not successful in defending the patentability and scope of our pending and issued patent claims. In addition, third parties may attempt to invalidate our intellectual property rights. Even if our rights are not directly challenged, disputes could lead to the weakening of our intellectual property rights. Our defense against any attempt by third parties to circumvent or invalidate our intellectual property rights could be costly to us, could require significant time and attention of our management and could have a material adverse effect on our business and our ability to successfully compete in the field of RNAi.

There are many issued and pending patents that claim aspects of oligonucleotide chemistry and modifications that we may need to apply to our siRNA therapeutic candidates. There are also many issued patents that claim targeting genes or portions of genes that may be relevant for siRNA drugs we wish to develop. Thus, it is possible that one or more organizations will hold patent rights to which we will need a license. If those organizations refuse to grant us a license to such patent rights on reasonable terms, we may not be able to market products or perform research and development or other activities covered by these patents.

If we become involved in patent litigation or other proceedings related to a determination of rights, we could incur substantial costs and expenses, substantial liability for damages or be required to stop our product development and commercialization efforts.

Third parties may sue us for infringing their patent rights. Likewise, we may need to resort to litigation to enforce a patent issued or licensed to us or to determine the scope and validity of proprietary rights of others. In addition, a third party may claim that we have improperly obtained or used its confidential or proprietary information. For example, in March 2011, Tekmira filed a civil complaint against us alleging, among other things, misappropriation of the plaintiffs’ confidential and proprietary information and trade secrets. In November 2012, we settled this litigation and restructured our contractual relationship with Tekmira. In connection with this restructuring, we incurred a $65.0 million charge to operating expenses during the quarter ended December 31, 2012. In addition, during the pendency of the litigation, we incurred significant costs, and the defense of this litigation diverted the attention of our management and other resources that would otherwise have been engaged in other activities.

Furthermore, third parties may challenge the inventorship of our patents or licensed patents. For example, in March 2011, the University of Utah, or Utah, filed a complaint in the United States District Court for the District of Massachusetts against us, Max Planck Gesellschaft Zur Foerderung Der Wissenschaften e.V. and Max Planck Innovation, together, Max Planck, Whitehead, MIT and UMass, claiming that a professor of Utah is the sole inventor, or in the alternative, a joint inventor of certain of our in-licensed patents. The original complaint was not served on any of the parties and, in July 2011, Utah filed an amended complaint containing substantially the same claims as the original complaint against us, Max Planck, Whitehead, MIT and UMass. The amended complaint alleges the defendants have incorrectly determined inventorship of some of our in-licensed patents and further claims unjust enrichment, unfair competition, false advertising and seeks correction of inventorship, injunctive relief and unspecified damages. In October 2011, we, Max Planck, Whitehead, MIT and UMass filed a motion to dismiss and UMass filed a motion to dismiss on separate grounds, which we, Max Planck, Whitehead and MIT have joined. In December 2011, Utah filed a second amended complaint dropping UMass as a defendant and adding as defendants several UMass officials. In June 2012, the Court denied both motions to dismiss. We, Max Planck, Whitehead, MIT and UMass filed an appeal of the Court’s ruling on the motion to dismiss for lack of jurisdiction and a motion requesting that the Court stay the case pending the outcome of the appeal. In July 2012, the Court stayed discovery in the case pending the outcome of the defendants’ appeal. Oral arguments in the appeal were heard in early March 2013 in the United States Court of Appeals for the Federal Circuit, or CAFC. In August 2013, the CAFC affirmed the lower Court’s ruling, in a split decision. We believe the majority made an error in law when affirming the lower Court’s decision, and in September 2013, we filed a petition with the CAFC for rehearing or rehearing en banc . In October 2013, the CAFC invited Utah to file an

answer to the petition. In November 2013, the CAFC denied our petition for rehearing or rehearing en banc and remanded the case back to the lower Court. In February 2014, we filed a petition for writ of certiorari from the Supreme Court and a motion to stay the lower Court’ proceedings pending a decision from the Supreme Court on our petition. We are awaiting the Courts’ decisions. We intend to vigorously defend ourselves in this matter, however, litigation is subject to inherent uncertainty and a court could ultimately rule against us.

In addition, in connection with certain license and collaboration agreements, we have agreed to indemnify certain third parties for certain costs incurred in connection with litigation relating to intellectual property rights or the subject matter of the agreements. The cost to us of any litigation or other proceeding relating to intellectual property rights, even if resolved in our favor, could be substantial, and litigation would divert our management’s efforts. Some of our competitors may be able to sustain the costs of complex patent litigation more effectively than we can because they have substantially greater resources. Uncertainties resulting from the initiation and continuation of any litigation could delay our research and development efforts and limit our ability to continue our operations.

If any parties successfully claim that our creation or use of proprietary technologies infringes upon or otherwise violates their intellectual property rights, we might be forced to pay damages, potentially including treble damages, if we are found to have willfully infringed on such parties’ patent rights. In addition to any damages we might have to pay, a court could require us to stop the infringing activity or obtain a license. Any license required under any patent may not be made available on commercially acceptable terms, if at all. In addition, such licenses are likely to be non-exclusive and, therefore, our competitors may have access to the same technology licensed to us. If we fail to obtain a required license and are unable to design around a patent, we may be unable to effectively market some of our technology and products, which could limit our ability to generate revenues or achieve profitability and possibly prevent us from generating revenue sufficient to sustain our operations. Moreover, we expect that a number of our collaborations will provide that royalties payable to us for licenses to our intellectual property may be offset by amounts paid by our collaborators to third parties who have competing or superior intellectual property positions in the relevant fields, which could result in significant reductions in our revenues from products developed through collaborations.

If we fail to comply with our obligations under any licenses or related agreements, we may be required to pay damages and could lose license or other rights that are necessary for developing and protecting our RNAi technology and any related product candidates that we develop, or we could lose certain rights to grant sublicenses.

Our current licenses impose, and any future licenses we enter into are likely to impose, various development, commercialization, funding, milestone, royalty, diligence, sublicensing, insurance, patent prosecution and enforcement, and other obligations on us. If we breach any of these obligations, or use the intellectual property licensed to us in an unauthorized manner, we may be required to pay damages and the licensor may have the right to terminate the license or render the license non-exclusive, which could result in us being unable to develop, manufacture and sell products that are covered by the licensed technology or enable a competitor to gain access to the licensed technology. For example, Tekmira has notified us that it believes it has achieved a $5.0 million milestone payment under our cross-license agreement relating to the manufacture of ALN-VSP clinical trial material for use in China. We have notified Tekmira that we do not believe that the milestone has been achieved under the terms of the cross-license agreement. In August 2013, we initiated binding arbitration proceedings seeking a declaratory judgment that Tekmira has not yet met the conditions of the milestone and is not entitled to payment at this time. If it is determined through arbitration that Tekmira has met the requirements of the milestone, we will have to pay Tekmira the milestone.

Moreover, our licensors may own or control intellectual property that has not been licensed to us and, as a result, we may be subject to claims, regardless of their merit, that we are infringing or otherwise violating the licensor’s rights. In addition, while we cannot currently determine the amount of the royalty obligations we will be required to pay on sales of future products, if any, the amounts may be significant. The amount of our future royalty obligations will depend on the technology and intellectual property we use in products that we successfully develop and commercialize, if any. Therefore, even if we successfully develop and commercialize products, we may be unable to achieve or maintain profitability.

Confidentiality agreements with employees and others may not adequately prevent disclosure of trade secrets and other proprietary information.

In order to protect our proprietary technology and processes, we rely in part on confidentiality agreements with our collaborators, employees, consultants, outside scientific collaborators and sponsored researchers, and other advisors. These agreements may not effectively prevent disclosure of confidential information and may not provide an adequate remedy in the event of unauthorized disclosure of confidential information. In addition, others may independently discover trade secrets and proprietary information, and in such cases we could not assert any trade secret rights against such party. Costly and time-consuming litigation could be necessary to enforce and determine the scope of our proprietary rights, and failure to obtain or maintain trade secret protection could adversely affect our competitive business position.

Risks Related to Competition

The pharmaceutical market is intensely competitive. If we are unable to compete effectively with existing drugs, new treatment methods and new technologies, we may be unable to commercialize successfully any drugs that we develop.

The pharmaceutical market is intensely competitive and rapidly changing. Many large pharmaceutical and biotechnology companies, academic institutions, governmental agencies and other public and private research organizations are pursuing the development of novel drugs for the same diseases that we are targeting or expect to target. Many of our competitors have:

•

much greater financial, technical and human resources than we have at every stage of the discovery, development, manufacture and commercialization of products;

•

more extensive experience in pre-clinical testing, conducting clinical trials, obtaining regulatory approvals, and in manufacturing, marketing and selling pharmaceutical products;

•

product candidates that are based on previously tested or accepted technologies;

•

products that have been approved or are in late stages of development; and

•

collaborative arrangements in our target markets with leading companies and research institutions.

We will face intense competition from drugs that have already been approved and accepted by the medical community for the treatment of the conditions for which we may develop drugs. We also expect to face competition from new drugs that enter the market. We believe a significant number of drugs are currently under development, and may become commercially available in the future, for the treatment of conditions for which we may try to develop drugs. These drugs may be more effective, safer, less expensive, or marketed and sold more effectively, than any products we develop. For example, we are developing patisiran for the treatment of ATTR patients suffering from FAP. We are aware of other approved products used to treat this disease, as well as product candidates in various stages of clinical development. Patisiran may not compete favorably with these products and product candidates, and even if approved, it may not achieve commercial success.

If we successfully develop product candidates, and obtain approval for them, we will face competition based on many different factors, including:

•

the safety and effectiveness of our products;

•

the ease with which our products can be administered and the extent to which patients accept relatively new routes of administration;

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the timing and scope of regulatory approvals for these products;

•

the availability and cost of manufacturing, marketing and sales capabilities;

•

price;

•

reimbursement coverage; and

•

patent position.

Our competitors may develop or commercialize products with significant advantages over any products we develop based on any of the factors listed above or on other factors. Our competitors may therefore be more successful in commercializing their products than we are, which could adversely affect our competitive position and business. Competitive products may make any products we develop obsolete or noncompetitive before we can recover the expenses of developing and commercializing our product candidates. Such competitors could also recruit our employees, which could negatively impact our level of expertise and the ability to execute on our business plan. Furthermore, we also face competition from existing and new treatment methods that reduce or eliminate the need for drugs, such as the use of advanced medical devices. The development of new medical devices or other treatment methods for the diseases we are targeting could make our product candidates noncompetitive, obsolete or uneconomical.

We face competition from other companies that are working to develop novel drugs and technology platforms using technology similar to ours. If these companies develop drugs more rapidly than we do or their technologies, including delivery technologies, are more effective, our ability to successfully commercialize drugs may be adversely affected.

In addition to the competition we face from competing drugs in general, we also face competition from other companies working to develop novel drugs using technology that competes more directly with our own. We are aware of multiple companies that are working in the field of RNAi. In addition, we granted licenses or options for licenses to Isis, GeneCare Research Institute Co., Ltd., Benitec Ltd., Arrowhead and its subsidiary, Calando Pharmaceuticals, Inc., Tekmira, Quark Pharmaceuticals, Inc., Sylentis S.A.U. and others under which these companies may independently develop RNAi therapeutics against a limited number of targets. Any of these companies may develop its RNAi technology more rapidly and more effectively than us.

In addition, as a result of agreements that we have entered into, Arrowhead, as the assignee of Roche, and Takeda have obtained non-exclusive licenses, and Novartis has obtained specific exclusive licenses for 31 gene targets, to certain aspects of our technology that give them the right to compete with us in certain circumstances. We also compete with companies working to develop antisense-based drugs. Like RNAi therapeutics, antisense drugs target mRNAs, in order to suppress the activity of specific genes. Isis is currently marketing an antisense drug and has several antisense product candidates in clinical trials, including one for the treatment of ATTR. The development of antisense drugs is more advanced than that of RNAi therapeutics, and antisense technology may become the preferred technology for drugs that target mRNAs to silence specific genes.

In addition to competition with respect to RNAi and with respect to specific products, we face substantial competition to discover and develop safe and effective means to deliver siRNAs to the relevant cell and tissue types. Safe and effective means to deliver siRNAs to the relevant cell and tissue types may be developed by our competitors, and our ability to successfully commercialize a competitive product would be adversely affected. In addition, substantial resources are being expended by third parties in the effort to discover and develop a safe and effective means of delivering siRNAs into the relevant cell and tissue types, both in academic laboratories and in the corporate sector. Some of our competitors have substantially greater resources than we do, and if our competitors are able to negotiate exclusive access to those delivery solutions developed by third parties, we may be unable to successfully commercialize our product candidates.

Risks Related to Our Common Stock

If our stock price fluctuates, purchasers of our common stock could incur substantial losses.

The market price of our common stock has fluctuated and may continue to fluctuate significantly in response to factors that are beyond our control. The stock market in general has recently experienced extreme price and volume fluctuations. The market prices of securities of pharmaceutical and biotechnology companies have been extremely volatile, and have experienced fluctuations that often have been unrelated or disproportionate to the operating performance of these companies. These broad market fluctuations could result in extreme fluctuations in the price of our common stock, which could cause purchasers of our common stock to incur substantial losses.

We may incur significant costs from class action litigation due to stock volatility.

Our stock price may fluctuate for many reasons, including as a result of public announcements regarding the progress of our development efforts or the development efforts of our collaborators and/or competitors, the addition or departure of our key personnel, variations in our quarterly operating results and changes in market valuations of pharmaceutical and biotechnology companies. When the market price of a stock has been volatile as our stock price may be, holders of that stock have occasionally brought securities class action litigation against the company that issued the stock. If any of our stockholders were to bring a lawsuit of this type against us, even if the lawsuit is without merit, we could incur substantial costs defending the lawsuit. The lawsuit could also divert the time and attention of our management.

Sales of additional shares of our common stock, including by us or our directors and officers, could cause the price of our common stock to decline.

Sales of substantial amounts of our common stock in the public market, or the availability of such shares for sale, by us or our officers and directors, or others, including the issuance of common stock upon exercise of outstanding options or restricted stock, could adversely affect the price of our common stock.

Genzyme’s ownership of our common stock could delay or prevent a change in corporate control.

Genzyme currently holds approximately 12% of our outstanding common stock and has the right to increase its ownership up to 30%, as well as the right to maintain its ownership percentage through the term of our collaboration, subject to certain limitations. This concentration of ownership may harm the market price of our common stock by:

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delaying, deferring or preventing a change in control of our company;

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impeding a merger, consolidation, takeover or other business combination involving our company; or

•

discouraging a potential acquirer from making a tender offer or otherwise attempting to obtain control of our company.

Anti-takeover provisions in our charter documents and under Delaware law and our stockholder rights plan could make an acquisition of us, which may be beneficial to our stockholders, more difficult and may prevent attempts by our stockholders to replace or remove our current management.

Provisions in our certificate of incorporation and our bylaws may delay or prevent an acquisition of us or a change in our management. In addition, these provisions may frustrate or prevent any attempts by our stockholders to replace or remove our current management by making it more difficult for stockholders to replace members of our board of directors. Because our board of directors is responsible for appointing the members of our management team, these provisions could in turn affect any attempt by our stockholders to replace current members of our management team. These provisions include:

•

a classified board of directors;

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a prohibition on actions by our stockholders by written consent;

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limitations on the removal of directors; and

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advance notice requirements for election to our board of directors and for proposing matters that can be acted upon at stockholder meetings.

In addition, our board of directors has adopted a stockholder rights plan, the provisions of which could make it difficult for a potential acquirer of Alnylam to consummate an acquisition transaction. Moreover, because we are incorporated in Delaware, we are governed by the provisions of Section 203 of the Delaware General Corporation Law, which prohibits a person who owns in excess of 15% of our outstanding voting stock from merging or combining with us for a period of three years after the date of the transaction in which the person acquired in excess of 15% of our outstanding voting stock, unless the merger or combination is approved in a prescribed manner. These provisions would apply even if the proposed merger or acquisition could be considered beneficial by some stockholders.

ITEM 2. UNREGISTERED SALES OF EQUITY SECURITIES AND USE OF PROCEEDS.

Our investor agreement with Genzyme provides Genzyme with the right, subject to certain exceptions, generally to maintain its ownership position in us until Genzyme owns less than 7.5% of our outstanding common stock, subject to certain additional limited rights of Genzyme to maintain its ownership percentage. In accordance with the investor agreement, as a result of our issuance of shares in connection with our acquisition of Sirna in March 2014, on March 25, 2014, Genzyme exercised its right to purchase an additional 344,448 shares of our common stock, at a purchase price of $66.88, the closing price of our common stock that day, and paid us $23.0 million. This purchase allowed Genzyme to maintain its ownership level of approximately 12% of our outstanding common stock.

This sale did not involve a public offering and is therefore exempt from registration under Section 4(a)(2) of the Securities Act of 1933, as amended.

ITEM 6. EXHIBITS.


2.1†*		Stock Purchase Agreement dated as of January 10, 2014 by and among the Registrant, Sirna Therapeutics, Inc., Merck Sharp & Dohme Corp., and solely for the purposes of certain specified provisions, Merck & Co., Inc.

10.1		2014 Annual Incentive Program.

10.2		Stock Purchase Agreement dated as of January 11, 2014 by and between the Registrant and Genzyme Corporation.

10.3†		Investor Agreement dated as of February 27, 2014 by and between the Registrant and Genzyme Corporation.

10.4†		Master Collaboration Agreement dated as of January 11, 2014 by and between the Registrant and Genzyme Corporation, including the Regional, Global and Co-Co License Terms Appended thereto.

12		Computation of Consolidated Ratios of Earnings/Deficiencies to Fixed Charges.

31.1		Certification of principal executive officer pursuant to Rule 13a-14(a) promulgated under the Securities Exchange Act of 1934, as amended.

31.2		Certification of principal financial officer pursuant to Rule 13a-14(a) promulgated under the Securities Exchange Act of 1934, as amended.



32.1		Certification of principal executive officer pursuant to Rule 13a-14(b) promulgated under the Securities Exchange Act of 1934, as amended, and Section 1350 of Chapter 63 of Title 18 of the United States Code.

32.2		Certification of principal financial officer pursuant to Rule 13a-14(b) promulgated under the Securities Exchange Act of 1934, as amended, and Section 1350 of Chapter 63 of Title 18 of the United States Code.

101		The following materials from the Registrant’s Quarterly Report on Form 10-Q for the quarter ended March 31, 2014, formatted in XBRL (Extensible Business Reporting Language): (i) the Condensed Consolidated Balance Sheets, (ii) the Condensed Consolidated Statements of Comprehensive Loss, (iii) the Condensed Consolidated Statements of Cash Flows, and (iv) Notes to Condensed Consolidated Financial Statements.

†	Indicates confidential treatment requested as to certain portions, which portions were omitted and filed separately with the Securities and Exchange Commission pursuant to a Confidential Treatment Request.

Schedules, exhibits and similar supporting attachments or agreements to the Stock Purchase Agreement are omitted pursuant to Item 601(b)(2) of Regulation S-K. The Registrant agrees to furnish a supplemental copy of any omitted schedule or similar attachment to the Securities and Exchange Commission upon request.

SIGNATURES

Pursuant to the requirements of the Securities Exchange Act of 1934, the Registrant has duly caused this Report to be signed on its behalf by the undersigned, thereunto duly authorized.


				ALNYLAM PHARMACEUTICALS, INC.

Date: May 9, 2014				/s/ John M. Maraganore
				John M. Maraganore, Ph.D.
				Chief Executive Officer (Principal Executive Officer)

Date: May 9, 2014				/s/ Michael P. Mason
				Michael P. Mason
				Vice President of Finance and Treasurer
				(Principal Financial and Accounting Officer)

Exhibit 2.1

STOCK PURCHASE AGREEMENT

by and among

ALNYLAM PHARMACEUTICALS, INC.,

SIRNA THERAPEUTICS, INC.,

MERCK SHARP & DOHME CORP., and

solely for purposes of Sections 3.19, 5.2, 5.6, 9.2(b)(ii), 9.2(d) and ARTICLE XI herein, MERCK & CO., INC.,

Dated: January 10, 2014

CERTAIN CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH “[***]”. A COMPLETE VERSION OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE SECRETARY OF THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES EXCHANGE ACT OF 1934.

TABLE OF CONTENTS


ARTICLE I

	Definitions and Rules of Construction	1

1.1.	Definitions	1

1.2.	Rules of Construction	16

ARTICLE II

	Purchase and Sale; Closing	16

2.1.	Closing	16

2.2.	Purchase and Sale	17

2.3.	Transactions at the Closing	17

2.4.	Development of Royalty Products	17

2.5.	Contingent Payments	18

2.6.	Tax Withholding	23

ARTICLE III

	Representations and Warranties of Seller	23

3.1.	Organization and Power	23

3.2.	Authorization and Enforceability	24

3.3.	Capitalization of the Company	24

3.4.	No Violation	25

3.5.	Governmental Authorizations and Consents	25

3.6.	Employees; Real Property; Employee Benefits; Environmental Matters	26

3.7.	Intellectual Property	27

3.8.	Contracts	28

3.9.	Compliance with Laws	29

3.10.	Financial Statements; No Undisclosed Liabilities	30

3.11.	Indebtedness. The Company will have no Indebtedness as of the Closing Date	31

3.12.	Litigation; Insurance	31

3.13.	Taxes and Tax Matters	31

3.14.	Investment Experience and Accredited Investor Status; Securities Laws Matters	32

3.15.	Acquiring Person	32


3.16.	Restricted Securities	32

3.17.	Legends	32

3.18.	No Brokers	32

3.19.	Sufficiency of Assets	33

3.20.	Disclaimer	33

3.21.	[***]	33

ARTICLE IV

	Representations and Warranties of Buyer	33

4.1.	Organization and Power	33

4.2.	Authorization and Enforceability	34

4.3.	No Violation	34

4.4.	Governmental Authorizations and Consents	34

4.5.	Litigation	35

4.6.	Financial Capacity	35

4.7.	No Brokers	35

4.8.	No Section 368(a) Reorganization	35

4.9.	Investigation	35

4.10.	No Inducement or Reliance; Independent Assessment	36

4.11.	Capitalization	36

4.12.	Valid Issuance of Stock Consideration	36

4.13.	Company SEC Documents; Financial Statements; NASDAQ Stock Market	36

4.14.	Offering	37

4.15.	No Integration	37

ARTICLE V

	Covenants	38

5.1.	Conduct of the Company	38

5.2.	Exclusive Dealing	40

5.3.	Access to Information Prior to the Closing	40

5.4.	Regulatory Filings; Notices	40

- ii -


5.5.	Intercompany Contracts	41

5.6.	Certain Tax Matters	42

5.7.	Preservation of Books and Records	44

5.8.	Proprietary Information	45

5.9.	Public Announcements	45

5.10.	Technology Transfer	45

5.11.	Certain Personnel Matters	46

5.12.	NASDAQ	46

5.13.	Lock-Up	46

5.14.	Limitations Following Lock-Up Terms	47

5.15.	Release	47

5.16.	Pre-Closing Transfer of Certain Excluded Assets	48

5.17.	Patent Files	48

5.18.	Additional Tech Transfer	48

ARTICLE VI

	Conditions to Closing	48

6.1.	Conditions to All Parties’ Obligations	48

6.2.	Conditions to Seller’s Obligations	49

6.3.	Conditions to Buyer’s Obligations	49

ARTICLE VII

	Deliveries by Seller and the Company at Closing	50

7.1.	Officer’s Certificate	50

7.2.	Share Certificates	50

7.3.	Tech Information	50

7.4.	Resignations of Directors and Officers	50

7.5.	Further Instruments	50

ARTICLE VIII

	Deliveries by Buyer at Closing	50

8.1.	Officer’s Certificate	50

- iii -


8.2.	Cash Consideration	50

8.3.	Stock Consideration	51

8.4.	Further Instruments	51

ARTICLE IX

	Indemnification; Survival	51

9.1.	Survival of Representations and Warranties; Time Limitations	51

9.2.	Indemnification	52

9.3.	Indemnification for Unreviewed Materials	55

9.4.	Indemnification for Product Liability Claims	56

ARTICLE X

	Termination	57

10.1.	Termination	57

10.2.	Procedure and Effect of Termination	58

ARTICLE XI

	Miscellaneous	58

11.1.	Expenses	58

11.2.	Notices	58

11.3.	Governing Law	59

11.4.	Entire Agreement	59

11.5.	Severability	60

11.6.	Amendment	60

11.7.	Effect of Waiver or Consent	60

11.8.	Parties in Interest; Limitation on Rights of Others	60

11.9.	Assignability	61

11.10.	Disclosure Schedules	61

11.11.	Jurisdiction; Court Proceedings; Waiver of Jury Trial; Arbitration for Tech Transfer Condition	61

11.12.	Baseball Arbitration for Determination of Sublicense Value	62

11.13.	No Other Duties	64

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11.14.	Reliance on Counsel and Other Advisors	64

11.15.	Remedies	64

11.16.	Specific Performance	64

11.17.	Counterparts	64

11.18.	Further Assurance	65

Exhibit A – In-License Agreement

Exhibit B – Out-License Agreement

Exhibit C – ACA

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STOCK PURCHASE AGREEMENT

STOCK PURCHASE AGREEMENT, dated as of January 10, 2014, by and among Alnylam Pharmaceuticals, Inc. a Delaware corporation (“ Buyer ”), Sirna Therapeutics, Inc., a Delaware corporation (the “ Company ”), Merck Sharp & Dohme Corp., a New Jersey corporation (“ Seller ”), and solely for purposes of Sections 3.19, 5.2, 5.6, 9.2(b)(ii), 9.2(d) and Article XI herein, Merck & Co., Inc., a New Jersey corporation (“ Merck ”).

RECITALS

WHEREAS, Buyer desires to purchase from Seller, and Seller desires to sell to Buyer, all of Seller’s right, title and interest in and to all of the outstanding shares of common stock of the Company, par value $0.01 per share (the “ Sirna Common Stock ”), upon the terms and subject to the conditions hereinafter set forth; and

WHEREAS, prior to Closing, Seller and the Company shall have entered into (i) a license agreement by and between Seller and the Company (the “ In-License Agreement ”) in the form attached hereto as Exhibit A , pursuant to which Seller grants the Company an exclusive license in respect of certain Intellectual Property of the Seller, (ii) a license agreement by and between Seller and the Company (the “ Out-License Agreement ”) in the form attached hereto as Exhibit B , pursuant to which the Company grants Seller a non-exclusive license in respect of certain Intellectual Property of the Company, and (iii) an asset contribution agreement by and between Seller and the Company (the “ ACA ”) in the form attached hereto as Exhibit C , pursuant to which the Seller transfers certain assets to the Company.

NOW THEREFORE, in consideration of the premises and the representations, warranties, covenants and agreements contained in this Agreement, and intending to be legally bound hereby, the parties hereto agree as follows:

ARTICLE I

Definitions and Rules of Construction

1.1.

Definitions .

As used in this Agreement, the following terms shall have the meanings set forth below:

“ Acquired Sirna Patents ” means those Patent Rights (a) owned by the Company on the Closing Date or (b) exclusively licensed to the Company pursuant to the In-License Agreement, including the Patent Rights listed on Section 1.1 of the Company Disclosure Schedule.

“ Affiliate ” means, as to any Person, any other Person that, directly or indirectly, is in control of, is controlled by, or is under common control with, such Person. For purposes of this definition, “control” of a Person means the power, directly or indirectly, either to (a) vote 50% or more of the securities having ordinary voting power for the election of directors of such

Person or (b) direct or cause the direction of the management and policies of such Person, whether by contract or otherwise. The Company shall be deemed for purposes of this Agreement an Affiliate of Seller prior to the Closing and of Buyer from and after the Closing.

“ Affiliated Group ” means any affiliated group within the meaning of Section 1504(a) of the Code or any similar group defined under a similar provision of state, local, or non-U.S. law.

“ Agreement ” means this Stock Purchase Agreement, as it may be amended from time to time.

“ Alnylam Product Liability Claim ” means a claim asserted by any Person (other than Buyer and its Affiliates), either under strict liability, negligence or other basis for liability, against a Seller Indemnitee arising out of or relating to any (a) defect or alleged defect in the Alnylam Licensed Products, including defects and alleged defects in the manufacturing, testing or design of Alnylam Licensed Products, (b) actions or omissions of Buyer or its Affiliates in connection with the use, testing, development, promotion, marketing, sale, distribution, or other commercialization of Alnylam Licensed Products, (c) labeling, inserts, instruction manuals, promotional activities or advertising supplied or compiled by Buyer or its Affiliates in connection with Alnylam Licensed Products, or (d) recall of Alnylam Licensed Products undertaken by Buyer or its Affiliates.

“ Alnylam Licensed Products ” means any Royalty Products and any other pharmaceutical, biopharmaceutical or biological preparation or substance, whether or not in final form, for sale by prescription, over-the-counter or any other method the sale, manufacture or use of which (a) in the absence of the In-License Agreement, would infringe at least one Valid Claim of a Merck Patent Right (as defined in the In-License Agreement), or (b) incorporates or embodies any other Company Intellectual Property.

“ Ancillary Documents ” means the In-License Agreement, the Out-License Agreement, the ACA, and such other documents being executed and delivered in connection with this Agreement and the transactions contemplated hereby.

“ ACA ” has the meaning set forth in the Recitals.

“ Arbitrator ” has the meaning set forth in Section 11.12(a).

“ Backup Product ” has the meaning set forth in Section 2.5(a).

“ Bona Fide Collaboration ” means (a) a collaboration between Buyer or its Affiliates and one or more Third Parties for the research, development, manufacturing and/or commercialization of one or more Royalty Products that (i) includes a license or sublicense to such Third Party under the Acquired Sirna Patents alone or in conjunction with other Patent Rights owned or controlled by Buyer and (ii) is established under a written agreement (or series of related written agreements, in each case) signed after the Closing Date in which Buyer or its

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Affiliate undertakes and performs research, development, manufacturing and/or commercialization activity with or on behalf of such Third Part(ies), (b) the grant by Buyer or its Affiliates of a license or sublicense to a Third Party under the Acquired Sirna Patents for the development and commercialization of a Merck Royalty Product pursuant to a written agreement (or a series of related written agreements, in each case) signed after the Closing Date, or (c) a license or sublicense of any Royalty Product to an entity in which Buyer or any of its Affiliates (other than Buyer’s 401(k) plan) beneficially owns at least ten percent (10%) of the outstanding equity interests or other interests convertible thereto.

“ Books and Records ” has the meaning set forth in Section 5.7(a).

“ Business Day ” means any day other than a Saturday, Sunday or day on which banks are closed in New York, New York. If any period expires on a day which is not a Business Day or any event or condition is required by the terms of this Agreement to occur or be fulfilled on a day which is not a Business Day, such period shall expire or such event or condition shall occur or be fulfilled, as the case may be, on the next succeeding Business Day.

“ Buyer ” has the meaning set forth in the Preamble.

“ Buyer Commercially Reasonable Discretion ” means Buyer’s discretion, exercised in good faith after following the same internal processes of Buyer’s, as applicable, and considering the same factors, for assessing whether to continue the progression into further non-clinical development, clinical development or commercialization activities of a Comparable Buyer Product to the applicable Merck Royalty Product or to otherwise exploit the Company Intellectual Property.

“ Buyer Commercially Reasonable Efforts ” means commercially reasonable efforts, made by or on behalf of Buyer, which are consistent with the efforts and resources and with the strategic prioritization typically applied by Buyer, including the level of financial and human resources available to and normally used by Buyer, to progress the non-clinical development, clinical development and commercialization of a Comparable Buyer Product to the applicable Merck Royalty Product. Buyer Commercially Reasonable Efforts shall be determined on a market-by-market and indication-by-indication basis for the particular Merck Royalty Product, and it is anticipated that the level of effort will be different for different markets, and will change over time, reflecting changes in the status of such Merck Royalty Product and the market(s) involved.

“ Buyer Common Stock ” means the common stock, par value $0.01 per share, of Buyer.

“ Buyer Disclosure Schedule ” means the disclosure schedule of even date herewith delivered by Buyer to the Company in connection with the execution and delivery of this Agreement.

“ Buyer Indemnitees ” has the meaning set forth in Section 9.2(b).

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“ Buyer Indemnitees Cap ” has the meaning set forth in Section 9.2(c)(ii).

“ Buyer Indemnitees Deductible ” has the meaning set forth in Section 9.2(c)(ii).

“ Buyer Material Adverse Effect ” means any change or effect, event, circumstance, occurrence, state of facts or development that would prevent Buyer from consummating the Contemplated Transactions; provided , that none of the following events, changes, developments, effects, conditions, circumstances, matters, occurrences or state of facts shall be taken into account in determining whether there has been or may be a Buyer Material Adverse Effect: (i) any change or development in United States financial or securities markets, general economic or business conditions, or political or regulatory conditions, (ii) any act of war, armed hostilities or terrorism, (iii) any change or development in the pharmaceuticals industry, (iv) any change in Law or GAAP or the interpretation or enforcement of either, (v) any termination or failure to renew by any Governmental Authority of any Permit of Buyer, (vi) the announcement, execution or consummation of this Agreement or any of the Ancillary Agreements or the consummation of any of the Contemplated Transactions, (vii) any change resulting from the actions or failure to act of the Company, Seller or Merck, or (viii) any change resulting from the failure of the Company or Seller to reasonably consent to any acts or actions requiring the Company’s or Seller’s consent under this Agreement and for which Buyer has sought such consent except, in the case of clauses (iii) or (iv), to the extent such events, changes, developments, effects, conditions, circumstances, matters, occurrences or state of facts have a materially disproportionate effect on Buyer (and which such materially disproportionate effect is durationally significant) relative to other Persons engaged in the pharmaceuticals industry.

“ Buyer Royalty Product ” means any Royalty Product that is not a Merck Royalty Product.

“ Cash Consideration ” has the meaning set forth in Section 2.2(b).

“ Closing ” has the meaning set forth in Section 2.1.

“ Closing Date ” has the meaning set forth in Section 2.1.

“ COBRA ” has the meaning set forth in Section 3.6(b).

“ Code ” means the Internal Revenue Code of 1986, as amended.

“ Commercial Software ” means commercially-available Software licensed pursuant to a standard license agreement and used internally (and not licensed or sublicensed to third parties) by the Company in connection with its business as currently conducted.

“ Company ” has the meaning set forth in the Preamble.

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“ Company Disclosure Schedule ” means the disclosure schedule of even date herewith delivered by Seller to the Buyer in connection with the execution and delivery of this Agreement.

“ Company Intellectual Property ” means all Intellectual Property owned or in-licensed by the Company.

“ Company IP Agreements ” means all Contracts to which the Company is a party relating to the license, sublicense, creation, development, disclosure, or transfer of Intellectual Property, other than (a) shrink-wrap or click-through licenses of Commercial Software, and (b) non-exclusive licenses of Intellectual Property incidental to the sale or purchase of products or services in the ordinary course of business.

“ Company Material Adverse Effect ” means any change or effect, event, circumstance, occurrence, state of facts or development that (a) would reasonably be likely to have a material adverse effect on the business, operations or financial condition of the Company, or (b) would prevent the Company or Seller from consummating the Contemplated Transactions; provided , that none of the following events, changes, developments, effects, conditions, circumstances, matters, occurrences or state of facts shall be taken into account in determining whether there has been or may be a Company Material Adverse Effect: (i) any change or development in United States financial or securities markets, general economic or business conditions, or political or regulatory conditions, (ii) any act of war, armed hostilities or terrorism, (iii) any change or development in the pharmaceuticals industry, (iv) any change in Law or GAAP or the interpretation or enforcement of either, (v) any termination or failure to renew by any Governmental Authority of any Permit of the Company, (vi) the announcement, execution or consummation of this Agreement or any of the Ancillary Agreements or the consummation of any of the Contemplated Transactions, or (vii) any change resulting from the failure of Buyer to reasonably consent to any acts or actions requiring Buyer’s consent under this Agreement and for which the Company has sought such consent except, in the case of clauses (iii) or (iv), to the extent such events, changes, developments, effects, conditions, circumstances, matters, occurrences or state of facts have a materially disproportionate effect on the Company (and which such materially disproportionate effect is durationally significant) relative to other Persons engaged in the pharmaceuticals industry.

“ Company Released Parties ” has the meaning set forth in Section 5.15(a).

“ Company Releasing Parties ” has the meaning set forth Section 5.15(b).

“ Comparable Buyer Product ” means, with respect to a particular Merck Royalty Product, a product or product candidate of similar strategic importance to Buyer, with similar technical characteristics, with what Buyer reasonably believes to be a similar commercial potential at a similar stage in its development or product life, taking into account all payments due to Seller and its Affiliates under this Agreement and the Ancillary Documents and all other relevant factors, including without limitation, technical, legal, scientific and/or medical factors such as the nature of the product, the clinical setting in which it is expected to be used, stage of

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development, mechanism of action, efficacy and safety relative to competitive products in or expected to be introduced into the marketplace, difficulties associated with technology transfer, process development, scale-up or manufacturing, safety issues, legal difficulties and intellectual property ownership, actual or anticipated Regulatory Authority approved labeling, the nature and extent of market exclusivity (including patent coverage and regulatory exclusivity), cost and likelihood of obtaining Regulatory Approval, and projected risk-adjusted economic return (including likely pricing and reimbursement status).

“ Confidentiality Agreement ” means the Mutual Confidential Disclosure Agreement between Seller and Buyer dated October 2, 2013.

“ Contemplated Transactions ” means the purchase and sale of the Sirna Common Stock as contemplated by this Agreement.

“ Contingent Payment ” has the meaning set forth in Section 2.5.

“ Contract ” means any written agreement, license, contract, arrangement, understanding, obligation or commitment to which a party is bound.

“ Disposition ” or “ Dispose of ” means any (i) offer, pledge, sale, contract to sell, sale of any option or contract to purchase, purchase of any option or contract to sell, grant of any option, right or warrant for the sale of, or other disposition of or transfer of any shares of Buyer Common Stock, including, without limitation, any “short sale,” hedging or similar arrangement, or (ii) swap or any other agreement or any transaction that transfers, in whole or in part, directly or indirectly, the economic consequence of ownership of shares of Buyer Common Stock, whether any such swap or transaction is to be settled by delivery of securities, in cash or otherwise.

“ Disputed Items ” has the meaning set forth in Section 11.11(c).

“ DOJ ” has the meaning set forth in Section 5.4(a).

“ Employee Plan ” means any “employee benefit plan” as defined by Section 3(3) of ERISA, all specified fringe benefit plans as defined in Section 6039D of the Code, and all other bonus, incentive compensation, deferred compensation, profit sharing, stock option, stock appreciation right, stock bonus, stock purchase, employee stock ownership, savings, severance, change in control, supplemental unemployment, layoff, salary continuation, retirement, pension, health, life insurance, disability, accident, group insurance, vacation, holiday, sick leave, fringe benefit or welfare plan, and any other employee compensation or benefit plan, policy, practice or Contract (whether qualified or nonqualified, effective or terminated, written or unwritten) and any trust, escrow, or other Contract related thereto that (i) is maintained or contributed to by the Company and (ii) provides benefits to, or describes policies or procedures applicable to, any current or former director, officer, employee or service provider of the Company, or the dependents of any such Person, regardless of how (or whether) liabilities for the provision of benefits are accrued or assets are acquired or dedicated with respect to the funding thereof.

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“ End Date ” has the meaning set forth in Section 10.1(c).

“ Environmental Law ” means any Law (including without limitation principles of common law, directives, statutes, their implementing laws and regulations, related judicial and administrative orders and binding legal interpretations thereof) applicable to the Company relating to pollution or protection of the environment, natural resources, human health or safety, including without limitation Laws relating to the generation, handling, use, presence, transportation, recycling, take-back, disposal, release or threatened release of any Hazardous Substance.

“ Equity Securities ” of any Person means any and all shares of capital stock, warrants or options of such Person, and all securities exchangeable for or convertible or exercisable into, any of the foregoing.

“ ERISA ” means the Employee Retirement Income Security Act of 1974, as amended.

“ Existing Buyer Patent ” means any Patent Right that Buyer or its Affiliate has the right to practice or otherwise exploit, on an exclusive or non-exclusive basis, whether by ownership or pursuant to a license obtained prior to the Closing Date, and in either case other than pursuant to this Agreement.

“ FDA ” has the meaning set forth in Section 3.9(a).

“ Filing ” means the filing of an NDA with a Regulatory Authority; provided , however , that if a Regulatory Authority must accept the filing of an NDA in order to commence review, “Filing” of an NDA means such acceptance by such Regulatory Authority.

“ First Commercial Sale ” means with respect to a Royalty Product in a country, the first commercial sale in such country of such Royalty Product. First Commercial Sale will not include a sale of a Royalty Product to a Related Party, or sales of Royalty Products to be used for clinical trials or on the disposition of a Royalty Product in reasonable quantities by Buyer or its Related Parties as samples (promotion or otherwise) or as donations (for example, to non-profit institutions or government agencies for a non-commercial purpose).

“ FTC ” has the meaning set forth in Section 5.4(a).

“ GAAP ” means generally accepted accounting principles as set forth in the opinions and pronouncements of the Accounting Principles Board of the American Institute of Certified Public Accountants and statements and pronouncements of the Financial Accounting Standards Board or in such other statements by such other Person as may be approved by a significant segment of the accounting profession in the United States.

“ Generic Product ” has the meaning set forth in Section 2.5(c)(iv)(2).

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“ Governmental Authority ” means any nation or government, any foreign or domestic federal, state, county, municipal or other political instrumentality or subdivision thereof and any foreign or domestic entity or body exercising executive, legislative, judicial, regulatory, administrative or taxing functions of or pertaining to government, including any court and any official of any of the foregoing.

“ Governmental Consents ” has the meaning set forth in Section 3.5.

“ Hazardous Substance ” means any substances, mixtures, chemicals, products, materials or wastes that, pursuant to Environmental Law, are listed, classified, characterized, defined or regulated as hazardous, biohazardous, dangerous, infectious, toxic, a pollutant or a contaminant, including without limitation petroleum, petroleum products or by-products, friable asbestos, biological agents, genetically engineered or modified materials, blood-borne pathogens, bacterial or fungal materials, medical waste, unused or “off-spec” products, any material or equipment containing radon or other radioactive materials or polychlorinated biphenyls.

“ HSR Act ” means the Hart-Scott-Rodino Antitrust Improvements Act of 1976, as amended.

“ Income Tax ” means any U.S. federal, state, local or non-U.S. tax measured by or imposed on net income.

“ Income Tax Return ” means any Tax Return relating to Income Tax.

“ Indebtedness ” means all obligations and indebtedness of the Company for borrowed money, or guarantees thereof.

“ Indemnification Notice ” has the meaning set forth in Section 9.3(b).

“ Indemnitee ” has the meaning set forth in Section 9.2(d)(i).

“ Indemnitor ” has the meaning set forth in Section 9.2(d)(i).

“ In-License Agreement ” has the meaning set forth in the recitals.

“ Intellectual Property ” means all United States and non-United States: (a) patents and patent applications, (b) copyrights, including copyrights in Software, (c) trademarks, service marks, trade dress, trade names, brand names, domain names and other identifiers of source or goodwill, together with all goodwill associated therewith, (d) trade secrets, know-how and other confidential and proprietary information (collectively, “ Know-How ”), and (e) all registrations and applications for registration of any of the foregoing, anywhere in the world.

“ Knowledge of Buyer ” means the actual knowledge as of the date hereof of any of the following personnel of Buyer within the scope of their employment responsibilities and without independent inquiry or investigation: John Maraganore, Ph.D. (Buyer’s Chief Executive Officer) and Barry Greene (Buyer’s President and Chief Operating Officer).

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“ Knowledge of Seller ” means the actual knowledge as of the date hereof of any of the following personnel of Seller and its Affiliates within the scope of their employment responsibilities and without independent inquiry or investigation: Kimberly Folander, Lawrence Senour, Scott Kauffman, Laura Ginkel, Iain Dukes, Roger Perlmutter and Alan Tamarelli.

“ Laws ” means all laws, Orders, statutes, codes, regulations, ordinances, orders, decrees, rules, or other requirements with similar effect of any Governmental Authority.

“ Licensee ” means a Third Party to whom Buyer or its Affiliates have granted a license or sublicense under the Acquired Sirna Patents with respect to a Royalty Product pursuant to a Bona Fide Collaboration.

“ Lien ” means, with respect to any asset (including any security), any option, claim, mortgage, lien, security interest, pledge, charge or other encumbrance or restrictions of any kind in respect of such asset, other than any license of, option to license, or covenant not to assert claims of infringement, misappropriation or other violation with respect to, Intellectual Property.

“ Litigation ” has the meaning set forth in Section 3.12.

“ Loss ” or “ Losses ” means all claims, losses, liabilities, damages, costs and expenses, including, without limitation, reasonable attorneys’ fees, provided , that (i) Losses shall not include consequential damages, special damages, punitive damages, or lost profits, in each case if and to the extent incurred by an Indemnitee (as distinguished from such amounts incurred by a third party for which and to whom any Indemnitee may be responsible under any Laws or under any Contracts providing for any Indemnitee to provide indemnification of such amounts), and (ii) for purposes of computing Losses incurred by an Indemnitee, there shall be deducted an amount equal to the amount of any insurance proceeds, indemnification payments, contribution payments and reimbursements received by the Indemnitee, and an amount equal to the amount of any Tax savings realized by the Indemnitee as a result of the Loss.

“ Major Market Country ” means any of the United States, Japan, United Kingdom, Germany, France, Italy or Spain.

“ Material Contracts ” has the meaning set forth in Section 3.8(a).

“ Material Permits ” has the meaning set forth in Section 3.9(c).

“ Merck ” has the meaning set forth in the Preamble.

“ Merck Affiliated Group ” means any Affiliated Group of which Merck is the common parent.

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“ Merck Product Liability Claim ” means a claim asserted by any Person (other than Seller and its Affiliates), either under strict liability, negligence or other basis for liability, against a Buyer Indemnitee arising out of or relating to any (a) defect or alleged defect in the Merck Licensed Products, including defects and alleged defects in the manufacturing, testing or design of Merck Licensed Products, (b) actions or omissions of Seller or its Affiliates in connection with the use, testing, development, promotion, marketing, sale, distribution, or other commercialization of Merck Licensed Products, (c) labeling, inserts, instruction manuals, promotional activities or advertising supplied or compiled by Seller or its Affiliates in connection with Merck Licensed Products, or (d) recall of Merck Licensed Products undertaken by Seller or its Affiliates.

“ Merck Licensed Products ” means any pharmaceutical, biopharmaceutical or biological preparation or substance, whether or not in final form, for sale by prescription, over-the-counter or any other method the sale, manufacture or use of which would, in the absence of the Out-License Agreement, (a) infringe at least one Valid Claim of a Sirna Patent Right (as defined in the Out-License Agreement), or (b) incorporate or embody any Sirna Know-How (as defined in the Out-License Agreement).

“ Merck Royalty Product ” means the Existing Clinical Candidates, as defined in the Out-License Agreement.

“ MiR34 ” means one or more miR-34a, miR-34b, miR-34c and miR-449, whether based on the native miRNA oligomer or a chemically modified RNA oligomer designed to provide the function of the particular miR-34 miRNA.

“ MiR34 Therapeutic Product ” means any oligonucleotide or oligonucleotide derivative-based therapeutic Product, to replace, enhance or suppress endogenous MiR34 activity, given either alone or in combination with one or more Products. Solely for purposes of this definition of “MiR34 Therapeutic Product,” “Product(s)” means any pharmaceutical, biopharmaceutical or biological preparation or substance, whether or not in final form.

“ mRNA ” means messenger RNA.

“ Naked License ” means a license or sublicense for the research, development and/or commercialization of RNAi Products that is granted by Buyer or its Affiliates under any Acquired Sirna Patents to a Third Party pursuant to a written agreement signed after the Closing Date, and that is not granted in connection with a Bona Fide Collaboration.

“ NDA ” means a new drug application or similar application or submission filed with a Regulatory Authority to obtain marketing authorization for a pharmaceutical product in that country or in that group of countries.

“ NDA Approval ” means, with respect to a Royalty Product in a country or jurisdiction, the approval of an NDA for such Royalty Product by the applicable Regulatory Authority in such country or jurisdiction and receipt of sufficient authorization from such Regulatory Authority to market and sell such Royalty Product in such country or jurisdiction, including all separate pricing and/or reimbursement approvals that may be required. Moreover,

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if a centralized filing with the European Medicines Agency is not made for the relevant Royalty Product, but Buyer or its Related Party decides to pursue Regulatory Approval in Europe for such product using the mutual recognition procedure or on an individual country basis, then the milestone will be deemed to be achieved upon the First Commercial Sale of such Royalty Product in the first Major Market Country in the European Union.

“ Neutral Arbitrator ” means an independent arbitrator as Buyer and Seller may agree, or, if they cannot agree within a reasonable time, one selected by the President of the American Arbitration Association.

“ Net Sales ” means, with respect to a Royalty Product in a country, the gross amount invoiced by Buyer and its Related Parties on sales or other dispositions in such country of such Royalty Product during the applicable Royalty Term to Third Parties that are not Licensees, less reasonable and customary deductions for the following, all determined in accordance with GAAP, consistently applied: (a) to the extent allowed and taken, sales returns and allowances, granted or accrued, including trade, quantity and cash discounts and any other adjustments, including those granted on account of price adjustments, billing errors, rejected goods, damaged or defective goods, recalls, returns, rebates, chargebacks, reimbursements or similar payments actually granted or given to wholesalers or other distributors, buying groups, health care insurance carriers or other institutions that are specifically identifiable as relating to a Royalty Product; (b) customs or excise duties, sales tax, consumption tax, value added tax, and other similar taxes (except income taxes) measured by the production, sale, or delivery of goods; (c) duties relating to sales and any payments in respect of sales to the United States government, any State government or any foreign government, or to any governmental authority, or with respect to any government subsidized program or managed care organization; and (d) transportation, importation, freight and other handling expenses not otherwise paid by the customer that are specifically identifiable as relating to a Royalty Product.

If Buyer or its Related Parties sells any Royalty Product in the form of a combination product containing (i) a Royalty Product and (ii) one or more active ingredients that are not such Royalty Product (whether such elements are combined in a single formulation and/or package, as applicable, or formulated and/or packaged separately but sold together for a single price) (a “ Combination Product ”), Net Sales of such Combination Product for the purpose of determining the royalty due to Seller pursuant to Section 2.5(c) will be calculated by multiplying actual Net Sales of such Combination Product by the fraction A/(A+B) where A is the invoice price of such Royalty Product if sold separately, and B is the total invoice price of the other active ingredient(s) in the combination if sold separately. If, on a country-by-country basis, such other active ingredient or ingredients in the Combination Product are not sold separately in such country, but such Royalty Product component of the Combination Product is sold separately in such country, Net Sales for the purpose of determining royalties due to Seller pursuant to Section 2.5(c) for the Combination Product will be calculated by multiplying actual Net Sales of such Combination Product by the fraction A/C where A is the invoice price of such Royalty Product component if sold separately, and C is the invoice price of the Combination Product. If, on a country-by-country basis, such Royalty Product component is not sold

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separately in such country, Net Sales for the purposes of determining royalties due to Seller pursuant to Section 2.5(c) for the Combination Product will be D/(D+E) where D is the fair market value of the portion of the Combination Products that contains such Royalty Product and E is the fair market value of the portion of the Combination Products containing the other active ingredient(s) included in such Combination Product, as such fair market values are determined in good faith by Buyer, based upon commercially reasonable standards and available market information.

“ Obligations ” has the meaning set forth Section 5.15(a).

“ Orders ” means all judgments, orders, writs, injunctions, decisions, rulings, decrees and awards of any Governmental Authority.

“ Original Product ” has the meaning set forth in Section 2.5(a).

“ Out-License Agreement ” has the meaning set forth in the recitals.

“ Patent Rights ” means any and all patents and patent applications (which for the purpose of this Agreement shall be deemed to include certificates of invention and applications for certificates of invention), including provisionals, divisionals, continuations, continuations-in-part, reissues, renewals, substitutions, registrations, re-examinations, revalidations, extensions, supplementary protection certificates, pediatric exclusivity periods and the like of any such patents and patent applications, and foreign equivalents of the foregoing, anywhere in the world.

“ Permits ” has the meaning set forth in Section 3.9(c).

“ Permitted Lien ” means (a) Liens reflected or reserved against or otherwise disclosed in the balance sheet that is a part of the Unaudited Financial Statements, (b) Liens for Taxes, assessments and other governmental charges not yet due and payable or due but not delinquent or being contested in good faith, and (c) Liens created by this Agreement or any of the Ancillary Documents, or in connection with Contemplated Transactions.

“ Person ” means any individual, person, entity, general partnership, limited partnership, limited liability partnership, limited liability company, corporation, joint venture, trust, business trust, cooperative, association, foreign trust or foreign business organization.

“ Phase 2 Study ” means a human clinical trial in any country that would satisfy the requirements of 21 CFR 312.21(b).

“ Phase 3 Study ” means a human clinical trial in any country that would satisfy the requirements of 21 CFR 312.21(c).

“ Pre-Closing Tax Period ” means any taxable period (or portion thereof) ending on or prior to the Closing Date.

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“ Regulatory Approval ” means all approvals from the relevant Regulatory Authority necessary to market and sell a Royalty Product in any country.

“ Regulatory Authority ” means any applicable government regulatory authority, domestic or foreign, involved in granting approvals for the manufacturing or marketing of a Royalty Product, including, in the United States, the United States Food and Drug Administration, and any successor governmental authority having substantially the same function.

“ Related Parties ” means Buyer’s Affiliates and Licensees.

“ Resolution Period ” has the meaning set forth in Section 11.11(c).

“ Restraints ” has the meaning set forth in Section 6.1(a).

“ RNA ” means ribonucleic acid.

“ RNAi ” means RNA interference, which is the natural biological mechanism by which natural or modified RNA (or other nucleic acid) molecules inhibit gene expression in a sequence-specific manner.

“ RNAi Product ” means a product (i) containing, comprised or based on siRNAs or modified siRNAs, and (ii) designed to modulate the expression of a target mRNA and its encoded gene products through RNA interference, but excluding (A) MiR34 and (B) any MiR34-specific component of any MiR34 Therapeutic Product.

“ RNAi Technology Platform ” means the proprietary technology platform of the Company (including its predecessor entity, Ribozyme, Inc.) pertaining to the use and exploitation of RNAi as acquired by Merck’s Affiliate on December 29, 2006 upon that Merck Affiliate’s acquisition of the Company, as such technology platform was further modified, enhanced and improved by Merck and/or its Affiliates after such acquisition.

“ RNAi Therapeutic Products ” means any oligonucleotide or oligonucleotide derivative-based therapeutic Products, whether alone or in combination with any one or more other Products, that function through RNAi, but excluding any MiR34-specific component of any MiR34 Therapeutic Product. Solely for purposes of this definition of “RNAi Therapeutic Products,” “Product(s)” means any pharmaceutical, biopharmaceutical or biological preparation or substance, whether or not in final form.

“ Royalty Product ” means an RNAi Product, the manufacture, use, or sale of which would infringe a Valid Claim of an Acquired Sirna Patent that is not an Existing Buyer Patent in the country of manufacture, use or sale.

“ Royalty Term ” has the meaning set forth in Section 2.5(c)(iii).

“ Seller ” has the meaning set forth in the Preamble.

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“ Seller Indemnitees ” has the meaning set forth in Section 9.2(a).

“ Seller Indemnitees Deductible ” has the meaning set forth in Section 9.2(c)(i).

“ Seller Releasing Parties ” has the meaning set forth in Section 5.15(a).

“ Seller Released Parties ” has the meaning set forth in Section 5.15(b).

“ siRNA ” means any of “small interfering RNA”, “short interfering RNA” and “silencing RNA”.

“ Sirna Common Stock ” has the meaning set forth in the Recitals.

“ Software ” means computer software and databases, together with, as applicable, object code, source code, firmware and embedded versions thereof and documentation related thereto.

“ Stock Consideration ” has the meaning set forth in Section 2.2(b).

“ Sublicense Value ” means that portion of any payments (a) actually received by Buyer or its Affiliate from its licensee or sublicensee in consideration for the grant of a Naked License to such licensee or sublicensee and (b) attributable specifically to the Acquired Sirna Patents being licensed or sublicensed pursuant to such Naked License (subject to the applicable adjustments under the applicable Naked License agreement for royalty stacking and generic entry. Such payments include, but are not limited to, license fees, milestone payments, license maintenance fees, royalties, and value attributable to the premium received by Buyer above fair market value of any Buyer equity issued. Sublicense Value excludes loaned or reimbursable amounts (including research and patent expense reimbursements), payments at reasonable cost for the supply of products or for research or other services provided by Buyer or its Affiliates and fair market value consideration for the purchase of an equity interest in Buyer or its Affiliates in conjunction with the issuance of such license or sublicense). In the event that Buyer or its Affiliate grant more than one Naked License to the same Third Party during any twelve (12) month period, such Naked Licenses collectively shall be treated as one Naked License to such Third Party for the purposes of determining Sublicense Value. In the event that, during any twelve (12) month period, Buyer or its Affiliate grant to the same Third Party or its Affiliate both a Naked License and a license under other Intellectual Property owned by or licensed to Buyer or its Affiliate, such licenses collectively shall be treated as one Naked License to such Third Party for the purposes of determining Sublicense Value.

“ Sublicense Value Share Notice ” has the meaning set forth in Section 2.5(e)(iii).

“ Subsequent Lock-Up Period ” has the meaning set forth in Section 5.13(b).

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“ Tax ” or “ Taxes ” means any U.S. federal, state, local or non-U.S. income, profits, franchise, gross receipts, license, environmental, customs duty, capital stock, severances, stamp, payroll, sales, employment, unemployment, social security (or similar), disability, use, property, withholding, excise production, registration, value added, occupancy, Transfer, alternative or add-on minimum, estimated, or other tax, duties or assessment of any nature whatsoever, including any interest, penalty or addition thereto, whether disputed or not.

“ Tax Contest ” means any audit, hearing, proposed adjustment, arbitration, deficiency, assessment, suit, dispute, claim, proceeding or other litigation commenced, filed or otherwise initiated or convened to investigate or resolve the existence and extent of a liability for Taxes.

“ Tax Return ” means any report, return, statement, claim for refund or other written information (including elections, declarations, disclosures, schedules, estimates and information returns) relating to Taxes, including any amendment thereto.

“ Taxing Authority ” means any government or any subdivision, agency, commission or authority thereof, or any quasi-governmental or private body, having jurisdiction over the assessment, determination, collection or other imposition of Taxes.

“ Tech Information ” has the meaning set forth in Section 5.10.

“ Tech Transfer Condition ” has the meaning set forth in Section 5.10.

“ Tech Transfer Objection Notice ” has the meaning set forth in Section 5.10.

“ Third Party ” means a Person other than Seller and its Affiliates and Buyer and its Affiliates.

“ Third Party Claim ” has the meaning set forth in Section 9.2(d)(ii)(A).

“ Total Consideration ” has the meaning set forth in Section 2.2(b).

“ Transfer Taxes ” means all transfer, documentary, sales, use, stamp, registration and other such Taxes and fees (including any penalties and interest) incurred in connection with the Contemplated Transactions (including any transfer or similar Tax imposed by any Governmental Authority).

“ Treasury Regulations ” means the regulations promulgated under the Code.

“ Unreviewed Materials ” has the meaning set forth in Section 9.3(a).

“ Valid Claim ” means a claim of an issued and unexpired Patent Right that has not been revoked or held unpatentable, unenforceable or invalid by a decision of a court or other governmental agency of competent jurisdiction (which decision is not reversible, appealable or has not been appealed within the time allowed for appeal), and which claim has not been disclaimed, denied or admitted to be invalid or unenforceable through reissue, re-examination or disclaimer or otherwise.

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1.2.

Rules of Construction .

Unless the context otherwise requires:

(a) A capitalized term has the meaning assigned to it;

(b) An accounting term not otherwise defined has the meaning assigned to it in accordance with GAAP;

(c) References in the singular or to “him,” “her,” “it,” “itself,” or other like references, and references in the plural or the feminine or masculine reference, as the case may be, shall also, when the context so requires, be deemed to include the plural or singular, or the masculine or feminine reference, as the case may be;

(d) References to Articles and Sections and Exhibits shall refer to articles and sections and exhibits of this Agreement, unless otherwise specified;

(e) The headings in this Agreement are for convenience and identification only and are not intended to describe, interpret, define or limit the scope, extent or intent of this Agreement or any provision thereof;

(f) This Agreement shall be construed without regard to any presumption or other rule requiring construction against the party that drafted and caused this Agreement to be drafted; and

(g) All monetary figures shall be in United States dollars unless otherwise specified; and

(h) References to “including” in this Agreement means “including, without limitation,” whether or not so specified.

ARTICLE II

Purchase and Sale; Closing

2.1.

Closing .

Subject to Article X, the closing of the Contemplated Transactions (the “ Closing ”) will take place at the offices of Fried, Frank, Harris, Shriver & Jacobson LLP, One New York Plaza, New York, NY 10004, at 4:00 P.M. local time on the fifth Business Day immediately following the day on which the last of the conditions set forth in Article VI (other than those conditions that by their nature are to be satisfied at the Closing, but subject to the satisfaction or waiver of those conditions) are satisfied or waived in accordance with this Agreement, or on such other date as Buyer and Seller may otherwise agree. The day on which the Closing actually occurs is referred to herein as the “ Closing Date .”

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2.2.

Purchase and Sale .

(a) Subject to the terms and conditions set forth in this Agreement, and in reliance upon the representations, warranties, and covenants contained in this Agreement, at the Closing, Buyer shall purchase from Seller, and Seller shall sell, transfer and assign to Buyer, all of the Sirna Common Stock.

(b) In consideration for the Sirna Common Stock, Seller shall receive from Buyer (i) $25,000,000 (the “ Cash Consideration ”) and (ii) 2,520,044 shares of Buyer Common Stock (the “ Stock Consideration ,” and the Stock Consideration together with the Cash Consideration, the “ Total Consideration ”).

2.3.

Transactions at the Closing .

(a) At the Closing, simultaneous with Buyer’s receipt of the Sirna Common Stock and applicable instruments of transfer from Seller, Buyer shall (i) pay to Seller in consideration for the Sirna Common Stock, an amount equal to the Cash Consideration, by wire transfer of immediately available funds to an account designated by Seller, which such account shall be designated by Seller no fewer than three (3) Business Days prior to the Closing Date, and (ii) issue and deliver to Seller 85% of the Stock Consideration, including all other documents and instruments of issuance or transfer necessary to vest in Seller all of the right, title and interest in and to 85% of the Stock Consideration as of the Closing Date, free and clear of all Liens, other than restrictions expressly provided under this Agreement and/or under applicable Laws.

(b) Within 5 Business Days following the satisfaction of the Tech Transfer Condition in all material respects, Buyer shall issue and deliver to Seller 15% of the Stock Consideration, including all other documents and instruments of issuance or transfer necessary to vest in Seller all of the right, title and interest in and to 15% of the Stock Consideration as of the date thereof, free and clear of all Liens, other than restrictions expressly provided under this Agreement and/or under applicable Laws.

(c) At or prior to the Closing, Seller shall cause the Company to pay Seller an aggregate amount equal to the cash of the Company as of the Closing in the form of a dividend. Immediately prior to the Closing, all amounts owed pursuant to intercompany agreements or arrangements either to Seller or its Affiliates by the Company or to the Company by Seller or its Affiliates shall be extinguished and shall no longer be outstanding upon the Closing.

2.4.

Development of Royalty Products .

(a) Following the Closing, Buyer shall use Buyer Commercially Reasonable Discretion, to decide whether (i) to continue the progression of each Merck Royalty Product into further non-clinical development, clinical development or commercialization activities; and (ii) to otherwise exploit the Company Intellectual Property including by incorporation of Company Intellectual Property into a Buyer RNAi Product. To the extent that Buyer so decides to continue the progression of a Merck Royalty Product, Buyer shall use Buyer Commercially Reasonable Efforts to so progress such Merck Royalty Product or to find a collaborator or licensee to share or assume responsibility for such progression.

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(b) In respect of any applicable Merck Royalty Product, notwithstanding Buyer’s collaboration with a licensee or collaborator in accordance with the second sentence of Section 2.4(a), Buyer shall be solely responsible to Seller for all Contingent Payments relating to any such Merck Royalty Product.

2.5.

Contingent Payments .

In addition to the Total Consideration, each of the following amounts (each, a “ Contingent Payment ”) shall be payable by Buyer to Seller:

(a) Development Milestones : Buyer will make milestone payments to Seller based on achievement of the following development milestone events by Buyer or its Related Parties for each Royalty Product as set forth below. Each milestone payment by Buyer to Seller hereunder will be payable only once with respect to each Royalty Product that is comprised of or based on a different RNAi Product, regardless of the number of times achieved with respect to any such Royalty Product. Furthermore, in the event that further clinical development of a Buyer Royalty Product with respect to which one or more milestones payments have been made (an “ Original Product ”) is halted, and such Buyer Royalty Product is replaced in development by a different Buyer Royalty Product comprised of or based on an RNAi Product different from the RNAi Product in the Original Product but directed at the same target (a “ Backup Product ”), then Buyer will not be obligated to make any payments with respect to milestones achieved by the Backup Product for which Seller has already made a milestone payment with respect to the Original Product.

(i) Merck Royalty Product :

(A) $[***] upon [***];

(B) An additional $[***] upon [***];

(D) An additional $[***] upon [***].

(ii) Buyer Royalty Product :

(A) $[***] upon [***]; and

(B) An additional $[***] upon [***].

(b) Sales Milestones : Buyer will make milestone payments to Seller based on achievement of the following milestone events as set forth below. Each sales milestone payment by Buyer to Seller hereunder will be payable only once with respect to each Merck Royalty Product that is comprised of or based on a different RNAi Product, regardless of the number of times achieved with respect to any such Royalty Product.

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(i) $[***] upon [***] $[***]; and

(ii) An additional $[***] upon [***] ($[***]).

(i) Merck Royalty Products : Subject to Sections 2.5(c)(iii), (iv) and (v) below, a royalty of [***] percent ([***]) of Net Sales of each Merck Royalty Product.

(ii) Buyer Royalty Products : Subject to Sections 2.5(c)(iii), (iv) and (v) below, a royalty based on aggregate calendar year Net Sales of each Buyer Royalty Product as follows:


Aggregate Calendar Year Net Sales		Royalty (as a percentage of Net Sales)
$[*] - $[*]		[***]%
$[*]-$[*]		[***]%
Greater than $[***]		[***]%

Royalties on aggregate calendar year Net Sales shall be paid at the rate applicable to the portion of such aggregate Net Sales within each of the Net Sales levels above during such calendar year.

(iii) Royalty Term . Except as otherwise provided herein, royalties shall be payable on a Royalty Product-by-Royalty Product and country-by-country basis commencing on the First Commercial Sale of a Royalty Product in such country and continuing during any period in which there is a Valid Claim of an Acquired Sirna Patent in such country that would be infringed by the manufacture, use or sale of such Royalty Product in such country (such period, as applicable, the “ Royalty Term ”).

(iv) Royalty Adjustments:

(1) Third Party Royalties . Subject to Section 2.5(c)(iv)(3), if Buyer or any of its Related Parties obtains a license or similar right from any Person other than Buyer or its Related Parties under any Patent Rights covering technology that Buyer believes is reasonably necessary for the research, development, manufacture or commercialization of such Royalty Product, and if

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Buyer or any of its Related Parties is required to pay to such Person a royalty, license fees or milestone payments to obtain such license or similar right with respect to such Royalty Product, then the royalties due pursuant to Section 2.5(c)(i) and (ii), as the case may be, will be reduced by [***] percent ([***]) of the amount of the royalty, license fees or milestone payments reasonably attributable to such Royalty Product and paid to such Person.

(2) Generic Products . Subject to Section 2.5(c)(iv)(3), if in any calendar quarter after the First Commercial Sale of a Royalty Product in a country, the market share of all Generic Product(s) in such country is equal to or greater than [***] percent ([***]) of the amount of aggregate sales of such Royalty Product and all Generic Product(s) in such country, then the royalties payable by Buyer to Seller in respect of such Royalty Product in such country shall be reduced in such calendar quarter to [***] percent ([***]) of the royalties that would otherwise be payable to Seller in such calendar quarter with respect to such Royalty Product in such country pursuant to Section 2.5(c)(i) or (ii), as the case may be. “ Generic Product ” means any pharmaceutical product that contains the same biologically active ingredient(s) (or regulatory equivalents thereof, such as those delineated in 37 C.F.R. §1.710(b)(1)) as are contained in the applicable Royalty Product.

(3) Limitations . Notwithstanding the foregoing, the royalties payable to Seller will not be reduced in any such event to less than [***] percent ([***]) of the amounts set forth in Section 2.5(c)(i) or (ii), as the case may be, solely by reason of any reduction under this Section 2.5(c)(iv)(2).

(v) Other Royalty Provisions . Only one royalty will be due with respect to the same unit of Royalty Product. No royalties will be due upon the sale or other transfer among Buyer and its Related Parties, but in such cases the royalty will be due and calculated upon Buyer’s and its Related Parties’ Net Sales to the first independent Third Party. No royalties will accrue on the sale or other disposition of a Royalty Product by Buyer or its Related Parties for use in a clinical study sponsored or funded by Buyer or on the disposition of a Royalty Product in reasonable quantities by Buyer or its Related Parties as samples (promotion or otherwise) or as donations (for example, to non-profit institutions or government agencies for a non-commercial purpose).

(d) Sublicense Value Share . In the event that Buyer or its Affiliate grants a Naked License, Buyer will pay Seller an amount equal to [***] percent ([***]) of any Sublicense Value with respect to such Naked License; provided, that solely with respect to Sublicense Value received as royalties on sales of Royalty Products, Seller shall be entitled to receive the greater of (i) [***] percent ([***]) of the Sublicense Value received as royalties on sales of Royalty Products, or (ii) a royalty of [***] percent ([***]) of annual Net Sales of Royalty Products by a licensee or sublicensee under a Naked License (subject to the terms of Sections 2.5(c)(iii), (iv) and (v)), in each case of clauses (i) and (ii) above, as apportioned for the relative value received under such Naked License that is attributable specifically to the Acquired Sirna Patents being licensed or sublicensed.

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(e) Payment Obligations and Reports .

(i) Payment Account . Any Contingent Payments shall be paid to Seller by wire transfer of immediately available funds to such bank account in the United States as may be designated in writing by Seller from time to time. In the case of sales of Royalty Products outside the United States by Buyer and its Related Parties, the rate of exchange to be used in computing the amount of currency equivalent in United States dollars due will be made at the rate of exchange utilized by Buyer (or its Licensee, if applicable) in its worldwide accounting system, prevailing on the last day of the applicable calendar quarter.

(ii) Milestone Payments . Buyer will notify Seller in writing of the achievement of each of the milestone events set forth in Sections 2.5(a)(i) and (ii) and subject to Section 2.5(g) pay to Seller the Contingent Payment amounts set forth in such sections with respect to such milestone event within [***] days of such achievement of the relevant milestone event.

(iii) Sublicense Value Share Payments . Buyer will notify Seller in writing promptly of the grant of a Naked License. Within [***] days of such notice Buyer will provide Seller with the relevant texts of all documents governing the Naked License transaction together with a good faith determination of each element of the Sublicense Value for such Naked License and the resulting calculation of Seller’s Sublicense Value share pursuant to Section 2.5(d), and will explain the basis on which such determination and calculation has been made by Buyer (such notice, a “ Sublicense Value Share Notice ”). Concurrent with the Sublicense Value Share Notice, Buyer will remit to Seller any payment then due as set forth in the Sublicense Value Share Notice. If Seller in good faith believes the determination of Sublicense Value in the Sublicense Value Share Notice does not reasonably reflect the relative value attributable to the Acquired Sirna Patents in such Naked License transaction, it shall notify Buyer in writing of its belief (and the basis of such belief) within [***] days after receiving Buyer’s Sublicense Value Share Notice. If despite good faith efforts Buyer and Seller are unable to agree upon such Sublicense Value within [***] days of Seller’s notice, then the dispute will be referred to the Buyer’s CEO and the Seller’s President of Research and Development (or their respective designees) for resolution. If these executive officers are unable to agree within [***] days after the dispute is referred to them, then either Buyer or Seller may request that a third party determine such Sublicense Value by baseball arbitration pursuant to Section 11.12. Buyer’s obligation to make further payments to Seller pursuant to Section 2.5(d) with respect to such Naked License transaction will be suspended during the pendency of such dispute and any arbitration.

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(iv) Royalty Payments and Reports . Within [***] days after the end of each calendar quarter after the First Commercial Sale of a Royalty Product or the grant of a Naked License, as the case may be, Buyer will deliver to Seller a report containing the following information for the prior calendar quarter:

(1) a calculation of Net Sales of each Royalty Product that is sold by Buyer and its Related Parties, if any;

(2) the achievement of any of the milestone events in Section 2.5(b);

(3) subject to Section 2.5(e)(iii), a calculation of Sublicense Value with respect to each Naked License as set forth in Section 2.5(d) (if any) and specifically: (x) the amount of Sublicense Value, if any, received by Buyer from its licensees and sublicensees of such Naked License pursuant to the terms of the Naked License agreement, specifically including any amounts received as royalties on sales of Royalty Products, and (y) a calculation of Net Sales of such Royalty Products by such licensees and sublicensees pursuant to such Naked License agreement, if any, in each case as necessary to determine the Sublicense Value calculation set forth in Section 2.5(d);

(4) the amount of Taxes, if any, withheld to comply with applicable law; and

(5) a calculation of payments due to Seller with respect to the foregoing (including the calculation of any royalty adjustments pursuant to Section 2.5(c)(iv), the calculation of any royalty due in lieu of a share of Sublicense Value as set forth in Section 2.5(d) and any calculation of currency conversion). Concurrent with these reports, Buyer will remit to Seller any payment due for the applicable calendar quarter. All such reports will be considered Confidential Information of Buyer and will be maintained in confidence by Seller. If no royalties or other payments are due to Seller for such reporting period, the report will so state.

(f) Records and Audit Right . Buyer will keep, and will require all its Related Parties to keep, correct and complete books of accounts and other records containing all information and data that may be necessary to ascertain and verify the royalties and other amounts payable under this Agreement. Until the expiration of the last Royalty Term, Seller has the right from time to time (not to exceed once during each calendar year) to have an independent certified public accountant inspect such books and records of Buyer and/or its Affiliates at Seller’s expense. Such inspection will be conducted after reasonable prior notice by Seller to Buyer during Buyer’s ordinary business hours, will not be more frequent than once during each calendar year and may cover only the three (3) year period immediately preceding the date of the audit. Any such independent certified accountant will be reasonably acceptable to Buyer, will execute Buyer’s standard form of confidentiality agreement (subject to reasonable modifications agreed by Buyer and such independent certified accountant), and will be permitted to share with Seller solely its findings with respect to the accuracy of the royalties and other

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amounts reported as payable under this Agreement. If such accounting determines that Buyer paid Seller less than the amount properly due in respect of any calendar quarter, then Buyer will reimburse Seller such amount, and if the amount underpaid exceeds [***] percent ([***]) of the amount actually due or $[***], Buyer will also reimburse Seller for the costs of such accounting (including the fees and expenses of the certified public accountant). In the event such accounting determines that Buyer paid Seller more than the amount properly due in respect of any calendar quarter, then any excess payments made by Buyer will be credited against future amounts due to Seller from Buyer, or if no such future amounts are reasonably expected to be due to Seller from Buyer, then Seller will reimburse Buyer for any overpayment by Buyer.

2.6.

Tax Withholding .

If Buyer concludes that it is required by law to withhold Taxes from any payment to Seller, Buyer shall provide commercially reasonable written notice to Seller of its intention to withhold, and the basis for such withholding, prior to withholding and paying the required amount to the appropriate Governmental Authority. Buyer will promptly provide Seller with all information relating to such withholding that is reasonably requested by Seller including, without limitation, original receipts or other evidence reasonably desirable and sufficient to allow Seller to document such tax withholdings for purposes of claiming foreign tax credits and similar benefits.

ARTICLE III

Representations and Warranties of Seller

Except as set forth in the Company Disclosure Schedule (it being agreed that any matter disclosed in the Company Disclosure Schedule with respect to any section of this Agreement shall be deemed to have been disclosed with respect to any other section to the extent the applicability thereto is reasonably apparent), Seller hereby represents and warrants to Buyer as follows:

3.1.

Organization and Power .

Each of the Company, Seller and Merck is a corporation or legal entity duly incorporated or organized, validly existing and in good standing under the Laws of its respective jurisdiction of its incorporation or organization. Each of the Company, Seller and Merck has full power and authority to execute, deliver and perform its obligations under this Agreement and the Ancillary Documents to which it is a party and to consummate the transactions contemplated hereby and thereby. The Company has all power and authority, and possesses all governmental licenses and permits necessary to enable it to own or lease and to operate its properties and assets and carry on its business as currently conducted, and is qualified to do business and is in good standing (with respect to jurisdictions that recognize the concept of good standing) as a foreign corporation in each jurisdiction where the ownership, or operation of its properties or assets or conduct of its business requires such qualification, except such power, authority, licenses, permits and qualification the absence of which do not have, and would not reasonably be expected to have, either individually or in the aggregate, a Company Material Adverse Effect.

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Prior to the date of this Agreement, Seller has delivered or made available to Buyer accurate and complete copies of the Amended and Restated Certificate of Incorporation, as currently in effect, of the Company.

3.2.

Authorization and Enforceability .

The execution and delivery of this Agreement and the Ancillary Documents to which the Company, Seller or Merck is a party, the performance by each of the Company, Seller and Merck of its obligations under this Agreement and the Ancillary Documents to which it is a party, and the consummation by each of the Company, Seller and Merck of the transactions contemplated hereby and thereby have been duly authorized by the Company, Seller and Merck and no other corporate proceedings on the part of the Company, Seller or Merck (including, without limitation, any shareholder vote or approval) are necessary to authorize the execution and delivery of this Agreement and the Ancillary Documents to which the Company, Seller or Merck is a party, the performance by each of the Company, Seller and Merck of its obligations under this Agreement and the Ancillary Documents to which it is a party, or the consummation by each of the Company, Seller and Merck of the transactions contemplated hereby and thereby. This Agreement is, and each of the Ancillary Documents to be executed and delivered at the Closing by the Company, Seller and/or Merck will be at the Closing, duly authorized, executed and delivered by the Company, Seller and/or Merck, as the case may be, and constitute, or as of the Closing Date will constitute, valid and legally binding agreements of the Company, Seller and/or Merck, as the case may be, enforceable against the Company, Seller and/or Merck, as the case may be, in accordance with their terms, subject to bankruptcy, insolvency, reorganization and other Laws of general applicability relating to or affecting creditors’ rights generally and to general equity principles.

3.3.

Capitalization of the Company .

(a) The Company . The authorized capital stock of the Company consists of 100 shares of Sirna Common Stock, of which 100 shares are issued and outstanding, and no shares of preferred stock. Seller is the record and beneficial owner of all of the outstanding shares of Sirna Common Stock. All outstanding shares of Sirna Common Stock (i) have been duly authorized and validly issued, (ii) are fully paid and non-assessable, (iii) are owned beneficially and of record by Seller, free and clear of any Lien, and (iv) were issued in compliance with applicable securities Laws or exemptions therefrom. Except for the shares of Sirna Common Stock owned and held by Seller, at the close of business on the date hereof, no shares of capital stock or other Equity Securities of the Company were issued, reserved for issuance or outstanding. The Company does not have any outstanding securities convertible into or exchangeable or exercisable for any shares of its capital stock or any rights to subscribe for or to purchase, or any agreements providing for the issuance (contingent or otherwise) of any shares of its capital stock. The Company is not, and Seller is not, a party to any right of first refusal, right of first offer, proxy, voting agreement, voting trust, registration rights agreement or shareholders agreement with respect to the sale or voting of any shares of capital stock of the Company or any securities convertible into or exchangeable or exercisable for any shares of capital stock of the Company. The Company does not have outstanding any bonds, debentures,

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notes or other obligations the holders of which have the right to vote (or which are convertible into or exercisable for securities having the right to vote) with the stockholders of the Company on any matter.

(b) Subsidiaries . The Company has no subsidiaries, and is not obligated to make any investment (whether in the form of a loan, capital contribution, or similar investment) in any other Person.

3.4.

No Violation .

The execution and delivery by the Company, Seller and Merck of this Agreement and the Ancillary Documents to which the Company, Seller or Merck is a party, the performance by each of the Company, Seller and Merck of its obligations under this Agreement and the Ancillary Documents to which it is a party, and the consummation by each of the Company, Seller and Merck of the transactions contemplated hereby and thereby will not (a) conflict with or violate any provision of the certificate of incorporation, bylaws or other similar organizational documents of the Company, Seller or Merck, (b) assuming that all consents, approvals and authorizations contemplated by Section 3.5 have been obtained and all filings described therein have been made, conflict with or violate any Law applicable to the Company, Seller or Merck or by which its or any of their respective properties is bound or affected, (c) to the Knowledge of Seller, as of the date hereof, result in a breach, violation or infringement of, or constitute (with or without due notice or lapse of time or both) a default (or give rise to the creation of any Lien (other than Permitted Liens) or any right of termination, amendment, cancellation or acceleration) under, any of the terms, conditions or provisions of any Material Contract, (d) except as set forth in Section 3.4(d) of the Company Disclosure Schedule, to the Knowledge of Seller, change the rights or obligations of any party under any Material Contract, or (e) result in the creation of, or require the creation of, any Lien upon any shares of capital stock of the Company, except, in the cases of clauses (b), (c) or (d), to the extent such conflict, liability or Lien does not have and would not reasonably be expected to have, either individually or in the aggregate, a Company Material Adverse Effect.

3.5.

Governmental Authorizations and Consents .

No consents, licenses, approvals or authorizations of, or registrations, declarations, filings with or notices to, any Governmental Authority (“ Governmental Consents ”) are required to be obtained or made by the Company, Seller or Merck in connection with the execution, delivery, performance, validity and enforceability of this Agreement or any Ancillary Documents to which the Company, Seller or Merck is, or is to be, a party or the consummation by the Company, Seller or Merck of the transactions contemplated hereby and thereby, other than (a) a filing with the FTC and the DOJ under the HSR Act and (b) those Governmental Consents listed in Section 3.5 of the Company Disclosure Schedule, and except for those for which the failure to obtain such Governmental Consents does not have and would not reasonably be expected to have, either individually or in the aggregate, a Company Material Adverse Effect.

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3.6.

Employees; Real Property; Employee Benefits; Environmental Matters .

(a) Except as set forth in Section 3.6 of the Company Disclosure Schedule, the Company has no employees and has had no employees at any time during the twelve (12) months immediately preceding the date of this Agreement, and does not own or lease any real property.

(b) All amounts owed or that may become owed by the Company under the terms of any Employee Plan have been timely paid or will be paid by Seller, and the Company has no unfunded liability with respect to any deferred compensation, retirement, or other Employee Plan. The Company has complied with the applicable continuation requirements for each Employee Plan, including (i) Section 4980B of the Code and Sections 601 through 608, inclusive, of ERISA (“ COBRA ”) and (ii) any applicable state Law mandating welfare benefit continuation coverage for employees. Neither the Company nor any fiduciary of an Employee Plan has violated any requirements of ERISA except as would not, individually or in the aggregate, reasonably be expected to have a Company Material Adverse Effect. The Company has never contributed to, or had any obligation to contribute to, or has or ever had any liability with respect to: a “multiemployer plan” within the meaning of Section 3(37) of ERISA or Section 414(f) of the Code or a plan that has two or more contributing sponsors, at least two of whom are not under common control within the meaning of Section 413(c) of the Code.

(c) Except as would not, individually or in the aggregate, reasonably be expected to have a Company Material Adverse Effect: (i) no real property (including soils, groundwater, surface water, buildings or other structures thereon or thereunder) owned, operated, used or occupied by the Company has been contaminated as a result of release, spill, discharge or disposal of any Hazardous Substance during or, to the Knowledge of Seller, prior to, the ownership or operation or use by the Company, in each case that would be reasonably likely to require investigation and/or remediation pursuant to Environmental Law; (ii) no real property formerly owned or operated or used by the Company was contaminated as a result of release, spill, discharge or disposal of any Hazardous Substance during or, to the Knowledge of Seller, prior to, the ownership or operation or use by the Company, in each case that would be reasonably likely to require investigation and/or remediation pursuant to Environmental Law; (iii) the Company has not received any written notice, demand, letter, claim or request for information from any Governmental Authority or other third party indicating that the Company may be in material violation of or subject to material liability under any Environmental Law or arising from Hazardous Substances; (iv) the Company is not subject to any material order, decree, injunction or other arrangement with any Governmental Authority or a party to any indemnity or any other agreement with any third party under any Environmental Law or otherwise relating to any Hazardous Substances; and (v) the Company has obtained in a timely manner, maintained in effect, and is in material compliance with, all Permits required by applicable Environmental Law in connection with the business of the Company. The Company has delivered, or made available to Buyer, true and complete copies and results of any reports, studies, analyses, tests or monitoring possessed or initiated by the Company pertaining to Environmental Law.

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3.7.

Intellectual Property .

(a) Subject to the consummation of the transactions contemplated in the Ancillary Documents, Section 3.7(a) of the Company Disclosure Schedule includes all (i) material patents and patent applications owned by the Company on the date of this Agreement and (ii) material trademark registrations and applications, material copyright registrations and applications, and material domain name registrations and applications, in each case, owned by the Company on the date of this Agreement ((i) and (ii), collectively, the “ Owned Intellectual Property ”), except that, notwithstanding any other provision of this Agreement, Seller makes no representations or warranties with respect to (A) the Intellectual Property identified on Section 3.7(a)(iii) of the Company Disclosure Schedule or (B) any other patents, patent applications, or other Intellectual Property owned by the Company that are directed to ribozyme technology .

(b) Subject to the consummation of the transactions contemplated in the Ancillary Documents, and except as set forth in Section 3.7(b) of the Company Disclosure Schedule, as of the date of this Agreement (i) to the Knowledge of Seller, each item of Owned Intellectual Property is valid, subsisting and enforceable, and (ii) the Company is the exclusive owner of all Owned Intellectual Property, free and clear of any Liens, exclusive licenses, or non-exclusive licenses not granted in the ordinary course of business.

(c) Subject to the consummation of the transactions contemplated in the Ancillary Documents, and except as set forth in Section 3.7(c) of the Company Disclosure Schedule, on the date of this Agreement no Owned Intellectual Property is subject to any (i) outstanding order, ruling, judgment or decree of a Governmental Authority adversely affecting the use thereof or rights thereto by the Company, or (ii) pending (or, to the Knowledge of Seller, threatened) opposition, cancellation, nullification, interference, public protest, domain name dispute, reexamination, reissue or other proceeding before a Governmental Authority or Internet domain name registrar (other than the review of pending applications by applicable Governmental Authorities). Buyer acknowledges that for purposes of Section 3.7(c)(ii), any opposition, cancellation, nullification, interference, public protest, domain name dispute, reexamination, reissue or other proceeding that has been initiated but with respect to which process or other comparable notice has not been served on or delivered to Seller or the Company will be deemed to be “threatened” rather than “pending.”

(d) Subject to the consummation of the transactions contemplated in the Ancillary Documents, and except as set forth in Section 3.7(d) of the Company Disclosure Schedule, no Affiliate of Seller (other than Company) owns or holds an in-license to any Owned Intellectual Property.

(e) To the Knowledge of Seller, the operation of the business of the Company does not, as of the date of this Agreement, infringe or misappropriate any Intellectual Property of any third parties in any material respect. To the Knowledge of Seller, as of the date of this Agreement, no third party is infringing or misappropriating in any material respect any Intellectual Property owned by the Company. Except as set forth in Section 3.7(e) of the Company Disclosure Schedule, as of the date of this Agreement no claim, action, litigation or

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other proceeding alleging misappropriation or infringement of Owned Intellectual Property or the Intellectual Property of any other Person is pending (or, to the Knowledge of Seller, is threatened) by or against the Company (including but not limited to cease and desist letters or offers for license). As of the date of this Agreement, there is no claim pending against the Company by any indemnitee of the Company to indemnify that indemnitee for infringement or misappropriation of Intellectual Property. No claim, action, litigation or other proceeding alleging misappropriation or infringement of the Intellectual Property of any other Person is pending (or, to the Knowledge of Seller, is threatened) by or against Merck or any of its Affiliates with respect to the research, development, manufacture, sale or use of RNAi Products or the use of the RNAi Technology Platform (including but not limited to cease and desist letters or offers for license) as of the date of this Agreement. Buyer acknowledges that (i) the representations and warranties set forth in this Section 3.7(e) are (A) subject to the consummation of the transactions contemplated in the Ancillary Documents and (B) the only representations and warranties Seller makes in this Agreement with respect to infringement, misappropriation or other violation of Intellectual Property, and (ii) for purposes of this Section 3.7(e), any claim, action, litigation or other proceeding that has been initiated but with respect to which process or other comparable notice has not been served on or delivered to Seller or the Company will be deemed to be “threatened” rather than “pending.”

(f) Except as would not, individually or in the aggregate, reasonably be expected to have a Company Material Adverse Effect, and except as a result of any Contracts that Buyer is subject to prior to the consummation of the Contemplated Transactions or any Material Contracts (or, to the Knowledge of Seller, any other Contract that the Company is subject to prior to the consummation of the Contemplated Transactions), the execution, delivery and performance by the Company of the Contemplated Transactions will not (i) alter, impair, diminish or result in the loss of any rights or interests of the Company in any Company Intellectual Property, (ii) grant or require the Company to grant to any Person any rights with respect to any Company Intellectual Property (other than under the Out-License Agreement) that the Person did not have prior to the consummation of the Contemplated Transactions, or (iii) subject the Company to any increase in or acceleration of royalties or other payments in respect of any Intellectual Property licensed to the Company (except as expressly contemplated under this Agreement). The Company has taken and is now taking reasonable measures under the circumstances to maintain the confidentiality of any material trade secrets constituting Company Intellectual Property .

3.8.

Contracts .

(a) Material Contracts . To the Knowledge of Seller, as of the date hereof, Parts I and II of Section 3.8(a) of the Company Disclosure Schedule, together, constitute a true and complete list of all of the following Contracts to which the Company is a party or by which the Company and/or its assets are bound (the “ Material Contracts ”):

(i) Contracts evidencing any obligations of the Company with respect to the issuance, sale, repurchase or redemption of any Equity Securities of the Company;

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(ii) all Company IP Agreements that are material to the operation of the business of the Company, other than “material transfer agreements” in customary form entered into in the ordinary course of business;

(iii) Contracts relating to any Litigation involving the Company at any time since the acquisition of the Company by an Affiliate of Seller;

(iv) Contracts limiting the freedom of the Company to engage in any line of business, acquire any entity or compete with any Person or in any market or geographical area;

(v) Contracts concerning any joint venture, or any research, development, manufacturing or commercialization collaboration or partnership;

(vi) Contracts to supply or manufacture any materials for any third party;

(vii) Contracts with any director or officer of the Company;

(viii) all Contracts not otherwise listed above involving reasonably anticipated payments to or from the Company in excess of $250,000 per annum.

(b) Status of Material Contracts . To the Knowledge of Seller, as of the date hereof, a true and complete copy of each Material Contract has been made available to Buyer. Except as disclosed in Section 3.8(b) of the Company Disclosure Schedule, to the Knowledge of Seller, all Material Contracts listed on Part I of Section 3.8(a) of the Company Disclosure Schedule are valid, binding and in full force and effect , and are enforceable by the Company in accordance with their respective terms, subject to bankruptcy, insolvency, reorganization and other Laws of general applicability relating to or affecting creditors’ rights generally and to general equity principles. To the Knowledge of Seller, as to each such Material Contract, there does not exist thereunder as of the date hereof any breach or default on the part of the Company or, to the Knowledge of Seller, any other party to such Material Contract. The Company has in all material respects performed all material obligations required to be performed by it to date under each such Material Contract. To the Knowledge of Seller, neither the Company nor Seller has received, as of the date hereof, notice of the existence of any event or condition that constitutes, or, after notice or lapse of time or both, will constitute a default on the part of the Company under any such Material Contract, except where such default has not had, and would not reasonably be expected to have, either individually or in the aggregate, a Company Material Adverse Effect.

3.9.

Compliance with Laws .

(a) To the Knowledge of Seller, since January 1, 2011, the Company has conducted its business in accordance with all applicable federal, state, local or foreign Laws in all material respects, including Laws enforced by the United States Food and Drug

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Administration (“ FDA ”) or any similar applicable state or foreign regulatory or Governmental Authorities. The Company is not debarred under the Federal Food, Drug and Cosmetic Act or otherwise excluded from or restricted in any manner from participation in, any government program related to pharmaceutical products and, to the Knowledge of Seller, does not employ or use the services of any individual or entity that is or, during the time when such individual or entity was employed by or providing services to the Company, was debarred or otherwise excluded or restricted. As of the date hereof, no investigation or review by any Governmental Authority with respect to the Company is pending or to the Knowledge of Seller, threatened, nor has any Governmental Authority indicated an intention to conduct the same, except for such investigations or reviews that would not have, and would not reasonably be expected to have, either individually or in the aggregate, a Company Material Adverse Effect.

(b) Since the acquisition of the Company by an Affiliate of Seller, neither the Company nor, to the Knowledge of Seller, any director, officer, agent, employee or third party representative acting for or on behalf of the Company has been in violation of the U.S. Foreign Corrupt Practices Act of 1977, as amended, or any other anti-bribery or anti-corruption laws applicable to the Company in any manner that would reasonably be expected, individually or in the aggregate, to result in Company Material Adverse Effect.

(c) To the Knowledge of Seller, the Company has all governmental permits, licenses, franchises, variances, exemptions, orders issued or granted by a Governmental Authority and all other authorizations, consents and approvals issued or granted by a Governmental Authority (“ Permits ”) necessary to conduct the business of the Company as presently conducted, except those the absence of which would not have, and would not reasonably be expected to have, either individually or in the aggregate, a Company Material Adverse Effect (the “ Material Permits ”). There is not pending or, to the Knowledge of Seller, threatened before any Governmental Authority any proceeding, notice of violation, order of forfeiture or complaint or investigation against the Company relating to any Material License, in each case, except as would not have, and would not reasonably be expected to have, either individually or in the aggregate, a Company Material Adverse Effect.

3.10.

Financial Statements; No Undisclosed Liabilities .

(a) Seller has delivered to Buyer: (i) unaudited balance sheets of the Company as at December 31, 2010, 2011 and 2012 and the related unaudited statements of income, including the notes thereto; and (ii) an unaudited balance sheet of the Company as of the nine months ended September 30, 2013, and the related unaudited statements of income. Each of the financial statements delivered pursuant to this Section 3.10 were prepared in good faith and, to the Knowledge of Seller, present, in all material respects, the financial condition of the Company as of the date thereof.

(b) The Company has no liabilities, whether accrued, absolute, fixed or contingent, other than (i) liabilities specifically identified in Section 3.10 of the Company Disclosure Schedule, (ii) liabilities incurred under this Agreement, (iii) liabilities incurred in the ordinary course of business, (iv) liabilities that currently are not, and would not reasonably be expected to have, either individually or in the aggregate, a Company Material Adverse Effect and (v) liabilities disclosed on the Company Disclosure Schedule.

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(c) Seller has, to the Knowledge of Seller, made available to Buyer copies of all minute books and written records in the possession of Seller or the Company.

3.11.

Indebtedness . The Company will have no Indebtedness as of the Closing Date.

3.12.

Litigation; Insurance .

(a) Except as set forth in Section 3.12 of the Company Disclosure Schedule, as of the date hereof, there are no civil, criminal or administrative claims, actions, suits, inquiries, investigations or proceedings (“ Litigation ”) pending or, to the Knowledge of Seller, threatened against or involving the Company or its properties or business , at Law or in equity or before any Governmental Authority. The Company is not subject to any Order arising from any Litigation.

(b) The Company is not party to any insurance policies issued by any third party insurance company.

3.13.

Taxes and Tax Matters .

(a) The Company has not been a member of an Affiliated Group filing a consolidated federal Income Tax Return other than a Merck Affiliated Group. The Company has prepared in good faith and duly and timely filed (taking into account any valid extension of time within which to file) all Income Tax Returns and other material Tax Returns that it was required to file, and all such filed Tax Returns are accurate and complete in all material respects. The Company has timely paid or caused to be paid all Income Taxes and other material Taxes that are required to be paid by the Company (whether or not shown on any Tax Return), including all Taxes required to have been withheld and paid by the Company in connection with any amounts paid or owing to any employee, independent contractor, stockholder, creditor or other third party. All material deficiencies asserted in writing or assessments made as a result of any examinations or other audits by federal, state, local or foreign Taxing Authorities have been paid in full or settled. The Company has neither waived any statute of limitations in respect of Income Taxes nor agreed to any extension of time with respect to an Income Tax assessment or deficiency. No federal or material state, local or foreign Tax audit or administrative or judicial proceeding is pending or being conducted with respect to the Company, and the Company has not received from any federal, state, local or foreign Taxing Authority any written notice indicating an intent to open an audit. The Company has not engaged in any “listed transaction” within the meaning of Section 1.6011-4(b)(2) of the Treasury Regulations. The Company has no material liability for the Taxes of any Person (other than the Company) under Treasury Regulation Section 1.1502-6 (or any comparable provision of state, local or foreign Law), as a transferee or successor, by contract or otherwise.

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(b) Neither the execution and delivery of this Agreement nor the consummation of the Contemplated Transactions will (either alone or in conjunction with any other event) result in, cause the accelerated vesting, funding or delivery of, or increase the amount or value of, any payment or benefit to any employee, officer or director of the Company.

3.14.

Investment Experience and Accredited Investor Status; Securities Laws Matters .

Seller is an “accredited investor” (as defined in Regulation D under the Securities Act). Seller has such knowledge and experience in financial or business matters that it is capable of evaluating the merits and risks of the receipt of the Stock Consideration. Seller is acquiring the Stock Consideration for Seller’s own account and for the purpose of investment and not with a view to distribution or resale thereof.

3.15.

Acquiring Person .

As of the date of this Agreement, neither Seller nor any of its Affiliates beneficially owns, or will beneficially own (as determined pursuant to Rule 13d-3 under the Exchange Act without regard for the number of days in which a Person has the right to acquire such beneficial ownership), any securities of Buyer.

3.16.

Restricted Securities

Seller understands that the Stock Consideration, when issued, shall be “restricted securities” under the federal securities Laws inasmuch as they are being acquired from Buyer in a transaction not involving a public offering and that under such Laws the Stock Consideration may be resold without registration under the Securities Act only in certain limited circumstances. Seller represents that it is familiar with Rule 144 of the Securities Act, as presently in effect.

3.17.

Legends

Seller understands that the certificates representing the Stock Consideration shall bear the following legends:

(a) “These securities have not been registered under the Securities Act of 1933. They may not be sold, offered for sale, pledged or hypothecated in the absence of a registration statement in effect with respect to the securities under the Securities Act or an opinion of counsel (which counsel shall be reasonably satisfactory to Buyer) that such registration is not required or unless sold pursuant to Rule 144 of the Securities Act.”; and

(b) any legend required by applicable state securities Laws.

3.18.

No Brokers .

None of the Company, Seller or Merck (or any of its Affiliates) have employed or incurred any liability to any broker, finder or agent for any brokerage fees, finder’s fees, commissions or other amounts with respect to this Agreement, the Ancillary Documents or the transactions contemplated hereby and thereby.

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3.19.

Sufficiency of Assets .

Except as set forth in Section 3.19 of the Company Disclosure Schedule, on the Closing Date, to the Knowledge of Seller, the Company will hold, as owner or licensee, all Patent Rights and Know-How of Merck and its Affiliates (other than the Company) that constitute the RNAi Technology Platform, subject to the rights in Intellectual Property granted in the Out-License Agreement.

3.20.

Disclaimer .

Notwithstanding anything to the contrary contained in this Agreement, neither the Company, Seller nor any of its Affiliates, representatives or advisors has made, or shall be deemed to have made, to Buyer or any other Person any representations or warranty with respect to this Agreement, the Ancillary Documents or the transactions contemplated hereby and thereby other than those expressly made by the Company in this Article III. Without limiting the generality of the foregoing, no representation or warranty has been made or is being made herein to Buyer, its Related Parties or any of their respective representatives (i) as to merchantability, suitability or fitness for a particular purpose, or quality, with respect to any tangible assets or as to the condition or workmanship thereof or the absence of any defects therein, whether latent or patent (or any other representation or warranty referred to in section 2-312 of the uniform commercial code of any applicable jurisdiction), or (ii) with respect to any projections, forecasts, business plans, estimates or budgets delivered to or made available to Buyer, its Related Parties, or any of their respective representatives.

3.21.

[***].

(a) [***].

(b) [***].

ARTICLE IV

Representations and Warranties of Buyer

Except as set forth in the Buyer Disclosure Schedule (it being agreed that any matter disclosed in the Buyer Disclosure Schedule with respect to any section of this Agreement shall be deemed to have been disclosed with respect to any other section to the extent the applicability thereto is reasonably apparent), Buyer hereby represents and warrants to Seller as follows:

4.1.

Organization and Power .

Buyer is a corporation duly incorporated, validly existing and in good standing under the Laws of the state of Delaware and has full power and authority to execute, deliver and perform its obligations under this Agreement and the Ancillary Documents to which it is a party and to consummate the transactions contemplated hereby and thereby.

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4.2.

Authorization and Enforceability .

The execution and delivery of this Agreement and the Ancillary Documents to which Buyer is a party, the performance by Buyer of its obligations under this Agreement and the Ancillary Documents to which it is a party, and the consummation by Buyer of the transactions contemplated hereby and thereby have been duly authorized by Buyer, and no other corporate proceedings on the part of Buyer (including, without limitation, any shareholder vote or approval) are necessary to authorize the execution and delivery of this Agreement and the Ancillary Documents to which Buyer is a party, the performance by Buyer of its obligations under this Agreement and the Ancillary Documents to which it is a party, or the consummation by Buyer of the transactions contemplated hereby and thereby. This Agreement is, and each of the Ancillary Documents to be executed and delivered at the Closing by Buyer will be at the Closing, duly authorized, executed and delivered by Buyer and constitute, or as of the Closing Date will constitute, valid and legally binding agreements of Buyer enforceable against Buyer, in accordance with their terms, subject to bankruptcy, insolvency, reorganization and other Laws of general applicability relating to or affecting creditors’ rights generally and to general equity principles.

4.3.

No Violation .

The execution and delivery by Buyer of this Agreement and the Ancillary Documents to which Buyer is a party, the performance by Buyer of its obligations under this Agreement and the Ancillary Documents to which it is a party, and the consummation of the transactions contemplated hereby and thereby will not (a) conflict with or violate any provision of the certificate of incorporation, bylaws or similar organizational documents of Buyer, or (b) assuming that all consents, approvals and authorizations contemplated by Section 4.4 have been obtained and all filings described therein have been made, conflict with or violate in any material respect any Law applicable to Buyer or by which its respective properties are bound or affected. Neither Buyer nor its Affiliates are subject to any Contract that would have a Buyer Material Adverse Effect.

4.4.

Governmental Authorizations and Consents .

No Governmental Consents are required to be obtained or made by Buyer in connection with the execution, delivery, performance, validity and enforceability of this Agreement or any Ancillary Documents to which Buyer is, or is to be, a party, or the consummation by Buyer of the transactions contemplated hereby and thereby, other than (a) a filing with the FTC and the DOJ under the HSR Act and (b) those Governmental Consents listed in Section 4.4 of the Buyer Disclosure Schedule, and except for those for which the failure to obtain such Governmental Consents does not have and would not reasonably be expected to have, either individually or in the aggregate, a Buyer Material Adverse Effect. All representations, warranties, statements or other communications, whether express or implied, made by Buyer to any Governmental Authority in connection with any Governmental Consents shall be true and correct.

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4.5.

Litigation .

There is no Litigation pending or, to the Knowledge of Buyer, threatened against or involving Buyer which questions the validity of this Agreement or any of the Ancillary Documents to which it is a party or seeks to prohibit, enjoin or otherwise challenge Buyer’s ability to consummate the Contemplated Transactions.

4.6.

Financial Capacity .

Buyer has, or has access to, and will have available on the Closing Date, funds in an amount that is sufficient to pay the Cash Consideration as required by and in accordance with this Agreement.

4.7.

No Brokers .

Neither Buyer nor or any of its Affiliates has employed or incurred any liability to any broker, finder or agent for any brokerage fees, finder’s fees, commissions or other amounts with respect to this Agreement, the Ancillary Documents or the Contemplated Transactions.

4.8.

No Section 368(a) Reorganization .

Neither Buyer nor any of Buyer’s Affiliates has any plan or intention to (i) merge or liquidate the Company into Buyer or any subsidiary of Buyer (including by causing or permitting the Company to become an entity that is disregarded as separate from Buyer or any subsidiary of Buyer, in each case, within the meaning of Treasury Regulation Section 301.7701-3(b)(1)(ii)), or (ii) take any other action that could reasonably be expected to cause the sale of the Sirna Common Stock by Seller to Buyer pursuant to this Agreement to qualify as a “reorganization” within the meaning of Section 368(a) of the Code.

4.9.

Investigation .

Buyer is knowledgeable about the industry in which the Company operates and the Laws and regulations applicable to the Company’s business and operations, and is experienced in the acquisition and management of businesses. Buyer has been afforded reasonable access to the books and records, facilities and personnel of the Company for purposes of conducting a due diligence investigation of the Company. Buyer has conducted a reasonable due diligence investigation of the Company and has received answers to all inquiries it has made with respect to the Company that are satisfactory to Buyer. Buyer does not have any knowledge of any inaccuracy or failure to be true of any of the representations or warranties of the Company in Article III or in any of the Ancillary Documents; provided, however, that Buyer does not make the representation in this sentence with respect to the representations of Seller set forth in Sections 3.1, 3.2, 3.3 or 3.13.

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4.10.

No Inducement or Reliance; Independent Assessment .

(a) With respect to this Agreement, the Ancillary Documents and the Contemplated Transactions, Buyer has not been induced by and has not relied upon any representations, warranties or statements, whether express or implied, made by the Company or Seller (or their Affiliates, officers, directors, employees, agents or representatives) that are not expressly set forth in Article III hereof (including the Company Disclosure Schedule), whether or not any such representations, warranties or statements were made in writing or orally.

(b) With respect to this Agreement, the Ancillary Documents and the Contemplated Transactions, Buyer acknowledges that none of the Company or Seller (or their Affiliates, officers, directors, employees, agents or representatives) makes, will make or has made any representation or warranty, express or implied, as to the prospects of the Company or its profitability for Buyer, or with respect to any forecasts, projections or business plans made available to Buyer (or its Affiliates, officers, directors, employees, agents or representatives) in connection with Buyer’s review of the Company.

4.11.

Capitalization .

The authorized capital of Buyer as of the date hereof consists of: (i) 125,000,000 shares of Buyer Common Stock of which, as of December 31, 2013, (x) 63,754,582 shares are issued and 63,739,607 are outstanding, and (y) 11,369,175 shares are reserved for issuance pursuant to Buyer’s stock incentive plans, of which 8,712,895 shares are issuable upon the exercise of stock options outstanding on the date hereof and (ii) 5,000,000 shares of preferred stock, par value $.01 per share, of which 125,000 have been designated as Series A Junior Participating Preferred Stock, and of which no shares are issued and outstanding as of the date of this Agreement. All of the issued and outstanding shares of Buyer Common Stock (A) have been duly authorized and validly issued, (B) are fully paid and non-assessable and (C) were issued in compliance with all applicable federal and state securities Laws or exemptions therefrom.

4.12.

Valid Issuance of Stock Consideration .

When issued and delivered in accordance with the terms hereof, the Stock Consideration shall be duly authorized, validly issued, fully paid and nonassessable, free from any liens, encumbrances or restrictions on transfer, including preemptive rights, rights of first refusal or other similar rights, other than as arising as a result of any action by Seller under federal or state securities Laws.

4.13.

Company SEC Documents; Financial Statements; NASDAQ Stock Market .

(a) Since December 31, 2012, Buyer has timely filed all required reports, schedules, forms, statements and other documents (including exhibits and all other information incorporated therein), and any required amendments to any of the foregoing, with the SEC (the “ Buyer SEC Documents ”). As of their respective filing dates, each of Buyer SEC Documents

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complied in all material respects with the requirements of the Securities Act of 1933, as amended (the “ Securities Act ”), and the Securities Exchange Act of 1934, as amended (the “ Exchange Act ”), and the rules and regulations of the SEC promulgated thereunder applicable to such Buyer SEC Documents, and no Buyer SEC Documents when filed, declared effective or mailed, as applicable, contained any untrue statement of a material fact or omitted to state a material fact required to be stated therein or necessary in order to make the statements therein, in light of the circumstances under which they were made, not misleading.

(b) The financial statements of Buyer included in its Annual Report on Form 10-K for the fiscal year ended December 31, 2012 and in its quarterly reports on Form 10-Q for the quarterly periods ended September 30, 2013, June 30, 2013, and March 31, 2013 comply as to form in all material respects with applicable accounting requirements and the published rules and regulations of the SEC with respect thereto, have been prepared in accordance with United States generally accepted accounting principles applied on a consistent basis during the periods involved (except as may be indicated in the notes thereto) and fairly present in all material respects the financial position of Buyer as of the dates thereof and the results of its operations and cash flows for the periods then ended. Except (i) as set forth in Buyer SEC Documents or (ii) for liabilities incurred in the ordinary course of business subsequent to the date of the most recent balance sheet contained in Buyer SEC Documents, Buyer has no liabilities, whether absolute or accrued, contingent or otherwise, other than those that would not, individually or in the aggregate, have a material adverse effect on the business, assets, liabilities, financial condition, property or results of operations of Buyer.

(c) As of the date of this Agreement, the Buyer Common Stock is listed on The NASDAQ Global Select Market, and Buyer has taken no action designed to, or which to its knowledge is likely to have the effect of, terminating the registration of the Buyer Common Stock under the Exchange Act or delisting the Buyer Common Stock from The NASDAQ Global Select Market. As of the date of this Agreement, Buyer has not received any notification that, and has no knowledge that, the SEC or The NASDAQ Stock Market LLC is contemplating terminating such listing or registration.

4.14.

Offering .

Subject to the accuracy of Seller’s representations set forth in Sections 3.14–3.17, the offer and issuance of the Stock Consideration to be issued in conformity with the terms of this Agreement constitute transactions which are exempt from the registration requirements of the Securities Act and from all applicable state registration or qualification requirements. Neither Buyer nor any Person acting on its behalf will take any action that would cause the loss of such exemption.

4.15.

No Integration .

Buyer has not, directly or through any agent, sold, offered for sale, solicited offers to buy or otherwise negotiated in respect of, any security (as defined in the Securities Act) which is or will be integrated with the Stock Consideration issued pursuant to this Agreement in a manner that would require the registration of the Stock Consideration under the Securities Act.

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ARTICLE V

Covenants

5.1.

Conduct of the Company .

(a) Except (i) to the extent compelled or required by applicable Law, (ii) as otherwise permitted or contemplated by this Agreement, (iii) as set forth in Section 5.1 of the Company Disclosure Schedule, or (iv) as consented to in writing by Buyer (which consent shall not be unreasonably withheld or delayed), during the period from the date hereof to the Closing Date, Seller shall cause the Company to, and the Company shall, conduct its business in the ordinary course, consistent with past practice (immediately before the date of this Agreement) and (x) use commercially reasonable efforts to maintain its assets and properties, and (y) so maintain its books and records.

(b) Without limiting the generality of the foregoing, except (i) to the extent compelled or required by applicable Law, (ii) as otherwise permitted or contemplated by this Agreement, (iii) as set forth in Section 5.1 of the Company Disclosure Schedule, (iv) in the ordinary course of business, consistent with past practice (immediately before the date of this Agreement) or (v) as consented to in writing by Buyer (which consent shall not be unreasonably withheld or delayed), during the period from the date hereof to the Closing Date, Seller shall cause the Company not to, and the Company shall not:

(i) modify or amend any of the organizational documents of the Company;

(ii) issue, or authorize the issuance of, any Equity Securities of the Company;

(iii) split, combine, redeem or reclassify, or purchase or otherwise acquire any Equity Securities of the Company;

(iv) declare or pay any cash or non-cash dividend or make any cash or non-cash distribution in respect of any of its Equity Securities;

(v) incur or suffer to exist any Indebtedness (or, for clarity, to guarantee the indebtedness of any Person), or make any loan, advance or capital contribution to or investment in any Person;

(vi) enter into any new Material Contract or any amendment, waiver or modification of any Material Contract existing as of the date of this Agreement and, for emphasis and without limiting the generality of the preceding language, enter into any Contract that purports to limit, curtail or restrict the kinds of businesses which it may conduct, or the Persons with whom it can compete;

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(vii) hire any employees, acquire or lease any real property, or engage in the conduct of any new line of business (although, for clarity, Buyer’s consent shall not be required for Seller to hire any employees to conduct the business of the Company in the ordinary course, consistent with past practice (immediately before the date of this Agreement));

(viii) acquire by merging or consolidating with, or by purchasing a substantial equity interest in or substantial portion of the assets of, any corporation, limited liability company, partnership, joint venture, association or other business organization or division thereof;

(ix) acquire from any other Person assets with a value or purchase price in the aggregate in excess of $100,000, except in the ordinary course of business, consistent with past practice (immediately before the date of this Agreement);

(x) divest, sell, abandon or fail to maintain, or otherwise dispose of, license or encumber any material asset of the Company (including but not limited to any material Company Intellectual Property);

(xi) commence any litigation or settle any litigation or other proceeding or other investigation by or against the Company of the Company or relating to any of their businesses, properties or assets, other than settlements;

(xii) adopt a plan or agreement of complete or partial liquidation, dissolution, merger, consolidation, restructuring, recapitalization or other material reorganization of the Company;

(xiii) change its accounting policies or procedures except to the extent required to conform with GAAP;

(xiv) change its fiscal year; or

(xv) authorize, agree, resolve or consent to any of the foregoing.

(c) Nothing contained in this Agreement shall give to Buyer, directly or indirectly, rights to control or direct the operations of the Company prior to the Closing Date. Prior to the Closing Date, the Company shall exercise, consistent with the terms and conditions of this Agreement, complete control and supervision of its operations. Notwithstanding anything to the contrary in this Agreement, no consent of Buyer shall be required with respect to any matter set forth in this Section 5.1 or elsewhere in this Agreement to the extent that the requirement of such consent would violate or conflict with applicable Law.

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5.2.

Exclusive Dealing .

During the period from the date hereof through the Closing Date, Seller and Merck shall not, directly or indirectly, through any of their Affiliates, representatives or otherwise, solicit offers from, negotiate with or in any manner initiate, encourage, discuss, accept or consider any proposal of any other person or entity relating to the acquisition of any of the capital stock of the Company (whether by direct purchase, merger, consolidation or otherwise) or to the acquisition or license of any of the assets of the Company, Seller, Merck or any of their Affiliates that would, if consummated, be inconsistent with the Contemplated Transactions. For the avoidance of any doubt, the restrictions set forth in this Section 5.2 shall not apply with respect to MiR34 or MiR34 Therapeutic Products.

5.3.

Access to Information Prior to the Closing .

During the period from the date hereof through the Closing Date, the Company shall, and Seller shall cause the Company to, give Buyer and its authorized representatives reasonable access during regular business hours to all offices, facilities, books and records of the Company as Buyer may reasonably request; provided , that (a) Buyer and its representatives shall take such action as is deemed necessary in the reasonable judgment of Seller and the Company to schedule such access and visits through a designated officer of the Company and in such a way as to avoid disrupting in any material respect the normal business of the Company, (b) the Company shall not be required to take any action which would constitute a waiver of the attorney-client or other privilege or would compromise Seller’s confidential information not related to the Company, (c) the Company need not supply Buyer with any information which, in the reasonable judgment of Seller or the Company, the Company is under a contractual or legal obligation not to supply and (d) in no event shall Buyer be permitted to conduct any sampling of soil, sediment, groundwater, surface water or building material.

5.4.

Regulatory Filings; Notices .

(a) As soon as reasonably practicable following the date hereof (and in any event no later than ten (10) Business Days from the date hereof) and pursuant to the applicable requirements of the HSR Act and the rules and regulations thereunder, the parties shall cause to be filed with the United States Federal Trade Commission (“ FTC ”) and the Antitrust Division of the United States Department of Justice (“ DOJ ”) Notification and Report Forms relating to the Contemplated Transactions. Buyer and Seller each shall (i) promptly supply the other party with any information which may be required in order to effectuate such filings and (ii) respond as promptly as practicable to any inquiries received from the FTC or the DOJ for additional information or documentation. Each of Buyer and Seller shall (x) promptly notify the other party of any material communication between that party and the FTC or the DOJ and, subject to applicable Law, discuss with and permit the other party to review in advance any proposed written communication to any of the foregoing; (y) consult with the other party, to the extent practicable, in advance of participating in any substantive meeting or discussion with the FTC, DOJ, or any other Governmental Authority with respect to any filings, investigation or inquiry concerning the Contemplated Transactions and, to the extent permitted by such government authority, give the other party the opportunity to attend and participate thereat; and (z) to the extent practicable and subject to applicable Law, furnish the other party with copies of all written

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correspondence and communications between them and their affiliates and their respective representatives on the one hand, and any Governmental Authority or members of their respective staffs on the other hand, with respect to the Contemplated Transactions. Each of the parties shall use reasonable best efforts to take, or cause to be taken, all actions and to do, or cause to be done, and to assist and cooperate with the other parties in doing, all things, necessary, proper or advisable to make effective as promptly as practicable, but in no event later than the End Date, the Contemplated Transactions, including obtaining HSR clearance and approvals, if any, from the Governmental Authorities set forth in Section 5.4 of the Company Disclosure Schedule.

(b) In furtherance and not in limitation of the foregoing, Buyer shall use its reasonable best efforts to take any and all steps necessary to avoid or eliminate impediments or objections, if any, that may be asserted with respect to the Contemplated Transactions under any antitrust, competition or trade regulatory requirement of Law so as to enable the parties hereto to close the Contemplated Transactions as promptly as practicable, in order to avoid the entry of, or to effect the dissolution of, any injunction, temporary restraining order, or other order in any suit or proceeding, which would otherwise have the effect of preventing or materially delaying the Closing, provided that nothing contained in this Agreement shall require or obligate Buyer, Seller or Merck to sell, divest, dispose of, license, or otherwise restrict its freedom to operate or hold separate any businesses, products lines, or assets of Buyer or the Company. In addition, Buyer shall use its reasonable best efforts to defend through litigation on the merits any claim asserted in court by any party in order to avoid entry of, or to have vacated or terminated, any decree, order or judgment (whether temporary, preliminary or permanent) that would restrain, prevent, or delay the Closing of the Contemplated Transactions.

5.5.

Intercompany Contracts .

(a) Except for the Ancillary Documents and any Contracts entered into in connection with the Contemplated Transactions, all Contracts between the Company, on the one hand, and Seller or any of its Affiliates (other than the Company), on the other hand, shall be terminated as of the Closing Date, and the Company shall have no obligation under any such Contract after the Closing Date and Seller and its Affiliates shall have no surviving rights under such Contracts.

(b) Effective upon the Closing, Seller and Merck shall assign to the Company all of Seller’s and/or Merck’s right, title and interest in and to any confidentiality agreements to which Seller and/or Merck (or any agent of Seller and/or Merck) may be a party pertaining to confidentiality of information of the Company in connection with any prospective sale or transfer of the outstanding equity interests of the Company or all or substantially all of the assets of the Company. Seller will request the return or destruction of information covered by such agreements within five Business Days of the date of this Agreement to the broadest extent permitted by such agreements.

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5.6.

Certain Tax Matters .

(a) Any Tax sharing, allocation, indemnity or similar agreement between any Merck Affiliated Group and the Company shall be terminated as of the Closing Date, and the Company shall have no obligation under any such agreement after the Closing Date.

(b) Merck shall (i) include the income of the Company on Merck’s consolidated federal Income Tax Returns (and any similar state, local or non-U.S. Income Tax Return) for all Pre-Closing Tax Periods and file all such Income Tax Returns when due (taking into account applicable extensions) and (ii) pay any Income Taxes attributable to such income. The Company shall furnish Tax information to Merck for inclusion in Merck’s Tax Returns in accordance with the Company’s past practice. The income of the Company shall be apportioned to (x) the period up to and including the Closing Date and (y) the period after the Closing Date, by closing the books of the Company as of the end of the Closing Date. Seller shall indemnify Buyer for any Losses incurred by Buyer as a result of any failure by the Merck Affiliated Group to file all Income Tax Returns it was required to file, or a failure to timely pay or cause to be paid all Income Taxes it was required to pay (whether or not shown on any Income Tax Return), for each taxable period during which the Company was a member of the Merck Affiliated Group.

(c) Merck shall have the exclusive right to represent its interests and the interests of the Company in any Tax Contest relating to Income Tax Returns described in Section 5.6(b). Neither Buyer nor any of its Affiliates (including the Company) shall be entitled in any way to compromise, release, waive, settle, modify or pay any claim with respect to Taxes for which Merck is responsible under Section 5.6(b) without the prior written consent of Merck.

(d) Neither Buyer nor any of its Affiliates (including the Company) shall, without the prior written consent of Merck, file or cause to be filed any Tax Return or claim for Tax refund with respect to (or relating to the income, properties or operations of) the Company if such filing reasonably could be expected to affect the Tax liability of Merck or the Company for any Pre-Closing Tax Period. Merck shall be entitled to any Tax refunds (including any interest included therein by the applicable Taxing Authority) of or relating to the Company for any Pre-Closing Tax Period, including any Tax refunds that take the form of a credit against the Tax liability of the Company. If Buyer or any of its Affiliates (including the Company) receives any such refund to which Merck is entitled hereunder, Buyer shall, within ten (10) days of receipt, pay, or cause to be paid, the amount of such refund (including any interest included therein by the Taxing Authority) to Merck.

(e) At Merck’s request, Buyer shall cause the Company to make and/or join with Merck in making any Tax election for a Pre-Closing Tax Period, unless the making of such election would be reasonably likely to have a material adverse impact on Buyer or the Company for any taxable period beginning after the Closing Date.

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(f) Subject to Section 5.6(h), Buyer, the Company and Merck shall cooperate fully, as and to the extent reasonably requested by any party, in connection with the filing of Tax Returns pursuant to this Section 5.6 and any Tax Contest. Such cooperation shall include the retention and (upon another party’s request) the provision of records and information which are reasonably relevant to any such Tax Contest and making employees available on a mutually convenient basis to provide additional information and explanation of any material provided hereunder. Buyer, the Company and Merck agree (x) to retain all books and records with respect to Tax matters pertinent to the Company relating to any taxable period beginning before the Closing Date until the expiration of the statute of limitations (and, to the extent notified by Buyer, the Company or Merck, any extensions thereof) of the respective taxable periods, and to abide by all record retention agreements entered into with any Taxing Authority, and (y) to give the others reasonable written notice prior to transferring, destroying or discarding any such books and records and, if another so requests, Buyer, the Company or Merck, as the case may be, shall allow the other to take possession of such books and records.

(g) Merck shall provide Buyer with pro forma income tax information for the Company for the taxable period ending on the Closing Date. Buyer shall not, and shall cause the Company and Buyer’s Affiliates not to, take any position on any Tax Return, in any administrative or judicial proceeding, or otherwise, that is inconsistent with such pro forma income tax information.

(h) No provision of this Agreement shall be construed to require Merck to provide to any Person, before, on or after the Closing Date, any right to access or to review any Tax Return or Tax work papers of Merck or any Affiliate of Merck (including any consolidated, combined, affiliated or unitary Tax Return that includes Merck or any Affiliate of Merck, and any pro forma Tax Return used to create any such consolidated, combined, affiliated or unitary Tax Return), excluding the pro forma income tax information of the Company to be provided pursuant to Section 5.6(g).

(i) Any Transfer Taxes shall be paid fifty percent (50%) by Buyer and fifty percent (50%) by Seller. The party required by Law to do so will file all necessary Tax Returns and other documentation with respect to all such Transfer Taxes and, if required by applicable Law, the other parties will, and will cause their Affiliates to, join in the execution of any such Tax Returns and other documentation.

(j) Buyer shall indemnify Merck for any Tax owed by Merck resulting from any transaction engaged in by the Company on the Closing Date after the Closing that is not in the ordinary course of business. Buyer and Merck agree all transactions occurring on the Closing Date after the Closing that are not in the ordinary course of business shall be reported on Buyer’s or the Company’s Income Tax Returns, to the extent permitted by Treasury Regulation Section 1.1502-76(b)(1)(ii)(B) (or any similar provision of state, local or non-U.S. Law).

(k) Neither Buyer, the Company nor any of Buyer’s Affiliates shall make an election under Section 338(g) of the Code with respect to the transactions contemplated hereby and thereby.

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(l) For a period of two (2) years from and after the Closing Date, neither Buyer, the Company nor any of Buyer’s Affiliates shall (i) merge or liquidate the Company into Buyer or any subsidiary of Buyer (including by causing or permitting the Company to become an entity that is disregarded as separate from Buyer or any subsidiary of Buyer, in each case, within the meaning of Treasury Regulation Section 301.7701-3(b)(1)(ii)), or (ii) take any other action that causes, or could reasonably be expected to cause, the sale of the Sirna Common Stock by Seller to Buyer pursuant to this Agreement to qualify as a “reorganization” within the meaning of Section 368(a) of the Code.

(m) Neither Buyer, the Company nor any of Buyer’s Affiliates shall take any action with respect to the Company subsequent to the Closing that would cause the transactions contemplated hereby and thereby to constitute part of a transaction that is the same as, or substantially similar to, the “Intermediary Transaction Tax Shelter” described in Internal Revenue Service Notices 2001-16 and 2008-111.

(n) The parties agree that for Income Tax purposes the sale of the Sirna Common Stock by Seller to Buyer pursuant to this Agreement is intended to be treated as a taxable sale of Sirna Common Stock under Section 1001(a) of the Code, and not as a “reorganization” within the meaning of Section 368(a) of the Code. The parties shall report such sale for Income Tax purposes in a manner consistent with the foregoing, and shall not take any position on any Tax Return, in any administrative or judicial proceeding, or otherwise, that is inconsistent with the foregoing.

5.7.

Preservation of Books and Records .

For a period of six (6) years from the Closing Date or such longer time as may be required by Law:

(a) Buyer shall not and shall cause its Affiliates not to dispose of or destroy any of the books and records of the Company relating to periods prior to the Closing (the “ Books and Records ”) without first offering to turn over possession thereof to Seller by written notice to Seller at least sixty (60) days prior to the proposed date of such disposition or destruction.

(b) Buyer shall and shall cause its Affiliates to allow Seller and its agents access to all Books and Records on reasonable notice and at reasonable times at Buyer’s principal place of business or at any location where any Books and Records are stored, and Seller shall have the right, at its own expense, to make copies of any Books and Records; provided , that any such access or copying shall be had or done in such a manner so as not to unduly interfere with the normal conduct of Buyer’s business.

(c) Buyer shall and shall cause its Affiliates to make available to Seller upon reasonable notice to Seller and at reasonable times and upon written request (i) Buyer’s personnel to assist Seller in locating and obtaining any Books and Records, and (ii) any of Buyer’s personnel whose assistance or participation is reasonably required by Seller or any of its Affiliates in anticipation of, or preparation for, existing or future litigation or other matters in

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which Sellers or any of its Affiliates are involved. Seller shall reimburse Buyer for Buyer’s reasonable out-of-pocket expenses incurred in performing the covenants contained in this Section 5.7.

5.8.

Proprietary Information .

Prior to the Closing Date, the Company was routinely supplied copies of proprietary information of Seller and its Affiliates and their various operations unrelated to the Company. Although Seller has attempted to recover such information from the Company, some may still be present within the Company. In addition, it is possible that Seller may inadvertently transfer some of Seller’s proprietary information as part of the transfer of the RNAi Technology Platform that will take place in connection with this Agreement. Buyer therefore agrees that it will not use or disclose such information for any purpose whatsoever, and shall destroy any remaining copies in its possession that it discovers or identifies as such after the Closing. In the event Seller inadvertently transfers to Buyer or its Affiliates any proprietary or confidential information, data or materials of Seller or its Affiliates (other than the Company) other than as intended by this Agreement, Buyer shall, promptly after learning of such inadvertent transfer, notify Merck and either destroy or return such information, data or materials as instructed by Merck.

5.9.

Public Announcements .

The initial press release regarding this Agreement and the Contemplated Transactions shall be made at such time and in such form as Buyer and Seller agree, provided , that in the event that the parties cannot agree, either party shall be permitted to make any disclosure required by Law. Prior to the Closing, none of Buyer, the Company or Seller will issue or make any subsequent press release or public statement with respect to this Agreement or the Contemplated Transactions without the prior consent of Buyer and the Company, except as may be required by Law; provided , that the party proposing to issue any press release or similar public announcement or communication in compliance with any such disclosure obligations shall use commercially reasonable efforts to consult in good faith with the other party before doing so. Buyer agrees that in the event it is required by law to publicly file this Agreement, it shall seek confidential treatment of all dollar amounts, thresholds, time periods and percentages in Section 2.5 and use reasonable best efforts to obtain such treatment or otherwise maintain the confidentiality thereof.

5.10.

Technology Transfer .

On or prior to the Closing, the technology assets listed on Section 5.10 of the Company Disclosure Schedule (the “ Tech Information ”) shall have been transferred by Seller to the Company by delivery of a hard drive to Buyer at Closing (such delivery of the Tech Information, the “ Tech Transfer Condition ”). Buyer shall have 60 days after the date such transfer occurs to confirm that the Tech Transfer Condition has been satisfied in all material respects. If Buyer believes, in good faith, that the Tech Transfer Condition has not been satisfied in all material respects, Buyer shall have [***] days after the end of such 60-day period to

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deliver to Seller written notice setting forth its objections in reasonable detail (a “ Tech Transfer Objection Notice ”). In the event that such written notice is delivered, such dispute shall be governed exclusively by the dispute resolution provisions set forth in Section 11.11(c) and the Tech Transfer Condition shall only be deemed satisfied and finally resolved in accordance therewith. In the event that such written notice is not delivered within such [***]-day period, then the Tech Transfer Condition shall be deemed satisfied as of the end of such [***]-day period. If the Tech Transfer Condition is satisfied in all material respects (but not in all respects), then during the [***]-month period following such satisfaction of the Tech Transfer Condition, Seller shall work in good faith with Buyer to seek to satisfy the Tech Transfer Condition in all respects.

5.11.

Certain Personnel Matters .

Neither Buyer nor any of its Affiliates or representatives shall contact or attempt to contact directly any employees at any time during which they are employed by Seller or its Affiliates, but shall instead coordinate all such efforts only through Seller.

5.12.

NASDAQ .

Buyer shall cause the Stock Consideration to be listed for trading on The NASDAQ Global Select Market.

5.13.

Lock-Up .

(a) For a period of six (6) months from the Closing Date (the “ Initial Lock-Up Period ”), without the prior written approval of Buyer, Seller shall not Dispose of (i) any of the Stock Consideration, together with any shares of Buyer Common Stock issued in respect thereof as a result of any stock split, stock dividend, share exchange, merger, consolidation or similar recapitalization, and (ii) any Buyer Common Stock issued as (or issuable upon the exercise of any warrant, right or other security that is issued as) a dividend or other distribution with respect to, or in exchange or in replacement of, the shares of Buyer Common Stock described in clause (i) of this sentence.

(b) For a period of six (6) months from and including the date of expiration or termination of the Initial Lock-Up Period (the “ Subsequent Lock-Up Period ”), without the prior written approval of Buyer, Seller shall not Dispose of (i) fifty percent (50%) of the Stock Consideration, together with any shares of Buyer Common Stock issued in respect thereof as a result of any stock split, stock dividend, share exchange, merger, consolidation or similar recapitalization, and (ii) any Buyer Common Stock issued as (or issuable upon the exercise of any warrant, right or other security that is issued as) a dividend or other distribution with respect to, or in exchange or in replacement of, the shares of Buyer Common Stock described in clause (i) of this sentence.

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(c) In the event that Buyer executes a Naked License prior to the end of the Initial Lock-Up Period, the Initial Lockup Period shall immediately terminate on the execution date of such Naked License; provided, however, that the selling restrictions and limitations set forth in Section 5.14 applicable during and following the Subsequent Lock-Up Period, shall remain applicable.

(d) Notwithstanding anything to the contrary herein, Buyer shall take all actions in accordance with applicable law that may be required to ensure the transferability of the Stock Consideration following the expiration of the applicable restrictions on Dispositions set forth in Sections 5.13(a) and/or 5.13(b), including the removal of restrictive legends on any share certificates representing any portion of the Stock Consideration.

5.14.

Limitations Following Lock-Up Terms .

(a) During the Subsequent Lock-Up Period, Seller shall not (i) on any day, Dispose of more than [***]% of the Stock Consideration that is not subject to the Subsequent

Lock-Up Period or (ii) in any calendar month, Dispose of more than [***]% of the Stock Consideration that is not subject to the Subsequent Lock-Up Period.

(b) Following the Subsequent Lock-Up Period, Seller shall not (i) on any day, Dispose of more than 10% of the Stock Consideration or (ii) in any calendar month, Dispose of more than [***]% of the Stock Consideration.

(c) Seller shall not Dispose of the Stock Consideration in any manner other than through open market transactions, unless otherwise approved in advance and in writing by Buyer.

5.15.

Release .

(a) From and after the Closing, Seller, on behalf of itself and its Affiliates and each of its and their respective officers, directors, employees, agents, successors and assigns (collectively, the “ Seller Releasing Parties ”), hereby releases, acquits and forever discharges the Company and any and all of its successors and assigns, together with its present and former directors and officers (collectively, the “ Company Released Parties ”), from any and all manner of claims, actions, suits, damages, and liabilities in law or equity (the “ Obligations ”), which any Seller Releasing Party has against any of the Company Released Parties; provided , however , that the foregoing notwithstanding and, for the avoidance of doubt, this release shall not include any Obligations arising out of this Agreement, the Ancillary Documents or the transactions contemplated hereby and thereby, and such Obligations shall not be deemed released by this Section 5.15(a). This release shall become effective only upon completion of the Closing and prior to such date shall have no force or effect and shall not be legally binding on the parties.

(b) From and after the Closing, the Company on behalf of itself and each of its and their respective officers, directors, employees, agents, successors and assigns (collectively, the “ Company Releasing Parties ”), hereby releases, acquits and forever discharges Seller and any and all of its successors and assigns, together with its present and former directors and officers (collectively, the “ Seller Released Parties ”), from any and all manner of Obligations,

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which any Company Releasing Party has against any of the Seller Released Parties; provided , however , that the foregoing notwithstanding and, for the avoidance of doubt, this release shall not include any Obligations arising out of this Agreement, the Ancillary Documents or the transactions contemplated hereby and thereby, and such Obligations shall not be deemed released by this Section 5.15(b). This release shall become effective only upon completion of the Closing and prior to such date shall have no force or effect and shall not be legally binding on the parties.

5.16. Pre-Closing Transfer of Certain Excluded Assets . Prior to the Closing, the Company shall transfer to Seller the equipment listed on Section 5.16 of the Company Disclosure Schedule.

5.17. Patent Files . On or prior to the Closing, Seller shall cause to be delivered to the Company, at Buyer’s expense, copies in a reasonably usable format of all records that, to Seller’s Knowledge, are in Seller’s or its Affiliates’ possession relating to the prosecution or maintenance of the active pending patent applications included in the Owned Intellectual Property. As soon as reasonably practical after the Closing, Seller shall cause to be delivered to the Company, at Buyer’s expense, copies in a reasonably usable format of all records that, to Seller’s Knowledge, are in Seller’s or its Affiliates’ possession relating to the prosecution or maintenance of all other patents and patent applications included in the Owned Intellectual Property.

5.18. Additional Tech Transfer . At Closing, Seller shall deliver a hard drive to Buyer containing certain data related to the RNAi Technology Platform.

ARTICLE VI

Conditions to Closing

6.1.

Conditions to All Parties’ Obligations .

The obligations of the parties to consummate the Contemplated Transactions are subject to the fulfillment prior to or at the Closing of each of the following conditions (any or all of which may be waived by the parties):

(a) No Injunction . No Governmental Authority or federal or state court of competent jurisdiction shall have enacted, issued, promulgated, enforced or entered any statute, rule, regulation, Order or other notice (whether temporary, preliminary or permanent) (collectively, the “ Restraints ”), in any case which is in effect and which prevents or prohibits consummation of the Contemplated Transactions; provided , that each of the Parties shall use its commercially reasonable efforts to cause any such Restraint to be vacated or lifted.

(b) HSR Act . Any applicable waiting period under the HSR Act relating to the transactions contemplated hereby and thereby shall have expired or been terminated.

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6.2.

Conditions to Seller’s Obligations .

The obligations of Seller to consummate the Contemplated Transactions are subject to the fulfillment at or prior to the Closing of each of the following conditions (any or all of which may be waived in whole or in part by Seller):

(a) Representations and Warranties . The representations and warranties of Buyer contained in Article IV hereof shall be true and correct as of the Closing Date as though made as of the Closing Date (except for representations and warranties which address matters only as of a specific date, which representations and warranties shall continue as of the Closing Date to be true and correct as of such specific date), without giving effect to any supplement to the Buyer Disclosure Letter, except to the extent that the failure to be so true and correct would not have a Buyer Material Adverse Effect.

(b) Performance . Buyer shall have performed and complied in all material respects with all agreements and covenants required by this Agreement to be so performed or complied with by Buyer at or prior to the Closing.

6.3.

Conditions to Buyer’s Obligations .

The obligations of Buyer to consummate the Contemplated Transactions are subject to the fulfillment at or prior to the Closing of each of the following conditions (any or all of which may be waived in whole or in part by Buyer):

(a) Representations and Warranties . The representations and warranties of Seller contained in Article III hereof which are modified by Company Material Adverse Effect shall be true and correct as of the Closing Date as though made as of the Closing Date (except for representations and warranties which address matters only as of a specific date, which representations and warranties shall continue as of the Closing Date to be true and correct as of such specific date) without giving effect to any supplement to the Company Disclosure Letter. The representations and warranties of Seller contained in Article III hereof which are not modified by Company Material Adverse Effect shall be true and correct as of the Closing Date as though made as of the Closing Date (except for representations and warranties which address matters only as of a specific date, which representations and warranties shall continue as of the Closing Date to be true and correct as of such specific date), without giving effect to any supplement to the Company Disclosure letter, except to the extent that the failure to be so true and correct would not have a Company Material Adverse Effect.

(b) Performance . Seller and the Company shall have performed and complied in all material respects with all agreements and covenants required by this Agreement to be so performed or complied with by Seller and the Company at or prior to the Closing.

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ARTICLE VII

Deliveries by Seller and the Company at Closing

On the Closing Date, Seller shall deliver or cause to be delivered to Buyer:

7.1.

Officer’s Certificate .

An officer’s certificate signed by a senior officer of the Company and Seller to the effect set forth in Sections 6.3(a) and 6.3(b).

7.2.

Share Certificates .

Certificates (which may not be originals) representing all of the shares of Sirna Common Stock, endorsed in blank (or accompanied by stock powers executed in blank) and otherwise in proper form for transfer.

7.3.

Tech Information .

The Tech Information in media or other form in accordance with Section 5.10.

7.4.

Resignations of Directors and Officers .

Written resignations, dated as of the Closing Date, of the directors of the Company, and those officers of the Company listed in Section 7.4 of the Company Disclosure Schedule.

7.5.

Further Instruments .

Such documents of further assurance reasonably necessary and typical for transactions similar to the Contemplated Transactions in order to complete the Contemplated Transactions.

ARTICLE VIII

Deliveries by Buyer at Closing

On the Closing Date, Buyer shall deliver or cause to be delivered to Seller:

8.1.

Officer’s Certificate .

A certificate signed by an authorized signatory of Buyer to the effect set forth in Sections 6.2(a) and 6.2(b).

8.2.

Cash Consideration .

The Cash Consideration, by wire transfer of immediately available funds, to the account designated by Seller.

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8.3.

Stock Consideration .

Certificate or certificates representing 85% of the Stock Consideration.

8.4.

Further Instruments .

Such documents of further assurance reasonably necessary and typical for transactions similar to the Contemplated Transactions in order to complete the Contemplated Transactions.

ARTICLE IX

Indemnification; Survival

9.1.

Survival of Representations and Warranties; Time Limitations .

(a) The representations and warranties of the Parties contained in Article III and Article IV hereof shall survive the Closing; provided, that, subject to the last sentence of this Section 9.1, such representations and warranties shall terminate on the date that is the eighteenth (18) month anniversary of the Closing Date. Notwithstanding the foregoing, (1) the representations and warranties of Seller contained in (A) Section 3.1 (Organization and Power), Section 3.2 (Authorization and Enforceability), Section 3.3 (Capitalization of the Company), Section 3.14 (Investment Experience and Accredited Investor Status; Securities Laws Matters), and Section 3.18 (Brokers) shall survive the Closing indefinitely, and (B) Section 3.6(b) (Employee Benefits) and Section 3.13 (Taxes) (shall survive for sixty (60) days following the expiration of the applicable statute of limitations, and (2) the representations and warranties of Buyer contained in Section 4.1 (Organization and Power), Section 4.2 (Authorization and Enforceability), and Section 4.7 (Brokers) shall survive the Closing indefinitely. All covenants and agreements contained herein which by their terms contemplate full performance at or prior to Closing shall terminate upon Closing. All covenants and agreements contained herein which by their terms, require performance after the Closing shall survive the Closing in accordance with their terms. The period of time a representation or warranty or covenant or agreement survives the Closing pursuant to this Section 9.1(a) shall be the “ Survival Period ” with respect to such representation or warranty or covenant or agreement. In the event notice of any claim for indemnification under this Section 9.1(a) shall have been given within the applicable Survival Period and such claim has not been finally resolved by the expiration of such Survival Period, the representations or warranties or covenants or agreements that are the subject of such claim shall survive, but only to the extent of and in the amount of and for the sole purpose of the claim as made prior to the expiration of the Survival Period, until such claim is finally resolved.

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9.2.

Indemnification .

(a) By Buyer . Subject to the provisions of Section 9.1, from and after the Closing, Buyer agrees to indemnify, defend and hold harmless Seller, its Affiliates, and their respective officers, directors, employees, shareholders, members, partners, agents, representatives, successors and assigns (collectively, “ Seller Indemnitees ”) from and against all Losses incurred by any of the Seller Indemnitees arising out of or relating to: (i) any breach of any representation or warranty made by Buyer in this Agreement together with the Exhibits hereto or the Buyer Disclosure Schedule, or (ii) any breach of any covenant or agreement of Buyer contained in this Agreement together with the Exhibits hereto or the Buyer Disclosure Schedule.

(b) By Seller; By Merck .

(i) Subject to the provisions of Section 9.1 and 9.2(b)(ii), from and after the Closing, Seller agrees to indemnify, defend and hold harmless Buyer, its Affiliates, and their respective officers, directors, employees, shareholders, members, partners, agents, representatives, successors and assigns (collectively, “ Buyer Indemnitees ”) from and against all Losses incurred by any of Buyer Indemnitees arising out of or relating to: (A) any breach of any representation or warranty made by Seller in this Agreement together with the Exhibits hereto, the Company Disclosure Schedule; (B) any breach of any covenant or agreement of Seller contained in this Agreement together with the Exhibits hereto, the Company Disclosure Schedule; or (C) any liability of the Company arising by virtue of its status, prior to the Closing, as a member of a consolidated group or as a member of a controlled group.

(ii) Subject to the provisions of Section 9.1, from and after the Closing, Seller and Merck, joint and severally, agree to indemnify, defend and hold harmless Buyer Indemnitees from and against all Losses incurred by any of Buyer Indemnitees arising out of or relating to any breach of any covenant or agreement of Seller and/or Merck contained in Section 5.2 and 5.6.

(i) Buyer shall not be required to indemnify Seller Indemnitees with respect to any claim for indemnification arising out of or relating to matters described in Section 9.2(a)(i) unless and until the aggregate amount of all such claims for such matters exceeds $1.75 million, in which event Seller Indemnitees will be entitled to recover Losses arising out of or relating to such matters only to the extent in excess thereof (the “ Seller Indemnitees Deductible ”); provided that Buyer shall be required to indemnify Seller Indemnities for any Losses arising out of or relating to any breach of any representation or warranty set forth in Sections 4.1-4.2, and 4.7 without regard to any application of the Seller Indemnitees Deductible. No Losses shall be included in determining whether the Seller Indemnitees Deductible has been reached unless a notice seeking indemnification for such Losses has been given by Seller Indemnitees to Buyer in accordance with Sections 9.2(d)(i) or 9.2(d)(ii)(A).

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(ii) Seller shall not be required to indemnify Buyer Indemnitees with respect to any claim for indemnification arising out of or relating to matters described in Section 9.2(b)(i)(A) unless and until the aggregate amount of all such claims for such matters exceeds $1.75 million, in which event Buyer Indemnitees will be entitled to recover Losses arising out of or relating to such matters only to the extent in excess thereof (the “ Buyer Indemnitees Deductible ”); provided that Seller shall be required to indemnify Buyer Indemnities for any Losses arising out of or relating to any breach of any representation or warranty set forth in Sections 3.1-3.3, 3.6(b), 3.13 and 3.18 (the “ Specified Representations ”) without regard to any application of the Buyer Indemnitees Deductible. Seller’s maximum liability to Buyer Indemnitees with respect to any claim for indemnification arising out of or relating to matters described in Section 9.2(b)(i)(A) and Section 9.2(b)(i)(D) shall not exceed, in the aggregate, 25% of the value of the Total Consideration on the Closing Date (less any losses realized by Seller upon the sale of all or any portion of the Stock Consideration) (the “ Buyer Indemnitees Cap ”). No Losses shall be included in determining whether the Buyer Indemnitees Deductible has been reached unless a notice seeking indemnification for such Losses has been given by Buyer Indemnitees to Seller in accordance with Sections 9.2(d)(i) or 9.2(d)(ii)(A).

(iii) Subject to (and without limiting the limitations of) Section 9.2(c), notwithstanding any other provision of this Agreement, the maximum aggregate amount payable by Seller to Buyer Indemnitees pursuant to this Article IX (other than with respect to the Specified Representations) shall be an amount equal to the value of the Total Consideration on the Closing Date (less any losses realized by Seller upon the sale of all or any portion of the Stock Consideration).

(d) Procedure .

(i) Direct Claims . If either a Buyer Indemnitee, on the one hand, or a Seller Indemnitee, on the other hand, shall have a claim for indemnification hereunder (the “ Indemnitee ”) for any claim other than a claim asserted by a third party, the Indemnitee shall, as promptly as is practicable, give written notice to the party from whom indemnification is sought (the “ Indemnitor ”) of the nature and, to the extent practicable, a good faith estimate of the amount, of the claim, which notice must certify that the Indemnitee has in good faith already sustained some (though not necessarily all) Losses with respect to such claim. The failure to make prompt delivery of such written notice by the Indemnitee to the Indemnitor (so long as a notice pursuant to this Section 9.2(d)(i), including the requisite certification, is given before the expiration of the applicable period set forth in Section 9.1) shall not relieve the Indemnitor from any liability under this Section 9.2 with respect to such matter, except to the extent the Indemnitor is actually prejudiced by failure to give such notice.

(ii) Third-Party Actions .

(A) If an Indemnitee receives notice or otherwise obtains knowledge of any matter or any threatened matter that may give rise to an indemnification claim against the Indemnitor (the “ Third Party Claim ”), then the Indemnitee shall promptly, and in any event within twenty (20) days of the receipt of notice or other knowledge of any such claim

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against the Indemnitor, deliver to the Indemnitor a written notice describing, to the extent practicable, such matter in reasonable detail and such notice must be accompanied by a copy of any written notice of the third party claimant to the Indemnitee asserting the Third Party Claim. The failure to make prompt delivery of such written notice or of the copy of the written notice of the third party claimant by the Indemnitee to the Indemnitor (so long as a notice pursuant to this Section 9.2(d)(ii)(A) that includes any written notice of the third party claimant is given before the expiration of the applicable period set forth in Section 9.1) shall not relieve the Indemnitor from any liability under this Section 9.2 with respect to such matter, except to the extent the Indemnitor is actually prejudiced by failure to give such notice. The Indemnitee shall deliver to the Indemnitor copies of all other notices and documents (including court papers) received by the Indemnitee relating to the Third Party Claim. The Indemnitor shall have the right, at its option, to assume the defense of any such matter with its own counsel. Prior to the time the Indemnitee is notified by the Indemnitor as to whether the Indemnitor will assume the defense of such third Party Claim, the Indemnitee shall take all actions reasonably necessary to timely preserve the collective rights of the parties with respect to such Third Party Claim, including responding timely to legal process.

(B) If the Indemnitor elects to assume the defense of and indemnification for any such matter, then:

(1) notwithstanding anything to the contrary contained in this Agreement, the Indemnitor shall not be required to pay or otherwise indemnify the Indemnitee against any attorneys’ fees or other expenses incurred on behalf of the Indemnitee in connection with such matter following the Indemnitor’s election to assume the defense of such matter, unless (x) the Indemnitor fails to defend diligently the action or proceeding within ten (10) days after receiving notice of such failure from the Indemnitee, (y) the Indemnitee reasonably shall have concluded (upon advice of its counsel) that there may be one or more legal defenses available to such Indemnitee or other Indemnitees that are not available to the Indemnitor, or (z) the Indemnitee reasonably shall have concluded (upon advice of its counsel) that, with respect to such claims, the Indemnitee and the Indemnitor may have different, conflicting, or adverse legal positions or interests;

(2) the Indemnitee shall, at its own expense, make available to the Indemnitor all books, records and other documents and materials that are under the direct or indirect control of the Indemnitee or any of the Indemnitee’s agents and that the Indemnitor considers necessary or desirable for the defense of such matter, and cooperate in all reasonable ways with, and make its employees and advisors available or otherwise render reasonable assistance to, the Indemnitor and its agents; and

(3) the Indemnitor shall not, without the written consent of the Indemnitee, which shall not be unreasonably withheld or delayed, settle or compromise any pending or threatened Litigation in respect of which indemnification may be sought hereunder (whether or not the Indemnitee is an

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actual or potential party to such Litigation) or consent to the entry of any judgment which does not, to the extent that the Indemnitee may have any liability with respect to such Litigation, include as an unconditional term thereof the delivery by the claimant or plaintiff to the Indemnitee of a written release of the Indemnitee from all liability in respect of such Litigation.

(C) If the Indemnitor elects not to assume the defense of and indemnification for such matter, then the Indemnitee shall proceed diligently to defend such matter with the assistance of counsel reasonably satisfactory to the Indemnitor; provided , that the Indemnitee shall not settle, adjust or compromise such matter, or admit any liability with respect to such matter, without the prior written consent of the Indemnitor.

(D) The procedures in this Section 9.2(d)(ii) shall not apply to Tax Contests described in Section 5.6(c) or to direct claims of Seller Indemnitees or Buyer Indemnitees.

(e) Subrogation . To the extent that the Indemnitor makes or is required to make any indemnification payment to the Indemnitee, the Indemnitor shall be entitled to exercise, and shall be subrogated to, any rights and remedies (including rights of indemnity, rights of contribution and other rights of recovery) that the Indemnitee or any of the Indemnitee’s Affiliates may have against any other Person with respect to any Losses to which such indemnification payment is directly related, so long as the Indemnitee is not adversely affected thereby.

(f) No Setoff Right . Buyer may not, under any circumstances, set off any amount to which it claims to be entitled from Seller or Merck, as the case may be, including any amounts that may be owed under this Article IX or otherwise, against amounts otherwise payable under any provision of this Agreement.

(g) Exclusive Remedies Following the Closing Date . Following the Closing Date, the indemnification provisions of this Article IX shall be the sole and exclusive remedy of the Indemnitees, whether in contract, tort or otherwise, for all matters arising under or in connection with this Agreement and the Contemplated Transactions, including, without limitation, for any inaccuracy or breach of any representation, warranty, covenant or agreement set forth herein.

9.3.

Indemnification for Unreviewed Materials .

(a) The parties acknowledge that Merck has identified approximately 500 boxes of materials related to the Company that have been in storage and have not yet been reviewed by Merck, Seller, the Company or Buyer (the “ Unreviewed Materials ”). Within 60 days after the Closing, Seller shall deliver to Buyer (either electronically or in hard copy format) all Unreviewed Materials except to the extent they constitute property or confidential information of Merck or its Affiliates (other than the Company) (the “ Company Unreviewed Materials ”). The cost of delivering the Company Unreviewed Materials to Buyer shall be borne equally by Seller and Buyer.

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(b) After receipt of the Company Unreviewed Materials, Buyer shall have 120 days to review them. If, during such 120-day period, Buyer believes in good faith that the failure to include any of the Company Unreviewed Materials in the Seller Disclosure Schedules gives rise to a breach of any of the representations and warranties of Seller in Article III (without taking into account, for this purpose, any “to the Knowledge of Seller” qualifiers), then Buyer may deliver notice thereof to Seller. In order to be effective, such notice must (i) be delivered in good faith, (ii) be in writing, (iii) set forth in reasonable detail the reasons Buyer believes such breach exists (including the identity of, and a true and complete copy of, the Company Unreviewed Material giving rise to the breach, the identification of the specific representation breached and an explanation in reasonable detail of why the representation is breached), (iv) include a good faith estimate of the amount of actual Losses incurred as a result of the breach and (iv) be delivered to Seller within 10 days after the end of such 120-day period (an “ Indemnification Notice ”).

(c) If Buyer fails to properly and timely deliver an Indemnification Notice within such 10-day period, then none of the Seller Indemnitees shall have any liability or obligation to any of the Buyer Indemnitees with respect to any Losses arising from or related to the Company Unreviewed Materials. If Buyer properly and timely delivers an Indemnification Notice within such 10-day period, then the indemnification procedures set forth in Section 9.2(d) shall be applicable with respect to such claims, except that (x) Seller shall not be required to indemnify Buyer Indemnitees with respect to any such claims unless and until the aggregate amount of all such claims exceeds $2.5 million, in which event Buyer Indemnitees will be entitled to recover Losses arising out of or relating to such claims only to the extent in excess thereof and (y) Seller’s maximum liability for all Losses (other than with respect to the Specified Representations) claimed pursuant to this Section 9.3 shall not exceed, in the aggregate, 25% of the value of the Total Consideration on the Closing Date (less any losses realized by Seller upon the sale of all or any portion of the Stock Consideration).

9.4.

Indemnification for Product Liability Claims .

(a) Seller agrees to indemnify, defend and hold harmless the Buyer Indemnitees from and against all Losses incurred by any of the Buyer Indemnitees arising out of or relating to any Merck Product Liability Claim, except to the extent any such Loss arises out of or relates to (i) the Company’s breach of the In-License Agreement or the Out-License Agreement, or (ii) any matter for which Buyer is obligated to indemnify, defend and hold harmless Seller or its Affiliates under this Agreement.

(b) Buyer agrees to indemnify, defend and hold harmless the Seller Indemnitees from and against all Losses incurred by any of the Seller Indemnitees arising out of or relating to any Alnylam Product Liability Claim, except to the extent any such Loss arises out of or relates to (i) Seller’s breach of the In-License Agreement or the Out-License Agreement, or (ii) any matter for which Seller is obligated to indemnify, defend and hold harmless Buyer or its Affiliates under this Agreement.

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ARTICLE X

Termination

10.1.

Termination .

This Agreement may be terminated and the transactions contemplated hereby may be abandoned:

(a) at any time, by mutual written agreement of Seller and Buyer; or

(b) at any time, by either Seller or Buyer if any Restraint having any of the effects set forth in Section 6.1(a) of this Agreement shall be in effect and have become final and nonappealable; or

(c) by written notice from Buyer, if a breach of or failure to perform any representation, warranty, covenant or agreement on the part of Seller set forth herein shall have occurred, which breach or failure to perform (i) would give rise to the failure of a condition set forth in Section 6.3(a) or 6.3(b), and (ii) after receipt by Seller of written notice from Buyer of such breach or failure to perform, cannot be or has not been cured on or prior to the date that is six (6) months from the date hereof, which date shall be extended automatically by an additional three (3) months in the event that at the end of such 6-month date all of the conditions in Article VI are satisfied (or capable of being satisfied) other than the condition in Section 6.1(b) (the “ End Date ”), provided , that Buyer is not then in breach with respect to any of its representations, warranties, covenants or other agreements contained in this Agreement;

(d) by written notice from Seller, if a breach of or failure to perform any representation, warranty, covenant or agreement on the part of Buyer set forth herein shall have occurred, which breach or failure to perform (i) would give rise to the failure of a condition set forth in Section 6.2(a) or 6.2(b), and (ii) after receipt by Buyer of written notice from Seller of such breach or failure to perform, cannot be or has not been cured on or prior to the End Date, provided , that Seller is not then in breach with respect to any of its representations, warranties, covenants or other agreements contained in this Agreement;

(e) by written notice from Buyer, if the Closing has not occurred on or before the End Date, provided , that Buyer is not then in breach with respect to any of its representations, warranties, covenants or other agreements contained in this Agreement; or

(f) by written notice from Seller, if the Closing has not occurred on or before the End Date, provided , that Seller is not then in breach with respect to any of its representations, warranties, covenants or other agreements contained in this Agreement.

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10.2.

Procedure and Effect of Termination .

In the event of the termination of this Agreement and the abandonment of the Contemplated Transactions, written notice thereof shall be given by a terminating party to the other parties, and this Agreement shall terminate and the Contemplated Transactions shall be abandoned without further action by any of the parties. If this Agreement is terminated pursuant to Section 10.1:

(a) Buyer shall promptly cause to be returned to the Company or destroy all documents and information obtained in connection with this Agreement and the Contemplated Transactions and all documents and information obtained in connection with Buyer’s investigation of the Company from the Company or its representatives, including any copies made by or supplied to Buyer or any of Buyer’s agents of any such documents or information.

(b) No party hereto shall have any obligation or liability to the other parties hereto, except that the parties hereto shall remain bound by the provisions of this Section 10.2 and Article XI and by the provisions of the Confidentiality Agreement; provided , that nothing herein shall relieve a defaulting or breaching party from any liability or damages arising out of its breach of any covenant or agreement in this Agreement.

ARTICLE XI

Miscellaneous

11.1.

Expenses .

All fees and expenses incurred in connection with the this Agreement and the Ancillary Agreements shall be paid by the party incurring such expenses, whether or not the transactions contemplated hereby and thereby are consummated.

11.2.

Notices .

All notices and other communications given or made pursuant hereto shall be in writing and shall be deemed to have been duly given or made (a) as of the date delivered, if delivered personally, (b) on the date the delivering party receives confirmation, if delivered by facsimile, (c) three (3) Business Days after being mailed by registered or certified mail (postage prepaid, return receipt requested) or (d) one (1) Business Day after being sent by overnight courier (providing proof of delivery), to the parties at the following addresses (or at such other address for a party as shall be specified in a notice given in accordance with this Section 11.2):

If to Seller, Merck or, prior to the Closing, the Company:

Merck Sharp & Dohme Corp.

One Merck Drive

P.O. Box 100

Whitehouse Station, NJ 08889

Attn: Office of the Secretary

Fax: (908) 735-1214

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With a copy (which shall not constitute notice) to:

Fried, Frank, Harris, Shriver & Jacobson LLP

One New York Plaza

New York, NY 10004

Attn: David Shine, Esq.

Fax: (212) 859-4000

If to Buyer or, after the Closing, the Company:

Alnylam Pharmaceuticals, Inc.

300 Third Street, 3 ^rd Floor

Cambridge, MA 02142

Attn: Chief Executive Officer

Fax: (617) 551-8101

With a copy (which shall not constitute notice) to:

Faber Daeufer & Itrato PC

950 Winter Street, Suite 4500

Waltham, MA 02451

Attn: Joseph L. Faber

Fax: (781) 795-4747

11.3.

Governing Law .

This Agreement shall in all respects be governed by, and construed in accordance with, the Laws (excluding conflict of laws rules and principles) of the State of New York applicable to agreements made and to be performed entirely within such State, including all matters of construction, validity and performance, provided , that the definition of Company Material Adverse Effect shall be governed by, and construed in accordance with, the Laws (excluding conflict of laws rules and principles) of the State of Delaware applicable to agreements made and to be performed entirely within such State, including all matters of construction, validity and performance.

11.4.

Entire Agreement .

This Agreement, together with the Exhibits hereto, the Company Disclosure Schedule, the Buyer Disclosure Schedule, the Ancillary Documents and the Confidentiality Agreement, constitute the entire agreement of the parties relating to the subject matter hereof and supersede all prior Contracts or agreements, whether oral or written.

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11.5.

Severability .

Should any provision of this Agreement or the application thereof to any Person or circumstance be held invalid or unenforceable to any extent: (a) such provision shall be ineffective to the extent, and only to the extent, of such unenforceability or prohibition and shall be enforced to the greatest extent permitted by Law, (b) such unenforceability or prohibition in any jurisdiction shall not invalidate or render unenforceable such provision as applied (i) to other Persons or circumstances or (ii) in any other jurisdiction, and (c) such unenforceability or prohibition shall not affect or invalidate any other provision of this Agreement.

11.6.

Amendment .

Neither this Agreement nor any of the terms hereof may be terminated, amended, supplemented or modified orally, but only by an instrument in writing signed by Buyer and Seller; provided , that the observance of any provision of this Agreement may be waived in writing by the party that will lose the benefit of such provision as a result of such waiver.

11.7.

Effect of Waiver or Consent .

No waiver or consent, express or implied, by any party to or of any breach or default by any party in the performance by such party of its obligations hereunder shall be deemed or construed to be a consent or waiver to or of any other breach or default in the performance by such party of the same or any other obligations of such party hereunder. No single or partial exercise of any right or power, or any abandonment or discontinuance of steps to enforce any right or power, shall preclude any other or further exercise thereof or the exercise of any other right or power. Failure on the part of a party to complain of any act of any party or to declare any party in default, irrespective of how long such failure continues, shall not constitute a waiver by such party of its rights hereunder until the applicable statute of limitation period has run.

11.8.

Parties in Interest; Limitation on Rights of Others .

The terms of this Agreement shall be binding upon, and inure to the benefit of, the parties hereto and their respective legal representatives, successors and assigns (including, in the case of Buyer, any transferees or assignees of the Company or some or all of the Company’s assets). For the avoidance of doubt, any and all amounts payable (or that may become payable) to Seller pursuant to Section 2.5 shall continue to be payable notwithstanding any license or sublicense by Buyer or its Affiliates of any Intellectual Property underlying any of the provisions of Section 2.5. Nothing in this Agreement, whether express or implied, shall be construed to give any Person (other than the parties hereto and their respective legal representatives, successors and assigns and as expressly provided herein) any legal or equitable right, remedy or claim under or in respect of this Agreement or any covenants, conditions or provisions contained herein, as a third party beneficiary or otherwise.

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11.9.

Assignability .

Neither this Agreement nor any rights or obligations hereunder may be assigned by any party hereto without the prior written consent of the other parties hereto.

11.10.

Disclosure Schedules .

No reference to or disclosure of any item or other matter in the Company Disclosure Schedule or the Buyer Disclosure Schedule shall be construed as an admission or indication that such item or other matter is material (nor shall it establish a standard of materiality for any purpose whatsoever) or that such item or other matter is required to be referred to or disclosed in the Company Disclosure Schedule or the Buyer Disclosure Schedule. The information set forth in the Company Disclosure Schedule and the Buyer Disclosure Schedule is disclosed solely for the purposes of this Agreement, and no information set forth therein shall be deemed to be an admission by any party hereto to any third party of any matter whatsoever, including any violation of Law or breach of any Contract. The Company Disclosure Schedule and the Buyer Disclosure Schedule and the information and disclosures contained therein are intended only to qualify and limit the representations, warranties and covenants of the Company and Buyer, respectively, contained in this Agreement. Nothing in the Company Disclosure Schedule or the Buyer Disclosure Schedule is intended to broaden the scope of any representation or warranty contained in this Agreement or create any covenant. Matters reflected in the Company Disclosure Schedule and the Buyer Disclosure Schedule are not necessarily limited to matters required by the Agreement to be reflected in the Company Disclosure Schedule and the Buyer Disclosure Schedule, respectively. Such additional matters are set forth for informational purposes and do not necessarily include other matters of a similar nature.

11.11.

Jurisdiction; Court Proceedings; Waiver of Jury Trial; Arbitration for Tech Transfer Condition .

(a) Subject to Section 11.12, any Litigation against any party to this Agreement arising out of or in any way relating to this Agreement shall be brought in any federal or state court located in the State of New York in New York County and each of the parties hereby submits to the exclusive jurisdiction of such courts for the purpose of any such Litigation; provided , that a final judgment in any such Litigation shall be conclusive and may be enforced in other jurisdictions by suit on the judgment or in any other manner provided by Law. Each party irrevocably and unconditionally agrees not to assert (1) any objection which it may ever have to the laying of venue of any such Litigation in any federal or state court located in the State of New York in New York County, (2) any claim that any such Litigation brought in any such court has been brought in an inconvenient forum and (3) any claim that such court does not have jurisdiction with respect to such Litigation. To the extent that service of process by mail is permitted by applicable Law, each party irrevocably consents to the service of process in any such Litigation in such courts by the mailing of such process by registered or certified mail, postage prepaid, at its address for notices provided for herein.

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(b) Each party irrevocably and unconditionally waives any right to a trial by jury and agrees that any of them may file a copy of this paragraph with any court as written evidence of the knowing, voluntary and bargained-for agreement among the parties irrevocably to waive its right to trial by jury in any Litigation.

(c) If Buyer delivers a Tech Transfer Objection Notice, Seller and Buyer shall, within ten (10) days following delivery of such notice (or such longer period as they may mutually agree in writing) (the “ Resolution Period ”), attempt in good faith to resolve their differences with respect to the disputed items specified in such notice (the “ Disputed Items ”), and all other items and aspects of Seller’s performance of its obligations under Section 5.10 that are not then in dispute will be final, binding and conclusive, absent fraud. Any resolution by Seller and Buyer during the Resolution Period as to any Disputed Item shall be set forth in writing and will be final, binding and conclusive, absent fraud. If Seller and Buyer do not resolve all Disputed Items by the end of the Resolution Period, then all Disputed Items remaining in dispute will be submitted to the Neutral Arbitrator. The Neutral Arbitrator shall act as an arbitrator to determine only those Disputed Items remaining in dispute, consistent with this Section 11.11(c) , and shall request a statement from Buyer and Seller regarding such Disputed Items. The scope of the disputes to be arbitrated by the Neutral Arbitrator is limited to the Disputed Items not resolved in the Resolution Period, and the Neutral Arbitrator is not allowed to make any determination other than whether the Tech Transfer Condition has been satisfied. All fees and expenses relating to the work, if any, to be performed by the Neutral Arbitrator will be shared equally between Buyer and Seller. The Neutral Arbitrator will deliver to Buyer and Seller a written determination (such determination to be based solely on information provided to the Neutral Arbitrator by Buyer and Seller) of the Disputed Items submitted to the Neutral Arbitrator within thirty (30) days of receipt of such Disputed Items, which determination will be final, binding and conclusive, absent fraud. If any party fails to submit a statement regarding any Disputed Item within the timeframe set forth above or within the timeframe required by the Neutral Arbitrator or otherwise fails to give the Neutral Arbitrator access as reasonably requested, then the Neutral Arbitrator shall render a decision based solely on the evidence timely submitted and the access afforded to the Neutral Arbitrator by the other party.

11.12.

Baseball Arbitration for Determination of Sublicense Value .

Disputes over the allocation of Sublicense Value described in Section 2.5(e)(iii) as referable for baseball arbitration under this Section 11.12 shall be resolved by arbitration as follows:

(a) Buyer and Seller shall jointly engage an arbitrator through JAMS (or its successor) (the “ Arbitrator ”). JAMS shall appoint the Arbitrator if the Buyer and Seller do not agree on which one to select within thirty (30) days. Buyer and Seller agree that the arbitrator shall be a lawyer with at least fifteen (15) years experience or a former judge of a court of general jurisdiction, and shall be experienced in matters regarding issues of a similar nature, and shall be neutral, independent, disinterested, and impartial.

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(b) If JAMS has any rules specific to baseball arbitration at the time a Party requests the baseball arbitration, then those rules shall apply. If JAMS does not have any such specific rules, then the most applicable procedural rules of JAMS shall apply. In each case, the applicable rules shall be modified to the extent in conflict with this Section 11.12. The place of arbitration shall be New York, New York or such other place as Buyer and Seller may mutually agree.

(c) In the case of a dispute under Section 2.5(e)(iii), Buyer shall disclose to the Arbitrator and to Seller (if it has not already done so) the relevant texts of all documents governing the Naked License transaction. Within thirty (30) days after such disclosure, Buyer and Seller shall each make its detailed proposal as to its calculation of Sublicense Value for such Naked License transaction, taking into account the portion of the aggregate Sublicense Value attributable to the Acquired Sirna Patents. Each of Buyer and Seller shall provide its proposal within sixty (60) days after the appointment of the Arbitrator, and each such proposal shall not exceed thirty (30) pages (including supporting materials and explanation). Buyer and Seller shall each be allowed three (3) depositions as part of the discovery process not to exceed fifteen (15) hours in the aggregate (or more if the Arbitrator deems them reasonably necessary), and each may perform reasonable document discovery to the extent determined by the Arbitrator. Buyer and Seller shall each disclose its proposal simultaneously to the other party and to the Arbitrator. The Arbitrator may hold hearings including both Buyer and Seller and in which each of Buyer and Seller may make a presentation or present witnesses for no more than four (4) hours. The Arbitrator may also question Buyer and Seller and hear their answers to the Arbitrator’s questions for no more than an additional eight (8) hours. Neither Buyer nor Seller shall engage in ex parte communications with the Arbitrator. The Arbitrator shall choose one of the parties’ proposals to become the arbitral award, and shall render his or her decision within ninety (90) days after the Arbitrator is selected.

(d) The Arbitrator shall choose the proposal for Sublicense Value that more fairly and reasonably allocates Buyer’s revenue from the Naked License transaction to the Acquired Sirna Patents, taking into account the provisions of Section 2.5(d). The Arbitrator shall not make the allocation based purely on the number of Patent Rights in the deal that are and are not Acquired Sirna Patents. Rather, the Arbitrator’s decision shall be based upon a qualitative inquiry into which Patent Rights and other Intellectual Property and assets included in the Naked License transaction are responsible for the value being realized and monetized in such transaction, and in what proportions.

(e) The Arbitrator’s selection shall be final and binding on Buyer and Seller with respect to the particular Naked License transaction absent proven fraud. Buyer and Seller shall each bear its own costs of arbitration, and shall share equally the costs for the Arbitrator and the arbitration process, unless the Arbitrator chooses to award costs and attorneys’ fees to Buyer or Seller in whole or in part, which the Arbitrator is hereby fully empowered to do. All information disclosed to the Arbitrator or to the other party by a party shall be Confidential Information of the disclosing party (except to the extent containing Confidential Information previously disclosed hereunder by the other party).

- 63 -

11.13.

No Other Duties .

The only duties and obligations of the parties under this Agreement are as specifically set forth in this Agreement, and no other duties or obligations shall be implied in fact, Law or equity, or under any principle of fiduciary obligation.

11.14.

Reliance on Counsel and Other Advisors .

Each party has consulted such legal, financial, technical or other expert as it deems necessary or desirable before entering into this Agreement. Each party represents and warrants that it has read, knows, understands and agrees with the terms and conditions of this Agreement.

11.15.

Remedies .

All remedies, either under this Agreement or by Law or otherwise afforded to the parties hereunder, shall be cumulative and not alternative, and any Person having any rights under any provision of this Agreement will be entitled to enforce such rights specifically, to recover damages by reason of any breach of this Agreement and to exercise all other rights granted by Law, equity or otherwise.

11.16.

Specific Performance .

The parties agree that irreparable damage would occur in the event that any of the provisions of this Agreement were not performed in accordance with their specific terms or were otherwise breached. Accordingly, the parties agree that, in addition to any other remedies, each party shall be entitled to enforce the terms of this Agreement by a decree of specific performance without the necessity of proving the inadequacy of money damages as a remedy. Each party hereby waives any requirement for the securing or posting of any bond in connection with such remedy. Each party further agrees that the only permitted objection that it may raise in response to any action for equitable relief is that it contests the existence of a breach or threatened breach of this Agreement.

11.17.

Counterparts .

This Agreement may be executed by facsimile signatures (or signatures otherwise transmitted electronically) and in any number of counterparts with the same effect as if all signatory parties had signed the same document. All counterparts shall be construed together and shall constitute one and the same instrument.

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11.18.

Further Assurance .

If at any time after the Closing any further action is necessary or desirable to fully effect the Contemplated Transactions, each of the parties shall take such further action (including the execution and delivery of such further instruments and documents) as any other party reasonably may request.

(signature pages follow)

- 65 -

IN WITNESS WHEREOF, each of the parties hereto has caused this Agreement to be duly executed and delivered in its name and on its behalf, all as of the day and year first above written.


ALNYLAM PHARMACEUTICALS, INC.

By:		/s/ Barry Greene
Name:		Barry Greene
Title:		President & COO

Alnylam Signature Page to Stock Purchase Agreement

- 66 -

IN WITNESS WHEREOF, each of the parties hereto has caused this Agreement to be duly executed and delivered in its name and on its behalf, all as of the day and year first above written.


SIRNA THERAPEUTICS, INC.

By:		/s/ Roger M. Perlmutter
Name:		Roger M. Perlmutter, M.D., Ph.D.
Title:		EVP and President
		Merck Research Laboratories

MERCK SHARP & DOHME CORP.

By:		/s/ Kenneth C. Frazier
Name:		Kenneth C. Frazier
Title:		Chairman, President and Chief Executive Officer

MERCK & CO., INC.

By:		/s/ Kenneth C. Frazier
Name:		Kenneth C. Frazier
Title:		Chairman, President and Chief Executive Officer

[Merck Signature Page to Stock Purchase Agreement]

Exhibit 10.1

Alnylam Pharmaceuticals, Inc.

2014 Annual Incentive Program

Summary Description

In March 2014, the Compensation Committee of the Board of Directors (the “Board”) of Alnylam Pharmaceuticals, Inc. (“Alnylam” or the “Company”) approved the 2014 Annual Incentive Program (the “Bonus Plan”) to incent and reward all regular employees based upon their performance relative to pre-established 2014 corporate and individual goals and objectives, and retain company employees by establishing an important element of Alnylam’s total rewards package consistent with Alnylam’s compensation philosophy and operating strategy.

Eligibility

All regular employees, who are employed by the Company both before October 1, 2014 and on January 15, 2015 (collectively, “Plan Participants”), are eligible to receive an annual cash bonus (a “Bonus Award”) based upon achievement of individual and corporate goals and objectives for 2014. The Compensation Committee may, in its discretion, include employees who join the Company after October 1, 2014 as Plan Participants. Bonus Awards for Plan Participants who have been employed with the Company for less than one year as of December 31, 2014 may be pro-rated by the Compensation Committee, in its discretion.

Goals

The corporate goals for 2014 were proposed by the Company’s executive officers and approved by the Board. Bonus Awards for the Company’s executive officers will be based entirely upon achievement of the corporate goals and each executive officer’s contributions to the achievement of those goals. Individual objectives for Plan Participants who are non-executive officers were approved by the Committee. Individual objectives for all other Plan Participants were approved by the employees’ direct supervisor and the appropriate officer of the Company.

Awards

Under the Bonus Plan, each Plan Participant has an established target award, as set forth in the table below, representing a percentage of the Plan Participant’s annual base salary for 2014 (a “Target Award”).


2014 Annual Incentive Program Target Awards
Title/Level	Target Award (% of Base Salary)
Chief Executive Officer		60	%
President and Chief Operating Officer		50	%
Executive Vice President		50	%
Senior Vice President		40	%
Vice President		30	%
Senior Director/Director		20	%
Associate Director		15	%
Senior Professionals		10	%
All Other Regular Employees		7.5	%

Bonus Awards under the Bonus Plan, if any, will be determined by first establishing a bonus pool (the “Bonus Pool”). The Bonus Pool will be calculated by (1) aggregating each Plan Participant’s Target Award and then (2) multiplying that sum by a modifier established by the Compensation Committee that is based on the Company’s performance as measured against the 2014 corporate goals (the “Corporate Performance Level”). The Corporate Performance Level for 2014 will range from 0% to 120%; provided, however, that the Corporate Performance Level can only exceed 100% upon the achievement of specified clinical development goals and further provided that, if the Corporate Performance Level for 2014 falls below a threshold of 50%, no Bonus Awards will be paid under the Bonus Plan.

The Bonus Pool will then be allocated among the Plan Participants based upon a consideration of each Plan Participant’s title/level and salary (as reflected by their Target Award percentage) and (i) with respect to Plan Participants who are executive officers, the Corporate Performance Level, as well as each executive officer’s contributions to achievement of the 2014 corporate goals, and (ii) with respect to all other Plan Participants, their 2014 year-end performance ratings, which shall be determined by their performance against their individual objectives for 2014, overall job performance and support of the Company’s core values.

The Compensation Committee retains the discretion under the Bonus Plan to adjust upward or downward any Bonus Award and/or the Bonus Pool as it deems appropriate.

In December 2014, the Compensation Committee plans to evaluate the Company’s performance against the established corporate goals, as well as the individual performance and contributions of the Plan Participants, establish the Bonus Pool and determine the amount of the Bonus Awards, if any, to be granted under the Bonus Plan. Any Bonus Awards granted to Plan Participants under the Bonus Plan are expected to be made in cash and to be paid in January 2015.

Administration; Amendment

The Bonus Plan is administered by the Compensation Committee. The Compensation Committee has full power and authority to interpret and make all decisions regarding the Bonus Plan, and its decisions and interpretations are final and binding on all Plan Participants. The Compensation Committee or the full Board may amend the Bonus Plan in any manner at any time without the consent of any Plan Participant.

Exhibit 10.2

STOCK PURCHASE AGREEMENT

By and Between

GENZYME CORPORATION

AND

ALNYLAM PHARMACEUTICALS, INC.

Dated as of January 11, 2014

TABLE OF CONTENTS


	Page
1. Definitions		1

1.1 Defined Terms		1
1.2 Additional Defined Terms		4

2. Purchase and Sale of Common Stock		5

3. Closing Date; Deliveries		5

3.1 Closing Date		5
3.2 Deliveries		5

4. Representations and Warranties of the Company		6

4.1 Organization, Good Standing and Qualification		6
4.2 Capitalization and Voting Rights		7
4.3 Subsidiaries		7
4.4 Authorization		7
4.5 No Defaults		8
4.6 No Conflicts		9
4.7 No Governmental Authority or Third Party Consents		9
4.8 Valid Issuance of Shares		9
4.9 Litigation		9
4.10 Licenses and Other Rights; Compliance with Laws		9
4.11 Company SEC Documents; Financial Statements; Nasdaq Stock Market		10
4.12 Absence of Certain Changes		11
4.13 Internal Controls; Disclosure Controls and Procedures		11
4.14 Intellectual Property		11
4.15 Tax Returns, Payments and Elections		12
4.16 Offering		12
4.17 No Integration		12
4.18 Brokers’ or Finders’ Fees		13
4.19 Not Investment Company		13

5. Representations and Warranties of the Investor		13

5.1 Organization; Good Standing		13
5.2 Authorization		13
5.3 No Conflicts		13
5.4 No Governmental Authority or Third Party Consents		14
5.5 Purchase Entirely for Own Account		14
5.6 Disclosure of Information		14
5.7 Investment Experience and Accredited Investor Status		14
5.8 Acquiring Person		14
5.9 Restricted Securities		14
5.10 Legends		14
5.11 Financial Assurances		15


6. Covenants of the Company			15

6.1 Conduct of the Business Pending Closing			15
6.2 Share Legend Removal			15

7. Investor’s Conditions to Closing			15

7.1 Representations and Warranties			15
7.2 Representations and Warranties in the Master Agreement			16
7.3 Covenants			16
7.4 Investor Agreement			16
7.5 No Material Adverse Effect			16
7.6 Listing			16
7.7 Rights Agreement; DGCL			16

8. Company’s Conditions to Closing			16

8.1 Representations and Warranties			16
8.2 Covenants			17
8.3 Investor Agreement			17

9. Mutual Conditions to Closing			17

9.1 HSR Act Qualification			17
9.2 Absence of Litigation			17
9.3 No Prohibition			17

10. Termination			17

10.1 Ability to Terminate			17
10.2 Effect of Termination			18

11. Additional Covenants and Agreements			18

11.1 Market Listing			18
11.2 Notification under the HSR Act			19
11.3 Assistance and Cooperation			20
11.4 Effect of Waiver of Condition to Closing			20

12. Miscellaneous			20

12.1 Governing Law; Submission to Jurisdiction			20
12.2 Waiver			20
12.3 Notices			21
12.4 Entire Agreement			21
12.5 Amendments			21
12.6 Headings; Nouns and Pronouns; Section References			21
12.7 Severability			21
12.8 Assignment			22
12.9 Successors and Assigns			22
12.10 Counterparts			22
12.11 Third Party Beneficiaries			22
12.12 No Strict Construction			22
12.13 Survival of Warranties			22
12.14 Remedies			22
12.15 Expenses			23

Exhibit A – Form of Cross Receipt

Exhibit B – Form of Investor Agreement

Exhibit C – Notices

iii

STOCK PURCHASE AGREEMENT

THIS STOCK PURCHASE AGREEMENT (this “ Agreement ”), dated as of January 11, 2014, by and between Genzyme Corporation (the “ Investor ”), a Massachusetts corporation, with its principal place of business at 500 Kendall Street, Cambridge, MA 02142, and Alnylam Pharmaceuticals, Inc. (the “ Company ”), a Delaware corporation, with its principal place of business at 300 Third Street, Cambridge, MA 02142.

WHEREAS, pursuant to the terms and subject to the conditions set forth in this Agreement, the Company desires to issue and sell to the Investor, and the Investor desires to subscribe for and purchase from the Company, certain shares of common stock, par value $.01 per share, of the Company (the “ Common Stock ”); and

WHEREAS, in partial consideration for Investor’s willingness to enter into this Agreement, the Company and Investor are entering into the Master Agreement dated as of the date hereof, pursuant to which (i) the Company will grant Investor certain licenses, options to obtain licenses, and other rights relating to the Company’s siRNA products targeting human genes as potential treatments for orphan diseases and under which Company and Investor will collaborate to develop and commercialize such siRNA products, and (ii) Company and Investor will enter into exclusive discussions and negotiations to potentially enter into an agreement under which Company and Investor would collaborate to advance new technologies for the delivery of siRNA to the central nervous system with the objective of enabling the discovery of siRNA products for the treatment of CNS disorders, and Investor will obtain certain rights to the technology discovered in such collaborations.

NOW, THEREFORE, in consideration of the following mutual promises and obligations, and for good and valuable consideration, the adequacy and sufficiency of which are hereby acknowledged, the Investor and the Company agree as follows:

1. Definitions .

1.1 Defined Terms . When used in this Agreement, the following terms shall have the respective meanings specified therefor below:

“ Affiliate ” shall mean, with respect to a Person, any other Person which controls, is controlled by or is under common control with the applicable Person. For purposes of this definition, “control” shall mean: (a) in the case of corporate entities, direct or indirect ownership of at least fifty percent (50%) of the stock or shares entitled to vote for the election of directors, or otherwise having the power to control or direct the affairs of such Person; and (b) in the case of non-corporate entities, direct or indirect ownership of at least fifty percent (50%) of the equity interest or the power to direct the management and policies of such non-corporate entities.

“ Agreement ” shall have the meaning set forth in the Preamble, including all Exhibits attached hereto.

“ Antitrust Laws ” means any federal, state or foreign law, regulation or decree, including the HSR Act, designed to prohibit, restrict or regulate actions for the purpose or effect of monopolization or restraint of trade.

“ Business Day ” shall mean a day on which commercial banking institutions in New York, New York are open for business.

“ Co-Co License Terms ” means the Co-Co License and Collaboration Terms attached to the Master Agreement as Appendix C .

“ Collaboration Agreement ” shall mean the Master Agreement and each of the License Terms.

“ Collaboration Assets ” shall mean any of the Company’s assets related to any Core Pipeline Program, Option Product or Collaboration Product (including ALN-TTR02 and ALN-TTRsc), each as defined in the Master Agreement.

“ Collaboration Material Adverse Effect ” shall mean any effect that, individually or when taken together with all other Effects, has (i) a material adverse effect on the Collaboration Assets, taken as a whole, or (ii) a material adverse effect on the Company’s ability to perform its obligations under the Collaboration Agreement or to initiate or continue Core Pipeline Programs.

“ Cross Receipt ” shall mean an executed document signed by each of the Company and the Investor, in substantially the form of Exhibit A attached hereto.

“ DOJ ” means the U.S. Department of Justice.

“ Effect ” shall have the meaning set forth in the definition of “Material Adverse Effect.”

“ FTC ” means the U.S. Federal Trade Commission.

“ Global License Terms ” means the Global License and Collaboration Terms attached to the Master Agreement as Appendix B .

“ Governmental Authority ” shall mean any applicable government authority, court, tribunal, arbitrator, agency, department, legislative body, commission or other instrumentality of (a) any government of any country or territory, (b) any nation, state, province, county, city or other political subdivision thereof or (c) any supranational body.

“ HSR Act ” means the Hart-Scott-Rodino Antitrust Improvements Act of 1976, as amended.

“ Intellectual Property ” shall mean shall mean trademarks, trade names, trade dress, service marks, copyrights, and similar rights (including registrations and applications to register or renew the registration of any of the foregoing), patents and patent applications, trade secrets, and any other similar intellectual property rights.

“ Intellectual Property License ” shall mean any license, permit, authorization, approval, contract or consent granted, issued by or with any Person relating to the use of Intellectual Property.

“ Investor Agreement ” shall mean that certain Investor Agreement between the Investor and the Company, to be dated as of the Closing Date, in the form of Exhibit B attached hereto, as the same may be amended from time to time.

“ Law ” or “ Laws ” shall mean all laws, statutes, rules, regulations, orders, judgments, injunctions and/or ordinances of any Governmental Authority.

“ License Terms ” means the Regional License Terms, the Co-Co License Terms, or the Global License Terms, as applicable.

“ Master Agreement ” shall mean that certain Master Agreement between Investor and Company, of even date herewith.

“ Material Adverse Effect ” shall mean any change, event or occurrence (each, an “Effect”) that, individually or when taken together with all other Effects, has (i) a material adverse effect on the business, financial condition, assets, results of operations or prospects of the Company and its subsidiaries, taken as a whole, or (ii) a material adverse effect on the Company’s ability to perform its obligations, or consummate the Transaction, in accordance with the terms of this Agreement, except in the case of (i) or (ii) to the extent that any such Effect results from or arises out of: (A) changes in conditions in the United States or global economy or capital or financial markets generally, including changes in interest or exchange rates, (B) changes in general legal, regulatory, political, economic or business conditions or changes in generally accepted accounting principles in the United States or interpretations thereof that, in each case, generally affect the biotechnology or biopharmaceutical industries, (C) the announcement of this Agreement or the Collaboration Agreement, or the identity of the Investor, (D) any change in the trading prices or trading volume of the Common Stock (it being understood that the facts giving rise to or contributing to any such change may be deemed to constitute, or be taken into account when determining whether there has been or will be, a Material Adverse Effect, except to the extent any of such facts is an Effect referred in clauses (A) through (H) of this definition), (E) acts of war, sabotage or terrorism, or any escalation or worsening of any such acts of war, sabotage or terrorism, (F) earthquakes, hurricanes, floods or other natural disasters, (G) any action taken by the Company with the Investor’s written consent, (H) any breach, violation or non-performance by the Investor or any of its Affiliates under the Collaboration Agreement, or (I) shareholder litigation arising out of or in connection with the execution, delivery or performance of the Transaction Agreements or the Collaboration Agreement; provided, that with respect to clauses (A), (B), (E) and (F) such Effect does not have a materially disproportionate and adverse effect on the Company relative to other companies in the biotechnology or biopharmaceutical industries.

“ Merger Control Authorities ” means all relevant Governmental Authorities under applicable Antitrust Laws, including the FTC and DOJ.

“ Organizational Documents ” shall mean (i) the Restated Certificate of Incorporation of the Company dated as of June 3, 2004, as amended through the date of this Agreement and (ii) the Amended and Restated Bylaws of the Company, as amended through the date of this Agreement.

“ Person ” shall mean any individual, partnership, limited liability company, firm, corporation, trust, unincorporated organization, government or any department or agency thereof or other entity, as well as any syndicate or group that would be deemed to be a Person under Section 13(d)(3) of the Exchange Act.

“ Regional License Terms ” means the Regional License and Collaboration Terms attached to the Master Agreement as Appendix A .

“ Third Party ” shall mean any Person (other than a Governmental Authority) other than the Investor, the Company or any Affiliate of the Investor or the Company.

“ Transaction ” means the issuance and sale of the Shares by the Company, and the purchase of the Shares by the Investor, in accordance with the terms hereof.

“ Transaction Agreements ” shall mean this Agreement and the Investor Agreement.

1.2 Additional Defined Terms . In addition to the terms defined in Section 1.1, the following terms shall have the respective meanings assigned thereto in the sections indicated below:


Defined Term		Section

Aggregate Purchase Price		Section 2

Closing		Section 3.1

Closing Date		Section 3.1

Common Stock		Preamble

Company		Preamble

Company Rights		Section 4.14(b)

Company SEC Documents		Section 4.11(a)

Exchange Act		Section 4.11(a)

Initial Antitrust Requirements		Section 11.2

Investor		Preamble

LAS		Section 4.7

Modified Clause		Section 12.7

Permits		Section 4.10


Defined Term		Section

Proprietary Rights		Section 4.14(b)

Rights Plan		Section 4.4(c)

Rights Plan Amendment		Section 4.4(c)

SEC		Section 4.7

Securities Act		Section 4.11(a)

Share Amount		Section 2

Shares		Section 2

Termination Date		Section 10.1(b)

2. Purchase and Sale of Common Stock . Subject to the terms and conditions of this Agreement, at the Closing, the Company shall issue and sell to the Investor, free and clear of all liens, other than any liens arising as a result of any action by the Investor, and the Investor shall purchase from the Company, a number of shares of Common Stock equal to the Share Amount (the “ Shares ”), for an aggregate purchase price of US $700,000,000.00. (the “ Aggregate Purchase Price ”). The “ Share Amount ” shall equal 8,766,338; provided, however, that in the event of any stock dividend, stock split, combination of shares, recapitalization or other similar change in the capital structure of the Company after the date hereof and on or prior to the Closing which affects or relates to the Common Stock, the Share Amount shall be adjusted proportionately.

3. Closing Date; Deliveries .

3.1 Closing Date . Subject to the satisfaction or waiver of all the conditions to the Closing set forth in Sections 7, 8 and 9 hereof, the closing of the purchase and sale of the Shares hereunder (the “ Closing ”) shall be held on the third (3 ^rd ) Business Day after the satisfaction of the conditions to Closing set forth in Sections 7, 8 and 9 (other than those conditions that by their nature are to be satisfied at the Closing, but subject to the satisfaction at such time of such conditions), at 10:00 a.m. Boston time, at the offices of Goodwin Procter LLP, 53 State Street, Boston, Massachusetts 02109, or at such other time, date and location as the parties may agree. The date the Closing occurs is hereinafter referred to as the “ Closing Date .”

3.2 Deliveries .

(a) Deliveries by the Company . At the Closing, the Company shall deliver to the Investor a stock certificate, registered in the name of the Investor, representing the Shares, and the Company shall instruct its transfer agent to register such issuance at the time of such issuance. The Company shall also deliver at the Closing: (i) a duly executed Cross Receipt; (ii) a certificate in form and substance reasonably satisfactory to the Investor and duly executed on behalf of the Company by an authorized executive officer of the Company, certifying that the

conditions to Closing set forth in Section 7 of this Agreement have been fulfilled; (iii) a duly executed Investor Agreement; and (iv) a certificate of the secretary of the Company dated as of the Closing Date certifying (A) that attached thereto is a true and complete copy of the Amended and Restated Bylaws of the Company as in effect at the time of the actions by the Board of Directors of the Company referred to in clause (B) below, and on the Closing Date; (B) that attached thereto is a true and complete copy of all resolutions adopted by the Board of Directors of the Company authorizing the execution, delivery and performance of the Transaction Agreements and the Transaction and that all such resolutions are in full force and effect and are all the resolutions adopted in connection with the transactions contemplated hereby as of the Closing Date; (C) that attached thereto is a true and complete copy of the Company’s Restated Certificate of Incorporation as in effect at the time of the actions by the Board of Directors of the Company referred to in clause (B) above, and on the Closing Date; and (D) as to the incumbency and specimen signature of any officer of the Company executing a Transaction Agreement on behalf of the Company.

(b) Deliveries by the Investor . At the Closing, the Investor shall deliver, or cause to be delivered, to the Company the Aggregate Purchase Price by wire transfer of immediately available United States funds to an account designated by the Company. The Company shall notify the Investor in writing of the wiring instructions for such account not less than three (3) Business Days before the Closing Date. The Investor shall also deliver, or cause to be delivered, at the Closing: (i) a duly executed Cross Receipt; (ii) a certificate in form and substance reasonably satisfactory to the Company duly executed by an authorized executive officer of the Investor certifying that the conditions to Closing set forth in Section 8 of this Agreement have been fulfilled; (iii) a duly executed Investor Agreement; and (iv) a certificate of the secretary of the Investor dated as of the Closing Date certifying as to the incumbency and specimen signature of any officer executing a Transaction Agreement on behalf of the Investor.

4. Representations and Warranties of the Company . The Company hereby represents and warrants to the Investor that:

4.1 Organization, Good Standing and Qualification .

(a) The Company is a corporation duly organized, validly existing and in good standing under the laws of the State of Delaware. The Company has all requisite corporate power and corporate authority to own, lease and operate its properties and assets, to carry on its business as now conducted, and as proposed to be conducted as described in the Company SEC Documents, to enter into the Transaction Agreements and the Collaboration Agreement, to issue and sell the Shares and to carry out the other transactions contemplated by the Transaction Agreements and the Collaboration Agreement.

(b) The Company is qualified to transact business and is in good standing in each jurisdiction in which the character of the properties owned, leased or operated by the Company or the nature of the business conducted by the Company makes such qualification necessary, except where the failure to be so qualified would not have or be reasonably likely to have a Material Adverse Effect.

4.2 Capitalization and Voting Rights .

(a) The authorized capital of the Company as of the date hereof consists of: (i) 125,000,000 shares of Common Stock of which, as of December 31, 2013, (x) 63,754,582 shares are issued and 63,739,607 shares are outstanding and (y) 11,369,175 shares are reserved for issuance pursuant to the Company’s stock incentive plans, of which 8,712,895 shares are issuable upon the exercise of stock options outstanding on the date hereof and (ii) 5,000,000 shares of preferred stock, par value $.01 per share, of which 125,000 have been designated as Series A Junior Participating Preferred Stock, and of which no shares are issued and outstanding as of the date of this Agreement. All of the issued and outstanding shares of Common Stock (A) have been duly authorized and validly issued, (B) are fully paid and non-assessable and (C) were issued in compliance with all applicable federal and state securities Laws and not in violation of any preemptive rights.

(b) All of the authorized shares of Common Stock are entitled to one (1) vote per share.

(c) Except as described or referred to in Section 4.2(a) above and as provided in the Investor Agreement, as of the date hereof, there are not: (i) any outstanding equity securities, options, warrants, rights (including conversion or preemptive rights) or other agreements pursuant to which the Company is or may become obligated to issue, sell or repurchase any shares of its capital stock or any other securities of the Company or (ii) except as set forth in the Investor Agreement, any restrictions on the transfer of capital stock of the Company other than pursuant to state and federal securities Laws.

(d) Except as provided in the Investor Agreement, the Company is not a party to or subject to any agreement or understanding relating to the voting of shares of capital stock of the Company or the giving of written consents by a stockholder or director of the Company.

(e) The issuance of the Shares contemplated by this Agreement will also constitute the issuance of any associated rights under the Rights Agreement, dated July 13, 2005, by and between the Company and EquiServe Trust Company, N.A.

4.3 Subsidiaries . Other than Alnylam (Bermuda) Ltd., a subsidiary formed subsequent to the filing of the Company’s most recent Annual Report on Form 10-K, the Company has disclosed all of its subsidiaries required to be disclosed pursuant to Item 601(b)(21) of Regulation S-K in an exhibit to its Annual Report on Form 10-K for the fiscal year ended December 31, 2012 filed on February 19, 2013. The Company or a wholly-owned subsidiary of the Company holds all of the outstanding equity interest of each subsidiary.

4.4 Authorization .

(a) All requisite corporate action on the part of the Company, its directors and stockholders required by applicable Law for the authorization, execution and delivery by the Company of the Transaction Agreements and the Collaboration Agreement, and the performance of all obligations of the Company hereunder and thereunder, including the authorization, issuance and delivery of the Shares, has been taken.

(b) This Agreement and the Collaboration Agreement have been, and upon the execution and delivery of the Investor Agreement by the Company at the Closing, the Investor Agreement will be, duly executed and delivered by the Company, and upon the due execution and delivery of this Agreement and the Collaboration Agreement by the Investor, this Agreement and the Collaboration Agreement will constitute, and upon the due execution and delivery of the Investor Agreement by the Investor, the Investor Agreement will constitute, valid and legally binding obligations of the Company, enforceable against the Company in accordance with their respective terms (except with respect to the Investor Agreement and the Collaboration Agreement as such enforceability may be limited by (i) applicable bankruptcy, insolvency, reorganization, moratorium or other Laws of general application relating to or affecting enforcement of creditors’ rights and (ii) rules of Law governing specific performance, injunctive relief or other equitable remedies and limitations of public policy).

(c) No “Distribution Date”, “Stock Acquisition Date”, “Section 11(a)(ii) Event” or “Section 13 Event”, each as defined in the Rights Plan (as defined below), will have occurred solely by virtue of the execution and delivery of this Agreement by the Company and the Investor. The Company’s Board of Directors has approved and directed the Company’s officers to implement an amendment (the “ Rights Plan Amendment ”) to the Rights Agreement, dated July 13, 2005, by and between the Company and EquiServe Trust Company, N.A. (the “ Rights Plan ”). Pursuant to such Rights Plan Amendment, the execution of this Agreement and the Investor Agreement, the performance of Investor’s and its Affiliates’ obligations under this Agreement and the Investor Agreement and the exercise of the Investor’s and its Affiliates’ rights under this Agreement and the Investor Rights Agreement (including the issuance of the Shares and the potential acquisition of additional shares of Common Stock by Investor to the extent permitted thereunder) will not result in (A) the Investor becoming or having become an “Acquiring Person” under the Rights Plan and (B) any of a “Stock Acquisition Date,” a “Distribution Date,” a “Section 11(a)(ii) Event” or a “Section 13 Event” (as such terms in clause (A) and (B) are defined in the Rights Plan). Further, the Company’s Board of Directors has approved the issuance of the Shares to the Investor hereunder, and all other transactions occurring pursuant to or as permitted by the Investor Agreement and the Master Agreement (including any other agreements or documents referenced therein), including the acquisition of shares of Common Stock other than the Shares by the Investor or any Affiliate consistent with the terms of the Investor Agreement, in a manner that satisfies Section 203(a)(1) of the Delaware General Corporation Law such that Section 203 will not apply to any “business combination” between the Company and the Investor or any Affiliate occurring pursuant to or as permitted by this Agreement or the Investor Agreement or the Master Agreement.

(d) No stop order or suspension of trading of the Common Stock has been imposed by Nasdaq, the SEC or any other Government Authority and remains in effect.

4.5 No Defaults . The Company is not in default under or in violation of (a) its Organizational Documents, (b) any provision of applicable Law or any ruling, writ, injunction, order, Permit, judgment or decree of any Governmental Authority or (c) any agreement, arrangement or instrument, whether written or oral, by which the Company or any of its assets are bound, except, in the case of subsections (b) and (c), as would not have or be reasonably likely to have a Material Adverse Effect. To the knowledge of the Company, there exists no condition, event or act which after notice, lapse of time, or both, would constitute a default or violation by the Company under any of the foregoing, except, in the case of subsections (b) and (c), as would not have or be reasonably likely to have a Material Adverse Effect.

4.6 No Conflicts . The execution, delivery and performance of the Transaction Agreements and the Collaboration Agreement, and compliance with the provisions hereof and thereof, by the Company do not and shall not: (a) violate any provision of applicable Law or any ruling, writ, injunction, order, permit, judgment or decree of any Governmental Authority, (b) constitute a breach of, or default under (or an event which, with notice or lapse of time or both, would become a default under) or conflict with, or give rise to any right of termination, cancellation or acceleration of, any agreement, arrangement or instrument, whether written or oral, by which the Company or any of its assets are bound, (c) result in any encumbrance upon any of the Shares, other than restrictions on resale pursuant to securities laws, or on any of the properties or assets of the Company or any subsidiary or (d) violate or conflict with any of the provisions of the Company’s Organizational Documents, except, in the case of subsections (a), (b) and (c) as would not have or be reasonably likely to have a Material Adverse Effect with respect to this Agreement or the Investor Agreement or a Collaboration Material Adverse Effect with respect to the Collaboration Agreement.

4.7 No Governmental Authority or Third Party Consents . No consent, approval, authorization or other order of, or filing with, or notice to, any Governmental Authority or other Third Party is required to be obtained or made by the Company in connection with the authorization, execution and delivery by the Company of any of the Transaction Agreements or the Collaboration Agreement, or with the authorization, issue and sale by the Company of the Shares, except (i) such filings as may be required to be made with the Securities and Exchange Commission (the “ SEC ”) and with any state blue sky or securities regulatory authority, which filings shall be made in a timely manner in accordance with all applicable Laws, (ii) as required pursuant to the HSR Act and (iii) with respect to the Shares, the filing with The Nasdaq Stock Market LLC of, and the absence of unresolved issues with respect to, a Notification Form: Listing of Additional Shares (the “ LAS ”).

4.8 Valid Issuance of Shares . When issued, sold and delivered at the Closing in accordance with the terms hereof for the Aggregate Purchase Price, the Shares will be duly authorized, validly issued, fully paid and nonassessable, free from any liens, encumbrances or restrictions on transfer, including preemptive rights, rights of first refusal or other similar rights, other than as arising pursuant to the Investor Agreement, as a result of any action by the Investor or under federal or state securities Laws.

4.9 Litigation . Except as set forth in the Company SEC Documents filed prior to the date of this Agreement, there is no action, suit, proceeding or investigation pending (of which the Company has received notice or otherwise has knowledge) or, to the Company’s knowledge, threatened, against the Company or which the Company intends to initiate which has had or is reasonably likely to have a Material Adverse Effect.

4.10 Licenses and Other Rights; Compliance with Laws . The Company has all franchises, permits, licenses and other rights and privileges (“ Permits ”) necessary to permit it to own its properties and to conduct its business as presently conducted and is in compliance

thereunder, except where the failure to be in compliance does not and would not be reasonably likely to have a Material Adverse Effect. To the Company’s knowledge, it has not taken any action that would interfere with the Company’s ability to renew all such Permit(s), except where the failure to renew such Permit(s) would not have or be reasonably likely to have a Material Adverse Effect. The Company is and has been in compliance with all Laws applicable to its business, properties and assets, and to the products and services sold by it, except where the failure to be in compliance does not and would not have or be reasonably likely to have a Material Adverse Effect.

4.11 Company SEC Documents; Financial Statements; Nasdaq Stock Market .

(a) Since December 31, 2012, the Company has timely filed all required reports, schedules, forms, statements and other documents (including exhibits and all other information incorporated therein), and any required amendments to any of the foregoing, with the SEC (the “ Company SEC Documents ”). As of their respective filing dates, each of the Company SEC Documents complied in all material respects with the requirements of the Securities Act of 1933, as amended (the “ Securities Act ”), and the Securities Exchange Act of 1934, as amended (the “ Exchange Act ”), and the rules and regulations of the SEC promulgated thereunder applicable to such Company SEC Documents, and no Company SEC Documents when filed, declared effective or mailed, as applicable, contained any untrue statement of a material fact or omitted to state a material fact required to be stated therein or necessary in order to make the statements therein, in light of the circumstances under which they were made, not misleading.

(b) As of the date of this Agreement, other than as has been disclosed to the Investor, there are no outstanding or unresolved comments in comment letters received from the SEC or its staff. As of the date of this Agreement, none of the Company’s subsidiaries is subject to the reporting requirements of Section 13(a) or 15(d) under the Exchange Act.

(c) The financial statements of the Company included in its Annual Report on Form 10-K for the fiscal year ended December 31, 2012 and in its quarterly reports on Form 10-Q for the quarterly periods ended September 30, 2013, June 30, 2013, and March 31, 2013 comply as to form in all material respects with applicable accounting requirements and the published rules and regulations of the SEC with respect thereto, have been prepared in accordance with United States generally accepted accounting principles applied on a consistent basis during the periods involved (except as may be indicated in the notes thereto) and fairly present in all material respects the financial position of the Company as of the dates thereof and the results of its operations and cash flows for the periods then ended. Except (i) as set forth in the Company SEC Documents or (ii) for liabilities incurred in the ordinary course of business subsequent to the date of the most recent balance sheet contained in the Company SEC Documents, the Company has no liabilities, whether absolute or accrued, contingent or otherwise, other than those that would not, individually or in the aggregate, have or be reasonably likely to have a Material Adverse Effect. There are no material unconsolidated subsidiaries of the Company or any material off-balance sheet arrangements of any type (including any off-balance sheet arrangement required to be disclosed pursuant to Item 303(a)(4) of Regulation S-K promulgated under the Securities Act) that have not been so described in the SEC Documents filed prior to the date hereof nor any obligations to enter into any such arrangements.

(d) The Common Stock is listed on The Nasdaq Global Select Market, and the Company has taken no action designed to, or which to its knowledge is likely to have the effect of, terminating the registration of the Common Stock under the Exchange Act or delisting the Common Stock from The Nasdaq Global Select Market. As of the date of this Agreement, the Company has not received any notification that, and has no knowledge that, the SEC or The Nasdaq Stock Market LLC is contemplating terminating such listing or registration.

4.12 Absence of Certain Changes .

(a) Except as disclosed in the Company SEC Documents filed prior to the date hereof, since December 31, 2012, there has not occurred any Effect that has caused or would reasonably be expected to cause a Material Adverse Effect.

(b) Except as set forth in the Company SEC Documents filed prior to the date hereof, since December 31, 2012, the Company has not (i) declared or paid any dividends, or authorized or made any distribution upon or with respect to any class or series of its capital stock, or (ii) sold, exchanged or otherwise disposed of any of its material assets or rights.

(c) Since December 31, 2012, the Company has not admitted in writing its inability to pay its debts generally as they become due, filed or consented to the filing against it of a petition in bankruptcy or a petition to take advantage of any insolvency act, made an assignment for the benefit of creditors, consented to the appointment of a receiver for itself or for the whole or any substantial part of its property, or had a petition in bankruptcy filed against it, been adjudicated a bankrupt, or filed a petition or answer seeking reorganization or arrangement under the federal bankruptcy laws or any other laws of the United States or any other jurisdiction.

4.13 Internal Controls; Disclosure Controls and Procedures . The Company maintains internal control over financial reporting as defined in Rule 13a-15(f) under the Exchange Act. The Company has implemented the “disclosure controls and procedures” (as defined in Rules 13a-15(e) and 15d-15(e) under the Exchange Act) required in order for the Principal Executive Officer and Principal Financial Officer of the Company to engage in the review and evaluation process mandated by the Exchange Act, and is in compliance with such disclosure controls and procedures in all material respects. Each of the Principal Executive Officer and the Principal Financial Officer of the Company (or each former Principal Executive Officer of the Company and each former Principal Financial Officer of the Company, as applicable) has made all certifications required by Sections 302 and 906 of the Sarbanes-Oxley Act of 2002 with respect to all reports, schedules, forms, statements and other documents required to be filed by the Company with the SEC.

4.14 Intellectual Property .

(a) The Intellectual Property that is owned by the Company is owned free from any liens or restrictions, and all of the Company’s material Intellectual Property Licenses are in full force and effect in accordance with their terms, are free of any liens or

restrictions, and neither the Company nor to the Company’s knowledge any other party thereto, is in material breach of any such material Intellectual Property License, and no event has occurred that with notice or lapse of time or both would constitute such a breach or default thereunder or would result in the termination thereof or would cause or permit the acceleration or other change of any right or obligation of the loss of any benefit thereunder by the Company except (i) for such failures to be in full force and effect, such liens or restrictions, and such material breaches that would not reasonably be expected to have a Material Adverse Effect, or (ii) as set forth in any such Intellectual Property License. Except as set forth in the Company SEC Documents, there is no legal claim or demand of any Person pertaining to, or any proceeding which is pending (of which the Company has received notice or otherwise has knowledge) or, to the knowledge of the Company, threatened, (i) challenging the right of the Company in respect of any Company Intellectual Property, or (ii) that claims that any default exists under any Intellectual Property License, except, in the case of (i) and (ii) above, where any such claim, demand or proceeding would not have or reasonably be expected to have a Material Adverse Effect.

(b) Except as set forth in the Company’s SEC Documents: (i) the Company or one of its subsidiaries owns, free and clear of any lien or encumbrance, or has a valid license to, or has an enforceable right to use, as it is used or held for use, all U.S. and non-U.S. patents, trade secrets, know-how, trademarks, service marks, copyrights, and other proprietary and intellectual property rights, and all grants and applications with respect to the foregoing (collectively, the “ Proprietary Rights ” ) necessary for the conduct of the Company’s business, the absence of which would not have or reasonably be expected to have a Material Adverse Effect (such Proprietary Rights owned by or licensed to the Company collectively, the “ Company Rights ” ); and (ii) the Company and its subsidiaries have taken reasonable measures to protect the Company Rights, consistent with prudent commercial practices in the biotechnology industry, except where failure to take such measures would not have or reasonably be expected to have a Material Adverse Effect.

4.15 Tax Returns, Payments and Elections . The Company has filed all tax returns and reports as required, and within the time prescribed, by law and has paid or made provision for the payment of all accrued and unpaid taxes to which the Company is subject and which are not currently due and payable, except where any failure would not have a Material Adverse Effect.

4.16 Offering . Subject to the accuracy of the Investor’s representations set forth in Sections 5.5, 5.6, 5.7, 5.9 and 5.10, the offer, sale and issuance of the Shares to be issued in conformity with the terms of this Agreement constitute transactions which are exempt from the registration requirements of the Securities Act and from all applicable state registration or qualification requirements. Neither the Company nor any Person acting on its behalf will take any action that would cause the loss of such exemption.

4.17 No Integration . The Company has not, directly or through any agent, sold, offered for sale, solicited offers to buy or otherwise negotiated in respect of, any security (as defined in the Securities Act) which is or will be integrated with the Shares sold pursuant to this Agreement in a manner that would require the registration of the Shares under the Securities Act.

4.18 Brokers’ or Finders’ Fees . No broker, finder, investment banker or other Person is entitled to any brokerage, finder’s or other fee or commission from the Company in connection with the transactions contemplated by the Transaction Agreements and the Collaboration Agreement.

4.19 Not Investment Company . The Company is not, and solely after receipt of the Aggregate Purchase Price, will not be, an “investment company” as defined in the Investment Company Act of 1940, as amended.

5. Representations and Warranties of the Investor . The Investor hereby represents and warrants to the Company, that:

5.1 Organization; Good Standing . The Investor is a corporation duly organized, validly existing and in good standing under the laws of Massachusetts. The Investor has or will have all requisite power and authority to enter into the Transaction Agreements and the Collaboration Agreement, to purchase the Shares and to perform its obligations under and to carry out the other transactions contemplated by the Transaction Agreements and the Collaboration Agreement.

5.2 Authorization . All requisite action on the part of the Investor and its directors and stockholders, required by applicable Law for the authorization, execution and delivery by the Investor of the Transaction Agreements and the Collaboration Agreement, and the performance of all of its obligations thereunder, including the subscription for and purchase of the Shares, has been taken. This Agreement and the Collaboration Agreement have been, and upon the execution and delivery of the Investor Agreement at the Closing by the Investor, the Investor Agreement will be, duly executed and delivered by the Investor and upon the due execution and delivery thereof by the Company, will constitute valid and legally binding obligations of the Investor, enforceable against the Investor in accordance with their respective terms (except with respect to the Investor Agreement and the Collaboration Agreement as such enforceability may be limited by (i) applicable bankruptcy, insolvency, reorganization, moratorium or other Laws of general application relating to or affecting enforcement of creditors’ rights and (ii) rules of Law governing specific performance, injunctive relief or other equitable remedies and limitations of public policy).

5.3 No Conflicts . The execution, delivery and performance of the Transaction Agreements and the Collaboration Agreement, and compliance with the provisions thereof, by the Investor do not and shall not: (a) violate any provision of applicable Law or any ruling, writ, injunction, order, permit, judgment or decree of any Governmental Authority, (b) constitute a breach of, or default under (or an event which, with notice or lapse of time or both, would become a default under) or conflict with, or give rise to any right of termination, cancellation or acceleration of, any agreement, arrangement or instrument, whether written or oral, by which the Investor or any of its assets, are bound, or (c) violate or conflict with any of the provisions of the Investor’s organizational documents (including any articles or memoranda of organization or association, charter, bylaws or similar documents), except as would not impair or adversely affect the ability of the Investor to consummate the Transactions and perform its obligations under the Transaction Agreements and the Collaboration Agreement.

5.4 No Governmental Authority or Third Party Consents . No consent, approval, authorization or other order of any Governmental Authority or other Third Party is required to be obtained by the Investor in connection with the authorization, execution and delivery of any of the Transaction Agreements or the Collaboration Agreement, or with the subscription for and purchase of the Shares, except as required pursuant to the HSR Act.

5.5 Purchase Entirely for Own Account . The Shares shall be acquired for investment for the Investor’s own account, not as a nominee or agent, and not with a view to the resale or distribution of any part thereof, and the Investor has no present intention of selling, granting any participation or otherwise distributing the Shares. The Investor does not have and will not have as of the Closing any contract, undertaking, agreement or arrangement with any Person to sell, transfer or grant participation to a Person any of the Shares.

5.6 Disclosure of Information . The Investor has received all the information from the Company and its management that the Investor considers necessary or appropriate for deciding whether to purchase the Shares hereunder. The Investor further represents that it has had an opportunity to ask questions and receive answers from the Company regarding the Company, its financial condition, results of operations and prospects and the terms and conditions of the offering of the Shares sufficient to enable it to evaluate its investment.

5.7 Investment Experience and Accredited Investor Status . The Investor is an “accredited investor” (as defined in Regulation D under the Securities Act). The Investor has such knowledge and experience in financial or business matters that it is capable of evaluating the merits and risks of the investment in the Shares to be purchased hereunder.

5.8 Acquiring Person . As of the date of this Agreement and immediately prior to the Closing, neither the Investor nor any of its Affiliates beneficially owns, or will beneficially own (as determined pursuant to Rule 13d-3 under the Exchange Act without regard for the number of days in which a Person has the right to acquire such beneficial ownership, and without regard to Investor’s rights under this Agreement), any securities of the Company, except for securities that may be owned by employee benefit plans of the Investor or its Affiliates in the ordinary course of business.

5.9 Restricted Securities . The Investor understands that the Shares, when issued, will be “restricted securities” under the federal securities Laws inasmuch as they are being acquired from the Company in a transaction not involving a public offering and that under such Laws the Shares may be resold without registration under the Securities Act only in certain limited circumstances. The Investor represents that it is familiar with Rule 144 of the Securities Act, as presently in effect.

5.10 Legends . The Investor understands that any certificates representing the Shares shall bear the following legends:

(a) “These securities have not been registered under the Securities Act of 1933. They may not be sold, offered for sale, pledged or hypothecated in the absence of a registration statement in effect with respect to the securities under the Securities Act or an opinion of counsel (which counsel shall be reasonably satisfactory to Alnylam Pharmaceuticals, Inc.) that such registration is not required or unless sold pursuant to Rule 144 of the Securities Act.”;

(b) “The securities represented by this certificate are subject to and shall be transferable only upon the terms and conditions of an Investor Agreement by and between Alnylam Pharmaceuticals, Inc. and Genzyme Corporation, a copy of which is on file with the Secretary of Alnylam Pharmaceuticals, Inc.”

5.11 Financial Assurances . As of the date hereof and as of the Closing Date, the Investor has and will have access to cash in an amount sufficient to pay to the Company the Aggregate Purchase Price.

6. Covenants of the Company .

6.1 Conduct of the Business Pending Closing . During the period from the date hereof until the Closing, except as consented to in writing by the Investor, the Company shall not (i) declare, set aside or pay any dividend or make any other distribution or payment (whether in cash, stock or property or any combination thereof) in respect of its capital stock or (ii) make any other actual, constructive or deemed distribution in respect of any shares of its capital stock or otherwise make any payments to stockholders in their capacity as such, except pursuant to repurchases of equity pursuant to the terms of its equity compensation plans.

6.2 Share Legend Removal . The legend set forth in Section 5.10 hereof shall be removed from any certificate evidencing the Shares (or if the Shares are held in book-entry form, any restrictions on transfer noted with respect thereto shall be removed) and the Company shall, or shall cause its transfer agent to, issue, no later than three (3) business days from receipt of a request from the Investor pursuant to this Section 6.2, a certificate or certificates evidencing all or a portion of the Shares, as requested by the Investor, without such legend if such legend removal is in compliance with Sections 4 and 5 of the Investor Agreement and: (i) such securities have been resold under an effective registration statement under the Securities Act, (ii) such securities have been or will be transferred in compliance with Rule 144 under the Securities Act, (iii) such securities are eligible for resale pursuant to Rule 144(b)(1)(i) under the Securities Act or (iv) the Investor shall have provided the Company with an opinion of counsel, reasonably satisfactory to the Company, stating that such securities may lawfully be transferred without registration under the Securities Act (assuming for this purpose that the Investor is not an affiliate of the Issuer).

6.3 Amendment of Rights Plan . Prior to the Closing, the Company shall adopt an amendment to the Rights Plan containing the substance of the Rights Plan Amendment.

7. Investor’s Conditions to Closing . The Investor’s obligation to purchase the Shares at the Closing is subject to the fulfillment as of such Closing of the following conditions (unless waived in writing by the Investor):

7.1 Representations and Warranties . The representations and warranties made by the Company in Section 4 hereof shall be true and correct as of the date of this Agreement and as of the Closing Date as though made on and as of such Closing Date, except to the extent such representations and warranties are specifically made as of a particular date, in which case

such representations and warranties shall be true and correct as of such date; provided , however , that for purposes of this Section 7.1, all such representations and warranties of the Company (other than Sections 4.1(a), 4.2, 4.3, 4.4, 4.5(a), 4.6(d), 4.8, 4.11 and 4.13 of this Agreement) shall be deemed to be true and correct for purposes of this Section 7.1 unless the failure or failures of such representations and warranties to be so true and correct, without regard to any “material,” “materiality” or “Material Adverse Effect” qualifiers set forth therein, individually or in the aggregate, has had or would reasonably be expected to have a Material Adverse Effect.

7.2 Representations and Warranties in the Master Agreement . The representations and warranties made by the Company in Sections 8.2.1, 8.2.2, 8.2.5, 8.2.7, 8.2.9 and 8.2.10 of the Master Agreement shall be true and correct as of the Closing Date as though made on and as of such Closing Date, except to the extent such representations and warranties are specifically made as of a particular date, in which case such representations and warranties shall be true and correct as of such date; provided , however , that for purposes of this Section 7.2, all such representations and warranties of the Company (other than Sections 8.2.1 and 8.2.2 of the Master Agreement) shall be deemed to be true and correct for purposes of this Section 7.2 unless the failure or failures of such representations and warranties to be so true and correct, without regard to any “material” or “materiality” qualifiers set forth therein, individually or in the aggregate, has had or would reasonably be expected to have a Collaboration Material Adverse Effect.

7.3 Covenants . All covenants and agreements contained in this Agreement to be performed or complied with by the Company on or prior to the Closing Date shall have been performed or complied with in all material respects.

7.4 Investor Agreement . The Company shall have duly executed and delivered to the Investor, pursuant to Section 3.2(a) of this Agreement, the Investor Agreement, and (subject to execution by the Investor) such agreement shall be in full force and effect.

7.5 No Material Adverse Effect . From and after the date of this Agreement until the Closing Date, there shall have occurred no event that has caused or would reasonably be expected to cause a Material Adverse Effect or a Collaboration Material Adverse Effect.

7.6 Listing . The Shares shall be eligible for listing on the Nasdaq Global Select Market.

7.7 Rights Agreement; DGCL . The representations in Section 4.4(c) shall be true and correct in all respects and the Company shall have performed the covenants in Section 6.3 in all respects.

8. Company’s Conditions to Closing . The Company’s obligation to issue and sell the Shares at the Closing is subject to the fulfillment as of such Closing of the following conditions (unless waived in writing by the Company):

8.1 Representations and Warranties . The representations and warranties made by the Investor in Section 5 hereof shall be true and correct as of the date of this Agreement and as of the Closing Date as though made on and as of such Closing Date, except to the extent such representations and warranties are specifically made as of a particular date, in which case such

representations and warranties shall be true and correct as of such date, in the case of Sections 5.1-5.4, and 5.11, except where any failure to be true and correct would not have a material adverse effect on the Investor’s ability to perform its obligations, or consummate the Transaction in accordance with the terms of this Agreement, in the case of Section 5.5, 5.6 and 5.7, except where any inaccuracy would not result in the issuance of the Shares hereunder failing to qualify as an offering of securities not involving any public offering under the federal securities Laws, and in the case of Section 5.8, except where any inaccuracy would not be material on the Investor’s ability to perform its obligations, or consummate the Transaction in accordance with the terms of this Agreement.

8.2 Covenants . All covenants and agreements contained in this Agreement to be performed or complied with by the Investor on or prior to the Closing Date shall have been performed or complied with in all material respects.

8.3 Investor Agreement . The Investor shall have duly executed and delivered to the Company, pursuant to Section 3.2(b) of this Agreement, the Investor Agreement, and (subject to execution by the Company) such agreement shall be in full force and effect.

9. Mutual Conditions to Closing . The obligations of the Investor and the Company to consummate the Closing are subject to the fulfillment as of the Closing Date of the following conditions:

9.1 HSR Act Qualification . The filings required under the HSR Act in connection with this Agreement shall have been made and the required waiting period shall have expired or been terminated as of the Closing Date.

9.2 Absence of Litigation . There shall be no action, suit, proceeding or investigation by a Governmental Authority pending or currently threatened in writing against the Company or the Investor that questions the validity of any of the Transaction Agreements, the right of the Company or the Investor to enter into any Transaction Agreement or to consummate the transactions contemplated hereby or thereby or which, if determined adversely, would impose substantial monetary damages on the Company or the Investor as a result of the consummation of the transactions contemplated by any Transaction Agreement.

9.3 No Prohibition . No provision of any applicable Law and no judgment, injunction (preliminary or permanent), order or decree that prohibits, makes illegal or enjoins the consummation of the Transaction shall be in effect

10. Termination .

10.1 Ability to Terminate . This Agreement may be terminated at any time prior to the Closing by:

(a) mutual written consent of the Company and the Investor;

(b) either the Company or the Investor, upon written notice to the other after one hundred and twenty (120) days from the date hereof (the “ Termination Date ”), if the Transaction shall not have been consummated by the Termination Date; provided further ,

however , that the right to terminate this Agreement under this Section 10.1(b) shall not be available to any party whose failure to fulfill any obligation under this Agreement has been the cause of, or resulted in, the failure to consummate the transactions contemplated hereby prior to the Termination Date;

(c) either the Company or the Investor, upon written notice to the other, if any of the mutual conditions to the Closing set forth in Section 9 shall have become incapable of fulfillment by the Termination Date and shall not have been waived in writing by the other party; provided , however , that the right to terminate this Agreement under this Section 10.1(c) shall not be available to any party whose failure to fulfill any obligation under this Agreement has been the cause of, or resulted in, the failure to consummate the transactions contemplated hereby prior to the Termination Date;

(d) the Company, upon written notice to the Investor, so long as the Company is not then in breach of its representations, warranties, covenants or agreements under this Agreement such that any of the conditions set forth in Section 8.1 or 8.2, as applicable, could not be satisfied by the Termination Date, (i) upon a breach of any covenant or agreement on the part of the Investor set forth in this Agreement, or (ii) if any representation or warranty of the Investor shall have been or become untrue, in each case such that any of the conditions set forth in Section 8.1 or 8.2, as applicable, could not be satisfied by the Termination Date;

(e) the Investor, upon written notice to the Company, so long as the Investor is not then in breach of its representations, warranties, covenants or agreements under this Agreement such that any of the conditions set forth in Section 7.1, 7.2 or 7.3, as applicable, could not be satisfied by the Termination Date, upon a breach of any covenant or agreement on the part of the Company set forth in this Agreement, or if any representation or warranty of the Company shall have been or become untrue, in each case such that any of the conditions set forth in Section 7.1, 7.2 or 7.3, as applicable, could not be satisfied by the Termination Date.

10.2 Effect of Termination . In the event of the termination of this Agreement pursuant to Section 10.1 hereof, (a) this Agreement (except for this Section 10.2 and Section 12 hereof (other than Section 12.13), and any definitions set forth in this Agreement and used in such sections) shall forthwith become void and have no effect, without any liability on the part of any party hereto or its Affiliates, and (b) all filings, applications and other submissions made pursuant to this Agreement, to the extent practicable, shall be withdrawn from the agency or other Person to which they were made or appropriately amended to reflect the termination of the transactions contemplated hereby; provided , however , that nothing contained in this Section 10.2 shall relieve any party from liability for fraud or any intentional or willful breach of this Agreement.

11. Additional Covenants and Agreements .

11.1 Market Listing . From the date hereof through the Closing Date, Company shall use all reasonable efforts to (a) maintain the listing and trading of the Common Stock on The Nasdaq Global Select Market and (b) effect the listing of the Shares on The Nasdaq Global Select Market, including submitting the LAS to The Nasdaq Stock Market LLC no later than fifteen (15) calendar days prior to the Closing Date.

11.2 Notification under the HSR Act .

(a) As promptly as practicable, but not later than the tenth (10 ^th ) business day following the date of this Agreement, each of Investor and Company shall make or cause to be made under applicable Antitrust Law the notifications and filings listed on Schedule 11.2 of this Agreement (the “ Initial Antitrust Requirements ”). Each party shall be responsible for its own costs and expenses associated with the notifications and filings under applicable Antitrust Law, and Investor shall pay the applicable premerger filing fee under the HSR Act. Each party shall use its commercially reasonable efforts to obtain the expiration or termination of the applicable waiting period under the HSR Act, and to obtain the termination or expiration of any other applicable waiting periods or any necessary approvals or consents under any other applicable Antitrust Law, including the Initial Antitrust Requirements, at the earliest possible date after the date of filing.

(b) Each of Investor and Company shall: (i) reasonably cooperate with each other in connection with any investigation or other inquiry relating to the transactions contemplated by the Transaction Agreements and the Collaboration Agreement; (ii) reasonably keep the other party informed of any communication received by such party from, or given by such party to, the FTC, the DOJ or any other Merger Control Authority and of any communication received or given in connection with any proceeding by a private party, in each case regarding the transactions contemplated by the Transaction Agreements or the Collaboration Agreement; (iii) promptly respond to and certify substantial compliance with any inquiries or requests received from the FTC, the DOJ or any other Merger Control Authorities for additional information or documentation; (iv) reasonably consult with each other in advance of any meeting or conference with the FTC, the DOJ or any other Merger Control Authority, and to the extent permitted by the FTC, the DOJ or such other Merger Control Authority and reasonably determined by such party to be appropriate under the circumstances, give the other party or their counsel the opportunity to attend and participate in such meetings and conferences; and (v) permit the other party or their counsel to the extent reasonably practicable to review in advance, and in good faith consider the views of the other party or their counsel concerning, any submission, filing or communication (and documents submitted therewith) intended to be given by it to the FTC, the DOJ or any other Merger Control Authority; provided , however , such party shall be under no obligation to reschedule any meetings or conferences with the FTC, the DOJ or any other Merger Control Authority to enable the other party to attend.

(c) Notwithstanding anything to the contrary in this Agreement, the terms “commercially reasonable efforts” or “reasonable efforts” do not require that either party (i) offer, negotiate, commit to or effect, by consent decree, hold separate order, trust or otherwise, the sale, divestiture, license or other disposition of any capital stock, assets, rights, products or businesses of Investor, Company or their respective Affiliates, (ii) agree to any restrictions on the activities of Investor, Company or their respective Affiliates, or (iii) pay any material amount or take any other action to prevent, effect the dissolution of, vacate, or lift any decree, order, judgment, injunction, temporary restraining order, or other order in any suit or proceeding that would otherwise have the effect of preventing or delaying any of the transactions contemplated by the Transaction Agreements or the Collaboration Agreement.

11.3 Assistance and Cooperation . Prior to the Closing, upon the terms and subject to the conditions set forth in this Agreement, each of the parties agrees to use all reasonable efforts to take, or cause to be taken, all actions and to do, or cause to be done, and to assist and cooperate with the other party in doing, all things necessary, proper or advisable to consummate and make effective, in the most expeditious manner practicable, the transactions contemplated by this Agreement, including using all reasonable efforts to accomplish the following: (a) taking all reasonable acts necessary to cause the conditions precedent set forth in Sections 7, 8 and 9 to be satisfied (including, in the case of the Company, promptly notifying the Investor of any notice from The Nasdaq Stock Market LLC with respect to the LAS); (b) taking all reasonable actions necessary to obtain all necessary actions or non-actions, waivers, consents, approvals, orders and authorizations from Governmental Authorities and the making of all necessary registrations, declarations and filings (including registrations, declarations and filings with Governmental Authorities, if any); and (c) taking reasonable steps to obtain all necessary consents, approvals or waivers from Third Parties.

11.4 Effect of Waiver of Condition to Closing . In the event that, as of the Closing, the Investor waives the condition regarding a Material Adverse Effect set forth in Section 7.5 of this Agreement, the Investor shall be deemed to have waived any right of recourse against the Company for, and agreed not to sue the Company in respect of, any and all events or inaccuracies in any representations or warranties of the Company (a) that, as of the Closing, have caused or would reasonably be expected to cause such Material Adverse Effect and (b) of which the Investor had notice in writing from the Company at least two (2) business days prior to the Closing.

12. Miscellaneous .

12.1 Governing Law; Submission to Jurisdiction . This Agreement shall be governed by and construed in accordance with the Laws of the State of Delaware, without regard to the conflict of laws principles thereof that would require the application of the Law of any other jurisdiction. Any action brought, arising out of, or relating to this Agreement shall be brought in the Court of Chancery of the State of Delaware. Each party hereby irrevocably submits to the exclusive jurisdiction of said Court in respect of any claim relating to the validity, interpretation and enforcement of this Agreement, and hereby waives, and agrees not to assert, as a defense in any action, suit or proceeding in which any such claim is made that it is not subject thereto or that such action, suit or proceeding may not be brought or is not maintainable in such courts, or that the venue thereof may not be appropriate or that this agreement may not be enforced in or by such courts. The parties hereby consent to and grant the Court of Chancery of the State of Delaware jurisdiction over such parties and over the subject matter of any such claim and agree that mailing of process or other papers in connection with any such action, suit or proceeding in the manner provided in Section 12.3 or in such other manner as may be permitted by law, shall be valid and sufficient thereof.

12.2 Waiver . Waiver by a party of a breach hereunder by the other party shall not be construed as a waiver of any subsequent breach of the same or any other provision. No delay or omission by a party in exercising or availing itself of any right, power or privilege hereunder shall preclude the later exercise of any such right, power or privilege by such party. No waiver shall be effective unless made in writing with specific reference to the relevant provision(s) of this Agreement and signed by a duly authorized representative of the party granting the waiver.

12.3 Notices . All notices, instructions and other communications hereunder or in connection herewith shall be in writing, shall be sent to the address of the relevant party set forth on Exhibit C attached hereto and shall be (a) delivered personally, (b) sent by registered or certified mail, return receipt requested, postage prepaid, (c) sent via a reputable nationwide overnight courier service or (d) sent by facsimile transmission, with a confirmation copy to be sent by registered or certified mail, return receipt requested, postage prepaid. Any such notice, instruction or communication shall be deemed to have been delivered upon receipt if delivered by hand, three (3) Business Days after it is sent by registered or certified mail, return receipt requested, postage prepaid, one (1) Business Day after it is sent via a reputable nationwide overnight courier service or when transmitted with electronic confirmation of receipt, if transmitted by facsimile (if such transmission is made during regular business hours of the recipient on a Business Day; or otherwise, on the next Business Day following such transmission). Either party may change its address by giving notice to the other party in the manner provided above.

12.4 Entire Agreement . This Agreement and the Investor Agreement (once executed), contain the entire agreement among the parties with respect to the subject matter hereof and thereof and supersede all prior and contemporaneous arrangements or understandings, whether written or oral, with respect hereto and thereto.

12.5 Amendments . No provision in this Agreement shall be supplemented, deleted or amended except in a writing executed by an authorized representative of each of the Investor and the Company.

12.6 Headings; Nouns and Pronouns; Section References . Headings in this Agreement are for convenience of reference only and shall not be considered in construing this Agreement. Whenever the context may require, any pronouns used herein shall include the corresponding masculine, feminine or neuter forms, and the singular form of names and pronouns shall include the plural and vice-versa. References in this Agreement to a section or subsection shall be deemed to refer to a section or subsection of this Agreement unless otherwise expressly stated.

12.7 Severability . If, under applicable Laws, any provision hereof is invalid or unenforceable, or otherwise directly or indirectly affects the validity of any other material provision(s) of this Agreement in any jurisdiction (“ Modified Clause ”), then, it is mutually agreed that this Agreement shall endure and that the Modified Clause shall be enforced in such jurisdiction to the maximum extent permitted under applicable Laws in such jurisdiction; provided that the parties shall consult and use all reasonable efforts to agree upon, and hereby consent to, any valid and enforceable modification of this Agreement as may be necessary to avoid any unjust enrichment of either party and to match the intent of this Agreement as closely as possible, including the economic benefits and rights contemplated herein.

12.8 Assignment . Except for an assignment by the Investor of this Agreement or any rights hereunder to an Affiliate (which assignment will not relieve the Investor of any obligation hereunder), neither this Agreement nor any of the rights or obligations hereunder may be assigned by either the Investor or the Company without (a) the prior written consent of Company in the case of any assignment by the Investor or (b) the prior written consent of the Investor in the case of an assignment by the Company.

12.9 Successors and Assigns . This Agreement shall be binding upon and inure to the benefit of the parties hereto and their respective successors and permitted assigns.

12.10 Counterparts . This Agreement may be executed in counterparts, each of which shall be deemed an original but which together shall constitute one and the same instrument.

12.11 Third Party Beneficiaries . None of the provisions of this Agreement shall be for the benefit of or enforceable by any Third Party, including any creditor of any party hereto, except that each Affiliate of the Investor is an express third party beneficiary entitled to enforce this agreement directly against the Company. No Third Party shall obtain any right under any provision of this Agreement or shall by reason of any such provision make any claim in respect of any debt, liability or obligation (or otherwise) against any party hereto.

12.12 No Strict Construction . This Agreement has been prepared jointly and will not be construed against either party.

12.13 Survival of Warranties . The representations and warranties of the Company and the Investor contained in this Agreement shall survive the Closing for eighteen (18) months, except for (a) the representations and warranties set forth in Sections 4.1, 4.2, 4.4, 4.5(a), 4.6(d), 4.8, 4.15, 4.16, 4.17, 5.1, 5.2, 5.3(c), 5.5, 5.7, 5.8, 5.9 and 5.10, which shall survive forever and (b) the representation and warranty of the Investor in Section 5.11, which shall not survive the Closing. The parties hereby acknowledge and agree that the rights of the parties hereunder are special, unique and of extraordinary character, and that if any party refuses or otherwise fails to act, or to cause its Affiliates to act, in accordance with the provisions of this Agreement, such refusal or failure would result in irreparable injury to the Company or the Investor as the case may be, the exact amount of which would be difficult to ascertain or estimate and the remedies at law for which would not be reasonable or adequate compensation. Accordingly, if any party refuses or otherwise fails to act, or to cause its Affiliates to act, in accordance with the provisions of this Agreement, then, in addition to any other remedy which may be available to any damaged party at law or in equity, such damaged party will be entitled to seek specific performance and injunctive relief, without posting bond or other security, and without the necessity of proving actual or threatened damages, which remedy such damaged party will be entitled to seek in any court of competent jurisdiction.

12.14 Remedies . The rights, powers and remedies of the parties under this Agreement are cumulative and not exclusive of any other right, power or remedy which such parties may have under any other agreement or Law. No single or partial assertion or exercise of any right, power or remedy of a party hereunder shall preclude any other or further assertion or exercise thereof.

12.15 Expenses . Each party shall pay its own fees and expenses in connection with the preparation, negotiation, execution and delivery of the Transaction Agreements.

( Signature Page Follows )

IN WITNESS WHEREOF, the parties have executed and delivered this Agreement as of the date first above written.


GENZYME CORPORATION

By:	/s/ David Meeker
	Name:	David Meeker, M.D.
	Title:	President and Chief Executive Officer
	Date:	January 11, 2014

ALNYLAM PHARMACEUTICALS, INC.

By:	/s/ John M. Maraganore
	Name:	John M. Maraganore, Ph.D.
	Title:	Chief Executive Officer
	Date:	January 11, 2014

Signature Page to Stock Purchase Agreement

EXHIBIT A

FORM OF CROSS RECEIPT

CROSS RECEIPT

Alnylam Pharmaceuticals, Inc. (the “Company”) hereby acknowledges receipt from Genzyme Corporation (the “Investor”) on [ ], 2014 of US$700,000,000.00, representing the purchase price for 8,766,338 shares of Common Stock, par value $.01 per share, of the Company, pursuant to that certain Stock Purchase Agreement, dated as of January 11, 2014, by and between the Investor and the Company.


ALNYLAM PHARMACEUTICALS, INC.

By:
		Name:
		Title:

The Investor hereby acknowledges receipt from the Company on [ ], 2014 of 8,766,338 shares of Common Stock, par value $.01 per share, of the Company, delivered pursuant to that certain Stock Purchase Agreement, dated as of January 11, 2014, by and between the Investor and the Company.


GENZYME CORPORATION

By:
		Name:
		Title:

By:
		Name:
		Title:

A-1

EXHIBIT B

FORM OF INVESTOR AGREEMENT

B-1

EXHIBIT C

NOTICES

(a)	If to Genzyme Corporation:

Genzyme Corporation

500 Kendall Street

Cambridge, MA 02142

Attention: President of Rare Disease

Facsimile No.: (617) 374-2424

with a copy to:

Genzyme Corporation

500 Kendall Street

Cambridge, MA 02142

Attention: General Counsel

Facsimile: (617) 252-7553

and to:

Ropes & Gray LLP

Prudential Tower

800 Boylston Street

Boston, MA 02199-3600

Attention: Christopher D. Comeau, Esq.

Facsimile: (617) 235-0507

(b)	If to the Company:

Alnylam Pharmaceuticals, Inc.

300 Third Street

Cambridge, MA 02142

Attention: Vice President – Legal

Facsimile: (617) 551-8101

with a copy to:

Goodwin Procter LLP

53 State Street

Boston, MA 02109

Attention: Mitchell S. Bloom, Esq,

Facsimile: (617) 523-1231

C-1

Exhibit 10.3

INVESTOR AGREEMENT

BY AND BETWEEN

GENZYME CORPORATION

AND

ALNYLAM PHARMACEUTICALS, INC.

DATED AS OF FEBRUARY 27, 2014

TABLE OF CONTENTS


	Page
1. Definitions		1

2. Registration Rights		9
2.1 Required Registration		9
2.2 Company Registration		10
2.3 Underwritten Required Registration Required; Priority in Underwritten Offering		11
2.4 Priority in Required Registration		12
2.5 Revocation of Required Registration		13
2.6 Effective Required Registrations		13
2.7 Continuous Effectiveness of Registration Statement		13
2.8 Obligations of the Company		14
2.9 Furnish Information		17
2.10 Expenses		17
2.11 Indemnification		17
2.12 SEC Reports		19
2.13 Assignment of Registration Rights		20

3. Restrictions on Beneficial Ownership		20
3.1 Standstill		20
3.2 Company Agreements		22

4. Restrictions on Dispositions		24
4.1 Lock-Up		24
4.2 Limitations Following Lock-Up Term		25
4.3 Certain Tender Offers		25
4.4 Offering Lock-Up		26

5. Voting Agreement		26
5.1 Voting of Securities		26
5.2 Certain Extraordinary Matters		28

6. Right of First Offer		28
6.1 Right of First Offer		28
6.2 Limitations		28
6.3 Expiration		30

7. Designated Director		30
7.1 Designated Director		30
7.2 Notice and Information Rights		32
7.3 Freedom to Pursue Opportunities		32


8. Information Rights			33
8.1 Information Rights			33
8.2 Financial Information and Reporting			33
8.3 Confidentiality			33

9. Termination of Certain Rights and Obligations			33
9.1 Termination of Registration Rights			33
9.2 Termination of Standstill Agreement			34
9.3 Termination of Restrictions on Dispositions			34
9.4 Termination of Voting Agreement and Offering Lock-Up			35
9.5 Termination of Right of First Offer			35
9.6 Effect of Termination			35

10. Miscellaneous			36
10.1 Governing Law; Submission to Jurisdiction			36
10.2 Waiver			36
10.3 Notices			36
10.4 Entire Agreement			37
10.5 Amendments			37
10.6 Headings; Nouns and Pronouns; Section References			37
10.7 Severability			37
10.8 Assignment			37
10.9 Successors and Assigns			37
10.10 Counterparts			37
10.11 Third Party Beneficiaries			37
10.12 No Strict Construction			38
10.13 Remedies			38
10.14 Specific Performance			38
10.15 No Conflicting Agreements			38
10.16 Rule 16b-3			38
10.17[***]			38

Exhibit A – Form of Irrevocable Proxy

Exhibit B – Notices

INVESTOR AGREEMENT

THIS INVESTOR AGREEMENT (this “ Agreement ”) is made as of February 27, 2014, by and among Genzyme Corporation (“ Investor ”), a Massachusetts corporation with its principal place of business at 500 Kendall Street, Cambridge, MA 02142, and Alnylam Pharmaceuticals, Inc. (the “ Company ”), a Delaware corporation with its principal place of business at 300 Third Street, Cambridge, MA 02142.

WHEREAS, the Stock Purchase Agreement, dated as of January 11, 2014, by and between the Investor and the Company (the “ Purchase Agreement ”) provides for the issuance and sale by the Company to the Investor, and the purchase by the Investor, of a number of shares of the Company’s common stock, par value $.01 per share (the “ Common Stock ”), equal to the Share Amount (as defined in the Purchase Agreement) (the “ Purchased Shares ”); and

WHEREAS, as a condition to consummating the transactions contemplated by the Purchase Agreement, the Investor and the Company have agreed upon certain rights and restrictions as set forth herein with respect to the Purchased Shares and other securities of the Company beneficially owned by the Investor and its Affiliates, and it is a condition to the closing under the Purchase Agreement that this Agreement be executed and delivered by the Investor and the Company.

NOW, THEREFORE, in consideration of the premises and mutual agreements hereinafter set forth, and for other valuable consideration, the receipt and sufficiency of which are hereby acknowledged, the parties hereto agree as follows:

1. Definitions . As used in this Agreement, the following terms shall have the following meanings:

(a) “ Acquisition Proposal ” shall have the meaning set forth in Section 3.1(c).

(b) “ Affiliate ” shall mean, with respect to a Person, any other Person which controls, is controlled by or is under common control with the applicable Person. For purposes of this definition, “control” shall mean: (a) in the case of corporate entities, direct or indirect ownership of at least fifty percent (50%) of the stock or shares entitled to vote for the election of directors, or otherwise having the power to control or direct the affairs of such Person; and (b) in the case of non-corporate entities, direct or indirect ownership of at least fifty percent (50%) of the equity interest or the power to direct the management and policies of such non-corporate entities.

(d) “ Agreement ” shall have the meaning set forth in the Preamble to this Agreement, including all Exhibits attached hereto.

(e) “ ALN-TTRsc ” shall have the meaning set forth in the Master Agreement.

(f) “ beneficial owner ,” “ beneficially owns ,” “ beneficial ownership ” and terms of similar import used in this Agreement shall, with respect to a Person, have the meaning set forth in Rule 13d-3 under the Exchange Act (i) assuming the full conversion into, and exercise and exchange for, shares of Common Stock of all Common Stock Equivalents beneficially owned by such Person and (ii) determined without regard for the number of days in which such Person has the right to acquire such beneficial ownership.

(g) “ Business Day ” shall mean a day on which commercial banking institutions in New York, New York are open for business.

(h) “ Change of Control ” shall mean, with respect to the Company, any of the following events: (i) any Person is or becomes the beneficial owner (except that a Person shall be deemed to have beneficial ownership of all shares that any such Person has the right to acquire, whether such right which may be exercised immediately or only after the passage of time), directly or indirectly, of a majority of the total voting power represented by all Shares of Then Outstanding Common Stock; (ii) the Company consolidates with or merges into another corporation or entity, or any corporation or entity consolidates with or merges into the Company, other than (A) a merger or consolidation which would result in the voting securities of the Company outstanding immediately prior to such merger or consolidation continuing to represent (either by remaining outstanding or by being converted into voting securities of the surviving entity or any parent thereof) a majority of the combined voting power of the voting securities of the Company or such surviving entity or any parent thereof outstanding immediately after such merger or consolidation, (B) a merger or consolidation which would result in a majority of the board of directors of the combined entity being comprised of members of the board of directors of the pre-transaction Company and the chief executive officer of the combined entity being the chief executive officer of the pre-transaction Company, in each case immediately following the consummation of such merger or consolidation, or (C) a merger or consolidation effected to implement a recapitalization of the Company (or similar transaction) in which no Person becomes the beneficial owner, directly or indirectly, of a majority of the total voting power of all Shares of Then Outstanding Common Stock or (iii) the Company conveys, transfers or leases all or substantially all of its assets to any Person other than a wholly owned Affiliate of the Company.

(i) “ Clinical Study ” shall have the meaning set forth in the Master Agreement.

(j) “ Closing Date ” shall have the meaning set forth in the Purchase Agreement.

(k) “ Co-Co License Terms ” shall mean the Co-Commercialization License and Collaboration Terms attached to the Master Agreement as Appendix C .

(l) “ Collaboration Agreement ” shall mean the Master Agreement, the Co-Co License Terms, the Global License Terms and the Regional License Terms.

(m) “ Common Stock ” shall have the meaning set forth in the Preamble to this Agreement.

(n) “ Common Stock Equivalents ” shall mean any options, warrants or other securities or rights convertible into or exercisable or exchangeable for, whether directly or following conversion into or exercise or exchange for other options, warrants or other securities or rights, shares of Common Stock.

(o) “ Company ” shall have the meaning set forth in the Preamble to this Agreement.

(p) “ Demand Request ” shall have the meaning set forth in Section 2.1.

(q) “ Designated Director ” shall have the meaning set forth in Section 7.1.

(r) “ Dilutive Event ” shall have the meaning set forth in Section 3.2(c).

(s) “ Director Information ” shall have the meaning set forth in Section 7.2.

(t) “ Disposition ” or “ Dispose of ” shall mean any (i) pledge, sale, contract to sell, sale of any option or contract to purchase, purchase of any option or contract to sell, grant of any option, right or warrant for the sale of, or other disposition of or transfer of any shares of Common Stock, or any Common Stock Equivalents, including, without limitation, any “short sale” or similar arrangement, or (ii) swap or any other agreement or any transaction that transfers, in whole or in part, directly or indirectly, the economic consequence of ownership of shares of Common Stock, whether any such swap or transaction is to be settled by delivery of securities, in cash or otherwise.

(u) “ Election Notice Date ” shall have the meaning set forth in Section 3.2(c).

(v) “ Excepted Compensatory Issuance ” shall have the meaning set forth in Section 6.2.

(w) “ Excepted Transactional Issuance ” shall have the meaning set forth in Section 6.2.

(x) “ Exchange Act ” shall mean the Securities Exchange Act of 1934, as amended, and the rules and regulations of the SEC promulgated thereunder.

(y) “ Exercise Period ” shall have the meaning set forth in Section 6.1.

(z) “ Extraordinary Matter ” shall have the meaning set forth in Section 5.2.

(aa) “ Filing Date ” shall mean (i) with respect to any Registration Statement to be filed on Form S-1 (or any applicable successor form), ninety (90) days after receipt by the Company of a Demand Request for such Registration Statement and (ii) with respect to any Registration Statement to be filed on Form S-3 (or any applicable successor form), thirty (30) days after receipt by the Company of a Demand Request for such Registration Statement.

(bb) “ Funds ” shall have the meaning set forth in Section 4.2.

(cc) “ Global License Terms ” shall mean the Global Product License and Collaboration Terms attached to the Master Agreement as Appendix B .

(dd) “ Global Licensed Product ” shall have the meaning set forth in the Master Agreement.

(ee) “ Governmental Authority ” shall mean any court, agency, authority, department, regulatory body or other instrumentality of any government or country or of any national, federal, state, provincial, regional, county, city or other political subdivision of any such government or country or any supranational organization of which any such country is a member.

(ff) “ Holders ” shall mean (but, in each case, only for so long as such Person remains an Affiliate of the Investor) the Investor and any Permitted Transferee thereof, if any, in accordance with Section 2.13.

(gg) “ Initiating Holder ” shall have the meaning set forth in Section 2.3.

(hh) “ Interference ” shall have the meaning set forth in Section 2.6.

(ii) “ Investor ” shall have the meaning set forth in the Preamble to this Agreement.

(jj) “ Irrevocable Proxy ” shall have the meaning set forth in Section 5.1.

(kk) “ Law ” or “ Laws ” shall mean all laws, statutes, rules, regulations, orders, judgments, injunctions and/or ordinances of any Governmental Authority.

(ll) “ License Terms ” shall mean the Regional License Terms, the Co-Co License Terms and the Global License Terms.

(mm) “ Lock-Up Term ” shall have the meaning set forth in Section 4.1.

(nn) “ Master Agreement ” shall mean that certain Master Collaboration Agreement between Investor and Company, dated as of January 11, 2014.

(oo) “ Modified Clause ” shall have the meaning set forth in Section 10.7.

(pp) “ New Securities ” shall have the meaning set forth in Section 6.1.

(qq) “ Offer Notice ” shall have the meaning set forth in Section 6.1.

(rr) “ Offeror ” shall have the meaning set forth in Section 3.1(c).

(ss) “ Other Holders ” shall mean any Person having rights to participate in a registration of the Company’s securities.

(tt) “ Ownership Threshold ” shall have the meaning set forth in Section 7.1

(uu) “ Permitted Transferee ” shall mean (i) a controlled Affiliate of the Investor that is wholly owned, directly or indirectly, by the Investor, or (ii) a controlling Affiliate of the Investor (or any controlled Affiliate of such controlling Affiliate) that wholly owns, directly or indirectly, the Investor; it being understood that for purposes of this definition “wholly owned” shall mean an Affiliate in which the Investor owns, directly or indirectly, at least ninety-nine percent (99%) of the outstanding capital stock of such Affiliate.

(vv) “ Person ” shall mean any individual, limited liability company, partnership, firm, corporation, association, trust, unincorporated organization, government or any department or agency thereof or other entity, as well as any syndicate or group that would be deemed to be a Person under Section 13(d)(3) of the Exchange Act.

(ww) “ Potential Standstill Term Expiration Date ” shall have the meaning set forth in Section 3.2(c).

(xx) “ Prospectus ” shall mean the prospectus forming a part of any Registration Statement, as supplemented by any and all prospectus supplements and as amended by any and all amendments (including post-effective amendments) and including all material incorporated by reference or explicitly deemed to be incorporated by reference in such prospectus.

(yy) “ Purchase Agreement ” shall have the meaning set forth in the Preamble to this Agreement, and shall include all Exhibits attached thereto.

(zz) “ Purchased Shares ” shall have the meaning set forth in the Preamble to this Agreement, and shall be adjusted for (i) any stock split, stock dividend, share exchange, merger, consolidation or similar recapitalization and (ii) any Common Stock issued as (or issuable upon the exercise of any warrant, right or other security that is issued as) a dividend or other distribution with respect to, or in exchange or in replacement of, the Purchased Shares.

(aaa) “ Regional License Terms ” shall mean the Regional Product License and Collaboration Terms attached to the Master Agreement as Appendix A .

(bbb) “ registers ,” “ registered ,” and “ registration ” refer to a registration effected by preparing and filing a Registration Statement or similar document in compliance with the Securities Act, and the declaration or ordering of effectiveness of such Registration Statement or document by the SEC.

(ccc) “ Registrable Securities ” shall mean (i) the Purchased Shares, together with any shares of Common Stock issued in respect thereof as a result of any stock split, stock dividend, share exchange, merger, consolidation or similar recapitalization and (ii) any Common Stock issued as (or issuable upon the exercise of any warrant, right or other security that is issued as) a dividend or other distribution with respect to, or in exchange or in replacement of, the shares of Common Stock described in clause (i) of this definition, excluding in all cases, however, (A) any Registrable Securities if and after they have been transferred to a Permitted Transferee in a transaction in connection with which registration rights granted hereunder are not assigned, or (B) any Registrable Securities sold to or through a broker or dealer or underwriter in a public distribution or a public securities transaction.

(ddd) “ Registration Expenses ” shall mean all expenses incurred by the Company in connection with any Required Registration pursuant to Section 2.1 or the Company’s compliance with Section 2.8, including, without limitation, all registration and filing fees, fees and expenses of compliance with securities or blue sky Laws (including reasonable fees and disbursements of counsel in connection with blue sky qualifications of any Registrable Securities), expenses of printing (i) certificates for any Registrable Securities in a form eligible for deposit with the Depository Trust Company or (ii) Prospectuses if the printing of Prospectuses is requested by Holders, messenger and delivery expenses, fees and disbursements of counsel for the Company and its independent certified public accountants (including the expenses of any management review, cold comfort letters or any special audits required by or incident to such performance and compliance), Securities Act liability insurance (if the Company elects to obtain such insurance), the reasonable fees and expenses of any special experts retained

by the Company in connection with such registration, fees and expenses of other Persons retained by the Company and the reasonable fees and expenses of one (1) counsel for the Holders of Registrable Securities in each Required Registration, selected by the Holders of a majority of the Registrable Securities to be included in such Required Registration. In addition, the Company will pay its internal expenses (including, without limitation, all salaries and expenses of its officers and employees performing legal or accounting duties), the expense of any annual audit and the fees and expenses incurred in connection with the listing of the Purchased Shares to be registered on each securities exchange, if any, on which equity securities issued by the Company are then listed or the quotation of such securities on any national securities exchange on which equity securities issued by the Company are then quoted.

(eee) “ Registration Rights Term ” shall have the meaning set forth in Section 2.1.

(fff) “ Registration Statement ” shall mean any registration statement of the Company under the Securities Act that covers any of the Registrable Securities pursuant to the provisions of this Agreement, including the related Prospectus, all amendments and supplements to such registration statement (including post-effective amendments), and all exhibits and all materials incorporated by reference or explicitly deemed to be incorporated by reference in such Registration Statement.

(ggg) “ Required Period ” with respect to a Required Registration shall mean the earlier of (i) the date on which all Registrable Securities covered by such Required Registration are sold pursuant thereto and (ii) one hundred twenty (120) days following the first day of effectiveness of the Registration Statement for such Required Registration, in each case subject to extension as set forth herein; provided, however, that in no event will the Required Period expire prior to the expiration of the applicable period referred to in Section 4(3) of the Securities Act and Rule 174 promulgated thereunder.

(hhh) “ Required Registration ” shall have the meaning set forth in Section 2.1.

(iii) “ Rights Plan ” shall have the meaning set forth in Section 3.2(a).

(jjj) “ SEC ” shall mean the United States Securities and Exchange Commission.

(kkk) “ Securities Act ” shall mean the Securities Act of 1933, as amended, and the rules and regulations of the SEC promulgated thereunder.

(lll) “ Selling Expenses ” shall mean all underwriting discounts and selling commissions applicable to the sale of Registrable Securities pursuant to this Agreement.

(mmm) “ Shares of Then Outstanding Common Stock ” shall mean, at any time, the issued and outstanding shares of Common Stock at such time, as well as all capital stock issued and outstanding as a result of any stock split, stock dividend, or reclassification of Common Stock distributable, on a pro rata basis, to all holders of Common Stock.

(nnn) “ Standstill Limit ” shall mean thirty percent (30%) of the Shares of Then Outstanding Common Stock.

(ooo) “ Standstill Parties ” shall have the meaning set forth in Section 3.1.

(ppp) “ Standstill Term ” shall mean the period from and after the date of this Agreement until the earlier of (i) the fifth (5th) anniversary of the earlier of (a) the expiration of the Term and (b) the termination of the Collaboration Agreement and (ii) the date on which (x) the beneficial ownership of the Investor and its Affiliates no longer represents at least 5% of the Shares of Then Outstanding Common Stock and (y) Investor delivers a written notice to the Company electing to terminate Section 3.1 (provided, however, that if the Investor and its Affiliates acquire beneficial ownership representing at least 5% of the Shares of Then Outstanding Common Stock at any time within one year after the beneficial ownership of the Investor and its Affiliates ceasing to represent at least 5% of the Shares of Then Outstanding Common Stock, the Standstill Term shall be automatically reinstated).

(qqq) “ Term ” shall mean the period beginning on the Closing Date and ending on the expiration of the last to expire of the Option Period (as defined in the Master Agreement) or any Royalty Term (as defined in any of the following License Terms) under the Regional License Terms, the Co-Co License Terms or the Global License Terms.

(rrr) “ Third Party ” shall mean any Person other than the Investor, the Company or any of their respective Affiliates.

(sss) “ Underwritten Registration ” or “ Underwritten Offering ” shall mean a registration in which Registrable Securities are sold to an underwriter for reoffering to the public.

(ttt) “ Violation ” shall have the meaning set forth in Section 2.11(a).

(uuu) “ Voting-Restricted Shares ” shall mean all shares of Common Stock held by the Investor and its Affiliates; however, if the shares of Common Stock held by the Investor and its Affiliates comprise or exceed twenty percent (20%) of the Shares of Then Outstanding Common Stock, the term “Voting-Restricted Shares” shall only apply to the number of shares of Common Stock held by the Investor and its Affiliates that is equal to 19.99% of the Shares of Then Outstanding Common Stock.

2.	Registration Rights .

2.1 Required Registration . If, at any time after the expiration of the Lock-Up Term but no later than the tenth (10 ^th ) anniversary of such expiration (the “ Registration Rights Term ”), the Company receives from any Holder or Holders a written request or requests (each, a “ Demand Request ”) that the Company file a Registration Statement under the Securities Act to effect the registration (a “ Required Registration ”) of Registrable Securities, the Company shall use all reasonable efforts to file a Registration Statement covering such Holders’ Registrable Securities as soon as practicable (and by the applicable Filing Date) and shall use all reasonable efforts to, as soon as practicable thereafter, effect the registration of the Registrable Securities to permit or facilitate the sale and distribution in an Underwritten Offering of all or such portion of such Holder’s or Holders’ Registrable Securities as are specified in such Demand Request, subject however, to the conditions and limitations set forth herein; provided , however , that the Company shall not be obligated to effect any registration of Registrable Securities upon receipt of a Demand Request pursuant to this Section 2.1 if:

(i) the Company has already completed three (3) Required Registrations;

(ii) (A) in the event that the market value of all Registrable Securities outstanding is equal to or greater than fifty million dollars ($50,000,000), the market value of the Registrable Securities proposed to be included in the registration, based on the average closing price during the ten (10) consecutive trading days period prior to the making of the Demand Request, is less than fifty million dollars ($50,000,000) or (B) in the event that the market value of all Registrable Securities outstanding is less than fifty million dollars ($50,000,000), the market value of the Registrable Securities proposed to be included in the registration, based on the average closing price during the ten (10) consecutive trading days period prior to the making of the Demand Request, is less than the lesser of (x) twenty-five million dollars ($25,000,000) or (y) the total market value of Registrable Securities outstanding.

(iii) the Company furnishes to the Holders a certificate signed by an authorized officer of the Company stating that (A) within ninety (90) days after receipt of the Demand Request under this Section 2.1, the Company will file a registration statement for the public offering of securities for the account of the Company (other than a registration of securities (x) issuable pursuant to an employee stock option, stock purchase or similar plan, (y) issuable pursuant to a merger, exchange offer or a transaction of the type specified in Rule 145(a) under the Securities Act or (z) in which the only securities being registered are securities issuable upon conversion of debt securities which are also being registered), or (B) the Company is engaged in a material transaction or has an undisclosed material corporate development, in either case, which would be required to be disclosed in the Registration Statement, and in the good faith judgment of the Company’s Board of Directors, such disclosure would be materially detrimental to the Company and its stockholders at such time (in which case, the Company shall disclose the matter as promptly as reasonably practicable and thereafter

file the Registration Statement, and each Holder agrees not to disclose any information about such material transaction to Third Parties until such disclosure has occurred or such information has entered the public domain other than through breach of this provision by such Holder), provided , however , that the Company shall have the right to only defer the filing of the Registration Statement pursuant to this subsection once in any twelve (12) month period and, such deferral may not exceed a period of more than one-hundred twenty (120) days after receipt of a Demand Request;

(iv) the Company has, within the twelve (12) month period preceding the date of the Demand Request, already effected one (1) Required Registration for any Holder pursuant to this Section 2.1; or

(v) at any time during the period between the Company’s receipt of the Demand Request and the completion of the Required Registration, any Holder is in breach of or has failed to cause its Affiliates to comply with the obligations and restrictions of Sections 3, 4 or 5 of this Agreement, the Company has provided notice of such breach to a Holder and such breach or failure is ongoing and has not been remedied; it being understood that (A) a one-time, inadvertent and de minimis breach of Section 4 shall not be deemed to be a breach of the obligations and restrictions under Section 4 for purposes of this Section 2.1(v) and (B) a de minimis breach of Section 3.1(a) hereof, or an inadvertent breach of Section 3.1(g) hereof arising from informal discussions covering general corporate or other business matters the purpose of which is not intended to effectuate or lead to any of the actions referred to in paragraphs (a) through (e) of Section 3.1, shall not be deemed to be a breach of the obligations and restrictions under Section 3.1 for purposes of this Section 2.1(v).

2.2 Company Registration . Effective from the expiration of the Lock-Up Term until the earlier of (a) the tenth (10 ^th ) anniversary of such expiration and (b) the date on which the Holders no longer beneficially own at least five percent (5%) of the Shares of Then Outstanding Common Stock, (provided, however, if the Holders reacquire beneficial ownership representing at least 5% of the Shares of Then Outstanding Common Stock at any time within ten (10) year period set forth in clause (a) of this Section 2.2, the provisions of this Section 2.2 shall automatically again become applicable to the Holders) the Company shall notify the Holders in writing at least ten (10) days prior to the filing of any Registration Statement including shares of Common Stock by one or more selling stockholders (other than the Holders) (“ Registration Notice ”) and will afford each Holder an opportunity, subject to the terms and conditions of this Agreement, to include in such Registration Statement the number of Registrable Securities then held by such Holder that such Holder wishes to include in such Registration Statement. Each Holder desiring to include in any such Registration Statement all or any part of the Registrable Securities held by such Holder shall, within five (5) days after receipt of the Registration Notice, so notify the Company in writing, and in such notification, inform the Company of the number of Registrable Securities such Holder wishes to include in such Registration Statement. If a Holder decides not to include Registrable Securities in any

Registration Statement thereafter filed by the Company, such Holder shall nevertheless continue to have the right to include Registrable Securities in any subsequent Registration Statement or Registration Statements as may be filed by the Company with respect to offerings of its securities, all upon the terms and conditions set forth herein. Each Holder shall keep confidential and not disclose to any third party (i) its receipt of any Registration Notice and (ii) any information regarding the proposed offering as to which such notice is delivered, except as required by law, regulation or as compelled by subpoena. If a registration pursuant to this Section 2.2 is an Underwritten Offering, the right of any such Holder to include Registrable Securities in such registration shall be conditioned upon such Holder’s participation in such underwriting and the inclusion of such Holder’s Registrable Securities in the underwriting to the extent provided herein. The Company and all Holders proposing to distribute their Registrable Securities through such underwriting shall enter into an underwriting agreement in customary form with the managing underwriter or underwriters selected for such underwriting. Notwithstanding any other provision of this Section 2, if the managing underwriter for the Underwritten Offering determines in good faith that marketing factors require a limitation of the number of shares of Registrable Securities to be included in such Underwritten Offering, then the managing underwriter may exclude shares (including up to 100% of the Registrable Securities) from the registration and the underwriting, with the number of Registrable Securities, if any, included in the registration and the underwriting being allocated to each of the Holders requesting inclusion of their Registrable Securities in such Registration Statement and all other Persons selling shares of Common Stock pursuant to such Registration Statement on a pro rata basis based on the total number of shares of Common Stock then held by each such Holder or other stockholder. Notwithstanding the foregoing, the Company shall have the right to terminate or withdraw any registration initiated by it under this Section 2.2 prior to the effectiveness of such registration whether or not any Holder has elected to include securities in such registration.

2.3 Underwritten Required Registration Required; Priority in Underwritten Offering . The underwriter for any Underwritten Offering requested pursuant to Section 2.1 shall be selected by a majority in interest of the Holders initiating the Required Registration hereunder (such Holder(s) initiating the registration request, the “ Initiating Holders ”) and shall be acceptable to the Company, such acceptance not to be unreasonably withheld, conditioned or delayed. The right of any Holder to include its Registrable Securities in the Underwritten Offering shall be conditioned upon such Holder’s participation in such Underwritten Offering and the inclusion of such Holder’s Registrable Securities to the extent provided herein. All Holders requesting the inclusion of their Registrable Securities in such Underwritten Offering shall (together with the Company as provided in Section 2.8(h)) enter into an underwriting agreement in customary form with the underwriter or underwriters selected for such Underwritten Offering. Notwithstanding any other provision of this Section 2, if the managing underwriter for the Underwritten Offering determines in good faith that marketing factors require a limitation of the number of shares of Registrable Securities to be included in such Underwritten Offering, then the Company shall so advise all Holders which requested inclusion of their Registrable Securities in such Underwritten Offering, and the number of shares of Registrable

Securities that may be included in such Underwritten Offering shall be allocated among the Holders in proportion (as nearly as practicable) to the amount of Registrable Securities of the Company owned by each Holder; provided , however , that the number of shares of Registrable Securities to be included in such Underwritten Offering shall not be reduced unless all other securities are first entirely excluded from such Underwritten Offering. In the event the Company advises the Holders of its intent to decrease the total number of Registrable Securities that may be included by the Holders in such Required Registration such that the number of Registrable Securities included in such Required Registration would be less than seventy-five percent (75%) of all Registrable Securities which the Holders requested be included in such Required Registration, then Holders representing a majority of the Registrable Securities requested to be included in such Required Registration will have the right to withdraw, on behalf of all Holders of all Registrable Securities requested to be so included, such Required Registration, in which case, such Required Registration will not count as a Required Registration for the purposes of Section 2.1(i), and the Company shall bear all Registration Expenses in connection therewith; provided , that , the right to withdraw a registration and have it not count as a Required Registration may only be exercised once by the Holders (taken collectively).

2.4 Priority in Required Registration . With respect to any Required Registration of Registrable Securities requested pursuant to Section 2.1, the Company may also (i) propose to sell shares of Common Stock on its own behalf and (ii) provide written notice of such Required Registration to Other Holders and permit all such Other Holders who request to be included in the Required Registration to include any or all Company securities held by such Other Holders in such Required Registration on the same terms and conditions as the Registrable Securities. Notwithstanding the foregoing, if the managing underwriter or underwriters of the Underwritten Offering to which any Required Registration relates advise the Company and the Holders of Registrable Securities that, in its good faith determination, the total amount of securities that such Holders, Other Holders, and the Company intend to include in such Required Registration is in an amount in the aggregate which would adversely affect the success of such Underwritten Offering, then such Required Registration shall include (i) first, all Registrable Securities of the Holders allocated, if the amount is less than all the Registrable Securities requested to be sold, pro rata on the basis of the total number of Registrable Securities held by such Holders; and (ii) second, as many other securities proposed to be included in the Required Registration by the Company and any Other Holders, allocated pro rata among the Company and such Other Holders, on the basis of the amount of securities requested to be included therein by the Company and each such Other Holder so that the total amount of securities to be included in such Underwritten Offering is the full amount that, in the written opinion of such managing underwriter, can be sold without materially and adversely affecting the success of such Underwritten Offering.

2.5 Revocation of Required Registration . With respect to one (1) Required Registration only, the Holders of at least a majority of the Registrable Securities to be included in a Registration Statement with respect to such Required Registration may, at any time prior to the effective date of such Registration Statement, on behalf of all Holders of all Registrable Securities requested to be included therein, revoke the request to have Registrable Securities included therein and revoke the request for such Required Registration by providing a written notice to the Company, in which case such Required Registration that has been revoked will be deemed not to have been effected and will not count as a Required Registration for purposes of Section 2.1(i) if, and only if, the Holders of Registrable Securities which had requested inclusion of Registrable Securities in such Required Registration promptly reimburse the Company for all Registration Expenses incurred by the Company in connection with such Required Registration. Notwithstanding the foregoing sentence, the parties agree and acknowledge that the Holders may revoke any Required Registration (without any obligation to reimburse the Company for Registration Expenses incurred in connection therewith) if such revocation is based on (i) a material adverse change in circumstances with respect to the Company and its subsidiaries, taken as a whole, caused by an act or failure to act by the Company or any of its subsidiaries and not known to any Holder at the time the Required Registration was first made or (ii) the Company’s failure to comply in any material respect with its obligations hereunder, and any such revocation based on an event described in (i) or (ii) above shall be exercisable at any time and shall not be counted as the one (1) revocation of a Required Registration permitted by the first sentence of this Section 2.5.

2.6 Effective Required Registrations . A Required Registration will not be deemed to be effected for purposes of Section 2.1(i) if the Registration Statement for such Required Registration has (a) not been declared effective by the SEC or (b) become effective in accordance with the Securities Act and the rules and regulations thereunder and not been kept effective for the Required Period. In addition, if after such Registration Statement has been declared or becomes effective, (i) the offering of Registrable Securities pursuant to such Registration Statement is interfered with by any stop order, injunction, or other order or requirement of the SEC or other governmental agency or court such that the continued offer and sale of Registrable Securities being offered pursuant to such Registration Statement would violate applicable Law and such stop order, injunction or other order or requirement of the SEC or other governmental agency or court does not result from any act or omission of any Holder whose Registrable Securities are registered pursuant to such Registration Statement (an “ Interference ”) and (ii) any such Interference is not cured within sixty (60) days thereof, such Required Registration will be deemed not to have been effected and will not count as a Required Registration. In the event such Interference occurs and is cured, the Required Period relating to such Registration Statement will be extended by the number of days of such Interference, including the date such Interference is cured.

2.7 Continuous Effectiveness of Registration Statement . The Company will use all reasonable efforts to cause each Registration Statement filed pursuant to this Section 2 to be declared effective by the SEC or to become effective under the Securities Act as promptly as practicable and to keep each such Registration Statement that has been declared or becomes effective continuously effective for the Required Period.

2.8 Obligations of the Company . Whenever required under Section 2.1 to effect the registration of any Registrable Securities, the Company shall, as expeditiously as reasonably possible:

(a) prepare and file with the SEC a Registration Statement with respect to such Registrable Securities sought to be included therein; provided that at least five (5) Business Days prior to filing any Registration Statement or Prospectus or any amendments or supplements thereto, the Company shall furnish to the Holders of the Registrable Securities covered by such Registration Statement, their counsel and the managing underwriter copies of all such documents proposed to be filed, and any such Holder shall have the opportunity to comment on any information pertaining solely to such Holder and its plan of distribution that is contained therein and the Company shall make the corrections reasonably requested by such Holder or the managing underwriter with respect to such information prior to filing any such Registration Statement or amendment;

(b) prepare and file with the SEC such amendments and post-effective amendments to any Registration Statement and any Prospectus used in connection therewith as may be necessary to keep such Registration Statement effective for the Required Period, and cause the Prospectus to be supplemented by any required prospectus supplement, and as so supplemented to be filed pursuant to Rule 424 under the Securities Act, to comply with the provisions of the Securities Act with respect to the disposition of all Registrable Securities covered by such registration statement for the Required Period; provided that at least five (5) Business Days prior to filing any such amendments and post effective amendments or supplements thereto, the Company shall furnish to the Holders of the Registrable Securities covered by such Registration Statement, their counsel and the managing underwriter copies of all such documents proposed to be filed, and any such Holder or managing underwriter shall have the opportunity to comment on any information pertaining solely to such Holder and its plan of distribution that is contained therein and the Company shall make the corrections reasonably requested by such Holder and the managing underwriter with respect to such information prior to filing any such Registration Statement or amendment;

(c) furnish to the Holders of Registrable Securities covered by such Registration Statement and the managing underwriter such numbers of copies of such Registration Statement, each amendment and supplement thereto, the Prospectus included in such Registration Statement (including each preliminary prospectus or free writing prospectus) in conformity with the requirements of the Securities Act, and such other documents as they may reasonably request in order to facilitate the disposition of Registrable Securities owned by them;

(d) notify the Holders of Registrable Securities covered by such Registration Statement, promptly after the Company shall receive notice thereof, of the time when such Registration Statement becomes or is declared effective or when any amendment or supplement or any Prospectus forming a part of such Registration Statement has been filed;

(e) notify the Holders of Registrable Securities covered by such Registration Statement promptly of any request by the SEC for the amending or supplementing of such Registration Statement or Prospectus or for additional information and promptly deliver to such Holders copies of any comments received from the SEC;

(f) notify the Holders promptly of any stop order suspending the effectiveness of such Registration Statement or Prospectus or the initiation of any proceedings for that purpose, and use all reasonable efforts to obtain the withdrawal of any such order or the termination of such proceedings;

(g) use all reasonable efforts to register and qualify the Registrable Securities covered by such Registration Statement under such other securities or blue sky Laws of such jurisdictions as shall be reasonably requested by the Holders, use all reasonable efforts to keep each such registration or qualification effective, including through new filings, or amendments or renewals, during the Required Period, and notify the Holders of Registrable Securities covered by such Registration Statement of the receipt of any written notification with respect to any suspension of any such qualification; provided , however , that the Company shall not be required in connection therewith or as a condition thereto to qualify to do business or to file a general consent to service of process in any such states or jurisdictions;

(h) enter into and perform its obligations under an underwriting agreement, in usual and customary form, with the managing underwriter of the Underwritten Offering pursuant to which such Registrable Securities are being offered;

(i) use all reasonable efforts to obtain: (A) at the time of effectiveness of the Registration Statement covering such Registrable Securities, a “cold comfort letter” from the Company’s independent certified public accountants covering such matters of the type customarily covered by “cold comfort letters” as the underwriters may reasonably request; and (B) at the time of any underwritten sale pursuant to such Registration Statement, a “bring-down comfort letter,” dated as of the date of such sale, from the Company’s independent certified public accountants covering such matters of the type customarily covered by “bring-down comfort letters” as the underwriters may reasonably request.

(j) promptly notify each Holder of Registrable Securities covered by such Registration Statement at any time when a Prospectus relating thereto is required to be delivered under the Securities Act of the happening of any event as a result of which the Prospectus included in such Registration Statement or any offering memorandum or other offering document includes an untrue statement of a material fact or omits to state any material fact required to be stated therein or necessary to make the statements therein not misleading in the light of the circumstances then existing, and promptly prepare a supplement or amendment to such Prospectus or file any other required document so that, as thereafter delivered to the purchasers of such Registrable Securities, such Prospectus will not contain an untrue statement of material fact or omit to state any fact necessary to make the statements therein not misleading;

(k) permit any Holder of Registrable Securities covered by such Registration Statement, which Holder in its reasonable judgment could reasonably be deemed to be an underwriter with respect to the Underwritten Offering pursuant to which such Registrable Securities are being offered, or to be a controlling Person of the Company, to reasonably participate in the preparation of such Registration Statement and to require the insertion therein of information to the extent concerning such Holder, furnished to the Company in writing, which in the reasonable judgment of such Holder and its counsel should be included;

(l) in connection with any Underwritten Offering, use all reasonable efforts to obtain an opinion or opinions addressed to the underwriter or underwriters in customary form and scope from counsel for the Company;

(m) upon reasonable notice and during normal business hours, subject to the Company receiving customary confidentiality undertakings or agreements from any Holder of Registrable Securities covered by such Registration Statement or other person obtaining access to Company records, documents, properties or other information pursuant to this subsection (m), make available for inspection by a representative of such Holder and any underwriter participating in any disposition of such Registrable Securities and any attorneys or accountants retained by any such Holder or underwriter, relevant financial and other records, pertinent corporate documents and properties of the Company, and use all reasonable efforts to cause the officers, directors and employees of the Company to supply all information reasonably requested by any such representative, underwriter, attorneys or accountants in connection with the Registration Statement;

(n) with respect to one (1) Required Registration which includes Registrable Securities the market value of which is at least one hundred million United States dollars ($100,000,000), participate, to the extent requested by the managing underwriter, in efforts extending for no more than three (3) days scheduled by such managing underwriter and reasonably acceptable to the Company’s senior management, to sell the Registrable Securities being offered pursuant to such Required Registration (including participating during such period in customary “roadshow” meetings with prospective investors);

(o) use all reasonable efforts to comply with all applicable rules and regulations of the SEC relating to such registration and make generally available to its security holders earning statements satisfying the provisions of Section 11(a) of the Securities Act, provided that the Company will be deemed to have complied with this Section 2.8(o) with respect to such earning statements if it has satisfied the provisions of Rule 158;

(p) if requested by the managing underwriter or any selling Holder, promptly incorporate in a prospectus supplement or post-effective amendment such information as the managing underwriter or any selling Holder reasonably requests to be included therein, with respect to the Registrable Securities being sold by such selling Holder, including, without limitation, the purchase price being paid therefor by the underwriters and with respect to any other terms of the Underwritten Offering of Registrable Securities to be sold in such offering, and promptly make all required filings of such prospectus supplement or post-effective amendment;

(q) cause the Registrable Securities covered by such Registration Statement to be listed on each securities exchange, if any, on which equity securities issued by the Company are then listed; and

(r) reasonably cooperate with each selling Holder and each underwriter participating in the disposition of such Registrable Securities and their respective counsel in connection with filings required to be made with the Financial Industry Regulatory Authority, Inc., if any.

2.9 Furnish Information . It shall be a condition precedent to the obligations of the Company to take any action pursuant to this Section 2 with respect to the Registrable Securities of any selling Holder that such Holder shall furnish to the Company such information regarding itself and the Registrable Securities held by it as shall be reasonably necessary to effect the registration of such Holder’s Registrable Securities.

2.10 Expenses . Except as specifically provided herein, all Registration Expenses shall be borne by the Company. All Selling Expenses incurred in connection with any registration hereunder shall be borne by the Holders of Registrable Securities covered by a Registration Statement, pro rata on the basis of the number of Registrable Securities registered on their behalf in such Registration Statement.

2.11 Indemnification . In the event any Registrable Securities are included in a Registration Statement under this Agreement:

(a) The Company shall indemnify and hold harmless each Holder including Registrable Securities in any such Registration Statement, any underwriter (as defined in the Securities Act) for such Holder and each Person, if any, who controls such Holder or underwriter within the meaning of Section 15 of the Securities Act or Section 20 of the Exchange Act and the officers, directors, owners, agents and employees of such controlling Persons, against any and all losses, claims, damages or liabilities (joint or several) to which they may become subject under any securities Laws including, without limitation, the Securities Act, the Exchange Act, or any other statute or common law of the United States or any other country or political subdivision thereof, or otherwise, including the amount paid in settlement of any litigation commenced or threatened (including any amounts paid pursuant to or in settlement of claims made under the indemnification or contribution provisions of any underwriting or similar agreement entered into by such Holder in connection with any offering or sale of securities covered by this Agreement), and shall promptly reimburse them, as and when incurred, for any legal or other expenses incurred by them in connection with investigating any claims and defending any actions, insofar as any such losses, claims, damages or liabilities (or actions in

respect thereof) arise out of or are based upon any of the following statements, omissions or violations (each, a “ Violation ”): (i) any untrue statement or alleged untrue statement of a material fact contained in or incorporated by reference into such Registration Statement, including any preliminary prospectus or final prospectus contained therein or any free writing prospectus or any amendments or supplements thereto, or in any offering memorandum or other offering document relating to the offering and sale of such securities or (ii) the omission or alleged omission to state therein a material fact required to be stated therein, or necessary to make the statements therein not misleading; provided , however , the Company shall not be liable in any such case for any such loss, claim, damage, liability or action to the extent that it (A) arises out of or is based upon a Violation which occurs solely in reliance upon and in conformity with written information furnished expressly for use in connection with such registration by such Holder; or (B) is caused by such Holder’s disposition of Registrable Shares during any period during which such Holder is obligated to discontinue any disposition of Registrable Shares as a result of any stop order suspending the effectiveness of any registration statement or prospectus with respect to Registrable Securities of which such Holder has received written notice.

(b) Each Holder including Registrable Securities in a registration statement shall indemnify and hold harmless the Company, each of its directors, each of its officers who has signed the registration statement, each Person, if any, who controls the Company within the meaning of Section 15 of the Securities Act or Section 20 of the Exchange Act and the officers, directors, owners, agents and employees of such controlling Persons, any underwriter, any other Holder selling securities in such registration statement and any controlling Person of any such underwriter or other Holder, against any losses, claims, damages or liabilities (joint or several) to which any of the foregoing Persons may become subject, under liabilities (or actions in respect thereto) which arise out of or are based upon any Violation, in each case to the extent (and only to the extent) that such Violation: (i) arises out of or is based upon a Violation which occurs solely in reliance upon and in conformity with written information furnished expressly for use in connection with such registration by such Holder; or (ii) is caused by such Holder’s disposition of Registrable Shares during any period during which such Holder is obligated to discontinue any disposition of Registrable Shares as a result of any stop order suspending the effectiveness of any registration statement or prospectus with respect to Registrable Securities of which such Holder has received written notice. Each such Holder shall pay, as incurred, any legal or other expenses reasonably incurred by any Person intended to be indemnified pursuant to this Section 2.11(b), in connection with investigating or defending any such loss, claim, damage, liability or action; provided , however , that the indemnity agreement contained in this Section 2.11(b) shall not apply to amounts paid in settlement of any such loss, claim, damage, liability or action if such settlement is effected without consent of the Holder, which consent shall not be unreasonably withheld.

(c) Promptly after receipt by an indemnified party under this Section 2.11 of notice of the commencement of any action (including any action by a Governmental Authority), such indemnified party shall, if a claim in respect thereof is to be made against any

indemnifying party under this Section 2.11, deliver to the indemnifying party a written notice of the commencement thereof and the indemnifying party shall have the right to participate in, and, to the extent the indemnifying party so desires, jointly with any other indemnifying party similarly noticed, to assume the defense thereof with counsel mutually satisfactory to the parties; provided , however , that an indemnified party shall have the right to retain its own counsel, with the reasonable fees and expenses to be paid by the indemnifying party, if representation of such indemnified party by the counsel retained by the indemnifying party would be inappropriate due to actual or potential differing interests between such indemnified party and any other party represented by such counsel in such proceeding. The failure to deliver written notice to the indemnifying party within a reasonable time of the commencement of any such action, if prejudicial to its ability to defend such action, shall relieve such indemnifying party of any liability to the indemnified party under this Section 2.11, but the omission so to deliver written notice to the indemnifying party shall not relieve it of any liability that it may have to any indemnified party otherwise than under this Section 2.11.

(d) In order to provide for just and equitable contribution to joint liability in any case in which a claim for indemnification is made pursuant to this Section 2.11 but it is judicially determined (by the entry of a final judgment or decree by a court of competent jurisdiction and the expiration of time to appeal or the denial of the last right of appeal) that such indemnification may not be enforced in such case notwithstanding the fact that this Section 2.11 provided for indemnification in such case, the Company and each Holder of Registrable Securities shall contribute to the aggregate losses, claims, damages or liabilities to which they may be subject (after contribution from others) in proportion to the relative fault of the Company, on the one hand, and such Holder, severally, on the other hand; provided , however , that in any such case, no Person guilty of fraudulent misrepresentation (within the meaning of Section 11(f) of the Securities Act) shall be entitled to contribution from any Person who was not guilty of such fraudulent misrepresentation; provided further , however , that in no event shall any contribution under this Section 2.11(d) on the part of any Holder exceed the net proceeds received by such Holder from the sale of Registrable Securities giving rise to such contribution obligation, except in the case of willful misconduct or fraud by such Holder.

(e) The obligations of the Company and the Holders under this Section 2.11 shall survive the completion of any offering of Registrable Securities in a registration statement under this Agreement and otherwise.

2.12 SEC Reports . With a view to making available to the Holders the benefits of Rule 144 under the Securities Act and any other rule or regulation of the SEC that may at any time permit a Holder to sell Registrable Securities of the Company to the public without registration, the Company agrees to at any time that it is a reporting company under Section 13 or 15(d) of the Exchange Act:

(a) file with the SEC in a timely manner all reports and other documents required of the Company under the Exchange Act; and

(b) furnish to any Holder, so long as such Holder owns any Registrable Securities, forthwith upon request (i) a written statement by the Company that it has complied with the reporting requirements of the Exchange Act, (ii) a copy of the most recent annual or quarterly report of the Company and such other reports and documents so filed by the Company, and (iii) such other information as may be reasonably requested in availing any Holder of any rule or regulation of the SEC (exclusive of Rule 144A) which permits the selling of any Registrable Securities without registration.

2.13 Assignment of Registration Rights . The rights to cause the Company to register any Registrable Securities pursuant to this Agreement may be assigned in whole or in part (but only with all restrictions and obligations set forth in this Agreement) by a Holder to a Permitted Transferee which acquires Registrable Securities from such Holder; provided , however , (a) such Holder shall, within five (5) days prior to such transfer, furnish to the Company written notice of the name and address of such Permitted Transferee, details of its status as a Permitted Transferee and details of the Registrable Securities with respect to which such registration rights are being assigned, (b) the Permitted Transferee, prior to or simultaneously with such transfer or assignment, shall agree in writing to be subject to and bound by all restrictions and obligations set forth in this Agreement, (c) the Investor shall continue to be bound by all restrictions and obligations set forth in this Agreement and (d) such transfer or assignment shall be effective only if immediately following such transfer or assignment the further disposition of such Registrable Securities by the Permitted Transferee is restricted under the Securities Act and other applicable securities Law.

3. Restrictions on Beneficial Ownership .

3.1 Standstill . During the Standstill Term, neither the Investor nor any of its Affiliates (collectively, the “ Standstill Parties ”) shall (and the Investor shall cause its Affiliates not to), except as expressly approved or invited in writing by the Company:

(a) directly or indirectly, acquire beneficial ownership of Shares of Then Outstanding Common Stock and/or Common Stock Equivalents, or make a tender, exchange or other offer to acquire Shares of Then Outstanding Common Stock and/or Common Stock Equivalents, if after giving effect to such acquisition, the Standstill Parties would beneficially own more than the Standstill Limit; provided , however , that notwithstanding the provisions of this Section 3.1(a), if the number of shares constituting Shares of Then Outstanding Common Stock is reduced or if the aggregate ownership of the Standstill Parties is increased as a result of a repurchase by the Company of Shares of Then Outstanding Common Stock, stock split, stock dividend or a recapitalization of the Company, the Standstill Parties shall not be required to dispose of any of their holdings of Shares of Then Outstanding Common Stock even though such action resulted in the Standstill Parties’ beneficial ownership totaling more than the Standstill Limit;

(b) directly or indirectly, (i) seek to have called any meeting of the stockholders of the Company, (ii) propose or nominate for election to the Company’s Board of Directors any person whose nomination has not been approved by a majority of the Company’s Board of Directors (excluding the Designated Director, if any) or (iii) unless a person referred to in the foregoing clause (ii) is nominated by a third party in connection with such party’s publicly announced and not withdrawn Acquisition Proposal (in which case the provisions of Section 5.1 shall apply to permit the Standstill Parties to either vote in accordance with the recommendation of the Company’s Board of Directors or in the same proportion as the votes cast by all other holders of all classes of voting securities of the Company), fail to cause to be voted in accordance with the recommendation of the Company’s Board of Directors with respect to such person for election to the Company’s Board of Directors any Shares of Then Outstanding Common Stock;

(c) directly or indirectly, encourage or support a tender, exchange or other offer or proposal by any other Person or group (an “ Offeror ”) the consummation of which would result in a Change of Control of the Company (an “ Acquisition Proposal ”); provided, however, that from and after the filing of a Schedule 14D-9 (or successor form of Tender Offer Solicitation/Recommendation Statement under Rule 14d-9 of the Exchange Act) by the Company recommending that stockholders accept any such offer, Investor shall not be prohibited from taking any of the actions otherwise prohibited by this Section 3.1(c) for so long as the Company maintains and does not withdraw such recommendation;

(d) directly or indirectly, solicit proxies or consents or become a participant in a solicitation (as such terms are defined in Regulation 14A under the Exchange Act) in opposition to the recommendation of a majority of the Company’s Board of Directors with respect to any matter, or seek to advise or influence any Person, with respect to voting of any Shares of Then Outstanding Common Stock of the Company;

(e) deposit any Shares of Then Outstanding Common Stock in a voting trust or subject any Shares of Then Outstanding Common Stock to any arrangement or agreement with respect to the voting of such Shares of Then Outstanding Common Stock;

(f) propose (i) any merger, consolidation, business combination, tender or exchange offer, purchase of the Company’s assets or businesses, or similar transaction involving the Company or (ii) any recapitalization, restructuring, liquidation or other extraordinary transaction with respect to the Company;

(g) act in concert with any Third Party to take any action in clauses (a) through (f) above, or form, join or in any way participate in a “partnership, limited partnership, syndicate, or other group” within the meaning of Section 13(d)(3) of the Exchange Act;

(h) enter into discussions, negotiations, arrangements or agreements with any Person relating to the foregoing actions referred to in (a) through (g) above; or

(i) request or propose to the Company’s Board of Directors, any member(s) thereof or any officer of the Company that the Company amend, waive, or consider the amendment or waiver of, any provisions set forth in this Section 3.1 (including this clause (i));

provided , however , that (A) nothing contained in this Section 3.1 shall prohibit the Investor from making confidential, non-public proposals to, or entering into confidential, non-public discussions, negotiations, arrangements or agreements with, the Company and with third parties with the express authorization of the Company, which the Investor or any Affiliate may request in a confidential, non-public manner, regarding a transaction or matter of the type described in the foregoing clauses (a) and (f), (B) the mere voting in accordance with Section 5 hereof of any voting securities of the Company held by the Investor or its Affiliates shall not constitute a violation of any of clauses (a) through (h) above, and (C) nothing in the foregoing clause (b) shall prohibit the Investor from proposing to the Company’s Nominating and Corporate Governance Committee (and not pursuant to the advance notice provisions set forth in the Company’s bylaws), in a confidential, non public manner, potential director candidates for consideration by the Company’s Nominating and Corporate Governance Committee, which candidates the Investor believes would be in the best interest of the Company and its stockholders.

3.2 Company Agreements .

(a) During the Standstill Term, the Company shall not take any action or omit to take any action that would prevent or impede the Investor or its Affiliates from acquiring beneficial ownership of Shares of Then Outstanding Common Stock and/or Common Stock Equivalents to the extent that, after giving effect to such acquisition, the Standstill Parties would beneficially own less than the Standstill Limit, including by adopting a shareholder rights plan applicable to the Standstill Parties that contains a threshold below the Standstill Limit if such shareholder rights plan does not otherwise permit the Investor to beneficially own up to the Standstill Limit, provided , however , that nothing contained in this Section 3.2(a) or elsewhere in this Agreement shall affect the Company’s ability to (i) take and disclose a position in accordance with Rule 14d-9, Rule 14e-2(a) or Item 1012(a) of Regulation M-A promulgated under the Exchange Act or (ii) make any disclosure to the Company’s stockholders, in each case if, in the good faith judgment of the Company’s Board of Directors, the failure to take such position and/or make such disclosure would be inconsistent with the directors’ fiduciary duties under applicable law or any disclosure requirements under applicable law. During the Standstill Term and notwithstanding the provisions of Section 5.1, Investor shall, and shall cause its Affiliates to, not take any action or omit to take any action that would prevent or impede the Company or its Affiliates from maintaining and enforcing the provisions of the Rights Agreement, dated July 13, 2005, by and between the Company and EquiServe Trust Company, N.A. (the “ Rights Plan ”) as in effect on the date hereof, as amended as contemplated by the Purchase Agreement, including without limitation, by voting (or, if applicable, by executing a written consent with respect to) all of its and their Shares of Then Outstanding Common Stock in favor of any renewal of such shareholder rights plan or adoption of a replacement shareholder

rights plan in each case that is materially consistent with the Rights Plan as in effect on the date hereof, as amended as contemplated by the Purchase Agreement, should the Company submit such renewal or adoption to the stockholders of the Company for their approval.

(b) Following expiration of the Standstill Term, the Company shall not take any action or omit to take any action that would force the Investor to dispose of any of its holdings of Shares of Then Outstanding Common Stock.

(c) Upon the expiration of the Standstill Term (the “ Potential Standstill Term Expiration Date ”), in the event that the Standstill Parties beneficially own, in the aggregate, at least twenty percent (20%) of the Shares of Then Outstanding Common Stock, the Investor may deliver to the Company not later than five (5) business days following a Potential Standstill Term Expiration Date a written notice electing to reinstate the provisions of Section 3 and Section 5 and continue the Standstill Term as provided in this Section 3.2(c) (the “ Election Notice Date ”). If such election is made, the provisions of Section 3 and Section 5 shall be reinstated and the provisions of such sections, including the Standstill Term, shall be deemed to have remained in effect at all times without interruption or tolling notwithstanding the occurrence of a Potential Standstill Term Expiration Date; provided , however , that the “Standstill Limit” shall instead be the percentage of Shares of Then Outstanding Common Stock beneficially owned, in the aggregate, by the Standstill Parties as of the Potential Standstill Term Expiration Date. Following the Election Notice Date, the “Standstill Term” shall terminate on the date on which the Standstill Parties beneficially own, in the aggregate, less than twenty percent (20%) of the Shares of Then Outstanding Common Stock; provided , however , that if the beneficial ownership of the Investor and its Affiliates in the aggregate is reduced below such threshold as a direct result of dilution suffered upon an issuance of securities by the Company pursuant to an Excepted Transactional Issuance (a “ Dilutive Event ”), the Standstill Term shall instead terminate upon the earliest of (x) Investor’s failure to provide written notice to the Company of its election to purchase additional securities within the five (5) business day period set forth in Section 6.2 related to the applicable Dilutive Event, (y) Investor’s failure to consummate such purchase of additional securities of the Company pursuant to Section 6.2 within the time period set forth therein related to the applicable Dilutive Event or (z) the date of Investor’s purchase of additional securities of the Company pursuant to Section 6.2 related to the applicable Dilutive Event if, immediately following the consummation of such purchase, the Investor and its Affiliates beneficially own, in the aggregate, less than twenty percent (20%) of the Shares of Then Outstanding Common Stock.

(d) If the Company (i) permits any other Person or group to own Shares of Then Outstanding Common Stock and/or Common Stock Equivalents in the aggregate exceeding the Standstill Limit or (ii) executes a transaction with any other Person or group that (i) results in said Person or group becoming the beneficial owner of Shares of Then Outstanding Common Stock and/or Common Stock Equivalents in an amount equal to or greater than the percentage ownership represented by the Purchased Shares on the date hereof and (ii) is a collaboration or other license agreement with the Company, the Company shall offer to the

Investor an opportunity to amend Sections 3 and 5 of this Agreement in a manner such that such provisions would be consistent with the “standstill” terms and conditions upon which the Company permitted such other Person or group to own and act (or fail to act) with respect to the Company and the Company’s Shares of Then Outstanding Common Stock and/or Common Stock Equivalents. This Section 3.2(d) shall terminate and be of no further force or effect on the date on which the Investor and its Affiliates beneficially own, in the aggregate, less than seven and a half percent (7.5%) of the Shares of Then Outstanding Common Stock; provided, however, that if the beneficial ownership of the Investor and its Affiliates in the aggregate is reduced below such threshold as a direct result of dilution suffered upon a Dilutive Event, this Section 3.2(d) shall instead terminate upon the earliest of (x) Investor’s failure to provide written notice to the Company of its election to purchase additional securities within the five (5) business day period set forth in Section 6.2 related to the applicable Dilutive Event, (y) Investor’s failure to consummate the purchase of additional securities of the Company pursuant to Section 6.2 within the time period set forth therein related to the applicable Dilutive Event or (z) the date of Investor’s purchase of additional securities of the Company pursuant to Section 6.2 related to the applicable Dilutive Event if, immediately following the consummation of such purchase, the Investor and its Affiliates beneficially own, in the aggregate, less than seven and a half percent (7.5%) of the Shares of Then Outstanding Common Stock.

4. Restrictions on Dispositions .

4.1 Lock-Up . From and after the date of this Agreement and until the earlier of (i) December 31, 2019, plus the amount of time by which either the Regional Option Outside Date (as defined in the Master Agreement) or the Global Option Outside Date (as defined in the Master Agreement) is extended beyond December 31, 2019 and (ii) six (6) months after the earlier of (a) the expiration of the Term and (b) the termination of the Collaboration Agreement (the “ Lock-Up Term ”), without the prior approval of the Company, the Investor shall not, and shall cause its Affiliates not to, Dispose of (x) any of the Purchased Shares or any shares of Common Stock beneficially owned by any Standstill Party as of the date of this Agreement, together with any shares of Common Stock issued in respect thereof as a result of any stock split, stock dividend, share exchange, merger, consolidation or similar recapitalization, and (y) any Common Stock issued as (or issuable upon the exercise of any warrant, right or other security that is issued as) a dividend or other distribution with respect to, or in exchange or in replacement of, the shares of Common Stock described in clause (x) of this sentence; provided , however , that the foregoing shall not prohibit the Investor from (A) transferring any of the foregoing to a Permitted Transferee, (B) Disposing of any of the foregoing in order to reduce the beneficial ownership of the Standstill Parties to 19.9% or other level, as advised in good faith and in writing by Sanofi’s certified public accountants, that would not require the Investor to include in its financial statements its portion of the Company’s financial results, of the Shares of Then Outstanding Common Stock, provided that any Disposition referred to in this clause (B) shall be subject to the restrictions and requirements set forth in Section 4.2, and (C) effective on or after the second anniversary of the date hereof, Disposing of up to twenty-five percent (25%)

of the foregoing if the market value of the Common Stock, based on the average closing price during the ten (10) consecutive trading days period prior to the Investor’s election to exercise this clause (C), is at least one-hundred percent (100%) higher than the market value of the Common Stock, based on the average closing price during the ten (10) consecutive trading days period prior to the date hereof, provided that any Disposition referred to in this clause (C) shall be subject to the restrictions and requirements set forth in Section 4.2.

4.2 Limitations Following Lock-Up Term . Except for any transfer of Registrable Securities by the Investor to a Permitted Transferee, the Investor shall not, and shall cause its Affiliates not to, Dispose of any Purchased Shares at any time after the expiration of the Lock-Up Term except (i) pursuant to a registered underwritten public offering in accordance with Section 2, (ii) in a manner consistent with the volume limitations set forth in Rule 144 under the Securities Act (whether or not such limitations would by their terms apply to such sales), (iii) pursuant to privately negotiated sales in transactions exempt from the registration requirements under the Securities Act to mutual funds or pension funds, each of which will not be required, based on its ownership of Shares of Then Outstanding Common Stock immediately following the contemplated transaction, to file a Schedule 13D with respect to its ownership of the Shares of Then Outstanding Common Stock disclosing in response to Item 4 of such filing any plans or proposals described in clauses (a) through (j) of such Item (the “ Funds ”), or to which the Company has no reasonable objection with respect to (x) the nature of the transferee or (y) the ability of the transferee to subsequently sell such Shares of Then Outstanding Common Stock and/or Common Stock Equivalents into the market without having a material and adverse impact on the market price of the Company’s Common Stock; provided that, in the case of this clause (iii), other than with respect to the Funds, any transferee that acquires more than five percent (5%) of the Shares of Then Outstanding Common Stock shall agree to be bound by the transfer limitations set forth in this Section 4.2 and the standstill limitations set forth in Section 3.1, or (iv) in any transaction approved by the Company; provided , however , that in any Underwritten Offering in accordance with Section 2.1, the Holders whose Registrable Securities are included in such Underwritten Offering shall request that the underwriter for such Underwritten Offering, and shall require that the underwriter for such Underwritten Offering shall agree in writing to, use all reasonable efforts to make as broad a distribution as reasonably practical and to prevent any Person, or Affiliates of such Person, other than the Funds, from purchasing in such offering Registrable Securities which would constitute, or result in such Person, together with such Person’s Affiliates, having beneficial ownership of, five percent (5%) or more of the total shares of Common Stock then outstanding.

4.3 Certain Tender Offers . Notwithstanding any other provision of this Section 4, this Section 4 shall not prohibit or restrict any Disposition of Purchased Shares by the Standstill Parties into (a) a tender offer by a Third Party which is not opposed by the Company’s Board of Directors (but only after the Company’s filing of a Schedule 14D-9, or any amendment thereto, with the SEC disclosing the recommendation of the Company’s Board of Directors with respect to such tender offer), unless Investor is then in breach of its obligations pursuant to Section 3.1 with respect to the tender offer or (b) an issuer tender offer by the Company.

4.4 Offering Lock-Up . If the Holders together beneficially own at least five percent (5%) of the Shares of Then Outstanding Common Stock, the Holders shall, if requested by the Company and an underwriter of Common Stock of the Company, agree not to Dispose of any Purchased Shares for a specified period of time, such period of time not to exceed ninety (90) days. Such agreement shall be in writing in a form satisfactory to the Company, the underwriter(s) in such offering and shall contain customary exceptions to the restrictions set forth therein. The Company may impose stop transfer instructions with respect to the Purchased Shares to the extent consistent with any such agreement until the end of the specified period of time. The foregoing provisions of this Section 4.4 shall apply to the Holders only if the Company’s directors, officers and any holders of an equal or greater number of Shares of Then Outstanding Common Stock that are party to a collaboration, license or similar agreement with the Company are subject to similar lock-up restrictions. Any discretionary waiver or termination of the restrictions of any or all of such agreements by the Company or the underwriters shall apply pro rata to all Holders subject to such agreements, based on the number of shares subject to such agreements.

5. Voting Agreement .

5.1 Voting of Securities . From and after the date of this Agreement, other than as permitted by Section 5.2 with respect to Extraordinary Matters or as required by Section 3.1(b) or 3.2(a), in any vote or action by written consent of the stockholders of the Company (including, without limitation, with respect to the election of directors), the Investor shall, and shall cause its respective Affiliates to, vote or execute a written consent with respect to the Voting-Restricted Shares, in the sole discretion of the Investor, either (a) in accordance with the recommendation of the Company’s Board of Directors or (b) in the case of a meeting of stockholders, if the Investor or an Affiliate of the Investor has delivered written notice to the Company at any time prior to the vote on any given matter (but in any event not less than five (5) Business Days prior to such vote), setting forth its intent to vote pursuant to this Section 5.1(b), in the same proportion as the votes cast by all other holders of all classes of voting securities of the Company (as estimated by the inspector of election immediately prior to the closing of the polls with respect to the vote on any given matter, subject to adjustment for the inspector of election’s final tabulation of votes cast). In the event that the Investor or an Affiliate of the Investor does not deliver timely written notice to the Company as provided in Section 5.1(b), such Person shall be deemed to have elected to vote the Voting-Restricted Shares of the Company as to which it is entitled to vote as provided in Section 5.1(a). In furtherance of this Section 5.1, the Investor hereby irrevocably appoints the Company and any individuals designated by the Company, and each of them individually, as the attorneys, agents and proxies, with full power of substitution and re-substitution in each of them, for the Investor, and in the name, place and stead of the Investor, to vote (or cause to be voted) in such manner as set forth in this Section 5.1 (but in any case, (i) in accordance with any written instruction from the

Investor, properly delivered under this Section 5.1, to vote as contemplated by clause (b) above, and (ii) excluding any matter that is an Extraordinary Matter described in Section 5.2) with respect to the Voting-Restricted Shares, and Section 3.1(b) and Section 3.2(a) with respect to all Shares of Then Outstanding Common Stock beneficially owned by Investor and its Affiliates, with respect to which the Investor is or may be entitled to vote at any meeting of the Company held after the date hereof, whether annual or special and whether or not an adjourned meeting (the “ Irrevocable Proxy ”). This Irrevocable Proxy is coupled with an interest, shall be irrevocable and binding on any successor in interest of the Investor and shall not be terminated by operation of law upon the occurrence of any event. This Irrevocable Proxy shall operate to revoke and render void any prior proxy as to any securities of the Company heretofore granted by the Investor which is inconsistent herewith. Notwithstanding the foregoing, the Irrevocable Proxy shall be effective if, at any annual or special meeting of the stockholders of the Company and at any adjournments or postponements of any such meetings, the Investor (A) fails to appear or otherwise fails to cause the Voting-Restricted Shares (in the case of matters referred to in this Section 5.1) and any securities of the Company (in the case of the matters referred to in Section 3) to be counted as present for purposes of calculating a quorum, or (B) fails to vote such securities of the Company in accordance with this Section 5.1, Section 3.1(b) and Section 3.2(a), in each case at least five (5) business days prior to the date of such stockholders’ meeting. The Irrevocable Proxy shall terminate upon the earlier of the expiration or termination of the voting agreement set forth in this Section 5.1. The Investor shall cause any Affiliate of the Investor that may from time to time own of record (or the record holder holding on behalf of such Affiliate if owned beneficially) Voting-Restricted Shares (in the case of matters referred to in this Section 5.1) and any securities of the Company (in the case of the matters referred to in Section 3.1(b) and 3.2(a)), if and when requested by the Company from time to time, to promptly execute and deliver to the Company an irrevocable proxy, substantially in the form of Exhibit A attached hereto, and irrevocably appoint the Company and any individuals designated by the Company, and each of them individually, with full power of substitution and resubstitution, as its attorney, agent and proxy to vote (or cause to be voted) such securities of the Company as to which such Affiliate is entitled to vote, in such manner as each such attorney, agent and proxy or his substitute shall in its, his or her sole discretion deem appropriate or desirable with respect to the matters set forth in this Section 5.1, Section 3.1(b) and Section 3.2(a) (the “ Affiliate Irrevocable Proxy ”). The Investor acknowledges, and shall cause its Affiliates to acknowledge, that any such proxy executed and delivered shall be coupled with an interest, shall constitute, among other things, an inducement for the Company to enter into this Agreement, shall be irrevocable and binding on any successor in interest of such Affiliate and shall not be terminated by operation of Law upon the occurrence of any event. Such proxy shall operate to revoke and render void any prior proxy as to any securities of the Company heretofore granted by such Affiliate, to the extent it is inconsistent herewith. The Investor acknowledges and agrees that it shall be a condition to any proposed transfer of any securities of the Company by the Investor to such Affiliate that such Affiliate execute and deliver to the Company an Affiliate Irrevocable Proxy, and that any purported transfer shall be void and of no force or effect if such Affiliate Irrevocable Proxy is not so executed and delivered at the closing of such transfer. Such proxy

shall terminate upon the earlier of the expiration or termination of this Section 5.1. For the avoidance of doubt, this Section 5 does not apply to any Shares of Then Outstanding Common Stock other than the Voting-Restricted Shares, except as otherwise expressly contemplated by Section 3.1(b) and Section 3.2(a). In the event the Company’s stockholders are permitted to act by written consent, the Company and the Investor shall each negotiate in good faith with the other provisions as consistent as possible with the foregoing to govern the voting of the Investor’s and its Affiliates’ Voting-Restricted Shares and Shares of Then Outstanding Common Stock as closely as practicable to the foregoing.

5.2 Certain Extraordinary Matters . The Investor and its Affiliates may vote, or execute a written consent with respect to, any or all of the Voting-Restricted Shares of the Company as to which they are entitled to vote or execute a written consent, as they may determine in their sole discretion, with respect to the following matters (each such matter being an “ Extraordinary Matter ”):

(a) any transaction which would result in a Change of Control; and

(b) any liquidation or dissolution of the Company

6. Right of First Offer .

6.1 Right of First Offer . Subject to the terms and conditions of this Section 6 and applicable securities laws, if the Company proposes to offer or sell any shares of Common Stock or any Common Stock Equivalents (the “ New Securities ”), the Company shall give written notice (the “ Offer Notice ”) to the Investor stating (a) its bona fide intention to offer such New Securities, (b) the number of such New Securities to be offered, and (c) the structure of the proposed offering or sale. By written notification to the Company within five (5) days after the date of the Offer Notice (the “ Exercise Period ”, the Investor may elect to purchase, upon the same terms and conditions as other purchasers in the offering or sale of the New Securities, up to that portion of such New Securities that would allow the Investor to maintain its percentage ownership of Shares of Then Outstanding Common Stock after the offering or sale of the New Securities. The Investor shall be entitled to apportion the right of first offer hereby granted to it in such proportions as it deems appropriate, among itself and its Permitted Transferees that are “accredited investors” within the meaning of Rule 501(a) under the Securities Act.

6.2 Limitations . The right of first offer in Section 6.1 shall not be applicable to:

(a) securities issued or issuable in exchange and as consideration for the bona fide acquisition of another corporation or entity by the Company by consolidation, merger, purchase of all or substantially all of the assets, or other bona fide reorganization in which the Company acquires, in a single transaction or series of related transactions, all or substantially all of the assets of such other corporation or entity or fifty percent (50%) or more of the voting power of such other corporation or entity or fifty percent (50%) or more of the equity ownership of such other entity;

(b) securities issued or issuable in exchange and as consideration for the rights obtained in research, collaboration, license, development, strategic alliance or other similar agreements or strategic partnerships;

(d) securities issued pursuant to arms’ length bank financings;

(e) shares of Common Stock and/or Common Stock Equivalents issued or issuable for compensatory purposes to employees, officers, directors, contractors, vendors, advisors or consultants of the Company or any of its subsidiaries (whether or not issued pursuant to a Company equity incentive plan);

(f) securities issued as a dividend, stock split or distribution on the Common Stock; and

(g) any right, option or warrant to acquire any securities set forth in Section 6.2(a)-(f) above.

provided, however, in the event the Company issues New Securities in a transaction to which the right of first offer in Section 6.1 shall not apply pursuant to Sections 6.2(a), 6.2(b) or 6.2(d) (an “ Excepted Transactional Issuance ”) or Section 6.2(e) (an “ Excepted Compensatory Issuance ”), the Company shall grant the Investor the right, upon the terms and conditions set forth in this paragraph, (i) to purchase a number of securities of the same type as the New Securities issued in the Excepted Transactional Issuance (except that securities purchased by the Investor in connection with an Excepted Transactional Issuance involving a public offering shall be registered under the Securities Act only to the extent permitted by applicable law) such that the percentage of Common Stock or any Common Stock Equivalents of the Company held by the Investor immediately after giving effect to the issuance of such New Securities and the issuance and purchase by the Investor of such securities pursuant to this Section 6.2 shall equal the percentage of Common Stock or any Common Stock Equivalents of the Company held by the Investor immediately prior to the Excepted Transactional Issuance and (ii) to purchase a number of securities of the same type as the New Securities issued in Excepted Compensatory Issuances during the previous calendar year such that the percentage of Common Stock or any Common Stock Equivalents of the Company held by the Investor immediately after giving effect to the issuance of such New Securities in such Excepted Compensatory Issuances and the issuance and purchase by the Investor of such securities pursuant to this Section 6.2 shall equal the percentage of Common Stock or any Common Stock Equivalents of the Company that would have been held by the Investor had the applicable Excepted Compensatory Issuances not been

made. The Company shall, within five (5) business days after the consummation of an Excepted Transactional Issuance and within ten (10) business days after the end of each calendar year in respect of Excepted Compensatory Issuances, provide written notice to the Investor of the offer described in this clause. The Investor shall have five (5) business days from the date of such notice to provide the Company with written notice of its election to exercise all or a portion of its purchase right under this clause, and such purchase shall be consummated within five (5) business days after the date of the Investor’s written election. The price per security for the offer related to an Excepted Transactional Issuance shall be the greater of (x) the per security price of the New Securities issued in the Excepted Transactional Issuance and (y) the closing price, if any, of the New Securities on the date of purchase by the Investor pursuant to this Section 6.2; provided, however, that if the price per security of the New Securities issued in the Excepted Transactional Issuance is greater than the closing market price of the New Securities on the date of the definitive agreement for such Excepted Transactional Issuance, the foregoing price formula shall not apply, and the price per security shall be the closing market price of the New Securities on the date of purchase by the Investor pursuant to this Section 6.2. The price per security for the offer related to Excepted Compensatory Issuances shall be the closing market price of the New Securities on the date of purchase by the Investor pursuant to this Section 6.2.

6.3 Expiration . In the event the Investor fails to exercise its right of first refusal within the Exercise Period for the entire amount of New Securities offered pursuant to Section 6.1 above, the Company shall have forty-five (45) days thereafter to it to sell or enter into an agreement (pursuant to which the sale of New Securities covered thereby shall be closed, if at all, within thirty (30) days from the date of such agreement) to sell the New Securities respecting which the Investor’s right of first refusal set forth in Section 6.1 was not exercised, at a price and upon terms no more favorable to the purchasers thereof than specified in the Offer Notice. In the event the Company has not sold within such forty-five (45) day period or entered into an agreement to sell the New Securities in accordance with the foregoing within such thirty (30) days, the Company shall not thereafter issue or sell any New Securities without first again offering such securities to the Investor in the manner provided in this Section 6. If the Investor fails to exercise its right to purchase New Securities within the Exercise Period for the entire amount of New Securities offered pursuant to Section 6.1 above, but nevertheless expresses thereafter an interest in participating in such offering prior to such offering having been effected, the Company will use commercially reasonable efforts to include the Investor in such offering if the Company, in its reasonable discretion, determines that the inclusion of the Investor at such later time will not adversely affect the success of such offering.

7. Designated Director .

7.1 Designated Director . In the event the Investor and its Affiliates acquire beneficial ownership, in the aggregate, of at least twenty percent (20%) of the Shares of Then Outstanding Common Stock (the “ Ownership Threshold ”), the Investor may, upon written notice to the Company elect to cause, and the Company shall cause, one individual selected by the Investor (the “ Designated Director ”) to be appointed as a member of the Company’s Board

of Directors within thirty (30) days after the Company’s receipt of such written notice. The Company will not require the Designated Director to personally enter into any non-disclosure agreement, and to the extent other directors of the Company enter into such agreements, the Company agrees that it will accept the Investor’s non-disclosure covenant in lieu of any such covenant from the Designated Director. In connection with each subsequent meeting of the stockholders of the Company at which the Designated Director’s term of service as a director is expiring, the Company shall cause the Designated Director to be nominated for re-election at such meeting and included within the slate of directors contained in the Company’s proxy statement, accompanied by a recommendation by the Company’s Board of Directors that such individual be elected as a director. In the event the Designated Director is nominated for re-election at a meeting of the stockholders of the Company but is not re-elected by the stockholders, the Company’s obligations pursuant to this Section 7 shall terminate with respect to such individual. Notwithstanding the foregoing sentence, in the event a Designated Director is not re-elected by the stockholders, the Investor retains the right to appoint a new Designated Director in accordance with this Section 7, and the Company’s obligations pursuant to this Section 7 remain in effect with respect to such new Designated Director. In the event a vacancy is created at any time by the death, disability, retirement, resignation or removal of a Designated Director, the Investor shall appoint a new Designated Director to fill the resulting vacancy. In the event a Designated Director is serving on the Company’s Board of Directors and the aggregate beneficial ownership of the Shares of Then Outstanding Common Stock held by the Investor and its Affiliates decreases below the Ownership Threshold, the Investor shall cause, at the request of the Company, the Designated Director to resign from the Company’s Board of Directors at such time as is deemed advisable by the Company’s Board of Directors (excluding the Designated Director), but in no event later than the next meeting of the stockholders of the Company at which members of the Company’s Board of Directors are elected; provided, however, that if the beneficial ownership of the Investor and its Affiliates in the aggregate is reduced below the Ownership Threshold as a direct result of dilution suffered upon an issuance of securities by the Company pursuant to a Dilutive Event, the Investor’s obligations under clauses (a) and (b) of this sentence shall instead be triggered if the beneficial ownership of the Investor and its Affiliates remains below the Ownership Threshold for the ensuing six (6) months and fifteen (15) days following the date on which the aggregate beneficial ownership of the Shares of Then Outstanding Common Stock held by the Investor and its Affiliates decreases below the Ownership Threshold. Notwithstanding the foregoing, this Section 7.1 shall terminate, and the Investor shall cause, upon delivery of written notice by the Company to the Investor within ten (10) business days after the occurrence of the applicable event (or, for purposes of clause (iii) below, within ten (10) business days after the Company’s knowledge of such event), the Designated Director to resign from the Company’s Board of Directors no later than at such time as is deemed advisable by the Company’s Board of Directors (excluding the Designated Director) and set forth in the notice referenced above, upon the earliest of (i) the date of termination of the Master Agreement by the Company pursuant to Section 12.2.3 (Termination of this Master Agreement for Cause) or Section 12.2.4 (Challenges of Patent Rights) of the Master Agreement, (ii) the date of termination of the Master Agreement by the Investor pursuant to Section 12.2.1 (Termination for Convenience) of the Master Agreement and (iii) material breach by the Investor or any of its Affiliates of Section 3.1 of this Agreement.

7.2 Notice and Information Rights . The Company shall notify the Designated Director of all regular and special meetings of the Company’s Board of Directors or any committee thereof of which the Designated Director is a member. Subject to the following sentence, the Company shall provide the Designated Director with copies of all notices, minutes, consents and other materials provided to all other directors (the “ Director Information ”) concurrently as such materials are provided to the other directors. The Designated Director will be afforded no less favorable treatment than any other member of the Company’s Board of Directors with respect to all matters, including, without limitation, expense reimbursement and indemnification consistent with those offered to all other members of the Company’s Board of Directors (including with respect to expense reimbursement and domestic travel unless and until the Company invites a non-U.S. person to join the Company’s Board of Directors) and reasonable access to Company information and management, except that (i) the Designated Director may be excluded from participation or deliberation by the Company’s Board of Directors or committees thereof in connection with issues involving: (a) the Collaboration Agreement or any other agreements between the Company and the Investor (as reasonably determined by the Company’s Board of Directors or relevant committee thereof), (b) matters of conflict or dispute between the Company and the Investor, or (c) any other matter which is confidential and in the reasonable determination of the Company’s Board of Directors, would be compromised by the presence of the Designated Director due to such Designated Director’s affiliation with the Investor and (ii) the Designated Director shall not have the right to receive Director Information with respect to the matters noted in clause (i) of this sentence.

7.3 Freedom to Pursue Opportunities . Each of the parties hereto expressly acknowledges and agrees that: (i) the Investor, its Affiliates and any Designated Director that is an employee of the Investor or any of its Affiliates have the right to, and shall have no duty (contractual or otherwise) not to, directly or indirectly engage in the same or similar business activities or lines of business as the Company or any of its subsidiaries, including those deemed to be competing with the Company or any of its subsidiaries; and (ii) in the event that the Investor, its Affiliates or any Designated Director that is an employee of the Investor or any of its Affiliates acquire knowledge of a potential transaction or matter (other than in the case of a Designated Director where knowledge of such transaction or matter was acquired by the Designated Director solely in his or her capacity as a Designated Director) that may be a corporate opportunity for each of the Company and the Investor, such Person shall have no duty (contractual or otherwise) to communicate or present such corporate opportunity to the Company or any of its subsidiaries, as the case may be, and, notwithstanding any provision of this Agreement to the contrary, shall not be liable to the Company or its Affiliates for any breach of any duty (contractual or otherwise) by reason of the fact that the Investor, its Affiliates or any Designated Director, directly or indirectly, pursues or acquires such opportunity for itself or another Person, directs such opportunity to another Person, or does not present such opportunity to the Company. Each Designated Director is an intended third party beneficiary of this provision, entitled to enforce it directly against the Company.

8. Information Rights .

8.1 Information Rights . During such time that a Designated Director is a member of the Company’s Board of Directors, the Investor and its Affiliates will be entitled to receive any information which the Designated Director receives or is entitled to receive; provided, however, that the Investor and its Affiliates may make such information available only to individuals who have a need to know such information for purposes of the Collaboration Agreement or the Investor’s or any Affiliate’s investment in the Company, including any outside service providers subject to a duty of confidentiality to the Investor or any Affiliate, such as auditors and legal counsel.

8.2 Financial Information and Reporting . The Company will provide to Investor or its designated Affiliate the financial information described in this Section 8.2 as well as any financial information reasonably requested by Investor so that Investor can manage and account for its investment in the Company, including to determine the fair value of the Company’s investment or assess whether the Company needs to account for the investment using the equity method of accounting or otherwise, including making its management available to Investor for reasonable inquiries regarding its financial statements and performance. If the Investor or its Affiliate (a) determines in good faith that such financial information is reasonably likely to be necessary with respect to the financial reporting of the Investor or its Affiliates and (b) provides the Company with written notice to such effect, then beginning as promptly as reasonably practicable but in no event later than the 120 ^th day following such notice, the Company will deliver via overnight delivery and electronic mail to the Investor or its Affiliate the information described in Exhibit C hereto by the dates indicated on Exhibit C (as such Exhibit C may be updated by the Investor from time to time to reflect changes in the financial reporting requirements of the Investor or its Affiliates).

8.3 Confidentiality . All confidential or proprietary information and data relating to the Company and its subsidiaries provided by the Company to either the Investor pursuant to this Section 8 or the Designated Director pursuant to Section 7 shall be deemed “Confidential Information” under the Master Agreement and accordingly shall be subject to the terms and conditions of the Master Agreement governing “Confidential Information.”

9. Termination of Certain Rights and Obligations .

9.1 T ermination of Registration Rights . Except for Section 2.11, which shall survive until the expiration of any applicable statutes of limitation, Section 2 shall terminate automatically and have no further force or effect upon the earliest to occur of:

(a) the expiration of the Registration Rights Term;

(b) the date on which the Common Stock ceases to be registered pursuant to Section 12 of the Exchange Act; and

9.2 Termination of Standstill Agreement . Section 3, other than Sections 3.2(b) and (c), shall terminate and have no further force or effect, upon the earliest to occur of:

(a) provided that none of the Standstill Parties has violated Section 3.1(c), (d) or (f) with respect to the Offeror referred to in this clause (a), the public announcement by the Company or any Offeror of any definitive agreement between the Company and such Offeror and/or any of its Affiliates providing for a Change of Control of the Company;

(b) the expiration of the Standstill Term (subject to revival as set forth in the definition of such term);

(d) a liquidation or dissolution of the Company;

provided , however , that if Section 3 terminates due to clause (a) above and such agreement is abandoned and no other similar transaction has been announced and not abandoned or terminated within ninety (90) days thereafter, the restrictions contained in Section 3 shall again be applicable until otherwise terminated pursuant to this Section 9.2.

9.3 Termination of Restrictions on Dispositions . Section 4 (other than Section 4.4) shall terminate and have no further force or effect upon the earliest to occur of:

(a) the consummation by an Offeror of a Change of Control of the Company;

(b) a liquidation or dissolution of the Company;

(d) if there has been a period of at least [***] months during which [***], the date that is the first day after the end of such [***] month period.

9.4 Termination of Voting Agreement and Offering Lock-Up . Section 5 and Section 4.4 shall terminate and have no further force or effect upon the earliest to occur of:

(a) the consummation by an Offeror of a Change of Control of the Company;

(b) a liquidation or dissolution of the Company;

(d) the expiration or termination of the Standstill Term.

9.5 Termination of Right of First Offer . Section 6 shall terminate and have no further force or effect upon the earliest to occur of:

(a) the date on which the Investor and its Affiliates beneficially own, in the aggregate, less than seven and a half percent (7.5%) of the Shares of Then Outstanding Common Stock; provided, however, that if the beneficial ownership of the Investor and its Affiliates in the aggregate is reduced below such threshold as a direct result of dilution suffered upon a Dilutive Event, Section 6 shall instead terminate upon the earliest of (x) Investor’s failure to provide written notice to the Company of its election to purchase additional securities within the five (5) business day period set forth in Section 6.2 related to the applicable Dilutive Event, (y) Investor’s failure to consummate the purchase of additional securities of the Company pursuant to Section 6.2 within the time period set forth therein related to the applicable Dilutive Event or (z) the date of Investor’s purchase of additional securities of the Company pursuant to Section 6.2 related to the applicable Dilutive Event if, immediately following the consummation of such purchase, the Investor and its Affiliates beneficially own, in the aggregate, less than seven and a half percent (7.5%) of the Shares of Then Outstanding Common Stock.

(b) the consummation by an Offeror of a Change of Control of the Company;

(d) the date on which the Common Stock ceases to be registered pursuant to Section 12 of the Exchange Act.

9.6 Effect of Termination . No termination pursuant to any of Sections 9.1, 9.2, 9.3, 9.4 or 9.5 shall relieve any of the parties (or the Permitted Transferee, if any) for liability for breach of or default under any of their respective obligations or restrictions under any terminated provision of this Agreement, which breach or default arose out of events or circumstances occurring or existing prior to the date of such termination.

10. Miscellaneous .

10.1 Governing Law; Submission to Jurisdiction . This Agreement shall be governed by and construed in accordance with the Laws of the State of Delaware, without regard to the conflict of laws principles thereof that would require the application of the Law of any other jurisdiction. Any action brought, arising out of, or relating to this Agreement shall be brought in the Court of Chancery of the State of Delaware. Each party hereby irrevocably submits to the exclusive jurisdiction of said Court in respect of any claim relating to the validity, interpretation and enforcement of this Agreement, and hereby waives, and agrees not to assert, as a defense in any action, suit or proceeding in which any such claim is made that it is not subject thereto or that such action, suit or proceeding may not be brought or is not maintainable in such courts, or that the venue thereof may not be appropriate or that this agreement may not be enforced in or by such courts. The parties hereby consent to and grant the Court of Chancery of the State of Delaware jurisdiction over such parties and over the subject matter of any such claim and agree that mailing of process or other papers in connection with any such action, suit or proceeding in the manner provided in Section 10.3 or in such other manner as may be permitted by law, shall be valid and sufficient thereof.

10.2 Waiver . Waiver by a party of a breach hereunder by another party shall not be construed as a waiver of any subsequent breach of the same or any other provision. No delay or omission by a party in exercising or availing itself of any right, power or privilege hereunder shall preclude the later exercise of any such right, power or privilege by such party. No waiver shall be effective unless made in writing with specific reference to the relevant provision(s) of this Agreement and signed by a duly authorized representative of the party granting the waiver.

10.3 Notices . All notices, instructions and other communications hereunder or in connection herewith shall be in writing, shall be sent to the address of the relevant party set forth on Exhibit B attached hereto and shall be (a) delivered personally, (b) sent by registered or certified mail, return receipt requested, postage prepaid, (c) sent via a reputable nationwide overnight courier service or (d) sent by facsimile transmission, with a confirmation copy to be sent by registered or certified mail, return receipt requested, postage prepaid. Any such notice, instruction or communication shall be deemed to have been delivered upon receipt if delivered by hand, three (3) Business Days after it is sent by registered or certified mail, return receipt requested, postage prepaid, one (1) Business Day after it is sent via a reputable nationwide overnight courier service or when transmitted with electronic confirmation of receipt, if transmitted by facsimile (if such transmission is made during regular business hours of the recipient on a Business Day; or otherwise, on the next Business Day following such transmission). Any party may change its address by giving notice to the other parties in the manner provided above.

10.4 Entire Agreement . This Agreement and the Purchase Agreement contain the entire agreement among the parties with respect to the subject matter hereof and thereof and supersede all prior and contemporaneous arrangements or understandings, whether written or oral, with respect hereto and thereto.

10.5 Amendments . No provision in this Agreement shall be supplemented, deleted or amended except in a writing executed by an authorized representative of each of the parties hereto.

10.6 Headings; Nouns and Pronouns; Section References . Headings in this Agreement are for convenience of reference only and shall not be considered in construing this Agreement. Whenever the context may require, any pronouns used herein shall include the corresponding masculine, feminine or neuter forms, and the singular form of names and pronouns shall include the plural and vice-versa. References in this Agreement to a section or subsection shall be deemed to refer to a section or subsection of this Agreement unless otherwise expressly stated.

10.7 Severability . If, under applicable Laws, any provision hereof is invalid or unenforceable, or otherwise directly or indirectly affects the validity of any other material provision(s) of this Agreement in any jurisdiction (“ Modified Clause ”), then, it is mutually agreed that this Agreement shall endure and that the Modified Clause shall be enforced in such jurisdiction to the maximum extent permitted under applicable Laws in such jurisdiction; provided that the parties shall consult and use all reasonable efforts to agree upon, and hereby consent to, any valid and enforceable modification of this Agreement as may be necessary to avoid any unjust enrichment of either party and to match the intent of this Agreement as closely as possible, including the economic benefits and rights contemplated herein.

10.8 Assignment . Neither this Agreement nor any rights or duties of a party hereto may be assigned by such party, in whole or in part, without (a) the prior written consent of the Company in the case of any assignment by the Investor, except as provided by Section 2.13 with respect to the Investor’s assignment to a Permitted Transferee; or (b) the prior written consent of the Investor in the case of an assignment by the Company.

10.9 Successors and Assigns . This Agreement shall be binding upon and inure to the benefit of the parties hereto and their respective successors and permitted assigns.

10.10 Counterparts . This Agreement may be executed in counterparts, each of which shall be deemed an original but which together shall constitute one and the same instrument.

10.11 Third Party Beneficiaries . None of the provisions of this Agreement shall be for the benefit of or enforceable by any Third Party other than a Designated Director and any Affiliate of the Investor. No Third Party with the exception of any Designated Director and any Affiliate of the Investor shall obtain any right under any provision of this Agreement or shall by reason of any such provision make any claim in respect of any debt, liability or obligation (or otherwise) against any party hereto.

10.12 No Strict Construction . This Agreement has been prepared jointly and will not be construed against any party.

10.13 Remedies . The rights, powers and remedies of the parties under this Agreement are cumulative and not exclusive of any other right, power or remedy which such parties may have under any other agreement or Law. No single or partial assertion or exercise of any right, power or remedy of a party hereunder shall preclude any other or further assertion or exercise thereof.

10.14 Specific Performance . The Company and the Investor hereby acknowledge and agree that the rights of the parties hereunder are special, unique and of extraordinary character, and that if any party refuses or otherwise fails to act, or to cause its Affiliates to act, in accordance with the provisions of this Agreement, such refusal or failure would result in irreparable injury to the Company or the Investor, as the case may be, the exact amount of which would be difficult to ascertain or estimate and the remedies at law for which would not be reasonable or adequate compensation. Accordingly, if any party refuses or otherwise fails to act, or to cause its Affiliates to act, in accordance with the provisions of this Agreement, then, in addition to any other remedy which may be available to any damaged party at law or in equity, such damaged party will be entitled to seek specific performance and injunctive relief, without posting bond or other security, and without the necessity of proving actual or threatened damages, which remedy such damaged party will be entitled to seek in any court of competent jurisdiction.

10.15 No Conflicting Agreements . The Investor hereby represents and warrants to the Company that neither it nor any of its Affiliates is, as of the date of this Agreement, a party to, and agrees that neither it nor any of its Affiliates shall, on or after the date of this Agreement, enter into any agreement that conflicts with the rights granted to the Company in this Agreement. The Company hereby represents and warrants to each Holder that it is not, as of the date of this Agreement, a party to, and agrees that it shall not, on or after the date of this Agreement, enter into, any agreement or approve any amendment to its Organizational Documents (as defined in the Purchase Agreement) with respect to its securities that conflicts with the rights granted to the Holders in this Agreement. The Company further represents and warrants that the rights granted to the Holders hereunder do not in any way conflict with the rights granted to any other holder of the Company’s securities under any other agreements.

10.16 Rule 16b-3 . If at any time in the future the Investor determines that Rule 16b-3 promulgated under the Exchange Act may be available to exempt from Section 16(b) of the Exchange Act a transaction between the Investor and the Company, the Company shall cooperate and use commercially reasonable efforts to take such actions, including by adopting appropriate resolutions of the Board of Directors of the Company, to permit the Investor to rely on such exemption.

10.17 [***] . [***].

( Signature Page Follows )

IN WITNESS WHEREOF, the parties have executed and delivered this Agreement as of the date first above written.


GENZYME CORPORATION

By:		/s/ David Meeker
		Name: David Meeker, M.D.
		Title: President and Chief Executive Officer

ALNYLAM PHARMACEUTICALS, INC.

By:		/s/ John M. Maraganore
		Name: John M. Maraganore, Ph.D.
		Title: Chief Executive Officer

EXHIBIT A

FORM OF IRREVOCABLE PROXY

In order to secure the performance of the duties of the undersigned pursuant to Section 5.1 of the Investor Agreement, dated as of February 27, 2014 (the “Agreement”), by and between Genzyme Corporation and Alnylam Pharmaceuticals, Inc. (the “ Company ”), the undersigned hereby irrevocably appoints the Company and any individual designated by the Company, and each of them individually, as the attorneys, agents and proxies, with full power of substitution and resubstitution in each of them, for the undersigned, and in the name, place and stead of the undersigned, to vote (or cause to be voted) in such manner as set forth in Section 5.1 of the Agreement (but in any case, (i) in accordance with any written instruction from the undersigned, properly delivered under Section 5.1 of the Agreement, to vote as contemplated by Section 5.1(b) of the Agreement and (ii) excluding any matter that is an Extraordinary Matter described in Section 5.2) with respect to all Voting-Restricted Shares (in the case of matters referred to in Section 5.1) and all securities of the Company (in the case of the matters referred to in Section 3.1(b) and Section 3.2(a)), which the undersigned is or may be entitled to vote at any meeting of the Company held after the date hereof, whether annual or special and whether or not an adjourned meeting. This proxy is coupled with an interest, shall be irrevocable and binding on any successor in interest of the undersigned and shall not be terminated by operation of law upon the occurrence of any event. This proxy shall operate to revoke and render void any prior proxy as to securities of the Company heretofore granted by the undersigned which is inconsistent herewith. Notwithstanding the foregoing, this irrevocable proxy shall be effective if, at any annual or special meeting of the stockholders of the Company (or any consent in lieu thereof) and at any adjournments or postponements of any such meetings, the undersigned (A) fails to appear or otherwise fails to cause its voting securities of the Company to be counted as present for purposes of calculating a quorum, or (B) fails to vote such voting securities in accordance with Sections 3.1(b), 3.2(a) or 5.1 of the Agreement, in each case at least five (5) business days prior to the date of such stockholders’ meeting. This proxy shall terminate upon the earlier of the expiration or termination of the voting agreement set forth in Section 5.1 of the Agreement.


[ ]

By:
		Name:
		Title:

A-1

EXHIBIT B

NOTICES

(a)	If to Genzyme Corporation:

Genzyme Corporation

500 Kendall Street

Cambridge, MA 02142

Attention: President of Rare Disease

Facsimile No.: (617) 374-2424

with a copy to:

Genzyme Corporation

500 Kendall Street

Cambridge, MA 02142

Attention: General Counsel

Facsimile: (617) 252-7553

and to:

Ropes & Gray LLP

Prudential Tower

800 Boylston Street

Boston, MA 02199-3600

Attention: Christopher D. Comeau, Esq.

Facsimile: (617) 235-0507

(b)	If to the Company:

Alnylam Pharmaceuticals, Inc.

300 Third Street

Cambridge, MA 02142

Attention: Vice President – Legal

Facsimile: (617) 551-8101

with a copy to:

Goodwin Procter LLP

53 State Street

Boston, MA 02109

Attention: Mitchell S. Bloom, Esq,

Facsimile: (617) 523-1231

B-1

EXHIBIT C

The below chart summarizes the type of information needed to apply the at equity method for an associate that is disclosing its financial statements under another referential than IFRS.


INFORMATION	Ref	PERIOD	TIMING	COMMENT
Issued and outstanding shares by classes (Common, Preferred...)		Quarter	D+5	Rights attached to each class of shares is also needed in order to determine the appropriate ownership interest
Outstanding potential rights (Options, Convertible rights)		Quarter	D+5
YTD consolidated income statement (USGAAP)	A	Month	D+7	Estimate could be used at this deadline – (final numbers required at D+11)
YTD statement of comprehensive income (USGAAP)	B	Quarter	D+7	Same
Equity Roll forward including detail of equity transactions (USGAAP)	C	Quarter	D+7	Same
Summarized balance sheet (USGAAP)	D	Quarter	D+7	Same
Main USGAAP/IFRS differences	E	Quarter	D+7	>5M$
Transactions between Sanofi & the Company	F	Quarter	D+7	P&L, OCI and Balance Sheet
Transactions between Sanofi & the Company		Half-year	D+7	Off balance sheet
List of the Company’s subsidiaries		Annual	D+7

Other information needed as part of a first application of the equity method:

- Detailed programs of share based payment awards as of 31 December 20Y-2, 31 December 20Y-1 and equity method date

C-1

The financial reporting schedules (referenced from A to F) to be obtained from the Company are presented below:

A/ YTD CONSOLIDATED INCOME STATEMENT (USGAAP)


Amounts in K$ (1)	YTD as of XX
	Total	Transactions with Sanofi
Net Sales
Other Revenue
Cost of goods sold
Gross profit
Research and development expense
Selling and general expenses
Other operating income & expense
Amortization of intangible assets
Impairment of intangible assets
Fair value re-measurement of contingent consideration liabilities
Operating income
Financial expense
Financial income
Income before tax and associates & JV
Income tax expense
Share of profit/(loss) of associates and JV
Net income
Attributable to non-controlling interests
Net income attributable to equity holders of the Company

(1)	Positive amount = income

C-2

B/ YTD CONSOLIDATED STATEMENT OF COMPREHENSIVE INCOME/LOSS (USGAAP)


Amounts in K$ (1)	Beginning period as of XX	Change in the period	Ending period as of XX
Net income
Other comprehensive income:
Actuarial gains (losses)
Tax effect on actuarial gains and losses
Unrealized gains & losses on available-for-sale financial assets
Tax effect on unrealized gains & losses on AFS
Cash flow hedge
Tax effect on cash flow hedge
Net investment hedge
Tax effect on net investment hedge
Change in currency translation difference
Other comprehensive income for the period, net of taxes
Total comprehensive income
Of which attributable to non-controlling interests

(1)	Positive amount = income

C-3

C/ EQUITY ROLL FORWARD (USGAAP)

Amounts in K$ (1)

Number
of
Shares

Capital

Additional
Paid in
Capital

Accumulated
retained
earnings

Other
Comprehensive
income (loss)

Non-controlling
interests

Total
Equity

Beginning balance as of XX

Net income for the period

Other comprehensive income for the period

Payment of dividends

Increase in capital (2)

Decrease in capital

Repurchase of Shares

Equity component of convertible notes

Purchase of convertible note

Warrants in connection of convertible notes

Share-based payments:

Increase in capital in connection with exercise of stock options

Increase in capital in connection with restricted shares

Share-based payment expense

Excess tax benefit from share-based payment expense

Other changes (3)

Ending balance as of XX

(1)	Positive amount = credit

(2)	Other than share-based payments

(3)	To be detailed

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D/ SUMMARIZED BALANCE SHEET (USGAAP)


Amounts in K$ (1)	YTD as of XX
	Total	Transactions with Sanofi
ASSETS
Non-current assets			(2	)
Accounts receivable
Deferred tax assets – current portion
Other current assets			(2	)
TOTAL ASSETS

(1)	Positive amount = debit balance

(2)	To be detailed


Amounts in K$ (1)	YTD as of XX
	Total	Transactions with Sanofi
LIABILITIES AND EQUITY
Equity
Deferred revenue non-current portion
Other non-current liabilities			(2	)
Accounts payable
Deferred revenue current portion
Other current liabilities			(2	)
TOTAL LIABILITIES AND EQUITY

(1)	Positive amount = credit balance

(2)	To be detailed

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E/IFRS-USGAAP differences


Amounts in K$	Note			Beginning period as of XX	Net income	OCI	Other Equity	Ending period as of XX	Income Statement line affected
R&D expense resulting from payments of rights to a product or technology (before regulatory approval)		(1	)
Amortization expense related to acquired R&D previously capitalized		(1	)
Impairment loss related to acquired R&D previously capitalized		(1	)
Lease classification including land		(2	)
Asset retirement obligations		(3	)
Inventory capitalized prior regulatory approval		(4	)
Reversal of inventory written off upon regulatory approval		(5	)
Inventory samples		(6	)
Deferred tax on intragroup inventory margin		(7	)
Executive Stock Purchase Plan		(8	)
Share based payments (Income tax)		(9	)
Actuarial gains & losses on postretirement benefits		(10	)
Prior service costs on postretirement employee benefits		(11	)

C-6


Expected return on plan asset	(12	)
Asset ceiling (net pension asset)	(13	)
Provision recognition – measurement	(14	)
Long term provision discounting	(15	)
Revenue recognition (TBD)
TOTAL

(1)

Capitalized under IFRS

(2)

Classification Operating versus Finance lease depending on criteria (IFRS/USGAAP)

(3)

Recognition criteria & measurement differences between IFRS and USGAAP

(4)

Fully written down under Sanofi’s accounting policy

(5)

Reversal permitted under IFRS

(6)

Net Residual Value is zero under Sanofi’s accounting policy

(7)

Based on the buyer’s rate under IFRS versus seller’s rate under USGAAP

(8)

Compensation expense under IFRS

(9)

Deferred tax based on intrinsic value at each balance sheet date under IFRS – Only tax expected above tax effect of cumulative expense is recognized through equity

(10)

Recognized immediately in OCI under IFRS

(11)

Recognized as expense in the period of plan amendments under IFRS

(12)

Expected return on plan assets determined by applying the discount rate under IFRS (market yields on high quality corporate bonds)

(13)

Limitation required under IFRS

(14)

Present obligation exists under IFRS and best estimate approach

(15)

Discounted required under IFRS when the effect is material (>5M€)

C-7

F/ TRANSACTIONS WITH SANOFI –

UPFRONT AND MILESTONE PAYMENTS:

Upfronts &
Milestones paid

by Sanofi

Amount in K$

Payment date

Deferred Revenue
Beginning period
as of XX(1)

Payment during
the period

Amount
recognized
as Revenue
during the
period (1)

Deferred
Revenue
Ending
period as
of XX (1)

(1)	Positive amount = credit amount in the balance sheet and income statement

OTHER ITEMS WITH P&L IMPACT:


	Amount in K$ (1)	Line impacted in the consolidated P&L
Product sales to Sanofi
Royalties paid by Sanofi
R&D expense incurred by the Company funded by Sanofi

(1)	Positive amount = income; Negative amount = expense

OTHER GAINS & LOSSES RELATING TO TRANSACTIONS WITH SANOFI

(Amounts >5M$) – to be detailed

Example: Gain or loss on non-current asset disposals to Sanofi.

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E XHIBIT 10.4

MASTER COLLABORATION AGREEMENT

by and between

ALNYLAM PHARMACEUTICALS, INC.

and

GENZYME CORPORATION

The Master Collaboration Agreement is not intended to provide any factual information about Alnylam. The Master Collaboration Agreement contains representations, warranties and covenants that Alnylam and Genzyme made to each other as of specific dates. The assertions embodied in those representations, warranties and covenants were made solely for purposes of the Master Collaboration Agreement between Alnylam and Genzyme and may be subject to important qualifications and limitations agreed to by Alnylam and Genzyme in connection with negotiating its terms, including being qualified by confidential disclosures exchanged between the parties in connection with the execution of the Master Collaboration Agreement. Moreover, the representations and warranties may be subject to a contractual standard of materiality that may be different from what may be viewed as material to investors or security holders, or may have been used for the purpose of allocating risk between Alnylam and Genzyme rather than establishing matters as facts. Moreover, information concerning the subject matter of the representations and warranties may change after the date of the Master Collaboration Agreement, which subsequent information concerning the subject matter of the representations and warranties may change after the date of the Master Collaboration Agreement, which subsequent information may or may not be fully reflected in Alnylam’s public disclosures. For the foregoing reasons, no person should rely on the representations and warranties as statements of factual information at the time they were made or otherwise.

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TABLE OF CONTENTS


	Page
1. OVERVIEW; DEFINITIONS		2

1.1. Overview of Transactions		2

1.2. Definitions		4

2. EFFECTIVENESS OF AGREEMENTS AND LICENSES		27

2.1. Effective Date		27

2.2. Effectiveness of Licenses to Collaboration Products		31

2.3. Cooperation		32

2.4. No Antitrust Undertakings		32

2.5. No Effect		32

3. GRANT AND EXERCISE OF OPTIONS		33

3.1. Alnylam Programs		33

3.2. Option Grants		37

3.3. Option Exercise Period		41

3.4. Exercise of an Option		45

3.5. Option Not Exercised		48

3.6. Exclusivity during Option Period		49

4. DEVELOPMENT AND PHARMACOVILIGANCE		51

4.1. Overview		51

4.2. Diligence		51

4.3. Scientific Records		52

4.4. Third Parties		52

4.5. Oversight		52

4.6. Pharmacovigilance		52

5. COLLABORATION MANAGEMENT		52

5.1. Alliance Joint Steering Committee		52

5.2. Pipeline Advisory Committee		57

5.3. IP Committee		58

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5.4. Manufacturing Committee			59

5.5. Product Joint Steering Committees			61

5.6. No Power to Amend			61

5.7. Confidentiality			61

5.8. Modifications			61

5.9. Other Governance Terms			61

6. MANUFACTURE AND SUPPLY OF THE COLLABORATION PRODUCTS			61

6.1. ALN-TTR02 Supply Agreements			61

6.2. Collaboration Product Supply Agreements			62

6.3. General Supply Agreement Requirements			62

6.4. Disputed Supply Agreement Terms			62

6.5. Transfer of Manufacturing Know-How			63

6.6. Establishment of Second Source and Back-Up Sources			63

6.7. Third Party Manufacturers and Subcontracting			63

6.8. Waivers			64

7. CONFIDENTIALITY AND PUBLICATION			64

7.1. Nondisclosure Obligation			64

7.2. Publication and Publicity			66

7.3. Press Release			67

8. REPRESENTATIONS, WARRANTIES AND COVENANTS			68

8.1. Mutual Representations and Warranties as of the Execution Date			68

8.2. Representations and Warranties of Alnylam			69

8.3. Warranty Disclaimer			71

8.4. Certain Covenants			72

9. ROYALTY REPORTS; PAYMENTS; AUDIT			74

9.1. Reports; Payment of Royalty			74

9.2. Audits			74

9.3. Payment Exchange Rate			75

9.4. Late Payments			75

9.5. Blocked Payments			75

9.6. Taxes			76

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10. INDEMNIFICATION; LIMITATION OF LIABILITY; INSURANCE			76

10.1. General Indemnification by Genzyme			76

10.2. General Indemnification by Alnylam			77

10.3. Product Liability			77

10.4. Indemnification Procedure			77

10.5. Limitation of Liability			78

10.6. Insurance			78

11. INTELLECTUAL PROPERTY			79

11.1. Prosecution and Maintenance of Patent Rights			79

11.2. Patent Prosecution Information Sharing			79

11.3. In-Licenses			79

11.4. Common Interest			82

12. TERM AND TERMINATION			83

12.1. Term			83

12.2. Termination Rights			83

12.3. Effect of Termination			84

13. MISCELLANEOUS			86

13.1. Assignment			86

13.2. Governing Law			86

13.3. Jurisdiction			86

13.4. Venue			86

13.5. Entire Agreement; Amendments			87

13.6. Severability			87

13.7. Headings			87

13.8. Waiver of Rule of Construction			87

13.9. Interpretation			87

13.10. No Implied Waivers; Rights Cumulative			88

13.11. Notices			88

13.12. Compliance with Export Regulations			89

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13.13.	Force Majeure	89

13.14.	Independent Parties	90

13.15.	Counterparts	90

13.16.	Performance by Affiliates	90

13.17.	Binding Effect; No Third Party Beneficiaries	90

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SCHEDULES


Schedule 1.2.7		Additional Alnylam In-Licenses

Schedule 1.2.21		ALN-AT3

Schedule 1.2.22		ALN-TTR Core Technology Patents

Schedule 1.2.24		ALN-TTR Product-Specific Patents

Schedule 1.2.26		ALN-TTR02

Schedule 1.2.29		ALN-TTRsc

Schedule 1.2.34		[***]

Schedule 1.2.71		Core Pipeline Program List

Schedule 1.2.80		Form of Exercise Notice

Schedule 1.2.82		Existing Alnylam In-Licenses

Schedule 1.2.88		Final Option Data Package

Schedule 1.2.116		Human POP Proposed Studies

Schedule 1.2.123		Initial Option Data Package

Schedule 1.2.134		Locked Core Pipeline Program List

Schedule 1.2.135		Locked Non-Core Pipeline Program List

Schedule 1.2.146		Named Pipeline Programs

Schedule 1.2.149		Non-Core Pipeline Program List

Schedule 1.2.159		Option Product Core Technology Patents

Schedule 1.2.162		Option Product-Specific Patents

Schedule 1.2.178		Potential Alnylam In-Licenses

Schedule 2.1.3.3		Exempted Third Party CNS Agreements

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Schedule 6.1		ALN-TTR02 Supply Agreement Terms

Schedule 6.2		Supply Agreement Terms

Schedule 7.3		Press Release

Schedule 8.2		Disclosure Schedule

Schedule 10.2		Identified Patent Rights

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APPENDICES


Appendix A		Regional License Terms

Appendix B		Global License Terms

Appendix C		Co-Co License Terms

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MASTER COLLABORATION AGREEMENT

THIS MASTER COLLABORATION AGREEMENT (this “ Master Agreement ”), entered into as of January 11, 2014 (the “ Execution Date ”), is entered into by and between Alnylam Pharmaceuticals, Inc., a corporation organized and existing under the laws of the State of Delaware (“ Alnylam ”), and, Genzyme Corporation, a corporation organized and existing under the laws of the Commonwealth of Massachusetts (“ Genzyme ”).

RECITALS:

WHEREAS , Alnylam, among other things, conducts programs to discover, to characterize and to develop siRNAs targeting human genes;

WHEREAS , the Parties have entered into that certain License and Collaboration Agreement dated as of October 18, 2012 (the “ Historical TTR Agreement ”) pursuant to which Alnylam granted Genzyme certain exclusive licenses and other rights with respect to the siRNAs known as ALN-TTR02 and ALN-TTRsc (and certain back-up and improvement products) in certain Asian countries;

WHEREAS , Alnylam and Genzyme desire to enter into the transactions contemplated by this Master Agreement, which will supersede and replace the Historical TTR Agreement and under which, among other things, (1) Genzyme shall have certain exclusive licenses and other rights with respect to ALN-TTR02 and ALN-TTRsc, including the exclusive right to Develop and Commercialize ALN-TTR02 and ALN-TTRsc on a regional basis outside North America and western Europe and the further right to co-Commercialize ALN-TTRsc with Alnylam in North America and western Europe, and (2) Genzyme shall have certain Options to obtain from Alnylam exclusive licenses and other rights to certain of Alnylam’s other siRNAs targeting human genes as potential treatments for Orphan Diseases (a) on a regional basis outside North America and western Europe, (b) with respect to certain siRNAs, on a global basis, or (c) with respect to a certain other siRNA on a regional basis outside North America and western Europe with the right to co-Commercialize such siRNA in North America and western Europe, in each case on terms and conditions set forth in this Master Agreement and the License Terms attached to this Master Agreement as Appendix A (Regional License Terms), Appendix B (Global License Terms) and Appendix C (Co-Co License Terms);

WHEREAS , Alnylam and Genzyme desire to enter into exclusive discussions and negotiations to potentially enter into an agreement under which the Parties would collaborate to advance new technology for the delivery of siRNA to the CNS with the objective of enabling the discovery of siRNAs for the treatment of CNS disorders, and Genzyme would obtain certain rights to the technology and products discovered in such collaboration;

WHEREAS , as partial consideration for Alnylam’s grant of the Options, licenses and other rights to Genzyme under the Collaboration Agreement, Genzyme desires to subscribe for and purchase from Alnylam, and Alnylam desires to issue and sell to Genzyme, certain shares of Common Stock pursuant to the terms and subject to the conditions set forth in the Stock Purchase Agreement; and

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WHEREAS , a more detailed overview of the transactions contemplated by this Master Agreement is set forth in Section 1.1 (Overview of Transactions) below.

NOW, THEREFORE , in consideration of the foregoing premises and the mutual covenants herein contained, the Parties hereby agree as follows:

1. OVERVIEW; DEFINITIONS

1.1. Overview of Transactions . This Master Agreement is part of the Collaboration Agreement between Genzyme and Alnylam under which the Parties are Developing and Commercializing ALN-TTR02 and ALN-TTRsc and under which Alnylam has granted Genzyme various Options to obtain licenses to Develop and Commercialize siRNAs generated by Alnylam’s Core Pipeline Programs, subject to the terms and conditions of this Master Agreement. As of the Effective Date, the Collaboration Agreement shall supersede and replace the Historical TTR Agreement pursuant to which Alnylam granted Genzyme certain exclusive licenses and other rights with respect to ALN-TTR02 and ALN-TTRsc in certain Asian countries. The Collaboration Agreement consists of: (a) this Master Agreement; (b) the Regional License Terms, which are attached to this Master Agreement as Appendix A ; (c) the Co-Co License Terms, which are attached to this Master Agreement as Appendix B ; (d) the Global License Terms, which are attached to this Master Agreement as Appendix C ; and (e) the schedules and exhibits attached to each of the foregoing. As of the Effective Date, ALN-TTR02 shall be a Regional Licensed Product and, as such, shall be governed by this Master Agreement and the Regional License Terms. As of the Effective Date, ALN-TTRsc shall be a Co-Co Licensed Product and, as such, shall be governed by this Master Agreement and the Co-Co License Terms.

This Master Agreement includes, among other things, the terms of the various Options granted to Genzyme ( i.e. , the Regional Option, the 2019 Trailing Regional Option, the 2021 Trailing Regional Option, the Co-Co/Global Option, the Global Option, the Additional Global Option and the Trailing Global Option), and the process for exercising such Options. The Master Agreement sets forth, among other things, the Parties’ obligations to one another with respect to the Core Pipeline Programs during the period when Genzyme may exercise such Options.

This Master Agreement also contains certain terms and conditions that are applicable to all of the “Collaboration Products” ( i.e. , siRNAs with respect to which Genzyme exercises one of its Options) after Genzyme exercises an Option with respect to any such Collaboration Product. For example, the Master Agreement describes portions of the overall governance structure for the Collaboration and also includes manufacture and supply terms, payment terms, confidentiality and publication provisions, indemnification, limitations of liability, insurance requirements, provisions regarding intellectual property and in-licenses, and miscellaneous provisions that are applicable to the Collaboration Products, subject to the terms and conditions of this Master Agreement and the applicable License Terms.

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Following Genzyme’s exercise of an Option for an siRNA generated by an Alnylam Core Pipeline Program (or, with respect to ALN-TTR02 and ALN-TTRsc, following the Effective Date of the Collaboration Agreement), the Development and Commercialization of the applicable siRNA will be governed by this Master Agreement and one of the 3 Appendices attached to the Master Agreement as follows:

(1) The Regional License Terms will govern the Parties’ joint Development and Commercialization of ALN-TTR02 and any siRNA for which Genzyme exercises a Regional Option, including the 2019 Trailing Regional Option or a 2021 Trailing Regional Option. Any such siRNA is referred to as a “Regional Licensed Product.” Under the Regional License Terms, Genzyme shall acquire a license to Develop and Commercialize Regional Licensed Products in only the Genzyme Territory.

(2) The Co-Co License Terms will govern the Parties’ joint Development and Commercialization of ALN-TTRsc, and will also govern the Parties’ joint Development and Commercialization of ALN-AT3 if Genzyme exercises the Co-Co/Global Option to acquire a license to Develop and Commercialize ALN-AT3 in the Genzyme Territory and to co-Commercialize ALN-AT3 in the Alnylam Territory. Each such siRNA is referred to as a “Co-Co Licensed Product.” Subject to the specific terms in this Master Agreement and to the Co-Co License Terms, the Co-Co License Terms are largely identical to the Regional License Terms with respect to the Genzyme Territory, but provide for additional terms governing the co-Commercialization of Co-Co Licensed Products in the Alnylam Territory.

(3) The Global License Terms will govern Genzyme’s Development and Commercialization of ALN-AS1 if Genzyme exercises the Co-Co/Global Option for ALN-AS1, and any siRNA for which Genzyme exercises the Global Option, the Additional Global Option or the Trailing Global Option. Each such siRNA is referred to as a “Global Licensed Product.” Under the Global License Terms, Genzyme shall acquire the exclusive right to Develop and Commercialize Global Licensed Products worldwide.

Unlike the Master Agreement, which contains terms that apply to all Collaboration Products, the License Terms include only terms that apply to the specific type of Collaboration Product to which the License Terms relate, such as economic terms, license grants, product-specific governance provisions, Development and Commercialization provisions, intellectual property provisions, and provisions relating to term and termination, including termination on a product-by-product basis, in each case subject to the specific terms of the License Terms.

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1.2. Definitions .

Unless specifically set forth to the contrary herein, the following terms, whether used in the singular or plural, shall have the respective meanings set forth below:

1.2.1. “2019 Trailing Regional Option ” has the meaning set forth in Section 3.2.1.2 (2019 Trailing Regional Option Grant).

1.2.2. “2021 Trailing Regional Option” has the meaning set forth in Section 3.2.1.3 (2021 Trailing Regional Option Grant).

1.2.3. “Acquirer” has the meaning set forth in Section 13.16.2 (Future Acquisition of a Party or its Business).

1.2.4. “Action” has the meaning set forth in Section 13.3 (Jurisdiction).

1.2.5. “Active Alnylam Program” means an Alnylam Program that has generated an siRNA (i) that achieved Clinical Success, (ii) that was administered to a patient in a Phase III Study, (iii) for which Development activities have not been terminated and (iv) in which Alnylam has retained commercial rights anywhere in the world.

1.2.6. “Additional Global Option” has the meaning set forth in Section 3.2.3.2 (Additional Global Option Grant).

1.2.7. “Additional Alnylam In-Licenses” means (a) with respect to ALN-TTR02, ALN-TTRsc and each Co-Co/Global Option Product, the Third Party agreements set forth on Schedule 1.2.7 ; and (b) with respect to each Option Product, the additional Third Party agreements that are identified in the applicable Option Data Package as “Additional Alnylam In-Licenses” for such Option Product (which, for clarity, shall include any of the Third Party agreements described in clause (a) if the Patent Rights licensed to Alnylam under such agreements, if issued, could be infringed by the Development, Manufacture or Commercialization of such Option Product in the Genzyme Territory).

1.2.8. “AF11 Lipid Nanoparticle Formulation” [***].

1.2.9. “Affiliate” means, with respect to a Person, any other Person which controls, is controlled by, or is under common control with the applicable Person. For purposes of this definition, “control” shall mean: (a) in the case of corporate entities, direct or indirect ownership of at least fifty percent (50%) of the stock or shares entitled to vote for the election of directors, or otherwise having the power to control or direct the affairs of such Person; and (b) in the case of non-corporate entities, direct or indirect ownership of at least fifty percent (50%) of the equity interest or the power to direct the management and policies of such non-corporate entities.

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1.2.10. “ALAS-1” means the human ALAS-1 gene (also known as ALAS, ALAS3, ALASH, aminolevulinate delta-synthase, Delta-ALA synthase, Delta-Aminolevulinate synthase 1, 5-aminolevulinic acid synthase 1, ALAS-H, 5-aminolevulinate synthase, MIG4, aminolevulinate synthase-1). As of the Execution Date, an example of an identifier for the ALAS-1 gene is NCBI RefSeq code NM_000688 and an example of an identifier for the ALAS-1 protein product is NCBI RefSeq code NP_000679.

1.2.11. “Alliance Joint Steering Committee” or “ AJSC ” means the Alliance Joint Steering Committee as more fully described in Section 5.1(Alliance Joint Steering Committee).

1.2.12. “Alliance Manager” has the meaning set forth in Section 5.1.3 (Alliance Managers).

1.2.13. “Alnylam Indemnitees” has the meaning set forth in Section 10.1 (General Indemnification by Genzyme).

1.2.14. “Alnylam In-Licenses” means any Existing Alnylam In-License or any Collaboration In-License to which Alnylam is a party.

1.2.15. “Alnylam Manufacturing Know-How” means any Know-How related to the Manufacture of Option Products or Collaboration Products (or oligonucleotides generally) Controlled by Alnylam at any time during the Term, to the extent such Know-How is disclosed or made available to Genzyme by or on behalf of Alnylam.

1.2.16. “Alnylam Program” means any Development program conducted by Alnylam or, subject to Section 13.16.2 (Future Acquisition of a Party or its Business), any of its Related Parties to Develop an siRNA targeting a human gene.

1.2.17. “Alnylam Supply Agreements” means the ALN-TTR02 Clinical Supply Agreement, the ALN-TTR02 Commercial Supply Agreement, each Clinical Supply Agreement and each Commercial Supply Agreement.

1.2.18. “Alnylam Territory” means with respect to any Regional Licensed Product or Co-Co Licensed Product, the countries of the United States, Canada, Austria, Belgium, Denmark, Finland, France, Germany, Greece, Ireland, Italy, Luxembourg, the Netherlands, Portugal, Spain, Sweden, the United Kingdom, Norway, Switzerland, Liechtenstein, Andorra, Iceland and Greenland.

1.2.19. “Alnylam Territory MMC” means [***].

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1.2.20. “ALN-AS1” means (i) the first siRNA that targets ALAS-1 that is generated by a Core Pipeline Program that achieves Human POP Study Completion or (ii) if the siRNA described in clause (i) fails to achieve Clinical Success, the next siRNA that is generated by a Core Pipeline Program and that targets ALAS-1.

1.2.21. “ALN-AT3” means (i) an siRNA Controlled by Alnylam, comprising the siRNA (#ALN-[***]) conjugated to a GalNAc Conjugate, as further described on Schedule 1.2.21 or (ii) if the siRNA described in clause (i) fails to achieve Clinical Success, the next siRNA that is generated by a Core Pipeline Program and that targets Antithrombin.

1.2.22. “ALN-TTR Core Technology Patents” means the Alnylam Core Technology Patents for ALN-TTR02 and the Alnylam Core Technology Patents for ALN-TTRsc. The TTR Core Technology Patents existing as of the Execution Date are those Patent Rights identified on Schedule 1.2.22 .

1.2.23. “ALN-TTR Patents” means the Alnylam Patents for ALN-TTR02 and the Alnylam Patents for ALN-TTRsc.

1.2.24. “ALN-TTR Product-Specific Patents” means the Alnylam Product-Specific Patents for ALN-TTR02 and the Alnylam Product-Specific Patents for ALN-TTRsc. The TTR Product-Specific Patents existing as of the Execution Date are those Patent Rights identified on Schedule 1.2.24 .

1.2.25. “ALN-TTR Technology” means the Alnylam Technology for ALN-TTR02 and the Alnylam Technology for ALN-TTRsc.

1.2.26. “ALN-TTR02” means an siRNA Controlled by Alnylam, comprising the siRNA (#AD[***]) formulated in an AF11 Lipid Nanoparticle Formulation, as further described on Schedule 1.2.26 .

1.2.27. “ALN-TTR Clinical Supply Agreement” has the meaning set forth in Section 6.1 (ALN-TTR02 Supply Agreements).

1.2.28. “ALN-TTR Commercial Supply Agreement” has the meaning set forth in Section 6.1 (ALN-TTR02 Supply Agreements).

1.2.29. “ALN-TTRsc” means an siRNA Controlled by Alnylam, comprising the siRNA (#AD[***]) conjugated to a Ga1NAc Conjugate, as further described on Schedule 1.2.29 . For the sake of clarity (but not for purposes of interpretation of the Collaboration Agreement), even though ALN-TTRsc will be a Co-Co Licensed Product that is subject to the Co-Co License Terms as of the Effective Date, ALN-TTRsc will be exclusively licensed to Genzyme in the Genzyme Territory in much the same way that ALN-TTR02 will be exclusively licensed to Genzyme in the Genzyme Territory under the Regional License Terms.

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1.2.30. “Antithrombin” means the human antithrombin gene and its protein product, antithrombin (also known as SERPINC1, antithrombin3, AT3 and ATIII). As of the Execution Date, an example of an identifier for the antithrombin gene is NCBI RefSeq code NM_000488 and an example of an identifier for the antithrombin protein product is NCBI RefSeq code NP_000479.

1.2.31. “Antitrust Laws” means any federal, state or foreign law, regulation or decree, including the HSR Act, designed to prohibit, restrict or regulate actions for the purpose or effect of monopolization or restraint of trade.

1.2.32. “Available Third Party Right” has the meaning set forth in Section 3.6.3 (ROFN for Available Third Party Rights).

1.2.33. “Back-Up Source” has the meaning set forth in Section 6.6 (Obligation to Establish).

1.2.34. [***].

1.2.35. “Blocking Patent Right” means a Patent Right Controlled by a Third Party that Covers a Collaboration Product.

1.2.36. “Bulk Drug Product” has the meaning set forth in Schedule 6.1 or Schedule 6.2 , as applicable.

1.2.37. “Bulk Drug Substance” has the meaning set forth in Schedule 6.1 or Schedule 6.2 , as applicable.

1.2.38. “Calendar Quarter” means the respective periods of three (3) consecutive calendar months ending on March 31, June 30, September 30 and December 31 of each calendar year.

1.2.39. “Carbohydrate Conjugate” means a carbohydrate ligand covalently linked to the 3’ end of the sense strand of an siRNA via a linker.

1.2.40. “cGMP” or “current Good Manufacturing Practices” means the then-current standards for manufacturing activities for pharmaceuticals, as set forth in the United States Federal Food, Drug, and Cosmetic Act, as amended, and applicable regulations promulgated thereunder, as amended from time to time, and such standards of good manufacturing practice as are required by other Governmental Authorities in countries in which Option Products or Collaboration Products are intended to be manufactured or sold.

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1.2.41. “Clinical Study” means a Phase I Study, Phase II Study, Phase III Study, Post-Marketing Study, Secondary Indication Study or other study (including a non-interventional study) in humans to obtain information regarding the product, including information relating to the safety, tolerability, pharmacological activity, pharmacokinetics, dose ranging or efficacy of the product.

1.2.42. “Clinical Success” means [***].

1.2.43. “Clinical Supply Agreement” has the meaning set forth in Section 6.2 (Collaboration Product Supply Agreements).

1.2.44. “CNS” has the meaning set forth in Section 2.1.3.1 (CNS Exploration Period).

1.2.45. “CNS Collaboration and License Agreement” has the meaning set forth in Section 2.1.3.1 (CNS Exploration Period).

1.2.46. “CNS Exploration Period” has the meaning set forth in Section 2.1.3.1 (CNS Exploration Period).

1.2.47. “CNS ROFN Exercise Notice” has the meaning set forth in Section 2.1.3.4 (ROFN for CNS).

1.2.48. “CNS ROFN Negotiation Period” has the meaning set forth in Section 2.1.3.4 (ROFN for CNS).

1.2.49. “CNS ROFN Non-Binding Offer” has the meaning set forth in Section 2.1.3.4 (ROFN for CNS).

1.2.50. “CNS ROFN Offer Period” has the meaning set forth in Section 2.1.3.4 (ROFN for CNS).

1.2.51. “CNS ROFN Period” has the meaning set forth in Section 2.1.3.4 (ROFN for CNS).

1.2.52. “Co-Co License Terms” means the Co-Commercialization License and Collaboration Terms attached hereto as Appendix C , under which (i) Alnylam and Genzyme shall amend, restate and supersede the Historical TTR Agreement in respect of ALN-TTRsc effective as of the Effective Date, and (ii) Alnylam may grant Genzyme a license to ALN-AT3 effective as of the applicable Option Exercise Date. For the sake of clarity (but not for purposes of interpretation of the Collaboration Agreement), each Co-Co Licensed Product that becomes subject to the Co-Co License Terms will be exclusively licensed to Genzyme in the Genzyme Territory in much the same way that each Regional Licensed Product will be exclusively licensed to Genzyme in the Genzyme

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Territory under the Regional License Terms, and will be licensed to Genzyme in the Alnylam Territory to the extent necessary to enable Genzyme to co-Commercialize such Co-Co Licensed Product in the Alnylam Territory as contemplated by the Co-Co License Terms.

1.2.53. “Co-Co Licensed Product” means (i) ALN-TTRsc as of the Effective Date and (ii) if Genzyme exercises the Co-Co/Global Option for ALN-AT3, then ALN-AT3 as of the applicable Option Exercise Date, in each case, for as long as the Co-Co License Terms apply to ALN-TTRsc or ALN-AT3. For the sake of clarity (but not for purposes of interpretation of the Collaboration Agreement), each Co-Co Licensed Product that becomes subject to the Co-Co License Terms will be exclusively licensed to Genzyme in the Genzyme Territory in much the same way that each Regional Licensed Product will be exclusively licensed to Genzyme in the Genzyme Territory under the Regional License Terms, and will be licensed to Genzyme in the Alnylam Territory to the extent necessary to enable Genzyme to co-Commercialize such Co-Co Licensed Product in the Alnylam Territory as contemplated by the Co-Co License Terms.

1.2.54. “Co-Co/Global Option” has the meaning set forth in Section 3.2.2 (Co-Co/Global Option Grant).

1.2.55. “Co-Co/Global Option Product” means either (i) ALN-AT3 or (ii) ALN-AS1.

1.2.56. “Co-Co/Global Option Trigger Notice” has the meaning set forth in Section 3.2.2.4 (Discontinuation of Second Co-Co/Global Option Product).

1.2.57. “Collaboration” means the collaboration of the Parties under the Collaboration Agreement.

1.2.58. “Collaboration Agreement” means this Master Agreement and each of the License Terms.

1.2.59. “Collaboration In-License” has the meaning set forth in Section 11.3.3.1 (Proposed In-Licenses).

1.2.60. “ Collaboration Product ” means any Regional Licensed Product, Co-Co Licensed Product or Global Licensed Product, after exercise of the applicable Option by Genzyme and the occurrence of the applicable Option Exercise Date and effectiveness of the applicable License Terms, following which any such Option Product shall cease to be an Option Product.

1.2.61. “Collaboration Product-Specific Payment” has the meaning set forth in Section 11.3.4.2 (Collaboration In-Licenses).

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1.2.62. “Commercial Indication” means [***].

1.2.63. “Commercial Supply Agreement” has the meaning set forth in Section 6.2 (Collaboration Product Supply Agreements).

1.2.64. “Commercialization” or “Commercialize” means any and all activities directed to marketing, promoting, distributing, importing, exporting, using, offering to sell and/or selling a product, and activities directed to obtaining pricing and reimbursement approvals, as applicable.

1.2.65. “Commercialization Plan” means (i) with respect a Regional Licensed Product, the Alnylam Territory Commercialization Plan and the Genzyme Territory Commercialization Plan, as such terms are defined under the Regional License Terms, and (ii) with respect to a Co-Co Licensed Product, the Co-Co Territory Commercialization Plan and the Genzyme Territory Commercialization Plan, as such terms are defined under the Co-Co License Terms.

1.2.66. “Common Stock” means shares of common stock, par value $.01 per share, of Alnylam.

1.2.67. “Confidential Information” means any and all confidential or proprietary information and data (including Option Product Technology, ALN-TTR Technology, Alnylam Technology (as defined in the License Terms), Genzyme Technology (as defined in the License Terms), Genzyme Manufacturing IP and Genzyme Disclosed Manufacturing Know-How (each as defined in the License Terms), Alnylam Manufacturing Know-How and Joint Collaboration IP (as defined in the License Terms)) and all other scientific, pre-clinical, clinical, regulatory, manufacturing, marketing, financial and commercial information or data, whether communicated in writing or orally or by any other method, which is or has been provided by one Party to the other Party in connection with the Collaboration Agreement, Stock Purchase Agreement, Investor Agreement or the Historical TTR Agreement. Option Product Technology, Alnylam Manufacturing Know-How and Alnylam Technology are the Confidential Information of Alnylam. Genzyme Technology, Genzyme Manufacturing IP and Genzyme Disclosed Manufacturing Know-How are the Confidential Information of Genzyme. Joint Collaboration IP and the terms of the Collaboration Agreement, Stock Purchase Agreement, Investor Agreement and the Historical TTR Agreement are the Confidential Information of both Parties, subject to Section 7.1 (Nondisclosure Obligation).

1.2.68. “Control”, “Controls ” or “Controlled by ” means, with respect to any Know-How, Patent Rights or other intellectual property right, the possession of (whether by ownership or license, other than pursuant to the Collaboration Agreement), the ability of a Person or its Affiliates to assign, transfer, or grant access to, or to grant a license or sublicense of, such item or right as provided for herein without violating the terms of any

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agreement or other arrangement with any Third Party existing at the time such Person would be required hereunder to assign, transfer or grant another Person such access or license or sublicense, provided that with respect to rights to any Third Party Know-How, Patent Rights or other intellectual property right that are licensed to, or otherwise obtained by, a Party pursuant to an agreement entered into by such Party, such Third Party Know-How, Patent Rights or other intellectual property right shall be deemed not to be under the Control of such Party unless the agreement pursuant to which such rights are obtained is an In-License.

1.2.69. “Core Pipeline Dispute” has the meaning set forth in Section 5.1.8.2 (Escalation).

1.2.70. “Core Pipeline Program” means an Alnylam Program, existing as of the Execution Date or initiated thereafter during the Option Period, to Develop an siRNA targeting a human gene, where [***]. Core Pipeline Programs include as of the Execution Date, without limitation, the Alnylam Programs identified on the Core Pipeline Program List.

1.2.71. “Core Pipeline Program List” means the non-limiting list of Core Pipeline Programs, attached hereto as Schedule 1.2.71 , as the same may be updated from time to time in accordance with Section 3.1.1 (Program Identification). The Core Pipeline Programs as of the Execution Date are listed on Schedule 1.2.71 .

1.2.72. “Cost of Goods” means, with respect to the supply of a Product: (a) where Alnylam or its Affiliates Manufacture such Product, the reasonable internal and external costs incurred by Alnylam and its Affiliates in Manufacturing such Product, including the fully allocated cost of Manufacture of such Product, consisting of direct material and direct labor costs (including direct material and labor costs incurred for facility start-up), plus overhead directly attributable to the Manufacture of such Product (including all directly incurred Manufacturing variances and a reasonable allocation of related Manufacturing administrative, facilities operations and facilities depreciation costs for such Product, but in all cases excluding corporate administrative overhead and/or costs associated with excess capacity), all calculated strictly in accordance with GAAP, and (b) where such Product is Manufactured by a Third Party manufacturer, the actual fees paid by Alnylam to the Third Party for the Manufacture and supply of such Product. Any CMC costs that can be classified under Costs of Goods pursuant to GAAP will be classified as such for the purposes of calculation of R&D Costs (as defined in the License Terms).

1.2.73. “Cover,” “Covering” or “Covers” means, as to a product and Patent Rights, that, in the absence of a license granted under, or ownership of, such Patent Rights, the manufacture, use, offer for sale, sale or importation of such product would infringe such Patent Rights or, as to a pending claim included in such Patent Rights, the manufacture, use, offer for sale, sale or importation of such product would infringe such Patent Rights if such pending claim were to issue in an issued patent.

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1.2.74. “CRO” means a contract research organization.

1.2.75. “Development,” “Developing” or “Develop” means under the Collaboration Agreement, with respect to Option Products, Collaboration Products and other siRNA, the research and development activities related to the generation, characterization, optimization, construction, use and production of Option Products, Collaboration Products or other siRNA, any other non-clinical, pre-clinical or clinical research and development activities related to the testing and qualification of Option Products, Collaboration Products or other siRNA, as applicable, including toxicology studies, statistical analysis and report writing, pre-clinical testing, formulation development, CMC activities, Clinical Studies, regulatory affairs and registration activities, and all other activities necessary to prepare and file applications for Regulatory Approval and to seek, obtain and maintain Regulatory Approval.

1.2.76. “Development Plan” means (i) with respect a Regional Licensed Product, the Global Development Plan, Alnylam Territory Development Plan and the Genzyme Territory Development Plan, as such terms are defined under the Regional License Terms, and (ii) with respect to a Co-Co Licensed Product, the Global Development Plan and the Genzyme Territory Development Plan, as such terms are defined under the Co-Co License Terms.

1.2.77. “DOJ” means the U.S. Department of Justice.

1.2.78. “Effective Date” has the meaning set forth in Section 2.1.1 (Effectiveness of Collaboration Agreement).

1.2.79 . “ EMA ” means the European Medicines Agency and any successor Governmental Authority having substantially the same function.

1.2.80. “ Exercise Notice ” means the written notice Genzyme delivers to Alnylam to exercise an Option with respect to an Option Product, in the form set forth on Schedule 1.2.80 , containing the information set forth in such form.

1.2.81. “ Existing Core Option Products ” means the Option Products of the following Core Pipeline Programs existing as of the Execution Date and listed on the following referenced Schedule as of the Execution Date: (i) the Named Pipeline Programs listed on Schedule 1.2.146 , (ii) the Core Pipeline Programs on the Locked Core Pipeline Program List set forth on Schedule 1.2.134 , and (iii) the Core Pipeline Programs listed in Section A (but not Section B) of Schedule 1.2.71 .

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1.2.82. “ Existing Alnylam In-Licenses ” means (a) with respect to ALN-TTR02, ALN-TTRsc and any Co-Co/Global Option Product for which Genzyme exercises an Option, the Third Party agreements set forth on Schedule 1.2.82 as of the Execution Date; (b) with respect to each Option Product, additional Third Party agreements that are identified in the applicable Option Data Package as “Existing Alnylam In-Licenses” for such Option Product (which, for clarity, shall include any of the Third Party agreements described in clause (a) if the Patent Rights and Know-How licensed to Alnylam under such agreements are necessary or useful for the Development, Manufacture or Commercialization of such Option Product in the Genzyme Territory); and (c) any Additional Alnylam In-License which is deemed to be an Existing Alnylam In-License pursuant to Section 11.3.1 (Additional Alnylam In-Licenses), in each case ((a), (b) and (c)) as such agreement may be amended or supplemented from time-to-time.

1.2.83. “ Existing Genzyme In-License ” means, with respect to a Collaboration Product, any agreement between Genzyme and a Third Party entered into on or prior to the Option Exercise Date for such Collaboration Product pursuant to which Genzyme Controls Know-How or Patent Rights that are necessary or useful to Develop, Manufacture or Commercialize such Collaboration Product in the Field under the applicable License Terms.

1.2.84. “ Execution Date ” has the meaning set forth in the preamble.

1.2.85. “ Expert ” has the meaning set forth in Section 5.1.8.3 (Resolution of Core Pipeline Disputes).

1.2.86. “ FDA ” means the United States Food and Drug Administration and any successor Governmental Authority having substantially the same function.

1.2.87. “ Field ” means the treatment, diagnosis or prevention of all human diseases.

1.2.88. “ Final Option Data Package ” means, with respect to an Option Product:

(a)

[***].

(b)

[***].

1.2.89. “ Finished Product ” has the meaning set forth in Schedule 6.1 or Schedule 6.2 , as applicable.

1.2.90. “ First Co-Co/Global Option Product ” has the meaning set forth in Section 3.2.2.1 (First Co-Co/Global Option Product).

1.2.91. “ FTC ” means the U.S. Federal Trade Commission.

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1.2.92. “ GAAP ” means generally accepted accounting principles as practiced in the United States or IFRS (International Financial Reporting Standards), in each case, consistently applied.

1.2.93. “ GalNAc Conjugate ” means a triantennary N-acetylgalactosamine ligand (GalNAc3) covalently linked to the 3’ end of the sense strand of the siRNA via a linker.

1.2.94. “ Genzyme Indemnitees ” has the meaning set forth in Section 10.2 (General Indemnification by Alnylam).

1.2.95. “ Genzyme Disclosed Manufacturing Know-How ” means Know-How (a) Controlled by Genzyme at any time during the Term that is useful in the Manufacture of a Regional Licensed Product and (b) that Genzyme, in its sole discretion, discloses in writing to Alnylam in the course of the Collaboration.

1.2.96. “ Genzyme In-Licenses ” means any Existing Genzyme In-License or any Collaboration In-License to which Genzyme is a party.

1.2.97. “ Genzyme Patent Jurisdictions ” means [***].

1.2.98. “ Genzyme Supply Agreement ” has the meaning set forth in Section 6.6.2.1(Qualification).

1.2.99. “ Genzyme Territory ” means (i) with respect to any Regional Licensed Product or Co-Co Licensed Product, all countries and territories of the world other than the Alnylam Territory and (ii) with respect to any Global Licensed Product, worldwide.

1.2.100. “ Genzyme Territory MMC ” means [***].

1.2.101. “ Global Development Plan ” has the meaning set forth in the applicable License Terms.

1.2.102. “ Global Development Strategy ” has the meaning set forth in the applicable License Terms.

1.2.103. “ Global/Additional Global Option Forfeiture ” has the meaning set forth in Section 3.4.2.2 (Exercise of Preserved Option).

1.2.104. “ Global License Terms ” means the Global Product License and Collaboration Terms attached hereto as Appendix B , under which Alnylam may grant Genzyme a license to (i) ALN-AS1 and/or (ii) a Global Option Product, in each case with such license to be effective as of the applicable Option Exercise Date.

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1.2.105. “ Global Licensed Product ” means (i) if Genzyme exercises the Co-Co/Global Option for ALN-AS1, then ALN-AS1 as of the applicable Option Exercise Date, and (ii) if Genzyme exercises the Global Option for any Global Option Product, then such Global Option Product as of the applicable Option Exercise Date, in each case for as long as the Global License Terms apply to such Co-Co/Global Option Product or such Global Option Product.

1.2.106. “ Global Option ” has the meaning set forth in Section 3.2.3.1 (Global Option Grant).

1.2.107. “ Global Option Outside Date ” means [***].

1.2.108. “ Global Option Period ” means the period beginning on the Effective Date and ending on the earlier of (i) the occurrence of the Option Exercise Date for the exercise of the Global Option and, if exercisable, the Additional Global Option and (ii) the Global Option Outside Date.

1.2.109. “ Global Option Product ” means any siRNA targeting a human gene that is generated by a Core Pipeline Program, where such Core Pipeline Program is not a Named Pipeline Program.

1.2.110. “ Global R&D Costs ” has the meaning ascribed thereto in each of the applicable License Terms.

1.2.111. “ Global Regulatory Costs ” has the meaning ascribed thereto in the Co-Co License Terms.

1.2.112. “ GLP ” or “Good Laboratory Practices” means, with respect to a particular Development activity or non-clinical study conducted by a Party, that such Development activity or non-clinical study (i) was conducted in accordance with “good laboratory practices” as set forth in 21 C.F.R. Part 58, the United States Animal Welfare Act, the International Conference on Harmonization’s (“ ICH ”) Guideline on Nonclinical Safety Studies for the Conduct of Human Clinical Trials for Pharmaceuticals or the ICH Guideline on Safety Pharmacology Studies for Human Pharmaceuticals or (ii) involved experimental research techniques that were performed for informational purposes only (whether or not included in a regulatory filing) or could not be performed by a GLP-compliant testing facility (with appropriate notice being given to the FDA in regulatory filings), and such Party employed the procedures and controls generally used by qualified experts in animal or preclinical studies of products comparable to those being developed by such Party.

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1.2.113. “ Governmental Authority ” means any applicable government authority, court, tribunal, arbitrator, agency, department, legislative body, commission or other instrumentality of (a) any government of any country or territory, (b) any nation, state, province, county, city or other political subdivision thereof or (c) any supranational body.

1.2.114. “ Historical TTR Agreement ” has the meaning set forth in the recitals.

1.2.115. “ HSR Act ” means the Hart-Scott-Rodino Antitrust Improvements Act of 1976, as amended.

1.2.116. “ Human POP Study ” means [***].

1.2.117. “ Human POP Study Completion ” means, with respect to an Option Product or other siRNA, the [***] day [***].

1.2.118. “ IFRS ” means International Financial Reporting Standards, as consistently applied.

1.2.119. “ Implementation Date ,” with respect to a Collaboration Product, has the meaning set forth in the License Terms applicable to such Collaboration Product.

1.2.120. “ IND ” means an Investigational New Drug application, Clinical Trial Application or similar application or submission for approval to conduct human clinical investigations filed with or submitted to a Regulatory Authority in conformance with the requirement of such Regulatory Authority, and any amendments thereto.

1.2.121. “ Indemnitee ” has the meaning set forth in Section 10.4 (Indemnification Procedure).

1.2.122. “ Initial Evaluation Period ” means, with respect to Option Product, the [***] day period beginning on the date that Genzyme acknowledges receipt of an Initial Option Data Package, as such period may be extended pursuant to Section 3.3.4.3 (Extension of Initial Evaluation Period and Option Exercise Period).

1.2.123. “ Initial Option Data Package ” means, with respect to an Option Product, the information set forth on Schedule 1.2.123 .

1.2.124. “ Initial Option Notice ” has the meaning set forth in Section 3.3.1 (Initial Option Data Package).

1.2.125. “ In-Licenses ” means, collectively, all Existing Alnylam In-Licenses, all Existing Genzyme In-Licenses and all Collaboration In-Licenses.

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1.2.126. “ Investor Agreement ” means that certain Investor Agreement between Genzyme and Alnylam, executed as of the Effective Date, as the same may be amended from time to time.

1.2.127. “ IP Committee ” means the intellectual property advisory committee as more fully described in Section 5.3 (IP Committee).

1.2.128. “ Know-How ” means all chemical or biological materials and other tangible materials, inventions, improvements, practices, discoveries, developments, data, information, technology, methods, protocols, formulas, knowledge, know-how, trade secrets, processes, assays, skills, experience, techniques and results of experimentation and testing, including pharmacological, toxicological and pre-clinical and clinical data and analytical and quality control data; provided , however , excluding in any event any Patent Right and Trademarks.

1.2.129. “ KPIs ” has the meaning set forth in Section 6.3 (General Supply Agreement Requirements).

1.2.130. “ Laws ” means all applicable laws, statutes, rules, regulations, orders, judgments, injunctions, ordinances or other pronouncements having the binding effect of law of any Governmental Authority, including if either Party is or becomes subject to a legal obligation to a Regulatory Authority or other Governmental Authority (such as a corporate integrity agreement or settlement agreement with a Governmental Authority).

1.2.131. “ License Terms ” means the Regional License Terms, the Co-Co License Terms or the Global License Terms, as applicable.

1.2.132. “ Licensed Target ” means, for each Collaboration Product, the human gene that is targeted by such Collaboration Product.

1.2.133. “ Lipid Nanoparticle Formulation ” means a lipid-based nanoparticle comprising more than one lipid species designed to enable delivery of siRNAs to mammalian cells.

1.2.134 . “ Locked Core Pipeline Program List ” means the list of Core Pipeline Programs, as the same may be updated from time to time in accordance with Section 3.1.1 (Program Identification), identifying those Core Pipeline Programs that shall remain Core Pipeline Programs for all purposes under the Collaboration Agreement, except as the Parties, each acting in its sole discretion, may later mutually agree in writing. The Core Pipeline Programs that exist as of the Execution Date and shall be included on the Locked Core Pipeline Program List are identified on Schedule 1.2.134 .

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1.2.135. “ Locked Non-Core Pipeline Program List ” means the list of Non-Core Pipeline Programs, as the same may be updated from time to time in accordance with Section 3.1.1 (Program Identification), identifying those Non-Core Pipeline Programs that shall remain Non-Core Pipeline Programs for all purposes under the Collaboration Agreement, except as the Parties, each acting in its sole discretion, may later mutually agree in writing. The Non-Core Pipeline Programs that exist as of the Execution Date and shall be included on the Locked Non-Core Pipeline Program List are identified on Schedule 1.2.135 .

1.2.136. “ Losses ” has the meaning set forth in Section 10.1 (General Indemnification by Genzyme).

1.2.137. “ Manufacturing ” or “ Manufacture ” means, as applicable, all activities associated with the production, manufacture, process of formulating, processing, filling, finishing, packaging, labeling, shipping, importing and storage of Collaboration Products or Option Products (including Bulk Drug Product, Bulk Drug Substance and Finished Product) including process development, process validation, stability testing, manufacturing scale-up, pre-clinical, clinical and commercial manufacture and analytical development, product characterization, quality assurance and quality control development, testing and release.

1.2.138. “ Manufacturing Committee ” means the manufacturing advisory committee as more fully described in Section 5.4 (Manufacturing Committee).

1.2.139. “ Manufacturing FTE ” means [***] hours of work per annum devoted to or in support of the Development or Manufacture of a Collaboration Product that is carried out by one or more qualified scientific or technical employees of a Party or its Affiliates.

1.2.140. “ Manufacturing FTE Rate ” means [***] per Manufacturing FTE, increased annually beginning, for the first time, on January 1, 2015 and thereafter on January 1 of each succeeding year by the percentage increase in the CPI as of December 31 of the then most recently ended calendar year over the level of the CPI on December 31, 2013.

1.2.141. “ Merger Control Authorities ” means all relevant Governmental Authorities under applicable Antitrust Laws, including the FTC and DOJ.

1.2.142. “ MicroRNA ” or “ miRNA ” means a structurally defined functional RNA molecule usually between nineteen (19) and twenty-five (25) nucleotides in length, which is derived from an endogenous, genetically-encoded non-coding RNA which is predicted to be processed into a hairpin RNA structure that is a substrate for the double-stranded RNA-specific ribonuclease Drosha and subsequently is predicted to serve as a substrate for the enzyme Dicer, a member of the RNase III enzyme family.

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1.2.143. “MicroRNA Mimic ” means a single-stranded or double-stranded oligonucleotide with the same or substantially similar-base composition and sequence (including chemically modified bases) as a particular natural miRNA and which is designed to mimic the activity of such miRNA. For clarity, miRNA Mimic excludes a double-stranded oligonucleotide which functions or is designed to function as an siRNA.

1.2.144. “ Minimum Annual Investment ” means [***],

1.2.145. “ MMC ” means any Alnylam Territory MMC or Genzyme Territory MMC.

1.2.146. “ Named Pipeline Programs ” means those Alnylam Programs listed on Schedule 1.2.146 .

1.2.147. “ NDA ” means a New Drug Application, Biologics License Application, Marketing Authorization Application or similar application or submission filed with a Regulatory Authority in a country or group of countries to obtain Regulatory Approval to market a product in that country or in that group of countries, and any amendments thereto.

1.2.148. “ Negotiation Period ” has the meaning set forth in Section 6.6.2.2 (Negotiating Period).

1.2.149. “ New Information ” has the meaning set forth in Section 3.4.2.3 (Exercise of Preserved Option).

1.2.150. “ Non-Core Pipeline Program List ” means the non-limiting list of Non-Core Pipeline Programs, attached hereto as Schedule 1.2.149 , as the same may be updated from time to time by Alnylam in accordance with Section 3.1.1 (Program Identification). The Non-Core Pipeline Programs as of the Execution Date are listed on Schedule 1.2.149 .

1.2.151. “ Non-Sales-Based Payment ” means any Third Party License Payment that is not a Sales-Based Payment.

1.2.152. “ Option ” means any Regional Option, the Co-Co/Global Option, the Global Option, the Additional Global Option, the 2019 Trailing Regional Option, any 2021 Trailing Regional Option or any Trailing Global Option, as applicable.

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1.2.153. “ Option Data Package ” means, with respect to an Option Product, the Initial Option Data Package or, if applicable, the Final Option Data Package for such Option Product.

1.2.154. “ Option Exercise Date ” means the date on which an Exercise Notice is deemed to have been given by Genzyme to Alnylam pursuant to Section 13.11 (Notices) or such later date as may be required pursuant to Section 2.2.2 (Effectiveness of Licenses to Collaboration Products).

1.2.155. “ Option Exercise Period ” means:

(a) with respect to any Regional Option Product or ALN-AT3, the period [***];

(b) with respect to ALN-AS1 or any Global Option Product, the period [***]; or

(c) if Alnylam delivers a Co-Co/Global Option Trigger Notice under Section 3.2.2.4 (Discontinuation of Second Co-Co/Global Option Product) for the First Co-Co/Global Option Product, the [***] day period following Genzyme’s acknowledgement of receipt of such notice, as such period may be extended pursuant to 3.3.4.3 (Extension of Initial Evaluation Period and Option Exercise Period).

1.2.156. “ Option Period ” means the period beginning on the Effective Date and ending on the date that no Option remains exercisable.

1.2.157. “ Option Preservation Notice ” has the meaning set forth in Section 3.3.2 (Initial Evaluation Period).

1.2.158. “ Option Product ” means any Regional Option Product (including any Trailing Regional Option Product), Co-Co/Global Option Product or Global Option Product (including any Trailing Global Option Product).

1.2.159. “ Option Product Core Technology Patents ” means Patent Rights Controlled by Alnylam during the Option Period that are reasonably necessary or useful to Develop, Commercialize, and/or Manufacture Option Products, other than Option Product-Specific Patents. Option Product Core Technology Patents include Patent Rights Controlled by Alnylam that claim [***]. The Option Product Core Technology Patents existing as of the Execution Date, solely in respect of the Existing Core Option Products, are those Patent Rights identified on Schedule 1.2.159 .

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1.2.160. “ Option Product Know-How ” means Know-How Controlled by Alnylam during the Term that is reasonably necessary or useful for Genzyme to Develop, Manufacture and/or Commercialize Option Products in the Field.

1.2.161. “ Option Product Patents ” means Option Product Core Technology Patents and Option Product-Specific Patents.

1.2.162. “ Option Product-Specific Patents ” means Patent Rights Controlled by Alnylam during the Term that claim [***]. The Option Product-Specific Patents existing as of the Execution Date, solely in respect of the Existing Core Option Products, are those Patent Rights identified on Schedule 1.2.162 .

1.2.163. “ Option Product Technology ” means, collectively, Option Product Know-How and Option Product Patents.

1.2.164. “ Optioned Target ” means, for each Option Product, the human gene that is intended to be targeted by the Option Product.

1.2.165 . “ Orphan Disease ” means [***].

1.2.166. “ Out-of-Pocket Costs ” means, with respect to certain activities hereunder, direct expenses paid or payable by either Party or its Affiliates to Third Parties and specifically identifiable and incurred (and invoiced) to conduct such activities for an Option Product or a Collaboration Product, as applicable, including payments to contract personnel.

1.2.167. “ Party ” means Genzyme or Alnylam.

1.2.168. “ Patent Challenge ” has the meaning set forth in Section 12.2.4 (Challenges of Patent Rights).

1.2.169. “ Patent Rights ” means (a) all issued patents (including any extensions, restorations by any existing or future extension or registration mechanism (including patent term adjustments, patent term extensions, supplemental protection certificates or the equivalent thereof), substitutions, confirmations, re-registrations, re-examinations, and patents of addition); (b) patent applications (including all provisional applications, substitutions, requests for continuation, continuations, continuations-in-part, divisionals and renewals); (c) inventor’s certificates; and (d) all equivalents of the foregoing in any country of the world.

1.2.170. “ Paying Party ” has the meaning set forth in Section 9.6 (Taxes).

1.2.171. “ Permitted Third Party Agreement ” has the meaning set forth in Section 3.6.3 (ROFN for Available Third Party Rights).

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1.2.172. “ Person ” means any natural person, corporation, unincorporated organization, partnership, association, sole proprietorship, joint stock company, joint venture, limited liability company, trust or government, or Governmental Authority, or any other similar entity.

1.2.173. “ Phase I Study” means a study in humans which provides for the introduction into humans of a product, conducted in healthy volunteers or patients, to obtain initial information on product safety, tolerability, pharmacological activity or pharmacokinetics, as further defined in 21 C.F.R. § 312.21(a) (or the equivalent thereof outside the United States).

1.2.174. “ Phase II Study ” means a study in humans of the safety, dose ranging or efficacy of a product, as further defined in 21 C.F.R. § 312.21(b) (or the equivalent thereof outside the United States).

1.2.175. “ Phase III Study ” means a study in humans of the efficacy and safety of a product, which is prospectively designed to demonstrate statistically whether such product is effective and safe for use in a particular indication in a manner sufficient (alone or together with one or more other such studies) to file an application for Regulatory Approval for the product. For the avoidance of doubt, the Parties acknowledge that, because of the nature of the diseases which the Collaboration Products are anticipated to treat, a Phase III Study for a Collaboration Product may not include all of the elements that a Phase III Study for other kinds of drug products may include ( e.g. , a Phase III Study for a Collaboration Product may be a single study and there may be no prospective plan to run a second pivotal clinical trial independent of such Phase III Study).

1.2.176. “ Pipeline Advisory Committee ” or “PAC” means the pipeline advisory committee as more fully described in Section 5.2 (Pipeline Advisory Committee).

1.2.177. “ Post-Marketing Study ” means a non-human or human clinical study of a Collaboration Product initiated after receipt of Regulatory Approval for such Collaboration Product in a country or territory, that is required by the Regulatory Authority in such country or territory to maintain the Regulatory Approval for such Collaboration Product in such country or territory, but excluding any Secondary Indication Study.

1.2.178. “ Potential Alnylam In-Licenses ” means, with respect to ALN-TTR02, ALN-TTRsc and each Option Product, the potential future Third Party agreements described on Schedule 1.2.178 .

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1.2.179. “ Product ” means a given quantity of Collaboration Product in one of Bulk Drug Substance, Bulk Drug Product or Finished Product form.

1.2.180. “ Proposed CNS Terms ” has the meaning set forth in Section 2.1.3.4 (ROFN for CNS).

1.2.181. “ Proposed In-License ” has the meaning set forth in Section 11.3.3.1 (Proposed In-Licenses).

1.2.182. “ Proposed In-License Notice ” has the meaning set forth in Section 11.3.3.1 (Proposed In-Licenses).

1.2.183. “ Receiving Party ” has the meaning set forth in Section 9.6 (Taxes).

1.2.184. “ Regional License Terms ” means those certain Regional Product License and Collaboration Terms between Genzyme and Alnylam, in the form of Appendix A attached hereto, under which (i) Alnylam and Genzyme shall amend, restate and supersede the Historical TTR Agreement in respect of ALN-TTR02, effective as of the Effective Date, and (ii) Alnylam may grant Genzyme a license to one or more Regional Licensed Products, effective as of the applicable Option Exercise Date.

1.2.185. “ Regional Licensed Product ” means (i) ALN-TTR02 as of the Effective Date, and (ii) if Genzyme exercises a Regional Option for any Regional Option Product, then such Regional Option Product as of the applicable Option Exercise Date, in each case for as long as the Regional License Terms applies to ALN-TTR02 or any such Regional Option Product.

1.2.186. “ Regional Option ” has the meaning set forth in Section 3.2.1.1 (Regional Option Grants).

1.2.187. “ Regional Option Outside Date ” means [***].

1.2.188. “ Regional Option Period ” means the period beginning on the Effective Date and ending on the Regional Option Outside Date.

1.2.189. “ Regional Option Product ” means an siRNA that is generated by a Core Pipeline Program. For clarity, any such siRNA shall constitute a Regional Option Product even if any such Regional Option Product is also a Co-Co/Global Option Product or a Global Option Product.

1.2.190. “ Regulatory Approval ” means any and all approvals, licenses, registrations or authorizations of any Regulatory Authority that are necessary for the marketing and sale of a product in a country or group of countries.

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1.2.191. “ Regulatory Authority ” means any Governmental Authority involved in granting approvals for the Development, Manufacturing, Commercialization, reimbursement or pricing of Option Products or Collaboration Products, including the FDA, the EMA, the Japanese Ministry of Health, Labour and Welfare (“ MHLW ”) and the Pharmaceuticals and Medical Devices Agency in Japan (“ PMDA ”).

1.2.192. “ Regulatory Briefing Document ” has the meaning set forth in Section 3.3.3.1 (Final Option Data Package).

1.2.193. “ Related Party ” means a Party’s Affiliates and permitted Sublicensees (as defined in any of the License Terms).

1.2.194. “ Residual Knowledge ” means knowledge, techniques, experience and Know-How that (a) are, or are based on any Confidential Information of the disclosing Party and (b) are retained in the unaided memory of any authorized representative of the receiving Party after having access to such Confidential Information. An individual’s memory shall be considered to be unaided if the individual has not intentionally memorized the Confidential Information for the purpose of retaining and subsequently using or disclosing it. In no event, however, shall Residual Knowledge include (i) any Genzyme Disclosed Manufacturing Know-How, (ii) any Alnylam Manufacturing Know-How or (iii) any Know-How to the extent (at any time, for such time) it is within the scope of any issued, valid and enforceable Patent Right Controlled by the disclosing Party under any License Terms.

1.2.195. “ ROFN Exercise Notice ” has the meaning set forth in Section 3.6.3 (ROFN for Available Third Party Rights).

1.2.196. “ ROFN Negotiation Period ” has the meaning set forth in Section 3.6.3 (ROFN for Available Third Party Rights)

1.2.197. “ ROFN Non-Binding Offer ” has the meaning set forth in Section 3.6.3 (ROFN for Available Third Party Rights)

1.2.198. “ ROFN Offer Notice ” has the meaning set forth in Section 3.6.3 (ROFN for Available Third Party Rights)

1.2.199. “ Safety Concern ” means (a) any safety concern required to be reported under 21 C.F.R. § 312.32(c)(1)(iii) (“Findings from animal or in vitro testing”) if an IND with respect to such Option Product was open at the time of the observation or (b) a material toxicity or material drug safety issue or a Serious Adverse Event reasonably related to an Option Product.

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1.2.200. “ Sales-Based Payment ” means any Third Party License Payment that is calculated based on sales of a product ( e.g. , royalties and sales milestones).

1.2.201. “ SDEA ” has the meaning set forth in Section 4.6 (Pharmacovigilance).

1.2.202. “ Second Co-Co/Global Option Product ” has the meaning set forth in Section 3.2.2.2 (Second Co-Co/Global Option Product).

1.2.203. “ Second Source ” has the meaning set forth in Section 6.6 (Establishment of Second Source).

1.2.204. “ Secondary Indication ” means a use of a Collaboration Product or Option Product for an indication that is not the first indication of such Collaboration Product or Option Product to receive Regulatory Approval, but is intended to be the subject of a supplemental application submitted to a Regulatory Authority that includes clinical trial data from a Clinical Study seeking Regulatory Approval to market the Collaboration Product or Option Product for such use.

1.2.205. “ Secondary Indication Study ” means a human clinical study of a Collaboration Product or Option Product that is not necessary for receipt of the first anticipated Regulatory Approval for such Collaboration Product or Option Product in a country or territory but is intended to support receipt of Regulatory Approval for a Secondary Indication.

1.2.206. “ Serious Adverse Event ” means an adverse drug experience or circumstance that results in any of the following outcomes (a) death, (b) life-threatening condition, (c) inpatient hospitalization or a significant prolongation of existing hospitalization, (d) persistent or significant disability or incapacity or substantial disruption of the ability to conduct normal life functions, (e) or a congenital anomaly/birth defect or (f) significant intervention required to prevent permanent impairment or damage.

1.2.207. “ siRNA ” means an oligonucleotide composition of native or chemically modified RNA that targets a gene through activation of the RNA interference pathway, and that is not a MicroRNA, MicroRNA antagonist or MicroRNA Mimic.

1.2.208. “ Stock Purchase Agreement ” means that certain Stock Purchase Agreement between Genzyme and Alnylam, executed as of the Execution Date, as the same may be amended from time to time.

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1.2.209. “ Supply Agreements ” means the Clinical Supply Agreements, the Commercial Supply Agreements, the ALN-TTR Clinical Supply Agreement and the ALN-TTR Commercial Supply Agreement.

1.2.210. “ Supply Expert ” has the meaning set forth in Section 6.3 (Disputed Supply Agreement Terms).

1.2.211. “ Supply Source Notice ” has the meaning set forth in Section 6.6.2.2 (Negotiating Period).

1.2.212. “Technology Transfer ” has the meaning set forth in Section 6.5 (Transfer of Manufacturing Know-How).

1.2.213. “ Tentative Core Pipeline Program ” has the meaning set forth in Section 3.1.1.3(b) (Pipeline Programs Lists).

1.2.214. “ Tentative Core Pipeline Program List ” has the meaning set forth in Section 3.1.1.3(b) (Pipeline Programs Lists).

1.2.215. “ Term ” has the meaning set forth in Section 12.1 (Term).

1.2.216. “ Territory ” means (i) with respect to Alnylam, the Alnylam Territory and (ii) with respect to Genzyme, the Genzyme Territory.

1.2.217. “ Third Party ” means an entity other than a Party and its Affiliates.

1.2.218. “ Third Party CNS Agreement ” has the meaning set forth in Section 2.1.3.2 (CNS Exclusivity).

1.2.219. “ Third Party License Payment ” means royalties, upfront fees, milestones or other amounts payable under an In-License in consideration for the rights granted under such In-License with respect to a Patent Right.

1.2.220. “ Third Party Pricing Terms ” means, in respect of the supply of a Product, (i) the cost per unit of Product, (ii) minimum order quantities (per batch and annually), (iii) firm order forecast requirements, (iv) cost, if any, for reserving capacity including any costs required to maintain compliance, and (v) capital costs, if any, to enable manufacturing.

1.2.221. “ Third Party Supply Agreement ” has the meaning set forth in Section 6.7 (Third Party Manufacturer as Second Source).

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1.2.222. “ Trademark ” means any trademark, trade name, service mark, service name, brand, domain name, trade dress, logo, slogan or other indicia of origin or ownership, including the goodwill and activities associated with each of the foregoing.

1.2.223. “ Trailing Global Option Product ” means a Global Option Product (i) [***].

1.2.224. “ Trailing Global Option ” has the meaning set forth in 3.2.3.3 (Trailing Global Option Grant).

1.2.225. “ Trailing Regional Option Product ” means a Regional Option Product [***].

1.2.226. “ Transition Period ” means the period beginning on Alnylam’s receipt of an Option Preservation Notice with respect to an Option Product and ending on the earlier of (x) the Option Exercise Date for such Option Product or (y) the expiration of the Option Exercise Period for such Option Product.

1.2.227. [***].

1.2.228. “ TTR ” means the human TTR gene and its protein product, transthyretin. As of the Execution Date, an example of an identifier for the human TTR gene is the NCBI RefSeq code NM_000371.3 and an example of an identifier for the human TTR gene protein product NCBI RefSeq code NP_000362.1.

1.2.229. “ Un-Blocking Genzyme In-License ” means, with respect to a Collaboration Product, any Collaboration In-License that Genzyme enters into in accordance with Section 11.3.3 (Collaboration In-Licenses) and pursuant to which Genzyme has a license to any Blocking Patent Right with respect to such Collaboration Product.

1.2.230. “ United States ” means the United States of America and its territories, possessions and commonwealths.

Capitalized terms used, but not defined, herein shall have the meanings ascribed to those terms in the License Terms.

2. EFFECTIVENESS OF AGREEMENTS AND LICENSES

2.1. Effective Date .

2.1.1. Effectiveness of Collaboration Agreement. Upon the occurrence of the Closing Date under the Stock Purchase Agreement (the “ Effective Date ”), the Collaboration Agreement, which consists of this Master Agreement and the License

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Terms listed below, shall automatically, with no further action by any Party, go into full force and effect and all of the obligations of the applicable Party set forth therein (including in this Master Agreement) shall become the binding obligations of the applicable Party thereto:

(a)

Regional License Terms;

(b)

Global License Terms; and

(c)

Co-Co License Terms.

2.1.2. Termination of Historical TTR Agreement. Simultaneous with the Collaboration Agreement going into full force and effect on the Effective Date, the Historical TTR Agreement shall be terminated in its entirety and superseded in its entirety by the Collaboration Agreement on the Effective Date, provided that all rights and obligations accrued under the Historical TTR Agreement shall continue for and against the Parties under the terms of the Collaboration Agreement.

2.1.3. CNS Collaboration.

2.1.3.1. CNS Exploration Period . During the [***] year period beginning on the Effective Date (the “ CNS Exploration Period ”), the Parties will use commercially reasonable efforts to assess the state of the art in the area of delivery of siRNAs to the central nervous system (“ CNS ”), including identifying Third Parties with relevant expertise and technology and, at Genzyme’s request, (a) develop a plan to jointly undertake research and development of siRNAs for delivery to the CNS and (b) negotiate in good faith and enter into a mutually agreeable collaboration and license agreement pursuant to which the Parties will conduct the research and development activities set forth in such plan (the “ CNS Collaboration and License Agreement ”), which CNS Collaboration and License Agreement shall contain customary and reasonable provisions for agreements of its type that may be agreed by the Parties, including provisions relating to governance, intellectual property ownership, prosecution and enforcement, regulatory interactions and approvals, term and termination, representations and warranties, indemnification, and confidentiality. Each Party will dedicate employees within its organization with appropriate expertise in CNS and/or rare diseases to conducting the activities described in this Section 2.1.3.

2.1.3.2. CNS Exclusivity . Subject to Section 2.1.3.3 (Exceptions to CNS Exclusivity), during the CNS Exploration Period, neither Party shall enter into any agreement with a Third Party regarding the development or commercialization of siRNAs delivered to the CNS (a “ Third Party CNS Agreement ”) without the prior written consent of the other Party, provided that Genzyme may terminate the CNS Exploration Period at any time upon written notice to Alnylam.

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2.1.3.3. Exceptions to CNS Exclusivity .

(a) Existing Third Party Agreements . None of the following agreements in existence or being negotiated on the Execution Date shall constitute a “Third Party CNS Agreement” for purposes of this Master Agreement: (i) the agreements between Genzyme and a Third Party that will be identified by Genzyme by the Effective Date and added to Schedule 2.1.3.3 and (ii) the agreements between Alnylam and a Third Party, listed on Schedule 2.1.3.3 , in each case ((i) and (ii)) as such agreements may be amended or restated in the future so long as such amendment or restatement does not expand the field of such agreement, and the activities thereunder and discussions with such Third Party in relation thereto.

(b) Future Third Party Agreements. The following shall not constitute “Third Party CNS Agreements” for purposes of this Master Agreement: (i) any agreement between a Party and a contractor, contract research organization, contract manufacturer or other Third Party, under which such Third Party only performs contract services on behalf of such Party, for the research, development or manufacture of siRNAs delivered to the CNS and for which no product-related commercial rights are granted or (ii) any agreement between a Party and an academic institution or non-profit institution, under which such Party and such institution collaborate with respect to the research, development or manufacture of siRNAs delivered to the CNS and for which no product-related commercial rights are granted.

(c) Internal Activities . Notwithstanding anything in this Section 2.1.3 (CNS Collaboration), either Party may conduct internal programs and other activities regarding the research, development, manufacture and commercialization of siRNAs to be delivered to the CNS.

2.1.3.4. ROFN for CNS .

(a) ROFN Process . If Genzyme makes a request to negotiate under Section 2.1.3.1, but the Parties do not enter into, a CNS Collaboration and License Agreement during the CNS Exploration Period and Genzyme does not terminate the CNS Exploration Period prior to its expiration, then, if at any time during the [***] year period following the CNS Exploration Period (the “ CNS ROFN

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Period ”), Alnylam desires to enter into a Third Party CNS Agreement, Alnylam shall so notify Genzyme in writing, which notice shall describe the proposed terms of such Third Party CNS Agreement (the “ Proposed CNS Terms ”). Upon receipt of such notice from Alnylam, Genzyme shall have [***] days from receipt of such written notice to notify Alnylam in writing as to whether Genzyme desires to negotiate an agreement with Alnylam with respect to the Proposed CNS Terms (a “ CNS ROFN Exercise Notice ”). If Genzyme delivers a CNS ROFN Exercise Notice prior to the expiration of such [***] day period, Genzyme shall have the exclusive right [***] days following the date that Genzyme delivers a CNS ROFN Exercise Notice (the “ CNS ROFN Offer Period ”) to negotiate with Alnylam and to make one or more written non-binding offers to Alnylam concerning the terms on which Genzyme would enter into an agreement with respect to the Proposed CNS Terms (the “ CNS ROFN Non-Binding Offer ”). If Genzyme delivers a CNS ROFN Non-Binding Offer to Alnylam prior to the expiration of the CNS ROFN Offer Period, Genzyme shall thereafter have the exclusive right for [***] days (or such longer period as may be mutually agreed by the Parties) (the “ CNS ROFN Negotiation Period ”), to finalize and enter into a definitive agreement with Alnylam with respect to the Proposed CNS Terms.

(b) Post-ROFN MFN . Alnylam shall not, during the CNS ROFN Offer Period or CNS ROFN Negotiation Period, enter into discussions, exchange information, or otherwise negotiate with any Third Party with respect to the Proposed CNS Terms. If (i) Genzyme does not provide a CNS ROFN Exercise Notice within [***] days of receiving notice of the Proposed CNS Terms, (ii) Genzyme does not provide a CNS ROFN Non-Binding Offer prior to the expiration of the CNS ROFN Offer Period prior to the expiration of the CNS ROFN Offer Period, or (iii) the Parties do not enter into a definitive agreement with respect to the Proposed CNS Terms prior to the expiration of the CNS ROFN Negotiation Period, then Alnylam shall be free to enter into an agreement with any Third Party with respect to such Proposed CNS Terms, provided that, for the remainder of the CNS ROFN Period, Alnylam shall not enter into an agreement with respect to such Proposed CNS Terms that are, in the aggregate, materially more favorable to such Third Party than the last terms offered in writing by Genzyme to Alnylam during the CNS ROFN Offer Period or CNS ROFN Negotiation Period, as applicable, unless Alnylam first re-offers to enter into an agreement with Genzyme on such more favorable terms and Genzyme does not accept such offer and enter into such agreement with Alnylam within [***] days after such re-offer. For clarity, prior to the CNS ROFN Offer Period and CNS ROFN Exercise Period, Alnylam shall be free to engage in discussions and exchange information with Third Parties with respect to development or commercialization of siRNAs delivered to the CNS, but shall not enter into any binding agreement with any Third Party with respect to such rights.

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(c) Notwithstanding the foregoing, in the event that Genzyme enters into any Third Party CNS Agreement following the Execution Date without the prior written consent of Alnylam, Genzyme’s exclusive rights under this Section 2.1.3 shall automatically convert to non-exclusive rights and the proviso set forth in Section 2.1.3.4(b) (Post-ROFN MFN) shall automatically no longer apply. The foregoing shall be Alnylam’s sole and exclusive remedy with respect to any breach of Section 2.1.3.2 (CNS Exclusivity) by Genzyme.

2.2. Effectiveness of Licenses to Collaboration Products . As promptly as practicable following Alnylam’s delivery of a Final Option Data Package to Genzyme, but not later than the applicable Option Exercise Date, Genzyme shall determine whether any filing or notification is necessary or advisable under any applicable Antitrust Law if Genzyme were to exercise the respective Option to take a license from Alnylam to Genzyme in respect of the corresponding Option Product pursuant to the applicable License Terms.

2.2.1. If Genzyme determines that a filing or notification under any applicable Antitrust Law is not necessary or advisable, then Genzyme shall indicate the same in the respective Exercise Notice for such Option.

2.2.2. If Genzyme determines that a filing or notification under any applicable Antitrust Law is necessary or advisable, then Genzyme shall indicate the same in the respective Exercise Notice for such Option and each of Genzyme and Alnylam shall make or cause to be made such notifications and filings as promptly as practicable (but in any event within [***] business days). Each Party shall be responsible for its own costs and expenses associated with such notifications and filings, and Genzyme shall pay any applicable premerger filing fee under the HSR Act. Each Party shall use its commercially reasonable efforts to obtain the expiration or termination of the applicable waiting period under the HSR Act, and to obtain the termination or expiration of any other applicable waiting periods or any necessary approvals or consents under any other applicable Antitrust Law, at the earliest possible date after the date of filing. Immediately following the later of the expiration or termination of the last such waiting period, or receipt of any necessary approvals or consents under any other applicable Antitrust Law, Genzyme shall send Alnylam written notice that all waiting periods under any applicable Antitrust Law have expired or been terminated and any necessary approvals or consents under any applicable Antitrust Law have been obtained. The effectiveness of the Option Exercise Date for the corresponding Collaboration Product, which will be the Implementation Date under the applicable License Terms, shall be deemed to be delayed until the date on which the last waiting period under any applicable Antitrust Law has expired or been terminated or on which the last approval or consent under such Antitrust Law is granted.

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2.3. Cooperation . Each of Genzyme and Alnylam shall: (i) reasonably cooperate with each other in connection with any investigation or other inquiry relating to the transactions contemplated by an Exercise Notice for an Option; (ii) reasonably keep the other Party informed of any communication received by such Party from, or given by such Party to, the FTC, the DOJ or any other Merger Control Authority and of any communication received or given in connection with any proceeding by a private party, in each case regarding the transactions contemplated by an Exercise Notice for an Option; (iii) promptly respond to and certify substantial compliance with any inquiries or requests received from the FTC, the DOJ or any other Merger Control Authorities for additional information or documentation; (iv) reasonably consult with each other in advance of any meeting or conference with the FTC, the DOJ or any other Merger Control Authority, and to the extent permitted by the FTC, the DOJ or such other Merger Control Authority and reasonably determined by such Party to be appropriate under the circumstances, give the other Parties or their counsel the opportunity to attend and participate in such meetings and conferences; and (v) permit the other Parties or their counsel to the extent reasonably practicable to review in advance, and in good faith consider the views of the other Parties or their counsel concerning, any submission, filing or communication (and documents submitted therewith) intended to be given by it to the FTC, the DOJ or any other Merger Control Authority; provided , however , such Party shall be under no obligation to reschedule any meetings or conferences with the FTC, the DOJ or any other Merger Control Authority to enable the other Party to attend.

2.4. No Antitrust Undertakings . Notwithstanding anything to the contrary in this Section 2, the term “commercially reasonable efforts” as used in this Section 2 does not require that either Party (i) offer, negotiate, commit to or effect, by consent decree, hold separate order, trust or otherwise, the sale, divestiture, license or other disposition of any capital stock, assets, rights, products or businesses of Genzyme, Alnylam or their respective Affiliates, (ii) agree to any restrictions on the activities of Genzyme, Alnylam or their respective Affiliates, or (iii) pay any material amount or take any other action to prevent, effect the dissolution of, vacate, or lift any decree, order, judgment, injunction, temporary restraining order, or other order in any suit or proceeding that would otherwise have the effect of preventing or delaying any of the transactions contemplated by an Exercise Notice for an Option.

2.5. No Effect .

2.5.1. Transaction Agreements. The Collaboration Agreement shall (i) not take effect until the occurrence of the Closing (as defined in the Stock Purchase Agreement) in accordance with its terms and (ii) become null and void and have no further force or effect in the event the Stock Purchase Agreement is terminated prior to the Closing in accordance with its terms.

2.5.2. License to an Option Product. At the election of either Party, immediately upon notice to the other Party, Genzyme’s exercise of an Option shall become null and void and have no further force or effect (i) in the event that the FTC or DOJ obtains a preliminary injunction against the Parties to enjoin the transactions contemplated by the Exercise Notice for such Option or (ii) in the event any applicable

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waiting periods shall not have expired or been terminated, or any necessary approvals or consents shall not have been obtained, under any applicable Antitrust Law on or prior to [***] months after the effectiveness of the filings and notifications contemplated by Section 2.2.2 (Effectiveness of Licenses to Collaboration Products). In addition, beginning on the [***] day following Genzyme’s delivery of an Exercise Notice with respect to an Option Product but prior to the Option Exercise Date for the corresponding Collaboration Product, Genzyme shall have the right to nullify its exercise of such Option by providing written notice to Alnylam. Following the voiding or nullification of Genzyme’s exercise of an Option for any reason under this Section 2.5, the Option Product previously subject to such Option shall be treated for all purposes under this Master Agreement, including Section 3.5, as an Option Product in respect of which Genzyme did not deliver an Exercise Notice to Alnylam.

3. GRANT AND EXERCISE OF OPTIONS

3.1. Alnylam Programs .

3.1.1. Program Identification.

3.1.1.1. Alnylam Development Updates . At each regularly scheduled meeting of the PAC during the Option Period, Alnylam shall advise the PAC of any Alnylam Program with respect to which, since the last PAC meeting, either (i) the existence of such Alnylam Program (and the target thereof) has been publicly disclosed by Alnylam, including as a result of the filing of an IND for such siRNA or (ii) [***]. In addition, Alnylam may elect to advise the PAC of any Alnylam Program at any time. The PAC shall discuss the selection of new targets for new Core Pipeline Programs and the research and development strategy for Option Products. Alnylam shall consider in good faith recommended new targets proposed by Genzyme.

3.1.1.2. PAC Categorization of Alnylam Programs . The PAC, acting reasonably, shall seek to determine whether such Alnylam Program is a Core Pipeline Program or a Non-Core Pipeline Program and advise the Parties of its consensus view (if any).

3.1.1.3. Pipeline Programs Lists .

(a) If the PAC recommends to the AJSC and to the Parties that any Alnylam Program is a Core Pipeline Program or a Non-Core Pipeline Program, then the Parties may agree that such Alnylam Program shall be identified on the Core Pipeline Program List or the Non-Core Program Pipeline List, respectively. Any Alnylam Program and the corresponding human gene and siRNA, for as long as listed on the Core Pipeline Program List or Non-Core Pipeline Program List, shall be treated as a Core Pipeline Program or Non-Core Pipeline Program, as applicable, for all purposes of this Master Agreement, subject to this Section 3.1.1.

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(b) If, within [***] days of the PAC meeting referred to in Section 3.1.1.2 (PAC Categorization of Alnylam Programs), the Parties, acting reasonably, are unable to agree on whether any such Alnylam Program is a Core Pipeline Program or a Non-Core Pipeline Program, then such Alnylam Program shall be deemed to be a “ Tentative Core Pipeline Program ” and shall be identified on a list of such Tentative Core Pipeline Programs (the “ Tentative Core Pipeline Program List ”) and, for the sake of clarity, except as provided in Section 3.1.1.5 (Requested Dispute Resolution), such disagreement shall not be subject to resolution pursuant to Section 5.1.8 (Decision-Making). Any Alnylam Program and the corresponding human gene and siRNA, for as long as listed on the Tentative Core Pipeline Program List, shall be treated as a Core Pipeline Program for purposes of Section 3.1.2.1 (Information Sharing for Core Pipeline Programs), Section 3.1.2.2 (Meetings with Regulatory Authorities), Section 3.1.2.3 (Design of Human POP Studies), Section 3.6 (Exclusivity during Option Period), Section 5.3.3 (IP Committee Responsibilities) and Section 11 (Intellectual Property), subject to Section 3.1.1 (Program Identification).

3.1.1.4. Locking of Alnylam Programs . Alnylam shall notify the PAC promptly after the first IND with respect to an Alnylam Program becomes, or is deemed to be, effective and (i) if such Alnylam Program is on the Core Pipeline Program List or Non-Core Pipeline Program List, it will automatically be moved to the Locked Core Pipeline Program List or the Locked Non-Core Pipeline Program List, as applicable, upon delivery of such notice; or (ii) if such Alnylam Program is on the Tentative Core Pipeline Program List, then the Parties will seek to reach consensus as to whether such Alnylam Program is a Core Pipeline Program or Non-Core Pipeline Program within [***] days after delivery of such notice. If the Parties agree on the categorization of such Tentative Core Pipeline Program within such [***] day period, such Alnylam Program will automatically be moved to the Locked Core Pipeline Program List or the Locked Non-Core Pipeline Program List, as applicable. If the Parties cannot agree within such [***] day period, either Party may submit the categorization of such Alnylam Program to the AJSC for resolution pursuant to Section 5.1.8 (Decision-Making) and, following any such resolution of such categorization, such Alnylam Program will automatically be moved to the Locked Core Pipeline Program List or the Locked Non-Core Pipeline Program List, as applicable. Once an Alnylam Program has been moved to the Locked Core Pipeline Program List or the Locked Non-Core Pipeline Program List, such Core Pipeline Programs shall remain Core Pipeline Programs and such Non-Core Pipeline Programs shall remain Non-Core

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Pipeline Programs, respectively, for all purposes under the Collaboration Agreement, except as the Parties, each acting in its sole discretion, may later mutually agree in writing. Notwithstanding the foregoing, if Alnylam enters into an agreement with a Third Party granting such Third Party any rights or options to a Non-Core Pipeline Program (or any siRNA arising therefrom) prior to the first IND with respect to such Non-Core Pipeline Program becoming effective, Alnylam shall notify the PAC of the existence of such an agreement (but not the counterparty thereto or any terms thereof) and the human gene(s) targeted by such Non-Core Pipeline Program (or any siRNA arising therefrom) and such Non-Core Pipeline Program will automatically then be moved to the “Locked Non-Core Pipeline Program List” as of the date of such agreement, [***].

3.1.1.5. Requested Dispute Resolution . If an Alnylam Program is not listed on the Locked Core Pipeline Program List or the Locked Non-Core Pipeline Program List and the Parties, at any time, are unable to agree on whether any such Alnylam Program is a Core Pipeline Program or a Non-Core Pipeline Program then, upon the request of either Party, such categorization of such Alnylam Program shall be submitted to the AJSC for resolution pursuant to Section 5.1.8 (Decision-Making), and, following resolution, such Alnylam Program will automatically be moved to the Locked Core Pipeline Program List or the Locked Non-Core Pipeline Program List, as applicable.

3.1.1.6. Updating Program Lists . Solely as an administrative manner, Alnylam shall be responsible for updating the Core Pipeline Program List, the Locked Core Pipeline Program List, the Non-Core Pipeline Program List, the Locked Non-Core Pipeline Program List and the Tentative Core Pipeline Program List from time to time, in all cases in accordance with this Section 3.1.1. Promptly following any such update, Alnylam shall provide a copy of the applicable list to each of the PAC representatives.

3.1.2. Core Pipeline Programs.

3.1.2.1. Information Sharing for Core Pipeline Programs .

(a) During the Option Period, Alnylam shall update the PAC, at each regularly scheduled meeting thereof, on the status of the Core Pipeline Programs, which update shall include a summary of the Development activities undertaken by Alnylam with respect to such Core Pipeline Programs since the last update provided to the PAC or planned to be undertaken by Alnylam. [***]. In addition, in connection with each regularly scheduled meeting of the PAC during the Option Period, Alnylam will provide to the PAC and Genzyme copies of all then-available preclinical, clinical, regulatory and supporting reports and material correspondence with Regulatory Authority with respect to any Core Pipeline

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Program and, if available, a copy of any Development plan for each Core Pipeline Program. Notwithstanding the foregoing, Alnylam shall not be obligated pursuant to the foregoing to provide information the disclosure of which would: (a) in the reasonable opinion of Alnylam’s counsel, adversely affect the attorney-client privilege between Alnylam and its counsel; or (b) violate or cause a breach by Alnylam of any confidentiality or non-disclosure agreement with any Third Party. Once Alnylam delivers an Initial Option Data Package for an Option Product, Alnylam will provide information related to such Option Product solely pursuant to Section 3.3 (Option Exercise Period), including Section 3.3.3.2 (Governance) if Genzyme delivers an Option Preservation Notice for such Option Product to Alnylam, and Alnylam shall not have any obligations related to such Option Product and its related Core Pipeline Program under Sections 3.1.1 (Program Identification), 4.5 (Oversight), 5 (Collaboration Management) or 11.2 (Patent Prosecution Information Sharing).

(b) Following the filing of an IND with respect to a Core Pipeline Program, Alnylam shall (x) promptly provide (i) any patent, regulatory or CMC information, (ii) any material, complete sets of preclinical or clinical data and (iii) raw data tables, in each case ((i), (ii) and (iii)) then available to Alnylam that Genzyme may reasonably request, to the extent that such information was not previously provided by Alnylam to Genzyme and subject to customary and reasonable due diligence procedures to preserve the confidential nature of any such information, regarding such Option Product to assist Genzyme in deciding whether to exercise an Option for such Option Product if and when any such Option becomes exercisable; and (y) afford to Genzyme and its representatives, reasonable access during normal business hours to Alnylam’s personnel that Genzyme may reasonably request regarding such Option Product to assist Genzyme in deciding whether to exercise an exercisable Option for such Option Product.

3.1.2.2. Meetings with Regulatory Authorities . Alnylam shall provide Genzyme with reasonable advance notice of any pre-IND meetings with any Regulatory Authority with respect to any Core Pipeline Program, or with as much advance notice as practicable under the circumstances. [***].

3.1.2.3. Design of Human POP Studies . During the Option Period, Alnylam shall reasonably consult with the AJSC regarding the design of each Human POP Study proposed to be conducted for any siRNA generated by a Core Pipeline Program. In addition, at least [***] days prior to submitting a final protocol for such Human POP Study to a Regulatory Authority as part of an IND, Alnylam shall submit a draft of such protocol (or, if a draft protocol is not available, a full protocol concept sheet) to the AJSC for review and comment. If a draft protocol was not available, Alnylam shall provide the draft protocol to the

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AJSC as soon as it becomes available. Alnylam shall reasonably consider in good faith any comments provided by the AJSC (or its members) within [***] days of the submission of such draft protocol or full protocol concept sheet to the AJSC; provided , however , in any event, the AJSC shall have at least [***] days to review and comment on the draft protocol. [***].

3.1.2.4. Improperly Designated Programs . In the event that (i) it is determined [***] and (iii) Alnylam continues to conduct such Alnylam Program following such [***] determination as a Non-Core Pipeline Program, but does not initiate a Phase II Study for any siRNA generated by such Non-Core Pipeline Program in a non-Orphan Disease or any cancer or infectious disease within [***] following the date on which such siRNA received Regulatory Approval in respect of an Orphan Disease, then Alnylam and Genzyme shall in good faith negotiate together the terms under which such siRNA could be deemed a Regional Option Product (even if such [***] year period ends after the expiration of the Regional Option Period), including [***]. Following agreement on such terms, Alnylam shall provide Genzyme with an Initial Option Notice with respect to the applicable siRNAs as soon as reasonably practicable. If the Parties are unable to agree upon the terms under which such siRNA could be deemed a Regional Option Product during the first [***] days of such negotiation, [***].

3.2. Option Grants .

3.2.1. Regional Option Grants.

3.2.1.1. Regional Option Grants . Alnylam hereby grants Genzyme a series of exclusive options (each, a “ Regional Option ”), under each of which Genzyme shall have the right, but not the obligation, to take a license on the terms set forth in the Regional License Terms to any Regional Option Product that achieves Human POP Study Completion during the Regional Option Period. Each Regional Option may be exercised by Genzyme at any time during the applicable Option Exercise Period for a Regional Option Product that achieves Human POP Study Completion in accordance with the terms and conditions set forth in Sections 3.3 (Option Exercise Period) and 3.4 (Exercise of an Option).

3.2.1.2. [***].

3.2.1.3. [***].

3.2.2. Co-Co/Global Option Grant. Alnylam hereby grants Genzyme one (1) exclusive option (the “ Co-Co/Global Option ”) under which Genzyme shall have the right, but not the obligation, to either (i) take a license on the terms set forth in the Global License Terms to ALN-AS1 or (ii) take a license on the terms set forth in the Co-Co

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License Terms to ALN-AT3. Genzyme may wait to exercise such Co-Co/Global Option until both ALN-AS1 and ALN-AT3 achieve Human POP Study Completion as described below in this Section 3.2.2, or may terminate such Co-Co/Global Option prior to both ALN-AS1 and ALN-AT3 achieving Human POP Study Completion (in which case, the Additional Global Option will become exercisable pursuant to Section 3.2.3.2 (Additional Global Option Grant)). The Co-Co/Global Option may be exercised by Genzyme at any time during the applicable Option Exercise Period for a Co-Co/Global Option Product in accordance with the terms and conditions set forth in Sections 3.3 (Option Exercise Period) and 3.4 (Exercise of an Option), subject to the conditions set forth in this Section 3.2.2.

3.2.2.1. First Co-Co/Global Option Product . For the first Co-Co/Global Option Product to achieve Human POP Study Completion (the “ First Co-Co/Global Option Product ”), Genzyme may do any of the following:

(a) exercise a Regional Option (or 2019 Trailing Regional Option or 2021 Trailing Regional Option, if and as applicable) for such First Co-Co/Global Option Product, in which case the Co-Co/Global Option shall remain exercisable with respect to the First Co-Co/Global Option Product on the terms set forth in Sections 3.2.2.2(a) (Second Co-Co/Global Option Product) and 3.2.2.4 (Discontinuation of Second Co-Co/Global Option Product);

(b) exercise the Co-Co/Global Option for the First Co-Co/Global Option Product, in which case the Co-Co/Global Option shall be fully exercised; or

(c) not exercise any Option for the First Co-Co/Global Option Product, in which case the Co-Co/Global Option shall cease to be exercisable with respect to the First Co-Co/Global Option Product but shall remain exercisable for the Second Co-Co/Global Option Product.

3.2.2.2. Second Co-Co/Global Option Product . For the second Co-Co/Global Option Product ( i.e. , if the First Co-Co/Global Option Product is ALN-AT3, then ALN-AS1 or, if the First Co-Co/Global Option Product is ALN-AS1, then ALN-AT3) to achieve Human POP Study Completion (the “ Second Co-Co/Global Option Product ”), Genzyme may do any of the following:

(a) exercise the Co-Co/Global Option for the First Co-Co/Global Option Product, in which case the Co-Co/Global Option shall be fully exercised;

(b) exercise the Co-Co/Global Option for the Second Co-Co/Global Option Product, in which case the Co-Co/Global Option shall be fully exercised;

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(c) exercise a Regional Option (or 2019 Trailing Regional Option or 2021 Trailing Regional Option, if and as applicable) for the Second Co-Co/Global Option Product, in which case, the Co-Co/Global Option shall be terminated in full and the Additional Global Option will become exercisable pursuant to Section 3.2.3.2 (Additional Global Option Grant) (for clarity, Genzyme may do both (a) and (c) of this Section 3.2.2.2); or

(d) not exercise any Option for the Second Co-Co/Global Option Product, in which case

(i) if the Second Co-Co/Global Option Product achieved Clinical Success (and Genzyme does not exercise the Co-Co/Global Option for the First Co-Co/Global Option Product or the Second Co-Co/Global Option Product or Genzyme has terminated the Co-Co/Global Option pursuant to Section 3.2.2.5 (Genzyme Elective Termination of Co-Co/Global Option)), the Co-Co/Global Option shall terminate in full at the end of the Option Exercise Period for the Second Co-Co/Global Option Product and the Additional Global Option will become exercisable pursuant to Section 3.2.3.2 (Additional Global Option Grant);

(ii) if the Second Co-Co/Global Option Product did not achieve Clinical Success, but the First Co-Co/Global Option Product did achieve Clinical Success (and Genzyme does not exercise the Co-Co/Global Option for the First Co-Co/Global Option Product or the Second Co-Co/Global Option Product or Genzyme has terminated the Co-Co/Global Option pursuant to Section 3.2.2.5 (Genzyme Elective Termination of Co-Co/Global Option)), then the Co-Co/Global Option shall terminate in full at the end of the Option Exercise Period for the Second Co-Co/Global Option Product and the Additional Global Option will become exercisable pursuant to Section 3.2.3.2 (Additional Global Option Grant);

(iii) if both the Second Co-Co/Global Option Product and the First Co-Co/Global Option Product failed to achieve Clinical Success, then the Co-Co/Global Option shall remain exercisable but only with respect to the next Co-Co/Global Option Product, if any, to achieve Clinical Success (the “ Back-Up Co-Co/Global Option Product ”).

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3.2.2.3. Back-Up Co-Co/Global Option Product . If the Co-Co/Global Option is exercisable with respect to the Back-Up Co-Co/Global Option Product pursuant to Section 3.2.2.2(d)(iii), Genzyme may do any of the following:

(a) exercise the Co-Co/Global Option for the Back-Up Co-Co/Global Option Product, in which case the Co-Co/Global Option shall be fully exercised; or

(b) not exercise the Co-Co/Global Option for the Back-Up Co-Co/Global Option Product, in which case the Co-Co/Global Option shall terminate in full at the end of the Option Exercise Period for the Back-Up Co-Co/Global Option Product and the Additional Global Option will become exercisable pursuant to Section 3.2.3.2 (Additional Global Option Grant).

3.2.2.4. Discontinuation of Second Co-Co/Global Option Product . If Genzyme exercises a Regional Option for the First Co-Co/Global Option Product and Alnylam decides to abandon or terminate Development of the other Co-Co/Global Option Product prior to achieving Human POP Study Completion, then Alnylam shall promptly deliver written notice of such abandonment or termination to Genzyme (any such notice, the “ Co-Co/Global Option Trigger Notice ”) and Genzyme may do either of the following:

(a) exercise the Co-Co/Global Option for the First Co-Co/Global Option Product, in which case the Co-Co/Global Option shall be fully exercised and the First Co-Co/Global Option Product shall cease to be a Regional Licensed Product; or

(b) not exercise the Co-Co/Global Option for the First Co-Co/Global Option Product, in which case the Co-Co/Global Option shall terminate in full at the end of the applicable Option Exercise Period, the First Co-Co/Global Option Product shall continue to be a Regional Licensed Product and the Additional Global Option will become exercisable pursuant to Section 3.2.3.2 (Additional Global Option Grant).

3.2.2.5. Genzyme Elective Termination of Co-Co/Global Option . At any time prior to the exercise of the Co-Co/Global Option, Genzyme may, in its sole discretion, terminate the Co-Co/Global Option by providing written notice of termination to Alnylam and, upon delivery of such notice, the Co-Co/Global Option shall irrevocably and perpetually terminate in full, the Option Exercise Period for the Co-Co/Global Option shall expire, and the Additional Global Option will become exercisable pursuant to Section 3.2.3.2 (Additional Global Option Grant).

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3.2.3. Global Option Grants.

3.2.3.1. Global Option Grant . Alnylam hereby grants Genzyme one (1) exclusive option (the “ Global Option ”), under which Genzyme shall have the right, but not the obligation, to take a license on the terms set forth in the Global License Terms to any Global Option Product for which it is anticipated that Human POP Study Completion will be achieved during the Global Option Period. The Global Option may be exercised by Genzyme at any time during the applicable Option Exercise Period for a Global Option Product for which a Human POP Study is conducted during the Global Option Period in accordance with the terms and conditions set forth in Sections 3.3 (Option Exercise Period) and 3.4 (Exercise of an Option). The Global Option shall terminate in full upon the Option Exercise Date for any Global Option Product with respect to which Genzyme exercises the Global Option.

3.2.3.2. [***].

3.2.3.3. [***].

3.3. Option Exercise Period .

3.3.1. Initial Option Data Package. As soon as is reasonably practicable on or after [***] (i) any Option Product that achieves Human POP Study Completion during the applicable Option Period or (ii) any Trailing Regional Option Product or Trailing Global Option Product that achieves Human POP Study Completion after the end of the applicable Option Period; (y) Genzyme notifies Alnylam that it desires to exercise the Co-Co/Global Option with respect to ALN-AS1 prior to the achievement of Human POP Study Completion; or (z) Genzyme notifies Alnylam that it desires to exercise the Global Option or the Additional Global Option with respect to a Global Option Product prior to the achievement of Human POP Study Completion, Alnylam shall complete all activities necessary for Alnylam to prepare a complete Initial Option Data Package for the applicable Option Product and provide a written notice to Genzyme (such notice, an “ Initial Option Notice ”). Alnylam shall include in each such Initial Option Notice::

(a) a letter indicating which Option(s) is(are) applicable to the Option Product;

(b) the Initial Option Data Package for the Option Product (and all such data therein shall be made available to Genzyme through an electronic data room promptly following the date that such Initial Option Notice is delivered); and

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Within [***] days after Genzyme’s receipt of an Initial Option Notice, Genzyme shall acknowledge receipt of such Initial Option Notice in writing to Alnylam or be deemed to have acknowledged such receipt as of such date. For clarity, if Genzyme requests the delivery of an Initial Option Notice with respect to ALN-AS1 or a Global Option Product prior to the time determined in accordance with clause (x) of this Section 3.3.1, Alnylam shall only be obligated to provide such information in the Initial Option Data Package as is available to Alnylam as of the date of such request from Genzyme.

3.3.2. Initial Evaluation Period. If an Initial Option Notice is delivered by Alnylam to Genzyme pursuant to clause (x) of Section 3.3.1 (Initial Option Package) ( i.e. , after an Option Product achieves Human POP Completion), then, if Genzyme desires to preserve its right to exercise an Option for such Option Product, Genzyme shall notify Alnylam in writing of Genzyme’s desire to exercise an Option and the type of Option that Genzyme desires to exercise (an “ Option Preservation Notice ”) prior to the expiration of the Initial Evaluation Period with respect to such Option Product. If Genzyme delivers an Option Preservation Notice to Alnylam prior to the expiration of the Initial Evaluation Period for an Option Product, then Section 3.3.3 (Effect of Option Preservation) shall apply. If Genzyme does not deliver an Option Preservation Notice to Alnylam prior to the expiration of the Initial Evaluation Period for an Option Product, then such Option Product shall be treated for all purposes under this Master Agreement, including Section 3.5 (Option Not Exercised), as an Option Product in respect of which Genzyme did not deliver an Exercise Notice to Alnylam.

3.3.3. Effects of Option Preservation. If Genzyme delivers an Option Preservation Notice prior to the expiration of the Initial Evaluation Period for an Option Product pursuant to Section 3.3.2 (Initial Evaluation Period), then the provisions of this Section 3.3.3 shall apply.

3.3.3.1. Final Option Data Package . Within [***] days after the earlier of [***], Alnylam shall complete all activities necessary for Alnylam to prepare a complete Final Option Data Package for the applicable Option Product and deliver such Final Option Data Package to Genzyme. Within [***] days after Genzyme’s receipt of a Final Option Data Package, Genzyme shall acknowledge receipt of such Final Option Data Package in writing to Alnylam or be deemed to have acknowledged such receipt as of such date. Notwithstanding the foregoing, Alnylam shall not deliver a Final Option Data Package to Genzyme unless and until all of the activities necessary to generate the information to be included in such Final Option Data Package have been completed.

3.3.3.2. Governance . At Genzyme’s request following the delivery of an Option Preservation Notice for an Option Product, the Parties shall form the committee that would be responsible for facilitating the Collaboration with respect to such Option Product under the applicable License Terms if Genzyme

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exercised the Option identified in such Option Preservation Notice ( i.e. if the identified Option is the Global Option, the Parties will form the JTT described in Section 5.1 (Joint Transition Team) of the Global License Terms; and if the identified Option is the Co-Co/Global Option, the Regional Option, the 2019 Trailing Regional Option or the 2021 Trailing Regional Option, the Parties will form the PJSC described in Section 5.1 (Product Joint Steering Committee) of the Co-Co License Terms or Section 5.1 (Product Joint Steering Committee) of the Regional License Terms, as applicable). Such committee shall have the responsibilities allocated to such committee under the applicable License Terms, except that such committee shall serve solely in an advisory committee and shall not have any decision-making authority with respect to the applicable Option Product unless and until Genzyme exercises an Option with respect to such Option Product. Such committee shall be disbanded if Genzyme does not exercise an Option with respect to the applicable Option Product prior to the end of the Option Exercise Period for such Option Product.

3.3.3.3. [***]

(a) [***]

(b) [***]

3.3.3.4. No Rights . Except for the right to exercise an Option in respect of an Option Product following receipt of a Final Option Data Package in respect thereof, Genzyme shall not obtain any ownership interest or other right to Develop or Commercialize (or to compel Alnylam Develop or Commercialize) such Option Product during the Transition Period, provided that the foregoing shall not relieve Alnylam of any of its obligations under this Master Agreement in respect of such Option Product during the Transition Period.

3.3.4. Updates to Option Data Packages.

3.3.4.1. Incomplete Option Data Package .

(a) Notice of Missing Information . Following receipt of an Option Data Package, Genzyme shall have [***] days to notify Alnylam if such Option Data Package is missing any information, which notice shall describe the information that is missing. Alnylam shall provide Genzyme with such missing information identified in such notice as soon as reasonably practicable (if and to the extent that such information is available to Alnylam).

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(b) Disputed Missing Information . If, notwithstanding any information subsequently delivered by Alnylam pursuant to Section 3.3.4.1(a) (Notice of Missing Information), Genzyme, acting in good faith, still believes that the Option Data Package is missing material information, then Genzyme shall have the right to request that the AJSC review the Option Data Package (including any information subsequently delivered by Alnylam pursuant to Section 3.3.4.1(a) (Notice of Missing Information) or Section 3.3.4.2 (Supplements to Option Data Package)) within [***] days and determine whether material information is then missing from such Option Data Package. The AJSC is hereby empowered to compel Alnylam to produce any missing material information (if and to the extent that such information is available to Alnylam) within [***] days of such order.

3.3.4.2. Supplements to Option Data Package . Following delivery of an Option Data Package, Alnylam shall have the right to provide supplemental updates to any of the information included in such Option Data Package. In addition, Alnylam shall be required to promptly provide supplemental update(s) to Genzyme if [***]. In either such case, any such supplemental information shall be deemed to constitute a part of such Option Data Package for all purposes of this Collaboration Agreement (and to supersede previously provided information, to the extent such supplement information is identified, or would reasonably be apparent to Genzyme, as superseding previously provided information [***].

3.3.4.3. Information Sharing during Initial Evaluation Period and Option Exercise Period . During the Option Exercise Period (including, if applicable, the Initial Evaluation Period) for an Option Product, Alnylam shall (a) promptly provide to Genzyme (i) any patent, regulatory or CMC information, (ii) any material, complete sets of preclinical or clinical data and (iii) raw data tables, in each case ((i), (ii) and (iii)) then available to Alnylam that Genzyme may reasonably request, to the extent that such information was not previously provided by Alnylam to Genzyme and subject to customary and reasonable due diligence procedures to preserve the confidential nature of any such information, regarding such Option Product to assist Genzyme in deciding whether to exercise an Option for such Option Product if and when any such Option becomes exercisable, and (b) afford to Genzyme and its representatives reasonable access during normal business hours to Alnylam’s personnel, in each case ((a) and (b)) that Genzyme may reasonably request regarding such Option Product to assist Genzyme in deciding whether to exercise the Option for such Option Product, to the extent that such information was not previously provided by Alnylam to Genzyme.

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3.3.4.4. Extension of Initial Evaluation Period and Option Exercise Period . If any information is provided to Genzyme following the receipt of an Option Data Package pursuant to Section 3.3.4.1 (Incomplete Data Option Package), 3.3.4.2 (Supplements to Option Data Package) or 3.3.4.3 (Information Sharing During Option Exercise Period) and such information is, in Genzyme’s reasonable discretion, material information not previously provided to Genzyme relating to the applicable Option Product, the Initial Evaluation Period or Option Exercise Period, as applicable, shall, if necessary and upon notice from Genzyme to Alnylam, be extended such that there is at least [***] days between Genzyme’s receipt of such material information and the expiration of such Initial Evaluation Period or Option Exercise Period, provided that in no event shall any Initial Evaluation Period or Option Exercise Period be extended by more than [***] days in the aggregate.

3.3.5. Information Excluded from Option Data Packages. Notwithstanding anything in this Master Agreement to the contrary, Alnylam shall not be obligated to include in any Option Data Package or to disclose pursuant to Section 3.3.4 (Updates to Option Data Packages) any information the disclosure of which would (i) in the reasonable opinion of Alnylam’s counsel, adversely affect the attorney-client privilege between Alnylam and its counsel or (ii) [***], and the exclusion of such information from any Option Data Package, as applicable, shall not constitute missing information for purposes of Section 3.3.4.1 (Incomplete Option Data Package), render the Option Data Package deficient in any respect or otherwise result in Genzyme having any right or claim against Alnylam. If material information may be excluded from any Option Data Package pursuant to clause (i) in the immediately preceding sentence, the Parties will enter into a common interest agreement designed to preserve such privilege and, after execution of such agreement, Alnylam will provide Genzyme with access to such information.

3.4. Exercise of an Option . Genzyme shall exercise an Option, if at all, by properly delivering a complete Exercise Notice in respect of such Option to Alnylam at any time during the respective Option Exercise Period for such Option.

3.4.1. [***].

3.4.2. Exercise of Preserved Option .

3.4.2.1. Except as provided in Section 3.4.2.3, in the event that Genzyme exercises an Option for an Option Product for which an Option Preservation Notice was delivered pursuant to Section 3.3.2 (Initial Evaluation Period), then Genzyme may only exercise the Option identified in such Option Preservation Notice for such Option Product.

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3.4.2.2. Except as provided in Section 3.4.2.3, if Genzyme identified the Global Option or the Additional Global Option as the Option it was preserving in an Option Preservation Notice and Genzyme does not deliver to Alnylam an Exercise Notice with respect to the exercise of such Option prior to the expiration of the applicable Option Exercise Period, then such Option shall terminate in full at the end of the Option Exercise Period and Genzyme shall not thereafter be permitted to exercise such unexercised Global Option or Additional Global Option, as applicable (such failure to deliver an Exercise Notice, a “ Global/Additional Global Option Forfeiture ”).

3.4.2.3. Notwithstanding the foregoing, if prior to the expiration of the Option Exercise Period for an Option Product (i) Genzyme receives material (a) clinical, GLP toxicology or nonclinical data or (b) regulatory guidance or a regulatory determination involving such Option Product, including in the Final Option Data Package, that was not included in (or, in the case of clause b, reasonably ascertainable from) the Initial Option Data Package or information presented to the AJSC or the PAC (and reflected in the written meeting minutes thereof) (such new data, regulatory guidance or a regulatory determination, “ New Information ”) and (ii) such New Information is adversely material to the expected clinical or commercial success of such Option Product such that Genzyme would not have exercised the Global Option or Additional Global Option if it possessed such New Information at the time it delivered such Option Preservation Notice, then Genzyme shall have the right (but not the obligation) to deliver an Option Exercise Notice to exercise a Regional Option during the applicable Option Exercise Period or it may elect not to exercise any Option with respect to such Option Product and, in either such case, Genzyme’s failure to exercise the Global Option or the Additional Global Option, as applicable, shall not constitute a Global/Additional Global Option Forfeiture and the Global Option or Additional Global Option, as applicable shall remain exercisable.

3.4.2.4. If development milestone(s) become payable under any License Terms, including because an Option Product is dosed in a patient in a Phase III Study, prior to the expiration of the Option Exercise Period for such Option Product and Genzyme exercises an Option in respect of such Option Product and such Option Product becomes a Collaboration Product, then Genzyme shall promptly, and in any event within [***] days following receipt of an invoice, pay such development milestone(s) to Alnylam as though such Option Product was a Collaboration Product at the time such development milestone(s) became payable Alnylam.

3.4.3. Regional Options. On the applicable Option Exercise Date for the exercise of any Regional Option, 2019 Trailing Regional Option or 2021 Trailing Regional Option, the applicable Regional Option Product or Trailing Regional Option

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Product shall automatically be deemed to be a Regional Licensed Product for all purposes under the Collaboration Agreement and the license from Alnylam to Genzyme for such Regional Licensed Product shall automatically, with no further action by any Party, go into full force and effect and all of the obligations of Alnylam and Genzyme set forth in the Regional License Terms, including the payment obligations set forth therein, shall become the binding obligations of the applicable Party in respect of such Regional Licensed Product. As part of the effectiveness of such license, the Regional License Terms shall automatically, with no further action by any Party, be deemed to be amended to incorporate the human gene target for such Regional Licensed Product as a Licensed Target under the Regional License Terms and to incorporate as part of the Regional License Terms or this Master Agreement the schedules, appendices and exhibits in respect of such Regional Licensed Product that were included in the last Option Data Package delivered by Alnylam for such Regional Licensed Product or, in the case of the Global Development Strategy for such Regional Licensed Product, mutually agreed upon by the Parties prior to the Option Exercise Date. The Parties may, at their option, prepare an updated version of the Regional License Terms and this Master Agreement that includes such schedules, appendices and exhibits.

3.4.4. Co-Co/Global Option.

3.4.4.1. ALN-AT3 . If Genzyme exercises the Co-Co/Global Option for ALN-AT3, then on the applicable Option Exercise Date, ALN-AT3 shall automatically be deemed to be Co-Co Licensed Product for all purposes under the Collaboration Agreement and the license from Alnylam to Genzyme to such Co-Co Licensed Product shall automatically, with no further action by any Party, go into full force and effect and all of the obligations of Alnylam and Genzyme set forth in the Co-Co License Terms, including the payment obligations set forth therein, shall become the binding obligations of the applicable Party in respect of ALN-AT3. As part of the effectiveness of such license, the Co-Co License Terms shall automatically, with no further action by any Party, be deemed to be amended to incorporate AT3 as a Licensed Target under the Co-Co License Terms and to incorporate as part of the Co-Co License Terms or this Master Agreement the schedules, appendices and exhibits in respect of such Co-Co Licensed Product that were included in the last Option Data Package delivered by Alnylam or, in the case of the Global Development Strategy for such Co-Co Licensed Product, mutually agreed upon by the Parties prior to the Option Exercise Date. The Parties may, at their option, prepare an updated version of the Co-Co License Terms and this Master Agreement that includes such schedules, appendices and exhibits.

3.4.4.2. ALN-AS1 . If Genzyme exercises the Co-Co/Global Option for ALN-AS1, then on the applicable Option Exercise Date, the applicable Co-Co/Global Option Product shall automatically be deemed to be a Global Licensed

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Product for all purposes under the Collaboration Agreement and the license from Alnylam to Genzyme to such Global Licensed Product shall automatically, with no further action by any Party, go into full force and effect and all of the obligations of Alnylam and Genzyme set forth in the Global License Terms, including the payment obligations set forth therein, shall become the binding obligations of the applicable Party in respect of such Global Licensed Product. As part of the effectiveness of such license, the Global License Terms shall automatically, with no further action by any Party, be deemed to be amended to incorporate ALN-AS1 as a Licensed Target under the Global License Terms and to incorporate as part of the Global License Terms or this Master Agreement the schedules, appendices and exhibits in respect of such Global Licensed Product that were included in the last Option Data Package delivered by Alnylam for such Global Licensed Product. The Parties may, at their option, prepare an updated version of the Global License Terms and this Master Agreement that includes such schedules, appendices and exhibits.

3.4.5. Global Options. On the applicable Option Exercise Date for the exercise of a Global Option or Trailing Global Option, the applicable Global Option Product or Trailing Global Option Product shall automatically be deemed to be a Global Licensed Product for all purposes under the Collaboration Agreement and the license from Alnylam to Genzyme to such Global Licensed Product shall automatically, with no further action by any Party, go into full force and effect and all of the obligations of Alnylam and Genzyme set forth in the Global License Terms, including the payment obligations set forth therein, shall become the binding obligations of the applicable Party in respect of such Global Licensed Product. As part of the effectiveness of such license, the Global License Terms shall automatically, with no further action by any Party, be deemed to be amended to incorporate the human gene target for such Global Licensed Product as a Licensed Target under the Global License Terms and to incorporate as part of the Global License Terms or this Master Agreement the schedules, appendices and exhibits in respect of such Global Licensed Product that were included in the last Option Data Package delivered by Alnylam for such Global Licensed Product. The Parties may, at their option, prepare an updated version of the Global License Terms and this Master Agreement that includes such schedules, appendices and exhibits.

3.4.6. Development and Commercialization Following Option Exercise. Following the Option Exercise Date for a Collaboration Product, the Development and Commercialization of such Collaboration Product shall thereafter be governed by the applicable License Terms.

3.5. Option Not Exercised . If Genzyme does not deliver to Alnylam an Exercise Notice, or if Genzyme elects and delivers written notice to Alnylam to terminate an Option, with respect to an Option Product prior to the expiration of the applicable Option Exercise Period, then Genzyme’s Option with respect to such Option Product shall expire, Genzyme’s other rights

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with respect to such Option Product (including any rights under Section 4 (Development and Pharmacovigilance) and Section 5 (Collaboration Management)), shall lapse, and Alnylam shall thereafter be free to Develop, Manufacture or Commercialize, alone or with one or more Third Parties, such Option Product, in each case without any further obligation to Genzyme. In addition, so long as Alnylam continues to actively Develop an Option Product following the expiration of Genzyme’s Option or Alnylam grants any rights to an Option Product to a Third Party, then other siRNAs Developed by Alnylam or any such Third Party (or its licensees or sublicensees, through multiple tiers) that target the same human gene as such Option Product (except for siRNAs described in clause (ii) of Section 1.2.21 (ALN-AT3) or clause (ii) of Section 1.2.20 (ALN-AS1) if any such siRNA is potentially subject to the Co-Co/Global Option) shall not be considered Option Products for purposes of this Master Agreement and Genzyme shall not have any Option hereunder with respect to such other siRNAs; provided , however , that if Alnylam ceases active Development of such Option Product, then the other siRNAs that target the same human gene as such Option Product shall again be considered Option Products for the purposes of this Master Agreement. [***].

3.6. Exclusivity during Option Period .

3.6.1. Exclusivity for Core Pipeline Programs. Subject to Section 13.16.2 (Future Acquisition of a Party or its Business), during the Option Period, Alnylam and its Affiliates shall not enter into any agreement with any Third Party that grants such Third Party any rights with respect to any Core Pipeline Program that would be in conflict with the Collaboration Agreement following an siRNA becoming a Collaboration Product under the Collaboration Agreement, provided that this restriction shall not apply to:

3.6.1.1. following the expiration of the Option Exercise Period for an Option Product, an agreement with a Third Party that grants such Third Party rights with respect to such Option Product and other siRNAs that target the same human gene as such Option Product;

3.6.1.2. an agreement with a Third Party that grants such Third Party rights with respect to any Named Pipeline Program (excluding ALN-TTR02, ALN-TTRsc, ALN-AT3 and ALN-AS1) solely in the Alnylam Territory, provided that Alnylam complies with the provisions of Section 3.6.3 (ROFN for Available Third Party Rights) and 3.6.4 (Permitted Third Party Agreements);

3.6.1.3. following the exercise of the Co-Co/Global Option with respect to either Co-Co/Global Option Product, an agreement with a Third Party that grants such Third Party rights with respect to the other Co-Co/Global Option Product solely in the Alnylam Territory, provided that Alnylam complies with the provisions of Section 3.6.3 (ROFN for Available Third Party Rights) and 3.6.4 (Permitted Third Party Agreements); or

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3.6.1.4. following the exercise of the Global Option, an agreement with a Third Party that grants such Third Party rights with respect to any Core Pipeline Program solely in the Alnylam Territory, provided that Alnylam complies with the provisions of Section 3.6.3 (ROFN for Available Third Party Rights) and 3.6.4 (Permitted Third Party Agreements).

3.6.2. Other Exclusivity Requirements in License Terms. Upon the exercise of any Option (which will cause an Option Product to become a Collaboration Product), the exclusivity provisions set forth in the applicable License Terms will go into effect with respect to such Collaboration Product.

3.6.3. ROFN for Available Third Party Rights. If Alnylam desires to enter into an agreement described in Section 3.6.1.2, 3.6.1.3 or 3.6.1.4, other than in accordance with Section 4.4 (Third Parties), then Alnylam shall so notify Genzyme in writing, which notice shall describe the rights that Alnylam intends to grant to a Third Party pursuant to such agreement (the “ Available Third Party Rights ”). Genzyme shall have [***] days from receipt of such written notice to notify Alnylam in writing as to whether Genzyme desires to negotiate for such Available Third Party Rights (a “ ROFN Exercise Notice ”). If Genzyme delivers a ROFN Exercise Notice prior to the expiration of such [***]-day period, Genzyme shall have the exclusive right for [***] days following the date that Genzyme delivers a ROFN Exercise Notice (the “ ROFN Offer Period ”) to negotiate with Alnylam and to make one or more written non-binding offers to Alnylam concerning the terms on which Genzyme would enter into an agreement to acquire the Available Third Party Rights (a “ ROFN Non-Binding Offer ”). If Genzyme delivers a ROFN Non-Binding Offer to Alnylam prior to the expiration of the ROFN Offer Period, Genzyme shall thereafter have the exclusive right for [***] days (or such longer period as may be mutually agreed by the Parties) (the “ ROFN Negotiation Period ”), to finalize and enter into a definitive agreement with Alnylam for the acquisition of such Available Third Party Rights. Alnylam shall not, during the ROFN Offer Period or Negotiation Period, enter into discussions, exchange information, or otherwise negotiate with any Third Party with respect to any of the Available Third Party Rights. If (i) Genzyme does not provide a ROFN Exercise Notice within [***] days of receiving notice of Available Third Party Rights, (ii) Genzyme does not provide a ROFN Non-Binding Offer prior to the expiration of the ROFN Offer Period, or (iii) the Parties do not execute a definitive agreement with respect to the Available Third Party Rights prior to the expiration of the ROFN Negotiation Period, then Alnylam shall be free to enter into an agreement with any Third Party with respect to such Available Third Party Rights (any such agreement, a “ Permitted Third Party Agreement ”), provided that, during the period of [***] months after the later of the expiration of the ROFN Offer Period or expiration of the ROFN Negotiation Period, Alnylam shall not enter into a Permitted Third Party Agreement with respect to such Available Third Party Rights on terms that are, in the aggregate, materially more favorable to such Third Party than the

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last terms offered in writing by Genzyme to Alnylam during the ROFN Offer Period or ROFN Negotiation Period, as applicable, unless (a) Alnylam first re-offers to enter into an agreement with Genzyme on such more favorable terms and Genzyme does not accept such offer and enter into such agreement with Alnylam within [***] days after such re-offer. For clarity, prior to the ROFN Offer Period and ROFN Exercise Period with respect to any Available Third Party Rights, Alnylam shall be free to engage in discussions and exchange information with Third Parties with respect to such Available Third Party Rights, but shall not enter into any binding agreement with any Third Party with respect to such Available Third Party Rights.

3.6.4. Permitted Third Party Agreements. If Alnylam enters into a Permitted Third Party Agreement pursuant to Section 3.6.3 (ROFN For Available Third Party Rights) with respect to any Regional Option Product, such Permitted Third Party Agreement shall be compliant with Alnylam’s obligations under, and consistent with the terms of, the Regional License Terms.

3.6.5. Gate-Keeping. Promptly following the Effective Date, Alnylam shall establish a commercially reasonable mechanism to ensure that it does not grant any Third Party any rights with respect to a Core Pipeline Program in violation of Section 3.6.1 (Exclusivity for Core Pipeline Programs), whether pursuant to a new agreement or an amendment to, or any action or inaction pursuant to, any agreement between a Third Party and Alnylam that is in effect on the Effective Date.

4. DEVELOPMENT AND PHARMACOVILIGANCE

4.1. Overview . Alnylam shall control and be responsible for the Development of its Core Pipeline Programs. In connection therewith, Alnylam shall be responsible for all communications, interactions and filings with, submissions to, and other actions related to, each Regulatory Authority regarding the Core Pipeline Programs.

4.2. Diligence . Subject to and without limiting any obligation set forth in any License Terms, during the Option Period, Alnylam shall use commercially reasonable efforts to initiate Core Pipeline Programs and undertake the Development of Option Products from its Core Pipeline Programs through achievement of Human POP Study Completion and thereafter through the end of the applicable Option Exercise Period in accordance with industry standards in the biotechnology and pharmaceutical industry. During the Transition Period, Alnylam shall use commercially reasonable efforts to Develop the applicable Option Product. In addition, both Parties shall use commercially reasonable efforts to plan for the transition to Genzyme of any Global Option Product during the applicable Transition Period upon the Implementation Date of the applicable License Terms.

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4.3. Scientific Records . Alnylam shall maintain scientific records, in sufficient detail and in sound scientific manner appropriate for patent and regulatory purposes and in compliance with GLP with respect to activities intended to be submitted in regulatory filings (including INDs), which shall fully and properly reflect all work done and results achieved in the performance of the Development activities with respect to potential Option Products by Alnylam.

4.4. Third Parties . Alnylam shall be entitled to utilize the services of Third Parties to perform the Development activities with respect to Option Products under this Master Agreement, provided that (a) Alnylam shall require that such Third Party operates in a manner consistent with the terms of the Collaboration Agreement and (b) Alnylam shall remain at all times fully liable for its responsibilities and (c) the Parties will make reasonable efforts to share through the PAC information regarding any prior experience with specific CROs that are anticipated to be engaged to perform work for any Core Pipeline Program. Alnylam shall require, however, that any such Third Party agreement (other than an agreement with an academic institution) include commercially reasonable confidentiality and non-use provisions that are, in the aggregate, not materially less stringent than those included in the Collaboration Agreement. Lastly, Alnylam shall use commercially reasonable efforts to obtain ownership of, and/or a fully sublicensable license under and to, any Know-How and Patent Rights that are developed by such Third Party in the performance of such agreement and are reasonably expected to be necessary or useful to Develop, Manufacture and/or Commercialize Option Products.

4.5. Oversight . The Collaboration shall be conducted under the oversight of the Alliance Joint Steering Committee which shall have the responsibilities outlined in the Collaboration Agreement.

4.6. Pharmacovigilance . At least [***], the Parties will negotiate in good faith and enter into a Safety Data Exchange Agreement (“ SDEA ”), which will define the pharmacovigilance responsibilities of the Parties and include safety data exchange procedures governing the coordination of collection, investigation, reporting and exchange of information concerning any adverse experiences, and any product quality and product complaints associated with adverse experiences, related to such Collaboration Product sufficient to enable each Party (and their respective Related Parties, if any) to comply with its legal and regulatory obligations. In addition, as appropriate, such SDEAs will include the safety data exchange procedures governing the exchange of information affecting the class ( e.g. , serious adverse events, emerging safety issues).

5. COLLABORATION MANAGEMENT

5.1. Alliance Joint Steering Committee .

5.1.1. Composition. The AJSC shall be comprised of three (3) representatives who are employees of each Party. Each Party shall appoint its respective representatives to the AJSC as of the Effective Date and may substitute one or more of its

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representatives, in its sole discretion, effective upon notice to the other Party of such change. Each Party shall have at least two (2) AJSC representatives who are executive level employees (vice president or above), and all AJSC representatives shall have appropriate expertise, seniority, decision-making authority and ongoing familiarity with the Collaboration. Additional representatives or consultants may from time to time, by mutual consent of the Parties, be invited to attend AJSC meetings, subject to such representatives and consultants (or the representative’s or consultant’s employer) undertaking confidentiality obligations, whether in a written agreement or by operation of law, no less stringent than the requirements of Section 7.1 (Nondisclosure Obligation).

5.1.2. AJSC Chairperson. The AJSC shall be co-chaired, with one chairperson designated by Alnylam and one chairperson designated by Genzyme, whose responsibilities shall include conducting meetings, including, when feasible, ensuring that objectives for each meeting are set and achieved. Responsibility for running each meeting of the AJSC will alternate between the chairpersons from meeting-to-meeting, with Alnylam’s chairperson running the first meeting.

5.1.3. Alliance Managers.

5.1.3.1. Each Party shall appoint an alliance manager who is an employee of such Party (each, an “ Alliance Manager ”). Each Alliance Manager will be responsible to ensure a collaborative work environment between the Parties to ensure that the alliance is run smoothly, professionally and productively. Each Alliance Manager shall act in his or her discretion to facilitate the execution of the Collaboration throughout their organization and will oversee and support implementation plans; promote effectiveness of the governance model and implementation of contractual provisions and lead any changes to enhance the alliance; and facilitate the AJSC (and other bodies) for effective decision making in a timely manner. The Alliance Managers will serve as a primary point of contact for the other Party under the Collaboration and will undertake such other tasks as are detailed in the Collaboration Agreement or as may be assigned by the AJSC. Each Alliance Manager shall attend each meeting of the AJSC. Each Party may change its Alliance Manager at any time in its sole discretion with written notice to the other Party.

5.1.3.2. The Alliance Managers shall be responsible for (i) scheduling meetings of the AJSC, (ii) setting agendas for meetings with solicited input from other members and (iii) for acting as secretary at each meeting and preparing the draft minutes of such meeting, which shall provide a description in reasonable detail of the discussions held at the meeting and a list of any actions, decisions or determinations approved by the AJSC. [***] days after each meeting, the drafting Alliance Manager shall provide the draft minutes to the other Alliance Manager for review and comment. The drafting Alliance Manager

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shall reasonably consider all comments from the other Alliance Manager that are provided within [***] days. The drafting Alliance Manager shall prepare and submit revised minutes for approval within [***] days after receipt of such comments or upon the expiration of such [***] day comment period. Beginning with Alnylam’s Alliance Manager, such responsibilities shall alternate between the Alliance Managers on a meeting-by-meeting basis after each meeting of the applicable committee.

5.1.4. Meetings. The AJSC shall meet in accordance with a schedule established by mutual written agreement of the Parties, but no less frequently than once per Calendar Quarter during the Term, provided that either Party may from time to time reasonably request that the AJSC meet to undertake its duties under Section 5.1.7(c), 5.1.7(d), 5.1.7(e), 5.1.7(f), 5.1.7(h) or 5.1.7(i). The location for any such meetings shall alternate between Alnylam and Genzyme facilities (or such other locations as are mutually agreed by the Parties). Alternatively, the AJSC may meet by means of teleconference, videoconference or other similar communications equipment. All meetings and proceedings for the AJSC or its subcommittees shall take place in English. Each Party shall bear its own expenses relating to attendance at such meetings by its representatives.

5.1.5. Subcommittee Minutes. For each subcommittee created pursuant to Section 5.1.6 (Subcommittees), each Party shall designate a secretary, who may be such Party’s Alliance Manager, to prepare draft minutes of each meeting, which shall provide a description in reasonable detail of the discussions held at the meeting and a list of any actions, decisions or determinations approved by such committee. Beginning with the Alnylam secretary, the responsibility for preparing the minutes shall alternate between the secretaries on a meeting-by-meeting basis after each meeting of such subcommittee. Within [***] days after each meeting, the drafting secretary shall provide the draft minutes to the other secretary for review and comment. The drafting secretary shall reasonably consider all comments from the other secretary that are provided within [***] days. The drafting secretary shall prepare and submit revised minutes for approval within [***] days after receipt of such comments or upon the expiration of such [***] day comment period.

5.1.6. Subcommittees.

5.1.6.1. The Parties or the AJSC shall have the right to create such subcommittees of the AJSC as they or it may deem appropriate or necessary (such as a finance subcommittee, or other appropriate subcommittees). Each such subcommittee shall report to the AJSC, which shall have authority to approve or reject recommendations or actions proposed thereby, subject to the terms of the Collaboration Agreement. Each Party shall bear its own expenses relating to attendance at any meetings of such subcommittees by its representatives. Each such subcommittee shall have a chairperson, designated by Alnylam, whose responsibilities shall include conducting meetings, including ensuring that objectives for each meeting are set and achieved.

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5.1.6.2. The Parties hereby establish a Pipeline Advisory Committee and an IP Committee as subcommittees of the AJSC, each of which shall have the responsibilities outlined in the Collaboration Agreement.

5.1.6.3. Each PJSC established pursuant to the License Terms will be a subcommittee of the AJSC; provided , however , that the membership, operation and responsibilities of each PJSC shall be governed by the applicable License Terms and not this Section 5.1.6. As a general matter, the Parties expect that the representatives on the AJSC will be more senior than the representatives on the PJSC(s).

5.1.7. AJSC Responsibilities. The AJSC shall have the following responsibilities with respect to the Development, Manufacturing and Commercialization of Option Products from the Core Pipeline Programs and Collaboration Products pursuant to the Collaboration:

(a) coordinating the activities of the Parties under the Collaboration, including budget matters;

(b) overseeing the AJSC’s subcommittees and ensuring effective participation in each such committee’s operations by any of its members;

(c) considering (but not deciding) whether any Clinical Study, or protocol therefor, will satisfy the criteria of a Human POP Study in accordance with Section 3.1.2.3 (Design of Human POP Studies), [***];

(d) attempting to resolve disputes as to whether an Alnylam Program should be categorized as a Core Pipeline Program or a Non-Core Pipeline Program;

(e) resolving whether an Option Data Package is missing information pursuant to Section 3.3.4.1(b) (Disputed Missing Information);

(f) resolving any disputed terms of any Supply Agreement under Section 6.3 (Disputed Supply Agreement Terms);

(g) reviewing the status of Collaboration Products, including material Development and Commercialization matters;

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(h) resolving disputes on behalf of each PJSC in accordance with, and subject to the limitations set forth in, the applicable License Terms;

(i) addressing any other matters referred to the AJSC by the terms of the Collaboration Agreement; and

(j) performing such other activities as the Parties agree in writing shall be the responsibility of the AJSC.

5.1.8. Decision-Making.

5.1.8.1. Voting . With respect to decisions of the AJSC, the representatives of each Party shall have collectively one vote on behalf of such Party. For each meeting of the AJSC, at least two (2) representatives of each Party shall constitute a quorum. Action on any matter may be taken at a meeting, by teleconference, by videoconference or by written agreement.

5.1.8.2. Escalation . The AJSC shall attempt to resolve any and all disputes before it for decision by consensus.

(a) If the AJSC is unable to reach consensus with respect to a dispute arising under this Master Agreement for a period in excess of [***] days, then the dispute shall be submitted to [***] for resolution. If such dispute cannot be resolved for a period in excess of [***] days following escalation (or such other period as the Parties may agree), then [***].

(b) If the AJSC is unable to reach consensus with respect to a dispute related to any Collaboration Product or otherwise arising under any of the License Terms, then the dispute shall be resolved as set forth in the applicable License Terms [***].

5.1.8.3. Resolution of Core Pipeline Disputes . [***].

5.1.9. Term. Either Party shall have the right to terminate the AJSC upon the expiration of the later to expire of (i) the Option Periods and (ii) all of the License Terms. Notwithstanding the foregoing, on a Regional Licensed Product-by-Regional Licensed Product basis and on a Global Licensed Product-by-Global Licensed Product basis, Alnylam shall have the right (but not the obligation) to continue to participate in the AJSC in relation to any such Collaboration Product following the earlier of (i) the [***] anniversary of the Option Exercise Date for such Collaboration Product and (ii) the termination of the Product Joint Steering Committee (as such term is defined in the Regional License Terms) or the Joint Transition Team (as such term is defined in the Global License Terms), as applicable, for such Collaboration Product.

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5.2. Pipeline Advisory Committee .

5.2.1. Composition. The Pipeline Advisory Committee shall be comprised of three (3) representatives who are employees of each Party. Each Party shall appoint its respective representatives to the PAC within thirty (30) days of the Effective Date, and from time to time may substitute one or more of its representatives, in its sole discretion, effective upon notice to the other Party of such change. Each Party shall have at least one PAC representative who is a senior level (vice president or above) employee. All PAC representatives shall have appropriate expertise, seniority, decision-making authority and ongoing familiarity with the Collaboration and each Party’s representatives collectively shall have relevant expertise in research, development and commercial matters. Additional representatives or consultants may from time to time, by mutual consent of the Parties, be invited to attend PAC meetings, subject to such representatives and consultants (or the representative’s or the consultant’s employer) undertaking confidentiality obligations, whether in a written agreement or by operation of law, no less stringent than the requirements of Section 7.1 (Nondisclosure Obligation).

5.2.2. Meetings. The PAC shall meet in person once per Calendar Quarter at Alnylam, provided that either Party may from time to time reasonably request that the PAC meet to undertake its duties under Section 3.1.1 (Program Identification) at a location mutually agreed by the Parties.

5.2.3. PAC Development Responsibilities. The PAC shall provide input to Alnylam and the AJSC regarding the following with respect to the Development of Option Products from the Core Pipeline Programs prior to their achieving Human POP Study Completion and pursuant to the Collaboration:

(a) the selection of targets for new Core Pipeline Programs;

(b) the inclusion of Alnylam Programs on the Tentative Core Pipeline Program List, Core Pipeline Program List and the Non-Core Pipeline Program List pursuant to Section 3.1.1 (Program Identification);

(c) reviewing and discussing periodic updates from Alnylam to the PAC regarding the development status of potential Option Products; and

(d) such other matters as the Parties agree in writing shall be the responsibility of the PAC.

5.2.4. Decision-Making. The PAC shall be an advisory committee for the Collaboration and to the AJSC. The PAC shall not have any final decision making power.

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5.2.5. Term. Either Party shall have the right to terminate the PAC upon the expiration of the last to expire of the Option Periods.

5.3. IP Committee .

5.3.1. Composition . The IP Committee shall be comprised of at least one (1) representative who is an employee of each Party. Each Party shall appoint its respective representatives to the IP Committee within thirty (30) days of the Effective Date, and from time to time, may substitute one or more of its representatives, in its sole discretion, effective upon notice to the other Party of such change. All IP Committee representatives shall have appropriate expertise, seniority, decision-making authority and ongoing familiarity with the Collaboration and each Party’s representatives collectively shall have relevant expertise in intellectual property portfolio management and licensing matters. Additional representatives or consultants may from time to time, by mutual consent of the Parties, be invited to attend IP Committee meetings, subject to such representatives and consultants (or the representative’s or consultant’s employer) undertaking confidentiality obligations, whether in a written agreement or by operation of law, no less stringent than the requirements of Section 7.1 (Nondisclosure Obligation).

5.3.2. Meetings. The IP Committee shall meet as necessary to carry out its duties under Section 5.3.3 (IP Committee Responsibilities), but no more often than once per Calendar Quarter, unless otherwise agreed by its members. The IP Committee shall meet in-person at Alnylam or Genzyme or, alternatively, by means of teleconference, videoconference or other similar communications equipment.

5.3.3. IP Committee Responsibilities. The IP Committee shall provide input to Alnylam regarding the following with respect to Option Products from the Core Pipeline Programs and as indicated in the Global License Terms, the Regional License Terms and the Co-Co License Terms:

(a) strategies for managing certain Patents Rights pursuant to Section 11.2 (Patent Prosecution Information Sharing);

(b) the necessity and terms of any Proposed In-License pursuant to Section 11.3.3.1 (Proposed In-Licenses); and

5.3.4. Decision-Making. The IP Committee shall be an advisory committee for the Collaboration and to Alnylam and shall make recommendations by consensus. The IP Committee shall not have any final decision making power. If there is a disagreement between the Parties’ representatives on the IP Committee, at either Party’s request, the General Counsel or other Senior Counsel of each Party will attend a follow-up meeting of the IP Committee to discuss the matter further. The IP Committee may escalate matters to the AJSC as it deems appropriate.

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5.3.5. Term. Either Party shall have the right to terminate the IP Committee upon the expiration of the last to expire of the Option Periods, except that no Party shall have the right to terminate the IP Committee in respect of the Collaboration Product(s) prior to the termination of the License Terms, as applicable. Notwithstanding the foregoing, on a Collaboration Product-by-Collaboration Product basis , Alnylam shall have the right (but not the obligation) to continue to participate in the IP Committee in relation to any such Collaboration Product following the [***] anniversary of the Option Exercise Date for such Collaboration Product.

5.4. Manufacturing Committee .

5.4.1. Composition. The Manufacturing Committee shall be comprised of at least one (1) representative who is an employee of each Party. Each Party shall appoint its respective representative to the Manufacturing Committee within thirty (30) days of the Effective Date, and from time to time, may substitute one or more of its representatives, in its sole discretion, effective upon notice to the other Party of such change. All Manufacturing Committee representatives shall have appropriate expertise, seniority, decision-making authority and ongoing familiarity with the Collaboration and each Party’s representatives collectively shall have relevant expertise in matters related to the Manufacturing and supply of human therapeutic products. Additional representatives or consultants may from time to time, by mutual consent of the Parties, be invited to attend Manufacturing Committee meetings, subject to such representatives and consultants (or the representative’s or consultant’s employer) undertaking confidentiality obligations, whether in a written agreement or by operation of law, no less stringent than the requirements of Section 7.1 (Nondisclosure Obligation).

5.4.2. Meetings. The Manufacturing Committee shall meet as necessary to carry out its duties under Section 5.4.3 (Manufacturing Committee Responsibilities), but no more often than once per Calendar Quarter, unless otherwise agreed by its members. The Manufacturing Committee shall meet in-person at Alnylam or Genzyme or, alternatively, by means of teleconference, videoconference or other similar communications equipment.

5.4.3. Manufacturing Committee Responsibilities. The Manufacturing Committee shall provide a forum for the discussion and review of matters related to the Manufacturing and supply of Collaboration Products, including the following:

(a) worldwide Manufacturing and sourcing strategies in support of the Development and Commercialization of Collaboration Products, including the strategic aspects of Manufacture and release of finished Collaboration Product;

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(b) use of Third Parties to Manufacture and supply any Collaboration Product;

(c) logistical strategies, capacity planning and inventory levels for each Collaboration Product for consistency with the then-current Development Plans and Commercialization Plans for such Collaboration Product;

(d) results of regulatory inspections related to Collaboration Products and reviewing steps to be taken by the Parties to address any deficiencies noted;

(e) capacity planning and supply continuity plans for each Collaboration Product for consistency with the then-current Development Plan and Commercialization Plan for such Collaboration Product; regulatory compliance related to the Manufacture of Collaboration Products;

(f) material quality-related issues concerning the Collaboration Products;

(g) costs of Manufacture;

(h) providing updates to the AJSC or a PJSC, as applicable, upon request relating to Manufacturing issues; and

(i) such other matters as the Parties agree in writing shall be the responsibility of the Manufacturing Committee.

5.4.4. Decision-Making. The Manufacturing Committee shall be an advisory committee for the Collaboration and shall make recommendations by consensus. The Manufacturing Committee shall not have any final decision making power.

5.4.5. Term. Either Party shall have the right to terminate the Manufacturing Committee upon the expiration of the last to expire of the (i) Option Periods, and (ii) all of the License Terms. Notwithstanding the foregoing, on a Regional Licensed Product-by-Regional Licensed Product basis and on a Global Licensed Product-by-Global Licensed Product basis, Alnylam shall have the right (but not the obligation) to continue to participate in the Manufacturing Committee in relation to any such Collaboration Product following the earlier of (i) the [***] anniversary of the Option Exercise Date for such Collaboration Product and (ii) the termination of the Product Joint Steering Committee (as such term is defined in the Regional License Terms) or the Joint Transition Team (as such term is defined in the Global License Terms), as applicable, for such Collaboration Product.

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5.5. Product Joint Steering Committees . Pursuant to the License Terms, the Parties will form a PJSC (as defined in each of the License Terms) that has certain responsibilities with respect to the Development and Commercialization of each Collaboration Product as set forth in the License Terms for such Collaboration Product. For the avoidance of doubt, the same representatives from each Party may serve on the PJSC for more than one Collaboration Product and, where membership of a PJSC for a Collaboration Product is the same as one or more other PJSCs for other Collaboration Product(s), such PJSCs may have a single meeting to discuss each Collaboration Product for which they have responsibility.

5.6. No Power to Amend . Unless otherwise agreed to by the Parties in writing, the AJSC, PAC, IP Committee, Manufacturing Committee and each PJSC will have only the powers expressly assigned to it in the Collaboration Agreement. In no event will any of them have any power to amend, modify, or waive compliance with this Agreement.

5.7. Confidentiality . All information disclosed by either Party or its representatives to the other Party or its representatives under this Section 5 shall be deemed to be Confidential Information of the disclosing Party and maintained in accordance with Section 7 (Confidentiality and Publication).

5.8. Modifications . The Parties shall meet from time to time to discuss whether any changes to the governance structure for the Collaboration are necessary or advisable.

5.9. Other Governance Terms . Governance provisions related to each Collaboration Product are located in the applicable License Terms.

6. MANUFACTURE AND SUPPLY OF THE COLLABORATION PRODUCTS

6.1. ALN-TTR02 Supply Agreements . Subject to the terms and conditions of this Section 6 (Manufacture and Supply of the Collaboration Products), within [***] days after receiving written notice from Genzyme requesting such negotiations, the Parties will negotiate in good faith and enter into a supply agreement (and any other necessary ancillary agreements) for clinical supply of ALN-TTR02 by Alnylam (or for Alnylam by Alnylam’s Third Party manufacturer) (the “ ALN-TTR02 Clinical Supply Agreement ”), which will be consistent with the terms set forth on Schedule 6.1 . In addition, at the request of Genzyme at least [***] months in advance of the first Regulatory Approval of ALN-TTR02 in the Genzyme Territory, the Parties will negotiate in good faith and enter into a supply agreement (and any other necessary ancillary agreements), before such [***]-month date, for commercial supply of ALN-TTR02 by Alnylam (or for Alnylam, by Alnylam’s Third Party manufacturer) (the “ ALN-TTR02 Commercial Supply Agreement ”), which will also be consistent with the terms set forth on Schedule 6.1 . Notwithstanding the foregoing, the breach of any such Manufacturing terms as applied to a Collaboration Product shall be treated as a breach under the Regional License Terms, and not under this Master Agreement. When the Parties enter into an ALN-TTR02 Clinical Supply Agreement or ALN-TTR02 Commercial Supply agreement, such agreement will supersede the terms set forth in Schedule 6.1 with respect to Manufacture and supply of ALN-TTR02.

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6.2. Collaboration Product Supply Agreements . Subject to the terms and conditions of this Section 6 (Manufacture and Supply of the Collaboration Products), following the Implementation Date with respect to any given Collaboration Product other than ALN-TTR02, and within [***] days following a written notice by Genzyme requesting such negotiation, the Parties will negotiate in good faith and enter into a supply agreement (and any other necessary ancillary agreements) for clinical supply of such Collaboration Product by Alnylam (or for Alnylam by Alnylam’s Third Party manufacturer) (each, a “ Clinical Supply Agreement ”), which will be consistent with the terms set forth on Schedule 6.2 . In addition, at least [***] months in advance of the first Regulatory Approval of each Collaboration Product (other than ALN-TTR02) the Parties will negotiate in good faith and enter into a supply agreement (and any other necessary ancillary agreements), before such [***]-month date, for commercial supply of such Collaboration Product by Alnylam (or for Alnylam by Alnylam’s Third Party manufacturer) (each, a “ Commercial Supply Agreement ”), which will also be consistent with the terms set forth on Schedule 6.2 ; provided , however , in the case of any Global Licensed Product, the Parties shall only negotiate and enter into a Commercial Supply Agreement at the request of Genzyme. Notwithstanding the foregoing, the breach of any such Manufacturing terms as applied to a Collaboration Product shall be treated as a breach under its respective License Terms, and not under this Master Agreement. When the Parties enter into a Clinical Supply Agreement or Commercial Supply Agreement, such agreement will supersede the terms set forth in Schedule 6.2 with respect to the Manufacture and supply of the applicable Collaboration Product.

6.3. General Supply Agreement Requirements . In addition to reflecting terms consistent with those set forth on Schedule 6.1 or Schedule 6.2 , as applicable, each Alnylam Supply Agreement will include key performance indicators for Alnylam (including criteria regarding Manufacturing capacity, quantity, timeliness of delivery, quality and cost that are consistent with prevailing industry standards for Third Party contract manufacturing agreements) (collectively, the “ KPIs ”). Further, for each Alnylam Supply Agreement for a given Collaboration Product, the Parties shall also enter into a quality technical agreement, which will be designed to ensure sufficient oversight by Genzyme of quality matters related to the Manufacture and testing of such Collaboration Product by Alnylam and its Third Party manufacturers and will set forth the quality responsibilities and obligations of both Genzyme and Alnylam.

6.4. Disputed Supply Agreement Terms . If the Parties are unable to reach agreement on any terms of any of the Alnylam Supply Agreements, as required by Sections 6.1 (ALN-TTR02 Supply Agreements), 6.2 (Collaboration Product Supply Agreements) and 6.3 (General Supply Agreement Requirements), then any such disputed terms shall be submitted to the AJSC for resolution pursuant to Section 5.1.8 (Decision-Making). If the AJSC is unable to resolve any such disputed terms, then those unresolved disputed terms shall be [***].

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6.5. Transfer of Manufacturing Know-How . [***].

6.6. Establishment of Second Source and Back-Up Sources .

6.6.1. [***].

6.6.2. [***].

6.6.2.1. [***].

6.6.2.2. [***].

6.6.2.3. [***].

6.6.2.4. [***].

6.6.2.5. [***].

6.7. Third Party Manufacturers and Subcontracting . If, following the Effective Date, either Party desires to enter into an agreement with a Third Party manufacturer for the supply of Product, then (a) the other Party shall have the right to review and approve (such approval not unreasonably withheld, conditioned or delayed) such Third Party manufacturer and (b) each Party shall keep the other Party reasonably informed through the Manufacturing Committee of the status of any proposed supply agreement to be entered into with any such Third Party manufacturer with respect to the Manufacture and supply of such Product (a “ Third Party Supply Agreement ”) and submit any such Third Party Supply Agreement to the Manufacturing Committee for review and good faith discussion prior to its execution. For the avoidance of doubt, if a Party is subject to an existing binding agreement with a Third Party manufacturer for the supply of Product as of the Effective Date (each an “ Existing Third Party Supply Agreement ”), then, provided that such existing binding agreement is not materially amended at any time following the Effective Date (i) such existing binding agreement shall be deemed a Third Party Supply Agreement and (ii) the provisions of clauses a and b (immediately above) shall not apply to such existing binding agreement or the Third Party manufacturer party thereto. Without the consent of the other Party, but subject to the terms of this Section 6, either Party may subcontract (in whole or in part) its Manufacturing obligations under any Alnylam Supply Agreement or Genzyme Supply Agreement, as applicable, to a qualified Third Party manufacturer pursuant to a binding Third Party Supply Agreement; provided , however , that (A) the subcontracting Party shall remain solely responsible to the other Party for the performance of the subcontracting Party’s obligations under each Alnylam Supply Agreement or Genzyme Supply Agreement, as applicable and (B) the terms and/or conditions of any Third Party Supply

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Agreement shall not in any way amend, modify or diminish the subcontracting Party’s obligations to the other Party under any Alnylam Supply Agreement or Genzyme Supply Agreement, as applicable. If the forecasting or order timing/method provisions of a Third Party Supply Agreement do not align with the corresponding provisions of a relevant Alnylam Supply Agreement or Genzyme Supply Agreement, as applicable, then, at the request of the subcontracting Party, the Parties shall discuss in good faith appropriate modifications to such Alnylam Supply Agreement or Genzyme Supply Agreement, as applicable, to bring the relevant provisions into alignment with such Third Party Supply Agreement, provided , however , that the non-subcontracting Party shall have no obligation to agree to any amendment to such Alnylam Supply Agreement or Genzyme Supply Agreement that can reasonably be expected to materially disadvantage the non-subcontracting Party.

6.8. Waivers . In the event that any Collaboration Product must be substantially Manufactured in the United States pursuant to applicable Law, then, at Genzyme’s request, Alnylam will use commercially reasonable efforts, at Genzyme’s expense, to secure a waiver of such requirement for such Collaboration Product under 35 U.S.C. § 204 or any analogous applicable Law outside the United States. If a waiver of the substantially manufactured requirement is obtained, then such Collaboration Product used or sold in the United States may be Manufactured as such waiver permits.

7. CONFIDENTIALITY AND PUBLICATION

7.1. Nondisclosure Obligation .

7.1.1. All Confidential Information disclosed by one Party to the other Party under the Collaboration Agreement, Stock Purchase Agreement and Investor Agreement shall be maintained in confidence by the receiving Party and shall not be disclosed to a Third Party or used for any purpose except as set forth herein without the prior written consent of the disclosing Party, except to the extent that such Confidential Information:

(a) is known by the receiving Party at the time of its receipt, and not through a prior disclosure by the disclosing Party, as documented by the receiving Party’s business records;

(b) is known to the public before its receipt from the disclosing Party, or thereafter becomes generally known to the public through no breach of the Collaboration Agreement, Stock Purchase Agreement or Investor Agreement by the receiving Party;

(c) is subsequently disclosed to the receiving Party by a Third Party who is not known by the receiving Party to be under an obligation of confidentiality to the disclosing Party; or

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(d) is developed by the receiving Party independently of Confidential Information received from the disclosing Party, as documented by the receiving Party’s business records.

7.1.2. Notwithstanding the obligations of confidentiality and non-use set forth above and in Section 7.1.3 below, a receiving Party may provide Confidential Information disclosed to it, and disclose the existence and terms of the Collaboration Agreement, Stock Purchase Agreement or Investor Agreement as may be reasonably required in order to perform its obligations and to exploit its rights under the Collaboration Agreement, Stock Purchase Agreement or Investor Agreement, and specifically to (i) Related Parties, and their employees, directors, agents, consultants, advisors or other Third Parties for the performance of its obligations hereunder (or for such entities to determine their interest in performing such activities) in accordance with the Collaboration Agreement, Stock Purchase Agreement or Investor Agreement in each case who are under an obligation of confidentiality with respect to such information that is no less stringent than the terms of this Section 7.1; (ii) governmental or other Regulatory Authorities in order to obtain patents or perform its obligations or exploit its rights under the Collaboration Agreement, Stock Purchase Agreement or Investor Agreement, provided that such Confidential Information shall be disclosed only to the extent reasonably necessary to do so; (iii) the extent required by Law, including by the rules or regulations of the United States Securities and Exchange Commission or similar regulatory agency in a country other than the United States or of any stock exchange or listing entity; (iv) any bona fide actual or prospective acquirers, underwriters, investors, lenders or other financing sources and any bona fide actual or prospective collaborators or strategic partners and to consultants and advisors of such Party, in each case who are under an obligation or confidentiality with respect to such information that is no less stringent than the terms of this Section 7.1; and (v) to Third Parties to the extent a Party is required to do so pursuant to the terms of an In-License. If a Party is required by Law to disclose Confidential Information that is subject to the non-disclosure provisions of this Section 7.1, such Party shall promptly inform the other Party of the disclosure that is being sought in order to provide the other Party an opportunity to challenge or limit the disclosure. Notwithstanding Section 7.1.1, Confidential Information that is required to be disclosed by Law shall remain otherwise subject to the confidentiality and non-use provisions of this Section 7.1. If either Party concludes that a copy of any of the Collaboration Agreement, Stock Purchase Agreement or Investor Agreement must be filed with the United States Securities and Exchange Commission or similar regulatory agency in a country other than the United States, such Party shall provide the other Party with a copy of such agreement showing any provisions hereof as to which the Party proposes to request confidential treatment, shall provide the other Party with an opportunity to comment on any such proposed redactions and to suggest additional redactions, and shall take such Party’s reasonable comments into consideration before filing such agreement.

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7.1.3. Alnylam acknowledges that Genzyme may use Confidential Information of Alnylam for purposes of making investment and voting decisions with respect to the shares of Common Stock owned by Genzyme, provided that (i) Genzyme hereby acknowledges to Alnylam that Genzyme is aware that the United States securities laws prohibit any Person who has material, non-public information concerning a company from purchasing or selling securities of such company or from communicating such information to any other Person under circumstances in which it is reasonably foreseeable that such Person is likely to purchase or sell such securities and (ii) Genzyme hereby acknowledges that it is are aware of the sanctions under the United States securities laws attaching to misuse or such improper disclosure of any material, non-public information relating to Alnylam.

7.1.4. Each Party recognizes that the value to the other Party of the transactions under the Collaboration Agreement, Stock Purchase Agreement and Investor Agreement depend, in part, on each Party protecting the secrecy of its Know-How. Therefore, without limiting any Party’s right’s right to license its Know-How, subject to the terms of the Collaboration Agreement, Stock Purchase Agreement or Investor Agreement, in any way it chooses, each Party shall use commercially reasonable efforts to protect the confidentiality of its Know-How as determined in such Party’s reasonable business judgment.

7.1.5. Notwithstanding any provision of the Collaboration Agreement to the contrary but subject to the occurrence of the Effective Date, Residual Knowledge shall not be considered Confidential Information for purposes of this Section 7.1.

7.2. Publication and Publicity .

7.2.1. Publication. Genzyme and Alnylam each acknowledge the other Party’s interest in publishing certain key results of the Collaboration. Each Party also recognizes the mutual interest in obtaining valid patent protection and in protecting trade secret information. Consequently, except for disclosures permitted pursuant to Section 7.1 (Nondisclosure Obligation) and 7.2.2 (Publicity), either Party wishing to make a publication or public presentation that contains the Confidential Information of the other Party shall deliver to the other Party a copy of the proposed written publication or presentation at least [***] days prior to submission for publication or presentation. The reviewing Party shall have the right (i) to propose modifications to the publication or presentation for patent reasons, trade secret reasons or business reasons, and the publishing Party shall remove all Confidential Information of the other Party if requested by the reviewing Party, or (ii) to request a reasonable delay in publication or presentation in order to protect patentable information. If the reviewing Party requests a delay, the publishing Party shall delay submission or presentation for a period of [***] days (or such shorter period as may be mutually agreed by the Parties) to enable the non-publishing Party to file patent applications protecting such Party’s rights in such

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information. With respect to any proposed publications or disclosures by investigators or academic or non-profit collaborators, such materials shall be subject to review under this Section 7.2.1 to the extent that Genzyme or Alnylam, as the case may be, has the right and ability (after using commercially reasonable efforts to obtain such right and ability) to do so.

7.2.2. Publicity. Except as set forth in Section 7.1 (Nondisclosure Obligation) and Section 7.2.1 (Publication) above and 7.3.2 (Press Release) below, the terms of any of the Collaboration Agreement, Stock Purchase Agreement or Investor Agreement may not be disclosed by either Party, and neither Party shall use the name, Trademark, trade name or logo of the other Party or its employees in any publicity, news release or disclosure relating to any of the Collaboration Agreement, Stock Purchase Agreement or Investor Agreement, its subject matter, or the activities of the Parties hereunder without the prior express written permission of the other Party, except as may be required by Law, including by the rules or regulations of the United States Securities and Exchange Commission, the French Financial Markets Authority, the French Prudential Supervisory Authority or similar regulatory agency in any country other than the United States or France or of any stock exchange or listing entity, or except as expressly permitted by the terms hereof.

7.3. Press Release .

7.3.1. Following the execution of the Collaboration Agreement, the Parties shall issue separate press releases in the forms set forth in Schedule 7.3 or such other forms mutually agreed by the Parties. After such initial press releases, except as provided in Section 7.3.2, neither Party shall issue a press release or public announcement relating to the Collaboration Agreement without the prior written approval of the other Party, which approval shall not be unreasonably withheld, conditioned or delayed, except that a Party may (i) once a press release or other public statement is approved in writing by both Parties, make subsequent public disclosure of the information contained in such press release or other written statement without the further approval of the other Party, and (ii) issue a press release or public announcement as required, in the reasonable judgment of such Party, by Law, including by the rules or regulations of the United States Securities and Exchange Commission, the French Financial Markets Authority, the French Prudential Supervisory Authority or similar regulatory agency in a country other than the United States or France or of any stock exchange or listing entity.

7.3.2. Notwithstanding anything in this Section 7.3 to the contrary, either Party may issue a press release or make a public disclosure relating to (i) the results of any Clinical Studies with respect to an Option Product, (ii) the exercise of an Option, (iii) the payment or receipt of a milestone payment under any License Terms with respect to a Collaboration Product and (iv) such Party’s Development, Manufacturing or Commercialization activities under any License Terms with respect to Collaboration

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Products in such Party’s Territory, provided that such press release or public disclosure does not disclose Confidential Information of the other Party. Furthermore, either Party may issue a press release or make a public disclosure relating to the other Party’s Development, Manufacturing or Commercialization activities with respect to the Collaboration Products in the other Party’s Territory, provided that (i) such press release or public disclosure does not disclose Confidential Information of the other Party and (ii) such press release or public disclosure merely repeats subject matter previously disclosed by the other Party in a manner that is substantially consistent with such prior disclosure. Prior to making any such disclosure under this Section 7.3.2, however, the Party making the disclosure shall provide the other Party with a draft of such proposed disclosure a reasonable time (but at least [***] business days) prior to disclosure to allow the other Party to review and comment prior to making any such disclosure, for the other Party’s review and comment, and the disclosing Party shall consider in good faith any timely comments provided by the other Party. Notwithstanding the foregoing, except as expressly permitted by clause (i), (ii) or (iii) above and subject to clause (ii) of Section 7.3.1, Alnylam may not issue any other press release or make a public disclosure relating to Genzyme’s activities for any Global Licensed Product without the prior written consent of Genzyme.

8. REPRESENTATIONS, WARRANTIES AND COVENANTS

8.1. Mutual Representations and Warranties as of the Execution Date . Each Party represents and warrants to the other Party that, as of the Execution Date:

8.1.1. such Party is a corporation duly organized, validly existing and in good standing under the laws of its jurisdiction of incorporation or formation;

8.1.2. such Party has all requisite corporate power and corporate authority to enter into the Collaboration Agreement and to carry out its obligations under the Collaboration Agreement;

8.1.3. all requisite corporate action on the part of such Party, its directors and stockholders required by applicable Law for the authorization, execution and delivery by such Party of the Collaboration Agreement, and the performance of all obligations of such Party under the Collaboration Agreement, has been taken;

8.1.4. the execution, delivery and performance of the Collaboration Agreement, and compliance with the provisions of the Collaboration Agreement, by such Party do not and shall not: (a) violate any provision of applicable Law or any ruling, writ, injunction, order, permit, judgment or decree of any Governmental Authority, (b) constitute a breach of, or default under (or an event which, with notice or lapse of time or both, would become a default under) or conflict with, or give rise to any right of termination, cancellation or acceleration of, any agreement, arrangement or instrument, whether

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written or oral, by which such Party or any of its assets are bound, or (c) violate or conflict with any of the provisions of such Party’s organizational documents (including any articles or memoranda of organization or association, charter, bylaws or similar documents), except, in the case of subsections (a) and (b), as would not have or be reasonably likely to have a Material Adverse Effect (as defined in the Stock Purchase Agreement);

8.1.5. no consent, approval, authorization or other order of, or filing with, or notice to, any Governmental Authority or other Third Party is required to be obtained or made by such Party in connection with the authorization, execution and delivery by the Company of the Collaboration Agreement, except as required pursuant to the HSR Act; and

8.1.6. such Party has not entered into any agreement with any Third Party that grants such Third Party any rights that would be in conflict with the Collaboration Agreement following an siRNA becoming a Collaboration Product under the Collaboration Agreement.

8.2. Representations and Warranties of Alnylam . Except as provided in Schedule 8.2 , Alnylam represent and warrants to Genzyme that, as of the Execution Date and, with respect to the representations in Sections 8.2.1, 8.2.2, 8.2.5, 8.2.7, 8.2.9 and 8.2.10 below, as of the Effective Date:

8.2.1. Alnylam is the sole and exclusive owner of, or otherwise Controls pursuant to an Existing Alnylam In-License, the Option Product Technology and the ALN-TTR Technology.

8.2.2. Alnylam has sufficient legal and/or beneficial title and ownership of, or sufficient license rights under, the Option Product Technology and ALN-TTR Technology to grant the licenses to such Option Product Technology and ALN-TTR Technology to Genzyme pursuant to the Collaboration Agreement.

8.2.3. (a) Schedule 1.2.22 (ALN-TTR Core Technology Patents), Schedule 1.2.24 (ALN-TTR Product-Specific Patents), Schedule 1.2.159 (Option Product Core Technology Patents) and Schedule 1.2.162 (Option Product-Specific Patents) collectively set forth a complete and accurate list of the ALN-TTR Patents and Option Product Patents owned, either solely or jointly, by Alnylam, and to Alnylam’s knowledge, Schedule 1.2.22 (ALN-TTR Core Technology Patents), Schedule 1.2.24 (ALN-TTR Product-Specific Patents), Schedule 1.2.159 (Option Product Core Technology Patents) and Schedule 1.2.162 (Option Product-Specific Patents) collectively set forth a complete and accurate list of the ALN-TTR Patents and Option Product Patents licensed, either exclusively or nonexclusively, to Alnylam, (b) to Alnylam’s knowledge, each issued ALN-TTR Patent and Option Product Patent remains in full force and effect and (c)

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Alnylam or its Affiliates have timely paid all filing and renewal fees payable with respect to such ALN-TTR Patents and Option Product Patents for which Alnylam controls prosecution and maintenance. Schedule 1.2.22 (ALN-TTR Core Technology Patents), Schedule 1.2.24 (ALN-TTR Product-Specific Patents), Schedule 1.2.159 (Option Product Core Technology Patents) and Schedule 1.2.162 (Option Product-Specific Patents) indicate whether each ALN-TTR Patent and Option Product Patent is owned exclusively by Alnylam, is owned jointly by Alnylam and one or more Third Parties, or is licensed to Alnylam. For each ALN-TTR Patent and Option Product Patent that is owned, but not owned exclusively, by Alnylam, or that is licensed to Alnylam, Schedule 1.2.22 (ALN-TTR Core Technology Patents), Schedule 1.2.24 (ALN-TTR Product-Specific Patents), Schedule 1.2.159 (Option Product Core Technology Patents) and Schedule 1.2.162 (Option Product-Specific Patents) identify the Third Party owner(s) and, if applicable, the Existing Alnylam In-License pursuant to which Alnylam Controls such ALN-TTR Patent or Option Product Patent. For each Option Product Core Technology Patent family (other than Patent Rights licensed from Isis Pharmaceuticals, Inc.) and each ALN-TTR Core Technology Patent family that is licensed, but not exclusively licensed, to Alnylam, Schedule 1.2.22 (ALN-TTR Core Technology Patents) or Schedule 1.2.159 (Option Product Core Technology Patents), as applicable indicates the non-exclusive nature of the license. For each Option Product-Specific Patent and ALN-TTR Product-Specific Patent that is licensed, but not exclusively licensed, to Alnylam, Schedule 1.2.24 (ALN-TTR Product-Specific Patents) or Schedule 1.2.162 (Option Product-Specific Patents), as applicable, indicates the non-exclusive nature of the license. Alnylam is the sole and exclusive owner of all Patent Rights identified in Schedule 1.2.22 (ALN-TTR Core Technology Patents), Schedule 1.2.24 (ALN-TTR Product-Specific Patents), Schedule 1.2.159 (Option Product Core Technology Patents) and Schedule 1.2.162 (Option Product-Specific Patents) as being owned exclusively by Alnylam and Controls all other Patent Rights identified on such schedules.

8.2.4. Schedule 1.2.82 (Existing Alnylam In-Licenses) sets forth a complete and accurate list of all agreements between Alnylam and a Third Party entered into prior to the Execution Date pursuant to which Alnylam Controls Know-How or Patent Rights that are necessary or useful to Develop, Manufacture or Commercialize ALN-TTR02, ALN-TTRsc or any Co-Co/Global Option Product in the Field, other than Additional Alnylam In-Licenses. [***].

8.2.5. Alnylam has complied with all applicable Laws, including any duties of candor to applicable patent offices, in connection with the filing, prosecution and maintenance of the ALN-TTR Patents and Option Product Patents.

8.2.6. To Alnylam’s knowledge, neither Alnylam nor its Affiliates are in breach or default under any Existing Alnylam In-License, and neither Alnylam nor its Affiliates have received any written notice of breach or default with respect to any Existing Alnylam In-License.

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8.2.7. Alnylam has obtained from all inventors of ALN-TTR Technology or Option Product Technology owned by Alnylam valid and enforceable agreements assigning to Alnylam each such inventor’s entire right, title and interest in and to all such ALN-TTR Technology or Option Product Technology, as applicable.

8.2.8. There is no (a) claim, demand, suit, proceeding, arbitration, inquiry, investigation or other legal action of any nature, civil, criminal, regulatory or otherwise, pending or, to Alnylam’s knowledge, threatened against Alnylam or any of its Affiliates or (b) judgment or settlement against or owed by Alnylam or any of its Affiliates, in each case in connection with the ALN-TTR Technology or Option Product Technology.

8.2.9. Alnylam owns or Controls all Know-How that is or has been used by Alnylam in the Development and Manufacture of ALN-TTR02, ALN-TTRsc and the Option Products, and has sufficient legal or beneficial title and ownership of, or sufficient license rights under such Know-How to transfer Know-How to Genzyme as provided in Section 6.5 (Transfer of Manufacturing Know-How).

8.2.10. Alnylam has conducted all Development activities with respect to the Core Pipeline Programs currently in existence in compliance with all applicable Laws, including current governmental regulations concerning, GLP, good clinical practices and cGMP.

8.2.11. True and complete copies of the agreements set forth on Schedule 1.2.82 (Existing Alnylam In-Licenses) and Schedule 1.2.7 (Additional Alnylam In-Licenses), and all of the agreements relating to any Option Product, ALN-TTR02 or ALN-TTRsc have been made available to Genzyme through an electronic data room.

For purposes of this Section 8.2 and where indicated in Section 8.4 (Certain Covenants), with respect to each instance of Option Product Technology, Option Product Patents, Option Product Core Technology Patents and Option Product-Specific Patents and Option Products, those definitions shall be limited to the Existing Core Option Products.

8.3. Warranty Disclaimer . EXCEPT AS OTHERWISE EXPRESSLY PROVIDED IN THE COLLABORATION AGREEMENT, STOCK PURCHASE AGREEMENT OR INVESTOR AGREEMENT, NEITHER PARTY MAKES ANY REPRESENTATION OR EXTENDS ANY WARRANTY OF ANY KIND, EITHER EXPRESS OR IMPLIED, TO THE OTHER PARTY WITH RESPECT TO ANY TECHNOLOGY, COLLABORATION PRODUCT, GOODS, SERVICES, RIGHTS OR OTHER SUBJECT MATTER OF THE COLLABORATION AGREEMENT AND HEREBY DISCLAIMS ALL IMPLIED WARRANTIES OF MERCHANTABILITY, FITNESS FOR A PARTICULAR PURPOSE AND NON-INFRINGEMENT WITH RESPECT TO ANY AND ALL OF THE FOREGOING. EACH PARTY HEREBY DISCLAIMS ANY REPRESENTATION OR WARRANTY THAT THE DEVELOPMENT, MANUFACTURE OR COMMERCIALIZATION OF ANY COLLABORATION PRODUCT PURSUANT TO THE COLLABORATION AGREEMENT SHALL BE SUCCESSFUL OR THAT ANY PARTICULAR SALES LEVEL WITH RESPECT TO ANY COLLABORATION PRODUCT SHALL BE ACHIEVED.

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8.4. Certain Covenants .

8.4.1. Compliance. Each Party and its Related Parties shall conduct the Collaboration and the Development, Manufacture and Commercialization of the Collaboration Products and any Option Products from the Core Pipeline Programs in material compliance with all applicable Laws, including current governmental regulations concerning GLP, good clinical practices and cGMP.

8.4.2. Clarifying Amendments. [***]. For clarity, such amendment will be an Existing Alnylam In-License for all purposes of the Collaboration Agreement.

8.4.3. Retention of Title. During the Option Period, Alnylam shall retain and maintain sufficient legal and/or beneficial title and ownership of, or sufficient license rights under, any Option Product Technology relating to a Core Pipeline Program to enable Alnylam to grant the licenses and rights to such Option Product Technology that would be granted to Genzyme under, and as reasonably necessary to practice, such Option Product Technology under the applicable License Terms if Genzyme exercised an Option with respect to such Option Product. Without limiting the generality of the foregoing, during the Option Period, Alnylam shall not sell, transfer, lease or otherwise dispose of any Option Product Technology, except to the extent expressly permitted under the Collaboration Agreement or to grant a security interest, lien or other encumbrance in, on or to any Option Product Technology as part of a financing transaction.

8.4.4. Know-How. Alnylam shall not use any Know-How that it does not Control in the Development or Manufacture of Option Products from the Core Pipeline Programs. Alnylam shall obtain sufficient legal or beneficial title and ownership of, or beneficial title and ownership of, or sufficient rights under, and as reasonably necessary to practice, any Know-How that is used by Alnylam in the Development or Manufacture of Option Products from the Core Pipeline Programs to grant the licenses and rights to such Know-How that would be granted to Genzyme pursuant to the applicable License Terms if Genzyme exercised an Option with respect to an Option Product from the Core Pipeline Programs.

8.4.5. In-Licenses. Alnylam shall use commercially reasonable efforts to maintain Control of all Know-How and Patent Rights licensed to Alnylam under the Existing Alnylam In-Licenses and Additional Alnylam In-Licenses that would be necessary or useful for Genzyme to Develop, Manufacture and/or Commercialize any Option Product in the Field in the Genzyme Territory pursuant to the License Terms that

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would apply to such Option Product if Genzyme exercised an Option for such Option Product. Alnylam shall use commercially reasonable efforts not to materially breach or be in material default under any of its obligations under any Alnylam In-License. Alnylam will not voluntarily amend or terminate any Alnylam In-License in a manner that would terminate rights that would be sublicensed to Genzyme if Genzyme exercised an Option with respect to an Option Product, other than Additional Alnylam In-Licenses. Alnylam will update Schedule 1.2.82 (Existing Alnylam In-Licenses) if, prior to the Effective Date, Alnylam enters into any agreement pursuant to which Alnylam Controls Patent Rights or Know-How necessary or useful to Develop, Manufacture or Commercialize any Option Product (where such term is limited for these purposes in accordance with the last sentence of Section 8.2), ALN-TTR02 or ALN-TTRsc in the Field in the Genzyme Territory.

8.4.6. No Debarment. Each Party shall commercially reasonable efforts to not use, in any capacity in connection with the Collaboration or the performance of its obligations under the Collaboration Agreement, any Person that has been debarred pursuant to Section 306 of the United States Federal Food, Drug, and Cosmetic Act, as amended, or that is the subject of a conviction described in such section. Each Party agrees to inform the other Party in writing immediately if it or any Person that is performing activities in the Collaboration or under the Collaboration Agreement, is debarred or is subject to debarment or is the subject of a conviction described in Section 306, or if any action, suit, claim, investigation or legal or administrative proceeding is pending or, to the best of the notifying Party’s knowledge, is threatened, relating to the debarment or conviction of the notifying Party or any Person or entity used in any capacity by such Party or any of its Affiliates in connection with the Collaboration or the performance of its other obligations under the Collaboration Agreement.

8.4.7. [***].

8.4.8. Potential License Agreements. [***].

8.4.9. [***].

8.4.10. Contractual Obligations. If any ALN-TTR Technology or Option Product Technology is subject to any funding agreement with any government or Governmental Authority or subject to any other agreement under which requirements and obligations will apply to Genzyme under the Collaboration Agreement, then, at Genzyme’s request, Alnylam will use commercially reasonable efforts, at Genzyme’s expense, to secure a waiver of any requirements or obligations of Genzyme under such agreements.

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8.4.11. [***].

9. ROYALTY REPORTS; PAYMENTS; AUDIT

9.1. Reports; Payment of Royalty . During the Term, following the First Commercial Sale of any Collaboration Product by or on behalf of a Party in such Party’s Territory under the applicable License Terms, such Party shall furnish to the other Party a written report within [***] days after the end of each Calendar Quarter showing, on a Collaboration Product-by-Collaboration Product and country-by-country basis [***]. Except as expressly provided in the Collaboration Agreement, all payments by one Party to the other Party under the Collaboration Agreement shall be non-refundable and non-creditable and not subject to set-off. Royalties shown to have accrued by each royalty report shall be due and payable [***] days following the date such royalty report is due. In addition, each Party selling a Collaboration Product shall prepare and deliver to the other Party any additional reports for sales in such selling Party’s Territory as required under any applicable Existing Genzyme In-Licenses, Existing Alnylam In-Licenses or Collaboration In-Licenses.

9.2. Audits .

9.2.1. On a Collaboration Product-by-Collaboration Product basis, upon the written request of a Party and not more than once in each Calendar Year, the other Party and its Related Parties shall permit an independent certified public accounting firm of internationally-recognized standing selected by the requesting Party and reasonably acceptable to the other Party, at the requesting Party’s expense except as set forth below, to have access during normal business hours to such of the records of the other Party as may be reasonably necessary to verify the accuracy of the royalty and other amounts payable or reports under the Collaboration Agreement in respect of such Collaboration Product (including Global R&D Costs (as defined in any of the License Terms) and Cost of Goods but excluding S&M Costs (as defined in the Co-Co License Terms)) for any year ending not more than [***] years prior to the date of such request for the sole purpose of verifying the basis and accuracy of payments made under the applicable License Terms in respect of such Collaboration Product. Notwithstanding the foregoing, a Party may not make more than [***] in a Calendar Year, [***].

9.2.2. If such accounting firm identifies a discrepancy made during such period, the appropriate Party shall pay the other Party the amount of the discrepancy, together with late-payment interest in accordance with Section 9.4 (Late Payments), within [***] days after the date the requesting Party delivers to the other Party such accounting firm’s written report so concluding, or as otherwise agreed by the Parties in writing. The fees charged by such accounting firm shall be paid by the requesting Party, unless such discrepancy represents an underpayment by the other Party of at least [***], on a Collaboration Product-by-Collaboration Product basis, of the total amounts due in respect of such Collaboration Product in the audited period, in which case such fees shall be paid by the other Party.

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9.2.3. Each Party shall comply with all applicable audit requirements in the In-Licenses and shall include in each sublicense granted by it pursuant to the License Terms a provision requiring any Sublicensee (as defined under the applicable License Terms) to make reports to the Party that is party to such In-License, to keep and maintain records of sales made pursuant to such sublicense and to grant access to such records by the independent accountant of the Party that is party to such In-License to the same extent required of a Party under the Collaboration Agreement.

9.2.4. Unless an audit for such year has been commenced prior to and is ongoing upon the [***] anniversary of the end of such year, the calculation of royalties, expense reimbursement and other payments payable with respect to such year shall be binding and conclusive upon both Parties, and each Party and its Related Parties shall be released from any further liability or accountability with respect to such royalties or expense reimbursement for such year.

9.2.5. Each Party shall treat all financial information subject to review under this Section 9.2 or under any sublicense agreement in accordance with the confidentiality and non-use provisions of Section 7 (Confidentiality and Publication), and shall cause its accounting firm to enter into a confidentiality agreement with the other Party or its Related Parties obligating it to retain all such information in confidence pursuant to such confidentiality agreement, which terms shall be no less stringent than the provisions of Section 7 (Confidentiality and Publication).

9.3. Payment Exchange Rate . All payments to be made under the Collaboration Agreement shall be made in United States dollars and shall be paid by bank wire transfer in immediately available funds to such bank account in the United States as may be designated in writing by the receiving Party from time to time. In the case of Net Sales made or expenses incurred by a Party and its Related Parties in currencies other than United States dollars during a Calendar Quarter, the rate of exchange to be used in computing the amount of United States dollars due shall be the rate of exchange utilized by such Party in its worldwide accounting system and calculated in accordance with GAAP.

9.4. Late Payments . Any amount owed by a Party to the other Party under the Collaboration Agreement that is not paid on or before the date such payment is due shall bear interest at a rate per annum equal to the lesser of (a) [***] or (b) the highest rate permitted by Law, calculated on the number of days such payments are paid after such payments are due and compounded monthly.

9.5. Blocked Payments . If, by reason of Laws in any jurisdiction in a Party’s Territory, it becomes impossible or illegal for a Party to transfer milestone payments, royalties or other payments under the Collaboration Agreement to the other Party, the payor shall promptly notify the payee. During any such period described above, the payor shall deposit such payments in local currency in the relevant jurisdiction to the credit of the payee in a recognized banking institution designated by the payee or, if none is designated by the payee within a period of [***] days, in a recognized banking institution selected by the payor and identified in a written notice given to the payee.

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9.6. Taxes . If a timely and appropriately completed and executed Internal Revenue Service Form W-9 is provided by the receiving Party to the paying Party, the Parties acknowledge and agree that no United States tax withholding shall be applied with respect to any milestone payments due under any License Terms. Each Party shall use reasonable efforts to minimize tax withholding on payments made to the other Party. Notwithstanding such efforts, if such Party concludes that tax withholdings under the Laws of any country are required with respect to payments to the other Party, such Party shall first notify the other Party and provide such Party with [***] days to determine whether there are actions such receiving Party can undertake to avoid such withholding. During this notice period, the paying Party shall refrain from making such payment until the receiving Party instructs the paying Party that (a) the receiving Party intends to take actions (satisfactory to both Parties) that shall obviate the need for such withholding, in which case the paying Party shall make such payment only after it is instructed to do so by the receiving Party, or (b) the paying Party should make such payment and withhold the required amount and pay it to the appropriate Governmental Authority. In such case, the withholding Party shall promptly provide the other Party with copies of receipts or other evidence reasonably required and sufficient to allow the other Party to document such tax withholdings adequately for purposes of claiming foreign tax credits and similar benefits. The Parties shall cooperate reasonably in completing and filing documents required under the provisions of any applicable tax laws or under any other applicable Law, in connection with the making of any required tax payment or withholding payment, or in connection with any claim to a refund of or credit for any such payment. The Parties shall cooperate to minimize such taxes in accordance with applicable Laws, including using reasonable efforts to access the benefits of any applicable treaties. [***].

10. INDEMNIFICATION; LIMITATION OF LIABILITY; INSURANCE

10.1. General Indemnification by Genzyme . Genzyme shall indemnify, hold harmless and defend Alnylam, its Related Parties, and their respective directors, officers, employees and agents (“ Alnylam Indemnitees ”) from and against any and all Third Party claims, suits, losses, liabilities, damages, costs, fees and expenses (including reasonable attorneys’ fees and litigation expenses) (collectively, “ Losses ”) arising out of or resulting from, directly or indirectly, (a) any breach of, or inaccuracy in, any representation or warranty made by Genzyme in the Collaboration Agreement, or any breach or violation of any covenant or agreement of Genzyme in or in the performance of the Collaboration Agreement, or (b) the negligence or willful misconduct by or of Genzyme and its Related Parties, and their respective directors, officers, employees and agents in the performance of Genzyme’s obligations under the Collaboration Agreement. Genzyme shall have no obligation to indemnify the Alnylam Indemnitees to the extent that the Losses arise out of or result from, directly or indirectly, any breach of, or inaccuracy in, any representation or warranty made by Alnylam in the

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Collaboration Agreement, or any breach or violation of any covenant or agreement of Alnylam in or in the performance of the Collaboration Agreement, or the negligence or willful misconduct by or of any of the Alnylam Indemnitees, or matters for which Alnylam is obligated to indemnify Genzyme under Section 10.2 (General Indemnification by Alnylam) or 10.3 (Product Liability).

10.2. General Indemnification by Alnylam . Alnylam shall indemnify, hold harmless, and defend Genzyme, its Related Parties and their respective directors, officers, employees and agents (“ Genzyme Indemnitees ”) from and against any and all Losses arising out of or resulting from, directly or indirectly, (a) any breach of, or inaccuracy in, any representation or warranty made by Alnylam in the Collaboration Agreement, or any breach or violation of any covenant or agreement of Alnylam in or in the performance of the Collaboration Agreement, (b) the negligence or willful misconduct by or of Alnylam and its Related Parties, and their respective directors, officers, employees and agents in the performance of Alnylam’s obligations under the Collaboration Agreement or (c) any infringement (including induced infringement) of any of the Patent Rights identified on Schedule 10.2 (Identified Patent Rights) arising from the Development, Manufacture or Commercialization of a Collaboration Product by Genzyme or its Affiliates. Alnylam shall have no obligation to indemnify the Genzyme Indemnitees to the extent that the Losses arise out of or result from, directly or indirectly, any breach of, or inaccuracy in, any representation or warranty made by Genzyme in the Collaboration Agreement, or any breach or violation of any covenant or agreement of Genzyme in or in the performance of the Collaboration Agreement, or the negligence or willful misconduct by or of any of the Genzyme Indemnitees, or matters for which Genzyme is obligated to indemnify Alnylam under Section 10.1 (General Indemnification by Genzyme) or 10.3 (Product Liability).

10.3. Product Liability . Subject to any Supply Agreements, any Losses arising out of Third Party product liability claims arising from the Development or Commercialization of Collaboration Products shall be (a) borne by Genzyme, to the extent such Losses were incurred with respect to the Development or Commercialization by or on behalf of Genzyme or its Related Parties of a Regional Licensed Product in or for the Genzyme Territory, a Co-Co Licensed Product in or for the Genzyme Territory, or a Global Licensed Product anywhere in or for the world by or on behalf of Genzyme and its Related Parties, (b) be borne by Alnylam, to the extent such Losses were incurred with respect to Development or Commercialization of a Regional Licensed Product in or for the Alnylam Territory by or on behalf of Alnylam and its Related Parties, and (c) be borne fifty percent (50%) by each of Genzyme and Alnylam, to the extent such Losses were incurred with respect to Development or Commercialization by or on behalf of Alnylam or its Related Parties of a Co-Co Licensed Product in or for the Alnylam Territory. The Party bearing such Losses in accordance with the immediately preceding sentence shall indemnify, hold harmless and defend the other Party and its Related Parties and their respective directors, officers, employees and agents from and against such Losses.

10.4. Indemnification Procedure . In the event of any such claim against any Genzyme Indemnitee or Alnylam Indemnitee (individually, an “ Indemnitee ”), the indemnified Party shall promptly notify the other Party in writing of the claim and the indemnifying Party

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shall manage and control, at its sole expense, the defense of the claim and its settlement. The Indemnitee shall cooperate with the indemnifying Party and may, at its option and expense, be represented in any such action or proceeding. The indemnifying Party shall not be liable for any settlements, litigation costs or expenses incurred by any Indemnitee without the indemnifying Party’s written authorization. Notwithstanding the foregoing, if the indemnifying Party believes that any of the exceptions to its obligation of indemnification of the Indemnitees set forth in Sections 10.1 (General Indemnification by Genzyme), 10.2 (General Indemnification by Alnylam) or 10.3 (Product Liability) may apply, the indemnifying Party shall promptly notify the Indemnitees, which shall then have the right to be represented in any such action or proceeding by separate counsel at their expense, provided that the indemnifying Party shall be responsible for payment of such expenses if the Indemnitees are ultimately determined to be entitled to indemnification from the indemnifying Party for the matters to which the indemnifying Party notified the Indemnitees that such exception(s) may apply.

10.5. Limitation of Liability . NEITHER PARTY HERETO SHALL BE LIABLE FOR SPECIAL, INCIDENTAL, CONSEQUENTIAL OR PUNITIVE DAMAGES ARISING OUT OF THE COLLABORATION AGREEMENT OR THE EXERCISE OF ITS RIGHTS HEREUNDER, INCLUDING LOST PROFITS ARISING FROM OR RELATING TO ANY BREACH OF THE COLLABORATION AGREEMENT, REGARDLESS OF ANY NOTICE OF SUCH DAMAGES, EXCEPT AS A RESULT OF A PARTY’S WILLFUL MISCONDUCT OR A BREACH OF SECTION 3.6 (EXCLUSIVITY DURING OPTION PERIOD), SECTION 7 (CONFIDENTIALITY AND PUBLICATION), SECTION 10.4.1 OF THE CO-CO LICENSE TERMS (EXCLUSIVITY), SECTION 9.4.1 OF THE GLOBAL LICENSE TERMS (EXCLUSIVITY) OR SECTION 8.4.1 OF THE REGIONAL LICENSE TERMS (EXCLUSIVITY). NOTHING IN THIS SECTION 10.5 IS INTENDED TO LIMIT OR RESTRICT THE INDEMNIFICATION RIGHTS OR OBLIGATIONS OF EITHER PARTY. NOTWITHSTANDING THE FOREGOING, ALNYLAM SHALL NOT BE LIABLE FOR ANY SPECIAL, INCIDENTAL, CONSEQUENTIAL OR PUNITIVE DAMAGES ARISING OUT OF ANY BREACH OF SECTION 3.6 (EXCLUSIVITY DURING OPTION PERIOD) UNLESS GENZYME BRINGS AN ACTION SEEKING SUCH DAMAGES WITHIN SIX (6) MONTHS AFTER THE EARLIER OF THE DATE ON WHICH THE TRANSACTION BETWEEN ALNYLAM AND A THIRD PARTY ENTERED INTO IN BREACH OF SECTION 3.6 (EXCLUSIVITY DURING OPTION PERIOD) FIRST BECOMES PUBLICLY KNOWN OR THE DATE ON WHICH ALNYLAM NOTIFIES GENZYME OF SUCH TRANSACTION.

10.6. Insurance . Each Party shall maintain insurance during the Term and for a period of at least two (2) years after the last commercial sale of any Collaboration Product generated under the Collaboration, with a reputable, solvent insurer in an amount appropriate for its business and products of the type that are the subject of the Collaboration Agreement, and for its obligations under the Collaboration Agreement. Specifically, each Party shall maintain product liability insurance and clinical trial liability insurance with limits of at least [***] per occurrence and in annual aggregate. Upon request, each Party shall provide the other Party with evidence of the existence and maintenance of such insurance coverage.

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11. INTELLECTUAL PROPERTY

11.1. Prosecution and Maintenance of Patent Rights . Alnylam has the sole responsibility to, at Alnylam’s discretion and sole expense (except as provided below), file, conduct prosecution, and maintain (including the defense of any interference or opposition proceedings), all Patent Rights comprising Option Product Core Technology Patents and Option Product-Specific Patents, in Alnylam’s name. Notwithstanding the foregoing, Alnylam shall file Option Product-Specific Patents in the Genzyme Patent Jurisdictions and shall use commercially reasonable efforts to prosecute and maintain such Patent Rights in the Genzyme Patent Jurisdictions and shall timely pay all filing (including during the pendency of any Patent Right) and renewal fees payable with respect thereto [***].

11.2. Patent Prosecution Information Sharing . Alnylam shall consult with Genzyme, through the IP Committee, on its strategy for the preparation, filing, prosecution, and maintenance of the Option Product Patents and shall consider in good faith timely comments from Genzyme thereon. Alnylam shall furnish to Genzyme, through the IP Committee or via electronic mail or such other method as mutually agreed by the Parties, copies of documents received from outside counsel in the course of filing, prosecution or maintenance of or filed with the relevant national patent offices with respect to the filing, prosecution and maintenance of all Option Product Core Technology Patents and Option Product-Specific Patents within a reasonable time after filing of such documents.

11.3. In-Licenses .

11.3.1. Additional Alnylam In-Licenses. In the event that a Patent Right licensed to Alnylam under an Additional Alnylam In-License actually is or will be infringed by Genzyme’s Commercialization of a Collaboration Product in the Genzyme Territory or Genzyme’s Manufacture or Development of such Collaboration Product in accordance with the applicable License Terms, then such Additional Alnylam In-License will thereafter automatically be deemed to be an Existing Alnylam In-License on a Collaboration Product-by-Collaboration Product basis, and all rights granted to Alnylam thereunder will be deemed to be “Controlled” by Alnylam and sublicensed to Genzyme under the applicable License Terms, effective as of the later of (a) the date the applicable Patent Right issues or (b) the date that Genzyme’s Commercialization of such Collaboration Product in the Genzyme Territory or Genzyme’s Manufacture of Development of such Collaboration Product in accordance with this Master Agreement and the applicable License Terms would infringe such Patent Right in the absence of a license thereunder from Alnylam.

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11.3.2. Existing Alnylam In-Licenses. In the event that Alnylam fails to identify a Third Party agreement under which Alnylam Controls Know-How or Patent Rights that are necessary or useful to Develop, Manufacture or Commercialize a Collaboration Product, then the Parties will amend the Schedules to the applicable License Terms to include such agreements within the definition of Existing Alnylam In-License or Additional Alnylam In-License. In any event, any Potential Alnylam In-License under which Alnylam Controls Know-How or Patent Rights that are necessary or useful to Develop, Manufacture or Commercialize a Collaboration Product will be deemed to be an Existing Alnylam In-License regardless of whether it is entered into before or after the Implementation Date for such Collaboration Product.

11.3.3. Collaboration In-Licenses.

11.3.3.1. Proposed In-Licenses . In the event that either Party desires to enter into an agreement with a Third Party pursuant to which such Party would acquire a license under any Patent Rights that are necessary or useful to Develop, Manufacture or Commercialize any Collaboration Product (a “ Proposed In-License ”), then such Party shall deliver a written notice to the other that may include the identity of such Third Party, a description of such Patent Rights and any proposed terms of such Proposed In-License (a “ Proposed In-License Notice ”) [***]. Within [***] days of delivery of the Proposed In-License Notice, the IP Committee shall meet to discuss the Proposed In-License and the proposing Party shall consider in good faith comments from the other Party. If the proposing Party enters into the Proposed In-License, and the non-proposing Party wishes to obtain a sublicense under such Proposed In-License, then the Proposed In-License shall be deemed to be a “ Collaboration In-License ” for all purposes under the Collaboration Agreement. For the sake of clarity, if the non-proposing Party does not wish to obtain a sublicense under a Proposed In-License, then none of the rights granted to the proposing Party thereunder will be deemed to be “Controlled” by the proposing Party and, if the proposing Party (or any of its sublicensees thereunder) has rights to enforce any Patent Rights licensed to the proposing Party thereunder, the proposing Party shall have the right to enforce such Patent Rights against the non-proposing Party.

11.3.3.2. Requirements for Collaboration In-Licenses . In entering into any Collaboration In-License (or Potential Alnylam In-License, in the case of Alnylam), each Party shall [***]. Any Patent Rights licensed to a Party under a Collaboration In-License shall be deemed to be Controlled by such Party for all purposes under the License Terms. The Party entering into a Collaboration In-License must notify the other Party promptly and provide the other Party with a copy of such Collaboration In-License.

11.3.3.3 . [***].

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11.3.4. Payments under In-Licenses.

11.3.4.1. In-Licenses that are not Collaboration In-Licenses .

(a) Except as provided under the Co-Co License Terms, Alnylam shall bear [***] of any Third Party License Payments that become payable during the Term under any (i) Existing Alnylam In-License or (ii) Potential Alnylam In-License that is entered into after the Execution Date that becomes an Existing Alnylam In-License pursuant to Section 11.3.2 (Existing Alnylam In-Licenses).

(b) Subject to Section 11.3.5 (Royalty Stacking), Genzyme shall bear [***] of any Third Party License Payments that become payable under any Existing Genzyme In-License or any Un-Blocking Genzyme In-License during the Term.

11.3.4.2. Collaboration In-Licenses . Any Third Party License Payment that becomes payable under any Collaboration In-License (other than a Potential Alnylam In-License) shall be allocated between the Parties as follows:

(a) if such Third Party License Payment becomes payable as a result of a Party’s activities under the License Terms with respect to a Collaboration Product and is either (i) [***] (a “ Collaboration Product-Specific Payment ”); and

(b) if such Third Party License Payment is not a Collaboration Product-Specific Payment, then [***].

(c) If the Parties cannot agree on whether a Third Party License Payment is a Collaboration Product-Specific Payment or not, or how to allocate a Third Party License Payment that is not a Collaboration Product-Specific Payment, the Parties shall submit the matter to the AJSC for resolution. If the AJSC cannot resolve the matter within [***] days of it being referred to them, the Parties shall submit the matter [***]. If the Party that is not a party to the Collaboration In-License disagrees with the allocation of a Third Party License Payment pursuant to this Section 11.3.4.2(c), then such Party may elect not to take a sublicense under such Collaboration In-License, in which case none of the rights granted to the other Party thereunder will be deemed to be “Controlled” by the other Party and, if the other Party has rights to enforce any Patent Rights licensed to such other Party thereunder, such other Party (or any of its sublicensees thereunder) shall have the right to enforce such Patent Rights against such Party.

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11.3.4.3. [***].

11.3.4.4. To the extent not otherwise deducted from payments by one Party to the other Party when determining Net Sales of any Collaboration Product and without duplication of Genzyme’s rights under Section 11.3.5 (Royalty Stacking), either Party that advances any payment for which the other Party is actually responsible under this Section 11.3.4 shall invoice the other Party for such advanced amount on a quarterly basis. The Party receiving such invoice shall make payment of such amount to the invoicing Party within [***] days of the date of such invoice and otherwise in accordance with Section 9 (Royalty Reports; Payments; Audits) of this Master Agreement.

11.3.5. [***].

11.3.6. Amendments to In-Licenses. If a Party amends an In-License to which it is a Party in a manner that increases the royalty payable by the other Party under such In-License without the prior written consent of the other Party, such Party shall be solely responsible for any such additional payments due under such In-License.

11.3.7. Stand-by Licenses. Upon Genzyme’s reasonable request during the Term, Alnylam shall reasonably cooperate in good faith with Genzyme’s efforts to obtain stand-by license agreements related to any Collaboration Product with respect to any Alnylam In-License, pursuant to which, upon termination of the relevant In-License, Genzyme would receive a direct license from the applicable Third Party licensor under any Patent Rights and Know-How that are sublicensed to Genzyme pursuant to the Collaboration Agreement. Such stand-by license agreement will be in a form approved in advance by Alnylam. Any costs incurred by Alnylam in cooperating with Genzyme’s efforts to obtain any such stand-by license agreement shall be reimbursed by Genzyme.

11.3.8. Breach or Termination of In-Licenses. In the event that (a) a Party receives notice of an alleged breach by such Party under an In-License to which it is a party, or (b) a Party intends to terminate an In-License to which it is a party, then such Party shall promptly, but in no event less than ten (10) days thereafter, provide written notice thereof to the other Party.

11.4. Common Interest . All information exchanged between the Parties representatives regarding the preparation, filing, prosecution, maintenance, or enforcement of the Patents Rights under this Section 11 will be deemed Confidential Information. In addition, the Parties acknowledge and agree that, with regard to such preparation, filing, prosecution, maintenance and enforcement of the Patents Rights under this Section 11, the interests of the Parties as collaborators and licensor and licensee are to obtain the strongest patent protection possible, and as such, are aligned and are legal in nature. The Parties agree and acknowledge that they have not waived, and nothing in this Master Agreement constitutes a waiver of, any legal privilege concerning the Patents Rights under this Section 11, including privilege under the common interest doctrine and similar or related doctrines.

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12. TERM AND TERMINATION

12.1. Term . The Collaboration Agreement shall be effective as of the Execution Date and, unless terminated earlier pursuant to Section 12.2 (Termination Rights), the Collaboration Agreement shall continue in effect until the later of (i) the expiration of the last to expire of the Option Periods and (ii) the last to expire of the License Terms (“ Term ”).

12.2. Termination Rights . This Master Agreement may not be terminated by either Party except as provided in this Section 12.2.

12.2.1. Termination for Convenience. Genzyme shall have the right to terminate the Collaboration Agreement in its entirety at any time after the Execution Date on six (6) months’ prior written notice to Alnylam, provided that any such termination for convenience of the Collaboration Agreement shall automatically be treated, without any other action or notice required of either Party, as a termination for convenience of each License Terms under Sections 10.2.1, 12.2.1 and 11.2.1 of the Regional License Terms, the Co-Co License Terms and the Global License Terms, respectively, and provided further that if termination under any such License Terms is not then possible, then Genzyme shall not have any right to terminate under this Section 12.2.1.

12.2.2. Termination of License Terms for Cause. The rights to a Collaboration Product under the applicable License Terms may be terminated for cause during the Term on a Collaboration Product-by-Collaboration Product basis pursuant Sections 10.2.2, 12.2.2 and 11.2.2 of the Regional License Terms, the Co-Co License Terms and the Global License Terms, respectively, as applicable.

12.2.3. Termination of this Master Agreement for Cause. This Master Agreement may be terminated at any time during the Term upon written notice by either Party if the other Party is in material breach of its obligations hereunder and has not cured such breach within thirty (30) days in the case of a payment breach, or within ninety (90) days in the case of all other breaches, after notice requesting cure of the breach; provided , however , that if any breach other than a payment breach is not reasonably curable within ninety (90) days and if a Party is making a bona fide effort to cure such breach, such termination shall be delayed for a time period to be agreed by both Parties, not to exceed an additional ninety (90) days, in order to permit such Party a reasonable period of time to cure such breach; provided , further , that in the event that the breach relates to a dispute between the Parties regarding Alnylam’s obligations to use commercially reasonable efforts to undertake the Development of Option Products from its Core Pipeline Programs and Alnylam disputes whether it has breached such obligation or whether such breach gives Genzyme the right to terminate this Master Agreement and initiates a legal action against Genzyme to resolve such dispute within the foregoing ninety (90) day cure period, then this Master Agreement shall not terminate during the pendency of such legal action; provided that if Alnylam is found in an unappealable decision by a court of

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competent jurisdiction or an appealable decision of a court of competent jurisdiction that has not been appealed in the time allowed for an appeal in such legal action to have materially breached this Master Agreement or if Alnylam admits in such legal action or settlement thereof that it has materially breached this Master Agreement then this Master Agreement shall terminate immediately following the Parties’ receipt of such decision or immediately following such admission, as applicable.

12.2.4. Challenges of Patent Rights. If, during the Term, Genzyme or any of its Affiliates (a) commences or participates in any action or proceeding (including any patent opposition or re-examination proceeding), or otherwise asserts any claim, challenging or denying the validity or enforceability of any claim of the Alnylam Core Technology Patents (as defined in any of the License Terms) that Covers any siRNA in any Option Product or Collaboration Product or is licensed by Genzyme under any License Terms or (b) actively assists any other Person in bringing or prosecuting any action or proceeding (including any patent opposition or re-examination proceeding) challenging or denying the validity or enforceability of any claim of such Patent Rights (each of (a) and (b), a “ Patent Challenge ”), then, to the extent permitted by the applicable Laws, Alnylam shall have the right, exercisable within sixty (60) days following receipt of notice regarding such Patent Challenge, in its sole discretion, to give notice to Genzyme that Alnylam may terminate the Collaboration Agreement ninety (90) days following such notice (or such longer period as Alnylam may designate in such notice), and, unless Genzyme or such Affiliate withdraws or causes to be withdrawn all such challenge(s) (or in the case of ex-parte proceedings, multi-party proceedings, or other Patent Challenges that Genzyme or Genzyme’s Affiliates do not have the power to unilaterally withdraw or cause to be withdrawn, Genzyme and Genzyme’s Affiliates cease actively assisting any other party to such Patent Challenge and, to the extent Genzyme or a Genzyme Affiliate is a party to such Patent Challenge, it withdraws from such Patent Challenge) within such ninety (90)-day period, Alnylam shall have the right to terminate the Collaboration Agreement by providing written notice thereof to Genzyme. The foregoing sentence shall not apply (i) with respect to any claim of an Alnylam Core Technology Patent that Covers any siRNA in any Option Product or Collaboration Product or is licensed by Genzyme under any License Terms that Alnylam first asserts against Genzyme or any of its Affiliates where the Patent Challenge is made in defense of such assertion, or (ii) with respect to any Patent Challenge commenced by a Third Party that after the Execution Date acquires or is acquired by Genzyme or its Affiliates or its or their business or assets, whether by stock purchase, merger, asset purchase or otherwise, but only with respect to Patent Challenges commenced prior to the closing of such acquisition.

12.3. Effect of Termination .

12.3.1. Termination of Collaboration Agreement for Convenience. Without limiting any other legal or equitable remedies that either Party may have, if the Collaboration Agreement is terminated by Genzyme pursuant to Section 12.2.1

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(Termination for Convenience) then (a) this Master Agreement and all Options granted to Genzyme hereunder shall terminate and (b) each of the License Terms shall terminate and the consequences of termination of the entire License Terms for convenience set forth in each of the License Terms shall apply.

12.3.2. Termination of Master Agreement for Cause. Without limiting any other legal or equitable remedies that either Party may have, if this Master Agreement is terminated by either Party pursuant to Section 12.2.3 (Termination of this Master Agreement for Cause), then (a) each of the License Terms shall survive and (b) this Master Agreement and all Options granted to Genzyme hereunder shall terminate, provided that any terms of this Master Agreement applicable to any Collaboration Product that is subject to any of the License Terms on the effective date of termination shall survive.

12.3.3. Termination of Collaboration Agreement for Patent Challenge. Without limiting any other legal or equitable remedies that either Party may have, if the Collaboration Agreement is terminated by Alnylam pursuant to Section 12.2.4 (Challenges of Patent Rights) then (a) this Master Agreement and all Options granted to Genzyme hereunder shall terminate and (b) each of the License Terms shall terminate and the consequences of termination of the entire License Terms for cause by Alnylam set forth in each of the License Terms shall apply.

12.3.4. Effect of Expiration or Termination; Survival. Expiration or termination of the Collaboration Agreement or this Master Agreement shall not relieve the Parties of any obligation accruing prior to such expiration or termination. Any expiration or termination of the Collaboration Agreement or this Master Agreement shall be without prejudice to the rights of either Party against the other accrued or accruing under the Collaboration Agreement or this Master Agreement, as applicable, prior to expiration or termination, including the obligation to pay royalties for the Collaboration Product sold prior to such expiration or termination or other payments under the Collaboration Agreement. The provisions of Sections 1 (Definitions), 7 (Confidentiality and Publication), 9 (Royalty Reports; Payments; Audit), 10 (Indemnification; Limitation of Liability; Insurance), 12 (Term and Termination) and 13 (Miscellaneous) shall survive any expiration or termination of the Collaboration Agreement and, in addition, the provisions of 2.1.3.3 (ROFN for CNS) and 3.1.2.4 (Improperly Designated Programs) shall survive any termination of the Collaboration Agreement by Genzyme pursuant to Section 12.2.3 (Termination of this Master Agreement for Cause). Except as otherwise set forth in this Section 12, upon termination or expiration of the Collaboration Agreement or this Master Agreement all rights and obligations of the Parties under the Collaboration Agreement or this Master Agreement, as applicable, shall cease.

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13. MISCELLANEOUS

13.1. Assignment . Except as provided in this Section 13.1, the Collaboration Agreement may not be assigned or otherwise transferred, nor may any right or obligation hereunder be assigned or transferred, by either Party without the written consent of the other Party. Notwithstanding the foregoing, either Party may, without the other Party’s written consent, assign the Collaboration Agreement and its rights and obligations hereunder in whole or in part to an Affiliate or to a party that acquires, by or otherwise in connection with, merger, sale of assets or otherwise, all or substantially all of the business of the assigning Party to which the subject matter of the Collaboration Agreement relates. The assigning Party shall remain responsible for the performance by its assignee of the Collaboration Agreement or any obligations hereunder so assigned. An assignment to an Affiliate shall terminate, and all rights so assigned shall revert to the assigning Party, if and when such Affiliate ceases to be an Affiliate of the assigning Party. Any purported assignment in violation of this Section 13.1 shall be void.

13.2. Governing Law . The Collaboration Agreement shall be construed and the respective rights of the Parties determined in accordance with the substantive Laws of the State of New York, notwithstanding any provisions of New York Law or any other Law governing conflicts of laws to the contrary, and the patent Laws of the relevant jurisdiction without reference to any rules of conflict of laws.

13.3. Jurisdiction . Each Party by its execution hereof, (a) hereby irrevocably submits to the jurisdiction of the United States District Court and state courts located in New York, New York for the purpose of any dispute arising between the Parties in connection with the Collaboration Agreement (each, an “ Action ”), except as otherwise expressly provided in the Collaboration Agreement; (b) hereby waives, to the extent not prohibited by applicable Law, and agrees not to assert, by way of motion, as a defense or otherwise, in any such Action, any claim that (i) it is not subject personally to the jurisdiction of the above-named court, (ii) its property is exempt or immune from attachment or execution, (iii) any such Action brought in the above-named court should be dismissed on grounds of forum non conveniens, should be transferred or removed to any court other than the above-named court, or should be stayed by reason of the pendency of some other proceeding in any other court other than the above-named court, or (iv) the Collaboration Agreement or the subject matter hereof may not be enforced in or by such court; and (c) hereby agrees not to commence any such Action other than before the above-named court. Notwithstanding the previous sentence a Party may commence any Action in a court other than the above-named court solely for the purpose of enforcing an order or judgment issued by the above-named court.

13.4. Venue . Each Party agrees that for any Action between the Parties arising in whole or in part under or in connection with the Collaboration Agreement, such Party bring Actions only in the federal courts of the United States of America located in New York, New York and any appellate court having jurisdiction over appeals from such courts. Each Party further waives any claim and shall not assert that venue should properly lie in any other location within the selected jurisdiction.

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13.5. Entire Agreement; Amendments . The Collaboration Agreement contains the entire understanding of the Parties with respect to the subject matter hereof, and supersedes all previous arrangements with respect to the subject matter hereof, whether written or oral, including, effective as of the Effective Date, that Mutual Confidential Disclosure Agreement between the Parties dated as of August 27, 2009, as amended through the Execution Date ( provided that all information disclosed or exchanged under such agreement will be treated as Confidential Information hereunder). This Master Agreement (other than the Appendices and Schedules attached hereto) may be amended, or any term hereof modified, only by a written instrument duly-executed by authorized representatives of both Parties hereto. The Appendices and Schedules attached hereto may be amended, or any term hereof modified, only by a written instrument duly-executed by authorized representatives of both Parties hereto, except to the extent expressly provided in the Collaboration Agreement.

13.6. Severability . If any provision hereof should be held invalid, illegal or unenforceable in any respect in any jurisdiction, the Parties hereto shall substitute, by mutual consent, valid provisions for such invalid, illegal or unenforceable provisions, which valid provisions in their economic effect are sufficiently similar to the invalid, illegal or unenforceable provisions that it can be reasonably assumed that the Parties would have entered into the Collaboration Agreement with such valid provisions. In case such valid provisions cannot be agreed upon, the invalid, illegal or unenforceable of one or several provisions of the Collaboration Agreement shall not affect the validity of the Collaboration Agreement as a whole, unless the invalid, illegal or unenforceable provisions are of such essential importance to the Collaboration Agreement that it is to be reasonably assumed that the Parties would not have entered into the Collaboration Agreement without the invalid, illegal or unenforceable provisions.

13.7. Headings . The captions to the Sections hereof are not a part of the Collaboration Agreement, but are merely for convenience to assist in locating and reading the several Sections hereof.

13.8. Waiver of Rule of Construction . Each Party has had the opportunity to consult with counsel in connection with the review, drafting and negotiation of the Collaboration Agreement. Accordingly, the rule of construction that any ambiguity in the Collaboration Agreement shall be construed against the drafting Party shall not apply.

13.9. Interpretation . Except where the context expressly requires otherwise, (a) the use of any gender herein shall be deemed to encompass references to either or both genders, and the use of the singular shall be deemed to include the plural (and vice versa); (b) the words “include”, “includes” and “including” shall be deemed to be followed by the phrase “without limitation” and shall not be interpreted to limit the provision to which it relates; (c) the word “will” shall be construed to have the same meaning and effect as the word “shall”; (d) any definition of or reference to any agreement, instrument or other document herein shall be construed as referring to such agreement, instrument or other document as from time to time

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M ASTER A GREEMENT

amended, supplemented or otherwise modified (subject to any restrictions on such amendments, supplements or modifications set forth herein); (e) any reference herein to any Person shall be construed to include the Person’s successors and assigns; (f) the words “herein”, “hereof” and “hereunder”, and words of similar import, shall be construed to refer to this Master Agreement or any of the License Terms in each of their entirety, as the context requires, and not to any particular provision hereof; (g) all references herein to Sections, Appendices or Schedules shall be construed to refer to Sections, Appendices or Schedules of this Master Agreement, and references to this Master Agreement include all Schedules hereto (but not Appendices); (h) the word “notice” means notice in writing (whether or not specifically stated) and shall include notices, consents, approvals and other written communications contemplated under the Collaboration Agreement; (i) provisions that require that a Party, the Parties or any committee hereunder “agree,” “consent” or “approve” or the like shall require that such agreement, consent or approval be specific and in writing, whether by written agreement, letter, approved minutes or otherwise (but excluding e-mail and instant messaging); (j) references to any specific law, rule or regulation, or article, section or other division thereof, shall be deemed to include the then-current amendments thereto or any replacement or successor law, rule or regulation thereof; and (k) the term “or” shall be interpreted in the inclusive sense commonly associated with the term “and/or.”

13.10. No Implied Waivers; Rights Cumulative . No failure on the part of Alnylam or Genzyme to exercise, and no delay in exercising, any right, power, remedy or privilege under the Collaboration Agreement, or provided by statute or at Law or in equity or otherwise, shall impair, prejudice or constitute a waiver of any such right, power, remedy or privilege or be construed as a waiver of any breach of the Collaboration Agreement or as an acquiescence therein, nor shall any single or partial exercise of any such right, power, remedy or privilege preclude any other or further exercise thereof or the exercise of any other right, power, remedy or privilege.

13.11. Notices . All notices which are required or permitted hereunder shall be in writing and sufficient if delivered personally, sent by facsimile (and promptly confirmed by personal delivery, registered or certified mail or overnight courier), sent by nationally-recognized overnight courier or sent by registered or certified mail, postage prepaid, return receipt requested, addressed as follows:


If to Alnylam, to:		Alnylam Pharmaceuticals, Inc. 300 Third Street Cambridge, Massachusetts 02142 Attention: Vice President - Legal Facsimile No.: (617) 551-8101

With a copy to:		Goodwin Procter LLP Exchange Place 53 State Street Boston, Massachusetts 02109 Attention: Kingsley L. Taft, Esq. Facsimile No.: (617) 523-1231

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M ASTER A GREEMENT



If to Genzyme, to:		Genzyme Corporation 500 Kendall Street Cambridge, Massachusetts 02142 Attention: Head of Rare Diseases Business Unit Facsimile No.: (617) 374-2424

With a copy to:		Genzyme Corporation 500 Kendall Street Cambridge, Massachusetts 02142 Attention: General Counsel Facsimile No.: (617) 252-7553

And to:		Ropes & Gray LLP Prudential Tower 800 Boylston Street Boston, MA 02199-3600 Attention: David M. McIntosh, Esq. Facsimile No.: (617) 235-0507

or to such other address as the Party to whom notice is to be given may have furnished to the other Party in writing in accordance herewith. In addition, each Party shall deliver a courtesy copy to the other Party’s Alliance Manager concurrently with such notice. Any such notice shall be deemed to have been given: (a) when delivered if personally delivered or sent by facsimile on a business day (or if delivered or sent on a non-business day, then on the next business day); (b) on receipt if sent by overnight courier; or (c) on receipt if sent by mail.

13.12. Compliance with Export Regulations . Neither Party shall export any technology licensed to it by the other Party under the Collaboration Agreement except in compliance with U.S. export Laws and regulations.

13.13. Force Majeure . Neither Party shall be held liable to the other Party nor be deemed to have defaulted under or breached the Collaboration Agreement for failure or delay in performing any obligation under the Collaboration Agreement to the extent that such failure or delay is caused by or results from causes beyond the reasonable control of the affected Party, potentially including embargoes, war, acts of war (whether war be declared or not), insurrections, riots, civil commotions, strikes, lockouts or other labor disturbances, fire, floods, or other acts of God. The affected Party shall notify the other Party of such force majeure circumstances as soon as reasonably practical, and shall promptly undertake all reasonable efforts necessary to cure such force majeure circumstances.

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M ASTER A GREEMENT

13.14. Independent Parties . It is expressly agreed that Alnylam and Genzyme shall be independent contractors and that the relationship between Alnylam and Genzyme shall not constitute a partnership, joint venture or agency. Alnylam shall not have the authority to make any statements, representations or commitments of any kind, or to take any action, which shall be binding on Genzyme, without the prior written consent of Genzyme, and Genzyme shall not have the authority to make any statements, representations or commitments of any kind, or to take any action, which shall be binding on Alnylam without the prior written consent of Alnylam.

13.15. Counterparts . The Agreement may be executed in two or more counterparts, including by facsimile or PDF signature pages, each of which shall be deemed an original, but all of which together shall constitute one and the same instrument.

13.16. Performance by Affiliates .

13.16.1. Use of Affiliates. Each Party acknowledges and accepts that the other Party may exercise its rights and perform its obligations under this Master Agreement either directly or through one or more of its Affiliates. A Party’s Affiliates will have the benefit of all rights (including all licenses) of such Party under this Master Agreement. Accordingly, in this Master Agreement “Genzyme” will be interpreted to mean “Genzyme and/or its Affiliates” and “Alnylam” will be interpreted to mean “Alnylam and/or its Affiliates” where necessary to give each Party’s Affiliates the benefit of the rights provided to such Party in this Master Agreement; provided , however , that in any event each Party will remain responsible for the acts and omissions, including financial liabilities, of its Affiliates.

13.16.2. Future Acquisition of a Party or its Business. [***].

13.17. Binding Effect; No Third Party Beneficiaries . As of the Execution Date, the Collaboration Agreement shall be binding upon and inure to the benefit of the Parties and their respective permitted successors and permitted assigns. Except as expressly set forth in the Collaboration Agreement, no Person other than the Parties and their respective Affiliates and permitted assignees hereunder shall be deemed an intended beneficiary hereunder or have any right to enforce any obligation of the Collaboration Agreement.

[THE REMAINDER OF THIS PAGE HAS BEEN LEFT INTENTIONALLY BLANK]

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IN WITNESS WHEREOF, the Parties have executed this Master Agreement as of the Execution Date.

Signature page to the Master Collaboration Agreement

M ASTER A GREEMENT

Schedule 1.2.7

ADDITIONAL ALNYLAM IN-LICENSES

Confidential Materials omitted and filed separately with the Securities and Exchange Commission. A total of 1 page was omitted.

[***]

M ASTER A GREEMENT

Schedule 1.2.21

ALN-AT3

ALN-AT3 is an investigational ribonucleic acid interference (RNAi) therapeutic agent that is comprised of active pharmaceutical ingredient ALN-[***] (see sequence and diagram below), [***].

[***]

M ASTER A GREEMENT

Schedule 1.2.22

ALN-TTR CORE TECHNOLOGY PATENTS

[***]

M ASTER A GREEMENT

Schedule 1.2.24

ALN-TTR PRODUCT-SPECIFIC PATENTS

[***]

M ASTER A GREEMENT

Schedule 1.2.26

ALN-TTR02

ALN-TTR02 is an investigational ribonucleic acid interference (RNAi) therapeutic agent that is comprised of active pharmaceutical ingredient [***].

Confidential Materials omitted and filed separately with the Securities and Exchange Commission. A total of 2 pages were omitted.

[***]

M ASTER A GREEMENT

Schedule 1.2.29

ALN-TTRsc

ALN-TTRsc is an investigational ribonucleic acid interference (RNAi) therapeutic agent that is comprised of active pharmaceutical ingredient [***].

Confidential Materials omitted and filed separately with the Securities and Exchange Commission. A total of 2 pages were omitted.

[***]

M ASTER A GREEMENT

Schedule 1.2.34

Confidential Materials omitted and filed separately with the Securities and Exchange Commission. A total of 1 page was omitted.

[***]

M ASTER A GREEMENT

Schedule 1.2.71

CORE PIPELINE PROGRAM LIST

Section A

Alnylam
siRNA
identifier

(if any)

Gene

Target

Name

Gene

Target

Symbol

NCBI

Human
Gene

NCBI’s

Reference
Sequences

Transcript*

NCBI’s

Reference
Sequences

Protein*

Alias(es)

Description

ALN-TTR02

TTR

7276

NM_000371

NP_000362

CTS; CTS1; HsT2651; PALB; TBPA

transthyretin

ALN-TTRsc

TTR

7276

NM_000371

NP_000362

CTS; CTS1; HsT2651; PALB; TBPA

transthyretin

ALN-AT3

AT3

SERPINC1

462

NM_000488

NP_000479

AT3; AT3D; ATIII; THPH7

serpin peptidase inhibitor, clade C (antithrombin), member 1

ALN-CC5

CC5

727

NM_001735

NP_001726

C5a; C5b; CPAMD4

complement component 5

ALN-AS1

ALAS1

211

NM_000688

NP_000679

ALAS; MIG4; ALAS3; ALASH

aminolevulinate, delta-, synthase 1

ALN-AAT

AAT

SERPINA1

5265

NM_000295

NP_000286

PI; A1A; AAT; PI1; A1AT; PRO2275; alpha1AT

serpin peptidase inhibitor, clade A (alpha-1 antiproteinase, antitrypsin), member 1

ALN-TMP

TMPRSS6

164656

NM_153609

NP_705837

IRIDA

transmembrane protease, serine 6

ALN-ANG

ANGPTL3

27329

NM_014495

NP_055310

ANL3; ANG-5; FHBL2; ANGPT5

angiopoietin-like 3

Updated as of: the Execution Date

M ASTER A GREEMENT

Confidential Materials omitted and filed separately with the Securities and Exchange Commission. A total of 1 page was omitted.

[***]

Updated as of: the Execution Date

Schedule 1.2.80

FORM OF EXERCISE NOTICE

Genzyme Corporation

500 Kendall Street

Cambridge, MA 02142

[ , 20 ]

Alnylam Pharmaceuticals, Inc.

300 Third Street

Cambridge, MA 02142

Attn: Vice President - Legal

Dear Sir or Madam:

In accordance with Sections 2.2 and 3.4 of that certain Master Collaboration Agreement by and between Alnylam Pharmaceuticals, Inc. (“ Alnylam ”) and Genzyme Corporation (“ Genzyme ”) executed as of January 11, 2014 (the “ Master Agreement ”), Genzyme hereby provides written notice exercising the option to acquire the Option Product(s) set forth in Exhibit A attached hereto, pursuant to the terms of the Master Agreement. Capitalized terms used but not defined herein will have the meanings assigned to them in the Master Agreement.

Please acknowledge receipt of this option exercise by countersigning this letter and returning it to me. Failure to return the letter countersigned will not affect the effectiveness of this option exercise by Genzyme.


Very truly yours, GENZYME CORPORATION

By:
		Name: Title:

cc:	Goodwin Proctor LLP

Exchange Place

55 State Street

Boston, MA 02109

Attn: Kingsley L. Taft, Esq.

Accepted and agreed:

ALNYLAM PHARMACEUTICALS, INC.




By:
		Name: Title:

Exhibit A

Option Product: .

Genzyme is exercising its option to acquire the Option Product(s) listed above, pursuant to:

the Regional License Terms

the Global License Terms (if applicable)

the Co-Co License Terms (if applicable)

Genzyme has determined that:

a filing or notification under applicable Antitrust Laws is not necessary.

a filing or notification must be made under applicable Antitrust Laws.

Summary of any such filing(s) or notification(s):

Schedule 1.2.82

EXISTING ALNYLAM IN-LICENSES

Confidential Materials omitted and filed separately with the Securities and Exchange Commission. A total of 1 page was omitted.

[***]

M ASTER A GREEMENT

Schedule 1.2.88

FINAL OPTION DATA PACKAGE

Confidential Materials omitted and filed separately with the Securities and Exchange Commission. A total of 1 page was omitted.

[***]

M ASTER A GREEMENT

Schedule 1.2.116

HUMAN POP PROPOSED STUDIES

Confidential Materials omitted and filed separately with the Securities and Exchange Commission. A total of 1 page was omitted.

[***]

M ASTER A GREEMENT

Schedule 1.2.123

INITIAL OPTION DATA PACKAGE

Confidential Materials omitted and filed separately with the Securities and Exchange Commission. A total of 2 pages were omitted.

[***]

M ASTER A GREEMENT

Schedule 1.2.134

LOCKED CORE PIPELINE PROGRAM LIST

Alnylam
siRNA
identifier

(if any)

Gene

Target

Name

Gene

Target

Symbol

NCBI

Human

Gene

NCBI’s

Reference

Sequences

Transcript*

NCBI’s

Reference

Sequences

Protein*

Alias(es)

Description

ALN-TTR02

TTR

7276

NM_000371

NP_000362

CTS; CTS1; HsT2651; PALB; TBPA

transthyretin

ALN-TTRsc

TTR

7276

NM_000371

NP_000362

CTS; CTS1; HsT2651; PALB; TBPA

transthyretin

ALN-AT3

AT3

SERPINC1

462

NM_000488

NP_000479

AT3; AT3D; ATIII; THPH7

serpin peptidase inhibitor, clade C (antithrombin), member 1

ALN-CC5

CC5

727

NM_001735

NP_001726

C5a; C5b; CPAMD4

complement component 5

ALN-AS1

ALAS1

211

NM_000688

NP_000679

ALAS; MIG4; ALAS3; ALASH

aminolevulinate, delta-, synthase 1

ALN-AAT

AAT

SERPINA1

5265

NM_000295

NP_000286

PI; A1A; AAT; PI1; A1AT; PRO2275; alpha1AT

serpin peptidase inhibitor, clade A (alpha-1 antiproteinase, antitrypsin), member 1

ALN-TMP

TMPRSS6

164656

NM_153609

NP_705837

IRIDA

transmembrane protease, serine 6

Updated as of: the Execution Date

Schedule 1.2.135

LOCKED NON-CORE PIPELINE PROGRAM LIST

Alnylam

siRNA

identifier

(if any)

Gene

Target

Name

Gene
Target
Symbol

NCBI
Human
Gene

NCBI’s
Reference
Sequences
Transcript*

NCBI’s
Reference
Sequences
Protein*

Alias(es)

Description

ALN-VSP

VEGF

VEGFA

7422

NM_003376

NP_003367

VPF;
VEGF;
MVCD1

Vacular
endothelial
growth
factor A

ALN-VSP

KSP (kinesin spindle protein)

KIF11

3832

NM_004523

NP_004514

EG5;
HKSP;
KNSL1;
MCLMR;
TRIP5

Kinesin
family
member 11

ALN-PCS

PCSK9

255738

NM_174936

NP_777596

FH3; PC9;
NARC1;
LDLCQ1;
NARC-1;
HCHOLA3

proprotein
convertase
subtilisin/
kexin type
9

ALN-RSV01

RSV genome

RSV
genome

N/A

NC_001803

N/A

RSV
Refseq
Genome

ALN-RSV02

RSV genome

RSV
genome

N/A

NC_001803

N/A

RSV
Refseq
Genome

ALN-HTT

HTT

3064

NM_002111

NP_002102

HD; IT15

huntingtin

[***]

Updated as of: the Execution Date

Schedule 1.2.146

NAMED PIPELINE PROGRAMS

Alnylam
siRNA
identifier

(if any)

Gene
Target
Name

Gene
Target
Symbol

NCBI
Human
Gene

NCBI’s
Reference
Sequences
Transcript*

NCBI’s
Reference
Sequences
Protein*

Alias(es)

Description

ALN-TTR02

TTR

7276

NM_000371

NP_000362

CTS; CTS1;
HsT2651;
PALB; TBPA

transthyretin

ALN-TTRsc

TTR

7276

NM_000371

NP_000362

CTS; CTS1;
HsT2651;
PALB; TBPA

transthyretin

ALN-AT3

AT3

SERPINC1

462

NM_000488

NP_000479

AT3; AT3D;
ATIII; THPH7

serpin peptidase
inhibitor, clade
C (antithrombin),
member 1

ALN-CC5

CC5

727

NM_001735

NP_001726

C5a; C5b;
CPAMD4

complement
component 5

ALN-AS1

ALAS1

211

NM_000688

NP_000679

ALAS;
MIG4; ALAS3;
ALASH

aminolevulinate,
delta-, synthase 1

ALN-AAT

AAT

SERPINA1

5265

NM_000295

NP_000286

PI; A1A; AAT;
PI1; A1AT;
PRO2275;
alpha1AT

serpin peptidase
inhibitor, clade
A (alpha-1
antiproteinase,
antitrypsin),
member 1

Updated as of: the Execution Date

M ASTER A GREEMENT

Schedule 1.2.149

NON-CORE PIPELINE PROGRAM LIST

Alnylam

siRNA

identifier

(if any)

Gene

Target

Name

Gene
Target
Symbol

NCBI
Human
Gene

NCBI’s
Reference
Sequences
Transcript*

NCBI’s
Reference
Sequences
Protein*

Alias(es)

Description

ALN-VSP

VEGF

VEGFA

7422

NM_003376

NP_003367

VPF;
VEGF;
MVCD1

Vacular
endothelial
growth
factor A

ALN-VSP

KSP (kinesin spindle protein)

KIF11

3832

NM_004523

NP_004514

EG5;
HKSP;
KNSL1;
MCLMR;
TRIP5

Kinesin
family
member 11

ALN-PCS

PCSK9

255738

NM_174936

NP_777596

FH3; PC9;
NARC1;
LDLCQ1;
NARC-1;
HCHOLA3

proprotein
convertase
subtilisin/
kexin type
9

ALN-RSV01

RSV genome

RSV
genome

N/A

NC_001803

N/A

RSV
Refseq
Genome

ALN-RSV02

RSV genome

RSV
genome

N/A

NC_001803

N/A

RSV
Refseq
Genome

ALN-HTT

HTT

3064

NM_002111

NP_002102

HD; IT15

huntingtin

[***]

Updated as of: the Execution Date

M ASTER A GREEMENT

Schedule 1.2.159

OPTION PRODUCT CORE TECHNOLOGY PATENTS

[***]

M ASTER A GREEMENT

Schedule 1.2.162

OPTION PRODUCT-SPECIFIC PATENTS

[***]

M ASTER A GREEMENT

Schedule 1.2.178

POTENTIAL ALNYLAM IN-LICENSES

Confidential Materials omitted and filed separately with the Securities and Exchange Commission. A total of 1 page was omitted.

[***]

M ASTER A GREEMENT

Schedule 2.1.3.3

Exempted Third Party CNS Agreements

Amended and Restated Collaboration Agreement dated as of July 27, 2007 by and between Alnylam Pharmaceuticals, Inc. and Medtronic, Inc.

M ASTER A GREEMENT

Schedule 6.1

ALN-TTR02 SUPPLY AGREEMENT TERMS

Confidential Materials omitted and filed separately with the Securities and Exchange Commission. A total of 3 pages were omitted.

[***]

M ASTER A GREEMENT

Schedule 6.2

SUPPLY AGREEMENT TERMS

Confidential Materials omitted and filed separately with the Securities and Exchange Commission. A total of 4 pages were omitted.

[***]

M ASTER A GREEMENT

Schedule 7.3

PRESS RELEASES

See attached.

M ASTER A GREEMENT

Schedule 8.2

DISCLOSURE SCHEDULE

Confidential Materials omitted and filed separately with the Securities and Exchange Commission. A total of 2 pages were omitted.

[***]

M ASTER A GREEMENT

Schedule 10.2

IDENTIFIED PATENT RIGHTS

Confidential Materials omitted and filed separately with the Securities and Exchange Commission. A total of 1 page was omitted.

[***]

E XECUTION V ERSION

APPENDIX A

REGIONAL PRODUCT LICENSE AND COLLABORATION

TERMS

AN APPENDIX TO THE MASTER COLLABORATION AGREEMENT

dated as of January 11, 2014

by and between

ALNYLAM PHARMACEUTICALS, INC.

and

GENZYME CORPORATION

R EGIONAL L ICENSE T ERMS

TABLE OF CONTENTS


		PAGE
1. RELATIONSHIP WITH MASTER AGREEMENT; DEFINITIONS			5

1.1.	Relationship with Master Agreement		5

1.2.	Definitions		6

2. DEVELOPMENT COLLABORATION			22

2.1.	Overview		22

2.2.	Development Plans		22

2.3.	Responsibilities for Development Activities and Costs		30

2.4.	Diligence		33

2.5.	Records; Reports; Information Sharing		34

2.6.	Third Parties		35

3. REGULATORY MATTERS			35

3.1.	Regulatory Filings and Interactions		35

3.2.	EMA Regulatory Strategy		38

3.3.	Costs of Regulatory Affairs		38

3.4.	Right of Reference		38

4. COMMERCIALIZATION OF THE LICENSED PRODUCTS			39

4.1.	Responsibility, Cost and Diligence		39

4.2.	Genzyme Territory Commercialization Plan		39

4.3.	Alnylam Territory Commercialization Plan		39

4.4.	Advertising and Promotional Materials		40

4.5.	Commercialization Reporting Obligations		40

4.6.	Recalls, Market Withdrawals or Corrective Actions		42

4.7.	Ex-Territory Sales; Export Monitoring		42

5. COLLABORATION MANAGEMENT			42

5.1.	Product Joint Steering Committee		42

5.2.	Appointment of Subcommittees, Project Teams and RLP Alliance Managers		43

5.3.	PJSC Meetings		44

5.4.	PJSC Minutes		44

- i -

R EGIONAL L ICENSE T ERMS



5.5.	PJSC Responsibilities	44

5.6.	PJSC Decision-Making	46

5.7.	Term of PJSC	47

5.8.	Alnylam Third Party Partner	47

6. LICENSES		49

6.1.	License Grants to Genzyme	49

6.2.	License Grants to Alnylam	51

6.3.	Joint Collaboration IP	52

6.4.	Compliance with In-Licenses	52

6.5.	Alnylam Territory Right of First Negotiation	53

6.6.	Bankruptcy	53

6.7.	No Other Rights	54

7. CERTAIN FINANCIAL TERMS		54

7.1.	Milestone Fees	54

7.2.	Royalties	56

8. REPRESENTATIONS, WARRANTIES AND COVENANTS		58

8.1.	Representations and Warranties of Alnylam	58

8.2.	Representations and Warranties of Genzyme	60

8.3.	Warranty Disclaimer	60

8.4.	Certain Covenants	60

9. INTELLECTUAL PROPERTY OWNERSHIP, PROTECTION AND RELATED MATTERS		62

9.1.	Inventorship	62

9.2.	Ownership	62

9.3.	Prosecution and Maintenance of Patent Rights	62

9.4.	Third Party Infringement	65

9.5.	Patent Term Extensions	67

9.6.	Common Interest	67

9.7.	Trademarks	67

9.8.	Cooperative Research and Technology (CREATE) Act Acknowledgment	68

10. TERM AND TERMINATION		69

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10.1.	Term	69

10.2.	Termination Rights	69

10.2.4.	Challenges of Patent Rights	71

10.3.	Effect of Termination	72

10.4.	Fundamental Breach of Alnylam’s Development Obligations	77

10.5.	Effect of Expiration or Termination; Survival	78

11. PERFORMANCE BY AFFILIATES		79

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SCHEDULES


Schedule 1.2.13-1		Alnylam Core Technology Patents for ALN-TTR02

Schedule 1.2.18-1		Alnylam Product-Specific Patents for ALN-TTR02

Schedule 2.2.1-1		Global Development Strategy for ALN-TTR02

Schedule 2.2.2.1-1		Global Development Plan for ALN-TTR02

Schedule 2.2.2.6(d)-1		Alnylam Territory Development Plan for ALN-TTR02

Schedule 2.2.4-1		Genzyme Territory Development Plan for ALN-TTR02

Schedule 8.1		Disclosure Schedule

Schedule 8.1.12		Existing Alnylam In-Licenses / Additional Alnylam In-Licenses

Schedule 8.4.1.3(c)		Exceptions to Exclusivity

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REGIONAL PRODUCT LICENSE AND COLLABORATION TERMS

THESE REGIONAL PRODUCT LICENSE AND COLLABORATION TERMS are Appendix A to the Master Agreement, dated as of the Execution Date, by and between Alnylam Pharmaceuticals, Inc., a corporation organized and existing under the laws of the State of Delaware (“ Alnylam ”), and Genzyme Corporation, a corporation organized and existing under the laws of the Commonwealth of Massachusetts (“ Genzyme ”).

RECITALS:

WHEREAS , Alnylam and Genzyme are parties to that certain Master Collaboration Agreement (dated as of the Execution Date) (the “ Master Agreement ”) pursuant to which Genzyme has an option to receive licenses and other rights with respect to Regional Licensed Products from Alnylam in the Genzyme Territory;

WHEREAS , the Parties have agreed that ALN-TTR02 is a Regional Licensed Product;

WHEREAS , Genzyme may exercise a Regional Option, 2019 Trailing Regional Option or 2021 Trailing Regional Option pursuant to the Master Agreement for any Regional Option Product thereunder and such Regional Option Product will then be deemed a Regional Licensed Product;

WHEREAS , the Parties desire for Alnylam to continue to develop such Regional Licensed Products for the Alnylam Territory and the Genzyme Territory;

WHEREAS, Alnylam desires to retain the right to commercialize such Regional Licensed Products in the Alnylam Territory; and

WHEREAS , Alnylam and Genzyme now wish to set forth the terms and conditions under which Genzyme will have the right to Develop and Commercialize such Regional Licensed Products in the Genzyme Territory.

NOW , THEREFORE , in consideration of the foregoing premises and the mutual covenants herein contained, the Parties hereby agree as follows:

1. RELATIONSHIP WITH MASTER AGREEMENT; DEFINITIONS

1.1. Relationship with Master Agreement . These Regional License Terms become effective on a Regional Licensed Product-by-Regional Licensed Product basis on the Implementation Date in accordance with the Master Agreement. The Master Agreement generally governs the Parties’ relationship with respect to Regional Licensed Products during the period of time before Genzyme exercises its Regional Option under the Master Agreement ( i.e ., before such product became a Regional Licensed Product). The Master Agreement also contains terms that are generally applicable to Regional Licensed Products, Global Licensed Products (as defined in the Master Agreement) and Co-Co Licensed Products (as defined in the Master

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Agreement). Accordingly, the following Sections of the Master Agreement are incorporated herein by reference: Section 2.2 (Effectiveness of Licenses to Collaboration Products); Section 5 (Collaboration Management); Section 6 (Manufacture and Supply of the Collaboration Products); Section 7 (Confidentiality and Publication); Section 9 (Royalty Reports; Payments; Audit); Section 10 (Indemnification; Limitation of Liability; Insurance); Section 12.2.4 (Challenges of Patent Rights); and Section 13 (Miscellaneous).

1.2. Definitions . Unless specifically set forth to the contrary herein, the following terms, whether used in the singular or plural, shall have the respective meanings set forth below:

1.2.1. “ Acquired Business ” has the meaning set forth in Section 11.3 (Acquired Programs).

1.2.2. “ Acquirer ” has the meaning set forth in Section 11.2 (Future Acquisition of a Party or its Business).

1.2.3. “ Additional Development Activities ” has the meaning set forth in Section 2.2.2.6(a) (Additional Development Proposals).

1.2.4. “ Additional Development Opt-In Date ” has the meaning set forth in Section 2.2.2.6(c)(iii) (Opt-In for Additional Development Activities).

1.2.5. “ Additional Development Opt-In Notice ” has the meaning set forth in Section 2.2.2.6(c)(iii) (Opt-In for Additional Development Activities).

1.2.6. “ Additional Development Proposal ” has the meaning set forth in Section 2.2.2.6(a) (Additional Development Proposals).

1.2.7. “ AF11 Lipid Nanoparticle Formulation ” has the meaning set forth in the Master Agreement.

1.2.8. “ Affiliate ” means, with respect to a Person, any other Person which controls, is controlled by, or is under common control with the applicable Person. For purposes of this definition, “control” shall mean: (a) in the case of corporate entities, direct or indirect ownership of at least fifty percent (50%) of the stock or shares entitled to vote for the election of directors, or otherwise having the power to control or direct the affairs of such Person; and (b) in the case of non-corporate entities, direct or indirect ownership of at least fifty percent (50%) of the equity interest or the power to direct the management and policies of such non-corporate entities.

1.2.9. “ AJSC ” has the meaning set forth in the Master Agreement.

1.2.10. “ ALN-TTR02 ” has the meaning set forth in the Master Agreement.

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1.2.11. “ ALN-TTR02 Clinical Supply Agreement ” has the meaning set forth in the Master Agreement.

1.2.12. “ ALN-TTR02 Commercial Supply Agreement ” has the meaning set forth in the Master Agreement.

1.2.13. “ Alnylam Core Technology Patents ” means Patent Rights Controlled by Alnylam during the Term that are [***]. The Alnylam Core Technology Patents existing as of the Effective Date for ALN-TTR02 are those Patent Rights identified on Schedule 1.2.13-1 . The Alnylam Core Technology Patents existing as of the Implementation Date for any other Regional Licensed Product will be identified as the “Alnylam Core Technology Patents” in the Option Data Package for such Regional Licensed Product provided by Alnylam to Genzyme under the Master Agreement and then attached hereto as Schedules 1.2.13-2 , 1.2.13-3 , and so forth.

1.2.14. “ Alnylam Developed siRNA Product ” means an siRNA with respect to which (a) Alnylam Controls Patent Rights Covering such siRNA, provided that once a product first satisfies the criterion set forth in this clause (a) such criterion shall be deemed satisfied at all times thereafter as to such product, and (b) Alnylam or an Affiliate of Alnylam plays(ed) a material role in the Development.

1.2.15. “ Alnylam In-License ” means any Existing Alnylam In-License or any Collaboration In-License to which Alnylam is a party.

1.2.16. “ Alnylam Know-How ” means Know-How Controlled by Alnylam during the Term that is reasonably necessary or useful for Genzyme to Develop, Manufacture and/or Commercialize Regional Licensed Products in the Field in the Genzyme Territory, other than Alnylam’s interest in Know-How included in Joint Collaboration IP.

1.2.17. “ Alnylam Patents ” means Alnylam Core Technology Patents and Alnylam Product-Specific Patents.

1.2.18. “ Alnylam Product-Specific Patents ” means Patent Rights Controlled by Alnylam during the Term that claim [***]. The Alnylam Product-Specific Patents existing as of the Effective Date for ALN-TTR02 are those Patent Rights identified on Schedule 1.2.18-1 . The Alnylam Product-Specific Patents existing as of the Implementation Date for any other Regional Licensed Product will be identified as the “Alnylam Product-Specific Patents” in the Option Data Package for such Regional Licensed Product provided by Alnylam to Genzyme under the Master Agreement and then attached hereto as Schedules 1.2.18-2 , 1.2.18-3 , and so forth. [***].

1.2.19. “ Alnylam Technology ” means, collectively, Alnylam Know-How, Alnylam Patents and Alnylam’s interest in Joint Collaboration IP.

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1.2.20. “ Alnylam Territory ” means the United States, Canada, Austria, Belgium, Denmark, Finland, France, Germany, Greece, Ireland, Italy, Luxembourg, the Netherlands, Portugal, Spain, Sweden, the United Kingdom, Norway, Switzerland, Liechtenstein, Andorra, Iceland and Greenland.

1.2.21. “ Alnylam Territory Commercialization Plan ” has the meaning set forth in Section 4.4 (Alnylam Territory Commercialization Plan).

1.2.22. “ Alnylam Territory Development Plan ” has the meaning set forth in Section 2.2.3 (Alnylam Territory Development Plan).

1.2.23. “ Alnylam Territory MMC ” [***].

1.2.24. “ Alnylam Trademark ” has the meaning set forth in Section 9.7(b) (Trademarks).

1.2.25. “ ANDA ” means an Abbreviated New Drug Application (or any successor application or procedure) as defined in regulations promulgated by the FDA under the FDCA, which ANDA is filed with or intended to be filed with the FDA (and, as applicable, any other analogous application filed with a Regulatory Authority in any country other than the U.S. in the Genzyme Territory) for Regulatory Approval for marketing and selling a Regional Licensed Product in the Genzyme Territory.

1.2.26. “ Appendix ” means this Appendix A (Regional Product License and Collaboration Terms).

1.2.27. “ Bankrupt Party ” has the meaning set forth in Section 6.6 (Bankruptcy).

1.2.28. “ Budget Adjustment Triggers ” has the meaning set forth in Section 2.2.2.3 (Managing and Amending Global Development Plans and Global Development Budgets).

1.2.29. “ Calendar Quarter ” means the respective periods of three (3) consecutive calendar months ending on March 31, June 30, September 30 and December 31 of each Calendar Year, provided that (a) the first Calendar Quarter of the Term shall begin on the Effective Date and end on the first to occur of March 31, June 30, September 30 or December 31 thereafter and the last Calendar Quarter of the Term shall end on the last day of the Term and (b) the first Calendar Quarter of a Royalty Term for a Regional Licensed Product in a country shall begin on the First Commercial Sale of a Regional Licensed Product in such country and end on the first to occur of March 31, June 30, September 30 or December 31 thereafter and the last Calendar Quarter of a Royalty Term shall end on the last day of such Royalty Term.

1.2.30. “ Calendar Year ” means each successive period of twelve (12) months commencing on January 1 and ending on December 31, provided that (a) the first Calendar Year of the Term shall begin on the Effective Date and end on the first December 31 thereafter and the

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last Calendar Year of the Term shall end on the last day of the Term and (b) the first Calendar Year of a Royalty Term for a Regional Licensed Product in a country shall begin on the First Commercial Sale of a Regional Licensed Product in such country and end on the first December 31 thereafter and the last Calendar Year of the Term shall end on the last day of such Royalty Term.

1.2.31. “ Carbohydrate Conjugate ” has the meaning set forth in the Master Agreement.

1.2.32. “ Clinical Study ” has the meaning set forth in the Master Agreement.

1.2.33. “ Co-Co/Global Option ” has the meaning set forth in the Master Agreement.

1.2.34. “ Co-Co License Terms ” has the meaning set forth in the Master Agreement.

1.2.35. “ Co-Co Licensed Product ” has the meaning set forth in the Master Agreement.

1.2.36. “ Collaboration In-License ” has the meaning set forth in the Master Agreement.

1.2.37. “ Commercialization ” or “ Commercialize ” has the meaning set forth in the Master Agreement.

1.2.38. “ Commercially Reasonable Efforts ” means [***].

1.2.39. “ Competing Program ” has the meaning set forth in Section 11.3 (Acquired Programs).

1.2.40. “ Competitive Infringement ” has the meaning set forth in Section 9.4.1 (Notices).

1.2.41. “ Confidential Information ” has the meaning set forth in the Master Agreement.

1.2.42. “ Control ”, “ Controls ” or “ Controlled by ” has the meaning set forth in the Master Agreement.

1.2.43. “ Cost of Goods ” has the meaning set forth in the Master Agreement.

1.2.44. “ Cover ,” “ Covering ” or “ Covers ” has the meaning set forth in the Master Agreement.

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1.2.45. “ CPI ” shall mean the Consumer Price Index – Urban Wage Earners and Clerical Workers, U.S. City Average, All Items, 1982-84 = 100, published by the United States Department of Labor, Bureau of Labor Statistics (or its successor equivalent index) in the United States.

1.2.46. “ CRO ” means a contract research organization.

1.2.47. “ Development ,” “ Developing ” or “ Develop ” has the meaning set forth in the Master Agreement.

1.2.48. “ Development Plan ” means, with respect to each Regional Licensed Product, (a) with respect to Alnylam, the Alnylam Territory Development Plan for such Regional Licensed Product, (b) with respect to Genzyme, the Genzyme Territory Development Plan for such Regional Licensed Product, and (c) with respect to both Parties, the Global Development Plan for such Regional Licensed Product.

1.2.49. “ Disputing Party ” has the meaning set forth in Section 2.3.1.2 (Global R&D Costs).

1.2.50. “ Effective Date ” means the date that the Master Agreement becomes effective in accordance with its terms.

1.2.51. “ EMA ” means the European Medicines Agency and any successor Governmental Authority having substantially the same function.

1.2.52. “ End of Phase II Package ” has the meaning set forth in Section 2.2.2.4(c)(ii).

1.2.53. “ EU ” means the European Union, as its membership may be altered from time to time, and any successor thereto.

1.2.54. “ Excess Global R&D Costs ” has the meaning set forth in Section 2.3.1.2 (Global R&D Costs).

1.2.55. “ Exclusivity Period ” means, on a Regional Licensed Product-by-Regional Licensed Product and country-by-country basis within the Genzyme Territory, [***].

1.2.56. “ Execution Date ” has the meaning set forth in the Master Agreement.

1.2.57. “ Existing Alnylam In-License ” has the meaning set forth in the Master Agreement.

1.2.58. “ Existing Genzyme In-License ” has the meaning set forth in the Master Agreement.

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1.2.59. “ FDA ” means the United States Food and Drug Administration and any successor Governmental Authority having substantially the same function.

1.2.60. “ FDCA ” means the United States Federal Food, Drug, and Cosmetic Act of 1938, as amended from time to time, and the regulations and guidelines promulgated thereunder.

1.2.61. “ Field ” means the treatment, diagnosis and/or prevention of all human diseases.

1.2.62. “ First Commercial Sale ” means, with respect to a country, the first sale for end use or consumption of a Regional Licensed Product in such country, except for compassionate use or patient access programs, after all Regulatory Approvals legally required for such sale have been granted by the Regulatory Authority of such country.

1.2.63. “ First Regulatory Approval by the EMA ” means, with respect to a Regional Licensed Product, the earlier of (i) if Regulatory Approval in the EU is sought through the EMA centralized procedure, receipt of Regulatory Approval for such Regional Licensed Product from the EMA or (ii) if Regulatory Approval in the EU is sought through a national authorization procedure, receipt of Regulatory Approval for such Regional Licensed Product in the first (1 ^st ) MMC country in the EU.

1.2.64. “ First Regulatory Approval in Japan ” means, with respect to a Regional Licensed Product, receipt of Regulatory Approval for such Regional Licensed Product in Japan.

1.2.65. “ Force Majeure ” means embargoes, war, acts of war (whether war be declared or not), terrorism, insurrections, riots, civil commotions, strikes, lockouts or other labor disturbances, fire, floods, or other acts of God.

1.2.66. “ Fundamental Breach ” [***].

1.2.67. “ GAAP ” has the meaning set forth in the Master Agreement.

1.2.68. “ GalNAc Conjugate ” has the meaning set forth in the Master Agreement.

1.2.69. “ Generic Competition ” means, with respect to a Regional Licensed Product in any country in the Genzyme Territory in a given Calendar Quarter, that, during such Calendar Quarter, (a) one or more Generic Products with respect to such Regional Licensed Product are commercially available in such country, and (b) Net Sales of such Regional Licensed Product in such country in such Calendar Quarter equal less than [***] of the average Net Sales of such Regional Licensed Product over the [***] consecutive Calendar Quarters immediately prior to the Calendar Quarter in which one or more Generic Products first became commercially available in such country.

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1.2.70. “ Generic Product ” means, on a Regional Licensed Product-by-Regional Licensed Product and country-by-country basis, a pharmaceutical product that (a) is sold by a Person that is not a Related Party of Genzyme under a marketing authorization granted by a Regulatory Authority in such country to a Third Party; (b) [***]; and (c) is approved by the Regulatory Authority in such country pursuant to an approval process that relies in part on pivotal safety and/or efficacy data in such Regulatory Authority’s previous grant of marketing authorization for such Regional Licensed Product.

1.2.71. “ Genzyme Collaboration IP ” means (a) any Know-How, first identified, discovered or developed solely by employees of Genzyme or its Affiliates or other persons not employed by Alnylam acting on behalf of Genzyme, in the conduct of the Collaboration and (b) any Patent Rights that claim or Cover such Know-How and are Controlled by Genzyme at any time during the Term. Genzyme Collaboration IP excludes Genzyme’s interest in Joint Collaboration IP, in each case (a) and (b), other than Genzyme Manufacturing IP.

1.2.72. “ Genzyme Disclosed Manufacturing Know-How ” means Know-How (a) Controlled by Genzyme at any time during the Term that is useful in the Manufacture of a Regional Licensed Product and (b) that Genzyme, in its sole discretion, discloses in writing to Alnylam in the course of the Collaboration.

1.2.73. “ Genzyme In-License ” means any Existing Genzyme In-License, Un-Blocking Genzyme In-License, or any Collaboration In-License to which Genzyme is a party.

1.2.74. “ Genzyme Know-How ” means Know-How Controlled by Genzyme during the Term that is reasonably necessary or useful for Alnylam to Develop, Commercialize and/or Manufacture Regional Licensed Products in the Field in the Alnylam Territory (other than Genzyme’s rights in Joint Collaboration IP, Genzyme Collaboration IP and Genzyme Manufacturing IP).

1.2.75. “ Genzyme Manufacturing IP ” means (a) any Know-How related to the Manufacture of Regional Licensed Products (or oligonucleotides generally) Controlled by Genzyme at any time during the Term, and (b) any Patent Rights that claim or cover such Know-How and are Controlled by Genzyme at any time during the Term, excluding Improvement Manufacturing Patent Rights and Genzyme Disclosed Manufacturing Know-How.

1.2.76. “ Genzyme Patent Jurisdiction ” has the meaning set forth in the Master Agreement.

1.2.77. “ Genzyme Patent Rights ” means those Patent Rights Controlled by Genzyme during the Term that are reasonably necessary or useful to Develop, Commercialize and/or Manufacture Regional Licensed Products in the Field in the Alnylam Territory; Genzyme Patent Rights excludes Patent Rights included in Genzyme Collaboration IP, Genzyme’s interest in Joint Collaboration IP and Genzyme Manufacturing IP.

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1.2.78. “ Genzyme Technology ” means, collectively, Genzyme Know-How, Genzyme Patent Rights, Genzyme Collaboration IP and Genzyme’s interest in Joint Collaboration IP, but excluding Genzyme Manufacturing IP.

1.2.79. “ Genzyme Territory ” means all countries and territories of the world other than the Alnylam Territory.

1.2.80. “ Genzyme Territory Commercialization Plan ” has the meaning set forth in Section 4.3 (Genzyme Territory Commercialization Plan).

1.2.81. “ Genzyme Territory Development Plan ” has the meaning set forth in Section 2.2.4 (Genzyme Territory Development Plan).

1.2.82. “ Genzyme Territory MMC ” [***].

1.2.83. “ Genzyme Trademark ” has the meaning set forth in Section 9.7(b) (Trademarks).

1.2.84. “ Global Branding Strategy ” has the meaning set forth in Section 4.5.1 (Global Branding).

1.2.85. “ Global Clinical Study ” has the meaning set forth in Section 2.2.2.5(b) (Oversight of the Global Development Plans).

1.2.86. “ Global Development Activity(ies) ” has the meaning set forth in Section 2.2.2.1 (Global Development Plans).

1.2.87. “ Global Development Budget ” has the meaning set forth in Section 2.2.2.2 (Global Development Budgets).

1.2.88. “ Global Development Plan ” has the meaning set forth in Section 2.2.2.1 (Global Development Plans).

1.2.89. “ Global Development Strategy ” has the meaning set forth in Section 2.2.1 (Global Development Strategy).

1.2.90. “ Global License Terms “has the meaning set forth in the Master Agreement.

1.2.91. “ Global Licensed Product ” has the meaning set forth in the Master Agreement.

1.2.92. “ Global R&D Cost Opt-In Date ” has the meaning set forth in Section 2.3.1.2 (Global R&D Costs).

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1.2.93. “ Global R&D Costs ” means, with respect to a Regional Licensed Product, R&D Costs incurred in connection with any Global Development Activity for such Regional Licensed Product.

1.2.94. “ Global R&D Costs Report ” has the meaning set forth in Section 2.3.1.2 (Global R&D Costs).

1.2.95. “ Governmental Authority ” means any applicable government authority, court, tribunal, arbitrator, agency, department, legislative body, commission or other instrumentality of (a) any government of any country or territory, (b) any nation, state, province, county, city or other political subdivision thereof or (c) any supranational body.

1.2.96. “ Human POP Study ” has the meaning set forth in the Master Agreement.

1.2.97. “ IFRS ” has the meaning set forth in the Master Agreement.

1.2.98. “ Implementation Date ” means, with respect to ALN-TTR02, the Effective Date and, with respect to each other Regional Licensed Product, the Option Exercise Date for such Regional Licensed Product.

1.2.99. “ Improvement Manufacturing Patent Right ” means a Patent Right owned exclusively by Genzyme or its Affiliates that claims an invention related to the Manufacture of a Regional Licensed Product that was made (a) by Genzyme or its Affiliates after the Effective Date in connection with Manufacturing Regional Licensed Products and (b) using Alnylam Know-How that, at the time such Alnylam Know-How was disclosed to Genzyme or its Affiliates, constituted Alnylam’s Confidential Information under Section 7 of the Master Agreement (Confidentiality and Publication).

1.2.100. “ IND ” has the meaning set forth in the Master Agreement.

1.2.101. “ In-License ” has the meaning set forth in the Master Agreement.

1.2.102. “ Infringement Action ” has the meaning set forth in Section 9.4.2(a) (Rights to Enforce – Genzyme Technology).

1.2.103. “ JCOT ” has the meaning set forth in Section 2.2.2.5 (Oversight of the Global Development Plans).

1.2.104. “ Joint Collaboration IP ” means, collectively, (a) any Know-How first identified, discovered or developed jointly by employee(s), agent(s) or consultant(s) acting on behalf of Alnylam or its Affiliates, on the one hand, and employee(s), agent(s) or consultant(s) acting on behalf of Genzyme or its Affiliates, on the other hand, in the conduct of the Collaboration that is Controlled by Alnylam and Genzyme, and (b) any Patent Rights that Cover such Know-How and are Controlled by Alnylam and Genzyme.

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1.2.105. “ Know-How ” has the meaning set forth in the Master Agreement.

1.2.106. “ Laws ” has the meaning set forth in the Master Agreement.

1.2.107. “Licensed Target” means, for ALN-TTR02, TTR, and for each other Regional Licensed Product, the human gene that is targeted by such Regional Licensed Product, as identified in the Option Data Package for such Regional Licensed Product and then attached hereto as Schedules 1.2.107-1 , 1.2.107-2 , and so forth.

1.2.108. “ Lipid Nanoparticle Formulation ” has the meaning set forth in the Master Agreement.

1.2.109. “ Manufacturing ” or “ Manufacture ” has the meaning set forth in the Master Agreement.

1.2.110. “ Manufacturing Claim ” means a claim within a Patent Right directed solely to Manufacturing a Regional Licensed Product.

1.2.111. “ MMC ” means any Alnylam Territory MMC or Genzyme Territory MMC.

1.2.112. “ NDA ” has the meaning set forth in the Master Agreement.

1.2.113. “ Net Sales ” means, with respect to a Regional Licensed Product, the aggregate gross invoiced sales prices from sales of all units of such Regional Licensed Product sold by Genzyme and its Related Parties to independent Third Parties (other than a Sublicensee) after deducting, if not previously deducted, from the amount invoiced or received:

(a) trade, quantity and cash discounts, credits or allowances actually given;

(b) returns, rejections or recalls (due to spoilage, damage, expiration of useful life or otherwise);

(c) Third Party rebates, chargebacks, hospital buying group/group purchasing organization administration fees or managed care organization rebates actually given;

(d) rebates and similar payments made with respect to sales paid for by any governmental or regulatory authority such as Federal or state Medicaid, Medicare or similar state program;

(e) distribution fees and sales commissions paid to Third Parties;

(f) retroactive price reductions or billing corrections;

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(g) value added, sales and use, excise and other similar taxes and surcharges, customary transportation and insurance, custom duties, and other governmental charges; and

(h) amounts previously included in Net Sales of such Regional Licensed Product that are adjusted or written-off by Genzyme or its Related Parties as bad debt or otherwise uncollectible in accordance with the standard practices of Genzyme or its Related Parties for writing off uncollectible amounts consistently applied; provided , however , if any such written-off amounts are subsequently collected, such collected amounts shall be included in Net Sales in the period in which they are subsequently collected.

Such amounts shall be determined from the books and records of Genzyme or its Related Parties, maintained in accordance with IFRS.

In the case of any sale or other disposal for value, such as barter or counter-trade, of a Regional Licensed Product, or part thereof, other than in an arm’s length transaction exclusively for cash, Net Sales shall be calculated as above on the value of the non-cash consideration received or the fair market price (if higher) of such Regional Licensed Product in the country of sale or disposal, as determined in accordance with IFRS.

Notwithstanding the foregoing, the following will not be included in Net Sales: (1) sales between or among Genzyme and its Related Parties (but Net Sales shall include sales to the first Third Party (other than a Sublicensee) by Genzyme or its Related Parties); (2) samples of Regional Licensed Product used to promote additional Net Sales, in amounts consistent with normal business practices of Genzyme; and (3) disposal or use of Regional Licensed Products in Clinical Studies or under compassionate use, patient assistance, named patient use, or test marketing programs or non-registrational studies or other similar programs or studies where the Regional Licensed Product is supplied without charge or at the actual manufacturing cost thereof (without allocation of indirect costs or any mark-up).

In the case where a Regional Licensed Product is sold as part of a Combination Product in a country in the Licensed Territory, Net Sales for the Regional Licensed Product included in such Combination Product in such country shall be calculated as follows:

(i) if the Regional Licensed Product is sold separately in such country and the other active ingredient or ingredients in the Combination Product are sold separately in such country, Net Sales for the Regional Licensed Product shall be calculated by multiplying actual Net Sales of such Combination Product in such country by the fraction A/(A+B), where A is the invoice price of the Regional Licensed Product when sold separately in such country and B is the total invoice price of the other active ingredient or ingredients in the Combination Product when sold separately in such country;

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(ii) if the Regional Licensed Product is sold separately in such country but the other active ingredient or ingredients in the Combination Product are not sold separately in such country, Net Sales for the Regional Licensed Product shall be calculated by multiplying actual Net Sales of such Combination Product in such country by the fraction A/D, where A is the invoice price of the Regional Licensed Product when sold separately in such country and D is the invoice price of the Combination Product in such country;

(iii) if the Regional Licensed Product is not sold separately in such country but the other active ingredient or ingredients in the Combinations Product are sold separately in such country, Net Sales for the Regional Licensed Product shall be calculated by multiplying actual Net Sales of such Combination Product by the fraction 1 – (B/D), where B is the invoice price of the other active ingredient or ingredients in the Combination Product when sold separately in such country and D is the invoice price of the Combination Product in such country; or

(iv) if neither the Regional Licensed Product nor the other active ingredient or ingredients in the Combination Product are sold separately in such country, the Parties shall determine Net Sales for the Regional Licensed Product in such Combination Product by mutual agreement based on the relative contribution of the Regional Licensed Product and each other active ingredient to the Combination Product, and shall take into account in good faith any applicable allocations and calculations that may have been made for the same period in other countries.

For purposes of this Section, “ Combination Product ” means a product that includes at least one active ingredient other than a Regional Licensed Product. Drug delivery vehicles, adjuvants, and excipients shall not be deemed to be “active ingredients”, except in the case where such delivery vehicle, adjuvant, or excipient is recognized by the FDA as an active ingredient in accordance with 21 C.F.R. 210.3(b)(7).

1.2.114. “ Non-Bankrupt Party ” has the meaning set forth in Section 6.6 (Bankruptcy).

1.2.115. “ Non-Disputing Party ” has the meaning set forth in Section 2.3.1.2(d) (Global R&D Costs).

1.2.116. “ Non-Proposing Party ” has the meaning set forth in Section 2.2.2.6(c) (Independent Performance of Additional Development Activities).

1.2.117. “ Option Data Package ” has the meaning set forth in the Master Agreement.

1.2.118. “ Option Exercise Date ” has the meaning set forth in the Master Agreement.

1.2.119. “ Party ” means Genzyme and/or Alnylam.

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1.2.120. “ Patent Challenge ” has the meaning set forth in Section 10.2.4 (Challenges of Patents).

1.2.121. “ Patent Rights ” has the meaning set forth in the Master Agreement.

1.2.122. “ Person ” means any natural person, corporation, unincorporated organization, partnership, association, sole proprietorship joint stock company, joint venture, limited liability company, trust or government, or any Governmental Authority, or any other similar entity.

1.2.123. “ Phase 2 Budget ” has the meaning set forth in Section 2.2.2.4 (Budget Caps; Adjustment and Compensation).

1.2.124. [***].

1.2.125. “ Phase 3 Budget ” has the meaning set forth in Section 2.2.2.4 (Budget Caps; Adjustment and Compensation).

1.2.126. [***].

1.2.127. “ Phase I Study ” has the meaning set forth in the Master Agreement.

1.2.128. “ Phase II Study ” has the meaning set forth in the Master Agreement.

1.2.129. “ Phase III Study ” has the meaning set forth in the Master Agreement.

1.2.130. “ Post-Marketing Study ” has the meaning set forth in the Master Agreement.

1.1.2. “ Post-Phase 3 Budget ” has the meaning set forth in Section 2.2.2.4 (Budget Caps; Adjustment and Compensation).

1.2.131. [***].

1.2.132. “ Product Joint Steering Committee ” or “ PJSC ” means the joint steering committee as more fully described in Section 5.1 (Product Joint Steering Committee).

1.2.133. “ Product Trademark(s) ” means the Trademarks used, or intended for use, in connection with the distribution, marketing, promotion and sale of the Regional Licensed Products. Product Trademarks specifically exclude the corporate names and logos of the Parties and their Affiliates. Product Trademark includes both the Alnylam Trademarks and the Genzyme Trademarks.

1.2.134. “ Promotional Materials ” has the meaning set forth in Section 4.5.2 (Alnylam A&P).

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1.2.135. “ Proposing Party ” has the meaning set forth in Section 2.2.2.6(a) (Additional Development Proposals).

1.2.136. “ R&D Costs ” means, with respect to a Regional Licensed Product, costs and expenses incurred in connection with the performance of any Development activity for such Regional Licensed Product, including [***].

1.2.137. “ R&D FTE ” means [***] of work per annum devoted to or in support of the Development or Manufacture of a Regional Licensed Product that is carried out by one or more qualified scientific or technical employees (excluding Third Party contractors) of a Party or its Affiliates.

1.2.138. “ R&D FTE Cost ” means, for any period, the R&D FTE Rate multiplied by the number of R&D FTEs in such period.

1.2.139. “ R&D FTE Rate ” means [***] per FTE, increased annually beginning on January 1, 2015 and thereafter on January 1 of each succeeding year by the percentage increase in the CPI as of December 31 of the then most recently ended Calendar Year over the level of the CPI on December 31, 2013.

1.2.140. “ Regional Licensed Product ” means: (i) ALN-TTR02 as of the Effective Date and (ii) if Genzyme exercises the Regional Option pursuant to the Master Agreement for any Regional Option Product, then such Regional Option Product as of the applicable Option Exercise Date. For the sake of clarity (but not for purposes of interpretation of the Collaboration Agreement), although ALN-TTRsc is not a Regional Licensed Product, it is exclusively licensed to Genzyme in the Genzyme Territory in much the same way that Regional Licensed Products are licensed to Genzyme in the Genzyme Territory under these Regional License Terms. As a Co-Co Licensed Product, however, ALN-TTRsc is licensed to Genzyme under the Co-Co License Terms, which also grant Genzyme a license to co-Commercialize ALN-TTRsc in the Alnylam Territory.

1.2.141. “ Regional Option Period ” has the meaning set forth in the Master Agreement.

1.2.142. “Regional Option Product” has the meaning set forth in the Master Agreement.

1.2.143. “ Regional Option ” has the meaning set forth in the Master Agreement.

1.2.144. “ Regional Out-of-Pocket Costs ” means, with respect to certain activities hereunder, direct expenses paid or payable by either Party or its Affiliates to Third Parties and specifically identifiable and incurred to conduct such activities for a Regional Licensed Product, including payments to contract personnel; provided , however , that amounts paid to contract sales and marketing personnel will not be considered Regional Out-of-Pocket Costs.

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1.2.145. “ Regulatory Approval ” has the meaning set forth in the Master Agreement.

1.2.146. “ Regulatory Authority ” has the meaning set forth in the Master Agreement.

1.2.147. “ Regulatory Exclusivity ” means, with respect to a Regional Licensed Product in a country, any exclusive marketing right, data exclusivity right, orphan drug designation or other country-wide exclusive right or status conferred by any Governmental Authority with respect to such Regional Licensed Product in such country, other than a Patent Right, that limits or prohibits a Person from [***].

1.2.148. “ Related Party ” means a Party’s Affiliates, permitted Sublicensees and, with respect to Alnylam, licensees in the Alnylam Territory.

1.2.149. “ Reverted Regional Licensed Product ” has the meaning set forth in Section 10.3.1.3(a) (Effects of Termination of Regional License Terms in Their Entirety by Alnylam for Cause or by Genzyme for Convenience).

1.2.150. “ RLP Alliance Manager ” has the meaning set forth in Section 5.2 (Appointment of Subcommittees, Project Teams and RLP Alliance Managers).

1.2.151. “ RLP Collaboration ” means the collaboration of the Parties in the Development, Manufacture and Commercialization of Regional Licensed Products under these Regional License Terms.

1.2.152. “RLP Clinical Supply Agreements” means, collectively, the ALN-TTR02 Clinical Supply Agreement and each other clinical supply agreement entered into between Alnylam and Genzyme as described in Section 6.2 of the Master Agreement (Collaboration Product Supply Agreements) pursuant to which Alnylam will provide clinical supplies of a specified Regional Licensed Product to Genzyme.

1.2.153. “RLP Commercial Supply Agreements” means, collectively, the ALN-TTR02 Commercial Supply Agreement and each other commercial supply agreement entered into between Alnylam and Genzyme as described in Section 6.2 of the Master Agreement (Collaboration Product Supply Agreements) pursuant to which Alnylam will provide commercial supplies of a specified Regional Licensed Product to Genzyme.

1.2.154. “ RLP Supply Agreements ” means, collectively, the RLP Clinical Supply Agreements and the RLP Commercial Supply Agreements.

1.2.155. “ Regional License Terms ” means this Appendix and the terms of the Master Agreement to the extent applicable to Regional Licensed Products.

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1.2.156. “ Royalty Term ” has the meaning set forth in Section 7.2.2 (Royalty Term).

1.2.157. “ Safety Concern ” has the meaning set forth in the Master Agreement.

1.2.158. “Secondary Indication ” has the meaning set forth in the Master Agreement.

1.2.159. “ Secondary Indication Study ” has the meaning set forth in the Master Agreement.

1.2.160. “ Serious Adverse Event ” has the meaning set forth in the Master Agreement.

1.2.161. “ siRNA ” has the meaning set forth in the Master Agreement.

1.2.162. “ SPCs ” has the meaning set forth in Section 9.5 (Patent Term Extensions).

1.2.163. “ Sublicensee ” means a Third Party to whom a Party grants a sublicense under any Alnylam Technology or Genzyme Technology, as the case may be, to Develop, Manufacture or Commercialize a Regional Licensed Product in the Field pursuant to Section 6.1.4 (Sublicensing Terms) or Section 6.2.4 (Sublicensing Terms).

1.2.164. “ Term ” has the meaning set forth in Section 10.1 (Term).

1.2.165. “ Territory ” means (a) with respect to Alnylam, the Alnylam Territory and (b) with respect to Genzyme, the Genzyme Territory.

1.2.166. “ Third Party ” has the meaning set forth in the Master Agreement.

1.2.167. “ Third Party Collaboration Agreement ” has the meaning set forth in Section 5.8 (Alnylam Third Party Partner).

1.2.168. “ Third Party License Payment ” has the meaning set forth in the Master Agreement.

1.2.169. “ Third Party Partner ” has the meaning set forth in Section 5.8 (Alnylam Third Party Partner).

1.2.170. “Trademark” has the meaning set forth in the Master Agreement.

1.2.171. “ TTR ” has the meaning set forth in the Master Agreement.

1.2.172. “ Un-Blocking Genzyme In-License ” has the meaning set forth in the Master Agreement.

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1.2.173. “United States” means the United States of America and its territories, possessions and commonwealths.

1.2.174. “ Valid Claim ” means a claim of: (a) an issued and unexpired patent, which claim has not been withdrawn, cancelled, abandoned, disclaimed, revoked or held unenforceable or invalid by an unappealable decision of a court or other governmental agency of competent jurisdiction, or has not been appealed within the time allowed for appeal, or by an appealed decision of a court or other governmental agency of competent jurisdiction where the appeal has been pending for more than [***] years (unless and until such decision is subsequently overturned on appeal) and which has not been abandoned, disclaimed, denied or admitted to be invalid or unenforceable through reissue, re-examination or disclaimer or otherwise; or (b) a patent application that has been pending less than [***] years from the date of filing of the earliest patent application from which such patent application claims priority, which claim has not been cancelled, withdrawn or abandoned or finally rejected by an administrative agency action from which no appeal can be taken.

1.2.175. “ [***] ” has the meaning set forth in Section 2.2.2.3(a) (Managing and Amending Global Development Plans and Global Development Budgets).

1.2.176. “ [***] Budget” has the meaning set forth in Section 2.2.2.3(a) (Managing and Amending Global Development Plans and Global Development Budgets).

1.2.177. “ [***] ” has the meaning set forth in Section 2.2.2.3(a) (Managing and Amending Global Development Plans and Global Development Budgets).

1.2.178. “ [***] Budget” has the meaning set forth in Section 2.2.2.3(a) (Managing and Amending Global Development Plans and Global Development Budgets).

2. DEVELOPMENT COLLABORATION

2.1. Overview . The Parties will collaborate in the Development of each Regional Licensed Product pursuant to the applicable Global Development Plan, Alnylam Territory Development Plan and Genzyme Territory Development Plan. The PJSC will have primary responsibility for the oversight of the Global Development Plans. Alnylam will have primary responsibility for execution of those Global Development Plans, and sole responsibility for the Alnylam Territory Development Plans, as described below. Genzyme will have sole responsibility for the Genzyme Territory Development Plans, as described below.

2.2. Development Plans .

2.2.1. Global Development Strategy . For each Regional Licensed Product, the key Development principles for such Regional Licensed Product will be set forth in a written summary of the global Development strategy for such Licensed Product, including the indication(s) (including Secondary Indications), for which Regulatory Approval will be sought (each, a “Global Development Strategy” ). The initial Global Development Strategy for ALN-

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TTR02 will be provided by Alnylam to Genzyme within [***] days after the Effective Date, agreed upon by the PJSC within [***] days after the Effective Date, and then attached hereto as Schedule 2.2.1-1 . The initial Global Development Strategy for each subsequent Regional Licensed Product will be included in the Option Data Package for such Regional Licensed Product, mutually agreed upon by the Parties prior to Genzyme’s exercise of the Regional Option with respect to such Regional Licensed Product in accordance with the Master Agreement, and then attached hereto as Schedules 2.2.1-2 , 2.2.1-3 and so forth. Any Global Development Strategy may be amended from time to time only by the PJSC responsible for the applicable Regional Licensed Product.

2.2.2. Global Development Plan.

2.2.2.1. Global Development Plans . For each Regional Licensed Product, the Development activities that are necessary or useful to be undertaken for such Regional Licensed Product to achieve initial Regulatory Approval for each of the indications to be sought pursuant to the Global Development Strategy in at least all of the MMCs in a proximal fashion (including the design of necessary or useful Clinical Studies) will be set forth in reasonable detail in a written work plan and time table (each, a “Global Development Plan” ). Alnylam will provide a draft of the initial Global Development Plan for ALN-TTR02 to Genzyme on or before [***], and within [***] days thereafter the PJSC will review, update and approve such Global Development Plan and it will be attached hereto as Schedule 2.2.2.1-1 . The initial Global Development Plan for each subsequent Regional Licensed Product will be included in the Option Data Package for such Regional Licensed Product provided by Alnylam to Genzyme under the Master Agreement, and within [***] days of the Implementation Date for such Regional Licensed Product the PJSC responsible for such Regional Licensed Product will review, update and approve such Global Development Plan and it will be attached hereto as Schedules 2.2.2.1-2 , 2.2.2.1-3 and so forth. Each Global Development Plan must, at all times, be consistent with the Global Development Strategy and include all Development activities that (i) are reasonably necessary to obtain initial Regulatory Approval of the applicable Regional Licensed Product in each MMC for each of the indications, including Secondary Indications, to be sought pursuant to the Global Development Strategy in a proximal fashion and (ii) Secondary Indication Studies included in the initial Global Development Plan or added pursuant to Section 2.2.2.6 (Secondary Indications) (all such Development activities collectively, the “ Global Development Activities ”); provided , however , that, unless otherwise agreed by the Parties, in no event will any Global Development Plan include (a) any Post-Marketing Study or Secondary Indication Study, except for Secondary Indication Studies included in the initial Global Development Plan or added to a Global Development Plan pursuant to Section 2.2.2.6 (Secondary Indications), (b) any Development activity solely intended or designed to achieve initial Regulatory Approval in a country other than an MMC or (c) after the last Regulatory

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Approval in all MMCs, any Development activity that is useful solely to achieve initial Regulatory Approval in a country that is not an MMC, except for Secondary Indication Studies included in the initial Global Development Plan or added to a Global Development Plan pursuant to Section 2.2.2.6 (Secondary Indications). Each Global Development Plan will allocate responsibility for the performance of each Global Development Activity to one of the Parties. The time table for the completion of the Global Development Activities included in each Global Development Plan will be designed to obtain initial Regulatory Approval of the applicable Regional Licensed Product in each MMC in a proximal fashion and as soon as reasonably possible. The terms of, and Development activities set forth in, each Global Development Plan will at all times be designed to be in compliance with all applicable Laws and in accordance with professional and ethical standards customary in the pharmaceutical industry.

2.2.2.2. Global Development Budgets . Each Global Development Plan will contain a [***] year rolling budget for the probable Global Development Activities to be performed during [***], and a forecast of the budgets for each subsequent Calendar Year thereafter through completion of all Global Development Activities set forth in any such Global Development Plan, provided that each initial Global Development Plan will also include such a budget for the partial Calendar Year commencing as of the date of such Global Development Plan and ending December 31 of such Calendar Year (each such [***] budget plus any such partial Calendar Year is a “ Global Development Budget ”). Each Global Development Budget will be updated annually by the PJSC responsible for the applicable Regional Licensed Product in accordance with Section 2.2.2.3 (Managing and Amending Global Development Plans and Global Development Budgets). The initial Global Development Budget for a Regional Licensed Product, and each update thereto, will be prepared by the PJSC in accordance with[***]

(a) [***];

(b) [***]

Alnylam will enter such Global Development Budget in a template that the Parties agree is efficient for both Parties to communicate such information.

2.2.2.3. Managing and Amending Global Development Plans and Global Development Budgets . The PJSC responsible for a Regional Licensed Product will update and amend the applicable Global Development Plan from time-to-time as it deems necessary and, until such time as no further Global Development Activities are occurring or expected to occur with respect to such Regional Licensed Product, the PJSC will update such Global Development Plan annually as follows:

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(a) No later than [***] of each Calendar Year, the applicable PJSC will prepare an updated draft of the Global Development Plan, which shall contain a proposed Global Development Budget covering [***].

(b) No later than [***] of each Calendar Year, the applicable PJSC will review and tentatively approve an updated Global Development Plan and Global Development Budget, and such updated Global Development Plan and Global Development Budget will become effective upon such tentative approval by the PJSC, provided that the Parties acknowledge and agree that each Party’s internal process for receiving final approval of such Global Development Plan and Global Development Budget from its Board of Directors and/or senior management may occur after [***] (but, in any event, before [***]) and such Global Development Plan and Global Development Budget will not become final unless and until such approvals are obtained [***].

2.2.2.4. [***] Adjustments and Compensation . In addition to the Global Development Budget for each Regional Licensed Product, Alnylam shall prepare, and submit to the PJSC for approval, three Development budget(s) for each Regional Licensed Product, the first of which shall cover the period commencing as of the Implementation Date for such Regional Licensed Product and ending on the anticipated date of initiation of the first Phase III Study for such Regional Licensed Product (as further described below, each a “ Phase 2 Budget ”), the second of which shall cover the period commencing as of the anticipated date of initiation of the first Phase III Study for such Regional Licensed Product and ending on the anticipated date of filing of an application for Regulatory Approval of such Regional Licensed Product in the first MMC (as further described below, each a “ Phase 3 Budget ”), and the third of which shall cover the period commencing as of the anticipated date of filing of an application for Regulatory Approval for such Regional Licensed Product in the first MMC and ending on the date that there are no further Development activities to performed under the Global Development Plan for such Regional Licensed Product (as further described below, each a “ Post-Phase 3 Budget ”), provided that if the period covered by the Post-Phase 3 Budget is longer than three (3) years, Alnylam shall prepare a new Post-Phase 3 Budget to cover each subsequent three (3) year period. Each Phase 2 Budget, Phase 3 Budget and Post-Phase 3 Budget shall be [***].

(a) Preparation of Phase 2 Budget, Phase 3 Budget and Post-Phase 3 Budget. Each Phase 2 Budget, Phase 3 Budget and Post-Phase 3 Budget submitted to the PJSC will be prepared by Alnylam in accordance with [***].

(b) [***].

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(i) Alnylam shall include a Phase 2 Budget [***] with the initial Global Development Plan for each Regional Licensed Product. Such Phase 2 Budget [***] shall become effective, subject to adjustment in accordance with the foregoing Section 2.2.2.4(b), upon the Implementation Date for the relevant Regional Licensed Product.

(ii) Alnylam shall provide to the PJSC for approval a Phase 3 Budget [***] for each Regional Licensed Product no less than [***] days prior to the anticipated initiation of the first Phase III Study for each Regional Licensed Product, along with top line data and data tables from any completed Phase II Studies and other completed non-clinical studies (including all Serious Adverse Event and Safety Concern data), as well as a draft of the end of Phase II briefing package, in each case to the extent not previously provided or made available to Genzyme (such budget, data and draft, collectively the “ End of Phase II Package ”). Such Phase 3 Budget [***] shall become effective at the end of such [***] day period.

(iii) Alnylam shall provide to the PJSC for approval a Post-Phase 3 Budget [***] for each Regional Licensed Product no less than [***] days prior to the anticipated completion of the first Phase III Study for each Regional Licensed Product. Such Post-Phase 3 Budget [***] shall become effective upon approval by the PJSC.

(d) [***].

2.2.2.5. Oversight of the Global Development Plans . The PJSC for ALN-TTR02 shall create a Joint Clinical Operations Team (“ JCOT ”), with two (2) representatives from each Party, to review, coordinate and provide such PJSC with feedback regarding:

(a) the implementation of the Global Development Plan for ALN-TTR02, including the implementation and management of the Global Development Activities set forth in such Global Development Plan;

(b) the performance of any Clinical Study included in such Global Development Activities (a “ Global Clinical Study ”) by any CRO retained by a Party to perform such Global Clinical Study, against the criteria and timelines in such Global Development Plan; and

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Unless otherwise agreed by the Parties, each Party’s representatives on the JCOT must be employees of such Party. The JCOT shall meet from time-to-time, in person or via teleconference, as it shall reasonably determine.

2.2.2.6. Secondary Indications .

(a) Additional Development Proposals . If a Party desires to conduct a Secondary Indication Study of a Regional Licensed Product for the purpose of seeking Regulatory Approval to market such Regional Licensed Product for a Secondary Indication, such Party (the “ Proposing Party ”) will submit to the PJSC responsible for such Regional Licensed Product a proposal to add such Secondary Indication Study to the applicable Global Development Plan (an “ Additional Development Proposal ”). Each Additional Development Proposal will describe in reasonable detail the Secondary Indication Study(ies) that the Proposing Party desires to conduct, including a synopsis of the trial, the proposed enrollment criteria, number of patients to be included, endpoints to be measured, and statistical design and powering (the “ Additional Development Activities ”), as well as a proposed timeline and budget and an analysis of the business opportunity and revenue potential for such Additional Development Activities and Secondary Indication.

(b) PJSC Decision Regarding Additional Development Activities . The PJSC shall approve or reject an Additional Development Proposal within [***] days after receipt thereof from the Proposing Party as set forth in this Section 2.2.2.6.

(i) If the PJSC approves an Additional Development Proposal, upon such an approval, the applicable Global Development Plan will be amended to include the Additional Development Activities, including the proposed timeline and budget for such Additional Development Activities, set forth in such Additional Development Proposal (as may be amended by the PJSC) upon such approval. Any Additional Development Activities included in a Global Development Plan pursuant to this Section 2.2.2.6(b) shall be deemed to be Global Development Activities for all purposes under these Regional License Terms (including the definition of Global R&D Costs).

(ii) If the PJSC fails to approve an Additional Development Proposal, upon such a failure, the Secondary Indication Study proposed in the Additional Development Proposal will not be deemed a Global Development Activity for any purpose under these Regional License Terms, and Sections 2.2.2.6(c) (Independent Performance of Additional Development Activities) and 2.2.2.6(d) (Opt-In for Additional Development Activities) shall apply.

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(i) If the PJSC fails to approve for inclusion in the Global Development Plan an Additional Development Proposal proposed by Alnylam for a Secondary Indication Study(ies) in the Alnylam Territory for a Regional Licensed Product, Alnylam may, upon notice to Genzyme, conduct the proposed Secondary Indication Study(ies) at its own expense; [***].

(ii) If, after receipt of Regulatory Approval for a Regional Licensed Product in an Alnylam Territory MMC, the PJSC fails to approve for inclusion in the Global Development Plan an Additional Development Proposal proposed by Genzyme for a Secondary Indication Study(ies) in the Genzyme Territory for such Regional Licensed Product, Genzyme may, upon notice to Alnylam, conduct the proposed Secondary Indication Study(ies) at its own expense [***].

(iii) Notwithstanding anything in Section 3.4 (Right of Reference) to the contrary, if the PJSC does not approve an Additional Development Proposal, unless and until the Non-Proposing Party delivers an Additional Development Opt-In Notice with respect to such Additional Development Activity, as described in Section 2.2.2.6(c)(iii) (Opt-In for Additional Development Activities), the Non-Proposing Party will not have any rights under Section 3.4 (Right of Reference) with respect to any information or data generated from any Secondary Indication Study that was the subject of the unapproved Additional Development Proposal. For avoidance of doubt, if the PJSC rejects for inclusion in all Development Plans an Additional Development Proposal for a Secondary Indication Study(ies) proposed by Genzyme prior to receipt of Regulatory Approval for a Regional Licensed Product in an MMC in the Alnylam Territory, then Genzyme shall not have any right to proceed with the Secondary Indication Study(ies) described therein unless and until the PJSC determines that such Additional Development Activities should be permitted or until otherwise permitted under this Section 2.2.2.6(c)(iii).

(d) Opt-In for Additional Development Activities . In the event that the Proposing Party conducts Secondary Indication Study(ies) pursuant to Section 2.2.2.6(c) (Independent Performance of Additional Development Activities), the Non-Proposing Party may elect, in its discretion and upon written notice to the Proposing Party no later than [***] days after the date on which the [***] (an “ Additional Development Opt-In Notice ”), to opt in with respect to any Secondary Indication Study that was the subject of such Additional Development Proposal that the Proposing Party elected to conduct in accordance with Section 2.2.2.6(c) (Independent Performance of Additional Development Activities), and then (i) such Secondary Indication Study shall be deemed to be a Global Development Activity under the Global Development Plan for the applicable Regional Licensed Product from and after the date on which such Additional Development Opt-In Notice is received by the Proposing Party (the “ Additional Development Opt-In Date ”); (ii) the then-current plan and budget of the Proposing Party with respect to such Secondary Indication Study shall be deemed to be included within, and part of, the Global Development Plan for such Regional Licensed Product as of the Additional Development Opt-In Date, and shall control with respect to such

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Secondary Indication Study unless and until an amendment to the Global Development Plan providing for a different or modified plan and budget is approved by the applicable PJSC; and (iii) the Non-Proposing Party will have all rights granted to it under Section 3.4 (Right of Reference) with respect to the information and data generated from such Secondary Indication Study as if such Secondary Indication Study was conducted under the Global Development Plan for such Regional Licensed Product [***].

2.2.2.7. Additional Clinical Study Sites in Genzyme Territory . With respect to any Clinical Study in a Global Development Plan, at Genzyme’s request, Alnylam will add a study site in a country in the Genzyme Territory, [***]. If Alnylam adds such a study site at Genzyme’s request, Genzyme will reimburse Alnylam for any incremental R&D FTE Costs or Regional Out-of-Pocket Costs required as a result of adding such study site. Genzyme will pay Alnylam such reimbursement within [***] days of receipt of an invoice from Alnylam.

2.2.3. Alnylam Territory Development Plan. The Development activities other than Global Development Activities to be undertaken with respect to each Regional Licensed Product by or on behalf of Alnylam with respect to the Alnylam Territory, including Secondary Indication Studies and Post-Marketing Studies, will be set forth in a written work plan and time table (each, an “ Alnylam Territory Development Plan ”). Each Alnylam Territory Development Plan shall be consistent with the requirements of the Global Development Strategy. Alnylam will prepare the Alnylam Territory Development Plan for ALN-TTR02 and then promptly thereafter will submit it to the PJSC for review and approval. Following approval by the PJSC, it will then be attached to the PJSC meeting minutes and deemed to be attached hereto as Schedule 2.2.2.6(d)-1 . The initial Alnylam Development Plan for each subsequent Regional Licensed Product will be prepared by Alnylam and following review and approval by the PJSC, will then be attached to the PJSC meeting minutes and deemed to be attached hereto as Schedules 2.2.2.6(d)-2 , 2.2.2.6(d)-3 and so forth on the Implementation Date for such Regional Licensed Product. Each Alnylam Territory Development Plan will set forth a rolling written work plan and time table with respect to the Development of and Secondary Indication Studies for the applicable Regional Licensed Product from the Implementation Date until the later of (a) two (2) years from date of such plan, and (b) receipt of Regulatory Approval for such Regional Licensed Product. Each Alnylam Territory Development Plan shall subsequently be updated by Alnylam from time-to-time at least once each Calendar Year not later than September 1 until such time as no further Development or Secondary Indication Studies are occurring or expected to occur with respect to the applicable Regional Licensed Product. Alnylam will present each Alnylam Territory Development Plan and any proposed amendments thereto to the applicable PJSC at least [***] days in advance of implementation of the Alnylam Territory Development Plan, and following review and approval by the PJSC, will then be attached to the PJSC meeting minutes and deemed to be attached hereto as the applicable Schedule. In addition, notwithstanding anything to the contrary in these Regional License Terms, Alnylam shall not conduct any Clinical Study for a Regional Licensed Product in a country in the Genzyme Territory after receipt of initial Regulatory Approval of such Regional Licensed Product in such country in the Genzyme Territory.

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2.2.4. Genzyme Territory Development Plan. Other than Global Development Activities, all Development activities to be undertaken with respect to each Regional Licensed Product by or on behalf of Genzyme with respect to the Genzyme Territory, including Secondary Indication Studies and Post-Marketing Studies, will be set forth in a written work plan and time table (each, a “ Genzyme Territory Development Plan ”). Each Genzyme Territory Development Plan shall be consistent with the requirements of the then-current Global Development Strategy ( provided that Alnylam did not exercise its deciding vote with respect thereto pursuant to Section 5.6.3 ([***]). Prior to [***], Genzyme will prepare the Genzyme Territory Development Plan for ALN-TTR02 and then promptly thereafter will submit it to the PJSC for review and approval. Following review and approval by the PJSC, it will then be attached to the PJSC meeting minutes and deemed to be attached hereto as Schedule 2.2.4-1 . The initial Genzyme Territory Development Plan for each subsequent Regional Licensed Product will be prepared by Genzyme and following review and approval by the PJSC, will then be attached to the PJSC meeting minutes and deemed to be and attached hereto as Schedules 2.2.4-2, 2.2.4-3 and so forth. Each Genzyme Territory Development Plan will set forth a rolling written work plan and time table with respect to the Development of and Secondary Indication Studies for the applicable Regional Licensed Product from the Implementation Date until the later of (a) two (2) years from date of such plan, and (b) receipt of Regulatory Approval for such Regional Licensed Product. Each Genzyme Territory Development Plan shall subsequently be updated by Genzyme from time-to-time at least once each Calendar Year not later than [***] until such time as no further Development or Secondary Indication Studies are occurring or expected to occur with respect to the applicable Regional Licensed Product. Genzyme will present each Genzyme Territory Development Plan and any proposed amendments thereto to the applicable PJSC at least [***] days in advance of implementation of the Genzyme Territory Development Plan, and following review and approval by the PJSC, will then be attached to the PJSC meeting minutes and deemed to be attached hereto as the applicable Schedule. In addition, notwithstanding anything to the contrary in these Regional License Terms, Genzyme shall not conduct any Clinical Study for a Regional Licensed Product in a country in the Alnylam Territory after receipt of initial Regulatory Approval of such Regional Licensed Product in such country in the Alnylam Territory.

2.3. Responsibilities for Development Activities and Costs .

2.3.1. Global Development .

2.3.1.1. Generally . With respect to each Regional Licensed Product, except to the extent that the Global Development Plan for such Regional Licensed Product allocates responsibility for any Global Development Activities to Genzyme, Alnylam shall be primarily responsible for the global Development of such Regional Licensed Product and all Development activities under such Global Development Plan. Each Party and its Affiliates shall conduct each

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Global Development Activity for which it is responsible in sound scientific manner and in compliance with applicable Law. Notwithstanding anything to the contrary in these Regional License Terms, neither Party will be obligated to undertake or continue any Global Development Activity if (a) such Party reasonably determines that performance of such Global Development Activity would violate applicable Law; or (b) with respect to any Global Clinical Study, (i) a Regulatory Authority or independent safety data review board for such Global Clinical Study has required or recommended termination or suspension of such Global Clinical Study or (ii) such Party believes in good faith that termination or suspension of such Global Clinical Study is warranted because of safety or tolerability risks or the lack of suitable risk benefit ratio to the study subjects. In the event that a Party determines not to undertake or continue any Global Development Activity in accordance with the immediately preceding sentence, such Party shall promptly notify the other Party of such determination, and shall use all reasonable efforts to notify and consult with the other Party prior to making such determination.

2.3.1.2. Global R&D Costs .

(a) With respect to ALN-TTR02, Alnylam shall be responsible for eighty percent (80%) of all Global R&D Costs and Genzyme shall be responsible for twenty percent (20%) of all Global R&D Costs, in each case for Global Development Activities that occur on or after [***], and amounts specified in clauses (ii) and (iii) of Section 2.3.1.2(c) below, if any. Alnylam shall be responsible for one-hundred percent (100%) of Global R&D Costs for Global Development Activities for ALN-TTR02 that occur prior to [***], except for amounts specified in clauses (ii) and (iii) of Section 2.3.1.2(c) below, if any.

(b) With respect to each other Regional Licensed Product, Alnylam shall be responsible for eighty percent (80%) of all Global R&D Costs and Genzyme shall be responsible for twenty percent (20%) of all Global R&D Costs, in each case for Global Development Activities that occur after the later of (i) [***] and (ii) the earlier of (A) the Implementation Date for such Regional Licensed Product and (B) the date of the dosing of the first patient in the first Clinical Study initiated subsequent to the Human POP Study for such Regional Licensed Product (such later date, the “Global R&D Cost Opt-In Date”), and amounts specified in clauses (ii) and (iii) of Section 2.3.1.2(c) below, if any. Alnylam shall be responsible for one-hundred percent (100%) of Global R&D Costs for Global Development Activities for any such Regional Licensed Product that occur prior to the Global R&D Cost Opt-In Date, except for amounts specified in clauses (ii) and (iii) of Section 2.3.1.2(c) below, if any.

(c) The Global R&D Costs to be shared by the Parties pursuant to Sections 2.3.1.2(a) and 2.3.1.2(b) above shall only include amounts that are within one or more of the following four (4) categories:

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(i) [***];

(ii) [***];

(iii) [***]

(iv) [***].

(d) For clarity, Global R&D Costs to be shared by the Parties pursuant to 2.3.1.2(a) and 2.3.1.2(b) shall exclude any amounts paid after the Global R&D Cost Opt-In Date to Third Parties with respect to services rendered or materials procured in connection with the conduct of any Clinical Study or other Development activities, in either case, that is completed prior to the Global R&D Cost Opt-In Date.

(e) Global R&D Costs for each Regional Licensed Product shall initially be borne by the Party incurring the cost or expense. Each Party will calculate and maintain records of Global R&D Costs incurred by it and its Affiliates with respect to a Regional Licensed Product and, within [***] days following the end of each Calendar Quarter, each Party shall submit to the other a report detailing the Global R&D Costs incurred by it and its Affiliates during such Calendar Quarter, and, if requested, reasonable supporting documentation will be provided (a “Global R&D Costs Report”). In addition, each Party shall use good faith efforts to notify the other Party of any material Global R&D Costs incurred by such Party during such Calendar Quarter within [***] days after the end of such Calendar Quarter. The Party that incurs more than its share of the total actual Global R&D Costs with respect to a Regional Licensed Product during any Calendar Quarter shall be paid by the other Party an amount of cash sufficient to reconcile to its agreed percentage of Global R&D Costs for such Regional Licensed Product, which payment shall be made within [***] days after delivery of the Global R&D Cost Reports for such Calendar Quarter. Notwithstanding the foregoing, if following receipt of a Global R&D Costs Report a Party (the “Disputing Party”) disputes any Global R&D Costs under such Global R&D Costs Report, it shall have [***] days to notify the other Party (the “Non-Disputing Party”). Upon receiving such notice from the Disputing Party, the Non-Disputing Party shall, at the reasonable request of the Disputing Party, provide to the Disputing Party supporting documentation relating to any such disputed Global R&D Costs. The Parties agree to use reasonable efforts to resolve any such dispute as soon as reasonably practicable, and any undisputed portion of Global R&D Costs in such Global R&D Costs Report shall be paid within [***] days after delivery of such Global R&D Costs Report. Once the Parties have resolved such dispute, any disputed amounts still owed by either Party will be paid within [***] days of resolution of such dispute.

(f) [***].

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(g) Notwithstanding anything to the contrary in these Regional License Terms, the Parties shall not share Global R&D Costs incurred in a Calendar Year with respect to Global Development Activities for a Regional Licensed Product to the extent such Global R&D Costs exceed [***] of the amounts included in the final [***] Budget that was applicable to such Current Calendar Year (the amount in excess of such [***] limit is the “ Excess Global R&D Costs ”). One hundred percent (100%) of any Excess Global R&D Costs for such Regional Licensed Product will be borne by the Party that incurred such Excess Global R&D Costs.

2.3.2. Genzyme Development. Except with respect to Global R&D Costs (which shall be shared by the Parties in accordance with Section 2.3.1.2 (Global R&D Costs)), Genzyme shall be responsible for one hundred percent (100%) of all costs and expenses incurred with respect to Development activities that are conducted by Genzyme pursuant to any Genzyme Territory Development Plan. Genzyme will conduct all Development of each Regional Licensed Product for the Genzyme Territory solely in accordance with the applicable Global Development Plan and Genzyme Territory Development Plan, as such Global Development Plan and Genzyme Territory Development Plan may be amended in accordance with these Regional License Terms, and in sound scientific manner and in compliance with applicable Law.

2.3.3. Alnylam Development. Except with respect to Global R&D Costs (which shall be shared by the Parties in accordance with Section 2.3.1.2 (Global R&D Costs)), Alnylam shall be responsible for one hundred percent (100%) of all costs and expenses incurred with respect to Development activities that are conducted by Alnylam pursuant to any Alnylam Territory Development Plan. Alnylam will conduct all Development of each Regional Licensed Product for the Alnylam Territory solely in accordance with the applicable Global Development Plan and Alnylam Territory Development Plan, as such Global Development Plan and Alnylam Territory Development Plan may be amended in accordance with these Regional License Terms, and in sound scientific manner and in compliance with applicable Law.

2.4. Diligence .

2.4.1. Genzyme Diligence. With respect to each Regional Licensed Product, Genzyme will use Commercially Reasonable Efforts to [***].

2.4.2. Alnylam Diligence. With respect to each Regional Licensed Product, Alnylam will use Commercially Reasonable Efforts to (a) Develop such Regional Licensed Product and obtain Regulatory Approval therefor by the FDA in the U.S. or by the EMA in the European Union; (b) perform the Global Development Activities allocated to it under the Global Development Plan for such Regional Licensed Product; and (c) perform the Development activities set forth in the Alnylam Territory Development Plan for such Regional Licensed Product, as such Alnylam Territory Development Plan may be amended in accordance with these Regional License Terms.

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2.5. Records; Reports; Information Sharing .

2.5.1. Development Activities Reports. Each Party will periodically provide to the PJSC responsible for a Regional Licensed Product, but in no event less than on a Calendar Quarter basis, or more frequently as reasonably requested by the other Party, an update regarding Development activities conducted by or on behalf of such Party with respect to such Regional Licensed Product, as well as any Secondary Indication Studies and Post-Marketing Studies conducted by or on behalf of such Party with respect to such Regional Licensed Product. The Parties will periodically report to the PJSC responsible for a Regional Licensed Product, but in no event less than on a Calendar Quarter basis, regarding their respective activities conducted under the Global Development Plan for such Regional Licensed Product. In addition, each Party will promptly share with the other Party all material developments and information that it comes to possess relating to the Development of any Regional Licensed Products, including Safety Concerns and study reports and data generated from Clinical Studies of such Regional Licensed Product.

2.5.2. Scientific Records. Each Party will maintain scientific records, in sufficient detail and in sound scientific manner appropriate for patent and regulatory purposes, which will fully and properly reflect all work done and results achieved in the performance of the Development activities and Secondary Indication Studies with respect to Regional Licensed Products by such Party.

2.5.3. Information Exchange and Development Assistance. Until the expiration or termination of the final Global Development Plan, upon the reasonable request of the other Party, each Party shall provide to the other Party, without additional compensation (except as provided in Section 6.5 of the Master Agreement (Transfer of Manufacturing Know-How)) and in a commercially reasonable format, Know-How Controlled by such Party and/or its Related Parties that is licensed to the other Party under these Regional License Terms (i.e. Know-How included in Genzyme Technology for Genzyme and Know-How included in Alnylam Technology for Alnylam) to the extent that it is reasonably necessary or useful for Developing a Regional Licensed Product in the requesting Party’s Territory or for obtaining or maintaining Regulatory Approval for a Regional Licensed Product in the requesting Party’s Territory, including copies of (a) all scientific information and data related to such Regional Licensed Product (including all data made, collected or otherwise generated in the conduct of any pre-clinical studies, Clinical Studies, Secondary Indication Studies or early access/named patient programs for the Regional Licensed Products, as well as CMC information), and (b) protocols and investigator brochures, in each case, that are reasonably necessary for the other Party (or its Related Parties) to perform its obligations or exploit its rights under these Regional License Terms with respect to such Regional Licensed Product. Notwithstanding the foregoing, Genzyme shall have no obligation to transfer or disclose to Alnylam any Know-How included in the Genzyme Manufacturing IP; provided , however , that if Genzyme elects, in its sole discretion, to transfer or disclose any such Know-How to Alnylam in writing, it shall be “ Genzyme Disclosed Manufacturing Know-How ” under these Regional License Terms and licensed to Alnylam in accordance with Section 6.2.3 (License to Genzyme Disclosed Manufacturing Know-How).

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2.5.4. Personnel. Each Party may request, through the PJSC or the other Party’s RLP Alliance Manager responsible for a Regional Licensed Product, that the other Party reasonably make available for consultation regarding the Development of such Regional Licensed Product certain of its employees engaged in Development activities and Secondary Indication Studies with respect to such Regional Licensed Product. The PJSC or the RLP Alliance Managers responsible for a Regional Licensed Product will reasonably coordinate, upon reasonable notice during normal business hours and at their respective places of employment, consultation between the Parties on the progress of the Development and Secondary Indication Studies for such Regional Licensed Product.

2.5.5. Confidentiality. All information exchanged by the Parties under this Section 2.5 will be deemed to be Confidential Information of the disclosing Party and maintained in accordance with Section 7 of the Master Agreement (Confidentiality and Publication).

2.6. Third Parties .

2.6.1. The Parties shall be entitled to utilize the services of Third Parties to perform their respective Development and Manufacturing activities under these Regional License Terms, provided that (a) each Party shall require that such Third Party operates in a manner consistent with these Regional License Terms, (b) each Party shall remain at all times fully liable for its respective responsibilities and (c) the Parties will make reasonable efforts to share, through the PJSC, information regarding any prior experience with specific CROs that are anticipated to be engaged to perform work under the Global Development Plan. Each Party shall require that any Third Party agreement entered into pursuant to this Section 2.6.1 include confidentiality and non-use provisions that are no less stringent than those set forth in Section 7 of the Master Agreement (Confidentiality and Publication) and shall obtain ownership of, and/or a fully sublicensable license under and to, any Know-How and Patent Rights that are developed by such Third Party in the performance of such agreement and are reasonably necessary or useful to Develop, Manufacture and/or Commercialize Regional Licensed Products in the Field. The Party utilizing the services of a Third Party service provider shall be solely responsible for direction of and communications with such Third Party, but such Party shall provide the other Party with reasonably detailed updates regarding any such activities from time to time.

2.6.2. [***].

3. REGULATORY MATTERS

3.1. Regulatory Filings and Interactions .

3.1.1. Responsibilities.

3.1.1.1. Pursuant to the Global Development Plan for a Regional Licensed Product and, except as otherwise provided in such Global Development Plan, except as otherwise set forth in Sections 3.1.1.2 and 3.2 (EMA Regulatory Strategy) below, each Party will be solely responsible for all regulatory matters relating to such Regional Licensed Product in its Territory and will own all INDs, NDAs and related regulatory documents submitted to the applicable Regulatory

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Authorities in its Territory with respect to such Regional Licensed Product, excluding any drug master files maintained by or on behalf of Alnylam, which shall be and remain Alnylam’s sole responsibility. Notwithstanding the foregoing, the Parties acknowledge that Alnylam shall continue to own all INDs, NDAs and related regulatory documents for ALN-TTR02 in the Genzyme Territory and the provisions of this Section 3.1.1 and Section 3.1.3 (Regulatory Meetings) shall not apply. Within [***] days after the Implementation Date for ALN-TTR02, the Parties will agree to such other arrangements as are appropriate for such regulatory documents. At Genzyme’s request, following the Implementation Date for a Regional License Product other than ALN-TTR02, Alnylam will promptly assign and transfer to Genzyme all INDs, NDAs and other regulatory documentation submitted to any Regulatory Authority in the Genzyme Territory with respect to such Regional Licensed Product that is in the possession and control of Alnylam, and each Party will submit to the applicable Regulatory Authority all filings, letters and other documentation necessary to effect such assignment and transfer no later than [***] days after such request for such Regional Licensed Product, in each case, excluding any drug master files maintained by or on behalf of Alnylam. Each Party will have the sole right to (i) oversee, monitor and coordinate all regulatory actions, communications and filings with, and submissions to, each Regulatory Authority in its Territory with respect to such Regional Licensed Product; (ii) interface, correspond and meet with each Regulatory Authority in its Territory with respect to such Regional Licensed Product, and (iii) seek and maintain all regulatory filings in its Territory with respect to such Regional Licensed Product.

3.1.1.2. Notwithstanding the foregoing, for every Clinical Study conducted under a Global Development Plan, Alnylam will draft the protocol, develop the IND strategy, and file INDs globally, including in the Genzyme Territory, after input and review by Genzyme, and Alnylam will use reasonable efforts to address any concerns raised by Genzyme in connection with such activities. Unless otherwise agreed by the Parties, on a country-by-country basis, following the acceptance or approval of the IND and the first dosing of the first patient in the first Phase III Study of the relevant Regional Licensed Product in such country, as set forth in Section 3.1.1.1 above, Alnylam will assign the IND in such country in the Genzyme Territory to Genzyme and from that point forward, Genzyme will be primarily responsible for the related regulatory activities with respect thereto in its Territory. [***]

3.1.2. Communications. Each Party will notify the PJSC responsible for each Regional Licensed Product in writing, including a brief description in English, of the principal issues raised in each material communication with Regulatory Authorities with respect to such Regional Licensed Product within [***] days after receipt thereof. Upon request, each Party will provide to the other Party: (a) at the providing Party’s expense, a summary translation of such material communications in English, (b) at the providing Party’s expense, complete copies of the

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original correspondence in their native language, or (c) at the requesting Party’s expense, a full translation of such material communications in English, in each case (a) through (c) within a reasonable period of time following such request. For the purposes of this Section 3.1, “material communications” with Regulatory Authorities include meetings with Regulatory Authorities and Regulatory Authority questions or concerns with respect to significant issues, including any of the following: key product quality attributes ( e.g ., purity), safety findings affecting the platform ( e.g. , Serious Adverse Events, emerging safety signals), clinical or nonclinical findings affecting patient safety, lack of efficacy or receipt or denial of Regulatory Approval.

3.1.3. Regulatory Meetings. Each Party shall provide the other Party with reasonable advance notice of all substantive meetings with the Government Authorities in its Territory pertaining to each Regional Licensed Product, and Alnylam shall provide Genzyme with reasonable advance notice of all substantive meetings with the Governmental Authorities in the Genzyme Territory pertaining to each Regional Licensed Product, or with as much advance notice as practicable under the circumstances. Each Party shall use reasonable efforts, to the extent reasonably practicable, to permit the other Party to have, at the other Party’s expense, mutually acceptable representatives of the other Party to attend, solely as a non-participating observer, material, substantive meetings, including pre-IND and end of Phase II Study meetings, with the Governmental Authorities within such Party’s Territory pertaining to such Regional Licensed Product; provided , however , that neither Party shall be obligated to change the schedule of such a meeting in order to accommodate the schedule of the other Party’s representatives. Prior to the acceptance or approval of the IND and the first dosing of the first patient in the first Phase III Study of a Regional Licensed Product by Alnylam in a country in the Genzyme Territory, Alnylam shall provide Genzyme with reasonable advance notice of all substantive meetings with Regulatory Authorities in the Genzyme Territory pertaining to such Regional Licensed Product, or with as much advance notice as practicable under the circumstances. Alnylam shall use reasonable efforts, to the extent reasonably practicable, to permit Genzyme to have, at Genzyme’s expense, mutually acceptable representatives of Genzyme to attend, as full and equal participants, material, substantive meetings, including pre-IND and end of Phase II Study meetings, with Regulatory Authorities in the Genzyme Territory pertaining to such Regional Licensed Product.

3.1.4. Submissions. Each Party shall provide the other Party with written notice of each of the following events with regard to each Regional Licensed Product within a reasonable period of time following the occurrence thereof, to the extent notice was not provided prior to the Implementation Date for such Regional Licensed Product: (a) the filing of any IND for such Regional Licensed Product; (b) the submission of any filings or applications for Regulatory Approval (including orphan drug applications and designations) of such Regional Licensed Product in such Party’s Territory to any Regulatory Authority and (c) receipt or denial of Regulatory Approval for such Regional Licensed Product obtained or denied; provided , however , that in all circumstances, each Party shall inform the other Party of such event prior to public disclosure of such event by such Party.

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3.2. EMA Regulatory Strategy . Within [***] before the anticipated MAA filing for a Regional Licensed Product, the PJSC will determine an EMA regulatory strategy for such Regional Licensed Product pursuant to which the PJSC will determine (a) whether Alnylam will seek Regulatory Approval for such Regional Licensed Product in the EU using the EMA centralized or a national authorization procedure and (b) whether Genzyme will file a duplicate license with respect to any MAA held by Alnylam in the Alnylam Territory [***]. In determining the EMA regulatory strategy, the Parties agree to reasonably consider in good faith each Party’s interests. In the event that Genzyme files a duplicate license in the Genzyme Territory, Alnylam will coordinate communications with EMA, and provide support to enable Genzyme to efficiently obtain such duplicate license to provide for marketing in Genzyme countries under a separate, Genzyme trade name, to the extent not inconsistent with the Global Branding Strategy for such Regional Licensed Product.

3.3. Costs of Regulatory Affairs . Except as provided in Section 2.3 (Responsibilities for Development Activities and Costs) and Section 3.1.1.2, each Party shall be responsible for all costs and expenses incurred in connection with applying for, obtaining and maintaining Regulatory Approval with respect to Regional Licensed Products in its Territory, and related regulatory affairs activities.

3.4. Right of Reference . Each Party hereby grants to the other Party, and at the request of the other Party will grant to the other Party’s Related Parties, a “Right of Reference,” as that term is defined in 21 C.F.R. § 314.3(b) (or any successor rule or analogous Law recognized outside of the United States), to, and a right to copy, access, and otherwise use, all information and data (including all CMC information as well as data made, collected or otherwise generated in the conduct of any Clinical Studies or Secondary Indication Studies or early access/named patient programs for the Regional Licensed Products) included in or used in support of any regulatory filing, Regulatory Approval, drug master file or other regulatory documentation (including orphan drug applications and designations) owned or controlled by such Party or its Related Parties that relates to (a) any Regional Licensed Product or (b) with respect to such information and data provided to Genzyme, the siRNA Controlled by Alnylam and known as ALN-TTR01, to the extent necessary or useful to obtain Regulatory Approval of a Regional Licensed Product in the Genzyme Territory, and such Party shall provide a signed statement to this effect, if requested by the other Party, in accordance with 21 C.F.R. § 314.50(g)(3) (or any successor or analogous Law outside of the United States). In addition, upon request of either Party (on behalf of itself or a Sublicensee), the other Party shall obtain and provide to the requesting Party certificates or other formal or official attestations concerning the regulatory status of the Regional Licensed Products in the Genzyme Territory or the Alnylam Territory, as applicable (e.g., Certificates of Free Sale, Certificates for Export, Certificates to Foreign Governments). Notwithstanding anything to the contrary in these Regional License Terms, neither Party shall withdraw or inactivate any regulatory filing that the other Party references or otherwise uses pursuant to this Section 3.4.

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4. COMMERCIALIZATION OF THE LICENSED PRODUCTS

4.1. Responsibility, Cost and Diligence .

4.1.1. Genzyme. Genzyme shall be solely responsible, at its expense, for all Commercialization activities relating to Regional Licensed Products in the Field in the Genzyme Territory. [***].

4.1.2. Alnylam. Alnylam shall be solely responsible, at its expense, for all Commercialization activities relating to Regional Licensed Products in the Field in the Alnylam Territory.

4.1.3. Joint Commercialization. In the event that the Parties mutually agree to conduct any joint Commercialization activities regarding a Regional Licensed Product, the Parties will (a) agree in writing to a written work plan and time table for conducting such activities; (b) agree in writing to management and governance mechanisms for such joint activities, including coordination of such activities through the PJSC responsible for such Regional Licensed Product; and (c) negotiate in good faith a budget therefor and an equitable allocation of costs between the Parties. At either Party’s request, the Parties will start discussion regarding beneficial joint Commercialization activities [***] years prior to the anticipated First Commercial Sale of the Regional Licensed Product, with any agreement to be preferably finalized not less than [***] years prior to the anticipated First Commercial Sale of the Regional Licensed Product.

4.2. Global Commercial Strategy . Within [***] days after the Implementation Date for a Regional Licensed Product, Alnylam shall provide and within [***] days after provision the PJSC shall review, update and approve a written summary of the global Commercial strategy for such Regional Licensed Product (the “ Global Commercial Strategy ”).

4.3. Genzyme Territory Commercialization Plan . No less than [***] months in advance of the reasonably expected first Regulatory Approval in the Genzyme Territory with respect to a Regional Licensed Product, and on an annual basis thereafter, Genzyme shall prepare and deliver to the PJSC responsible for such Regional Licensed Product for review a reasonable written plan that summarizes the Commercialization activities to be undertaken with respect to such Regional Licensed Product in the Genzyme Territory in the next Calendar Year and, to the extent commercially reasonable, Genzyme’s plans to obtain further Regulatory Approvals and Commercialize such Regional Licensed Product in countries in the Genzyme Territory in which Genzyme is not then Commercializing such Regional Licensed Product, and the dates by which such activities are targeted to be accomplished (the “ Genzyme Territory Commercialization Plan ”). Each Genzyme Territory Commercialization Plan shall be consistent with the requirements of the initial Global Commercialization Strategy or the most recently approved by the PJSC[***]. The Genzyme Territory Commercialization Plan for a Regional Licensed Product shall subsequently be updated and modified by Genzyme, from time to time at its discretion and no less frequently than once per Calendar Year, based upon, among other things, Genzyme’s Commercialization activities with respect to such Regional Licensed Product in the Genzyme Territory, a copy of which updated plan Genzyme will provide to the PJSC responsible for such Regional Licensed Product. [***].

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4.4. Alnylam Territory Commercialization Plan . No less than [***] months in advance of the reasonably expected first Regulatory Approval in the Alnylam Territory with respect to a Regional Licensed Product, and on an annual basis thereafter, Alnylam shall prepare and deliver to the PJSC responsible for such Regional Licensed Product for review a reasonable written plan that summarizes the Commercialization activities to be undertaken with respect to such Regional Licensed Product in the Alnylam Territory in the next Calendar Year and, to the extent commercially reasonable, Alnylam’s plans to obtain further Regulatory Approvals and Commercialize such Regional Licensed Product in countries in the Alnylam Territory in which Alnylam is not then Commercializing such Regional Licensed Product, and the dates by which such activities are targeted to be accomplished (the “ Alnylam Territory Commercialization Plan ”). The Alnylam Territory Commercialization Plan shall at all times remain consistent with the Global Commercialization Strategy. The Alnylam Territory Commercialization Plan for a Regional Licensed Product shall subsequently be updated and modified by Alnylam, from time to time at its discretion and no less frequently than once per Calendar Year, based upon, among other things, Alnylam’s Commercialization activities with respect to such Regional Licensed Product in the Alnylam Territory, a copy of which updated plan Alnylam will provide to the PJSC responsible for such Regional Licensed Product. [***].

4.5. Advertising and Promotional Materials .

4.5.1. Global Branding. Alnylam shall have the right, from time to time during the Term, to develop (and thereafter modify and update) a global branding strategy (including global positioning, colors and other visual branding elements) for each Regional Licensed Product for use in the Field throughout the world (the “ Global Branding Strategy ”), which the PJSC responsible for such Regional Licensed Product shall, in accordance with Sections 5.5.2(b) (PJSC Commercialization Responsibilities) and 5.6 (PJSC Decision-Making), review and approve, and which the Parties shall, following such review and approval, implement. Alnylam will submit the Global Branding Strategy for a Regional Licensed Product to the PJSC responsible for such Regional Licensed Product at least annually (or more frequently if reasonably requested by Genzyme). Alnylam shall consider in good faith any timely comments Genzyme may have with respect to any Global Branding Strategy, but shall have final decision-making authority with respect to such Global Branding Strategy. Notwithstanding the foregoing, Alnylam shall ensure that the Global Branding Strategy complies with applicable Laws in the Genzyme Territory, and that any branding elements selected for inclusion in the Global Branding Strategy do not infringe any Third Party trademarks or other intellectual property rights. If any such Global Branding Strategy infringes Third Party trademarks or other intellectual property rights or otherwise does not comply with applicable Law in the Genzyme Territory, Alnylam shall take action to end such infringement or other noncompliance (including by modifying such Global Branding Strategy) and Genzyme will not be obligated to implement such Global Branding Strategy in the Genzyme Territory pursuant to this Section 4.5.1 unless and until such infringement or noncompliance is ended.

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4.5.2. Alnylam A&P. Alnylam will be responsible for the creation, preparation, production, reproduction and filing with the applicable Regulatory Authorities, of relevant written sales, promotion and advertising materials relating to each Regional Licensed Product (“ Promotional Materials ”) for use in the Alnylam Territory. All such Promotional Materials will be compliant with applicable Law and, if applicable, consistent in all material respects with the Global Branding Strategy for such Regional Licensed Product. Alnylam will submit representative samples of its Promotional Materials developed by it for use in the Alnylam Territory to the PJSC, at least annually (or more frequently if reasonably requested by Genzyme). Alnylam shall consider in good faith any timely comments Genzyme may have with respect to any such Promotional Materials, but shall have final decision-making authority with respect to such Promotional Materials. Notwithstanding the foregoing, Alnylam will incorporate any changes to Promotional Materials requested by Genzyme in a timely fashion in cases where Genzyme indicates that believes in good faith based on the advice of counsel that such change is necessary to enable it to comply with any applicable Law.

4.5.3. Genzyme A&P. Genzyme will be responsible for the creation, preparation, production, reproduction and filing with the applicable Regulatory Authorities, of relevant Promotional Materials relating to each Regional Licensed Product for use in the Genzyme Territory. All such Promotional Materials will be compliant with applicable Law, consistent in all material respects with the Genzyme Territory Commercialization Plan and, if applicable, consistent in all material respects with the Global Branding Strategy for such Regional Licensed Product in the Genzyme Territory. Genzyme will submit representative samples of its Promotional Materials developed by it for use in the Genzyme Territory to the PJSC at least annually thereafter (or more frequently if reasonably requested by Alnylam). Genzyme shall consider in good faith any timely comments Alnylam may have with respect to any such Promotional Materials, but shall have final decision-making authority in the Genzyme Territory with respect to such Promotional Materials.

4.5.4. Reporting Obligations. Genzyme shall report to the PJSC responsible for a Regional Licensed Product in writing, by no later than each [***] following the first Regulatory Approval of such Regional Licensed Product in the Field in the Genzyme Territory (for the period ending December 31 of the prior Calendar Year), summarizing in reasonable detail Genzyme’s Commercialization activities for such Regional Licensed Product performed to date (or updating such report for activities performed since the last such report was given hereunder, as applicable). In addition, Genzyme shall provide Alnylam with written notice of the First Commercial Sale of each Regional Licensed Product in the Genzyme Territory within [***] days after such event; provided , however , that in all circumstances, Genzyme shall inform Alnylam of such event prior to public disclosure of such event by Genzyme. Each Party shall provide such other information to the PJSC responsible for a Regional Licensed Product as the other Party may reasonably request with respect to Commercialization of such Regional Licensed Product and shall keep such PJSC reasonably informed of such Party’s Commercialization activities with respect to such Regional Licensed Product.

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4.6. Commercialization Reporting Obligations . Each Party and its Related Parties shall be responsible for booking sales in its Territory. Each Party and its Related Parties may warehouse Regional Licensed Products both inside and outside of such Party’s Territory, provided that any sales with respect to such Regional Licensed Products are booked in such Party’s Territory. If a Party receives any orders for any Regional Licensed Product in the other Party’s Territory, it shall refer such orders to the other Party, to the extent it is not prohibited from doing so under applicable Law. Moreover, each Party and its Related Parties shall be solely responsible for handling all returns of any Regional Licensed Product sold in its Territory, as well as all aspects of Regional Licensed Product order processing, invoicing and collection, distribution, inventory and receivables of Regional Licensed Products sold in its Territory.

4.7. Recalls, Market Withdrawals or Corrective Actions . In the event that any Regulatory Authority issues or requests a recall or takes a similar action in connection with a Regional Licensed Product in a Territory, or in the event either Party determines that an event, incident or circumstance has occurred that may result in the need for a recall or market withdrawal of a Regional Licensed Product in its Territory, the Party notified of such recall or similar action, or the Party that desires such recall or similar action, shall within [***] hours notify the other Party’s RLP Alliance Manager and PJSC representatives thereof by telephone or e-mail. Each Party, in consultation with the other Party, shall decide whether to conduct a recall of a Regional Licensed Product in its own Territory and the manner in which any such recall shall be conducted (except in the case of a government mandated recall, when such Party may act without such advance notice but shall notify the other Party as soon as possible). Except as may otherwise be agreed to by the Parties, each Party shall bear the expense of any such recall in its own Territory. Each Party will make available all of its pertinent records that may be reasonably requested by the other Party in order to effect a recall of a Regional Licensed Product in the other Party’s Territory. The Parties’ rights and obligations under this Section 4.7 shall be subject to the terms of any supply agreement(s) entered into between the Parties. In the event of a conflict between the provisions of any such supply agreement and this Section 4.7, the provisions of such supply agreement shall govern.

4.8. [***]

4.8.1. [***]

4.8.2. [***].

5. COLLABORATION MANAGEMENT

5.1. Product Joint Steering Committee . The Parties shall establish a product joint steering committee (a “ PJSC ”) to facilitate the RLP Collaboration with respect to each Regional Licensed Product as follows:

5.1.1. Composition of the Product Joint Steering Committee. The Development and Commercialization of each Regional Licensed Product pursuant to the RLP Collaboration will be conducted under the oversight of a PJSC, which shall comprise three (3)

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representatives of each Party. The PJSC for ALN-TTR02 shall be established as of the Effective Date. Each Party shall appoint its respective representatives to the PJSC for each other Regional Licensed Product from time to time following the Implementation Date for such Regional Licensed Product, and may substitute one or more of its representatives on any PJSC, in its sole discretion, effective upon notice to the other Party of such change. Each Party shall have at least one representative on each PJSC who is a senior employee (vice president level or above), and all representatives on each PJSC shall have appropriate expertise, seniority, decision-making authority and ongoing familiarity with the RLP Collaboration and the applicable Regional Licensed Product. For the avoidance of doubt, the same representatives from each Party may serve on the PJSC for more than one Regional Licensed Product. Unless otherwise agreed by the Parties, each Party’s representatives on any PJSC must be employees of such Party. Additional representatives or consultants may from time to time, by mutual consent of the Parties, be invited to attend PJSC meetings, subject to such representatives and consultants undertaking confidentiality obligations, whether in a written agreement or by operation of law, no less stringent than the requirements of Section 7 of the Master Agreement (Confidentiality and Publication).

5.1.2. PJSC Chairperson. The chairperson of each PJSC shall rotate every twelve (12) months between a PJSC representative of Alnylam and a PJSC representative of Genzyme. The initial chairperson of each PJSC shall be a representative of Alnylam. Each PJSC chairperson’s responsibilities shall include chairing meetings, including ensuring that objectives for each meeting are set and achieved.

5.2. Appointment of Subcommittees, Project Teams and RLP Alliance Managers . Each PJSC shall be empowered to create such subcommittees and project teams as it may deem appropriate or necessary, such as for specific oversight of Development, Manufacturing, Commercialization or intellectual property issues relating to the Regional Licensed Product for which such PJSC is responsible. Each such project team created by a PJSC shall report to such PJSC, which shall have authority to approve or reject recommendations or actions proposed by such project team, subject to these Regional License Terms. For the avoidance of doubt, the same representatives from each Party may serve on the project team for more than one Regional Licensed Product. Each Party will designate an alliance manager for each Regional Licensed Product (each, a “ RLP Alliance Manager ”) to serve as a primary point of contact for the other Party with respect to all activities under the RLP Collaboration related to such Regional Licensed Product. Each RLP Alliance Manager’s responsibilities shall include (a) scheduling meetings of the PJSC at least once per Calendar Quarter, but more frequently if the PJSC determines it necessary; (b) setting agendas for PJSC meetings with solicited input from the RLP Alliance Manager for the other Party and other members of the PJSC; and (c) coordinating the delivery of draft minutes to the PJSC for review and final approval. Beginning with Alnylam’s RLP Alliance Manager, such responsibilities shall alternate between the RLP Alliance Managers from each Party on a meeting-by-meeting basis after each meeting of the applicable committee. Each Party may change any of its RLP Alliance Managers at any time in its sole discretion with written notice to the other Party, provided that each RLP Alliance Manager will be individually identified at all times and will have such experience, authority, responsibility and accountability as is reasonably sufficient to enable such person to fulfill his or her responsibilities as a RLP Alliance Manager under these Regional License Terms on behalf of the applicable Party.

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5.3. PJSC Meetings . Each PJSC shall meet in accordance with a schedule established by mutual written agreement of the Parties, but no less frequently than once per Calendar Quarter during the Term, with the location for such meetings alternating between Alnylam and Genzyme facilities (or such other locations as are mutually agreed by the Parties). Alternatively, a PJSC may meet by means of teleconference, videoconference or other similar communications equipment, but at least two (2) meetings of such PJSC per Calendar Year shall be conducted in person. All proceedings for each PJSC shall take place in English. Where the membership of a PJSC for a Regional Licensed Product is the same as one or more other PJSCs for other Regional Licensed Product(s), such PJSCs may have a single meeting to discuss each Regional Licensed Product for which they have responsibility. Each Party shall bear its own expenses relating to attendance at such meetings by its representatives.

5.4. PJSC Minutes . A RLP Alliance Manager shall be appointed secretary for each meeting of each PJSC and shall prepare minutes of the meeting, which shall provide a description in reasonable detail of the discussions held at the meeting and a list of any actions, decisions or determinations approved by such PJSC. Within [***] days after each meeting, the drafting RLP Alliance Manager shall provide the draft minutes to the other RLP Alliance Manager for review and comment. The drafting RLP Alliance Manager shall reasonably consider all comments from the other RLP Alliance Manager within [***] days. The drafting RLP Alliance Manager shall prepare and submit revised minutes within [***] days after receipt of such comments or upon expiration of such [***] day period.

5.5. PJSC Responsibilities .

5.5.1. PJSC Development Responsibilities. Each PJSC shall have the following responsibilities with respect to the Development of the Regional Licensed Product for which it is responsible:

(a) developing and approving updates and amendments to the Global Development Strategy for such Regional Licensed Product in accordance with Section 2.2.1 (Global Development Strategy);

(b) developing and approving updates and amendments to the Global Development Plan for such Regional Licensed Product in accordance with Section 2.2.2.3 (Managing and Amending Global Development Plans and Global Development Budgets);

(c) reviewing and approving the initial Genzyme Territory Development Plan and the initial Alnylam Territory Development Plan for such Regional Licensed Product in accordance with Sections 2.2.3 (Alnylam Territory Development Plan) and 2.2.4 (Genzyme Territory Development Plan);

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(d) reviewing and discussing updates and amendments to the Genzyme Territory Development Plan and the Alnylam Territory Development Plan for such Regional Licensed Product in accordance with Sections 2.2.3 (Alnylam Territory Development Plan) and 2.2.4 (Genzyme Territory Development Plan), and providing each Party with feedback regarding the same;

(e) reviewing and discussing updates provided by each Party regarding the Development of such Regional Licensed Product in such Party’s Territory in accordance with Section 2.5.1 (Development Activities Reports), and providing each Party with feedback regarding the same;

(f) monitoring and coordinating Development activities in the Genzyme Territory and the Alnylam Territory for such Regional Licensed Product, and regulatory and pharmacovigilance requirements and matters;

(g) reviewing and discussing updates provided by each Party regarding any Global Development Activities in accordance with the Global Development Plan for such Regional Licensed Product (including the Global Development Budget);

(h) approving a global list of clinical sites for each Global Clinical Study for such Regional Licensed Product;

(i) approving the appointment of the global CRO to manage any Phase II Study or Phase III Study for such Regional Licensed Product;

(j) overseeing any manufacturing and supply relationship between the Parties with respect to the Manufacture of such Regional Licensed Product for Development activities (subject to the provisions of the RLP Clinical Supply Agreement, if any); and

(k) performing such other activities as the Parties agree in writing shall be the responsibility of such PJSC or that are otherwise assigned to such PJSC under these Regional License Terms.

5.5.2. PJSC Commercialization Responsibilities. Each PJSC shall have the following responsibilities with respect to the Commercialization of the Regional Licensed Product for which it is responsible, to the extent permissible under applicable Laws:

(a) reviewing and discussing reports and information provided by each Party regarding the Commercialization of such Regional Licensed Product in such Party’s Territory in accordance with Section 4.6 (Commercialization Reporting Obligations);

(b) reviewing and approving, any Global Branding Strategy developed by Alnylam for such Regional Licensed Product in accordance with Section 4.5.1 (Global Branding);

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(c) reviewing and discussing the Genzyme Territory Commercialization Plan for such Regional Licensed Product and updates thereto provided by Genzyme pursuant to Section 4.3 (Genzyme Territory Commercialization Plan);

(d) reviewing and discussing Promotional Material for such Regional Licensed Product of both Parties in accordance with Sections 4.5.2 (–Alnylam A&P) and 4.5.3 (–Genzyme A&P);

(e) providing a forum for the Parties to discuss the Commercialization of such Regional Licensed Product in the Field worldwide, including coordination regarding Regional Licensed Product positioning and messaging, key opinion leader relationship management, medical affairs, and marketing and selling materials;

(f) providing a forum for the Parties to discuss collaborating on commercial activities with respect to such Regional Licensed Product that can be leveraged for both Parties’ respective Territories and how the Parties would share the costs of such mutually agreed joint Commercialization activities;

(g) overseeing any manufacturing and supply relationship between the Parties with respect to the Manufacture of such Regional Licensed Product for Commercialization activities (subject to the provisions of the RLP Commercial Supply Agreement, if any); and

(h) performing such other activities as the Parties agree in writing shall be the responsibility of such PJSC or that are otherwise assigned to such PJSC under these Regional License Terms.

5.6. PJSC Decision-Making .

5.6.1. PJSC Decisions . With respect to decisions of each PJSC, the representatives of each Party on such PJSC shall have collectively one vote on behalf of such Party. For each meeting of a PJSC, at least two (2) representatives of each Party shall constitute a quorum. Action on any matter may be taken at a meeting, by teleconference, videoconference or by written agreement. Each PJSC shall attempt to resolve any and all disputes before it for decision by consensus. For the avoidance of doubt, the phrase “approval by the PJSC” and similar phrases used in these Regional License Terms shall mean approval in accordance with this Section 5.6 (PJSC Decision-Making), including [***].

5.6.2. Escalation . If a PJSC is unable to reach a consensus with respect to any dispute for a period in excess of [***] days, then the dispute shall be submitted to the AJSC (as defined in the Master Agreement) at a meeting or meetings (whether in-person or by teleconference or videoconference). During such meeting(s), each Party shall provide analysis to support its position with respect to such dispute. If the dispute is still unresolved after a further [***] days, such dispute shall be [***].

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5.6.3. [***]. If a dispute cannot be resolved under Section 5.6.2 (Escalation), then, subject to Sections 5.6.4 [***]

5.6.3.1. [***]

5.6.3.2. [***]

5.6.3.3. [***]

5.6.4. [***]

5.6.4.1. [***]

5.6.4.2. [***]

5.6.5. [***]

(i) [***]

(ii) [***]

(iii) [***]

(iv) [***]

(v) [***]

5.7. Term of PJSC . With respect to each Regional Licensed Product, after the [***] anniversary of the Implementation Date for such Regional Licensed Product, Alnylam shall have the right, but not the obligation, to continue its participation in the PJSC responsible for such Regional Licensed Product.

5.8. Alnylam Third Party Partner . If, at any time during the Term, Alnylam enters into an agreement (a “ Third Party Collaboration Agreement ”) with one or more Third Party(ies) (each, a “ Third Party Partner ”) to Develop and/or Commercialize any Regional Licensed Product in the Field in the Alnylam Territory, Alnylam shall ensure that such agreement is consistent with these Regional License Terms.

5.8.1. Required Terms. Without limitation, Alnylam shall negotiate terms in the Third Party Collaboration Agreement (a) regarding intellectual property necessary to permit Alnylam to license or sublicense to Genzyme any Patent Rights and Know-How developed in the course of activities pursuant to the Third Party Collaboration Agreement that are necessary for Genzyme to Develop, Manufacture and Commercialize Regional Licensed Products in accordance with these Regional License Terms, if any; (b) providing Genzyme with a right of reference as set forth in Section 3.4 (Right of Reference); (c) requiring such Third Party Partner to maintain records substantially as set forth in Section 2.5.2 (Scientific Records); (d) enabling

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Alnylam to provide Genzyme with copies of data and reports, including Clinical Study reports, in a commercially reasonable format, made, collected or otherwise generated by or on behalf of the Third Party Partner in the conduct of any pre-clinical studies, Clinical Studies or early access/named patient programs for any Regional Licensed Products (excluding, for clarity, information generated in Secondary Indication Studies and CMC information), and protocols and investigator brochures related to any Regional Licensed Product, in each case that are reasonably necessary for Genzyme (or its Related Parties) to Develop and obtain Regulatory Approval for the Regional Licensed Products in the Genzyme Territory; (e) enabling Alnylam to provide Genzyme with information with respect to matters in the Third Party Partner’s territory as are required to be provided to Genzyme under Sections 2.5.1 (Development Activities Reports), 3.1.2 (Communications) (to the extent requiring a brief description in English of principal issues raised in material communications from Regulatory Authorities and otherwise to the extent reasonably necessary to assist Genzyme with obtaining Regulatory Approvals of Regional Licensed Products), and 3.1.4 (Submissions); (f) regarding pharmacovigilance that are consistent with Section 4.6 of the Master Agreement (Pharmacovigilance) and the SDEA; and (g) regarding recalls that are consistent with Section 4.7 (Recalls, Market Withdrawals or Corrective Actions).

5.8.2. [***].

5.8.3. Global Coordination Committee. Alnylam shall use reasonable efforts to include in any Third Party Collaboration Agreement relating to rights licensed to a Third Party Partner in the United States and/or major markets in Europe, the discretionary participation by such Third Party Partner with Genzyme and Alnylam in a global coordination committee, which shall include representatives of Alnylam, Genzyme and the Third Party Partner and which shall be responsible for facilitating discussions between the parties with respect to the global Development, Manufacture and Commercialization of Regional Licensed Products.

5.8.4. Notice. Alnylam shall promptly provide Genzyme with a copy of any fully executed Third Party Collaboration Agreement, which may be redacted to remove provisions which are not necessary to monitor compliance with this Section 5.8 and such Third Party Collaboration Agreement will be deemed Alnylam Confidential Information for the purposes of Section 7 of the Master Agreement (Confidentiality and Publication).

5.8.5. Sublicenses. If any Third Party Collaboration Agreement grants the Third Party Partner a sublicense under the Genzyme Technology, Alnylam shall ensure that such Third Party Collaboration agreement complies with Section 6.2.4 (Sublicensing Terms).

5.8.6. Breach; Responsibility. If Alnylam becomes aware of a material breach of the provisions of any Third Party Collaboration Agreement by a Third Party Partner, compliance with which is necessary for Alnylam’s compliance with these Regional License Terms, Alnylam shall promptly notify Genzyme of the particulars of the same and use Commercially Reasonable Efforts to cause the Third Party Partner to comply with all the provisions of the Third Party Collaboration Agreement necessary for Alnylam’s compliance with these Regional License Terms. Notwithstanding any Third Party Collaboration Agreement, Alnylam shall remain primarily liable to Genzyme for the performance of all of Alnylam’s obligations under, and Alnylam’s compliance with all provisions of, these Regional License Terms with respect to the entire Alnylam Territory.

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6. LICENSES

6.1. License Grants to Genzyme .

6.1.1. Development License in the Genzyme Territory. On a Regional Licensed Product-by-Regional Licensed Product basis, subject to these Regional License Terms (including Section 8.4.1.3(c) (Exclusivity)) and any RLP Clinical Supply Agreement, effective upon the Implementation Date for each Regional Licensed Product, Alnylam hereby grants Genzyme a non-transferable (except as provided in Section 13.1 of the Master Agreement (Assignment)), sublicensable (subject to Section 6.1.4 (Sublicensing Terms)) exclusive (even as to Alnylam) license under Alnylam Technology to Develop such Regional Licensed Product in the Field in the Genzyme Territory and the Alnylam Territory, in each case solely as and to the extent provided in any approved Genzyme Territory Development Plan or any Global Development Plan, and in each case, solely for Regulatory Approval and Commercialization in the Genzyme Territory. Notwithstanding the foregoing, Alnylam retains (a) the exclusive right under the Alnylam Technology, with the right to grant licenses through multiple tiers without restriction, to Develop Regional Licensed Products anywhere in the world for Regulatory Approval and Commercialization in the Alnylam Territory, and (b) the co-exclusive right (with Genzyme) to Develop each Regional Licensed Product anywhere in the world for Regulatory Approval and Commercialization by Genzyme in the Genzyme Territory in accordance with the Global Development Plan for such Regional Licensed Product.

6.1.2. Commercialization License in the Genzyme Territory. On a Regional Licensed Product-by-Regional Licensed Product basis, subject to these Regional License Terms (including Section 8.4.1.3(c) (Exclusivity)) and any RLP Commercial Supply Agreement, effective upon the Implementation Date for each Regional Licensed Product, Alnylam hereby grants Genzyme a non-transferable (except as provided in Section 13.1 of the Master Agreement (Assignment)), sublicensable (subject to Section 6.1.4 (Sublicensing Terms)) exclusive (even as to Alnylam) license under Alnylam Technology to Commercialize such Regional Licensed Product in the Field in the Genzyme Territory. Such license shall be royalty-bearing for the Royalty Term applicable to each Regional Licensed Product in each country in the Genzyme Territory, and, after the Royalty Term applicable to such Regional Licensed Product in such country, shall convert to a fully-paid perpetual exclusive license to Commercialize such Regional Licensed Product in the Field in such country.

6.1.3. Manufacturing Licenses. On a Regional Licensed Product-by-Regional Licensed Product basis, subject to these Regional License Terms (including Section 8.4.1.3(c)) and any RLP Clinical Supply Agreement and RLP Commercial Supply Agreement, effective upon the Implementation Date for each Regional Licensed Product, Alnylam hereby grants Genzyme a non-transferable (except as provided in Section 13.1 of the Master Agreement (Assignment)), sublicensable (subject to Section 6.1.4(Sublicensing Terms)), worldwide, exclusive (even as to Alnylam) license under Alnylam Technology to Manufacture

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such Regional Licensed Product inside or outside of the Genzyme Territory solely for Commercialization in the Genzyme Territory and, to the extent permitted pursuant to Section 2.3.2 (Genzyme Development), for Development for the Alnylam Territory. Notwithstanding the foregoing, Alnylam retains the exclusive right under the Alnylam Technology, with the right to grant licenses through multiple tiers without restriction, to Manufacture Regional Licensed Products anywhere in the world (a) for Development and Commercialization in the Alnylam Territory and, to the extent permitted pursuant to Section 2 (Development Collaboration) for Development in the Genzyme Territory, and (b) to supply (or have supplied to) Genzyme pursuant to the RLP Supply Agreements to be agreed by the Parties pursuant to Section 6.2 of the Master Agreement (Collaboration Product Supply Agreements).

6.1.4. Sublicensing Terms .

(a) Genzyme shall have the right to sublicense any of its rights under Sections 6.1.1 (Development License in the Genzyme Territory), 6.1.2 (Commercialization License in the Genzyme Territory) and 6.1.3 (Manufacturing Licenses) to any of its Affiliates or to any Third Party (which sublicensed rights may be further sublicensable through multiple tiers) without the prior consent of Alnylam, subject to the requirements of this Section 6.1.4. [***].

(b) Each sublicense granted by Genzyme pursuant to this Section 6.1.4 shall be subject and subordinate to these Regional License Terms and shall contain provisions consistent with those in these Regional License Terms. Genzyme shall promptly provide Alnylam with a copy of the fully executed sublicense agreement covering any sublicense granted hereunder (which copy may be redacted to remove provisions which are not necessary to monitor compliance with this Section 6.1.4), and each such sublicense agreement shall contain the following provisions: (i) a requirement that the Sublicensee comply with the confidentiality and non-use provisions of Section 7 of the Master Agreement (Confidentiality and Publication) with respect to Alnylam’s Confidential Information, (ii) if such sublicense agreement contains a sublicense of Regional Licensed Product Commercialization rights, such sublicense agreement shall also contain the following provisions: (x) a requirement that the Sublicensee submit applicable sales or other reports to Genzyme to the extent necessary or relevant to the reports required to be made or records required to be maintained under these Regional License Terms; and (y) the audit requirement set forth in Section 9.2 of the Master Agreement (Audits); and (iii) a requirement that the Sublicensee comply with the applicable provisions under any Alnylam In-License.

(c) If Genzyme becomes aware of a material breach of the provisions of any sublicense by any Genzyme Sublicensee, compliance with which is necessary for Genzyme’s compliance with these Regional License Terms, Genzyme shall promptly notify Alnylam of the particulars of the same and use Commercially Reasonable Efforts to cause the Sublicensee to comply with all the provisions of the sublicense necessary for Genzyme’s compliance with these Regional License Terms. [***]. Notwithstanding any sublicense, Genzyme shall remain primarily liable to Alnylam for the performance of all of Genzyme’s obligations under, and Genzyme’s compliance with all provisions of, these Regional License Terms.

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6.2. License Grants to Alnylam .

6.2.1. Commercialization License in the Alnylam Territory. Subject to these Regional License Terms, Genzyme hereby grants Alnylam a non-transferable (except as provided in Section 13.1 of the Master Agreement (Assignment)), sublicensable (subject to Section 6.2.4 (Sublicensing Terms)), non-exclusive, royalty-free license under Genzyme Collaboration IP to Develop and Commercialize Regional Licensed Products in the Field in the Alnylam Territory.

6.2.2. License to Improvement Manufacturing Patent Rights. Subject to these Regional License Terms, Genzyme hereby grants Alnylam a non-transferable (except as provided in Section 13.1 of the Master Agreement (Assignment)), sublicensable (subject to Section 6.2.4 (Sublicensing Terms)), worldwide, non-exclusive license under the Improvement Manufacturing Patent Rights, to Manufacture (a) Alnylam Developed siRNA Products targeting any human gene; and (b) Regional Licensed Products for Development and Commercialization in the Alnylam Territory and, to the extent permitted pursuant to Section 2.3.3 (Alnylam Development), for Development in the Field in the Genzyme Territory.

6.2.3. License to Genzyme Disclosed Manufacturing Know-How. Subject to these Regional License Terms, Genzyme hereby grants Alnylam a non-transferable (except as provided in Section 13.1 of the Master Agreement (Assignment)), sublicensable (subject to Section 6.2.4 (Sublicensing Terms)), worldwide, non-exclusive license under the Genzyme Disclosed Manufacturing Know-How to Manufacture Regional Licensed Products for Development and Commercialization in the Alnylam Territory and, to the extent permitted pursuant to Section 2.3.3 (Alnylam Development), for Development in the Field in the Genzyme Territory.

6.2.4.

Sublicensing Terms.

(a) Subject to Section 6.5 (Alnylam Territory Right of First Negotiation), Alnylam shall have the right to sublicense any of its rights under Section 6.2.1 (Commercialization License in the Alnylam Territory), 6.2.2 (License to Improvement Manufacturing Patent Rights) and 6.2.3 (License to Genzyme Disclosed Manufacturing Know-How) to [***].

(b) Each sublicense granted by Alnylam pursuant to this Section 6.2.4 shall be subject and subordinate to these Regional License Terms and shall contain provisions consistent with those in these Regional License Terms. Alnylam shall promptly provide Genzyme with a copy of the fully executed sublicense agreement covering any sublicense granted hereunder (which copy may be redacted to remove provisions which are not necessary to monitor compliance with this Section 6.2.4), and each such sublicense

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agreement shall contain the following provisions: (i) a requirement that the Sublicensee comply with the confidentiality and non-use provisions of Section 7 of the Master Agreement (Confidentiality and Publication) with respect to Genzyme’s Confidential Information and (ii) a requirement that the Sublicensee comply with the applicable provisions under any Genzyme In-License.

(c) If Alnylam becomes aware of a material breach of any sublicense by any Alnylam Sublicensee, compliance with which is necessary for Alnylam’s compliance with these Regional License Terms, Alnylam shall promptly notify Genzyme of the particulars of the same and use Commercially Reasonable Efforts to cause the Sublicensee to comply with all the provisions of the sublicense necessary for Alnylam’s compliance with these Regional License Terms. [***]. Notwithstanding any sublicense, Alnylam shall remain primarily liable to Genzyme for the performance of all of Alnylam’s obligations under, and Alnylam’s compliance with all provisions of, these Regional License Terms.

6.3. Joint Collaboration IP . Subject to the rights and licenses granted to, and the obligations (including royalty obligations) of, each Party under these Regional License Terms, either Party is entitled to practice Joint Collaboration IP for all purposes on a worldwide basis and license Joint Collaboration IP without consent of and without a duty of accounting to the other Party. Each Party will grant and hereby does grant all permissions, consents and waivers with respect to, and all licenses under, the Joint Collaboration IP, throughout the world, necessary to provide the other Party with such rights of use and exploitation of the Joint Collaboration IP, and will execute documents as necessary to accomplish the foregoing.

6.4. Compliance with In-Licenses . All licenses and other rights granted to Genzyme under this Section 6 are subject to the rights and obligations of Alnylam under the Alnylam In-Licenses. All licenses and other rights granted to Alnylam under this Section 6 are subject to the rights and obligations of Genzyme under the Genzyme In-Licenses. Each Party shall comply with all applicable provisions of the In-Licenses, and shall perform and take such actions as may be required to allow the Party that is party to such In-License to comply with its obligations thereunder, including obligations relating to sublicensing, patent matters, confidentiality, reporting, audit rights, indemnification and diligence. Without limiting the foregoing, each Party shall prepare and deliver to the other Party any additional reports required under the applicable In-Licenses and requested by such other Party, in each case sufficiently in advance to enable the Party that is party to such In-License to comply with its obligations under the applicable In-Licenses. Each Party agrees, upon the other Party’s request, to provide the other Party with copies of any In-Licenses to which it is a party. Confidential Information of the providing Party or its counterparty may be redacted from such copies, except to the extent that such information is required in order to enable the other Party to comply with its obligations to the providing Party under these Regional License Terms with respect to such In-License or in order to enable the providing Party to ascertain compliance with these Regional License Terms.

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6.5. Alnylam Territory Right of First Negotiation . If, at any time during the Term, Alnylam desires to grant any Third Party rights to Develop and/or Commercialize one or more Regional Licensed Product(s) in any portion of the Alnylam Territory, Alnylam shall notify Genzyme in writing of its intent. Genzyme shall have [***] days from receipt of such written notice to notify Alnylam in writing as to whether Genzyme desires to negotiate for such rights in such territory, and if Genzyme so notifies Alnylam that it does desire to negotiate for such rights in such territory, Genzyme shall have the exclusive right for [***] days from the date of such notification to Alnylam to negotiate with Alnylam and to make one or more written non-binding offers to Alnylam concerning the acquisition of such rights in such territory by Genzyme. Genzyme shall have the exclusive right for [***] days (or such longer period as may be mutually agreed by the Parties) after such [***] day period, to finalize and enter into a definitive agreement with Alnylam for such rights in such territory, provided that, if either Genzyme does not provide such written notice within such [***] day period or Genzyme does provide such written non-binding offer within such subsequent [***] day period, or Genzyme provides such notice of interest and such written offer but for any reason Genzyme and Alnylam do not enter into a definitive agreement within the [***] day negotiation period, Alnylam shall be free to enter into an agreement with a Third Party(ies) relating to such rights in such territory, without further obligation to Genzyme. Alnylam shall not, during the exclusive [***] day negotiating periods described above, enter into discussions, exchange information, or otherwise negotiate with any Third Party with respect to an agreement with respect to the Development and/or Commercialization of the applicable Regional Licensed Product(s) in the Alnylam Territory. Notwithstanding the foregoing, during the period of [***] months after the termination of any such negotiation that does not result in a definitive agreement between Alnylam and Genzyme, Alnylam shall not enter into a transaction with respect to such rights in such territory with any Third Party on terms that are, in the aggregate, materially more favorable to the Third Party than the last terms offered in writing by Genzyme to Alnylam unless Alnylam first re-offers such transaction to Genzyme on such more favorable terms and Genzyme does not accept such offer and enter into such transaction with Alnylam within [***] days after such re-offer. For clarity, prior to the exclusive negotiating periods described above, Alnylam shall be free to engage in discussions and exchange information with Third Parties with respect to the applicable Regional Licensed Product(s) rights, but shall not enter into any binding agreement with any Third Party with respect to such rights.

6.6. Bankruptcy . All rights and licenses granted under or pursuant to these Regional License Terms by a Party to the other, including those set forth in Sections 6.1 (License Grants to Genzyme), 6.2 (License Grants to Alnylam), and 3.4 (Right of Reference), are and shall otherwise be deemed to be, for purposes of Section 365(n) of the U.S. Bankruptcy Code, licenses of right to “intellectual property” as defined under Section 101 of the U.S. Bankruptcy Code. The Parties agree that the Parties and their respective Sublicensees, as sublicensees of such rights under these Regional License Terms, shall retain and may fully exercise all of their rights and elections under the U.S. Bankruptcy Code and any foreign counterpart thereto. The Parties further agree that upon commencement of a bankruptcy proceeding by or against a Party (the “ Bankrupt Party ”) under the Bankruptcy Code, the other Party (the “ Non-Bankrupt Party ”) will be entitled to a complete duplicate of, or complete access to (as the Non-Bankrupt Party

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deems appropriate), all such intellectual property and all embodiments of such intellectual property. Such intellectual property and all embodiments of such intellectual property will be promptly delivered to the Non-Bankrupt Party (a) upon any such commencement of a bankruptcy proceeding and upon written request by the Non-Bankrupt Party, unless the Bankrupt Party elects to continue to perform all of its obligations under these Regional License Terms, or (b) if not delivered under (a) above, upon the rejection of these Regional License Terms by or on behalf of the Bankrupt Party and upon written request by the Non-Bankrupt Party. Without limiting the foregoing, Alnylam hereby grants to Genzyme a right of access to and to obtain possession of (i) copies of research data, (ii) laboratory samples, (iii) samples of Regional Licensed Product, (iv) formulas, (v) laboratory notes and notebooks, (vi) data and results related to clinical trials, (vii) regulatory filings and approvals, (viii) rights of reference in respect of regulatory filings and approvals, (ix) pre-clinical research data and results, and (x) marketing, advertising and promotional materials, all of which (in clauses (i) through (x)) constitute “embodiments” of intellectual property pursuant to Section 365(n) of the Bankruptcy Code and (xi) all other embodiments of such intellectual property, and in respect of each of the foregoing clauses (i) through (xi), solely for the purpose of the exercise of Genzyme’s rights and licenses under these Regional License Terms, whether any of the foregoing are in Alnylam’s possession or control or in the possession and control of Third Parties. The Bankrupt Party (in any capacity, including debtor-in-possession) and its successors and assigns (including any trustee) agree not to interfere with the exercise by the Non-Bankrupt Party or its Related Parties of its rights and licenses to such intellectual property and such embodiments of intellectual property in accordance with these Regional License Terms, and agrees to assist the Non-Bankrupt Party and its Related Parties in obtaining such intellectual property and such embodiments of intellectual property in the possession or control of Third Parties as are reasonably necessary or desirable for the Non-Bankrupt Party to exercise such rights and licenses in accordance with these Regional License Terms. The foregoing provisions are without prejudice to any rights the Non-Bankrupt Party may have arising under the Bankruptcy Code or other Laws.

6.7. No Other Rights . Except as otherwise expressly provided in these Regional License Terms, under no circumstances shall a Party, as a result of these Regional License Terms, obtain any ownership interest or other right in any Know-How, Patent Rights or other intellectual property rights of the other Party, including items owned, controlled or developed by the other Party, or provided by the other Party to the receiving Party at any time pursuant to these Regional License Terms.

7. CERTAIN FINANCIAL TERMS

7.1. Milestone Fees .

7.1.1. Development Milestones for Regional Licensed Products. Genzyme shall provide Alnylam with written notice of the achievement by Genzyme or any of its Related Parties of any development milestone event set forth below in this Section 7.1.1 and Alnylam shall provide Genzyme with written notice of the achievement by Alnylam or any of its Related Parties of any development milestone event set forth below in this Section 7.1.1, in each case

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within [***] days after such event has occurred; provided , however , that the notifying Party shall inform the other Party of such event prior to any public disclosure of such event by the notifying Party. Alnylam shall invoice Genzyme within [***] days of receipt of such written notice by either Party, and Genzyme shall remit the associated development milestone payment within [***] days of the receipt of such invoice. Each development milestone payment by Genzyme to Alnylam hereunder shall be payable only once with respect to each Regional Licensed Product, regardless of the number of times a development milestone event is achieved with respect to any Regional Licensed Product.

7.1.1.1. Development Milestones for ALN-TTR02 . Genzyme shall pay Alnylam the following amounts upon achievement of the following development milestone events with respect to ALN-TTR02:


Development Milestone Event	Development Milestone Payment
[***]		[***]
[***]		[***]
[***]		[***]
[***]		[***]

7.1.1.2. Development Milestones for Regional Licensed Products other than ALN-TTR02 . Genzyme shall pay Alnylam the following amounts upon achievement of the following development milestone events with respect to any Regional Licensed Product other than ALN-TTR02:


Development Milestone Event	Development Milestone Payment
[***]		[***]
[***]		[***]
[***]		[***]
[***]		[***]

7.1.2. Sales Milestones for Regional Licensed Products other than ALN-TTR02. Genzyme shall provide Alnylam with written notice of the achievement by Genzyme or any of its Related Parties of any of the sales milestone events set forth below in this Section 7.1.2 within [***] days after such event has occurred. Alnylam shall invoice Genzyme within [***]days of receipt of such written notice, and Genzyme shall remit the associated sales milestone payment within [***] days of the receipt of such invoice.


Sales Milestone Event	Sales Milestone Payment
[***]		[***]

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[***].

7.2. Royalties .

7.2.1. Royalties Payable on Regional Licensed Products .

7.2.1.1. Royalties Payable on ALN-TTR02 . Subject to these Regional License Terms, Genzyme shall pay to Alnylam royalties on annual Net Sales by Genzyme and its Related Parties of ALN-TTR02 in the Genzyme Territory, as follows:


Calendar Year Net Sales of ALN-TTR02 in the Genzyme Territory		Royalty (as a percentage of Net Sales)
[***]		[***]
[***]		[***]
[***]		[***]

Royalties on annual Net Sales of ALN-TTR02 shall be paid at the rate applicable to the portion of Net Sales within each of the Net Sales levels above during such Calendar Year. By way of example only, if Genzyme receives [***]

[***]

7.2.1.2. Royalties Payable on Other Regional Licensed Products . Subject to these Regional License Terms, Genzyme shall pay to Alnylam royalties on annual Net Sales by Genzyme and its Related Parties of each Regional Licensed Product other than ALN-TTR02 in the Genzyme Territory, as follows:

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Calendar Year Net Sales of a Regional Licensed Product other than ALN-TTR02 in the Genzyme Territory		Royalty (as a percentage of Net Sales of a Regional Licensed Product)
[***]		[***]
[***]		[***]
[***]		[***]
[***]		[***]
[***]		[***]

By way of example only, if Genzyme receives [***]

[***]

7.2.2. Royalty Term. Subject to Section 7.2.6 (Royalty Floor), the period during which the royalties set forth in Section 7.2.1(Royalties Payable on Regional Licensed Products) shall be payable, on a Regional Licensed Product-by-Regional Licensed Product and country-by-country basis, shall commence with the First Commercial Sale of a Regional Licensed Product in a country and continue until the latest of (a) the expiration of the last Valid Claim of [***] in the country of sale; (b) the expiration of Regulatory Exclusivity for such Regional Licensed Product in such country; or (c) subject to the last sentence of this Section 7.2.2, the [***] anniversary of the First Commercial Sale of such Regional Licensed Product in such country (each such period, a “ Royalty Term ”). [***]

7.2.3. Third Party Royalty Offsets. Genzyme shall be permitted to reduce any royalties payable under Section 7.2.1 (Royalties Payable on Regional Licensed Products) for a Regional Licensed Product [***].

7.2.4. [***].

7.2.5. [***].

7.2.6. Royalty Floor. Anything in these Regional License Terms to the contrary notwithstanding, in no event during the applicable Royalty Term for a Regional Licensed Product in a country of the Genzyme Territory shall the royalties payable to Alnylam hereunder for such Regional Licensed Product in such country for any Calendar Quarter be reduced [***].

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7.2.7. Validation Information. At Genzyme’s request, Alnylam will provide Genzyme with such information as Genzyme may reasonably request to validate the amount of the royalty floor described in Section 7.2.6 (Royalty Floor).

8. REPRESENTATIONS, WARRANTIES AND COVENANTS

8.1. Representations and Warranties of Alnylam . Except as provided in the Disclosure Schedule to this Section 8.1 (which Disclosure Schedule with respect to ALN-TTR02 is attached hereto and with respect to any other Regional Licensed Product will be provided by Alnylam to Genzyme as part of the Option Data Package for such Regional Licensed Product), Alnylam represents and warrants to Genzyme that, with respect to each Regional Licensed Product other than ALN-TTR02, as of the Implementation Date, and, with respect to ALN-TTR02, as of the Execution Date:

8.1.1. Alnylam is the sole and exclusive owner of, or otherwise Controls pursuant to an Alnylam In-License, the Alnylam Technology, and all of the Alnylam Technology licensed to Genzyme hereunder in the Genzyme Territory that is solely and exclusively owned by Alnylam is free and clear of liens, charges or encumbrances other than licenses granted to Third Parties that are not inconsistent with the rights and licenses granted to Genzyme under these Regional License Terms.

8.1.2. Alnylam has sufficient legal and/or beneficial title and ownership of, or sufficient license rights under, the Alnylam Technology to grant the licenses to such Alnylam Technology granted to Genzyme pursuant to these Regional License Terms.

8.1.3. (a) Schedule 1.2.13 and Schedule 1.2.18 collectively set forth a complete and accurate list of the Alnylam Patents owned, either solely or jointly, by Alnylam, and to Alnylam’s knowledge, Schedule 1.2.13 and Schedule 1.2.18 collectively set forth a complete and accurate list of the Alnylam Patents licensed, either exclusively or nonexclusively, to Alnylam, (b) to Alnylam’s knowledge, each issued Alnylam Patent remains in full force and effect and (c) Alnylam or its Affiliates have timely paid all filing and renewal fees payable with respect to such Alnylam Patents for which Alnylam controls prosecution and maintenance. Schedule 1.2.13 and Schedule 1.2.18 indicate whether each Alnylam Patent is owned exclusively by Alnylam, is owned jointly by Alnylam and one or more Third Parties, or is licensed to Alnylam. For each Alnylam Patent that is owned, but not owned exclusively, by Alnylam, or that is licensed to Alnylam, Schedule 1.2.13 and Schedule 1.2.18 identify the Third Party owner(s) and, if applicable, the Alnylam In-License pursuant to which Alnylam Controls such Alnylam Patent. For each Alnylam Product-Specific Patent that is licensed, but not exclusively licensed, to Alnylam, Schedule 1.2.18 indicates the non-exclusive nature of the license. For each Alnylam Core Technology Patent family (other than Patent Rights licensed from Isis Pharmaceuticals, Inc.) that is licensed, but not exclusively licensed, to Alnylam, Schedule 1.2.13 indicates the non-exclusive nature of the license. Alnylam is the sole and exclusive owner of all Patent Rights identified in Schedule 1.2.13 and Schedule 1.2.18 as being owned exclusively by Alnylam and Controls all other Patent Rights identified on such schedules.

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8.1.4. To Alnylam’s knowledge, the Alnylam Product-Specific Patents, are, or, upon issuance, will be, valid and enforceable patents and no Third Party has challenged or threatened to challenge the scope, validity or enforceability of any Alnylam Product-Specific Patent (including, by way of example, through opposition or the institution or written threat of institution of interference, nullity or similar invalidity proceedings before the United States Patent and Trademark Office or any analogous foreign Governmental Authority).

8.1.5. Alnylam has complied with all applicable Laws, including any duties of candor to applicable patent offices, in connection with the filing, prosecution and maintenance of the Alnylam Patent Rights.

8.1.6. Alnylam owns or Controls all Know-How that is or has been used by Alnylam in the Development and Manufacture of such Regional Licensed Product, and has sufficient legal or beneficial title and ownership of, or sufficient license rights under such Know-How to transfer Know-How to Genzyme as provided in Section 6.4 of the Master Agreement (Transfer of Manufacturing Know-How).

8.1.7. Alnylam Controls all Know-How and Patent Rights licensed to Alnylam under the Existing Alnylam In-Licenses that is necessary or useful for Genzyme to Develop, Manufacture and/or Commercialize such Regional Licensed Product in the Field in the Genzyme Territory. Without limiting the generality of the foregoing, Alnylam has obtained all necessary consents and fulfilled all necessary conditions, if any, to sublicense to Genzyme under these Regional License Terms such Know-How and Patent Rights licensed to Alnylam under Existing Alnylam In-Licenses.

8.1.8. To Alnylam’s knowledge, neither Alnylam nor its Affiliates are in breach or default under any existing Alnylam In-License, and neither Alnylam nor its Affiliates have received any written notice of breach or default with respect to any existing Alnylam In-License.

8.1.9. Alnylam has obtained from all inventors of Alnylam Technology owned by Alnylam valid and enforceable agreements assigning to Alnylam each such inventor’s entire right, title and interest in and to all such Alnylam Technology.

8.1.10. To Alnylam’s knowledge, the use, Development, Manufacture or Commercialization by Alnylam or Genzyme (or their respective Related Parties) of such Regional Licensed Product as formulated and manufactured as of the Effective Date, or as intended to be formulated and manufactured as of the Effective Date (a) does not and will not infringe any issued patent of any Third Party and (b) will not infringe the claims of any published Third Party patent application when and if such claims were to issue in their current form.

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8.1.11. There is no (a) claim, demand, suit, proceeding, arbitration, inquiry, investigation or other legal action of any nature, civil, criminal, regulatory or otherwise, pending or, to Alnylam’s knowledge, threatened against Alnylam or any of its Affiliates or (b) judgment or settlement against or owed by Alnylam or any of its Affiliates, in each case in connection with the Alnylam Technology or such Regional Licensed Product.

8.1.12. For each Regional Licensed Product, other than ALN-TTR02, Schedule 8.1.12(a) (Existing Alnylam In-Licenses) sets forth a complete and accurate list of all agreements between Alnylam and a Third Party entered into prior to the Implementation Date for a Regional Licensed Product pursuant to which Alnylam Controls Know-How or Patent Rights that are necessary or useful to Develop, Manufacture or Commercialize such Regional Licensed Product in the Field other than Additional Alnylam In-Licenses. [***]. For the sake of clarity, representations and warranties similar to those made pursuant to this Section 8.1.12 with respect to Regional Licensed Products other than ALN-TTR02 are made with respect to ALN-TTR02 in the Master Agreement.

8.2. Representations and Warranties of Genzyme . Except as disclosed in Genzyme’s Exercise Notice for a Regional Licensed Product, Genzyme represents and warrants to Alnylam as of the Implementation Date for such Regional Licensed Product that is not a party to any agreement with a Third Party under which it Controls Know-How or Patent Rights that are sublicensed to Alnylam under these Regional License Terms with respect to such Regional Licensed Product.

8.3. Warranty Disclaimer . EXCEPT AS OTHERWISE EXPRESSLY PROVIDED IN THESE REGIONAL LICENSE TERMS, NEITHER PARTY MAKES ANY REPRESENTATION OR EXTENDS ANY WARRANTY OF ANY KIND, EITHER EXPRESS OR IMPLIED, TO THE OTHER PARTY WITH RESPECT TO ANY TECHNOLOGY, REGIONAL LICENSED PRODUCT, GOODS, SERVICES, RIGHTS OR OTHER SUBJECT MATTER OF THESE REGIONAL LICENSE TERMS AND HEREBY DISCLAIMS ALL IMPLIED WARRANTIES OF MERCHANTABILITY, FITNESS FOR A PARTICULAR PURPOSE AND NON-INFRINGEMENT WITH RESPECT TO ANY AND ALL OF THE FOREGOING. EACH PARTY HEREBY DISCLAIMS ANY REPRESENTATION OR WARRANTY THAT THE DEVELOPMENT, MANUFACTURE OR COMMERCIALIZATION OF ANY REGIONAL LICENSED PRODUCT PURSUANT TO THESE REGIONAL LICENSE TERMS WILL BE SUCCESSFUL OR THAT ANY PARTICULAR SALES LEVEL WITH RESPECT TO ANY REGIONAL LICENSED PRODUCT WILL BE ACHIEVED.

8.4. Certain Covenants.

8.4.1. [***]

8.4.1.1. [***]

(a) [***]

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(b) [***]

8.4.1.2. [***]

(a) [***]

(b) [***]

8.4.1.3. [***]

(a) [***]

(b) [***]

8.4.2. Compliance. Each Party and its Related Parties shall conduct the RLP Collaboration and the Development, Manufacture and Commercialization of the Regional Licensed Products in accordance with all Laws, including current governmental regulations concerning Good Laboratory Practices (as defined in the Master Agreement), good clinical practices and good manufacturing practices. In addition, if either Party is or becomes subject to a legal obligation to a Regulatory Authority or other Governmental Authority (such as a corporate integrity agreement or settlement agreement with a Governmental Authority), then the other Party shall perform such activities as may be reasonably requested by the obligated Party to enable the obligated Party to comply with its legal obligation to such Regulatory Authority with respect to the Regional Licensed Products.

8.4.3. Conflicting Transactions. During the Term, Alnylam shall not (a) transfer or assign any of its rights, title or interests in the Alnylam Technology other than as part of a transaction pursuant to which these Regional License Terms are also assigned and assumed in accordance with Section 13.1 of the Master Agreement (Assignment), or (b) enter into any agreement granting a license or other right under the Alnylam Technology that is inconsistent with these Regional License Terms.

8.4.4. Governmental Authority. If any of the Alnylam Technology is subject to any funding arrangement with any Governmental Authority, at Genzyme’s reasonable request, Alnylam will reasonably cooperate in seeking a waiver or other modification to such funding arrangement with respect to such Alnylam Technology.

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9. INTELLECTUAL PROPERTY OWNERSHIP, PROTECTION AND RELATED MATTERS

9.1. Inventorship . Inventorship for inventions and discoveries first made during the course of the performance of activities pursuant to these Regional License Terms shall be determined in accordance with United States patent Laws for determining inventorship.

9.2. Ownership . Alnylam shall own the entire right, title and interest in and to all inventions and discoveries (and Patent Rights claiming patentable inventions therein) first made or discovered solely by employees or consultants of Alnylam or acquired solely by Alnylam in the course of conducting the Collaboration. Genzyme shall own the entire right, title and interest in and to all inventions and discoveries (and Patent Rights claiming patentable inventions therein) first made or discovered solely by employees or consultants of Genzyme or acquired solely by Genzyme in the course of conducting the Collaboration. The Parties shall jointly own any inventions and discoveries (and Patent Rights claiming patentable inventions therein) first made or discovered jointly in the course of conducting the Collaboration.

9.3. Prosecution and Maintenance of Patent Rights .

9.3.1. IP Committee. The Parties agree that the IP Committee created pursuant to Section 5.3 of the Master Agreement (IP Committee) shall be responsible for overseeing and effecting the information sharing and consulting provisions under this Section 9.3.1.

9.3.2. Genzyme Technology.

(a) Subject to Section 9.3.2(b) below, Genzyme has the sole responsibility to, at Genzyme’s discretion and at Genzyme’s sole cost and expense, file, prosecute, and maintain (including the defense of any interference or opposition proceedings), all Patent Rights comprising Genzyme Technology (other than Joint Collaboration IP), in Genzyme’s name.

(b) In the event that Genzyme elects not to seek or continue to seek or maintain patent protection on any Genzyme Collaboration IP in the Alnylam Territory, Genzyme shall notify Alnylam at least [***] days before any such Patent Rights would become abandoned, no longer available or otherwise forfeited, and subject to the provisions of any applicable Genzyme In-License, Alnylam shall have the right (but not the obligation), at its sole cost and expense, to seek, prosecute and maintain in any country patent protection on such Genzyme Collaboration IP in the name of Genzyme. Genzyme shall use Commercially Reasonable Efforts to make available to Alnylam its authorized attorneys, agents or representatives, and/or such of its employees as are reasonably necessary to assist Alnylam in obtaining and maintaining the patent protection described under this Section 9.3.2(b). Genzyme shall sign or use Commercially Reasonable Efforts to have signed all legal documents as are reasonably necessary to file and prosecute such patent applications or to obtain or maintain such patents.

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9.3.3. Alnylam Technology. The following will apply with respect to Alnylam Patent Rights during the Term [***].

(a) Subject to Section 9.3.3(c) below, Alnylam has the sole responsibility to, at Alnylam’s discretion and at Alnylam’s sole cost and expense, file, conduct prosecution, and maintain (including the defense of any interference or opposition proceedings), all Patent Rights comprising Alnylam Technology (other than Joint Collaboration IP), in Alnylam’s name. Notwithstanding the foregoing, Alnylam shall file Alnylam Product-Specific Rights in the Genzyme Patent Jurisdictions (as defined in the Master Agreement) and shall use commercially reasonable efforts to prosecute and maintain such Patent Rights in the Genzyme Patent Jurisdictions and shall timely pay all filing and renewal fees payable with respect thereto.

(b) Notwithstanding the foregoing Section 9.3.3(a), Alnylam shall consult with Genzyme, including through the IP Committee, on its strategy for the preparation, filing, prosecution, and maintenance of all Alnylam Product-Specific Patents in the Genzyme Territory and the Alnylam Territory. Alnylam shall furnish Genzyme, via electronic mail or such other method as mutually agreed by the Parties, copies of proposed filings and documents received from outside counsel in the course of filing, prosecution or maintenance of and/or copies of documents filed with the relevant patent offices with respect to Alnylam Product-Specific Patents and such other documents directly related to the prosecution and maintenance of Alnylam Product-Specific Patents reasonably necessary for Genzyme to exercise its rights under this Section 9.3.3(b), and as applicable in sufficient time prior to filing such document or making any payment due thereunder to allow for review and comment by Genzyme and shall consider in good faith timely comments from Genzyme thereon. Alnylam shall furnish to Genzyme, via electronic mail or such other method as mutually agreed by the Parties, copies of documents received from outside counsel in the course of filing, prosecution or maintenance of and/or copies of documents filed with the relevant national patent offices with respect to the filing, prosecution, and maintenance of Alnylam Core Technology Patents within a reasonable time after the receipt and/or filing of such documents.

(c) In the event that Alnylam elects not to seek or continue to seek or maintain patent protection on any Alnylam Product-Specific Patent in the Genzyme Territory, Alnylam shall notify Genzyme at least [***] days before any such Patent Rights would become abandoned, no longer available or otherwise forfeited, and subject to the provisions of any applicable Alnylam In-License, Genzyme shall have the right (but not the obligation), at its sole cost and expense, to seek, prosecute and maintain in any country patent protection on any such Alnylam Product-Specific Patent in the Genzyme Territory. If Genzyme exercises such right, Alnylam shall thereafter and hereby does assign all right, title and interest in and to such Alnylam Product-Specific Patents to Genzyme. Alnylam shall use Commercially Reasonable Efforts to make available to Genzyme its authorized attorneys, agents or representatives, such of its employees as are reasonably necessary to assist Genzyme in obtaining and maintaining the patent protection described under this Section 9.3.3(b). Alnylam shall sign or use Commercially Reasonable Efforts to have signed all legal documents as are reasonably necessary to file and prosecute such patent applications or to obtain or maintain such patents.

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(d) [***]

9.3.4. Joint Collaboration IP.

(a) [***] shall have the first right to, at [***] discretion, file, prosecute and maintain (including the defense of any interference or opposition proceedings), all Patent Rights comprising Joint Collaboration IP, in the names of both Alnylam and Genzyme. [***] shall consult with [***] on the filing, prosecution and maintenance of all such Patent Rights. Each Party shall sign, or use Commercially Reasonable Efforts to have signed, all legal documents as are reasonably necessary to file and prosecute patent applications or to obtain or maintain patents in respect of such Joint Collaboration IP, at its own cost.

(b) [***] shall furnish [***], via electronic mail or such other method as mutually agreed by the Parties, copies of documents received from outside counsel in the course of such filing, prosecution or maintenance of Joint Collaboration IP and/or copies of documents relevant to such preparation, filing, prosecution, and maintenance in sufficient time prior to filing such document or making any payment due thereunder to allow for review and comment by [***] and shall consider in good faith timely comments from [***] thereon. [***] shall furnish to Genzyme, via electronic mail or such other method as mutually agreed by the Parties, copies of such documents as filed in the relevant patent offices.

(c) In the event [***] elects not to file or continue to prosecute or maintain patent protection on any Joint Collaboration IP, [***]shall have the right (but not the obligation) to file, prosecute and maintain Patent Rights comprising Joint Collaboration IP in the names of both Alnylam and Genzyme. [***] exercises such right, [***] shall use Commercially Reasonable Efforts to make available to [***] its authorized attorneys, agents or representatives, and/or such of its employees as are reasonably necessary to assist [***] in obtaining and maintaining the patent protection described under this Section 9.3.4(c). [***] shall sign or use Commercially Reasonable Efforts to have signed all legal documents as are reasonably necessary to file and prosecute such patent applications or to obtain or maintain such patents.

(d) The Parties shall share equally the out-of-pocket patent filing, prosecution and maintenance expenses incurred with respect to Patent Rights comprising Joint Collaboration IP.

9.3.5. Patent Miscellaneous. Each Party hereby agrees: (a) to make its employees, agents and consultants reasonably available to the other Party (or to the other Party’s authorized attorneys, agents or representatives), to the extent reasonably necessary to enable such

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Party to undertake patent prosecution; (b) to provide the other Party with copies of all material correspondence pertaining to prosecution with the patent offices; (c) to cooperate, if necessary and appropriate, with the other Party in gaining patent term extensions wherever applicable to Patent Rights licensed under these Regional License Terms; and (d) to endeavor in good faith to coordinate its efforts with the other Party to minimize or avoid interference with the prosecution and maintenance of the other Party’s patent applications.

9.3.6. [***]

9.3.6.1. [***]

9.3.6.2. [***]

9.3.6.3. [***]

9.4. Third Party Infringement .

9.4.1. Notices. Each Party shall promptly report in writing to the other Party any (a) known or suspected infringement of any Alnylam Technology, Genzyme Technology or Joint Collaboration IP or (b) unauthorized use or misappropriation of any Confidential Information or Know-How of a Party by a Third Party of which it becomes aware, in each case to the extent such infringing, unauthorized or misappropriating activities involve, as to a Regional Licensed Product, a competing product in the Field (a “ Competitive Infringement ”), and shall provide the other Party with all available evidence of such infringement, unauthorized use or misappropriation.

9.4.2. Rights to Enforce.

(a) Genzyme Technology . Subject to the provisions of any In-License, Genzyme shall have the sole and exclusive right to initiate an infringement or other appropriate suit (an “ Infringement Action ”) anywhere in the world against any Third Party as to any infringement, or suspected infringement, of any Patent Rights, or as to any use or suspected use without proper authorization of any Know-How comprising Genzyme Patent Rights, Genzyme Know-How or Genzyme Collaboration IP. Genzyme will consider in good faith any request from Alnylam to initiate an Infringement Action against any Third Party with respect to Competitive Infringement in the Alnylam Territory of Genzyme Patent Rights, Genzyme Know-How or Genzyme Collaboration IP licensed to Alnylam under Section 6 (Licenses); provided , however , that Genzyme shall not be required to initiate any such Infringement Action or permit Alnylam to initiate any such Infringement Action.

(b) Alnylam Technology . Subject to the provisions of any In-License, Genzyme shall have the first right to initiate an Infringement Action against any Third Party with respect to any Competitive Infringement in the Genzyme Territory of any Alnylam Product-Specific Patent or Joint Collaboration IP, or, with Alnylam’s prior

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written consent, Alnylam Core Technology Patent or Alnylam Know-How. Alnylam will consider in good faith any request from Genzyme to initiate an Infringement Action against any Third Party with respect to a Competitive Infringement in the Genzyme Territory of any Alnylam Core Technology Patent; provided , however , that Alnylam shall not be required to initiate any such Infringement Action or permit Genzyme to initiate any such Infringement Action.

(i) If within [***] days (or such shorter period of time as required by applicable Law to avoid loss of material enforcement rights) after Genzyme’s receipt of a notice of a Competitive Infringement with respect to any Alnylam Product-Specific Patent or Joint Collaboration IP, Genzyme does not initiate any Infringement Action against such Competitive Infringement in the Genzyme Territory, Alnylam may in its sole discretion, bring and control any Infringement Action in connection therewith at its sole cost and expense.

(ii) [***]

9.4.3. Procedures; Expenses and Recoveries. The Party having the right to initiate any Infringement Action under Section 9.4.2 (Rights to Enforce) above shall have the sole and exclusive right to select counsel for any such Infringement Action and shall pay all expenses of the suit, including attorneys’ fees and court costs and reimbursement of the other Party’s reasonable Regional Out-of-Pocket Costs in rendering assistance requested by the initiating Party. If required under applicable Law in order for the initiating Party to initiate and/or maintain the Infringement Action, or if either Party is unable to initiate or prosecute such Infringement Action solely in its own name or it is otherwise advisable to obtain an effective legal remedy, in each case, the other Party shall join as a party to such Infringement Action and will execute and cause its Affiliates to execute all documents necessary for the initiating Party to initiate litigation to prosecute and maintain such action. In addition, at the initiating Party’s request, the other Party shall provide reasonable assistance to the initiating Party in connection with an Infringement Action at no charge to the initiating Party except for reimbursement by the initiating Party of reasonable Regional Out-of-Pocket Costs incurred in rendering such assistance. The non-initiating Party shall have the right to participate and be represented in any such Infringement Action by its own counsel at its own expense. If the Parties obtain from a Third Party, in connection with such Infringement Action, any damages, license fees, royalties or other compensation (including any amount received in settlement of such litigation), after payment of any amounts required under any In-Licenses, the remaining amounts shall be allocated in all cases as follows:

(a) first, to reimburse each Party for all expenses of the Infringement Action incurred by the Parties, including attorneys’ fees and disbursements, court costs and other litigation expenses;

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(b) second, [***] of the balance to be paid to the Party initiating the Infringement Action; and

9.5. Patent Term Extensions .

9.5.1. Retained Alnylam Product-Specific Patents. Subject to the provisions of any Alnylam In-License, Alnylam shall use Commercially Reasonable Efforts to obtain all available supplementary protection certificates (“SPCs”) and other extensions of Alnylam Product-Specific Patents in the Genzyme Territory[***]. If more than one such Alnylam Product-Specific Patent is eligible for extension or patent term restoration in the Genzyme Territory, Genzyme will determine, in its sole discretion, a strategy that will be designed to maximize patent protection and commercial value for the Regional Licensed Product, and the Parties, subject to the provisions of any In-License, will seek patent term extensions, restorations and SPCs for Alnylam Product-Specific Patents in the Genzyme Territory in accordance with that strategy. Where required under national law, and subject to the other requirements of this Section 9.5, Alnylam will make the filings for such extensions, restorations and SPCs for Alnylam Product-Specific Patents in the Genzyme Territory as directed by Genzyme.

9.5.2. Further Assurances for SPCs. Each Party will execute such authorizations and other documents and take such other actions as may be reasonably requested by the other Party to obtain any such extensions, restorations and SPCs for Alnylam Product-Specific Patents in the Genzyme Territory, in accordance with this Section 9.5.

9.6. Common Interest . All information exchanged between the Parties representatives regarding the preparation, filing, prosecution, maintenance, or enforcement of the Patent Rights under this Section 9 will be deemed Confidential Information. In addition, the Parties acknowledge and agree that, with regard to such preparation, filing, prosecution, maintenance, and enforcement of the Patents Rights under this Section 9, the interests of the Parties as collaborators and licensor and licensee are to obtain the strongest patent protection possible, and as such, are aligned and are legal in nature. The Parties agree and acknowledge that they have not waived, and nothing in these Regional License Terms constitutes a waiver of, any legal privilege concerning the Patents Rights under this Section 9, including privilege under the common interest doctrine and similar or related doctrines.

9.7. Trademarks .

(a) Each Party has the right to use any trademark it owns or controls for Regional Licensed Products in its Territory at its sole discretion, and each Party and its Affiliates shall retain all right, title and interest in and to its and their respective corporate names and logos.

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(b) Genzyme will develop and propose, and the PJSC shall review and comment on, one or more Product Trademark(s) for use by Genzyme and its Related Parties throughout the Genzyme Territory. Such Product Trademark(s) considered by the PJSC may include, in Genzyme’s sole discretion, the Product Trademark(s) developed and/or used by Alnylam with respect to the Commercialization of Regional Licensed Products in the Alnylam Territory (the “ Alnylam Trademarks ”), but may not include other trademarks owned or controlled by Alnylam. Any Product Trademark(s) (other than the Alnylam Trademarks) that are used by Genzyme to promote and sell Regional Licensed Products in the Genzyme Territory are hereinafter referred to as the “ Genzyme Trademarks .” Alnylam (or its Related Parties, as appropriate) shall own all rights to Alnylam Trademarks, and all goodwill associated therewith, throughout the Alnylam Territory and the Genzyme Territory. Genzyme (or its Related Parties, as appropriate) shall own all rights to Genzyme Trademarks and all goodwill associated therewith, throughout the Genzyme Territory. Alnylam shall also own rights to any Internet domain names incorporating the applicable Alnylam Trademarks or any variation or part of such Alnylam Trademarks used as its URL address or any part of such address; and Genzyme shall also own rights to any Internet domain names incorporating the applicable Genzyme Trademarks or any variation or part of such Genzyme Trademarks used as its URL address or any part of such address.

(c) If Genzyme determines to use Alnylam Trademarks to promote and sell any Regional Licensed Product in the Genzyme Territory, then Alnylam and Genzyme shall enter into a separate trademark license agreement containing commercially reasonable and customary terms pursuant to which Alnylam will grant Genzyme an exclusive, royalty-free license to use the applicable Alnylam Trademark(s) to Commercialize Regional Licensed Products in the Genzyme Territory.

(d) In the event either Party becomes aware of any infringement of any Product Trademark by a Third Party, such Party shall promptly notify the other Party and the Parties shall consult with each other and jointly determine the best way to prevent such infringement, including by the institution of legal proceedings against such Third Party.

(e) For the avoidance of doubt, neither Party shall have any right to use the other Party’s or the other Party’s Affiliates’ corporate names or logos in connection with Commercialization of Regional Licensed Products.

9.8. Cooperative Research and Technology (CREATE) Act Acknowledgment . It is the intention of the Parties that these Regional License Terms are a “joint research agreement” as that phrase is defined in Section 35 U.S.C. 103(c).

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10. TERM AND TERMINATION

10.1. Term . These Regional License Terms shall be effective as of the Effective Date and, unless terminated earlier pursuant to Section 10.2 (Termination Rights), these Regional License Terms shall continue in effect on a Regional Licensed Product-by-Regional Licensed Product and country-by-country basis until expiration of the last Royalty Term to expire under these Regional License Terms (“ Term ”). Upon expiration of the Royalty Term for any particular Regional Licensed Product, all licenses of the Parties under Section 6 (Licenses) with respect to such Regional Licensed Product then in effect shall become fully paid-up, perpetual licenses.

10.2. Termination Rights . These Regional License Terms may be terminated by the Parties only as set forth in this Section 10.2.

10.2.1. Termination of a Regional Licensed Product for Convenience. Subject to the remainder of this Article 10, Genzyme shall have the right to terminate these Regional License Terms with respect to any particular Regional Licensed Product as follows:

(a) After initiation of the first Phase II Study for such Regional Licensed Product and prior to completion of such Phase II Study for such Regional Licensed Product, Genzyme shall have the right to terminate these Regional License Terms with respect to such Regional Licensed Product upon sixty (60) days prior written notice in the event that a Safety Concern occurs, provided that in the event of such termination Genzyme shall pay to Alnylam [***] of the Global R&D Costs incurred through the effective date of termination (not to exceed [***] wind down any ongoing Phase II Studies with respect to such Regional Licensed Product in an efficient manner consistent with patient safety, applicable Law and ethical standards.

(b) After initiation of the first Phase II Study for such Regional Licensed Product and prior to completion of such Phase II Study for such Regional Licensed Product, Genzyme shall have the right to terminate these Regional License Terms with respect to such Regional Licensed Product for any reason upon written notice (in which case, such termination shall become effective immediately upon Alnylam’s receipt of notice of such termination), provided that in the event of such termination Genzyme shall pay to Alnylam [***] of the Global R&D Costs incurred in any ongoing Phase II Studies for such Regional Licensed Product (not to exceed [***].

(c) Within sixty (60) days of Genzyme’s receipt of the Phase 3 Budget and End of Phase II Package, Genzyme shall have the right to terminate these Regional License Terms with respect to such Regional Licensed Product upon written notice to Alnylam (in which case, such termination shall become effective immediately upon Alnylam’s receipt of notice of such termination), provided that in the event of such termination Genzyme shall pay to Alnylam [***] of the Global R&D Costs incurred through the effective date of termination (not to exceed [***].

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(d) After initiation of the first Phase III Study for such Regional Licensed Product and prior to completion of such Phase III Study for such Regional Licensed Product, Genzyme shall have the right to terminate these Regional License Terms with respect to such Regional Licensed Product upon sixty (60) days prior written notice in the event that a Safety Concern occurs, provided that in the event of such termination Genzyme shall pay to Alnylam [***] of the Global R&D Costs incurred through the effective date of termination (not to exceed [***]) to wind down any ongoing Clinical Studies with respect to such Regional Licensed Product in an efficient manner consistent with patient safety, applicable Law and ethical standards.

(e) After initiation of the first Phase III Study for such Regional Licensed Product and Genzyme’s payment of the Phase III Study initiation milestone payment described in Section 7.1.1.2(i) (Development Milestones for Regional Licensed Products other than ALN-TTR02) (if applicable), Genzyme shall have the right to terminate these Regional License Terms with respect to such Regional Licensed Product at any time upon sixty (60) days prior written notice to Alnylam, provided that in the event of such termination Genzyme shall pay to Alnylam [***] of the Global R&D Costs incurred in conducting any ongoing Phase III Study with respect to such Regional Licensed Product through filing of the first NDA with respect to such Regional Licensed Product (not to exceed[***]).

(f) After completion of the first Phase III Study for such Regional Licensed Product, Genzyme shall have the right to terminate these Regional License Terms with respect to such Regional Licensed Product at any time upon sixty (60) days prior written notice to Alnylam.

10.2.2. Termination of a Regional Licensed Product for Cause. These Regional License Terms may be terminated with respect to any particular Regional Licensed Product at any time during the Term upon written notice by either Party if (a) the other Party is in material breach of its obligations hereunder with respect to such Regional Licensed Product and (b) the other Party has not cured such breach within thirty (30) days in the case of a payment breach, or within ninety (90) days in the case of all other breaches, after notice requesting cure of the breach; provided , however , that if any breach other than a payment breach is not reasonably curable within ninety (90) days and if a Party is making a bona fide effort to cure such breach, such termination shall be delayed for a time period to be agreed by both Parties, not to exceed an additional ninety (90) days, in order to permit such Party a reasonable period of time to cure such breach; and provided , further , that in the event that the breach relates to a dispute between the Parties regarding Genzyme’s obligations to use Commercially Reasonable Efforts in Developing or Commercializing such Regional Licensed Product and Genzyme disputes whether it has breached such obligation or whether such breach gives Alnylam the right to terminate these Regional License Terms with respect to such Regional Licensed Product and initiates a legal action against Alnylam to resolve such dispute within the foregoing sixty (60) day cure period, then these Regional License Terms shall not terminate during the pendency of such legal action, provided that if (i) Genzyme is found, in an unappealable decision by a court of competent

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jurisdiction or an appealable decision of a court of competent jurisdiction that has not been appealed in the time allowed for an appeal in such legal action, to have materially breached these Regional License Terms with respect to such Regional Licensed Product, or (ii) Genzyme admits in such legal action or settlement thereof that it has materially breached these Regional License Terms with respect to such Regional Licensed Product, then these Regional License Terms shall terminate immediately with respect to such Regional Licensed Product following the Parties’ receipt of such decision or immediately following such admission, as applicable.

10.2.3. Termination of Regional Licensed Product upon Exercise of the Co-Co/Global Option in respect of a Regional Licensed Product. These Regional License Terms shall automatically be terminated with respect to a Regional Licensed Product if Genzyme exercises the Co-Co/Global Option in respect of such Regional Licensed Product under Section 3.2.2 of the Master Agreement (Co-Co/Global Option Grant), which termination shall be effective as of the Option Exercise Date for the Co-Co/Global Option. In such event such former Regional Licensed Product shall be a Co-Co Licensed Product or a Global Licensed Product, as applicable, and shall be governed by either the Co-Co License Terms or the Global License Terms.

10.2.4. Challenges of Patent Rights. If, during the Term, Genzyme or any of its Affiliates (a) commences or participates in any action or proceeding (including any patent opposition or re-examination proceeding), or otherwise asserts any claim, challenging or denying the validity or enforceability of any Alnylam Product-Specific Patent or any claim thereof or (b) actively assists any other Person or entity in bringing or prosecuting any action or proceeding (including any patent opposition or re-examination proceeding) challenging or denying the validity or enforceability of any Alnylam Product-Specific Patent for a Regional Licensed Product or any claim thereof (each of (a) and (b), a “ Patent Challenge ”), then, to the extent permitted by the applicable Laws, Alnylam shall have the right, exercisable within sixty (60) days following receipt of notice regarding such Patent Challenge, in its sole discretion, to give notice to Genzyme that Alnylam may terminate these Regional Licensed Terms with respect to the Regional Licensed Product Covered by the Alnylam Product-Specific Patent that is the subject of the Patent Challenge (which termination will be effective ninety (90) days following such notice (or such longer period as Alnylam may designate in such notice)), and, unless Genzyme or such Affiliate withdraws or causes to be withdrawn all such challenge(s) (or in the case of ex-parte proceedings, multi-party proceedings, or other Patent Challenges that Genzyme or Genzyme’s Affiliates do not have the power to unilaterally withdraw or cause to be withdrawn, Genzyme and Genzyme’s Affiliates cease actively assisting any other party to such Patent Challenge and, to the extent Genzyme or a Genzyme Affiliate is a party to such Patent Challenge, it withdraws from such Patent Challenge) within such ninety (90)-day period, Alnylam will have the right to terminate these Regional License Terms with respect to such Regional Licensed Product by providing written notice thereof to Genzyme. The foregoing sentence shall not apply with respect to (i) any Alnylam Product-Specific Patent that Alnylam first asserts against Genzyme or any of its Affiliates where the Patent Challenge is made in defense of such assertion or (ii) any Patent Challenge commenced by a Third Party that, after the Effective Date, acquires or is acquired by Genzyme or its Affiliates or its or their business or assets, whether by stock purchase, merger, asset purchase or otherwise, but only with respect to Patent Challenges commenced prior to the closing of such acquisition.

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10.2.5. Abandonment of Development. At any time on or after [***], either Party may terminate these Regional License Terms in their entirety ( i.e. , with respect to all Regional Licensed Products) if (a) no Regional Licensed Product has received Regulatory Approval anywhere in the Genzyme Territory, (b) no Regional Licensed Product is being Developed for the Genzyme Territory, (c) no Global Development Plan or Genzyme Territory Development Plan is in effect for any Regional Licensed Product, provided that, if Genzyme provides Alnylam with a good faith Genzyme Territory Development Plan pursuant to Section 2.2.4 (Genzyme Territory Development Plan) during the termination notice period set forth below in this Section 10.2.5, then the condition set forth in this clause (c) shall be deemed not satisfied at such time and the applicable termination notice shall be deemed not to have effect, and (d) the absence of Development in the Genzyme Territory or a good faith Genzyme Territory Development Plan is not the result of a breach by the Party seeking to terminate these Regional License Terms of its obligations under Section 2.4 (Diligence). In order to terminate these Regional License Terms pursuant to this Section 10.2.5, the terminating Party must provide at least six (6) months’ prior written notice to the other Party referencing this Section 10.2.5 and specifying a termination date [***], provided that, with respect to any such termination by Alnylam, such notice must also include an update regarding the current status of Alnylam’s Development activities with respect to Regional Licensed Products.

10.3. Effect of Termination .

10.3.1. Effects of Termination by Genzyme for Cause .

10.3.1.1. Effects of Termination of Regional Licensed Product by Genzyme for Cause . Without limiting any other legal or equitable remedies that either Party may have, if these Regional License Terms are terminated by Genzyme with respect to any particular Regional Licensed Product pursuant to Section 10.2.2 (Termination of a Regional Licensed Product for Cause), then:

(a) these Regional License Terms shall continue to survive in all respects with respect to all Regional Licensed Products other than the terminated Regional Licensed Product;

(b) all license grants in these Regional License Terms with respect to the terminated Regional Licensed Product from either Party to the other shall immediately terminate;

(c) Genzyme shall as promptly as practicable transfer to Alnylam or Alnylam’s designee (i) possession and ownership of all Regulatory Approvals and pricing and reimbursement approvals relating to the Development, Manufacture or Commercialization of the terminated Regional Licensed Product, and (ii) copies of all non-clinical and clinical data and material regulatory correspondence relating to the terminated Regional Licensed Product, provided that Alnylam shall reimburse Genzyme for reasonable out-of-pocket expenses incurred by Genzyme in connection with such transfer;

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(d) Genzyme will assign and transfer to Alnylam, all rights, title and interests in and to any Alnylam Product-Specific Patents that relate solely to the terminated Regional Licensed Product that were assigned to Genzyme pursuant to Section 9.3.6 (Assignment of Alnylam Product-Specific Patents to Genzyme), provided that Alnylam shall reimburse Genzyme for reasonable out-of-pocket expenses incurred by Genzyme in connection with such assignment and transfer. In such event, Genzyme will execute and deliver a patent assignment relating to such Alnylam Product-Specific Patents in the same form used to assign such Patent Rights to Genzyme; and

(e) each Party shall promptly pay any amounts owed to the other Party as of the effective date of such termination.

10.3.1.2. Effects of Termination of Regional Licensed Product upon Exercise of the Co-Co/Global Option in respect of a Regional Licensed Product . Simultaneous with the Option Exercise Date for the Co-Co/Global Option in respect of a Regional Licensed Product that is ALN-AT3 or ALN-AS1, these Regional License Terms shall automatically be terminated with respect to such Regional Licensed Product pursuant to Section 10.2.2.3 (Termination of Regional Licensed Product upon Exercise of the Co-Co/Global Option in respect of a Regional Licensed Product), and all license grants in these Regional License Terms from either Party to the other shall immediately terminate with respect to the terminated Regional Licensed Product. In such event such former Regional Licensed Product shall be a Co-Co Licensed Product or a Global Licensed Product, as applicable, and shall be governed by either the Co-Co License Terms or the Global License Terms. For clarity, notwithstanding any such termination, these Regional License Terms shall continue to survive in all respects with respect to all Regional Licensed Products other than such terminated Regional Licensed Product.

10.3.1.3. Effects of Termination of Regional Licensed Product by Alnylam for Cause or by Genzyme for Convenience . Without limiting any other legal or equitable remedies that either Party may have, if these Regional License Terms are terminated with respect to any particular Regional Licensed Product by Genzyme pursuant to Section 10.2.1 (Termination of Regional Licensed Product for Convenience), by Alnylam under Section 10.2.2 (Termination of Regional Licensed Product for Cause) or by Alnylam under Section 10.2.4 (Challenges of Patent Rights), then the provisions of this Section 10.3.1.3 shall apply.

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(a) These Regional License Terms shall continue to survive in all respects with respect to all Regional Licensed Products other than the terminated Regional Licensed Product.

(b) All license grants in these Regional License Terms with respect to the terminated Regional Licensed Product from either Party to the other shall immediately terminate.

(c) Any other siRNAs Developed by Alnylam that target the same human gene as the terminated Regional Licensed Product shall not be considered Option Products for purposes of the Master Agreement; provided , however , that if Alnylam ceases active Development of such terminated Regional Licensed Product upon such termination, then the other siRNAs that target the same human gene as such Regional Licensed Product shall again be considered Option Products for the purposes of the Master Agreement. [***]

(d) Genzyme will grant to Alnylam, effective upon the effective date of termination and subject to the provisions of any applicable Genzyme In-License, a non-transferable, sublicensable (on terms consistent with Section 6.2.4 (Sublicensing Terms)), worldwide, non-exclusive, royalty-free license under any Collaboration IP and Genzyme Patent Rights that Cover the terminated Regional Licensed Product, in the form that such terminated Regional Licensed Product exists on the effective date of termination (a “ Reverted Regional Licensed Product ”), solely to the extent necessary to Develop and Commercialize the Reverted Regional Licensed Product in the Field in the Genzyme Territory. Notwithstanding the foregoing, if (i) any Patent Rights that Cover the Reverted Regional Licensed Product are Controlled by Genzyme pursuant to a Genzyme In-License and (ii) such Genzyme In-License cannot be assigned to Alnylam or does not relate exclusively to the Reverted Regional Licensed Product, Genzyme shall promptly disclose any payment obligations under such Genzyme In-License to Alnylam and such Genzyme Patent Rights shall be subject to the license granted in this Section 10.3.1.3(d) only if Alnylam agrees in writing to (A) reimburse Genzyme for one hundred percent (100%) of any amounts that become payable under such Genzyme In-License as a result of Alnylam’s exercise of the license granted in this Section 10.3.1.3(b), (B) comply with all applicable terms and conditions of such Genzyme In-License and (C) perform and take such actions as may be required to allow Genzyme to comply with its obligations under such Genzyme In-License.

(e) Genzyme will assign and transfer to Alnylam, all rights, title and interests in and to any Alnylam Product-Specific Patents that relate solely to the Reverted Regional Licensed Product that were assigned to Genzyme pursuant to Section 9.3.6 (Assignment of Alnylam Product-Specific Patents to Genzyme). In such event, Genzyme will execute and deliver a patent assignment relating to such Alnylam Product-Specific Patents in the same form used to assign such Patent Rights to Genzyme.

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(f) The license grants to Alnylam in Section 6.2 (License Grants to Alnylam) shall survive and shall be expanded to include the Genzyme Territory with respect to the Reverted Regional Licensed Product.

(g) Genzyme shall as promptly as practicable transfer to Alnylam or Alnylam’s designee (i) possession and ownership of all governmental or regulatory correspondence, conversation logs, filings and approvals (including all Regulatory Approvals and pricing and reimbursement approvals) solely relating to the Development, Manufacture or Commercialization of the Reverted Regional Licensed Product, (ii) copies of all data, reports, records and materials, and other sales and marketing related information in Genzyme’s possession or Control to the extent that such data, reports, records, materials or other information relate to the Development, Manufacture or Commercialization of the Reverted Regional Licensed Product, including all non-clinical and clinical data relating to the Reverted Regional Licensed Product, and customer lists and customer contact information and all adverse event data related to the Reverted Regional Licensed Product in Genzyme’s possession or Control, provided that, for a period of [***] months after the effective date of termination with respect to such Reverted Regional Licensed Product, Genzyme shall use Commercially Reasonable Efforts to obtain for Alnylam the right to access all such data, reports, records, materials, and other sales and marketing related information related to the Reverted Regional Licensed Product, and (iii) all records and materials in Genzyme’s possession or Control containing Confidential Information of Alnylam solely relating to the Reverted Regional Licensed Product. In addition, Genzyme shall appoint Alnylam as Genzyme’s and/or Genzyme’s Related Parties’ agent for all matters related to the Reverted Regional Licensed Product involving Regulatory Authorities in the Genzyme Territory until all Regulatory Approvals and other regulatory filings have been transferred to Alnylam or its designee.

(h) If the effective date of termination is after First Commercial Sale of the Reverted Regional Licensed Product, then Genzyme shall appoint Alnylam as its exclusive distributor of such Reverted Regional Licensed Product in the Genzyme Territory and grant Alnylam the right to appoint sub-distributors, until such time as all Regulatory Approvals in the Genzyme Territory have been transferred to Alnylam or its designee.

(i) If Genzyme or its Related Parties are Manufacturing finished product with respect to the Reverted Regional Licensed Product on the effective date of termination, at Alnylam’s option, Genzyme or its Related Parties shall supply such finished product to Alnylam in the Genzyme Territory on terms no less favorable than those on which Genzyme supplied such finished product prior to such termination to its most favored distributor in the Genzyme Territory, until the earlier of (i) such time as all Regulatory Approvals in the Genzyme Territory solely related to the Reverted Regional Licensed Product have been transferred to Alnylam or its designee, Alnylam has obtained all necessary manufacturing approvals and Alnylam has procured or developed its own source of such finished product supply or (ii) [***] months following the effective date of such termination.

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(j) If Alnylam so requests, and to the extent permitted under Genzyme’s obligations to Third Parties on the effective date of termination, Genzyme shall transfer to Alnylam any Third Party agreements relating solely and exclusively to the Development, Manufacture or Commercialization of the Reverted Regional Licensed Product to which Genzyme is a party (including any Genzyme In-License), subject to any required consents of such Third Party, which Genzyme shall use Commercially Reasonable Efforts to obtain promptly;

(k) Genzyme shall promptly transfer and assign to Alnylam all of Genzyme’s and its Affiliates’ rights, title and interests in and to the Genzyme Trademark(s) (but not any Genzyme house marks or any trademark containing the word “Genzyme” owned by Genzyme and used for the Reverted Regional Licensed Product in the Field in the Genzyme Territory) owned by Genzyme and used solely and exclusively for the Reverted Regional Licensed Products in the Field in the Genzyme Territory.

(l) Genzyme shall transfer to Alnylam any inventory of the Reverted Regional Licensed Products Controlled by Genzyme or its Affiliates as of the termination date at the actual price paid by Genzyme for such supply.

(m) Genzyme shall provide any other assistance reasonably requested by Alnylam for the purpose of allowing Alnylam or its designee to proceed expeditiously with the Development, Manufacture and Commercialization of the Reverted Regional Licensed Product in the Genzyme Territory, provided that Genzyme’s obligations under this clause (m) of Section 10.3.1.3 shall expire [***] months after the effective date of termination of such Reverted Regional Licensed Product.

(n) Genzyme shall execute all documents and take all such further actions as may be reasonably requested by Alnylam in order to give effect to the foregoing clauses.

10.3.2. Effects of Termination for Abandonment of Development. If these Regional License Terms are terminated in their entirety ( i.e. , with respect to all Regional Licensed Products) by either Party pursuant to Section 10.2.5 (Abandonment of Development), then the license granted to Alnylam under Section 6.2.2 (License to Improvement Manufacturing Patent Rights) shall survive and all other licenses granted in these Regional License Terms from either Party to the other shall immediately terminate and:

(a) Any other siRNAs Developed by Alnylam that target the same human gene as the terminated Regional Licensed Product shall not be considered Option Products for purposes of the Master Agreement; provided , however , that if Alnylam ceases active Development of such terminated Regional Licensed Product upon such termination, then the other siRNAs that target the same human gene as such Regional Licensed Product shall again be considered Option Products for the purposes of the Master Agreement. [***]

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(b) Genzyme shall as promptly as practicable transfer to Alnylam or Alnylam’s designee (i) possession and ownership of all Regulatory Approvals and pricing and reimbursement approvals relating to the Development, Manufacture or Commercialization of the terminated Regional Licensed Product, and (ii) copies of all non-clinical and clinical data and material regulatory correspondence relating to the terminated Regional Licensed Product.

(c) Genzyme will assign and transfer to Alnylam, all rights, title and interests in and to any Alnylam Product-Specific Patents that relate solely to the terminated Regional Licensed Product that were assigned to Genzyme pursuant to Section 9.3.6 (Assignment of Alnylam Product-Specific Patents to Genzyme). In such event, Genzyme will execute and deliver a patent assignment relating to such Alnylam Product-Specific Patents in the same form used to assign such Patent Rights to Genzyme.

(d) each Party shall promptly pay any amounts owed to the other Party as of the effective date of such termination.

10.4. Fundamental Breach of Alnylam’s Development Obligations . Without limiting Genzyme’s rights under Section 10.2.2 (Termination of a Regional Licensed Product for Cause) with respect to other material breaches, in the event that Alnylam commits a Fundamental Breach of its Development obligations under Section 2.4.2 (Alnylam Diligence) with respect to any particular Regional Licensed Product, and Genzyme does not terminate these Regional License Terms in their entirety ( i.e. , with respect to all Regional Licensed Products) or with respect to such Regional Licensed Product for cause pursuant to Section 10.2.2 (Termination of a Regional Licensed Product for Cause), then Genzyme may elect to receive the following remedies for such Fundamental Breach:

10.4.1.1. Genzyme’s obligation to pay development milestone fees under Section 7.1 (Milestone Fees) with respect to such Regional Licensed Product shall automatically terminate;

10.4.1.2. Genzyme will receive a credit, which Genzyme may offset against royalties and sales milestones due to Alnylam with respect to such Regional Licensed Product pursuant to Section 7 (Certain Financial Terms), in an amount equal to one hundred fifty percent (150%) of all costs and expenses (i) incurred by Genzyme to Develop such Regional Licensed Product for the Genzyme Territory that are in excess of the costs budgeted by Genzyme in connection with the Genzyme Territory Development Plan for such Regional Licensed Product in effect at the time of Alnylam’s Fundamental Breach of Section 2.4.2 (Alnylam Diligence) with respect to such Regional Licensed Product and (ii) are incurred by Genzyme as a direct consequence of Alnylam’s Fundamental Breach of Section 2.4.2 (Alnylam Diligence) with respect to such Regional Licensed Product;

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10.4.1.3. Genzyme may, in its discretion, terminate any or all of the following provisions of these Regional License Terms (or any subsection thereof) with respect to such Regional Licensed Product: Section 3.1.3 (Regulatory Meetings), Section 4.1.3 (Joint Commercialization), Section 4.3 (Genzyme Territory Commercialization Plan), Section 4.4 (Alnylam Territory Commercialization Plan), Section 4.5 (Advertising and Promotional Materials), Section 4.6 (Commercialization Reporting Obligations), and Section 5 (Collaboration Management); and

10.4.1.4. Without limiting Genzyme’s remedies under these Regional License Terms or otherwise with respect to breaches of Alnylam’s Development obligations under clause (a) of Section 2.4.2 (Alnylam Diligence) other than Fundamental Breaches, if Genzyme elects to receive the remedies set forth in this Section 10.4 with respect to a Fundamental Breach of its Development obligations under clause (a) of Section 2.4.2 (Alnylam Diligence) with respect to such Regional Licensed Product, such remedies shall be Genzyme’s sole and exclusive remedies with respect to such Fundamental Breach and Genzyme shall have no right to seek any further remedies or damages against Alnylam and its Affiliates with respect to such Fundamental Breach by Alnylam of clause (a) of Section 2.4.2 (Alnylam Diligence).

10.5. Effect of Expiration or Termination; Survival . Any expiration or termination of these Regional License Terms (a) shall not relieve the Parties of any obligation accruing prior to such expiration or termination and (b) shall be without prejudice to the rights of either Party against the other Party accrued or accruing under these Regional License Terms prior to such expiration or termination, including the obligation to pay royalties for any Regional Licensed Product sold prior to such expiration or termination. The following provisions shall survive any expiration or termination of these Regional License Terms in their entirety ( i.e. , with respect to all Regional Licensed Products) and, if these Regional License Terms expire or are terminated with respect to any particular Regional Licensed Product, shall survive with respect to such Regional Licensed Product: (a) Sections 1 (Definitions), 8.3 (Warranty Disclaimer), 9.1 (Inventorship), 9.2 (Ownership), 10.3 (Effect of Termination), 10.5 (Effect of Termination or Expiration; Survival) and Section 11 (Performance by Affiliates) of these Regional License Terms and (b) Sections 1 (Definitions), 7 (Confidentiality and Publication), 9 (Royalty Reports; Payments; Audit), 10 (Indemnification; Limitation of Liability; Insurance), 12 (Term and Termination) and 13 (Miscellaneous) of the Master Agreement. Section 7.2.6 (Royalty Floor) shall survive any termination or expiration of these Regional License Terms with respect to any Regional Licensed Product for royalties accruing prior to such termination or expiration. Section 9 of the Master Agreement (Royalty Reports; Payments; Audit) will survive for so long as any royalties are due under these Regional License Terms plus three (3) years. Except as otherwise set forth in this Section 10 or elsewhere in these Regional License Terms, upon termination or

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expiration of these Regional License Terms in their entirety, all rights and obligations of the Parties under these Regional License Terms shall cease, but, for clarity, expiration or termination of these Regional License Terms in their entirety ( i.e. , with respect to all Regional Licensed Products) shall not result in the termination or expiration of the Master Agreement or any License Terms. Upon termination or expiration of these Regional License Terms with respect to any particular Regional Licensed Product, all rights and obligations of the Parties under these Regional License Terms with respect to such Regional Licensed Product shall cease except as otherwise set forth in this Section 10 or elsewhere in these Regional License Terms, but, for clarity, such termination or expiration shall not affect the Parties’ rights and obligations under these Regional License Terms with respect to any other Regional Licensed Product.

11. PERFORMANCE BY AFFILIATES

11.1. Use of Affiliates . Each Party acknowledges and accepts that the other Party may exercise its rights and perform its obligations under these Regional License Terms either directly or through one or more of its Affiliates. A Party’s Affiliates will have the benefit of all rights (including all licenses) of such Party under these Regional License Terms. Accordingly, in these Regional License Terms “Genzyme” will be interpreted to mean “Genzyme and/or its Affiliates” and “Alnylam” will be interpreted to mean “Alnylam and/or its Affiliates” where necessary to give each Party’s Affiliates the benefit of the rights provided to such Party in these Regional License Terms; provided , however , that in any event each Party will remain responsible for the acts and omissions, including financial liabilities, of its Affiliates.

11.2. Future Acquisition of a Party or its Business . [***]

11.3. Acquired Programs .

11.3.1. [***]

11.3.2. [***]

11.4. For clarity, upon the closing of the acquisition of the stock and/or assets of Sirna Therapeutics, Inc. by Alnylam from Merck Sharpe & Dohme Corp., all relevant acquired intellectual property rights acquired in such transaction that may be Controlled by Alnylam (without any further action by Alnylam or Sirna Therapeutics, Inc.) shall become Controlled by Alnylam for the purposes of these Regional License Terms.

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Schedule 1.2.13-1

ALNYLAM CORE TECHNOLOGY PATENTS FOR ALN-TTR02

See attached.

[***]

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Schedule 1.2.18-1

ALNYLAM PRODUCT-SPECIFIC PATENTS FOR ALN-TTR02

See attached.

[***]

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Schedule 2.2.1-1

GLOBAL DEVELOPMENT STRATEGY FOR ALN-TTR02

(To be attached when developed pursuant to Section 2.2.1)

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Schedule 2.2.2.1-1

GLOBAL DEVELOPMENT PLAN FOR ALN-TTR02

(To be attached when developed pursuant to Section 2.2.2.1)

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Schedule 2.2.2.6(d)-1

ALNYLAM TERRITORY DEVELOPMENT PLAN FOR ALN-TTR02

(To be attached when developed pursuant to Section 2.2.2.6(d).)

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Schedule 2.2.4-1

GENZYME TERRITORY DEVELOPMENT PLAN FOR ALN-TTR02

(To be attached when developed pursuant to Section 2.2.4.)

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Schedule 8.1

DISCLOSURE SCHEDULE

See attached.

Confidential

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Confidential Materials omitted and filed separately with the Securities and Exchange Commission. A total of 2 pages were omitted.

[***]

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Schedule 8.1.12

(A) EXISTING ALNYLAM IN-LICENSES

(To be attached)

(B) ADDITIONAL ALNYLAM INLICENSES

(To be attached)

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Schedule 8.4.1.3(c)

EXCEPTIONS TO EXCLUSIVITY

Confidential Materials omitted and filed separately with the Securities and Exchange Commission. A total of 1 page was omitted.

[***]

APPENDIX B

GLOBAL PRODUCT LICENSE AND COLLABORATION TERMS

AN APPENDIX TO THE MASTER COLLABORATION AGREEMENT

dated as of January 11, 2014

by and between

ALNYLAM PHARMACEUTICALS, INC.

and

GENZYME CORPORATION

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TABLE OF CONTENTS


	Page
1. RELATIONSHIP WITH MASTER AGREEMENT; DEFINITIONS		1

1.1 Relationship with Master Agreement		1
1.2 Definitions		2

2. DEVELOPMENT		16

2.1 Overview		16
2.2 Transition		16
2.3 Global Development Plan		17
2.4 Development Costs		17
2.5 Diligence		18
2.6 Records; Reports; Information Sharing		18
2.7 Third Parties		19

3. REGULATORY MATTERS		20

3.1 Regulatory Filings and Interactions		20
3.2 Costs of Regulatory Affairs		21
3.3 Right of Reference		21

4. COMMERCIALIZATION OF THE GLOBAL LICENSED PRODUCTS		21

4.1 Responsibility, Cost and Diligence		21
4.2 Commercialization Summary		21
4.3 First Commercial Sale Reporting Obligations		21
4.4 Advertising and Promotional Materials		21
4.5 Sales and Distribution		22
4.6 Recalls, Market Withdrawals or Corrective Actions		22

5. TRANSITION MANAGEMENT		22

5.1 Joint Transition Team		22
5.2 Meetings		23
5.3 Minutes		23
5.4 JTT Responsibilities		23
5.5 Decision-Making		23
5.6 Term of JTT		24

6. MANUFACTURE AND SUPPLY OF THE GLOBAL LICENSED PRODUCTS		24

6.1 Manufacturing and Supply		24

7. LICENSES		24

7.1 License Grants to Genzyme		24

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7.2 License Grants to Alnylam			27
7.3 Joint Collaboration IP			28
7.4 In-Licenses			28
7.5 Right of First Negotiation			28
7.6 Bankruptcy			29
7.7 No Other Rights			30

8. CERTAIN FINANCIAL TERMS			30

8.1 Milestone Fees			30
8.2 Royalties			32

9. REPRESENTATIONS, WARRANTIES AND COVENANTS			35

9.1 Representations and Warranties of Alnylam			35
9.2 Representations and Warranties of Genzyme			37
9.3 Warranty Disclaimer			37
9.4 Certain Covenants			37

10. INTELLECTUAL PROPERTY OWNERSHIP, PROTECTION AND RELATED MATTERS			38

10.1 Inventorship			38
10.2 Ownership			38
10.3 Prosecution and Maintenance of Patent Rights			39
10.4 Third Party Infringement			43
10.5 Patent Term Extensions			45
10.6 Common Interest			46
10.7 Trademarks			46
10.8 Cooperative Research and Technology (CREATE) Act Acknowledgment			46

11. TERM AND TERMINATION			47

11.1 Term			47
11.2 Termination Rights			47
11.3 Effect of Termination			48
11.4 Effect of Expiration or Termination; Survival			51

12. PERFORMANCE BY AFFILIATES			52

12.1 Use of Affiliates			52
12.2 Future Acquisition of a Party or its Business			52
12.3 Acquired Programs			52

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SCHEDULES


Schedule 1.2.8		Alnylam Core Technology Patents

Schedule 1.2.15		Alnylam Product-Specific Patents

Schedule 1.2.96		Licensed Target

Schedule 9.1		Disclosure Schedule

Schedule 9.1.12		Existing Alnylam In-Licenses / Additional Alnylam In-Licenses

Schedule 9.4.1(e)		Exceptions to Exclusivity

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GLOBAL PRODUCT LICENSE AND COLLABORATION TERMS

THESE GLOBAL PRODUCT LICENSE AND COLLABORATION TERMS are Appendix B to the Master Collaboration Agreement, dated as of the Execution Date, by and between Alnylam Pharmaceuticals, Inc., a corporation organized and existing under the laws of the State of Delaware (“ Alnylam ”), and Genzyme Corporation, a corporation organized and existing under the laws of the Commonwealth of Massachusetts (“ Genzyme ”).

RECITALS:

WHEREAS , Alnylam and Genzyme are parties to that certain Master Collaboration Agreement (dated as of the Execution Date) (the “ Master Agreement ”) pursuant to which Genzyme has options to receive licenses and other rights with respect to up to two Global Licensed Products from Alnylam in the Licensed Territory;

WHEREAS , Genzyme may exercise its Co-Co/Global Option pursuant to the Master Agreement for ALN-AS1 and such siRNA will then become a Global Licensed Product;

WHEREAS , Genzyme may exercise its Global Option or Trailing Global Option pursuant to the Master Agreement for any Global Option Product thereunder and such Global Option Product will then be deemed a Global Licensed Product;

WHEREAS , if Genzyme does not exercise the Co-Co/Global Option pursuant to the Master Agreement for ALN-AS1 or ALN-AT3, Genzyme may exercise its Additional Global Option pursuant to the Master Agreement for any Global Option Product thereunder and such Global Option Product will then be deemed a Global Licensed Product; and

WHEREAS , Alnylam and Genzyme now wish to set forth the terms and conditions under which Genzyme will have the right to Commercialize such Global Licensed Products in the Licensed Territory.

NOW, THEREFORE , in consideration of the foregoing premises and the mutual covenants herein contained, the Parties hereby agree as follows:

1.	RELATIONSHIP WITH MASTER AGREEMENT; DEFINITIONS

1.1 Relationship with Master Agreement. These Global License Terms become effective on a Global Licensed Product-by-Global Licensed Product basis on the Implementation Date in accordance with the Master Agreement. The Master Agreement generally governs the Parties’ relationship with respect to Global Licensed Products during the period of time before Genzyme exercises its Co-Co/Global Option, Global Option or Additional Global Option under the Master Agreement ( i.e ., before such product became a Global Licensed Product). The Master Agreement also contains terms that are generally applicable to Global Licensed Products, Regional Licensed Products (as defined in the Master Agreement) and Co-Co Licensed Products (as defined in the Master Agreement). Accordingly, the following Sections of the Master Agreement are

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incorporated herein by reference: Section 2.2 (Effectiveness of Licenses to Collaboration Products); Section 5 (Collaboration Management); Section 6 (Manufacture and Supply of the Collaboration Products); Section 7 (Confidentiality and Publication); Section 9 (Royalty Reports; Payments; Audit); Section 10 (Indemnification; Limitation of Liability; Insurance); Section 12.2.4 (Challenges of Patent Rights); and Section 13 (Miscellaneous).

1.2 Definitions. Unless specifically set forth to the contrary herein, the following terms, whether used in the singular or plural, shall have the respective meanings set forth below:

1.2.1 “ Acquired Business ” has the meaning set forth in Section 12.3 (Acquired Programs).

1.2.2 “ Acquirer ” has the meaning set forth in Section 12.2 (Future Acquisition of a Party or its Business).

1.2.3 “ Additional Alnylam In-Licenses ” has the meaning set forth in the Master Agreement.

1.2.4 “ Additional Global Option ” has the meaning set forth in the Master Agreement.

1.2.5 “ AF11 Lipid Nanoparticle Formulation” has the meaning set forth in the Master Agreement.

1.2.6 “ Affiliate ” means, with respect to a Person, any other Person which controls, is controlled by, or is under common control with the applicable Person. For purposes of this definition, “control” means: (a) in the case of corporate entities, direct or indirect ownership of at least fifty percent (50%) of the stock or shares entitled to vote for the election of directors, or otherwise having the power to control or direct the affairs of such Person; and (b) in the case of non-corporate entities, direct or indirect ownership of at least fifty percent (50%) of the equity interest or the power to direct the management and policies of such non-corporate entities.

1.2.7 “ AJSC ” has the meaning set forth in the Master Agreement.

1.2.8 “ ALN-AS1 ” has the meaning set forth in the Master Agreement.

1.2.9 “ ALN-AT3 ” has the meaning set forth in the Master Agreement.

1.2.10 “ Alnylam Core Technology Patents ” means Patent Rights Controlled by Alnylam during the Term that are [***]. The Alnylam Core Technology Patents existing as of the Implementation Date for any Global Licensed Product will be identified as the “Alnylam Core Technology Patents” in the Option Data Package for such Global Licensed Product provided by Alnylam to Genzyme under the Master Agreement and then attached hereto as Schedules 1.2.8-1 and 1.2.8-2 , if applicable.

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1.2.11 “ Alnylam Developed siRNA Product ” means an siRNA with respect to which (a) Alnylam Controls Patent Rights Covering such siRNA, provided that once a product first satisfies the criterion set forth in this clause (a) such criterion shall be deemed satisfied at all times thereafter as to such product; and (b) Alnylam or an Affiliate of Alnylam plays(ed) a material role in the Development.

1.2.12 “ Alnylam In-License ” means any Existing Alnylam In-License or any Collaboration In-License to which Alnylam is a party.

1.2.13 “ Alnylam Know-How ” means Know-How Controlled by Alnylam during the Term that is reasonably necessary or useful for Genzyme to Develop, Manufacture and/or Commercialize Global Licensed Products in the Field in the Licensed Territory, other than Alnylam’s interest in Know-How included in Joint Collaboration IP.

1.2.14 “ Alnylam Patents ” means Alnylam Core Technology Patents and Alnylam Product-Specific Patents.

1.2.15 “ Alnylam Product-Specific Patents ” means Patent Rights Controlled by Alnylam during the Term that claim [***] . The Alnylam Product-Specific Patents existing as of the Implementation Date for any Global Licensed Product will be identified as the “Alnylam Product-Specific Patents” in the Option Data Package for such Global Licensed Product provided by Alnylam to Genzyme under the Master Agreement and then attached hereto as Schedules 1.2.15-2 and 1.2.15-3 , if applicable. [***]

1.2.16 “ Alnylam Technology ” means, collectively, Alnylam Know-How, Alnylam Patents and Alnylam’s interest in Joint Collaboration IP.

1.2.17 “ Alnylam Trademark ” has the meaning set forth in Section 10.7(a) (Trademarks).

1.2.18 “ ANDA ” means an Abbreviated New Drug Application (or any successor application or procedure) as defined in regulations promulgated by the FDA under the FDCA, which ANDA is filed with or intended to be filed with the FDA (and, as applicable, any other analogous application filed with a Regulatory Authority in any country other than the U.S. in the Licensed Territory) for Regulatory Approval for marketing and selling a Global Licensed Product in the Licensed Territory.

1.2.19 “ Back-Up Option ” has the meaning set forth in Section 7.1.5 (Back-Up Products).

1.2.20 “ Back-Up Option Exercise Notice ” has the meaning set forth in Section 7.1.5 (Back-Up Products).

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1.2.21 “ Back-Up Option Period ” means [***].

1.2.22 “ Back-Up Product ” has the meaning set forth in Section 7.1.5 (Back-Up Products).

1.2.23 “ Bankrupt Party ” has the meaning set forth in Section 7.6 (Bankruptcy).

1.2.24 “ Calendar Quarter ” means the respective periods of three (3) consecutive calendar months ending on March 31, June 30, September 30 and December 31 of each Calendar Year, provided that (a) the first Calendar Quarter of the Term shall begin on the Effective Date and end on the first to occur of March 31, June 30, September 30 or December 31 thereafter and the last Calendar Quarter of the Term shall end on the last day of the Term and (b) the first Calendar Quarter of a Royalty Term for a Global Licensed Product in a country shall begin on the First Commercial Sale of a Global Licensed Product in such country and end on the first to occur of March 31, June 30, September 30 or December 31 thereafter and the last Calendar Quarter of a Royalty Term shall end on the last day of such Royalty Term.

1.2.25 “ Calendar Year ” means each successive period of twelve (12) months commencing on January 1 and ending on December 31, provided that (a) the first Calendar Year of the Term shall begin on the Effective Date and end on the first December 31 thereafter and the last Calendar Year of the Term shall end on the last day of the Term and (b) the first Calendar Year of a Royalty Term for a Global Licensed Product in a country shall begin on the First Commercial Sale of a Global Licensed Product in such country and end on the first December 31 thereafter and the last Calendar Year of the Term shall end on the last day of such Royalty Term.

1.2.26 “ Carbohydrate Conjugate ” has the meaning set forth in the Master Agreement.

1.2.27 “ Clinical Study ” has the meaning set forth in the Master Agreement.

1.2.28 “ Co-Co/Global Option” has the meaning set forth in the Master Agreement.

1.2.29 “ Co-Co/Global Option Product ” has the meaning set forth in the Master Agreement.

1.2.30 “ Collaboration ” has the meaning set forth in the Master Agreement.

1.2.31 “ Collaboration In-License ” has the meaning set forth in the Master Agreement.

1.2.32 “ Collaboration Product ” has the meaning set forth in the Master Agreement.

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1.2.33 “ Commercialization ” or “ Commercialize ” has the meaning set forth in the Master Agreement.

1.2.34 “ Commercialization Summary ” has the meaning set forth in Section 4.2 (Commercialization Summary).

1.2.35 “ Commercially Reasonable Efforts ” means [***].

1.2.36 “ Competing Program ” has the meaning set forth in Section 12.3.1 (Acquired Programs).

1.2.37 “ Competitive Infringement ” has the meaning set forth in Section 10.4.1 (Notices).

1.2.38 “ Confidential Information ” has the meaning set forth in the Master Agreement.

1.2.39 “ Control ”, “ Controls ” or “ Controlled by ” has the meaning set forth in the Master Agreement.

1.2.40 “Cost of Goods ” has the meaning set forth in the Master Agreement.

1.2.41 “ Cover ,” “ Covering ” or “ Covers ” has the meaning set forth in the Master Agreement.

1.2.42 “ CPI ” means the Consumer Price Index – Urban Wage Earners and Clerical Workers, U.S. City Average, All Items, 1982-84 = 100, published by the United States Department of Labor, Bureau of Labor Statistics (or its successor equivalent index) in the United States.

1.2.43 “ Development ,” “ Developing ” or “ Develop ” has the meaning set forth in the Master Agreement.

1.2.44 “ Development Information ” has the meaning set forth in Section 2.2 (Transition).

1.2.45 “ Effective Date ” means the date that the Master Agreement becomes effective in accordance with its terms.

1.2.46 “ EMA ” means the European Medicines Agency and any successor Governmental Authority having substantially the same function.

1.2.47 “ EU ” means the European Union, as its membership may be altered from time to time, and any successor thereto.

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1.2.48 “ Exclusivity Period ” means, on a Global Licensed Product-by-Global Licensed Product and country-by-country basis within the Licensed Territory, the period of time commencing on the Implementation Date for such Global Licensed Product and continuing until the first to occur of (a) [***].

1.2.49 “ Existing Alnylam In-License ” has the meaning set forth in the Master Agreement.

1.2.50 “ Execution Date ” has the meaning set forth in the Master Agreement.

1.2.51 “ Exercise Notice ” has the meaning set forth in the Master Agreement.

1.2.52 “ Existing Genzyme In-License ” has the meaning set forth in the Master Agreement.

1.2.53 “ FDA ” means the United States Food and Drug Administration and any successor Governmental Authority having substantially the same function.

1.2.54 “ FDCA ” means the United States Federal Food, Drug, and Cosmetic Act of 1938, as amended from time to time, and the regulations and guidelines promulgated thereunder.

1.2.55 “ Field ” means the treatment, diagnosis and/or prevention of all human diseases.

1.2.56 “ First Commercial Sale ” means, with respect to a country, the first sale for end use or consumption of a Global Licensed Product in such country, except for compassionate use or patient access programs, after all Regulatory Approvals legally required for such sale have been granted by the Regulatory Authority of such country.

1.2.57 “ First Regulatory Approval by the EMA ” means, with respect to a Global Licensed Product, the earlier of (i) if Regulatory Approval in the EU is sought through the EMA centralized procedure, receipt of Regulatory Approval for such Global Licensed Product from the EMA or (ii) if Regulatory Approval in the EU is sought through a national authorization procedure, receipt of Regulatory Approval for such Global Licensed Product in the first (1 ^st ) MMC in the EU.

1.2.58 “ First Regulatory Approval in Japan ” means, with respect to a Global Licensed Product, receipt of Regulatory Approval for such Global Licensed Product in Japan.

1.2.59 “ GalNAc Conjugate ” has the meaning set forth in the Master Agreement.

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1.2.60 “ Generic Competition ” means, with respect to a Global Licensed Product in any country in the Licensed Territory in a given Calendar Quarter, that, during such Calendar Quarter, (a) one or more Generic Products with respect to such Global Licensed Product are commercially available in such country, and (b) Net Sales of such Global Licensed Product in such country in such Calendar Quarter equal less than [***] of the average Net Sales of such Global Licensed Product over the [***] consecutive Calendar Quarters immediately prior to the Calendar Quarter in which one or more Generic Products first became commercially available in such country.

1.2.61 “ Generic Product ” means, on a Global Licensed Product-by-Global Licensed Product and country-by-country basis, a pharmaceutical product that (a) is sold by a Person that is not a Related Party of Genzyme under a marketing authorization granted by a Regulatory Authority in such country to a Third Party; (b) [***] and (c) is approved by the Regulatory Authority in such country pursuant to an approval process that relies in part on pivotal safety and/or efficacy data in such Regulatory Authority’s previous grant of marketing authorization for such Global Licensed Product.

1.2.62 “ Genzyme Collaboration IP ” means (a) any Know-How, first identified, discovered or developed solely by employees of Genzyme or its Affiliates or other persons not employed by Alnylam acting on behalf of Genzyme, in the conduct of the Collaboration and (b) any Patent Rights that claim or cover such Know-How and are Controlled by Genzyme at any time during the Term. Genzyme Collaboration IP excludes Genzyme’s interest in Joint Collaboration IP, in each case (a) and (b), other than Genzyme Manufacturing IP.

1.2.63 “ Genzyme Disclosed Manufacturing Know-How ” means Know-How (a) Controlled by Genzyme at any time during the Term that is useful in the Manufacture of a Global Licensed Product and (b) that Genzyme, in its sole discretion, discloses in writing to Alnylam in the course of the Collaboration.

1.2.64 “ Genzyme In-License ” means any Existing Genzyme In-License, Un-Blocking Genzyme In-License or any Collaboration In-License to which Genzyme is a party.

1.2.65 “ Genzyme Know-How ” means Know-How Controlled by Genzyme during the Term that is reasonably necessary or useful for Alnylam to Develop, Commercialize and/or Manufacture Global Licensed Products in the Field in the Licensed Territory (other than Genzyme’s rights in Joint Collaboration IP, Genzyme Collaboration IP and Genzyme Manufacturing IP).

1.2.66 “ Genzyme Manufacturing IP ” means (a) any Know-How related to the Manufacture of Global Licensed Products (or oligonucleotides generally) Controlled by Genzyme at any time during the Term, and (b) any Patent Rights that claim or cover such Know-How and are Controlled by Genzyme at any time during the Term, excluding Improvement Manufacturing Patent Rights and Genzyme Disclosed Manufacturing Know-How.

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1.2.67 “ Genzyme Patent Jurisdictions ” has the meaning set forth in the Master Agreement.

1.2.68 “ Genzyme Patent Rights ” means those Patent Rights Controlled by Genzyme during the Term that are reasonably necessary or useful to Develop, Commercialize and/or Manufacture Global Licensed Products in the Field in the Licensed Territory. Genzyme Patent Rights excludes Patent Rights included in Genzyme Collaboration IP, Genzyme’s interest in Joint Collaboration IP and Genzyme Manufacturing IP.

1.2.69 “Genzyme Technology ” means, collectively, Genzyme Know-How, Genzyme Patent Rights, Genzyme Collaboration IP and Genzyme’s interest in Joint Collaboration IP, but excluding Genzyme Manufacturing IP.

1.2.70 “ Genzyme Trademarks ” has the meaning set forth in Section 10.7(a) (Trademarks).

1.2.71 “ Global Branding Strategy ” has the meaning set forth in Section 4.4.1 (Global Branding).

1.2.72 “ Global Development Plan ” has the meaning set forth in Section 2.3 (Global Development Plan).

1.2.73 “ Global License Terms ” means this Appendix B to the Master Agreement (Global Product License and Collaboration Terms) and the provisions of the Master Agreement to the extent applicable to Global Licensed Products.

1.2.74 “ Global Licensed Product ” means (i) if Genzyme exercises the Co-Co/Global Options for ALN-AS1 pursuant to the Master Agreement, then ALN-AS1 as of the applicable Option Exercise Date, (ii) if Genzyme exercises the Global Option or the Trailing Global Option for any Global Option Product pursuant to the Master Agreement, then such Global Option Product as of the applicable Option Exercise Date, (iii) if Genzyme exercises the Additional Global Option for any Global Option Product pursuant to the Master Agreement, then such Global Option Product as of the applicable Option Exercise Date, and (iv) if Genzyme exercises a Back-Up Option for any Back-Up Product pursuant to Section 7.1.5 (Back-Up Products), then such Back-Up Product as of the date of delivery of the Back-Up Option Exercise Notice, in each case (i) through (iv) above, for as long as the Global License Terms apply to ALN-AS1, such Global Option Product or such Back-Up Product.

1.2.75 “ Global Option ” has the meaning set forth in the Master Agreement.

1.2.76 “ Global Option Period ” has the meaning set forth in the Master Agreement.

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1.2.77 “ Global Option Product” has the meaning set forth in the Master Agreement.

1.2.78 “ Global Out-of-Pocket Costs ” means, with respect to certain activities hereunder, direct expenses paid or payable by either Party or its Affiliates to Third Parties and specifically identifiable and incurred to conduct such activities for a Global Licensed Product, including payments to contract personnel; provided, however, that amounts paid to contract sales and marketing personnel will not be considered Global Out-of-Pocket Costs.

1.2.79 “ GLP Clinical Supply Agreements ” means each clinical supply agreement entered into between Alnylam and Genzyme as described in Section 6.2 of the Master Agreement (Collaboration Product Supply Agreements) pursuant to which Alnylam will provide clinical supplies of a specified Global Licensed Product to Genzyme.

1.2.80 “ GLP Collaboration ” means the collaboration of the Parties in the Development, Manufacture and Commercialization of Global Licensed Products under these Global License Terms.

1.2.81 “ GLP Commercial Supply Agreements ” means each commercial supply agreement entered into between Alnylam and Genzyme as described in Section 6.2 of the Master Agreement (Collaboration Product Supply Agreements) pursuant to which Alnylam will provide commercial supplies of a specified Global Licensed Product to Genzyme.

1.2.82 “ GLP Supply Agreements ” means, collectively, the GLP Clinical Supply Agreements and the GLP Commercial Supply Agreements.

1.2.83 “ Good Laboratory Practices ” has the meaning set forth in the Master Agreement.

1.2.84 “ Governmental Authority ” means any applicable government authority, court, tribunal, arbitrator, agency, department, legislative body, commission or other instrumentality of (a) any government of any country or territory, (b) any nation, state, province, county, city or other political subdivision thereof or (c) any supranational body.

1.2.85 “ Human POP Study ” has the meaning set forth in the Master Agreement.

1.2.86 “ IFRS ” has the meaning set forth in the Master Agreement.

1.2.87 “ Implementation Date ” means (i) with respect to ALN-AS1 or each Global Licensed Product with respect to which Genzyme exercised the Global Option or Additional Global Option, the Option Exercise Date for ALN-AS1 or such Global Licensed Product, as applicable, and (ii) with respect to each Back-Up Product with respect to which Genzyme exercised the Back-Up Option, the date on which Genzyme sent to Alnylam the Back-Up Option Exercise Notice for such Back-Up Product under Section 7.1.5 (Back-Up Products).

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1.2.88 “ Improvement Manufacturing Patent Right ” means a Patent Right owned exclusively by Genzyme or its Affiliates that claims an invention related to the Manufacture of a Global Licensed Product that was made (a) by Genzyme or its Affiliates after the Effective Date in connection with Manufacturing Global Licensed Products and (b) using Alnylam Know-How that, at the time such Alnylam Know-How was disclosed to Genzyme or its Affiliates, constituted Alnylam’s Confidential Information under Section 7 of the Master Agreement (Confidentiality and Publication).

1.2.89 “ IND ” has the meaning set forth in the Master Agreement.

1.2.90 “ In-License ” has the meaning set forth in the Master Agreement.

1.2.91 “ Infringement Action ” has the meaning set forth in Section 10.4.2(a) (Rights to Enforce – Genzyme Technology).

1.2.92 “ Joint Collaboration IP ” means, collectively, (a) any Know-How first identified, discovered or developed jointly by employee(s), agent(s) or consultant(s) acting on behalf of Alnylam or its Affiliates, on the one hand, and employee(s), agent(s) or consultant(s) acting on behalf of Genzyme or its Affiliates, on the other hand, in the conduct of the Collaboration that is Controlled by Alnylam and Genzyme, and (b) any Patent Rights that Cover such Know-How and are Controlled by Alnylam and Genzyme.

1.2.93 “ Joint Transition Team ” or “ JTT ” means the transition team as more fully described in Section 5.1 (Joint Transition Team).

1.2.94 “ Know-How ” has the meaning set forth in the Master Agreement.

1.2.95 “ Laws ” has the meaning set forth in the Master Agreement.

1.2.96 “ Licensed Target ” means, for each Global Licensed Product, the human gene that is targeted by such Global Licensed Product, as identified in the Option Data Package for such Global Licensed Product and then attached hereto as Schedules 1.2.96-1 and 1.2.96-2 , if applicable.

1.2.97 “ Licensed Territory ” means worldwide.

1.2.98 “ Lipid Nanoparticle Formulation ” has the meaning set forth in the Master Agreement.

1.2.99 “ Manufacturing ” or “ Manufacture ” has the meaning set forth in the Master Agreement.

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1.2.100 “ Manufacturing Claim ” means a claim within a Patent Right directed solely to Manufacturing a Global Licensed Product.

1.2.101 “ MMC ” means [***].

1.2.102 “ NDA ” has the meaning set forth in the Master Agreement.

1.2.103 “ Net Sales ” means, with respect to a Global Licensed Product, the aggregate gross invoiced sales prices from sales of all units of such Global Licensed Product sold by Genzyme and its Related Parties to independent Third Parties (other than a Sublicensee) after deducting, if not previously deducted, from the amount invoiced or received:

(a) trade, quantity and cash discounts, credits or allowances actually given;

(b) returns, rejections or recalls (due to spoilage, damage, expiration of useful life or otherwise);

(c) Third Party rebates, chargebacks, hospital buying group/group purchasing organization administration fees or managed care organization rebates actually given;

(d) rebates and similar payments made with respect to sales paid for by any governmental or regulatory authority such as Federal or state Medicaid, Medicare or similar state program;

(e) distribution fees and sales commissions paid to Third Parties;

(f) retroactive price reductions or billing corrections;

(g) value added, sales and use, excise and other similar taxes and surcharges, customary transportation and insurance, custom duties, and other governmental charges; and

(h) amounts previously included in Net Sales of such Global Licensed Product that are adjusted or written-off by Genzyme or its Related Parties as bad debt or otherwise uncollectible in accordance with the standard practices of Genzyme or its Related Parties for writing off uncollectible amounts consistently applied; provided , however , if any such written-off amounts are subsequently collected, such collected amounts shall be included in Net Sales in the period in which they are subsequently collected.

Such amounts shall be determined from the books and records of Genzyme or its Related Parties, maintained in accordance with IFRS.

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In the case of any sale or other disposal for value, such as barter or counter-trade, of a Global Licensed Product, or part thereof, other than in an arm’s length transaction exclusively for cash, Net Sales shall be calculated as above on the value of the non-cash consideration received or the fair market price (if higher) of such Global Licensed Product in the country of sale or disposal, as determined in accordance with IFRS.

Notwithstanding the foregoing, the following will not be included in Net Sales: (1) sales between or among Genzyme and its Related Parties (but Net Sales shall include sales to the first Third Party (other than a Sublicensee) by Genzyme or its Related Parties); (2) samples of Global Licensed Product used to promote additional Net Sales, in amounts consistent with normal business practices of Genzyme; and (3) disposal or use of Global Licensed Products in Clinical Studies or under compassionate use, patient assistance, named patient use, or test marketing programs or non-registrational studies or other similar programs or studies where the Global Licensed Product is supplied without charge or at the actual manufacturing cost thereof (without allocation of indirect costs or any mark-up).

In the case where a Global Licensed Product is sold as part of a Combination Product in a country in the Licensed Territory, Net Sales for the Global Licensed Product included in such Combination Product in such country shall be calculated as follows:

(i)

if the Global Licensed Product is sold separately in such country and the other active ingredient or ingredients in the Combination Product are sold separately in such country, Net Sales for the Global Licensed Product shall be calculated by multiplying actual Net Sales of such Combination Product in such country by the fraction A/(A+B), where A is the invoice price of the Global Licensed Product when sold separately in such country and B is the total invoice price of the other active ingredient or ingredients in the Combination Product when sold separately in such country;

(ii)

if the Global Licensed Product is sold separately in such country but the other active ingredient or ingredients in the Combination Product are not sold separately in such country, Net Sales for the Global Licensed Product shall be calculated by multiplying actual Net Sales of such Combination Product in such country by the fraction A/D, where A is the invoice price of the Global Licensed Product when sold separately in such country and D is the invoice price of the Combination Product in such country;

(iii)

if the Global Licensed Product is not sold separately in such country but the other active ingredient or ingredients in the Combinations Product are sold separately in such country, Net Sales for the Global Licensed Product shall be calculated by multiplying actual Net Sales of such Combination Product by the fraction 1 – (B/D), where B is the invoice price of the other active ingredient or ingredients in the Combination Product when sold separately in such country and D is the invoice price of the Combination Product; or

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(iv)

if neither the Global Licensed Product nor the other active ingredient or ingredients in the Combination Product are sold separately in such country, the Parties shall determine Net Sales for the Global Licensed Product in such Combination Product by mutual agreement based on the relative contribution of the Global Licensed Product and each other active ingredient to the Combination Product, and shall take into account in good faith any applicable allocations and calculations that may have been made for the same period in other countries.

For purposes of this Section, “ Combination Product ” means a product that includes at least one active ingredient other than a Global Licensed Product. Drug delivery vehicles, adjuvants, and excipients shall not be deemed to be “active ingredients”, except in the case where such delivery vehicle, adjuvant, or excipient is recognized by the FDA as an active ingredient in accordance with 21 C.F.R. 210.3(b)(7).

1.2.104 “ Non-Bankrupt Party ” has the meaning set forth in Section 7.6 (Bankruptcy).

1.2.105 “ Option Data Package ” has the meaning set forth in the Master Agreement.

1.2.106 “ Option Exercise Date ” has the meaning set forth in the Master Agreement.

1.2.107 “ Party ” means Genzyme and/or Alnylam.

1.2.108 “ Patent Rights ” has the meaning set forth in the Master Agreement.

1.2.109 “ Person ” means any natural person, corporation, unincorporated organization, partnership, association, sole proprietorship joint stock company, joint venture, limited liability company, trust or government, or any Governmental Authority, or any other similar entity.

1.2.110 “ Phase III Study ” has the meaning set forth in the Master Agreement.

1.2.111 “ PJSC ” has the meaning set forth in the Regional License Terms (as defined in the Master Agreement) and the meaning set forth in the Co-Co License Terms (as defined in the Master Agreement).

1.2.112 “Product Trademark(s)” means the Trademarks used, or intended for use, in connection with the distribution, marketing, promotion and sale of the Global Licensed Products. Product Trademarks specifically exclude the corporate names and logos of the Parties and their Affiliates. Product Trademark includes both the Alnylam Trademarks and the Genzyme Trademarks.

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1.2.113 “ Promotional Materials ” has the meaning set forth in Section 4.4.2 (Promotional Materials).

1.2.114 “ R&D Cost Opt-In Date ” has the meaning set forth in Section 2.4(a) (Development Costs).

1.2.115 “ R&D Costs ” means, with respect to a Global Licensed Product, costs and expenses incurred in connection with the performance of any Development activity for such Global Licensed Product, including [***].

1.2.116 “ R&D FTE ” means [***] hours of work per annum devoted to or in support of the Development or Manufacture of a Global Licensed Product that is carried out by one or more qualified scientific or technical employees (excluding Third Party contractors) of a Party or its Affiliates.

1.2.117 “ R&D FTE Cost ” means, for any period, the R&D FTE Rate multiplied by the number of R&D FTEs in such period.

1.2.118 “ R&D FTE Rate ” means [***] per FTE, increased annually beginning on January 1, 2015 and thereafter on January 1 of each succeeding year by the percentage increase in the CPI as of December 31 of the then most recently ended calendar year over the level of the CPI on December 31, 2013.

1.2.119 “ Regulatory Approval ” has the meaning set forth in the Master Agreement.

1.2.120 “ Regulatory Authority ” has the meaning set forth in the Master Agreement.

1.2.121 “ Regulatory Exclusivity ” means, with respect to a Global Licensed Product in a country, any exclusive marketing right, data exclusivity right, orphan drug designation or other country-wide exclusive right or status conferred by any Governmental Authority with respect to such Global Licensed Product in such country, other than a Patent Right, that limits or prohibits a Person [***].

1.2.122 “ Related Party ” means a Party’s Affiliates and permitted Sublicensees.

1.2.123 “ Reverted Global Licensed Product ” has the meaning set forth in Section 11.3.2(b) (Effects of Termination of Global Licensed Product by Alnylam for Cause or by Genzyme for Convenience).

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1.2.124 “ Royalty Term ” has the meaning set forth in Section 8.2.2 (Royalty Term).

1.2.125 “ Serious Adverse Event ” has the meaning set forth in the Master Agreement.

1.2.126 “ siRNA ” has the meaning set forth in the Master Agreement.

1.2.127 “ SPCs ” has the meaning set forth in Section 10.5 (Patent Term Extensions).

1.2.128 “ Sublicensee ” means a Third Party to whom a Party grants a sublicense under any Alnylam Technology or Genzyme Technology, as the case may be, pursuant to Section 7.1.4 (Sublicensing Terms) or Section 7.2.3 (Sublicensing Terms).

1.2.129 “ Term ” has the meaning set forth in Section 11.1 (Term).

1.2.130 “ Third Party ” has the meaning set forth in the Master Agreement.

1.2.131 “ Third Party License Payment ” has the meaning set forth in the Master Agreement.

1.2.132 “ Trademark ” has the meaning set forth in the Master Agreement.

1.2.133 “ Trailing Global Option ” has the meaning set forth in the Master Agreement.

1.2.134 “ Transition Activities ” has the meaning set forth in Section 2.2 (Transition).

1.2.135 “ Transition Period ” means with respect to a Global Licensed Product, the period beginning on the Implementation Date for such Global Licensed Product and ending on the date that such period is terminated by Genzyme pursuant to Section 5.6 (Term of JTT).

1.2.136 “ Transition Plan ” has the meaning set forth in Section 2.2 (Transition).

1.2.137 “ Un-Blocking Genzyme In-License ” has the meaning set forth in the Master Agreement.

1.2.138 “ United States ” means the United States of America and its territories, possessions and commonwealths.

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1.2.139 “ Valid Claim ” means a claim of: (a) an issued and unexpired patent, which claim has not been withdrawn, cancelled, abandoned, disclaimed, revoked or held unenforceable or invalid by an unappealable decision of a court or other governmental agency of competent jurisdiction, or has not been appealed within the time allowed for appeal, or by an appealed decision of a court or other governmental agency of competent jurisdiction where the appeal has been pending for more than [***] years (unless and until such decision is subsequently overturned on appeal) and which has not been abandoned, disclaimed, denied or admitted to be invalid or unenforceable through reissue, re-examination or disclaimer or otherwise; or (b) a patent application that has been pending less than [***] years from the date of filing of the earliest patent application from which such patent application claims priority, which claim has not been cancelled, withdrawn or abandoned or finally rejected by an administrative agency action from which no appeal can be taken.

2. DEVELOPMENT

2.1 Overview. Genzyme will have the sole right to Develop Global Licensed Products in the Licensed Territory.

2.2 Transition. Within [***] days after the Implementation Date for a Global Licensed Product, Alnylam shall prepare and provide to Genzyme a draft plan for the transition of the Development of such Global Licensed Product from Alnylam to Genzyme (a “Transition Plan ”). Promptly following the delivery of such draft Transition Plan to Genzyme (and in any event no later than [***] days following such delivery), the JTT responsible for such Global Licensed Product shall finalize the Transition Plan for such Global Licensed Product. The Transition Plan for each Global Licensed Product will require Alnylam to, as soon as reasonably practicable following the Implementation Date with respect to such Global Licensed Product: (a) assign the Alnylam Product-Specific Patents to Genzyme pursuant to Section 10.3.6.1 (Assignment of Alnylam Product-Specific Patents); (b) transfer to Genzyme all Know-How Controlled by Alnylam that is reasonably necessary or useful for Developing such Global Licensed Product, or obtaining or maintaining Regulatory Approval for such Global Licensed Product in the Licensed Territory, including information and materials reasonably requested by Genzyme, in a format reasonably acceptable to Genzyme (which shall be specified in such Transition Plan, along with the process of transferring such Know-How); (c) assign to Genzyme all INDs and other regulatory filings submitted to, or filed with, any Regulatory Authority with respect to such Global Licensed Product, as well as any related regulatory documents submitted to any Regulatory Authority with respect to such Global Licensed Product, excluding any drug master files maintained by or on behalf of Alnylam; (d) transfer to Genzyme all written correspondence with any Regulatory Authority with respect to such Global Licensed Product and all written minutes of meetings and memoranda of oral communications with any Regulatory Authority with respect to such Global Licensed Product; (e) assign to Genzyme any Third Party agreements relating solely and exclusively to the Development of such Global Licensed Product to which Alnylam is a party (including any Alnylam In-License), subject to any required consents of such Third Party, which Alnylam shall use reasonable

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efforts to obtain; and (f) transfer to Genzyme any other information or materials reasonably requested by Genzyme that are reasonably necessary or useful for Development of such Global Licensed Product in the Licensed Territory (the items described in clauses (a) through (f) collectively, “ Development Information ”). The Transition Plan for each Global Licensed Product will also describe any Development activities with respect to such Global Licensed Product that Alnylam is required to perform as requested by Genzyme and mutually agreed upon by the Parties (“ Transition Activities ”). [***]. With respect to each of Alnylam’s employees who were engaged in the Development of a Global Licensed Product prior to the Implementation Date for such Global Licensed Product, Alnylam shall (i) commit a sufficient portion of such employee’s working hours to enable the completion of the activities set forth in the Transition Plan for such Global Licensed Product in accordance with the timeline set forth in such Transition Plan and (ii) make such employee available to Genzyme at Genzyme’s reasonable request until the obligations in such Transition Plan with respect to which such employee has or had relevant experience or knowledge are completed.

2.3 Global Development Plan. Within [***] days following the Implementation Date with respect to a Global Licensed Product, Genzyme shall provide the JTT responsible for such Global Licensed Product with a work plan and time table for the Development activities and Clinical Studies to be undertaken with respect to such Global Licensed Product in the Licensed Territory (a “ Global Development Plan ”). During the Transition Period with respect to a Global Licensed Product, Genzyme shall update the Global Development Plan for such Global Licensed Product annually and shall provide such updated Global Development Plan to the JTT responsible for such Global Licensed Product. Each JTT shall review and comment on each Global Development Plan submitted to it by Genzyme and Genzyme shall consider such JTT’s comments; provided , however , that Genzyme will have sole discretion and control over the contents of such Global Development Plan.

2.4 Development Costs .

(a) With respect to any Global Licensed Product, if Genzyme exercised the Co-Co/Global Option, Global Option or Additional Global Option with respect to such Global Licensed Product, Genzyme shall be responsible for one-hundred percent (100%) of all R&D Costs that occur after the later of (i) [***] (such later date, the “ R&D Cost Opt-In Date ”) and amounts specified in clauses (ii) and (iii) in Section 2.4(b) below, if any. Alnylam shall be responsible for one-hundred percent (100%) of R&D Costs for such Global Licensed Product that occur prior to the R&D Cost Opt-In Date, except for amounts specified in clauses (ii) and (iii) of Section 2.4(b) below, if any.

(b) The Global R&D Costs to be shared by the Parties pursuant to Section 2.4(a) above shall only include amounts that are within one or more of the following four (4) categories:

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(i)

[***]

(ii)

[***]

(iii)

[***]

(iv)

[***]

(c) For clarity, R&D Costs to be paid by Genzyme pursuant to Section 2.4(a) shall exclude any amounts paid after the R&D Cost Opt-In Date to Third Parties with respect to services rendered or services procured in connection with the conduct of any Clinical Study or Development activity that, in either case, is completed prior to the R&D Cost Opt-In Date.

(d) The amount of all R&D Costs to be paid by Genzyme pursuant to Section 2.4(a) and incurred by Alnylam prior to the delivery of the Option Data Package for a Global Licensed Product will be set forth therein.

(e) Alnylam will invoice Genzyme for the R&D Costs to be paid by Genzyme pursuant to Section 2.4(a) and incurred by Alnylam. Alnylam will provide copies of invoices from vendors and other supporting documentation as reasonably requested by Genzyme. Genzyme shall reimburse Alnylam within [***] days after receipt by Genzyme of such invoice. Genzyme shall reimburse Alnylam on a quarterly basis for R&D FTE Costs, Global Out-of-Pocket Costs and Cost of Goods incurred by Alnylam in the performance of Transition Activities, within [***] days after receipt by Genzyme of an invoice for such amounts from Alnylam.

2.5 Diligence. Genzyme will use Commercially Reasonable Efforts to [***].

2.6 Records; Reports; Information Sharing .

2.6.1 Development Activities . Following the Transition Period with respect to a Global Licensed Product, [***] Genzyme will provide to Alnylam, through the AJSC, an update regarding Development activities conducted by or on behalf of Genzyme with respect to such Global Licensed Product, as well as any Clinical Studies with respect to such Global Licensed Product conducted by Genzyme .

2.6.2 Scientific Records . Genzyme will maintain scientific records, in sufficient detail and in sound scientific manner appropriate for patent and regulatory purposes and in compliance with Good Laboratory Practices with respect to activities intended to be submitted in regulatory filings (including INDs and NDAs), which will fully and properly reflect all work done and results achieved in the performance of the Development activities and Clinical Studies with respect to Global Licensed Products.

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2.6.3 Information Exchange and Development Assistance . Following the completion of the Transition Plan with respect to a Global Licensed Product, Alnylam shall deliver to Genzyme, [***] and in a commercially reasonable format, any Development Information with respect to such Global Licensed Product that comes into Alnylam’s Control or possession. If, following the completion of the Transition Plan with respect to a Global Licensed Product, Alnylam discovers that it Controls or possesses any Development Information with respect to such Global Licensed Product that should have been transferred by Alnylam to Genzyme under the Transition Plan but that was not so transferred, Alnylam will promptly provide such Development Information to Genzyme.

2.6.4 Personnel . Genzyme may request that Alnylam reasonably make available for consultation regarding the Development of a Global Licensed Product certain of its employees engaged in Development activities with respect to such Global Licensed Product.

2.6.5 Confidentiality . All information exchanged by the Parties under this Section 2 will be deemed to be Confidential Information of the disclosing Party and maintained in accordance with Section 7 of the Master Agreement (Confidentiality and Publication); provided , however , that all Development Information with respect to a Global Licensed Product delivered by Alnylam to Genzyme pursuant to Section 2.2 (Transition) or 2.6.3 (Information Exchange and Development Assistance) shall be deemed to be Confidential Information of Genzyme.

2.7 Third Parties . The Parties shall be entitled to utilize the services of Third Parties to perform their respective Development and Manufacturing activities under these Global License Terms, provided that (a) each Party shall require that such Third Party operates in a manner consistent with the terms of these Global License Terms and (b) each Party shall remain at all times fully liable for its respective responsibilities. Each Party shall require that any such Third Party agreement include confidentiality and non-use provisions that are no less stringent than those set forth in Section 7 of the Master Agreement (Confidentiality and Publication) and shall obtain ownership of, and/or a fully sublicensable license under and to, any Know-How and Patent Rights that are developed by such Third Party in the performance of such agreement and are reasonably necessary or useful to Develop, Manufacture and/or Commercialize Global Licensed Products in the Field. The Party utilizing the services of a Third Party service provider shall be solely responsible for direction of and communications with such Third Party.

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3.	REGULATORY MATTERS

3.1 Regulatory Filings and Interactions.

3.1.1 Ownership of Regulatory Filings. Genzyme will own all INDs, NDAs and related regulatory documentation submitted to any Regulatory Authority in the Licensed Territory with respect to any Global Licensed Product, excluding any drug master files maintained by or on behalf of Alnylam. At Genzyme’s request following the Implementation Date for a Global Licensed Product, Alnylam will promptly assign and transfer to Genzyme all INDs, NDAs and other regulatory documentation submitted to any Regulatory Authority in the Licensed Territory with respect to such Global Licensed Product that is in the possession or control of Alnylam, excluding any drug master files maintained by or on behalf of Alnylam, and each Party will submit all filings, letters and other documentation necessary to effect such assignment and transfer to the applicable Regulatory Authority no later than [***] days after such request for such Global Licensed Product. Alnylam hereby appoints Genzyme as Alnylam’s agent for all matters related to each Global Licensed Product involving Regulatory Authorities in the Licensed Territory during the period beginning on the Implementation Date for such Global Licensed Product and ending on the date that the transfer of all INDs, NDAs and related regulatory documents filed with or submitted to any Regulatory Authority in the Licensed Territory that relate to such Global Licensed Product, excluding any drug master files maintained by or on behalf of Alnylam, becomes effective, and Genzyme hereby accepts such appointment.

3.1.2 Responsibilities for Regulatory Matters. Genzyme will be solely responsible for all regulatory matters relating to Global Licensed Products in the Licensed Territory, including (i) overseeing, monitoring and coordinating all regulatory actions, communications and filings with, and submissions to, each Regulatory Authority in the Licensed Territory with respect to Global Licensed Products; (ii) interfacing, corresponding and meeting with each Regulatory Authority in the Licensed Territory with respect to Global Licensed Products; and (iii) seeking and maintaining all regulatory filings in the Licensed Territory with respect to Global Licensed Products.

3.1.3 Communications with Regulatory Authorities. Genzyme will provide Alnylam, through the AJSC, as part of the quarterly updates regarding Development activities described in Section 2.6.1 (Development Activities), with a brief description in English, of the principal issues raised in any material communication with any Regulatory Authority in the Licensed Territory with respect to any Global Licensed Product during the preceding Calendar Quarter. For purposes of this Section 3.1.3, “material communication” with Regulatory Authorities include meetings with Regulatory Authorities and Regulatory Authority questions or concerns regarding significant issues, including any of the following: key product quality attributes ( e.g ., purity), safety findings affecting the platform ( e.g. , Serious Adverse Events, emerging safety signals), clinical or nonclinical findings affecting patient safety, or lack of efficacy.

3.1.4 Submissions . With respect to each Global Licensed Product, Genzyme shall provide Alnylam with prompt written notice of each of the following events (but in any event within [***] days) after the occurrence of such event in the Licensed Territory: (i) the filing of any IND for such Global Licensed Product; (ii) the submission of any filings or applications for Regulatory Approval (including orphan drug applications and designations) of such Global Licensed Product to any Regulatory Authority; and (iii) receipt or denial of Regulatory Approval for such Global Licensed Product; provided , however , that in all circumstances, Genzyme shall inform Alnylam of such event prior to public disclosure of such event by Genzyme.

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3.2 Costs of Regulatory Affairs . Genzyme shall be responsible for all costs and expenses incurred in connection with applying for Regulatory Approval with respect to Global Licensed Products in the Licensed Territory, and related regulatory affairs activities.

3.3 Right of Reference . Alnylam hereby grants to Genzyme, and at the request of Genzyme will grant to Genzyme’s Related Parties, a “Right of Reference,” as that term is defined in 21 C.F.R. § 314.3(b) (or any successor rule or analogous Law recognized outside of the United States), to, and a right to copy, access, and otherwise use, all information and data (including all CMC information as well as data made, collected or otherwise generated in the conduct of any Clinical Studies or early access/named patient programs for the Global Licensed Products) included in or used in support of any drug master file maintained by or on behalf of Alnylam or its Related Parties that relates to any Global Licensed Product to the extent necessary or useful to Develop, Manufacture or Commercialize Global Licensed Products in the Licensed Territory. Notwithstanding anything to the contrary in these Global License Terms, Alnylam shall not withdraw or inactivate any regulatory filing that the other Party references or otherwise uses pursuant to this Section 3.3.

4.	COMMERCIALIZATION OF THE GLOBAL LICENSED PRODUCTS

4.1 Responsibility, Cost and Diligence . Genzyme shall be solely responsible, at its expense, for all Commercialization activities relating to Global Licensed Products in the Field in the Licensed Territory. Genzyme shall use Commercially Reasonable Efforts to [***].

4.2 Commercialization Summary . No less [***] months in advance of the reasonably expected first Regulatory Approval in the Licensed Territory with respect to a Global Licensed Product, and annually thereafter, Genzyme shall prepare and deliver to Alnylam, through the AJSC, [***] (the “ Commercialization Summary ”).

4.3 First Commercial Sale Reporting Obligations . Genzyme shall provide Alnylam with written notice of the First Commercial Sale of each Global Licensed Product.

4.4 Advertising and Promotional Materials.

4.4.1 Global Branding. Genzyme shall have the sole right, from time to time during the Term, to develop (and thereafter modify and update) a global branding strategy (including global positioning, messages, logo, colors and other visual branding elements) for each Global Licensed Product for use in the Field throughout the Licensed

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Territory (the “ Global Branding Strategy ”) for review by the AJSC. Except as prohibited by applicable Law, the labeling for each Global Licensed Product shall include a reasonably prominent reference to such Global Licensed Product as being sold under license from Alnylam and, if applicable, a reasonably prominent reference to Alnylam as the manufacturer of such Global Licensed Product.

4.4.2 Promotional Materials . Genzyme will be responsible for the creation, preparation, production, reproduction and filing with the applicable Regulatory Authorities, of relevant written sales, promotion and advertising materials relating to each Global Licensed Product (“ Promotional Materials ”) for use in the Licensed Territory. All such Promotional Materials will be compliant with applicable Law.

4.5 Sales and Distribution . Genzyme and its Related Parties shall be solely responsible for booking sales and shall warehouse and distribute Global Licensed Products in the Licensed Territory.

4.6 Recalls, Market Withdrawals or Corrective Actions . In the event that any Regulatory Authority issues or requests a recall or takes a similar action in connection with a Global Licensed Product, Genzyme shall have the sole right to decide whether to conduct a recall and the manner in which any such recall shall be conducted. Genzyme shall bear the expense of any such recall.

5.	TRANSITION MANAGEMENT

5.1 Joint Transition Team. The Parties shall establish a joint transition team (a “ JTT ”) to facilitate the transition of each Global Licensed Product from Alnylam to Genzyme as follows:

5.1.1 Composition of the Joint Transition Team. The transition of each Global Licensed Product from Alnylam to Genzyme shall be conducted under the oversight of a JTT, which shall comprise three (3) representatives of each Party. Each Party shall appoint its respective representatives to the JTT for a Global Licensed Product within [***] days following the Implementation Date for such Global Licensed Product, and may substitute one or more of its representatives, in its sole discretion, effective upon notice to the other Party of such change. Each representative on a JTT shall have appropriate expertise and ongoing familiarity with the applicable Global Licensed Product and the GLP Collaboration generally. Additional representatives or consultants may from time to time, by mutual consent of the Parties, be invited to attend JTT meetings, subject to such representatives and consultants undertaking confidentiality obligations, whether in a written agreement or by operation of law, no less stringent than the requirements of Section 7 of the Master Agreement (Confidentiality and Publication).

5.1.2 JTT Chairperson. The JTT chairperson shall be a JTT representative of Genzyme. The JTT chairperson’s responsibilities shall include (a) scheduling meetings; (b) setting agendas for meetings with solicited input from other members; (c) coordinating the delivery of draft minutes to the JTT for review and final approval; and (d) conducting meetings, including ensuring that objectives for each meeting are set and achieved.

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5.2 Meetings . Each JTT shall meet in accordance with a schedule established by mutual written agreement of the Parties, but no less frequently than once per Calendar Quarter, with the location for such meetings alternating between Alnylam and Genzyme facilities (or such other locations as are mutually agreed by the Parties). Alternatively, a JTT may meet by means of teleconference, videoconference or other similar communications equipment. All proceedings for each JTT shall take place in English. Where the membership of a JTT for a Global Licensed Product is the same as one or more other JTTs for other Global Licensed Products or PJSCs for other Collaboration Products, such JTTs and PJSCs may have a single meeting to discuss each Global Licensed Product and other Collaboration Product for which they have responsibility. Each Party shall bear its own expenses relating to attendance at such meetings by its representatives.

5.3 Minutes . A secretary shall be appointed for each meeting of each JTT and shall prepare minutes of the meeting, which shall provide a description in reasonable detail of the discussions held at the meeting and a list of any actions, decisions or determinations approved by such JTT.

5.4 JTT Responsibilities . The JTT with respect to a Global Licensed Product shall have the following responsibilities with respect to such Global Licensed Product:

(a) finalizing and approving a Transition Plan for such Global Licensed Product that meets the requirements set forth in Section 2.2 (Transition), including any Transition Activities that Alnylam will be obligated to perform under such Transition Plan;

(b) reviewing and commenting on the initial Global Development Plan for such Global Licensed Product, and reviewing and commenting on updates to the Global Development Plan provided by Genzyme;

(c) overseeing any manufacturing and supply relationship between the Parties with respect to the Manufacture of such Global Licensed Product for Development activities (subject to the terms of the GLP Clinical Supply Agreement, if any); and

(d) performing such other activities as the Parties agree in writing shall be the responsibility of such JTT.

5.5 Decision-Making . Each JTT shall not have any decision-making authority with respect to any matters under these Global License Terms; provided , however , that each JTT shall have the authority to approve the Transition Plan for the Global Licensed Product for which such JTT is responsible. With respect to approving a

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Transition Plan, the representatives of each Party on a JTT shall have collectively one vote on behalf of such Party and such JTT shall attempt to approve such Transition Plan by consensus. If the applicable JTT fails to approve a Transition Plan for a Global Licensed Product within [***] days following the Implementation Date with respect to such Global Licensed Product, then the matter shall be submitted to the AJSC. If the matter is still unresolved after a further [***] days, then such matter shall be submitted to [***].

5.5.1 [***]

(a) [***]

(b) [***]

(d) [***]

(e) [***]

5.6 Term of JTT . After the commencement of a Phase III Study for a Global Licensed Product, either Party shall have the right to terminate the Transition Period with respect to such Global Licensed Product which will relieve the Parties’ obligations to participate in the JTT for such Global Licensed Product.

6.	MANUFACTURE AND SUPPLY OF THE GLOBAL LICENSED PRODUCTS

6.1 Manufacturing and Supply . The Manufacturing of each Global Licensed Product will be addressed in the Master Agreement and breach of such Manufacturing terms as applied to a Global Licensed Product shall be treated as a breach under these Global License Terms, and not under the Master Agreement.

7.	LICENSES

7.1 License Grants to Genzyme .

7.1.1 Development License. On a Global Licensed Product-by-Global Licensed Product basis, subject to the provisions of these Global License Terms (including Section 9.4.1(e) (Exclusivity)) and any GLP Clinical Supply Agreement, effective upon the Implementation Date for such Global Licensed Product, Alnylam hereby grants Genzyme a non-transferable (except as provided in Section 13.1 of the Master Agreement (Assignment)), sublicensable (subject to Section 7.1.4 (Sublicensing Terms)), exclusive (even as to Alnylam) license under Alnylam Technology other than Patent Rights assigned to Genzyme pursuant to Section 10.3.6.1 (Assignment of Alnylam Product-Specific Patents) to Develop such Global Licensed Product in the Field in the Licensed Territory.

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7.1.2 Commercialization License. On a Global Licensed Product-by-Global Licensed Product basis, subject to the provisions of these Global License Terms (including Section 9.4.1(e) (Exclusivity)) and any GLP Commercial Supply Agreement, effective upon the Implementation Date for such Global Licensed Product, Alnylam hereby grants Genzyme a non-transferable (except as provided in Section 13.1 of the Master Agreement (Assignment)), sublicensable (subject to Section 7.1.4 (Sublicensing Terms)), exclusive (even as to Alnylam) license under Alnylam Technology other than Patent Rights assigned to Genzyme pursuant to Section 10.3.6.1 (Assignment of Alnylam Product-Specific Patents) to Commercialize such Global Licensed Product in the Field in the Licensed Territory. Such license shall be royalty-bearing for the Royalty Term applicable to each Global Licensed Product in each country in the Licensed Territory, and, after the Royalty Term applicable to such Global Licensed Product in such country, shall convert to a fully-paid, perpetual license to Commercialize such Global Licensed Product in the Field in such country.

7.1.3 Manufacturing License. On a Global Licensed Product-by-Global Licensed Product basis, subject to the provisions of these Global License Terms (including Section 9.4.1(e) (Exclusivity)), any GLP Supply Agreement and any Third Party Supply Agreement, effective upon the Implementation Date for such Global Licensed Product, Alnylam hereby grants Genzyme a non-transferable (except as provided in Section 13.1 of the Master Agreement (Assignment)), sublicensable (subject to Section 7.1.4 (Sublicensing Terms)), worldwide, exclusive (even as to Alnylam) license under Alnylam Technology other than Patent Rights assigned to Genzyme pursuant to Section 10.3.6.1 (Assignment of Alnylam Product-Specific Patents) to Manufacture such Global Licensed Product. Notwithstanding the foregoing, Alnylam retains the right under the Alnylam Technology, with the right to grant licenses through multiple tiers without restriction, to Manufacture Global Licensed Products anywhere in the world to supply (or have supplied) Genzyme pursuant to any GLP Supply Agreement.

7.1.4 Sublicensing Terms.

(a) Subject to Section 7.5 (Right of First Negotiation), Genzyme shall have the right to sublicense any of its rights under Sections 7.1.1 (Development License), 7.1.2 (Commercialization License) and 7.1.3 (Manufacturing License) to any of its Affiliates or to any Third Party (which sublicensed rights may be further sublicensable through multiple tiers) without the prior consent of Alnylam, subject to the requirements of this Section 7.1.4. [***]

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(b) Each sublicense granted by Genzyme pursuant to this Section 7.1.4 shall be subject and subordinate to the provisions of these Global License Terms and shall contain provisions consistent with those in these Global License Terms. Genzyme shall promptly provide Alnylam with a copy of the fully executed sublicense agreement covering any sublicense granted hereunder (which copy may be redacted to remove provisions which are not necessary to monitor compliance with this Section 7.1.4), and each such sublicense agreement shall contain the following provisions: (i) a requirement that the Sublicensee comply with the confidentiality and non-use provisions of Section 7 of the Master Agreement (Confidentiality and Publication) with respect to Alnylam’s Confidential Information, (ii) if such sublicense agreement contains a sublicense of Global Licensed Product Commercialization rights, such sublicense agreement shall also contain the following provisions: (x) a requirement that the Sublicensee submit applicable sales or other reports to Genzyme to the extent necessary or relevant to the reports required to be made or records required to be maintained under these Global License Terms; and (y) the audit requirement set forth in Section 9.2 of the Master Agreement (Audits); and (iii) a requirement that the Sublicensee comply with the applicable provisions under any Alnylam In-License.

(c) If Genzyme becomes aware of a material breach of the terms of any sublicense by any Genzyme Sublicensee, compliance with which is necessary for Genzyme’s compliance with the terms of these Global License Terms, Genzyme shall promptly notify Alnylam of the particulars of the same and use Commercially Reasonable Efforts to cause the Sublicensee to comply with all the terms of the sublicense necessary for Genzyme’s compliance with the terms of these Global License Terms. [***] Notwithstanding any sublicense, Genzyme shall remain primarily liable to Alnylam for the performance of all of Genzyme’s obligations under, and Genzyme’s compliance with all provisions of, these Global License Terms.

7.1.5 Back-Up Products . Subject to Sections 12.2 (Future Acquisition of a Party or its Business), 12.3.1 (Acquired Programs), and 12.3.2 (Acquired Programs), Alnylam hereby grants to Genzyme a series of exclusive options (each, a “ Back-Up Option ”), under each of which Genzyme shall have the right, but not the obligation, to take a license on the terms set forth in the these Global License Terms to any siRNA that targets the same Licensed Target as a Global Licensed Product (a “ Back-Up Product ”) and for which Alnylam has determined the siRNA composition for which GLP toxicology studies will be conducted during the Back-Up Option Period. Genzyme may exercise the Back-Up Option with respect to such Back-Up Product by delivering written notice to Alnylam at any time during the Back-Up Option Period (the “ Back-Up Option Exercise Notice ”). Upon delivery of the Back-Up Option Exercise Notice to Alnylam, the applicable Back-Up Product shall automatically be deemed to be a Global Licensed Product for all purposes under the Collaboration Agreement and the license from Alnylam to Genzyme for such Global Licensed Product shall automatically, with no further action by any Party, go into full force and effect and all obligations of Alnylam and Genzyme set forth in these Global License Terms, including the payment obligations set forth herein, shall become the binding obligations of the applicable Party in respect of such Global Licensed Product. Upon the expiration of the Back-Up Option Period, all Back-Up Options not previously exercised shall automatically terminate.

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7.2 License Grants to Alnylam.

7.2.1 License to Improvement Manufacturing Patent Rights. Subject to the provisions of these Global License Terms, Genzyme hereby grants Alnylam a non-transferable (except as provided in Section 13.1 of the Master Agreement (Assignment)), sublicensable (subject to Section 7.2.3 (Sublicensing Terms)), worldwide, non-exclusive license under the Improvement Manufacturing Patent Rights, to Manufacture (a) Alnylam Developed siRNA Products targeting any human gene; and (b) Global Licensed Products for Development and Commercialization in the Licensed Territory by Genzyme.

7.2.2 License to Genzyme Disclosed Manufacturing Know-How. Subject to the provisions of these Global License Terms, Genzyme hereby grants Alnylam a non-transferable (except as provided in Section 13.1 of the Master Agreement (Assignment)), sublicensable (subject to Section 7.2.3 (Sublicensing Terms)), worldwide, non-exclusive license under the Genzyme Disclosed Manufacturing Know-How to Manufacture Global Licensed Products for Development and Commercialization in the Licensed Territory by Genzyme.

7.2.3 Sublicensing Terms.

(a) Subject to Section 7.5 (Right of First Negotiation), Alnylam shall have the right to sublicense any of its rights under Sections 7.2.1 (License to Improvement Manufacturing Patent Rights) and 7.2.2 (License to Genzyme Disclosed Manufacturing Know-How) (which sublicensed rights may be further sublicensable through multiple tiers) to [***].

(b) Each sublicense granted by Alnylam pursuant to this Section 7.2.3 shall be subject and subordinate to the provisions of these Global License Terms and shall contain provisions consistent with those in these Global License Terms. Alnylam shall promptly provide Genzyme with a copy of the fully executed sublicense agreement covering any sublicense granted hereunder (which copy may be redacted to remove provisions which are not necessary to monitor compliance with this Section 7.2.3), and each such sublicense agreement shall contain the following provisions: (i) a requirement that the Sublicensee comply with the confidentiality and non-use provisions of Section 7 of the Master Agreement (Confidentiality and Publication) with respect to Genzyme’s Confidential Information and (ii) a requirement that the Sublicensee comply with the applicable provisions under any Genzyme In-License.

(c) If Alnylam becomes aware of a material breach of any sublicense by any Alnylam Sublicensee, compliance with which is necessary for Alnylam’s compliance with the provisions of these Global License Terms, Alnylam shall promptly notify Genzyme of the particulars of the same and use Commercially Reasonable Efforts to cause the Sublicensee to comply with all the terms of the sublicense necessary for Alnylam’s compliance with the provisions of these Global License Terms. [***]. Notwithstanding any sublicense, Alnylam shall remain primarily liable to Genzyme for the performance of all of Alnylam’s obligations under, and Alnylam’s compliance with all provisions of, these Global License Terms.

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7.3 Joint Collaboration IP . Subject to the rights and licenses granted to, and the obligations (including royalty obligations) of, each Party under these Global License Terms, either Party is entitled to practice Joint Collaboration IP for all purposes on a worldwide basis and license Joint Collaboration IP without consent of and without a duty of accounting to the other Party. Each Party will grant and hereby does grant all permissions, consents and waivers with respect to, and all licenses under, the Joint Collaboration IP, throughout the world, necessary to provide the other Party with such rights of use and exploitation of the Joint Collaboration IP, and will execute documents as necessary to accomplish the foregoing.

7.4 In-Licenses.

7.4.1 Compliance with In-Licenses . All licenses and other rights granted to Genzyme under this Section 7 are subject to the rights and obligations of Alnylam under the Alnylam In-Licenses. All licenses and other rights granted to Alnylam under this Section 7 are subject to the rights and obligations of Genzyme under the Genzyme In-Licenses. Each Party shall comply with all applicable terms and conditions of the In-Licenses, and shall perform and take such actions as may be required to allow the Party that is party to such In-License to comply with its obligations thereunder, including obligations relating to sublicensing, patent matters, confidentiality, reporting, audit rights, indemnification and diligence. Without limiting the foregoing, each Party shall prepare and deliver to the other Party any additional reports required under the applicable In-Licenses and requested by such other Party, in each case sufficiently in advance to enable the Party that is party to such In-License to comply with its obligations under the applicable In-Licenses. Each Party agrees, upon the other Party’s request, to provide the other Party with copies of any In-Licenses to which it is a party. Confidential Information of the providing Party or its counterparty may be redacted from such copies, except to the extent that such information is required in order to enable the other Party to comply with its obligations to the providing Party under these Global License Terms with respect to such In-License or in order to enable the providing Party to ascertain compliance with the provisions of these Global License Terms.

7.5 Right of First Negotiation . If, at any time during the Term, Genzyme desires to grant any Third Party rights to Develop and/or Commercialize one or more Global Licensed Product(s) in the Field in any portion of the Licensed Territory (excluding customary distribution arrangements entered into in the ordinary course of business by Genzyme), Genzyme shall notify Alnylam in writing of its intent. Alnylam shall have [***] days from receipt of such written notice to notify Genzyme in writing as to whether Alnylam desires to negotiate for such rights in such territory, and if Alnylam so notifies Genzyme that it does desire to negotiate for such rights in such territory, Alnylam shall have the exclusive right for [***] days from the date of such notification to

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Genzyme to negotiate with Genzyme and to make one or more written non-binding offers to Genzyme concerning the acquisition of such rights in such territory by Alnylam. Alnylam shall have the exclusive right for [***] days (or such longer period as may be mutually agreed by the Parties) after such [***] day period, to finalize and enter into a definitive agreement with Genzyme for such rights in such territory, provided that if either Alnylam does not provide such written notice within such [***] day period or Alnylam does provide such written non-binding offer within such subsequent [***] day period, or Alnylam provides such notice of interest and such written offer but for any reason Genzyme and Alnylam do not enter into a definitive agreement within the [***] day negotiation period, Genzyme shall be free to enter into an agreement with a Third Party(ies) relating to such rights in such territory, without further obligation to Alnylam. Genzyme shall not, during the exclusive [***] and [***] day negotiating periods described above, enter into discussions, exchange information, or otherwise negotiate with any Third Party with respect to an agreement with respect to the Development and/or Commercialization of the applicable Global Licensed Product(s) in the Field in the Licensed Territory. Notwithstanding the foregoing, during the period of [***] months after the termination of any such negotiation that does not result in a definitive agreement between Alnylam and Genzyme, Genzyme shall not enter into a transaction with respect to such rights in such territory with any Third Party on terms that are, in the aggregate, materially more favorable to the Third Party than the last terms offered in writing by Alnylam to Genzyme unless Genzyme first re-offers such transaction to Alnylam on such more favorable terms and Alnylam does not accept such offer and enter into such transaction with Genzyme within [***] days after such re-offer. For clarity, prior to the exclusive negotiating periods described above, Genzyme shall be free to engage in discussions and exchange information with Third Parties with respect to the applicable Global Licensed Product(s) rights, but shall not enter into any binding agreement with any Third Party with respect to such rights.

7.6 Bankruptcy . All rights and licenses granted under or pursuant to these Global License Terms by a Party to the other, including those set forth in Sections 3.3 (Right of Reference), 7.1 (License Grants to Genzyme), 7.2 (License Grants to Alnylam), and 11.3.2(b) (Effects of Termination of Global Licensed Product by Alnylam for Cause or by Genzyme for Convenience), are and shall otherwise be deemed to be, for purposes of Section 365(n) of the U.S. Bankruptcy Code, licenses of right to “intellectual property” as defined under Section 101 of the U.S. Bankruptcy Code. The Parties agree that the Parties and their respective Sublicensees, as sublicensees of such rights under these Global License Terms, shall retain and may fully exercise all of their rights and elections under the U.S. Bankruptcy Code and any foreign counterpart thereto. The Parties further agree that upon commencement of a bankruptcy proceeding by or against a Party (the “ Bankrupt Party ”) under the Bankruptcy Code, the other Party (the “ Non-Bankrupt Party ”) will be entitled to a complete duplicate of, or complete access to (as the Non-Bankrupt Party deems appropriate), all such intellectual property and all embodiments of such intellectual property. Such intellectual property and all embodiments of such intellectual property will be promptly delivered to the Non-Bankrupt Party (a) upon any

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such commencement of a bankruptcy proceeding and upon written request by the Non-Bankrupt Party, unless the Bankrupt Party elects to continue to perform all of its obligations under these Global License Terms, or (b) if not delivered under (a) above, upon the rejection of these Global License Terms by or on behalf of the Bankrupt Party and upon written request by the Non-Bankrupt Party. Without limiting the foregoing, Alnylam hereby grants to Genzyme a right of access to and to obtain possession of (i) copies of research data, (ii) laboratory samples, (iii) samples of Global Licensed Product, (iv) formulas, (v) laboratory notes and notebooks, (vi) data and results related to clinical trials, (vii) regulatory filings and approvals, (viii) rights of reference in respect of regulatory filings and approvals, (ix) pre-clinical research data and results, (x) marketing, advertising and promotional materials, all of which (in clauses (i) through (x)) constitute “embodiments” of intellectual property pursuant to Section 365(n) of the Bankruptcy Code and (xi) all other embodiments of such intellectual property, and in respect of each of the foregoing clauses (i) through (xi), solely for the purpose of the exercise of Genzyme’s rights and licenses under these Global License Terms, whether any of the foregoing are in Alnylam’s possession or control or in the possession and control of Third Parties. The Bankrupt Party (in any capacity, including debtor-in-possession) and its successors and assigns (including any trustee) agrees not to interfere with the exercise by Non-Bankrupt Party or its Related Parties of its rights and licenses to such intellectual property and such embodiments of intellectual property in accordance with these Global License Terms, and agrees to assist the Non-Bankrupt Party and its Related Parties in obtaining such intellectual property and such embodiments of intellectual property in the possession or control of Third Parties as reasonably necessary or desirable for the Non-Bankrupt Party to exercise such rights and licenses in accordance with these Global License Terms. The foregoing provisions are without prejudice to any rights the Non-Bankrupt Party may have arising under the Bankruptcy Code or other Laws.

7.7 No Other Rights . Except as otherwise expressly provided in these Global License Terms, under no circumstances shall a Party, as a result of these Global License Terms, obtain any ownership interest or other right in any Know-How, Patent Rights or other intellectual property rights of the other Party, including items owned, controlled or developed by the other Party, or provided by the other Party to the receiving Party at any time pursuant to these Global License Terms.

8.	CERTAIN FINANCIAL TERMS

8.1 Milestone Fees .

8.1.1 Development Milestones for Global Licensed Products . Genzyme shall provide Alnylam with written notice of the achievement by Genzyme or any of its Related Parties of any development milestone event set forth below in this Section 8.1.1 within [***] days after such event has occurred; provided , however , that Genzyme shall inform Alnylam of such event prior to any public disclosure of such event by Genzyme. Alnylam shall invoice Genzyme within [***] days of receipt of such written notice by

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Alnylam, and Genzyme shall remit the associated development milestone payment within [***] days of the receipt of such invoice. Each development milestone payment by Genzyme to Alnylam hereunder shall be payable only once with respect to each Global Licensed Product, regardless of the number of times a development milestone event is achieved with respect to such Global Licensed Product.

8.1.1.1 Development Milestones for ALN-AS1 . Genzyme shall pay Alnylam the following amounts upon achievement of the following development milestone events with respect to ALN-AS1:


Development Milestone Event		Development Milestone Payment
[***]		[***]
[***]		[***]
[***]		[***]
[***]		[***]
[***]		[***]

8.1.1.2 Development Milestones for Global Licensed Products other than ALN-AS1 . Genzyme shall pay Alnylam the following amounts upon the first achievement of the following development milestone events with respect to each Global Licensed Product other than ALN-AS1:


Development Milestone Event		Development Milestone Payment
[***]		[***]
[***]		[***]
[***]		[***]
[***]		[***]
[***]		[***]

8.1.2 Sales Milestones for Global Licensed Products. Genzyme shall provide Alnylam with written notice of the achievement by Genzyme or any of its Related Parties of any sales milestone event set forth below in this Section 8.1.2 within [***] days after such event has occurred. Alnylam shall invoice Genzyme within [***] days of receipt of such written notice by Alnylam, and Genzyme shall remit the associated milestone payment within [***] days of the receipt of such invoice. Notwithstanding the foregoing, in the event that more than one of the sales milestone events is achieved simultaneously by a Global Licensed Product, Genzyme will make only one sales milestone payment at such time, which will be for the sales milestone event requiring the highest sales milestone payment; and further, payment for achievement of the lower sales milestone shall be due in the next Calendar Year. Each sales milestone payment by Genzyme to Alnylam hereunder shall be payable only once with respect to each Global Licensed Product, regardless of the number of times a sales milestone event is achieved with respect to such Global Licensed Product.

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8.1.2.1 Sales Milestones for ALN-AS1 . Genzyme shall pay Alnylam the following amounts upon achievement of the following sales milestone events with respect to ALN-AS1:


Sales Milestone Event	Sales Milestone Payment
(i) First Calendar Year in which Net Sales for ALN-AS1 exceeds [***]		[	***]
(ii) First Calendar Year in which Net Sales for ALN-AS1 exceeds [***]		[	***]
(i) First Calendar Year in which Net Sales for ALN-AS1 exceeds [***]		[	***]
(ii) First Calendar Year in which Net Sales for ALN-AS1 exceeds[***]		[	***]

8.1.2.2 Sales Milestones for Global Licensed Products other than ALN-AS1 . Genzyme shall pay Alnylam the following amounts upon achievement of the following sales milestone events with respect to each Global Licensed Product other than ALN-AS1:


Sales Milestone Event	Sales Milestone Payment
(i) First Calendar Year in which Net Sales for a Global Licensed Product (other than ALN-AS1) exceeds [***]		[	***]
(ii) First Calendar Year in which Net Sales for a Global Licensed Product (other than ALN-AS1) exceeds [***]		[	***]
(iii) First Calendar Year in which Net Sales for a Global Licensed Product (other than ALN-AS1) exceeds [***]		[	***]

8.2 Royalties .

8.2.1 Royalties Payable on Licensed Products. Subject to the provisions of these Global License Terms, Genzyme shall pay to Alnylam royalties on annual Net Sales of each Global Licensed Product by Genzyme and its Related Parties, as calculated on a Global Licensed Product-by-Global Licensed Product basis, in the Licensed Territory, as follows:

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Calendar Year Net Sales of a Global Licensed Product in the Licensed Territory		Royalty (as a percentage of Net Sales of such Global Licensed Product)
[***]		[***]
[***]		[***]
[***]		[***]
[***]		[***]
[***]		[***]

Royalties on annual Net Sales of each Global Licensed Product shall be paid at the rate applicable to [***]:

[***]

Royalties on annual Net Sales shall be paid at the rate applicable to the portion of such Net Sales within each of the Net Sales levels above during such Calendar Year.

8.2.2 Royalty Term. Subject to Section 8.2.6 (Royalty Floor), the period during which the royalties set forth in Section 8.2.1 (Royalties Payable on Licensed Products) shall be payable, on a Global Licensed Product-by-Global Licensed Product and country-by-country basis, shall commence with the First Commercial Sale of a Global Licensed Product in a country and continue until the latest of (a) the expiration of the last Valid Claim of [***] in the country of sale; (b) the expiration of Regulatory Exclusivity for such Global Licensed Product in such country; or (c) subject to the last sentence of this Section 8.2.2, the [***] anniversary of the First Commercial Sale of such Global Licensed Product in such country (each such period, a “ Royalty Term ”). [***].

8.2.3 Third Party Royalty Offsets . Genzyme shall be permitted to reduce any royalties payable under Section 8.2.1 (Royalties Payable on Licensed Products) for a Global Licensed Product by [***] percent ([***]) of any amounts for which Genzyme is responsible under Collaboration In-Licenses for such Global Licensed Product pursuant to Section 11.3 of the Master Agreement (In-Licenses) or under an Un-Blocking Genzyme In-License, but only to the extent that the relevant Third Party License Payment under such Collaboration In-License or Un-Blocking Genzyme In-License constitutes either royalties or a milestone payment based on sales of such Global Licensed Product; provided , however , that the royalties payable under Section 8.2.1 (Royalties Payable on Licensed Products) with respect to such Global Licensed Product shall not be reduced in any such event below [***]percent ([***]) of the amounts set forth in Section 8.2.1 (Royalties Payable on Licensed Products) and; provided , further , that if any of such

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amounts cannot be offset against royalties due with respect to such Global Licensed Product for any given royalty period due to the preceding proviso, such unused amount may be carried forward and offset against royalties due with respect to such Global Licensed Product in future royalty periods.

8.2.4 No Alnylam Patents or Regulatory Exclusivity. The royalties to be paid by Genzyme to Alnylam pursuant to Section 8.2.1 (Royalties Payable on Licensed Products) with respect to any Global Licensed Product shall be reduced to [***]percent ([***]) of the amounts otherwise payable pursuant to Section 8.2.1 (Royalties Payable on Licensed Products) with respect to Net Sales of such Global Licensed Product in a country of the Licensed Territory as to which both (a) the Manufacture, use, offer for sale, sale or importation of which is not Covered by any Valid Claim in any Alnylam Patent or in any Patent Right included in the Joint Collaboration IP in such country and (b) there is no applicable Regulatory Exclusivity in such country.

8.2.5 Royalty Adjustments for Generic Products. If, during a given Calendar Quarter when a Global Licensed Product is being Commercialized by or on behalf of Genzyme in a particular country in the Licensed Territory, there is Generic Competition in such country with respect to such Global Licensed Product, then, subject to Section 8.2.6 (Royalty Floor), the royalties payable pursuant to Section 8.2.1 (Royalties Payable on Licensed Products) on the Net Sales of such Global Licensed Product in such country shall thereafter be reduced to [***] percent ([***]) of the amounts otherwise payable pursuant to Section 8.2.1 (Royalties Payable on Licensed Products) with respect to such Global Licensed Product in such country for such Calendar Quarter for so long as such Generic Competition remains.

8.2.6 Royalty Floor. Anything in these Global License Terms to the contrary notwithstanding, in no event during the applicable Royalty Term for a Global Licensed Product in a country of the Licensed Territory shall the royalties payable to Alnylam hereunder for such Global Licensed Product in such country for any Calendar Quarter be reduced (a) by the application of the reductions or credits described in Sections 8.2.3 (Third Party Royalty Offsets) or 8.2.4 (No Alnylam Patents or Regulatory Exclusivity), whether taken together or separately, to less than [***]percent ([***]) of the royalties payable pursuant to Section 8.2.1 (Royalties Payable on Licensed Products) as to such Global Licensed Product in such country for such Calendar Quarter, or (b) by the application of the reductions or credits described in Sections 8.2.3 (Third Party Royalty Offset), 8.2.4 (No Alnylam Patents or Regulatory Exclusivity), 8.2.5 (Royalty Adjustments for Generic Products) and/or 10.4.2 (Rights to Enforce), whether taken together or separately, to less than the greater of (1) [***] percent ([***]) of the royalties payable pursuant to Section 8.2.1 (Royalties Payable on Licensed Products) as to such Global Licensed Product in such country for such Calendar Quarter, and (2) [***].

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8.2.7 Validation Information . At Genzyme’s request, Alnylam will provide Genzyme with such information as Genzyme may reasonably request to validate the amount of the royalty floor described in Section 8.2.6 (Royalty Floor).

9.	REPRESENTATIONS, WARRANTIES AND COVENANTS

9.1 Representations and Warranties of Alnylam . Except as provided in the Disclosure Schedule to this Section 9.1 (which Disclosure Schedule with respect to any Global Licensed Product will be provided by Alnylam to Genzyme as part of the Option Data Package for such Global Licensed Product), with respect to each Global Licensed Product, Alnylam represents and warrants to Genzyme that as of the Implementation Date for such Global Licensed Product:

9.1.1 Alnylam is the sole and exclusive owner of, or otherwise Controls pursuant to an Alnylam In-License, the Alnylam Technology, and all of the Alnylam Technology licensed to Genzyme hereunder in the Licensed Territory that is solely and exclusively owned by Alnylam is free and clear of liens, charges or encumbrances other than licenses granted to Third Parties that are not inconsistent with the rights and licenses granted to Genzyme under these Global License Terms.

9.1.2 Alnylam has sufficient legal and/or beneficial title and ownership of, or sufficient license rights under, the Alnylam Technology to grant the licenses to such Alnylam Technology granted to Genzyme pursuant to these Global License Terms.

9.1.3 (a) Schedule 1.2.8 and Schedule 1.2.15 collectively set forth a complete and accurate list of the Alnylam Patents owned, either solely or jointly, by Alnylam, and to Alnylam’s knowledge, Schedule 1.2.8 and Schedule 1.2.15 collectively set forth a complete and accurate list of the Alnylam Patents licensed, either exclusively or nonexclusively, to Alnylam, (b) to Alnylam’s knowledge, each issued Alnylam Patent remains in full force and effect and (c) Alnylam or its Affiliates have timely paid all filing and renewal fees payable with respect to such Alnylam Patents for which Alnylam controls prosecution and maintenance. Schedule 1.2.8 and Schedule 1.2.15 indicate whether each Alnylam Patent is owned exclusively by Alnylam, is owned jointly by Alnylam and one or more Third Parties, or is licensed to Alnylam. For each Alnylam Patent that is owned, but not owned exclusively, by Alnylam, or that is licensed to Alnylam, Schedule 1.2.8 and Schedule 1.2.15 identify the Third Party owner(s) and, if applicable, the Alnylam In-License pursuant to which Alnylam Controls such Alnylam Patent. For each Alnylam Product-Specific Patent that is licensed, but not exclusively licensed, to Alnylam, Schedule 1.2.15 indicates the non-exclusive nature of the license. For each Alnylam Core Technology Patent family (other than Patent Rights licensed from Isis Pharmaceuticals, Inc.) that is licensed, but not exclusively licensed, to Alnylam, Schedule 1.2.8 indicates the non-exclusive nature of the license. Alnylam is the sole and exclusive owner of all Patent Rights identified in Schedule 1.2.8 and Schedule 1.2.15 as being owned exclusively by Alnylam and Controls all other Patent Rights identified on such schedules.

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9.1.4 To Alnylam’s knowledge, the Alnylam Product-Specific Patents, are, or, upon issuance, will be, valid and enforceable patents and no Third Party has challenged or threatened to challenge the scope, validity or enforceability of any Alnylam Product-Specific Patent (including, by way of example, through opposition or the institution or written threat of institution of interference, nullity or similar invalidity proceedings before the United States Patent and Trademark Office or any analogous foreign Governmental Authority).

9.1.5 Alnylam has complied with all applicable Laws, including any duties of candor to applicable patent offices, in connection with the filing, prosecution and maintenance of the Alnylam Patent Rights.

9.1.6 Alnylam owns or Controls all Know-How that is or has been used by Alnylam in the Development and Manufacture of such Global Licensed Products, and has sufficient legal or beneficial title and ownership of, or sufficient license rights under such Know-How to transfer Know-How to Genzyme as provided in Section 6.4 of the Master Agreement (Transfer of Manufacturing Know-How).

9.1.7 Alnylam Controls all Know-How and Patent Rights licensed to Alnylam under the Existing Alnylam In-Licenses that is necessary or useful for Genzyme to Develop, Manufacture and/or Commercialize such Global Licensed Product in the Field in the Licensed Territory. Without limiting the generality of the foregoing, Alnylam has obtained all necessary consents and fulfilled all necessary conditions, if any, to sublicense to Genzyme under these Global License Terms such Know-How and Patent Rights licensed to Alnylam under Existing Alnylam In-Licenses.

9.1.8 To Alnylam’s knowledge, neither Alnylam nor its Affiliates are in breach or default under any existing Alnylam In-License, and neither Alnylam nor its Affiliates have received any written notice of breach or default with respect to any existing Alnylam In-License.

9.1.9 Alnylam has obtained from all inventors of Alnylam Technology owned by Alnylam valid and enforceable agreements assigning to Alnylam each such inventor’s entire right, title and interest in and to all such Alnylam Technology.

9.1.10 To Alnylam’s knowledge, the use, Development, Manufacture or Commercialization by Alnylam or Genzyme (or their respective Related Parties) of such Global Licensed Product as formulated and manufactured as of the Effective Date, or as intended to be formulated and manufactured as of the Effective Date (a) does not and will not infringe any issued patent of any Third Party and (b) will not infringe the claims of any published Third Party patent application when and if such claims were to issue in their current form.

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9.1.11 There is no (a) claim, demand, suit, proceeding, arbitration, inquiry, investigation or other legal action of any nature, civil, criminal, regulatory or otherwise, pending or, to Alnylam’s knowledge, threatened against Alnylam or any of its Affiliates or (b) judgment or settlement against or owed by Alnylam or any of its Affiliates, in each case in connection with the Alnylam Technology or such Global Licensed Product.

9.1.12 For each Global Licensed Product, Schedule 9.1.12(a) sets forth a complete and accurate list of all agreements between Alnylam and a Third Party entered into prior to the Implementation Date for a Global Licensed Product pursuant to which Alnylam Controls Know-How or Patent Rights that are necessary or useful to Develop, Manufacture or Commercialize such Global Licensed Product in the Field other than Additional In-Licenses. [***].

9.2 Representations and Warranties of Genzyme. Except as disclosed in Genzyme’s Exercise Notice, Genzyme represents and warrants to Alnylam as of the Implementation Date for such Global Licensed Product that it is not a party to any agreement with a Third Party under which it Controls Know-How or Patent Rights that are sublicensed to Alnylam under these Global License Terms with respect to such Global Licensed Products.

9.3 Warranty Disclaimer . EXCEPT AS OTHERWISE EXPRESSLY PROVIDED IN THESE GLOBAL LICENSE TERMS, NEITHER PARTY MAKES ANY REPRESENTATION OR EXTENDS ANY WARRANTY OF ANY KIND, EITHER EXPRESS OR IMPLIED, TO THE OTHER PARTY WITH RESPECT TO ANY TECHNOLOGY, GLOBAL LICENSED PRODUCT, GOODS, SERVICES, RIGHTS OR OTHER SUBJECT MATTER OF THESE GLOBAL LICENSE TERMS AND HEREBY DISCLAIMS ALL IMPLIED WARRANTIES OF MERCHANTABILITY, FITNESS FOR A PARTICULAR PURPOSE AND NON-INFRINGEMENT WITH RESPECT TO ANY AND ALL OF THE FOREGOING. EACH PARTY HEREBY DISCLAIMS ANY REPRESENTATION OR WARRANTY THAT THE DEVELOPMENT, MANUFACTURE OR COMMERCIALIZATION OF ANY GLOBAL LICENSED PRODUCT PURSUANT TO THESE GLOBAL LICENSE TERMS WILL BE SUCCESSFUL OR THAT ANY PARTICULAR SALES LEVEL WITH RESPECT TO ANY GLOBAL LICENSED PRODUCT WILL BE ACHIEVED.

9.4 Certain Covenants.

9.4.1 [***].

(a) [***]

(b) [***]

(d) [***]

(e) [***]

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9.4.2 Compliance. Each Party and its Related Parties shall conduct the GLP Collaboration and the Development, Manufacture and Commercialization of the Global Licensed Products in accordance with all Laws, including current governmental regulations concerning Good Laboratory Practices (as defined in the Master Agreement), good clinical practices and good manufacturing practices. In addition, if either Party is or becomes subject to a legal obligation to a Regulatory Authority or other Governmental Authority (such as a corporate integrity agreement or settlement agreement with a Governmental Authority), then the other Party shall perform such activities as may be reasonably requested by the obligated Party to enable the obligated Party to comply with its legal obligation to such Regulatory Authority with respect to the Global Licensed Products.

9.4.3 Conflicting Transactions . During the Term, Alnylam shall not (a) transfer or assign any of its rights, title or interests in the Alnylam Technology other than as part of a transaction pursuant to which these Global License Terms is also assigned and assumed in accordance with Section 13.1 of the Master Agreement (Assignment), or (b) enter into any agreement granting a license or other right under the Alnylam Technology that is inconsistent with the terms of these Global License Terms.

9.4.4 Governmental Authority . If any of the Alnylam Technology is subject to any funding arrangement with any Governmental Authority, at Genzyme’s reasonable request, Alnylam will reasonably cooperate in seeking a waiver or other modification to such funding arrangement with respect to such Alnylam Technology.

10.

INTELLECTUAL PROPERTY OWNERSHIP, PROTECTION AND RELATED MATTERS

10.1 Inventorship . Inventorship for inventions and discoveries first made during the course of the performance of activities pursuant to these Global License Terms shall be determined in accordance with United States patent Laws for determining inventorship.

10.2 Ownership . Alnylam shall own the entire right, title and interest in and to all inventions and discoveries (and Patent Rights claiming patentable inventions therein) first made or discovered solely by employees or consultants of Alnylam or acquired solely by Alnylam in the course of conducting the Collaboration. Genzyme shall own the entire right, title and interest in and to all inventions and discoveries (and Patent Rights claiming patentable inventions therein) first made or discovered solely by employees or consultants of Genzyme or acquired solely by Genzyme in the course of conducting the Collaboration. The Parties shall jointly own any inventions and discoveries (and Patent Rights claiming patentable inventions therein) first made or discovered jointly in the course of conducting the Collaboration.

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10.3 Prosecution and Maintenance of Patent Rights .

10.3.1 IP Committee. The Parties agree that the IP Committee created pursuant to Section 5.3 of the Master Agreement (IP Committee) shall be responsible for overseeing and effecting the information sharing and consulting provisions under this Section 10.3.

10.3.2 Genzyme Technology .

(a) Subject to Section 10.3.1(b) below, Genzyme has the sole responsibility, at Genzyme’s discretion and at Genzyme’s sole cost and expense, to file, prosecute and maintain (including the defense of any interference or opposition proceedings), all Patent Rights comprising Genzyme Technology (other than Joint Collaboration IP and Alnylam Product-Specific Patents assigned by Alnylam to Genzyme pursuant to Section 10.3.6.1 (Assignment of Alnylam Product-Specific Patents)), in Genzyme’s name.

(b) In the event that Genzyme elects not to seek or continue to seek or maintain patent protection on any Genzyme Collaboration IP in the Licensed Territory, Genzyme shall notify Alnylam at least [***] days before any such Patent Rights would become abandoned, no longer available or otherwise forfeited, and subject to the terms and conditions of any applicable Genzyme In-License, Alnylam shall have the right (but not the obligation), at its expense, to seek, prosecute and maintain in any country patent protection on such Genzyme Collaboration IP in the name of Genzyme. Genzyme shall use Commercially Reasonable Efforts to make available to Alnylam its authorized attorneys, agents or representatives, and such of its employees as are reasonably necessary to assist Alnylam in obtaining and maintaining the patent protection described under this Section 10.3.1(b). Genzyme shall sign or use Commercially Reasonable Efforts to have signed, all legal documents necessary to file and prosecute such patent applications or to obtain or maintain such patents.

10.3.3 Alnylam Technology and Alnylam Product-Specific Patents .

(a) Subject to Sections 10.3.3(b) and 10.3.3(c), Alnylam has the sole responsibility, at Alnylam’s discretion and at Alnylam’s sole cost and expense, to file, conduct prosecution and maintain (including the defense of any interference or opposition proceedings), all Patent Rights comprising Alnylam Technology (other than Alnylam Product-Specific Patents assigned to Genzyme and Joint Collaboration IP), in Alnylam’s name.

(b) Notwithstanding the foregoing Section 10.3.3(a), subject to the terms and conditions of any applicable Alnylam In-License, as between the Parties Genzyme shall have the first right, at its expense, to file, conduct prosecution and maintain (including the defense of any interference or opposition proceedings) all Alnylam Product-Specific Patents (regardless of whether such Alnylam Product-Specific Patents are Controlled by Alnylam or Genzyme). Genzyme shall consult with Alnylam, including through the IP

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Committee, on the preparation, filing, prosecution and maintenance of all Alnylam Product-Specific Patents but shall retain final decision making authority on such preparation, filing, prosecution and maintenance. Genzyme shall furnish Alnylam via electronic mail or other such method as mutually agreed by the Parties with copies of proposed filings and documents received from outside counsel in the course of such filing, prosecution or maintenance of and/or copies of documents filed with the relevant patent offices with respect to Alnylam Product-Specific Patents and such other documents directly related to the prosecution and maintenance of Alnylam Product-Specific Patents reasonably necessary for Alnylam to exercise its rights under this Section 10.3.3(b), and as applicable in sufficient time prior to filing such document or making any payment due thereunder to allow for review and comment by Alnylam. Genzyme shall consider in good faith timely input from Alnylam thereon, but Genzyme will make all decisions relating to the prosecution and maintenance of Alnylam Product-Specific Patents. Alnylam shall make available to Genzyme its authorized attorneys, agents or representatives, and such of its employees as are reasonably necessary to assist Genzyme in obtaining and maintaining the patent protection described under this Section 10.3.3(b). Alnylam shall sign, or have signed, all legal documents necessary to file and prosecute such patent applications or to obtain or maintain such patents.

(c) In the event that Genzyme elects not to seek or continue to seek or maintain patent protection on any Alnylam Product-Specific Patent in any country in the Licensed Territory, Genzyme shall notify Alnylam at least [***] days before such Alnylam Product-Specific Patent would become abandoned, no longer available or otherwise forfeit (including any decision by Genzyme not to continue to file and prosecute at least one patent application claiming priority to an Alnylam Product-Specific Patent issuing in any particular country). Alnylam shall have the right (but not the obligation), at its expense, to seek, prosecute and maintain in any country patent protection on any such Alnylam Product-Specific Patent (including the defense of any interference or opposition proceedings). If Alnylam exercises such right, the applicable Alnylam Product-Specific Patent (and all Patent Rights thereafter filed by or on behalf of Alnylam claiming priority thereto) shall no longer be treated as a “Alnylam Product-Specific Patent” hereunder, and if Controlled by Genzyme, Genzyme shall assign and transfer such Alnylam Product-Specific Patent to Alnylam. Genzyme shall make available to Alnylam its authorized attorneys, agents or representatives, such of its employees as are reasonably necessary to assist Alnylam in obtaining and maintaining the patent protection described under this Section 10.3.3(c). Genzyme shall sign, or have signed, all legal documents as are reasonably necessary to assist Alnylam in obtaining and maintaining the patent protection described under this Section 10.3.3(c).

10.3.4 Joint Collaboration IP.

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[***] shall consult with [***] on the filing, prosecution and maintenance of all such Patent Rights. Each Party shall sign, or use Commercially Reasonable Efforts to have signed, all legal documents as are reasonably necessary to file and prosecute patent applications or to obtain or maintain patents in respect of such Joint Collaboration IP, at its own cost.

(b) [***] shall furnish to [***] via electronic mail or other such method as mutually agreed by the Parties copies of documents received from outside counsel in the course of such filing, prosecution or maintenance of Joint Collaboration IP and/or copies of documents relevant to such preparation, filing, prosecution, and maintenance in sufficient time prior to filing such document or making any payment due thereunder to allow for review and comment [***] and shall consider in good faith timely comments from [***] thereon. [***] shall furnish to [***] via electronic mail or other such method as mutually agreed by the Parties copies of such documents as filed in the relevant patent offices.

(c) In the event that [***] elects not to file or continue to prosecute or maintain patent protection on any Joint Collaboration IP, Alnylam shall have the right (but not the obligation) to file, prosecute and maintain Patent Rights comprising Joint Collaboration IP in the names of both Alnylam and Genzyme at [***] sole cost and expense. If [***] exercises such right, [***] shall make available to [***] its authorized attorneys, agents or representatives, and such of its employees as are reasonably necessary to assist [***] in obtaining and maintaining the patent protection described under this Section 10.3.4(c). [***] shall sign, or use Commercially Reasonable Efforts to have signed, all legal documents as are reasonably necessary to file and prosecute such patent applications or to obtain or maintain such patents.

(d) [***] shall bear all out-of-pocket patent filing, prosecution and maintenance expenses incurred with respect to Patent Rights comprising Joint Collaboration IP.

10.3.5 Patent Miscellaneous. Each Party hereby agrees: (a) to make its employees, agents and consultants reasonably available to the other Party (or to the other Party’s authorized attorneys, agents or representatives), to the extent reasonably necessary to enable such Party to undertake patent prosecution; (b) to provide the other Party with copies of all material correspondence pertaining to prosecution with the patent offices; (c) to cooperate, if necessary and appropriate, with the other Party in gaining patent term extensions wherever applicable to Patent Rights licensed under these Global License Terms; and (d) to endeavor in good faith to coordinate its efforts with the other Party to minimize or avoid interference with the prosecution and maintenance of the other Party’s patent applications.

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10.3.6 Alnylam Product-Specific Patents .

10.3.6.1 Assignment of Alnylam Product-Specific Patents. On the Implementation Date with respect to a Global Licensed Product, Alnylam will assign and transfer to Genzyme, all rights, title, and interests in and to the Alnylam Product-Specific Patents with respect to such Global Licensed Product that are owned by Alnylam on the Implementation Date, and all claims and causes of action arising from or relating to such Alnylam Product-Specific Patents, including all rights to recovery for damages from infringement arising prior to, on or after the Implementation Date. On the Implementation Date for a Global Licensed Product, Alnylam will execute and deliver a confirmatory assignment relating to all Alnylam Product-Specific Patents with respect to such Global Licensed Product assigned to Genzyme under this Section 10.3.6.1 in a mutually agreed form.

10.3.6.2 Disclosure of Future Alnylam Product-Specific Patents. Upon becoming aware of any potentially patentable invention Controlled by Alnylam that would, if patented, be included within the definition of Alnylam Product-Specific Patents with respect to any Global Licensed Product, Alnylam will promptly disclose such invention to Genzyme in writing in reasonable detail via the IP Committee.

10.3.6.3 Covenants in Support of Assignment. Alnylam will provide all further cooperation which Genzyme reasonably determines is necessary to accomplish the complete transfer of the Alnylam Product-Specific Patents with respect to a Global Licensed Product, and all associated rights, to Genzyme on or after the Implementation Date for such Global Licensed Product, including executing and delivering further assignments, consents, releases and other commercially reasonable documentation, and providing good faith testimony by affidavit, declaration, deposition, in-person or other proper means and otherwise assisting Genzyme in support of any effort by Genzyme to establish, perfect, defend or enforce its rights in such Alnylam Product-Specific Patents through filing and prosecution of such Alnylam Product-Specific Patents, interferences, oppositions, other regulatory proceedings, litigation or other means. Alnylam will obtain the cooperation of the individual inventors of any inventions disclosed in such Alnylam Product-Specific Patents assigned to Genzyme pursuant to this Section 10.3.6, including (a) obtaining signatures of such inventors on any patent applications or other documentation reasonably necessary to obtain patent protection for such inventions and (b) procuring (at Genzyme’s expense) such inventors’ good faith testimony by affidavit, declaration, deposition in-person or other proper means in support of Genzyme’s efforts in establishing, perfecting, defending or enforcing patent rights to such inventions. To the extent Alnylam cannot transfer and assign the Alnylam Product-Specific Patents with respect to a Global Licensed Product, or any portion thereof, on the Implementation Date for such Global Licensed Product, then Alnylam will transfer and assign such Alnylam Product-Specific Patents to Genzyme at its first opportunity to do so

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and, pending such transfer and assignment, such Alnylam Product-Specific Patents will be deemed to be Alnylam Patents for all purposes under these Global License Terms. To the extent further transfer or assignment of such Alnylam Product-Specific Patents is required or permitted, and Alnylam has not executed and returned to Genzyme the form of assignment reasonably requested by Genzyme within [***] business days of the delivery of such assignment to Alnylam at the address for notices set forth in Section 13.11 of the Master Agreement (Notices), then Alnylam hereby irrevocably appoints Genzyme as its attorney-in-fact with the right, authority and ability to execute and enter into such assignment on behalf of Alnylam. Alnylam stipulates and agrees that such appointment is a right coupled with an interest and will survive the unavailability of Alnylam at any future time.

10.3.6.4 Grant-Back License . Subject to the provisions of these Global License Terms, Genzyme hereby grants Alnylam a non-exclusive, non-transferable license (with no right to sublicense) under the Alnylam Product-Specific Patents to the extent necessary to perform Alnylam’s obligations under these Global License Terms and any GLP Supply Agreement.

10.4 Third Party Infringement .

10.4.1 Notices. Each Party shall promptly report in writing to the other Party any (a) known or suspected infringement of any Alnylam Technology, Genzyme Technology, Genzyme Manufacturing IP or Joint Collaboration IP or (b) unauthorized use or misappropriation of any Confidential Information or Know-How of a Party by a Third Party of which it becomes aware, in each case to the extent such infringing, unauthorized or misappropriating activities involve, as to a Global Licensed Product, a competing product in the Field (a “ Competitive Infringement ”), and shall provide the other Party with all available evidence of such infringement, unauthorized use or misappropriation.

10.4.2 Rights to Enforce.

(b) Alnylam Technology . Subject to the provisions of any In-License, Genzyme shall have the first right to initiate an Infringement Action anywhere in the world against any Third Party with respect to any Competitive Infringement in the Licensed Territory of any Alnylam Product-Specific Patent or Joint Collaboration IP, or, with Alnylam’s prior written consent, Alnylam Core Technology Patent or Alnylam

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Know-How. Alnylam will consider in good faith any request from Genzyme to initiate an Infringement Action against any Third Party with respect to a Competitive Infringement in the Licensed Territory of any Alnylam Core Technology Patent; provided , however , that Alnylam shall not be required to initiate any such Infringement Action or permit Genzyme to initiate any such Infringement Action.

(c)

Step-In Right .

(i)

If, within [***] days (or such shorter period of time as required by applicable Law to avoid loss of material enforcement rights) after Genzyme’s receipt of a notice of a Competitive Infringement with respect to any Alnylam Product-Specific Patent or Joint Collaboration IP, Genzyme does not initiate any Infringement Action permitted hereunder against such Competitive Infringement in the Licensed Territory, Alnylam may elect, in its sole discretion, to bring and control an Infringement Action in connection therewith at its sole cost and expense by providing written notice of such election to Genzyme.

(ii)

If (A) there are no Alnylam Product-Specific Patents or Patent Rights included in Joint Collaboration IP that can be asserted against a Competitive Infringement in the Licensed Territory, for any reason other than the unwillingness of Genzyme to consent to such assertion of any Patent Rights included in the Joint Collaboration IP; (B) there are Alnylam Core Technology Patent(s) that can reasonably be asserted, but Alnylam refuses to either permit Genzyme to assert or itself assert at least one of such Alnylam Core Technology Patent(s) that can reasonably be asserted against a Competitive Infringement in the Licensed Territory; and (C) Genzyme and Alnylam are unable to stop the Competitive Infringement through enforcement of any other Patent Rights or Know-How Controlled by either Party, then the royalties to be paid by Genzyme to Alnylam pursuant to Section 8.2 (Royalties), with respect to the applicable Global Licensed Product in the countries in the Licensed Territory where such Competitive Infringement exists, shall be reduced by [***] during the period when the conditions in the foregoing clauses (A), (B) and (C) exist and such Competitive Infringement continues, subject to the limitations set forth in Section 8.2 (Royalties).

10.4.3 Procedures; Expenses and Recoveries. The Party having the right to initiate any Infringement Action under Section 10.4.2 (Rights to Enforce) above shall have the sole and exclusive right to select counsel for any such Infringement Action and shall pay all expenses of such Infringement Action, including attorneys’ fees and court costs and reimbursement of the other Party’s reasonable Global Out-of-Pocket Costs in rendering assistance requested by the initiating Party. If required under applicable Law in order for the initiating Party to initiate and/or maintain such Infringement Action, or if

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either Party is unable to initiate or prosecute such Infringement Action solely in its own name or it is otherwise advisable to obtain an effective legal remedy, in each case, the other Party shall join as a party to such Infringement Action and will execute, and cause its Affiliates to execute, all documents necessary for the initiating Party to initiate litigation to prosecute and maintain such Infringement Action. In addition, at the initiating Party’s request, the other Party shall provide reasonable assistance to the initiating Party in connection with an Infringement Action at no charge to the initiating Party except for reimbursement by the initiating Party of reasonable Global Out-of-Pocket Costs incurred in rendering such assistance. The non-initiating Party shall have the right to participate and be represented in any such Infringement Action by its own counsel at its own expense. If the Parties obtain from a Third Party, in connection with such Infringement Action, any damages, license fees, royalties or other compensation (including any amount received in settlement of such litigation), after payment of any amounts required under any In-Licenses, the remaining amounts shall be allocated in all cases as follows:

(i)

first, to reimburse each Party for all expenses of such Infringement Action incurred by the Parties, including attorneys’ fees and disbursements, court costs and other litigation expenses;

(ii)

second [***] of the balance to be paid to the Party initiating such Infringement Action; and

(iii)

third, the remainder to the other Party.

Notwithstanding the foregoing, in the event that Alnylam elects to itself assert an Alnylam Core Technology Patent against a Competitive Infringement in the Licensed Territory, the Parties shall each be entitled to [***] of the balance of any recovery therefrom after reimbursement of expenses as described in clause (i) above.

10.5 Patent Term Extensions .

10.5.1 Retained Alnylam Product-Specific Patent Rights. Subject to the provisions of any Alnylam In-License, Alnylam shall use Commercially Reasonable Efforts to obtain all available supplementary protection certificates (“ SPCs ”) and other extensions of Alnylam Product-Specific Patents in the Licensed Territory that are not assigned to Genzyme pursuant to Section 10.3.5. If more than one Alnylam Product-Specific Patent is eligible for extension or patent term restoration in the Licensed Territory, Genzyme will determine, in its sole discretion, a strategy that will be designed to maximize patent protection and commercial value for the Global Licensed Product, and the Parties, subject to the provisions of any In-License, will seek patent term extensions, restorations and SPCs for Alnylam Product-Specific Patents in the Licensed Territory in accordance with that strategy. Where required under national law, and subject to the other requirements of this Section 10.5, Alnylam will make the filings for such extensions, restorations and SPCs for Alnylam Product-Specific Patents in the Licensed Territory as directed by Genzyme.

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10.5.2 Further Assurances for SPCs. Each Party will execute such authorizations and other documents and take such other actions as may be reasonably requested by the other Party to obtain any such extensions, restorations and SPCs for Alnylam Product-Specific Patents in the Licensed Territory, in accordance with this Section 10.5.

10.6 Common Interest . All information exchanged between the Parties’ representatives regarding the preparation, filing, prosecution, maintenance, or enforcement of the Patent Rights under this Section 10 will be deemed Confidential Information. In addition, the Parties acknowledge and agree that, with regard to such preparation, filing, prosecution, maintenance and enforcement of the Patent Rights under this Section 10, the interests of the Parties as collaborators and licensor and licensee are to obtain the strongest patent protection possible, and as such, are aligned and are legal in nature. The Parties agree and acknowledge that they have not waived, and nothing in these Global License Terms constitutes a waiver of, any legal privilege concerning the Patent Rights under this Section 10, including privilege under the common interest doctrine and similar or related doctrines.

10.7 Trademarks .

(a) Genzyme has the sole and exclusive right to select and develop one or more Product Trademark(s) for use by Genzyme and its Related Parties throughout the Licensed Territory. Such Product Trademark(s) may not include trademarks owned or Controlled by Alnylam (“ Alnylam Trademarks ”) and no right or license to any Alnylam Trademarks are conveyed hereunder to Genzyme. Any Product Trademark(s) that are used by Genzyme to promote and sell Licensed Products in the Licensed Territory are hereinafter referred to as the “ Genzyme Trademarks .” Genzyme (or its Related Parties, as appropriate) shall own all rights to Genzyme Trademarks and all goodwill associated therewith, throughout the Licensed Territory. Genzyme shall also own rights to any Internet domain names incorporating the applicable Genzyme Trademarks or any variation or part of such Genzyme Trademarks used as its URL address or any part of such address.

(b) In the event that Alnylam becomes aware of any infringement of any Product Trademark by a Third Party, Alnylam shall promptly notify Genzyme and the Parties shall consult with each other and jointly determine the best way to prevent such infringement, including by the institution of legal proceedings against such Third Party.

10.8 Cooperative Research and Technology (CREATE) Act Acknowledgment . It is the intention of the Parties that these Global License Terms are a “joint research agreement” as that phrase is defined in Section 35 U.S.C. 103(c).

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11.

TERM AND TERMINATION

11.1 Term . These Global License Terms shall be effective as of the Implementation Date and, unless terminated earlier pursuant to Section 11.2 (Termination Rights), these Global License Terms shall continue in effect on a Global Licensed Product-by-Global Licensed Product and country-by-country basis until expiration of the last Royalty Term to expire under these Global License Terms (“ Term ”). Upon expiration of the Royalty Term for a Global Licensed Product, all licenses of the Parties under Section 7 (Licenses) with respect to such Global Licensed Product then in effect shall become fully paid-up, perpetual, exclusive licenses.

11.2 Termination Rights . These Global License Terms may be terminated by the Parties only as set forth in this Section 11.2.

11.2.1 Termination of Global Licensed Product for Convenience . Subject to the remainder of this Article 11, Genzyme shall have the right to terminate these Global License Terms with respect to any particular Global Licensed Product at any time after the Implementation Date on six (6) months prior written notice to Alnylam.

11.2.2 Termination of Global Licensed Product for Cause . These Global License Terms may be terminated with respect to any Global Licensed Product at any time during the Term upon written notice by either Party if (a) the other Party is in material breach of its obligations hereunder with respect to such Global Licensed Product, (b) such material breach relates to such Global Licensed Product and (c) the other Party has not cured such breach within thirty (30) days in the case of a payment breach, or within ninety (90) days in the case of all other breaches, after notice requesting cure of the breach; provided , however , that if any breach other than a payment breach is not reasonably curable within ninety (90) days and if a Party is making a bona fide effort to cure such breach, such termination shall be delayed for a time period to be agreed by both Parties, not to exceed an additional ninety (90) days, in order to permit such Party a reasonable period of time to cure such breach; provided , further , that in the event that the breach relates to a dispute between the Parties regarding Genzyme’s obligations to use Commercially Reasonable Efforts in Developing or Commercializing such Global Licensed Product and Genzyme disputes whether it has breached such obligation or whether such breach gives Alnylam the right to terminate these Global License Terms with respect to such Global Licensed Product and initiates a legal action against Alnylam to resolve such dispute within the foregoing sixty (60) day cure period, then these Global License Terms shall not terminate during the pendency of such legal action, provided that if (i) Genzyme is found, in an unappealable decision by a court of competent jurisdiction or an appealable decision of a court of competent jurisdiction that has not been appealed in the time allowed for an appeal in such legal action, to have materially breached these Global License Terms with respect to such Global Licensed Product, or (ii) Genzyme admits in such legal action or settlement thereof that it has materially breached these Global License Terms with respect to such Global Licensed Product, then these Global License Terms shall terminate immediately with respect to such Global Licensed Product following the Parties’ receipt of such decision or immediately following such admission, as applicable.

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11.3 Effect of Termination .

11.3.1 Effects of Termination of Global Licensed Product by Genzyme for Cause . Without limiting any other legal or equitable remedies that either Party may have, if these Global License Terms are terminated by Genzyme with respect to any Global Licensed Product pursuant to Section 11.2.2 (Termination of Global Licensed Product for Cause), then the provisions of this Section 11.3.1 shall apply:

(a) These Global License Terms shall terminate with respect to the rights and licenses granted to Genzyme for such terminated Global Licensed Product but shall continue to survive in all respects with respect to all Global Licensed Products other than the terminated Global Licensed Product.

(b) All License grants in these Global License Terms from either Party to the other with respect to the terminated Global Licensed Product shall immediately terminate.

(c) The Back-Up Option shall terminate with respect to all Back-Up Products for the terminated Global Licensed Product; provided , however , that such Back-Up Products shall, as of such date, be considered Option Products for the purposes of the Master Agreement, and the Options granted under the Master Agreement to siRNA that targets the same gene as the terminated Global Licensed Product shall again apply in accordance with the terms and conditions set forth in the Master Agreement;

(d) Genzyme shall as promptly as practicable transfer to Alnylam or Alnylam’s designee (i) possession and ownership of all Regulatory Approvals and pricing and reimbursement approvals relating to the Development, Manufacture or Commercialization of the terminated Global Licensed Product, and (ii) copies of all non-clinical and clinical data and material regulatory correspondence relating to the terminated Global Licensed Product, provided that Alnylam shall reimburse Genzyme for any reasonable out-of-pocket expenses incurred by Genzyme in connection with such transfer;

(e) Genzyme will assign and transfer to Alnylam, all rights, title and interests in and to any Alnylam Product Specific Patents that relate solely to the terminated Global Licensed Product that were assigned to Genzyme pursuant to Section 10.3.5 (Alnylam Product-Specific Patents), provided that Alnylam shall reimburse Genzyme for any reasonable out-of-pocket expenses incurred by Genzyme in connection with such assignment and transfer. In such event, Genzyme will execute and deliver a patent assignment relating to such Alnylam Product-Specific Patents in the form reasonably requested by Alnylam; and

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(f) each Party shall promptly pay any amounts owed to the other Party as of the effective date of such termination.

11.3.2 Effects of Termination of Global Licensed Product by Alnylam for Cause or by Genzyme for Convenience . Without limiting any other legal or equitable remedies that either Party may have, if these Global License Terms are terminated with respect to any Global Licensed Product by Genzyme pursuant to Section 11.2.1 (Termination of Global Licensed Product for Convenience) or by Alnylam pursuant to Section 11.2.2 (Termination of Global Licensed Product for Cause), then the provisions of this Section 11.3.2 shall apply:

(b) The license grants to Alnylam in Section 7.2 (License Grants to Alnylam) shall survive such termination with respect to the Reverted Global Licensed Product.

(c) Genzyme will grant to Alnylam, effective upon the effective date of termination and subject to the terms of any applicable Genzyme In-License, a non-transferable, sublicensable (on terms consistent with Section 7.1.4 (Sublicensing Terms)), worldwide, non-exclusive, royalty-free license under any Genzyme Collaboration IP and Genzyme Patent Rights that Cover any Global Licensed Product that is being Developed or Commercialized by Genzyme pursuant to these Global License Terms on the effective date of termination, in the form that such Global Licensed Product exists on the effective date of termination (a “ Reverted Global Licensed Product ”), solely to the extent necessary to Develop and Commercialize the Reverted Global Licensed Product in the Field in the Licensed Territory. Notwithstanding the foregoing, if (i) any Patent Rights that Cover any Reverted Global Licensed Product are Controlled by Genzyme pursuant to a Genzyme In-License and (ii) such Genzyme In-License cannot be assigned to Alnylam or does not relate exclusively to the Reverted Global Licensed Product, Genzyme shall promptly disclose any payment obligations under such Genzyme In-License to Alnylam and such Genzyme Patent Rights shall be subject to the license granted in this Section 11.3.2(b) only if Alnylam agrees in writing to (A) reimburse Genzyme for one hundred percent (100%) of any amounts that become payable under such Genzyme In-License as a result of Alnylam’s exercise of the license granted in this Section 11.3.2(b), (B) comply with all applicable terms and conditions of such Genzyme In-License and (C) perform and take such actions as may be required to allow Genzyme to comply with its obligations under such Genzyme In-License.

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(d) The Back-Up Option shall terminate with respect to all Back-Up Products for the terminated Global Licensed Product and such Back-Up Product shall be treated as an Option Product for which Genzyme has not exercised an Option for purposes of Section 3.5 of the Master Agreement;

(e) Genzyme will assign and transfer to Alnylam, all rights, title and interests in and to any Alnylam Product Specific Patents that relate solely to the terminated Global Licensed Product that were assigned to Genzyme pursuant to Section 10.3.5 (Alnylam Product-Specific Patents). In such event, Genzyme will execute and deliver a patent assignment relating to such Alnylam Product-Specific Patents in the form reasonably requested by Alnylam;

(f) Genzyme shall as promptly as practicable transfer to Alnylam or Alnylam’s designee (i) possession and ownership of all governmental or regulatory filings and approvals (including all Regulatory Approvals and pricing and reimbursement approvals) and material correspondence and conversation logs relating to the Development, Manufacture or Commercialization of the Reverted Global Licensed Product and all Genzyme Trademarks, (ii) copies of all data, reports, records and materials, and other sales and marketing related information in Genzyme’s possession or Control to the extent that such data, reports, records, materials or other information relate to the Development, Manufacture or Commercialization of the Reverted Global Licensed Product, including all non-clinical and clinical data relating to the Reverted Global Licensed Product, and customer lists and customer contact information and all adverse event data related to the Reverted Global Licensed Product in Genzyme’s possession or Control, provided that for a period of [***] months after the effective date of termination with respect to such Reverted Global Licensed Product, Genzyme shall use Commercially Reasonable Efforts to obtain for Alnylam the right to access all such data, reports, records, materials, and other sales and marketing related information), and (iii) all records and materials in Genzyme’s possession or Control containing Confidential Information of Alnylam exclusively related to the Reverted Global Licensed Product. In addition, Genzyme shall appoint Alnylam as Genzyme’s and/or Genzyme’s Related Parties’ agent for all Reverted Global Licensed Product-related matters involving Regulatory Authorities in the Licensed Territory until all Regulatory Approvals and other regulatory filings have been transferred to Alnylam or its designee.

(g) If the effective date of termination is after First Commercial Sale of the Reverted Global Licensed Product, then Genzyme shall appoint Alnylam as its exclusive distributor of the Reverted Global Licensed Product in the Licensed Territory and grant Alnylam the right to appoint sub-distributors, until such time as all Regulatory Approvals in the Licensed Territory have been transferred to Alnylam or its designee.

(h) If Genzyme or its Related Parties are Manufacturing finished product with respect to the Reverted Global Licensed Product on the effective date of termination, at Alnylam’s option, Genzyme or its Related Parties shall supply such finished product to

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Alnylam in the Licensed Territory on terms no less favorable than those on which Genzyme supplied such finished product prior to such termination to its most favored distributor in the Licensed Territory, until the earlier of (i) such time as all Regulatory Approvals in the Licensed Territory related to the Reverted Global Licensed Product have been transferred to Alnylam or its designee, Alnylam has obtained all necessary manufacturing approvals and Alnylam has procured or developed its own source of such finished product supply or (ii) [***] months following the effective date of termination.

(i) If Alnylam so requests, and to the extent permitted under Genzyme’s obligations to Third Parties on the effective date of termination, Genzyme shall transfer to Alnylam any Third Party agreements relating solely and exclusively to the Development, Manufacture or Commercialization of the Reverted Global Licensed Product to which Genzyme is a party (including any Genzyme In-License), subject to any required consents of such Third Party, which Genzyme shall use Commercially Reasonable Efforts to obtain promptly.

(j) Genzyme shall promptly transfer and assign to Alnylam all of Genzyme’s and its Affiliates’ rights, title and interests in and to the Genzyme Trademark(s) exclusively used in connection with the Reverted Global Licensed Product (but not any Genzyme house marks or any trademark containing the word “Genzyme”) owned by Genzyme and used for the Reverted Global Licensed Product in the Field in the Licensed Territory.

(k) Genzyme shall transfer to Alnylam any inventory of the Reverted Global Licensed Product Controlled by Genzyme or its Affiliates as of the termination date at the actual price paid by Genzyme for such supply.

(l) Genzyme shall provide any other assistance reasonably requested by Alnylam for the purpose of allowing Alnylam or its designee to proceed expeditiously with the Development, Manufacture and Commercialization of the Reverted Global Licensed Product in the Licensed Territory; provided that Genzyme’s obligations under this clause shall expire [***] months after the effective date of termination of such Reverted Global Licensed Product.

(m) Genzyme shall execute all documents and take all such further actions as may be reasonably requested by Alnylam in order to give effect to the foregoing clauses.

11.4 Effect of Expiration or Termination; Survival . Any expiration or termination of these Global License Terms (a) shall not relieve the Parties of any obligation accruing prior to such expiration or termination and (b) shall be without prejudice to the rights of either Party against the other Party accrued or accruing under these Global License Terms prior to such expiration or termination, including the obligation to pay royalties for any Global Licensed Product sold prior to such expiration or termination. If these Global License Terms expire or are terminated with respect to any Global Licensed Product, the following provisions shall survive with respect to such

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Global Licensed Product: (a) Sections 1 (Definitions), 9.3 (Warranty Disclaimer), 10.1 (Inventorship), 10.2 (Ownership), 11.3 (Effect of Termination), and 11.4 (Effect of Expiration or Termination; Survival), 12 (Performance of Affiliates) of these Global License Terms, and (b) Sections 1 (Definitions), 7 (Confidentiality and Publication), 9 (Royalty Reports; Payments; Audits), 10 (Indemnification; Limitation of Liability; Insurance), 12 (Term and Termination) and 13 (Miscellaneous) of the Master Agreement. Section 8.2.6 (Royalty Floor) shall survive any termination or expiration of these Global License Terms with respect to royalties accruing prior to such termination or expiration. Section 9 of the Master Agreement (Royalty Reports; Payments; Audit) shall survive for so long as any royalties are due under these Global License Terms plus three (3) years. Except as otherwise set forth in this Section 11, upon termination or expiration of these Global License Terms in their entirety ( i.e. , with respect to all Global Licensed Products), all rights and obligations of the Parties under these Global License Terms shall cease, but, for clarity, such expiration or termination of these Global License Terms shall not result in the termination or expiration of the Master Agreement or any License Terms. Upon termination or expiration of these Global License Terms with respect to any particular Global Licensed Product, all rights and obligations of the Parties under these Global License Terms with respect to such Global Licensed Product shall cease, but such termination or expiration shall not affect the Parties’ rights and obligations under these Global License Terms with respect to any other Global Licensed Product.

12.

PERFORMANCE BY AFFILIATES

12.1 Use of Affiliates . Each Party acknowledges and accepts that the other Party may exercise its rights and perform its obligations under these Global License Terms either directly or through one or more of its Affiliates. A Party’s Affiliates will have the benefit of all rights (including all licenses) of such Party under these Global License Terms. Accordingly, in these Global License Terms “Genzyme” will be interpreted to mean “Genzyme and/or its Affiliates” and “Alnylam” will be interpreted to mean “Alnylam and/or its Affiliates” where necessary to give each Party’s Affiliates the benefit of the rights provided to such Party in these Global License Terms; provided , however , that in any event each Party will remain responsible for the acts and omissions, including financial liabilities, of its Affiliates.

12.2 Future Acquisition of a Party or its Business . [***]

12.3 Acquired Programs .

12.3.1 [***]

12.3.2 [***].

12.3.3 For clarity, upon the closing of the acquisition of the stock and/or assets of Sirna Therapeutics, Inc. by Alnylam from Merck Sharpe & Dohme Corp., all relevant acquired intellectual property rights acquired in such transaction that may be Controlled by Alnylam (without any further action by Alnylam or Sirna Therapeutics, Inc.) shall become Controlled by Alnylam for the purposes of these Global License Terms.

[Remainder of page intentionally left blank]

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SCHEDULE 1.2.8

ALNYLAM CORE TECHNOLOGY PATENTS

SCHEDULE 1.2.8-1:

[ To be added from the applicable Option Data Package ]

SCHEDULE 1.2.8-2:

[ To be added from the applicable Option Data Package ]

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SCHEDULE 1.2.15

ALNYLAM PRODUCT-SPECIFIC PATENTS

SCHEDULE 1.2.15-1:

[ To be added from the applicable Option Data Package ]

SCHEDULE 1.2.15-2:

[ To be added from the applicable Option Data Package ]

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SCHEDULE 1.2.96

LICENSED TARGET

SCHEDULE 1.2.96-1:

[ To be added from the applicable Option Data Package ]

SCHEDULE 1.2.96-2:

[ To be added from the applicable Option Data Package ]

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SCHEDULE 9.1

DISCLOSURE SCHEDULE

SCHEDULE 9.1-1:

[ To be added from the applicable Option Data Package ]

SCHEDULE 9.1-2:

[ To be added from the applicable Option Data Package ]

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SCHEDULE 9.1.12

(A) EXISTING ALNYLAM IN-LICENSES

[ To be added from the applicable Option Data Package ]

(B) ADDITIONAL ALNYLAM IN-LICENSES

[ To be added from the applicable Option Data Package ]

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SCHEDULE 9.4.1(e)

EXCEPTIONS TO EXCLUSIVITY

Confidential Materials omitted and filed separately with the Securities and Exchange Commission. A total of 1 page was omitted.

[***]

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E XECUTION V ERSION

APPENDIX C

CO-CO PRODUCT LICENSE AND COLLABORATION TERMS

AN APPENDIX TO THE MASTER COLLABORATION AGREEMENT

dated as of January 11, 2014

by and between

ALNYLAM PHARMACEUTICALS, INC.

and

GENZYME CORPORATION

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TABLE OF CONTENTS


1. RELATIONSHIP WITH MASTER AGREEMENT; DEFINITIONS			1

2. DEVELOPMENT COLLABORATION			20

2.1. Overview			20

2.2. Development Plans			20

2.3. Joint Responsibilities for Development Activities and Costs			26

2.4. Diligence			29

2.5. Records; Reports; Information Sharing			29

2.6. Third Parties			31

3. REGULATORY MATTERS			31

3.1. Regulatory Filings and Interactions in the Genzyme Territory			31

3.2. Regulatory Filings and Interactions in the Co-Co Territory			33

3.3. EMA Regulatory Strategy			35

3.4. Costs of Regulatory Affairs			35

3.5. Right of Reference			35

4. COMMERCIALIZATION OF THE LICENSED PRODUCTS			36

4.1. Responsibility, Cost and Diligence			36

4.2. Co-Co Territory Commercialization			36

4.3. Genzyme Territory Commercialization Plan			39

4.4. Advertising and Promotional Materials			39

4.5. Commercialization Reporting Obligations			41

4.6. Recalls, Market Withdrawals or Corrective Actions			42

4.7. Export Monitoring			42

5. COLLABORATION MANAGEMENT			42

5.1. Product Joint Steering Committee			42

5.2. Appointment of Subcommittees, Project Teams and CLP Alliance Managers			43

5.3. PJSC Meetings			44

5.4. PJSC Minutes			44

5.5. PJSC Development Responsibilities			44

5.6. PJSC Commercialization Responsibilities			45

5.7. PJSC Decision-Making			46

5.8. Term of PJSC			47

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6. MANUFACTURE AND SUPPLY OF CO-CO LICENSED PRODUCTS			48

6.1. Supply Agreements			48

7. LICENSES			48

7.1. License Grants to Genzyme			48

7.2. License Grants to Alnylam			51

7.3. Joint Collaboration IP			52

7.4. In-Licenses			52

7.5. Bankruptcy			53

7.6. No Other Rights			53

8. FINANCIAL TERMS FOR GENZYME TERRITORY			54

8.1. Milestone Fees			54

8.2. Royalties			55

9. FINANCIAL TERMS FOR CO-CO TERRITORY			56

10. REPRESENTATIONS, WARRANTIES AND COVENANTS			56

10.1. Representations and Warranties of Alnylam			56

10.2. Representations and Warranties of Genzyme			58

10.3. Warranty Disclaimer			58

10.4. Certain Covenants			59

11. INTELLECTUAL PROPERTY OWNERSHIP, PROTECTION AND RELATED MATTERS			60

11.1. Inventorship			60

11.2. Ownership			60

11.3. Prosecution and Maintenance of Patent Rights			60

11.4. Third Party Infringement			63

11.5. Patent Term Extensions			66

11.6. Common Interest			67

11.7. Trademarks			67

11.8. Cooperative Research and Technology (CREATE) Act Acknowledgment			68

12. TERM AND TERMINATION			68

12.1. Term			68

12.2. Termination Rights			68

12.3. Effect of Termination			71

12.4. Fundamental Breach of Alnylam’s Development Obligations			76

12.5. Effect of Expiration or Termination; Survival			76

13. PERFORMANCE BY AFFILIATES			77

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SCHEDULES


Schedule 1.2.14-1		Alnylam Core Technology Patents for ALN-TTRsc

Schedule 1.2.19-1		Alnylam Product-Specific Patents for ALN-TTRsc

Schedule 2.2.1-1		Global Development Strategy for ALN-TTRsc

Schedule 2.2.2-1		Global Development Plan for ALN-TTRsc

Schedule 2.2.3-1		Genzyme Territory Development Plan for ALN-TTRsc

Schedule 2.7		TTRsc/02 Arbitration Criteria

Schedule 4.2-1		Co-Co Territory Commercialization Plan for ALN-TTRsc

Schedule 10.1-1		Disclosure Schedule

Schedule 10.1.12		Existing Alnylam In-Licenses / Additional Alnylam In-Licenses

Schedule 10.4.1.4		Exceptions to Exclusivity

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C O -C O L ICENSE T ERMS

CO-CO PRODUCT LICENSE AND COLLABORATION TERMS

THESE CO-CO PRODUCT LICENSE AND COLLABORATION TERMS are Appendix C to the Master Agreement, dated as of the Execution Date, by and between Alnylam Pharmaceuticals, Inc., a corporation organized and existing under the laws of the State of Delaware (“ Alnylam ”) and, Genzyme Corporation, a corporation organized and existing under the laws of the Commonwealth of Massachusetts (“ Genzyme ”).

RECITALS:

WHEREAS , Alnylam and Genzyme are parties to that certain Master Collaboration Agreement (dated as of the Execution Date) (the “ Master Agreement ”) pursuant to which Genzyme has an option to receive licenses and other rights with respect to Co-Co Licensed Products from Alnylam in the Genzyme Territory;

WHEREAS , the Parties have agreed that ALN-TTRsc is a Co-Co Licensed Product;

WHEREAS , Genzyme may exercise its Co-Co/Global Option pursuant to the Master Agreement for the siRNA known as ALN-AT3 (or a successor siRNA Controlled by Alnylam that targets Antithrombin) and such siRNA will then become a Co-Co Licensed Product;

WHEREAS , the Parties desire for Alnylam to continue to develop such Co-Co Licensed Products for the Co-Co Territory and the Genzyme Territory; and

WHEREAS , Alnylam and Genzyme now wish to set forth the terms and conditions under which Genzyme will have the right to Develop and Commercialize such Co-Co Licensed Products in the Genzyme Territory and co-Commercialize with Alnylam such Co-Co Licensed Products in the Co-Co Territory.

NOW, THEREFORE , in consideration of the foregoing premises and the mutual covenants herein contained, the Parties hereby agree as follows:

1. RELATIONSHIP WITH MASTER AGREEMENT; DEFINITIONS

1.1. Relationship with Master Agreement . These Co-Co License Terms become effective on a Co-Co Licensed Product-by-Co-Co Licensed Product basis on the Implementation Date in accordance with the Master Agreement. The Master Agreement generally governs the Parties’ relationship with respect to Co-Co Licensed Products during the period of time before Genzyme exercises its Co-Co/Global Option under the Master Agreement ( i.e. , before such product became a Co-Co Licensed Product). The Master Agreement also contains terms that are generally applicable to Co-Co Licensed Products, Global Licensed Products (as defined in the Master Agreement) and Regional Licensed Products (as defined in the Master Agreement). Accordingly, the following Sections of the Master Agreement are incorporated herein by reference: Section 2.2 (Effectiveness of Licenses to Collaboration Products); Section 5 (Collaboration Management); Section 6 (Manufacture and Supply of the Collaboration Products); Section 7 (Confidentiality and Publication); Section 9 (Royalty Reports; Payments; Audit); Section 10 (Indemnification; Limitation of Liability; Insurance); Section 12.2.4 (Challenges of Patent Rights); and Section 13 (Miscellaneous).

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1.2. Definitions . Unless specifically set forth to the contrary herein, the following terms, whether used in the singular or plural, shall have the respective meanings set forth below:

1.2.1. “ Acquired Business ” has the meaning set forth in Section 13.3 (Acquired Programs).

1.2.2. “ Acquirer ” has the meaning set forth in Section 13.2 (Future Acquisition of a Party or its Business).

1.2.3. “ Additional Development Activities ” has the meaning set forth in Section 2.2.2.5(a) (Additional Development Proposals).

1.2.4. “ Additional Development Opt-In Date ” has the meaning set forth in Section 2.2.2.5(d)(i) (Opt-In for Additional Development Activities).

1.2.5. “ Additional Development Opt-In Notice ” has the meaning set forth in Section 2.2.2.5(d)(i) (Opt-In for Additional Development Activities).

1.2.6. “ Additional Development Proposal ” has the meaning set forth in Section 2.2.2.5(a) (Additional Development Proposals).

1.2.7. “AF11 Lipid Nanoparticle Formulation” has the meaning set forth in the Master Agreement.

1.2.9. “ AJSC ” has the meaning set forth in the Master Agreement.

1.2.10. “ ALN-AT3 ” has the meaning set forth in the Master Agreement.

1.2.11. “ ALN-TTR02 ” has the meaning set forth in the Master Agreement.

1.2.12. “ ALN-TTRsc ” has the meaning set forth in the Master Agreement.

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1.2.13. “ ALN-TTRsc Global R&D Cost Opt-In Date ” has the meaning set forth in Section 2.3.1.2(a) (Global R&D Costs).

1.2.14. “ Alnylam Core Technology Patents ” means Patent Rights Controlled by Alnylam during the Term that are [***]. The Alnylam Core Technology Patents existing as of the Effective Date for ALN-TTRsc are those Patent Rights identified on Schedule 1.2.14-1 . The Alnylam Core Technology Patents existing as of the Implementation Date for ALN-AT3 will be identified as the “Alnylam Core Technology Patents” in the Option Data Package for ALN-AT3 provided by Alnylam to Genzyme under the Master Agreement and then attached hereto as Schedule 1.2.14-2 .

1.2.15. “Alnylam Developed siRNA Product” means an siRNA with respect to which (a) Alnylam Controls Patent Rights Covering such siRNA, provided that once a product first satisfies the criterion set forth in this clause (a) such criterion shall be deemed satisfied at all times thereafter as to such product, and (b) Alnylam or an Affiliate of Alnylam plays(ed) a material role in the Development.

1.2.16. “ Alnylam In-License ” means any Existing Alnylam In-License or any Collaboration In-License to which Alnylam is a party.

1.2.17. “ Alnylam Know-How ” means Know-How Controlled by Alnylam during the Term that is reasonably necessary or useful for Genzyme to Develop, Manufacture and/or Commercialize Co-Co Licensed Products in the Field in the Genzyme Territory, other than Alnylam’s interest in Know-How included in Joint Collaboration IP.

1.2.18. “ Alnylam Patents ” means Alnylam Core Technology Patents and Alnylam Product-Specific Patents.

1.2.19. “ Alnylam Product-Specific Patents ” means Patent Rights Controlled by Alnylam during the Term [***]. The Alnylam Product-Specific Patents existing as of the Effective Date for ALN-TTRsc are those Patent Rights identified on Schedule 1.2.19-1 . The Alnylam Product-Specific Patents existing as of the Implementation Date for ALN-AT3 will be identified as the “Alnylam Product-Specific Patents” in the Option Data Package for ALN-AT3 provided by Alnylam to Genzyme under the Master Agreement and then attached hereto as Schedule 1.2.19-2 . [***]

1.2.20. “ Alnylam Technology ” means, collectively, Alnylam Know-How, Alnylam Patents and Alnylam’s interest in Joint Collaboration IP.

1.2.21. “ Alnylam Trademark ” has the meaning set forth in Section 11.7(b) (Trademarks).

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1.2.22. “ ANDA ” means an Abbreviated New Drug Application (or any successor application or procedure) as defined in regulations promulgated by the FDA under the FDCA, which ANDA is filed with or intended to be filed with the FDA (and, as applicable, any other analogous application filed with a Regulatory Authority in any country other than the U.S. in the Genzyme Territory) for Regulatory Approval for marketing and selling a Co-Co Licensed Product in the Genzyme Territory.

1.2.23. “ Antithrombin ” has the meaning set forth in the Master Agreement.

1.2.24. “ Appendix ” means this Appendix B (Co-Co License and Collaboration Terms).

1.2.25. “ ATTR ” means the human disease TTR-mediated amyloidosis.

1.2.26. “ Back-Up Option ” has the meaning set forth in Section 7.1.5 (Back-Up Products).

1.2.27. “Back-Up Option Exercise Notice” has the meaning set forth in Section 7.1.5 (Back-Up Products).

1.2.28. “ Back-Up Option Period ” means (i) with respect to a Back-Up Product for ALN-TTRsc, the period beginning with the Implementation Date for ALN-TTRsc and ending on [***] and (ii) with respect to a Back-Up Product for ALN-AT3, the period beginning with the Implementation Date for ALN-AT3 and ending on [***].

1.2.29.

1.2.30. “ Back-Up Product ” has the meaning set forth for in Section 7.1.5 (Back-Up Products).

1.2.31. “ Bankrupt Party ” has the meaning set forth in Section 7.5 (Bankruptcy).

1.2.32. “ Budget Adjustment Triggers ” has the meaning set forth in Section 2.2.2.3 (Managing and Amending Global Development Plans and Global Development Budgets).

1.2.33. “ Calendar Quarter ” means the respective periods of three (3) consecutive calendar months ending on March 31, June 30, September 30 and December 31 of each Calendar Year, provided that (a) the first Calendar Quarter of the Term shall begin on the Effective Date and end on the first to occur of March 31, June 30, September 30 or December 31 thereafter and the last Calendar Quarter of the Term shall end on the last day of the Term and (b) the first Calendar Quarter of a Royalty Term for a Co-Co Licensed Product in a country shall begin on the First Commercial Sale of a Co-Co Licensed Product in such country and end on the first to occur of March 31, June 30, September 30 or December 31 thereafter and the last Calendar Quarter of a Royalty Term shall end on the last day of such Royalty Term.

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1.2.34. “ Calendar Year ” means each successive period of twelve (12) months commencing on January 1 and ending on December 31, provided that (a) the first Calendar Year of the Term shall begin on the Effective Date and end on the first December 31 thereafter and the last Calendar Year of the Term shall end on the last day of the Term and (b) the first Calendar Year of a Royalty Term for a Co-Co Licensed Product in a country shall begin on the First Commercial Sale of a Co-Co Licensed Product in such country and end on the first December 31 thereafter and the last Calendar Year of the Term shall end on the last day of such Royalty Term.

1.2.35. “ Carbohydrate Conjugate ” has the meaning set forth in the Master Agreement.

1.2.36. “ Clinical Study ” has the meaning set forth in the Master Agreement.

1.2.37. “ CLP Alliance Manager ” has the meaning set forth in Section 5.2 (Appointment of Subcommittees, Project Teams and CLP Alliance Managers).

1.2.38. “ Co-Co Clinical Supply Agreements ” means, collectively, the ALN-TTRsc Clinical Supply Agreement and the ALN-AT3 Clinical Supply Agreement entered into between Alnylam and Genzyme as described in Section 6.2 of the Master Agreement (Collaboration Product Supply Agreements) pursuant to which Alnylam will provide clinical supplies of the specified Co-Co Licensed Product to Genzyme.

1.2.39. “ Co-Co Collaboration ” means the collaboration of the Parties in the Development, Manufacture and Commercialization of a Co-Co Licensed Product under these Co-Co License Terms.

1.2.40. “ Co-Co Commercial Supply Agreements ” means, collectively, the ALN-TTRsc Commercial Supply Agreement and the ALN-AT3 Commercial Supply Agreement entered into between Alnylam and Genzyme as described in Section 6.2 of the Master Agreement (Collaboration Product Supply Agreements) pursuant to which Alnylam will provide commercial supplies of the specified Co-Co Licensed Product to Genzyme.

1.2.41. “ Co-Co/Global Option ” has the meaning set forth in the Master Agreement.

1.2.42. “ Co-Co License Terms ” means this Appendix and the terms of the Master Agreement to the extent applicable to Co-Co Licensed Products.

1.2.43. “ Co-Co Licensed Product ” means (i) ALN-TTRsc as of the Effective Date, (ii) if Genzyme exercises the Co-Co/Global Options for ALN-AT3 pursuant to the Master Agreement, then ALN-AT3 as of the applicable Option Exercise Date, and (iii) if Genzyme exercises a Back-Up Option for any Back-Up Product pursuant to Section 7.1.5 (Back-Up Products), then such Back-Up Product as of the date of delivery of the Back-Up Option Exercise Notice, in each case (i) through (iii) above, for as long as the Co-Co License Terms apply to ALN-TTRsc, ALN-AT3, or such Back-Up Product. For the sake of clarity (but not for purposes of interpretation of the Collaboration Agreement), each Co-Co Licensed Product that becomes subject to the Co-Co License Terms will be exclusively licensed to Genzyme in the Genzyme Territory in much the same way that each Regional Licensed Product will be exclusively

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licensed to Genzyme in the Genzyme Territory under the Regional License Terms, but also will be licensed to Genzyme in the Alnylam Territory to the extent necessary to enable Genzyme to co-Commercialize such Co-Co Licensed Product in the Alnylam Territory as contemplated by these Co-Co License Terms.

1.2.44. “ Co-Co Out-of-Pocket Costs ” means, with respect to certain activities hereunder, direct expenses paid or payable by either Party or its Affiliates to Third Parties and specifically identifiable and incurred to conduct such activities for a Co-Co Licensed Product, including payments to contract personnel; provided , however , that amounts paid to contract sales and marketing personnel will not be considered Co-Co Out-of-Pocket Costs.

1.2.45. “ Co-Co Supply Agreements ” means, collectively, the Co-Co Clinical Supply Agreements and the Co-Co Commercial Supply Agreements.

1.2.46. “ Co-Co Territory ” means the United States, Canada, Austria, Belgium, Denmark, Finland, France, Germany, Greece, Ireland, Italy, Luxembourg, the Netherlands, Portugal, Spain, Sweden, the United Kingdom, Norway, Switzerland, Liechtenstein, Andorra, Iceland and Greenland.

1.2.47. “ Co-Co Territory Commercialization Budget ” has the meaning set forth in Section 4.2.3 (Co-Co Territory Commercialization Budget).

1.2.48. “ Co-Co Territory Commercialization Plan ” has the meaning set forth in Section 4.2.1 (Co-Co Territory Commercialization Plan).

1.2.49. “ Co-Co Territory Development Milestone Payments ” means any Third Party License Payment that is payable as a result of the achievement of a Development milestone in the Co-Co Territory.

1.2.50. “ Co-Co Territory MMC ” means [***].

1.2.51. “ Collaboration In-License ” has the meaning set forth in the Master Agreement.

1.2.52. “ Commercialization ” or “ Commercialize ” has the meaning set forth in the Master Agreement.

1.2.53. “ Commercially Reasonable Efforts ” means [***].

1.2.54. “ Competing Program ” has the meaning set forth in Section 13.3 (Acquired Programs).

1.2.55. “ Competitive Infringement ” has the meaning set forth in Section 11.4.1 (Notices).

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1.2.56. “ Confidential Information ” has the meaning set forth in the Master Agreement.

1.2.57. “ Control, ” “ Controls ” or “ Controlled by ” has the meaning set forth in the Master Agreement.

1.2.58. “ Cost of Goods ” has the meaning set forth in the Master Agreement.

1.2.59. “ Cover ,” “ Covering ” or “ Covers ” has the meaning set forth in the Master Agreement.

1.2.60. “ CPI ” shall mean the Consumer Price Index – Urban Wage Earners and Clerical Workers, U.S. City Average, All Items, 1982-84 = 100, published by the United States Department of Labor, Bureau of Labor Statistics (or its successor equivalent index) in the United States.

1.2.61. “ CRO ” means a contract research organization.

1.2.62. “ Development ,” “ Developing ” or “ Develop ” has the meaning set forth in the Master Agreement.

1.2.63. “ Development Plan ” means, with respect to each Co-Co Licensed Product, (a) with respect to Genzyme, the Genzyme Territory Development Plan for such Co-Co Licensed Product and (b) with respect to both Parties, the Global Development Plan for such Co-Co Licensed Product.

1.2.64. “ Disputing Party ” has the meaning set forth in Section 2.3.1.2 (Global R&D Costs).

1.2.65. “ Effective Date ” means the date that the Master Agreement becomes effective in accordance with its terms.

1.2.66. “ EMA ” means the European Medicines Agency and any successor Governmental Authority having substantially the same function.

1.2.67. “ End of Phase II Package ” has the meaning set forth in Section 2.2.2.4(c)(ii).

1.2.68. “ EU ” means the European Union, as its membership may be altered from time to time, and any successor thereto.

1.2.69. “ Excess Global R&D Costs ” has the meaning set forth in Section 2.3.1.2 (Global R&D Costs).

1.2.70. “ Exclusivity Period ” means, on a Co-Co Licensed Product-by-Co-Co Licensed Product and country-by-country basis within the Genzyme Territory [***].

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1.2.71. “ Execution Date ” has the meaning set forth in the Master Agreement.

1.2.72. “ Existing Alnylam In-License ” has the meaning set forth in the Master Agreement.

1.2.73. “ Existing Genzyme In-License ” has the meaning set forth in the Master Agreement.

1.2.74. “ FAP ” has the meaning set forth in Section 2.7 (ALN-TTRsc/ALN-TTR02).

1.2.75. “ FDA ” means the United States Food and Drug Administration and any successor Governmental Authority having substantially the same function.

1.2.76. “ FDCA ” means the United States Federal Food, Drug, and Cosmetic Act of 1938, as amended from time to time, and the regulations and guidelines promulgated thereunder.

1.2.77. “ Field ” means the treatment, diagnosis and/or prevention of all human diseases.

1.2.78. “ First Commercial Sale ” means, with respect to a country, the first sale for end use or consumption of a Co-Co Licensed Product in such country, except for compassionate use or patient access programs, after all Regulatory Approvals legally required for such sale have been granted by the Regulatory Authority of such country.

1.2.79. “ First Regulatory Approval by the EMA ” means, with respect to a Co-Co Licensed Product, the earlier of (i) if Regulatory Approval in the EU is sought through the EMA centralized procedure, receipt of Regulatory Approval for such Co-Co Licensed Product from the EMA or (ii) if Regulatory Approval in the EU is sought through a national authorization procedure, receipt of Regulatory Approval for such Co-Co Licensed Product in the first (1st) MMC in the EU.

1.2.80. “ First Regulatory Approval in Japan ” means, with respect to a Co-Co Licensed Product, receipt of Regulatory Approval for such Co-Co Licensed Product in Japan.

1.2.81. “ Force Majeure ” means embargoes, war, acts of war (whether war be declared or not), terrorism, insurrections, riots, civil commotions, strikes, lockouts or other labor disturbances, fire, floods or other acts of God.

1.2.82. “ Fundamental Breach ” [***].

1.2.83. “GAAP” has the meaning set forth in the Master Agreement.

1.2.84. “ GalNAc Conjugate ” has the meaning set forth in the Master Agreement.

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1.2.85. “ Generic Competition ” means, with respect to a Co-Co Licensed Product in any country in the Genzyme Territory in a given Calendar Quarter, that, during such Calendar Quarter, (a) one or more Generic Products with respect to such Co-Co Licensed Product are commercially available in such country, and (b) Net Sales of such Co-Co Licensed Product in such country in such Calendar Quarter equal less than [***] of the average Net Sales of such Co-Co Licensed Product over the [***] consecutive Calendar Quarters immediately prior to the Calendar Quarter in which one or more Generic Products first became commercially available in such country.

1.2.86. “ Generic Product ” means, on a Co-Co Licensed Product-by-Co-Co Licensed Product and country-by-country basis, a pharmaceutical product that (a) is sold by a Person that is not a Related Party of Genzyme under a marketing authorization granted by a Regulatory Authority in such country to a Third Party; (b) [***]; and (c) is approved by the Regulatory Authority in such country pursuant to an approval process that relies in part on pivotal safety and/or efficacy data in such Regulatory Authority’s previous grant of marketing authorization for such Co-Co Licensed Product.

1.2.87. “ Genzyme Collaboration IP ” means (a) any Know-How, first identified, discovered or developed solely by employees of Genzyme or its Affiliates or other persons not employed by Alnylam acting on behalf of Genzyme, in the conduct of the Collaboration and (b) any Patent Rights that claim or Cover such Know-How and are Controlled by Genzyme at any time during the Term. Genzyme Collaboration IP excludes Genzyme’s interest in Joint Collaboration IP, in each case (a) and (b), other than Genzyme Manufacturing IP.

1.2.88. “ Genzyme Disclosed Manufacturing Know-How ” means Know-How (a) Controlled by Genzyme at any time during the Term that is useful in the Manufacture of a Co-Co Licensed Product and (b) that Genzyme, in its sole discretion, discloses in writing to Alnylam in the course of the Collaboration.

1.2.89. “ Genzyme In-License ” means any Existing Genzyme In-License, Un-Blocking Genzyme In-License, or any Collaboration In-License to which Genzyme is a party.

1.2.90. “ Genzyme Know-How ” means Know-How Controlled by Genzyme during the Term that is reasonably necessary or useful for Alnylam to Develop, Commercialize and/or Manufacture Co-Co Licensed Products in the Field in the Co-Co Territory (other than Genzyme’s rights in Joint Collaboration IP, Genzyme Collaboration IP and Genzyme Manufacturing IP).

1.2.91. “ Genzyme Manufacturing IP ” means (a) any Know-How related to the Manufacture of Co-Co Licensed Products (or oligonucleotides generally) Controlled by Genzyme at any time during the Term, and (b) any Patent Rights that claim or cover such Know-How and are Controlled by Genzyme at any time during the Term, excluding Improvement Manufacturing Patent Rights and Genzyme Disclosed Manufacturing Know-How.

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1.2.92. “ Genzyme Patent Jurisdictions ” has the meaning set forth in the Master Agreement.

1.2.93. “ Genzyme Patent Rights ” means those Patent Rights Controlled by Genzyme during the Term that are reasonably necessary or useful to Develop, Commercialize and/or Manufacture Co-Co Licensed Products in the Field in the Co-Co Territory. Genzyme Patent Rights excludes Patent Rights included in Genzyme Collaboration IP, Genzyme’s interest in Joint Collaboration IP and Genzyme Manufacturing IP.

1.2.94. “ Genzyme Technology ” means, collectively, Genzyme Know-How, Genzyme Patent Rights, Genzyme Collaboration IP and Genzyme’s interest in Joint Collaboration IP, but excluding Genzyme Manufacturing IP.

1.2.95. “ Genzyme Territory ” means all countries and territories of the world other than the Co-Co Territory.

1.2.96. “ Genzyme Territory Commercialization Plan ” has the meaning set forth in Section 4.3 (Genzyme Territory Commercialization Plan).

1.2.97. “ Genzyme Territory Development Plan ” has the meaning set forth in Section 2.2.3 (Genzyme Territory Development Plan).

1.2.98. “ Genzyme Territory MMC ” [***].

1.2.99. “ Genzyme Trademark ” has the meaning set forth in Section 11.7(b) (Trademarks).

1.2.100. “ Global Branding Strategy ” has the meaning set forth in Section 4.4.1 (Global Branding).

1.2.101. “ Global Clinical Study ” has the meaning set forth in Section 5.5.5 (PJSC Development Responsibilities).

1.2.102. “ Global Development Activity(ies) ” has the meaning set forth in Section 2.2.2.1 (Global Development Plans).

1.2.103. “ Global Development Budget ” has the meaning set forth in Section 2.2.2.2 (Global Development Budgets).

1.2.104. “ Global Development Plan ” has the meaning set forth in Section 2.2.2.1 (Global Development Plans).

1.2.105. “ Global Development Strategy ” has the meaning set forth in Section 2.2.1 (Global Development Strategy).

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1.2.106. “ Global Option Period ” has the meaning set forth in the Master Agreement.

1.2.107. “ Global R&D Cost Opt-In Date ” has the meaning set forth in Section 2.3.1.2 (Global R&D Costs).

1.2.108. “ Global R&D Costs ” means, with respect to a Co-Co Licensed Product, R&D Costs incurred in connection with any Global Development Activity for such Co-Co Licensed Product.

1.2.109. “ Global R&D Costs Report ” has the meaning set forth in Section 2.3.1.2 (Global R&D Costs).

1.2.110. “ Global Regulatory Costs ” has the meaning set forth in Section 2.2.2.2 (Global Development Budgets).

1.2.111. “ Governmental Authority ” means any applicable government authority, court, tribunal, arbitrator, agency, department, legislative body, commission or other instrumentality of (a) any government of any country or territory, (b) any nation, state, province, county, city or other political subdivision thereof or (c) any supranational body.

1.2.112. “ Gross Margin ” means, with respect to a Co-Co Licensed Product in the Co-Co Territory, [***].

1.2.113. “ Human POP Study ” has the meaning set forth in the Master Agreement.

1.2.114. “ IFRS ” has the meaning set forth in the Master Agreement.

1.2.115. “ Implementation Date ” means (i) with respect to ALN-TTRsc, the Effective Date, (ii) with respect to ALN-AT3, the Option Exercise Date for ALN-AT3, and (iii) with respect to each Back-Up Product with respect to which Genzyme exercised the Back-Up Option, the date on which Genzyme sent to Alnylam the Back-Up Option Exercise Notice for such Back-Up Product under Section 7.1.5 (Back-Up Products).

1.2.116. “ Improvement Manufacturing Patent Right ” means a Patent Right owned exclusively by Genzyme or its Affiliates that claims an invention related to the Manufacture of a Co-Co Licensed Product that was made (a) by Genzyme or its Affiliates after the Effective Date in connection with Manufacturing Co-Co Licensed Products and (b) using Alnylam Know-How that, at the time such Alnylam Know-How was disclosed to Genzyme or its Affiliates, constituted Alnylam’s Confidential Information under Section 7 of the Master Agreement (Confidentiality and Publication).

1.2.117. “ IND ” has the meaning set forth in the Master Agreement.

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1.2.118. “ In-License ” has the meaning set forth in the Master Agreement.

1.2.119. “ Infringement Action ” has the meaning set forth in Section 11.4.2(a) (Genzyme Technology).

1.2.120. “ Joint Collaboration IP ” means, collectively, (a) any Know-How first identified, discovered or developed jointly by employee(s), agent(s) or consultant(s) acting on behalf of Alnylam or its Affiliates, on the one hand, and employee(s), agent(s) or consultant(s) acting on behalf of Genzyme or its Affiliates, on the other hand, in the conduct of the Collaboration that is Controlled by Alnylam and Genzyme, and (b) any Patent Rights that Cover such Know-How and are Controlled by Alnylam and Genzyme.

1.2.121. “ Know-How ” has the meaning set forth in the Master Agreement.

1.2.122. “ Laws ” has the meaning set forth in the Master Agreement.

1.2.123. “ Licensed Target ” means, for ALN-TTRsc, TTR, and, if the Co-Co/Global Option is exercised for ALN-AT3, then Antithrombin.

1.2.124. “ Lipid Nanoparticle Formulation ” has the meaning set forth in the Master Agreement.

1.2.125. “ Litigation Expenses ” has the meaning set forth in Section 11.4.3 (Procedures; Expenses and Recoveries).

1.2.126. “ Manufacturing ” or “ Manufacture ” has the meaning set forth in the Master Agreement.

1.2.127. “ Manufacturing Claim ” means a claim within a Patent Right directed solely to Manufacturing a Co-Co Licensed Product.

1.2.128. “ MMC ” means any Co-Co Territory MMC or Genzyme Territory MMC.

1.2.129. “ NDA ” has the meaning set forth in the Master Agreement.

1.2.130. “ Net Sales ” means, with respect to a Co-Co Licensed Product, the aggregate gross invoiced sales prices from sales of all units of such Co-Co Licensed Product sold by a Party and its Related Parties to independent Third Parties (other than a Sublicensee) after deducting, if not previously deducted, from the amount invoiced or received:

(a) trade, quantity and cash discounts, credits or allowances actually given;

(b) returns, rejections or recalls (due to spoilage, damage, expiration of useful life or otherwise);

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(c) Third Party rebates, chargebacks, hospital buying group/group purchasing organization administration fees or managed care organization rebates actually given;

(d) rebates and similar payments made with respect to sales paid for by any governmental or regulatory authority such as Federal or state Medicaid, Medicare or similar state program;

(e) distribution fees and sales commissions paid to Third Parties;

(f) retroactive price reductions or billing corrections;

(g) value added, sales and use, excise and other similar taxes and surcharges, customary transportation and insurance, custom duties, and other governmental charges; and

(h) amounts previously included in Net Sales of such Co-Co Licensed Product that are adjusted or written-off by such Party or its Related Parties as bad debt or otherwise uncollectible in accordance with the standard practices of such Party or its Related Parties for writing off uncollectible amounts consistently applied; provided , however , if any such written-off amounts are subsequently collected, such collected amounts shall be included in Net Sales in the period in which they are subsequently collected.

For Genzyme, such amounts shall be determined from the books and records of Genzyme or its Related Parties, maintained in accordance with IFRS. For Alnylam, such amounts shall be determined from the books and records of Alnylam or its Related Parties, maintained in accordance with GAAP.

In the case of any sale or other disposal for value, such as barter or counter-trade, of a Co-Co Licensed Product, or part thereof, other than in an arm’s length transaction exclusively for cash, Net Sales shall be calculated as above on the value of the non-cash consideration received or the fair market price (if higher) of such Co-Co Licensed Product in the country of sale or disposal, as determined in accordance with IFRS or GAAP, as applicable.

Notwithstanding the foregoing, the following will not be included in Net Sales for a Party: (1) sales between or among such Party and its Related Parties (but Net Sales shall include sales to the first Third Party (other than a Sublicensee) by such Party or its Related Parties); (2) samples of Co-Co Licensed Product used to promote additional Net Sales, in amounts consistent with normal business practices of such Party; and (3) disposal or use of Co-Co Licensed Products in Clinical Studies or under compassionate use, patient assistance, named patient use, or test marketing programs or non-registrational studies or other similar programs or studies where the Co-Co Licensed Product is supplied without charge or at the actual manufacturing cost thereof (without allocation of indirect costs or any mark-up).

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In the case where a Co-Co Licensed Product is sold as part of a Combination Product in a country in the Licensed Territory, Net Sales for the Co-Co Licensed Product included in such Combination Product in such country shall be calculated as follows:

(i)

if the Co-Co Licensed Product is sold separately in such country and the other active ingredient or ingredients in the Combination Product are sold separately in such country, Net Sales for the Co-Co Licensed Product shall be calculated by multiplying actual Net Sales of such Combination Product in such country by the fraction A/(A+B), where A is the invoice price of the Co-Co Licensed Product when sold separately in such country and B is the total invoice price of the other active ingredient or ingredients in the Combination Product when sold separately in such country;

(ii)

if the Co-Co Licensed Product is sold separately in such country but the other active ingredient or ingredients in the Combination Product are not sold separately in such country, Net Sales for the Co-Co Licensed Product shall be calculated by multiplying actual Net Sales of such Combination Product in such country by the fraction A/D, where A is the invoice price of the Co-Co Licensed Product when sold separately in such country and D is the invoice price of the Combination Product in such country;

(iii)

if the Co-Co Licensed Product is not sold separately in such country but the other active ingredient or ingredients in the Combinations Product are sold separately in such country, Net Sales for the Co-Co Licensed Product shall be calculated by multiplying actual Net Sales of such Combination Product by the fraction 1 – (B/D), where B is the invoice price of the other active ingredient or ingredients in the Combination Product when sold separately in such country and D is the invoice price of the Combination Product in such country; or

(iv)

if neither the Co-Co Licensed Product nor the other active ingredient or ingredients in the Combination Product are sold separately in such country, the Parties shall determine Net Sales for the Co-Co Licensed Product in such Combination Product by mutual agreement based on the relative contribution of the Co-Co Licensed Product and each other active ingredient to the Combination Product, and shall take into account in good faith any applicable allocations and calculations that may have been made for the same period in other countries.

For purposes of this Section, “ Combination Product ” means a product that includes at least one active ingredient other than a Co-Co Licensed Product. Drug delivery vehicles, adjuvants, and excipients shall not be deemed to be “active ingredients”, except in the case where such delivery vehicle, adjuvant, or excipient is recognized by the FDA as an active ingredient in accordance with 21 C.F.R. § 210.3(b)(7).

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1.2.131. “Non-Bankrupt Party” has the meaning set forth in Section 7.5 (Bankruptcy).

1.2.132. “Non-Disputing Party” has the meaning set forth in Section 2.3.1.2 (Global R&D Costs).

1.2.133. “ Option Data Package ” has the meaning set forth in the Master Agreement.

1.2.134. “ Option Exercise Date ” has the meaning set forth in the Master Agreement.

1.2.135. “ Option Exercise Notice ” has the meaning set forth in the Master Agreement.

1.2.136. “ Party ” means Genzyme and/or Alnylam.

1.2.137. “ Patent Challenge ” has the meaning set forth in Section 12.2.3 (Challenges of Patent Rights).

1.2.138. “ Patent Rights ” has the meaning set forth in the Master Agreement.

1.2.139. “ Person ” means any natural person, corporation, unincorporated organization, partnership, association, sole proprietorship joint stock company, joint venture, limited liability company, trust or government, or any Governmental Authority, or any other similar entity.

1.2.140. “ Phase 2 Budget ” has the meaning set forth in Section 2.2.2.4 (Budget Caps; Adjustment and Compensation).

1.2.141. [***].

1.2.142. “ Phase 3 Budget ” has the meaning set forth in Section 2.2.2.4 (Budget Caps; Adjustment and Compensation).

1.2.143. [***].

1.2.144. “ Phase I Study ” has the meaning set forth in the Master Agreement.

1.2.145. “ Phase II Study ” has the meaning set forth in the Master Agreement.

1.2.146. “ Phase III Study ” has the meaning set forth in the Master Agreement.

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1.2.147. “ Post-Marketing Study ” has the meaning set forth in the Master Agreement.

1.2.148. “ Post-Phase 3 Budget ” has the meaning set forth in Section 2.2.2.4 (Budget Caps; Adjustment and Compensation).

1.2.149. [***].

1.2.150. “ Product Joint Steering Committee ” or “ PJSC ” means the joint steering committee as more fully described in Section 5.1 (Product Joint Steering Committee).

1.2.151. “ Product Trademark(s) ” means the Trademarks used, or intended for use, in connection with the distribution, marketing, promotion and sale of the Co-Co Licensed Products. Product Trademarks specifically exclude the corporate names and logos of the Parties and their Affiliates. Product Trademark includes both the Alnylam Trademarks and the Genzyme Trademarks.

1.2.152. “ Promotional Materials ” has the meaning set forth in Section 4.4.2 (Alnylam A&P).

1.2.153. “ Proposing Party ” has the meaning set forth in Section 2.2.2.5(a) (Additional Development Proposals).

1.2.154. “ R&D Costs ” means, with respect to a Co-Co Licensed Product, costs and expenses incurred in connection with the performance of any Development activity for such Co-Co Licensed Product, including [***].

1.2.155. “ R&D FTE ” means [***] of work per annum devoted to or in support of the Development or Manufacture of a Co-Co Licensed Product that is carried out by one or more qualified scientific or technical employees (excluding Third Party contractors) of a Party or its Affiliates.

1.2.156. “ R&D FTE Cost ” means, for any period, the R&D FTE Rate multiplied by the number of R&D FTEs in such period.

1.2.157. “ R&D FTE Rate ” means [***] per FTE, increased annually beginning on January 1, 2015 and thereafter on January 1 of each succeeding year by the percentage increase in the CPI as of December 31 of the then most recently ended Calendar Year over the level of the CPI on December 31, 2013.

1.2.158. “ Regulatory Approval ” has the meaning set forth in the Master Agreement.

1.2.159. “ Regulatory Authority ” has the meaning set forth in the Master Agreement.

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1.2.160. “ Regulatory Exclusivity ” means, with respect to a Co-Co Licensed Product in a country, any exclusive marketing right, data exclusivity right, orphan drug designation or other country-wide exclusive right or status conferred by any Governmental Authority with respect to such Co-Co Licensed Product in such country, other than a Patent Right, that limits or prohibits a Person [***].

1.2.161. “ Related Party ” means a Party’s Affiliates, permitted Sublicensees and, with respect to Alnylam, licensees in the Co-Co Territory.

1.2.162. “ Reverted Co-Co Licensed Product ” has the meaning set forth in Section 12.3.2(b) (Effects of Termination by Alnylam for Cause or by Genzyme for Convenience).

1.2.163. “ Royalty Term ” has the meaning set forth in Section 8.2.2 (Royalty Term).

1.2.164. “ S&M Activities ” means, with respect to a Co-Co Licensed Product in the Co-Co Territory, all sales and marketing activities in the Co-Co Territory Commercialization Budget for such Co-Co Licensed Product.

1.2.165. “ S&M Costs ” means, with respect to a Co-Co Licensed Product, costs and expenses incurred in connection with the performance of any S&M Activities for such Co-Co Licensed Product in the Co-Co Territory, including S&M FTE Costs and fees charged by Third Party service providers and other Co-Co Out-of-Pocket Costs.

1.2.166. “S&M FTE” means [***] of work per annum devoted to or in support of S&M Activities for a Co-Co Licensed Product that is carried out by one or more qualified employees of, or contract sales and marketing personnel engaged by, a Party or its Affiliates. For purposes of calculating S&M FTEs with respect to S&M Activities for a Co-Co Licensed Product:

(a) [***]

(b) [***]

1.2.167. “ S&M FTE Costs ” means, on a Co-Co Licensed Product-by-Co-Co Licensed Product and country-by-country basis, the S&M FTE Rate for such country multiplied by the total number of S&M FTEs allocated to a Party in such country pursuant to the Co-Co Territory Commercialization Budget for such Co-Co Licensed Product in such Calendar Year.

1.2.168. “ S&M FTE Rate ” means, on a country-by-country basis, the then-current FTE rate for a Genzyme S&M FTE in such country.

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1.2.169. “ Safety Concern ” has the meaning set forth in the Master Agreement.

1.2.170. “ Secondary Indication ” has the meaning set forth in the Master Agreement.

1.2.171. “ Secondary Indication Study ” has the meaning set forth in the Master Agreement.

1.2.172. “ Serious Adverse Event ” has the meaning set forth in the Master Agreement.

1.2.173. “ siRNA ” has the meaning set forth in the Master Agreement.

1.2.174. “ SPCs ” has the meaning set forth in Section 11.5 (Patent Term Extensions).

1.2.175. “ Sublicensee ” means a Third Party to whom a Party grants a sublicense under any Alnylam Technology or Genzyme Technology, as the case may be, to Develop, Manufacture or Commercialize a Co-Co Licensed Product in the Field pursuant to Section 7.1.4 (Sublicensing Terms) or Section 7.2.4 (Sublicensing Terms).

1.2.176. “ Term ” has the meaning set forth in Section 12.1 (Term).

1.2.177. “ Territory ” means (a) with respect to Alnylam, the Co-Co Territory and (b) with respect to Genzyme, the Genzyme Territory.

1.2.178. “Third Party” has the meaning set forth in the Master Agreement.

1.2.179. “Third Party License Payment” has the meaning set forth in the Master Agreement.

1.2.180. “Trademark” has the meaning set forth in the Master Agreement.

1.2.181. “TTR” has the meaning set forth in the Master Agreement.

1.2.182. “ Un-Blocking Genzyme In-License ” has the meaning set forth in the Master Agreement.

1.2.183. “United States” means the United States of America and its territories, possessions and commonwealths.

1.2.184. “Valid Claim ” means a claim of: (a) an issued and unexpired patent, which claim has not been withdrawn, cancelled, abandoned, disclaimed, revoked or held unenforceable or invalid by an unappealable decision of a court or other governmental agency of competent jurisdiction, or has not been appealed within the time allowed for appeal, or by an

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appealed decision of a court or other governmental agency of competent jurisdiction where the appeal has been pending for more than [***] years (unless and until such decision is subsequently overturned on appeal) and which has not been abandoned, disclaimed, denied or admitted to be invalid or unenforceable through reissue, re-examination or disclaimer or otherwise; or (b) a patent application that has been pending less than [***] years from the date of filing of the earliest patent application from which such patent application claims priority, which claim has not been cancelled, withdrawn or abandoned or finally rejected by an administrative agency action from which no appeal can be taken.

1.2.185. “[***]” has the meaning set forth in Section 2.2.2.3(a) (Managing and Amending Global Development Plans and Global Development Budgets).

1.2.186. “[***] Budget ” has the meaning set forth in Section 2.2.2.3(a) (Managing and Amending Global Development Plans and Global Development Budgets).

1.2.187. “[***]” has the meaning set forth in Section 2.2.2.3(a) (Managing and Amending Global Development Plans and Global Development Budgets).

1.2.188. “[***] Budget ” has the meaning set forth in Section 2.2.2.3(a) (Managing and Amending Global Development Plans and Global Development Budgets).

2. DEVELOPMENT COLLABORATION

2.1. Overview . The Parties will collaborate in the Development of each Co-Co Licensed Product pursuant to the applicable Global Development Plan and Genzyme Territory Development Plan. The PJSC will have primary responsibility for the oversight of the Global Development Plans, with Alnylam having primary responsibility for execution of those Global Development Plans, and Genzyme will have sole responsibility for the Genzyme Territory Development Plans, as described below.

2.2. Development Plans .

2.2.1. Global Development Strategy. For each Co-Co Licensed Product, the key Development principles for such Co-Co Licensed Product will be set forth in a written summary of the global Development strategy for such Co-Co Licensed Product, including the indication(s) (including Secondary Indications), for which Regulatory Approval will be sought (each, a “ Global Development Strategy ”). The initial Global Development Strategy for ALN-TTRsc will be provided by Alnylam to Genzyme within [***] days after the Effective Date, agreed upon by the PJSC within [***] days after the Effective Date, and then attached hereto as Schedule 2.2.1-1 . The initial Global Development Strategy for ALN-AT3 will be included in the Option Data Package, mutually agreed upon by the Parties prior to Genzyme’s exercise of the Co-Co/Global Option with respect to ALN-AT3 in accordance with the Master Agreement, and then attached hereto as Schedule 2.2.1-2 . Any Global Development Strategy may be amended from time to time only by the PJSC responsible for the applicable Co-Co Licensed Product.

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2.2.2. Global Development Plan.

2.2.2.1. Global Development Plans . For each Co-Co Licensed Product, the Development activities that are necessary or useful to be undertaken for such Co-Co Licensed Product to achieve initial Regulatory Approval for each of the indications to be sought pursuant to the Global Development Strategy in at least all of the MMCs in a proximal fashion (including the design of necessary or useful Clinical Studies) will be set forth in reasonable detail in a written work plan and time table (each, a “ Global Development Plan ”). Alnylam will provide a draft of the initial Global Development Plan for ALN-TTRsc to Genzyme on or before March 31, 2014, and within [***] days thereafter the PJSC will review, update and approve such Global Development Plan and it will be attached hereto as Schedule 2.2.2-1 . The initial Global Development Plan for ALN-AT3 will be prepared by Alnylam and included in the Option Data Package for ALN-AT3 provided by Alnylam to Genzyme under the Master Agreement, and if Genzyme exercises the Co-Co/Global Option for ALN-AT3, within [***] days of the Implementation Date for ALN-AT3 the PJSC responsible for ALN-AT3 will review, update and approve such Global Development Plan and it will be attached hereto as Schedule 2.2.2-2 . Each Global Development Plan must, at all times, be consistent with the Global Development Strategy and include all Development activities that (i) are reasonably necessary to obtain initial Regulatory Approval of the applicable Co-Co Licensed Product in at least each MMC for each of the indications, including Secondary Indications, to be sought pursuant to the Global Development Strategy in a proximal fashion, (ii) Post-Marketing Studies for the Co-Co Territory and (iii) Secondary Indication Studies included in the initial Global Development Plan or added pursuant to Section 2.2.2.5 (Secondary Indications) (all such Development activities, collectively, the “ Global Development Activities ”); provided , however , that, unless otherwise agreed by the Parties, in no event will any Global Development Plan include (a) any Post-Marketing Study in the Genzyme Territory, (b) any Secondary Indication Study, except for Secondary Indication Studies included in the initial Global Development Plan or added to a Global Development Plan pursuant to Section 2.2.2.4 (Secondary Indications) or (c) after the last Regulatory Approval in all MMCs, any Development activity that is useful solely to achieve initial Regulatory Approval in a country in the Genzyme Territory that is not a Genzyme Territory MMC, except for Secondary Indication Studies included in the initial Global Development Plan or added to a Global Development Plan pursuant to Section 2.2.2.5 (Secondary Indications). In addition, for the period following the first Regulatory Approval in an MMC of a Co-Co Licensed Product, the Global Development Plan (and the Global Development Activities thereunder) must be established by the PJSC in a manner that reconciles the Parties’ preferences regarding short- and long-term profitability of such Co-Co Licensed Product. Each Global Development Plan will allocate responsibility for the performance of each Global Development Activity to one of the Parties. The time table for the

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completion of the Global Development Activities included in each Global Development Plan will be designed to obtain initial Regulatory Approval of the applicable Co-Co Licensed Product in each MMC in a proximal fashion and as soon as reasonably possible. The terms of, and Development activities set forth in, each Global Development Plan will at all times be designed to be in compliance with all applicable Laws and in accordance with professional and ethical standards customary in the pharmaceutical industry.

2.2.2.2. Global Development Budgets . Each Global Development Plan will contain a [***] year rolling budget for the probable Global Regulatory Costs and probable Global Development Activities to be performed during the [***], and a forecast of the budgets for each subsequent Calendar Year thereafter through completion of all Global Development Activities set forth in any such Global Development Plan, provided that each initial Global Development Plan will also include such a budget for the partial Calendar Year commencing as of the date of such Global Development Plan and ending December 31 of such Calendar Year (each such [***] budget plus any such partial Calendar Year is a “ Global Development Budget ”). Each Global Development Budget will be updated annually by the PJSC responsible for the applicable Co-Co Licensed Product in accordance with Section 2.2.2.3 (Managing and Amending Global Development Plans and Global Development Budgets). The initial Global Development Budget for a Co-Co Licensed Product, and each update thereto, will be prepared by the PJSC in accordance with [***]:

(a) [***]

(b) [***]

(d) [***]

Alnylam will enter such Global Development Budget in a template that the Parties agree is efficient for both Parties to communicate such information.

2.2.2.3. Managing and Amending Global Development Plans and Global Development Budgets . The PJSC responsible for a Co-Co Licensed Product will update and amend the applicable Global Development Plan from time-to-time as it deems necessary and, until such time as no further Global Development Activities are occurring or expected to occur with respect to such Co-Co Licensed Product, the PJSC will update such Global Development Plan annually as follows:

(a) No later than [***] of each Calendar Year, the applicable PJSC will prepare an updated draft of the Global Development Plan, which shall contain a proposed Global Development Budget[***].

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2.2.2.4. [***]; Adjustments and Compensation . In addition to the Global Development Budget for each Co-Co Licensed Product, Alnylam shall prepare, and submit to the PJSC for approval, three (3) Development budget(s) for each Co-Co Licensed Product, the first of which shall cover the period commencing as of the Implementation Date for such Co-Co Licensed Product and ending on the anticipated date of initiation of the first Phase III Study for such Co-Co Licensed Product (as further described below, each a “ Phase 2 Budget ”), the second of which shall cover the period commencing as of the anticipated date of initiation of the first Phase III Study for such Co-Co Licensed Product and ending on the anticipated date of filing of an application for Regulatory Approval of such Co-Co Licensed Product in the first MMC (as further described below, each a “ Phase 3 Budget ”) and the third of which shall cover the period commencing as of the anticipated date of filing of an application for Regulatory Approval for such Co-Co Licensed Product in the first MMC and ending on the date that there are no further Development activities to be performed under the Global Development Plan for such Co-Co Licensed Product (as further described below, each a “ Post-Phase 3 Budget ”), provided that if the period covered by the Post-Phase 3 Budget is longer than three (3) years, Alnylam shall prepare a new Post-Phase 3 Budget to cover each subsequent three (3) year period. Each Phase 2 Budget, Phase 3 Budget and Post-Phase 3 Budget [***].

(b) [***]

(i)

Alnylam shall include a Phase 2 Budget [***] with the initial Global Development Plan for each Co-Co Licensed Product. Such Phase 2 Budget [***] shall become effective, subject to adjustment in accordance with the foregoing Section 2.2.2.4(b), upon the Implementation Date for the relevant Co-Co Licensed Product.

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(ii)

Alnylam shall provide to the PJSC for approval a Phase 3 Budget [***] for each Co-Co Licensed Product no less than [***] days prior to the anticipated initiation of the first Phase III Study for each Co-Co Licensed Product, along with the top line data and data tables from any completed Phase II Studies and other completed non-clinical studies (including all Serious Adverse Event and Safety Concern data), as well as a draft of the end of Phase II briefing package, in each case to the extent not previously provided or made available to Genzyme (such budget, data and draft, collectively the “ End of Phase II Package ”). Such Phase 3 Budget [***] shall become effective at the end of such [***] day period.

(iii)

Alnylam shall provide to the PJSC for approval a Post-Phase 3 Budget [***] for each Co-Co Licensed Product no less than [***] days prior to the anticipated completion of the first Phase III Study for each Co-Co Licensed Product. Such Post-Phase 3 Budget [***] shall become effective upon approval by the PJSC.

(d)

[***]

2.2.2.5. Secondary Indications .

(a) Additional Development Proposals. If a Party desires to conduct a Secondary Indication Study of a Co-Co Licensed Product for the purpose of seeking Regulatory Approval to market such Co-Co Licensed Product for a Secondary Indication, such Party (the “ Proposing Party ”) will submit to the PJSC responsible for such Co-Co Licensed Product a proposal to add such Secondary Indication Study to the applicable Global Development Plan (an “ Additional Development Proposal ”). Each Additional Development Proposal will describe in reasonable detail the Secondary Indication Study(ies) that the Proposing Party desires to conduct, including a synopsis of the trial, the proposed enrollment criteria, number of patients to be included, endpoints to be measured, and statistical design and powering (the “ Additional Development Activities ”), as well as a proposed timeline and budget and an analysis of the business opportunity and revenue potential for such Additional Development Activities and Secondary Indication.

(b) PJSC Decision Regarding Additional Development Activities. The PJSC shall approve or reject an Additional Development Proposal within [***] days after receipt thereof from the Proposing Party as set forth in this Section 2.2.2.5.

(i)

If the PJSC approves an Additional Development Proposal, upon such an approval, the applicable Global Development Plan will be amended to include the Additional Development Activities, including the proposed

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timeline and budget for such Additional Development Activities, set forth in such Additional Development Proposal (as may be amended by the PJSC) upon such approval. Any Additional Development Activities included in a Global Development Plan pursuant to this Section 2.2.2.5(b) shall be deemed to be Global Development Activities for all purposes under these Co-Co License Terms (including the definition of Global R&D Costs).

(ii)

If the PJSC fails to approve an Additional Development Proposal, upon such a failure, the Secondary Indication Study proposed in the Additional Development Proposal will not be deemed a Global Development Activity for any purpose under these Co-Co License Terms, and Sections 2.2.2.5(c) (Independent Performance of Additional Development Activities) and Section 2.2.2.5(d) (Opt-In for Additional Development Activities) shall apply.

(c)

Independent Performance of Additional Development Activities.

(i)

If the PJSC fails to approve for inclusion in the Global Development Plan an Additional Development Proposal proposed by Alnylam for a Secondary Indication Study(ies) for a Co-Co Licensed Product, Alnylam may, upon notice to Genzyme, conduct the proposed Secondary Indication Study(ies) at its own expense [***].

(ii)

If the PJSC fails to approve for inclusion in the Global Development Plan an Additional Development Proposal proposed by Genzyme for a Secondary Indication Study(ies) for such Co-Co Licensed Product, Genzyme may, upon notice to Alnylam, conduct the proposed Secondary Indication Study(ies) at its own expense [***].

(iii)

Notwithstanding anything in Section 3.5 (Right of Reference) to the contrary, the Non-Proposing Party with respect to an Additional Development Activity that is permitted to be conducted in accordance with this Section 2.2.2.5 will not have any rights under Section 3.5 (Right of Reference) with respect to any information or data generated from such Additional Development Activity, except as described in Section 2.2.2.5(d) (Opt-In for Additional Development Activities).

(d)

Opt-In for Additional Development Activities.

(i)

In the event that the Proposing Party conducts Secondary Indication Study(ies) pursuant to Section 2.2.2.5(c) (Independent Performance of Additional Development Activities), the Non-Proposing Party may elect, in its discretion and upon written notice to the Proposing Party prior to the date on which [***] (an “ Additional Development Opt-In Notice ”), to

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opt in with respect to any Secondary Indication Study that was the subject of such Additional Development Proposal that the Proposing Party elected to conduct in accordance with Section 2.2.2.5(c) (Independent Performance of Additional Development Activities), and then (i) such Secondary Indication Study shall be deemed to be a Global Development Activity under the Global Development Plan for the applicable Co-Co Licensed Product from and after the date on which such Additional Development Opt-In Notice is received by the Proposing Party (the “ Additional Development Opt-In Date ”); (ii) the then-current plan and budget of the Proposing Party with respect to such Secondary Indication Study shall be deemed to be included within, and part of, the Global Development Plan for such Co-Co Licensed Product as of the Additional Development Opt-In Date, and shall control with respect to such Secondary Indication Study unless and until an amendment to the Global Development Plan providing for a different or modified plan and budget is approved by the applicable PJSC; and (iii) the Non-Proposing Party will have all rights granted to it under Section 3.5 (Right of Reference) with respect to the information and data generated from such Secondary Indication Study as if such Secondary Indication Study was conducted under the Global Development Plan for such Co-Co Licensed Product, [***].

(ii)

If the Non-Proposing Party does not provide an Additional Development Opt-In Notice to the Proposing Party prior to the date on which Regulatory Approval for the applicable Co-Co Licensed Product is granted by a Regulatory Authority in an MMC for the Secondary Indication proposed by such Proposing Party, then, as of the date of such Regulatory Approval, the Non-Proposing Party shall be deemed to have opted in and the Non-Proposing Party will have all rights granted to it under Section 3.5 (Right of Reference) with respect to the information and data generated from such Secondary Indication Study as if such Secondary Indication Study was conducted under the Global Development Plan for such Co-Co Licensed Product, [***].

2.2.2.6. Additional Clinical Study Sites in Genzyme Territory . With respect to any Clinical Study in a Global Development Plan, at Genzyme’s request, Alnylam will add a study site in a country in the Genzyme Territory [***]. If Alnylam adds such a study site at Genzyme’s request, Genzyme will reimburse Alnylam for any incremental R&D FTE Costs or Co-Co Out-of-Pocket Costs required as a result of adding such study site. Genzyme will pay Alnylam such reimbursement within [***] days of receipt of an invoice from Alnylam.

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2.2.3. Genzyme Territory Development Plan. Other than Global Development Activities, all Development activities to be undertaken with respect to each Co-Co Licensed Product by or on behalf of Genzyme with respect to the Genzyme Territory, including Secondary Indication Studies and Post-Marketing Studies, will be set forth in a written work plan and time table (each, a “ Genzyme Territory Development Plan ”). Each Genzyme Territory Development Plan shall be consistent with the requirements of the then-current Global Development Strategy. The Genzyme Territory Development Plan for ALN-TTRsc will be prepared by Genzyme and delivered to the applicable PJSC by [***] and, following review and approval by the PJSC, will then be attached to the PJSC meeting minutes and deemed to be attached hereto as Schedule 2.2.3-1 . If Genzyme exercises the Co-Co/Global Option with respect to ALN-AT3, the initial Genzyme Territory Development Plan for ALN-AT3 (if any) will be prepared by Genzyme and following review and approval by the PJSC, will then be attached to the PJSC meeting minutes and deemed to be attached hereto as Schedule 2.2.3-2 . Each Genzyme Territory Development Plan will set forth a rolling written work plan and time table with respect to the Development of and Secondary Indication Studies for the applicable Co-Co Licensed Product from the Implementation Date until such time as no further Development or Secondary Indication Studies are occurring or expected to occur with respect to the applicable Co-Co Licensed Product. Genzyme will update each such Genzyme Territory Development Plan from time-to-time but at least annually on or before [***]. Genzyme will present each Genzyme Territory Development Plan and any proposed amendments thereto to the applicable PJSC at least [***] days in advance of implementation of the Genzyme Territory Development Plan, and following review and approval by the PJSC, will then be attached to the PJSC meeting minutes and deemed to be attached hereto as the applicable Schedule.

2.3. Joint Responsibilities for Development Activities and Costs .

2.3.1. Global Development.

2.3.1.1. Generally . With respect to each Co-Co Licensed Product, the PJSC will have overall responsibility for oversight of the global Development of each Co-Co Licensed Product and all Development activities under such Global Development Plan. Alnylam shall have overall responsibility for execution under the Global Development Plan and each Party, in turn, shall be responsible for execution of the activities allocated to it under the Global Development Plan. Each Party and its Affiliates shall conduct each Global Development Activity for which it is responsible solely in accordance with the Global Development Plan (as such Global Development Plan may be amended from time to time in accordance with these Co-Co License Terms) in sound scientific manner and in compliance with applicable Law. Notwithstanding anything to the contrary in these Co-Co License Terms, neither Party will be obligated to undertake or continue any Global Development Activity if (a) such Party reasonably determines that performance of such Global Development Activity would violate applicable Law; or (b) with respect to any Global Clinical Study, (i) a Regulatory Authority or independent safety data review board for such Global Clinical Study has required or recommended termination or suspension of such Global Clinical Study or (ii) such Party believes in good faith that termination or suspension of such Global

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Clinical Study is warranted because of safety or tolerability risks or the lack of suitable risk benefit ratio to the study subjects. In the event that a Party determines not to undertake or continue any Global Development Activity in accordance with the immediately preceding sentence, such Party shall promptly notify the other Party of such determination, and shall use all reasonable efforts to notify and consult with the other Party prior to making such determination.

2.3.1.2. Global R&D Costs .

(a) With respect to ALN-TTRsc, each Party shall be responsible for fifty percent (50%) of all Global Regulatory Costs and Global R&D Costs for Global Development Activities that occur after the later of (i) [***] and (ii) [***] (such later date, the “ ALN-TTRsc Global R&D Cost Opt-In Date ”), and amounts specified in clauses (ii) and (iii) of Section 2.3.1.2(c) below, if any. Alnylam shall be responsible for one-hundred percent (100%) of Global Regulatory Costs and Global R&D Costs for Global Development Activities for ALN-TTRsc that occur prior to the ALN-TTRsc Global R&D Cost Opt-In Date, except for amounts specified in clauses (ii) and (iii) of Section 2.3.1.2(c) below, if any.

(b) With respect to ALN-AT3, if Genzyme exercises the Co-Co/Global Option, each Party shall be responsible for fifty percent (50%) of all Global Regulatory Costs and Global R&D Costs for Global Development Activities that occur after the later of (i) [***] and (ii) [***] (such later date, the “ ALN-AT3 Global R&D Cost Opt-In Date ,” and together with the ALN-TTRsc Global R&D Cost Opt-In Date, the “ Global R&D Cost Opt-In Date ”), and amounts specified in clauses (ii) and (iii) in Section 2.3.1.2(c) below, if any. Alnylam shall be responsible for one-hundred percent (100%) of Global Regulatory Costs and Global R&D Costs for Global Development Activities for such Co-Co Licensed Product that occur prior to the ALN-AT3 Global R&D Cost Opt-In Date, except for amounts specified in clauses (ii) and (iii) of Section 2.3.1.2(c) below, if any.

(c) The Global R&D Costs to be shared by the Parties pursuant to Sections 2.3.1.2(a) and 2.3.1.2(b) above shall only include amounts that are within one or more of the following four (4) categories:

(i) [***]

(ii) [***]

(iii) [***]

(iv) [***]

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(d) For clarity, Global Regulatory Costs and Global R&D Costs to be shared by the Parties pursuant to Section 2.3.1.2(a) and Section 2.3.1.2(b) shall exclude any amounts paid after the Global R&D Cost Opt-In Date to Third Parties with respect to services rendered or materials procured in connection with the conduct of any Clinical Study or other Development activity that, in either case, is completed prior to the Global R&D Cost Opt-In Date.

(e) Global R&D Costs and Global Regulatory Costs for each Co-Co Licensed Product shall initially be borne by the Party incurring the cost or expense. Each Party will calculate and maintain records of Global R&D Costs and Global Regulatory Costs incurred by it and its Affiliates with respect to each Co-Co Licensed Product and, within [***] days following the end of each Calendar Quarter, each Party shall submit to the other a report detailing the Global R&D Costs and Global Regulatory Costs incurred by it and its Affiliates during such Calendar Quarter, and, if requested, reasonable supporting documentation will be provided (a “ Global R&D Costs Report ”). In addition, each Party shall use good faith efforts to notify the other Party of any material Global R&D Costs and Global Regulatory Costs incurred by such Party during such Calendar Quarter within [***] days after the end of such Calendar Quarter. The Party that incurs more than its share of the total actual Global R&D Costs and Global Regulatory Costs with respect to a Co-Co Licensed Product during any Calendar Quarter shall be paid by the other Party an amount of cash sufficient to reconcile to its agreed percentage of Global R&D Costs and Global Regulatory Costs for such Co-Co Licensed Product, which payment shall be made within [***] days after delivery of the Global R&D Cost Reports for such Calendar Quarter. Notwithstanding the foregoing, if following receipt of a Global R&D Costs Report a Party (the “ Disputing Party ”) disputes any Global R&D Costs or Global Regulatory Costs under such Global R&D Costs Report, it shall have [***] days to notify the other Party (the “ Non-Disputing Party ”). Upon receiving such notice from the Disputing Party, the Non-Disputing Party shall, at the reasonable request of the Disputing Party, provide to the Disputing Party supporting documentation relating to any such disputed Global R&D Costs or Global Regulatory Costs. The Parties agree to use reasonable efforts to resolve any such dispute as soon as reasonably practicable, and any undisputed portion of Global R&D Costs or Global Regulatory Costs in such Global R&D Costs Report shall be paid within [***] days after delivery of such Global R&D Costs Report. Once the Parties have resolved such dispute, any disputed amounts still owed by either Party will be paid within [***] days of resolution of such dispute.

(f) [***]

(g) Notwithstanding anything to the contrary in these Co-Co License Terms, the Parties shall not share Global R&D Costs incurred in a Calendar Year with respect to Global Development Activities for a Co-Co Licensed Product to the extent such Global R&D Costs exceed [***] of the amounts included in the final [***] Budget that was applicable to such Current Calendar Year (the amount in excess of such [***] limit is the “ Excess Global R&D Costs ”). One hundred percent (100%) of any Excess Global R&D Costs for such Co-Co Licensed Product will be borne by the Party that incurred such Excess Global R&D Costs.

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2.3.2. Genzyme Development. Except with respect to Global R&D Costs (which shall be shared by the Parties in accordance with Section 2.3.1.2 (Global R&D Costs)), Genzyme shall be responsible for one hundred percent (100%) of all costs and expenses incurred with respect to Development activities that are conducted by Genzyme pursuant to any Genzyme Territory Development Plan. Genzyme will conduct all Development of each Co-Co Licensed Product for the Genzyme Territory solely in accordance with the applicable Global Development Plan and Genzyme Territory Development Plan, as such Global Development Plan and Genzyme Territory Development Plan may be amended in accordance with these Co-Co License Terms, and in sound scientific manner and in compliance with applicable Law.

2.3.3. Alnylam Development. Alnylam will conduct all Development of each Co-Co Licensed Product for the Co-Co Territory solely in accordance with the applicable Global Development Plan, as such Global Development Plan may be amended in accordance with these Co-Co License Terms, and in sound scientific manner and in compliance with applicable Law.

2.4. Diligence .

2.4.1. Genzyme Diligence. With respect to each Co-Co Licensed Product, Genzyme will use Commercially Reasonable Efforts to [***].

2.4.2. Alnylam Diligence. With respect to each Co-Co Licensed Product, Alnylam will use Commercially Reasonable Efforts to (a) Develop such Co-Co Licensed Product and obtain Regulatory Approval therefor in (i) each Co-Co Territory MMC, and (ii) any other country(ies) within the Co-Co Territory where the PJSC determines that it is commercially reasonable to seek Regulatory Approval (taking into account all relevant factors as provided in the definition of Commercially Reasonable Efforts); and (b) perform the Global Development Activities allocated to it under the Global Development Plan for such Co-Co Licensed Product in accordance with the Global Development Plan.

2.5. Records; Reports; Information Sharing .

2.5.1. Development Activities Reports. Each Party will periodically provide to the PJSC responsible for a Co-Co Licensed Product, but in no event less than on a Calendar Quarter basis, or more frequently as reasonably requested by the other Party, an update regarding Development activities conducted by or on behalf of such Party with respect to such Co-Co Licensed Product, as well as any Secondary Indication Studies and Post-Marketing Studies conducted by or on behalf of such Party with respect to such Co-Co Licensed Product. The Parties will periodically report to the PJSC responsible for a Co-Co Licensed Product, but in no event less than on a Calendar Quarter basis, regarding their respective activities conducted under the Global Development Plan for such Co-Co Licensed Product. In addition, each Party will promptly share with the other Party all material developments and information that it comes to possess relating to the Development of any Co-Co Licensed Products, including Safety Concerns and study reports and data generated from Clinical Studies of such Co-Co Licensed Product.

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2.5.3. Information Exchange and Development Assistance. Until the expiration or termination of the final Global Development Plan, upon the reasonable request of the other Party, each Party shall provide to the other Party, without additional compensation (except as provided in Section 6.5 (Transfer of Manufacturing Know-How) of the Master Agreement) and in a commercially reasonable format, Know-How Controlled by such Party and/or its Related Parties that is licensed to the other Party under these Co-Co License Terms ( i.e. , Know-How included in Genzyme Technology for Genzyme and Know-How included in Alnylam Technology for Alnylam) to the extent that it is reasonably necessary or useful for Developing a Co-Co Licensed Product in the requesting Party’s Territory or for obtaining or maintaining Regulatory Approval for a Co-Co Licensed Product in the requesting Party’s Territory, including copies of (a) all scientific information and data related to such Co-Co Licensed Product (including all data made, collected or otherwise generated in the conduct of any pre-clinical studies, Clinical Studies, Secondary Indication Studies or early access/named patient programs for the Co-Co Licensed Products, as well as CMC information), and (b) protocols and investigator brochures, in each case, that are reasonably necessary for the other Party (or its Related Parties) to perform its obligations or exploit its rights under these Co-Co License Terms with respect to such Co-Co Licensed Product. Notwithstanding the foregoing, Genzyme shall have no obligation to transfer or disclose to Alnylam any Know-How included in the Genzyme Manufacturing IP; provided , however , that if Genzyme elects, in its sole discretion, to transfer or disclose any such Know-How to Alnylam in writing, it shall be “ Genzyme Disclosed Manufacturing Know-How ” under these Co-Co License Terms and licensed to Alnylam in accordance with Section 7.2.3 (License to Genzyme Disclosed Manufacturing Know-How).

2.5.4. Personnel. Each Party may request, through the PJSC or the other Party’s CLP Alliance Manager responsible for a Co-Co Licensed Product, that the other Party reasonably make available for consultation regarding the Development of such Co-Co Licensed Product certain of its employees engaged in Development activities and Secondary Indication Studies with respect to such Co-Co Licensed Product. The PJSC or the CLP Alliance Managers responsible for a Co-Co Licensed Product will reasonably coordinate, upon reasonable notice during normal business hours and at their respective places of employment, consultation between the Parties on the progress of the Development and Secondary Indication Studies for such Co-Co Licensed Product.

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2.6. Third Parties .

2.6.1. Use of Third Parties. The Parties shall be entitled to utilize the services of Third Parties to perform their respective Development and Manufacturing activities under these Co-Co License Terms, provided that (a) each Party shall require that such Third Party operates in a manner consistent with these Co-Co License Terms, (b) each Party shall remain at all times fully liable for its respective responsibilities and (c) the Parties will make reasonable efforts to share, through the PJSC, information regarding any prior experience with specific CROs that are anticipated to be engaged to perform work under the Global Development Plan. Each Party shall require that any Third Party agreement entered into pursuant to this Section 2.6.1 include confidentiality and non-use provisions that are no less stringent than those set forth in Section 7 of the Master Agreement (Confidentiality and Publication) and shall obtain ownership of, and/or a fully sublicensable license under and to, any Know-How and Patent Rights that are developed by such Third Party in the performance of such agreement and are reasonably necessary or useful to Develop, Manufacture and/or Commercialize Co-Co Licensed Products in the Field. The Party utilizing the services of a Third Party service provider shall be solely responsible for direction of and communications with such Third Party, but such Party shall provide the other Party with reasonably detailed updates regarding any such activities from time to time.

2.6.2. [***].

2.7. [***].

3. REGULATORY MATTERS

3.1. Regulatory Filings and Interactions in the Genzyme Territory .

3.1.1. Ownership of Regulatory Filings.

3.1.1.1. Genzyme will own all INDs, NDAs and related regulatory documentation submitted to any Regulatory Authority in the Genzyme Territory with respect to any Co-Co Licensed Product. At Genzyme’s request following the Implementation Date for a Co-Co Licensed Product, Alnylam will promptly assign and transfer to Genzyme all INDs, NDAs and other regulatory documentation submitted to any Regulatory Authority in the Genzyme Territory with respect to such Co-Co Licensed Product that is in the possession or control of Alnylam, and each Party will submit all filings, letters and other documentation necessary to effect such assignment and transfer to the applicable Regulatory Authority no later than [***] days after such request for such Co-Co Licensed Product, in each case, excluding any drug master files maintained by or on behalf of Alnylam, which shall be and remain Alnylam’s sole responsibility. Alnylam hereby appoints Genzyme as Alnylam’s agent for all matters related to each Co-Co Licensed Product involving Regulatory Authorities in the Genzyme Territory during the period beginning on the Implementation Date for such Co-Co Licensed

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Product and ending on the date that the transfer of all INDs, NDAs and related regulatory documents filed with or submitted to any Regulatory Authority in the Genzyme Territory that relate to such Co-Co Licensed Product becomes effective, and Genzyme hereby accepts such appointment, excluding any drug master files maintained by or on behalf of Alnylam, which shall be and remain Alnylam’s sole responsibility.

3.1.1.2. Notwithstanding the foregoing, for every Clinical Study conducted under a Global Development Plan, Alnylam will draft the protocol, develop the IND strategy, and file INDs globally, including in the Genzyme Territory, after input and review by Genzyme and Alnylam will use reasonable efforts to address any concerns raised by Genzyme in connection with such activities. Unless otherwise agreed by the Parties, on a country-by-country basis, following the acceptance or approval of the IND and the first dosing of the first patient in the first Phase III Study of the relevant Co-Co Licensed Product in such country, Alnylam will assign the IND in such country, as set forth in Section 3.1.1.1, in the Genzyme Territory to Genzyme and from that point forward, Genzyme will be primarily responsible for the related regulatory activities with respect thereto in its Territory. [***]

3.1.2. Responsibilities for Regulatory Matters. Pursuant to the Global Development Plan for a Co-Co Licensed Product and, except as otherwise provided in such Global Development Plan, Genzyme will be solely responsible for all regulatory matters relating to such Co-Co Licensed Product in the Genzyme Territory, including (i) overseeing, monitoring and coordinating all regulatory actions, communications and filings with, and submissions to, each Regulatory Authority in the Genzyme Territory with respect to such Co-Co Licensed Product; (ii) interfacing, corresponding and meeting with each Regulatory Authority in the Genzyme Territory with respect to such Co-Co Licensed Product; and (iii) seeking and maintaining all regulatory filings in the Genzyme Territory with respect to such Co-Co Licensed Product, excluding any drug master files maintained by or on behalf of Alnylam, which shall be and remain Alnylam’s sole responsibility.

3.1.3. Communications with Regulatory Authorities. Genzyme will promptly (and in any event no later than [***] days) notify the Alnylam representatives on the PJSC responsible for a Co-Co Licensed Product in writing, including a brief description in English, of the principal issues raised in any material communication with any Regulatory Authority in the Genzyme Territory with respect to such Co-Co Licensed Product. Upon Alnylam’s reasonable request after receiving a notice from Genzyme in accordance with the immediately preceding sentence, Genzyme will provide to Alnylam: (i) at Genzyme’s expense, a summary translation of the applicable material communication in English; (ii) at Genzyme’s expense, complete copies of the original correspondence with the applicable Regulatory Authority in their native language; or (iii) at Alnylam’s expense, a full translation of the applicable material communication in English, in each case (i) through (iii) within a reasonable period of time following such request. For purposes of this Section 3.1.3, “material communication” will include any meetings with

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Regulatory Authorities, or questions or concerns from Regulatory Authorities, regarding significant issues, such as key product quality attributes ( e.g. , purity), safety findings affecting the platform ( e.g. , Serious Adverse Events, emerging safety signals), clinical or nonclinical findings affecting patient safety or lack of efficacy, or receipt or denial of Regulatory Approval.

3.1.4. Meetings with Regulatory Authorities. Genzyme shall provide Alnylam with reasonable advance notice of all substantive meetings with Regulatory Authorities in the Genzyme Territory pertaining to each Co-Co Licensed Product, or with as much advance notice as practicable under the circumstances. Genzyme shall use reasonable efforts, to the extent reasonably practicable, to permit Alnylam to have, at Alnylam’s expense, mutually acceptable representatives of Alnylam attend, solely as a non-participating observers, material, substantive meetings (including pre-IND and end of Phase II Study meetings) with Regulatory Authorities in the Genzyme Territory pertaining to such Co-Co Licensed Product; provided , however , that Genzyme shall not be obligated to change or re-schedule any such meeting in order to accommodate the schedule of Alnylam’s representatives. Prior to the acceptance or approval of the IND and the first dosing of the first patient in the first Phase III Study of a Co-Co Licensed Product in a country in the Genzyme Territory, Alnylam shall provide Genzyme with reasonable advance notice of all substantive meetings with Regulatory Authorities in the Genzyme Territory pertaining to such Co-Co Licensed Product, or with as much advance notice as practicable under the circumstances. Alnylam shall use reasonable efforts, to the extent reasonably practicable, to permit Genzyme to have, at Genzyme’s expense, mutually acceptable representatives of Genzyme attend, as full and equal participants, material, substantive meetings (including pre-IND and end of Phase II Study meetings) with Regulatory Authorities in the Genzyme Territory pertaining to such Co-Co Licensed Product.

3.1.5. Submissions. With respect to each Co-Co Licensed Product, Genzyme shall provide Alnylam with prompt written notice of each of the following events (but in any event within [***] days) after the occurrence of such event in the Genzyme Territory: (i) the filing of any IND for such Co-Co Licensed Product; and (ii) the submission of any filings or applications for Regulatory Approval (including orphan drug applications and designations) of such Co-Co Licensed Product to any Regulatory Authority; provided , however , that in all circumstances, Genzyme shall inform Alnylam of such event prior to public disclosure of such event by Genzyme.

3.2. Regulatory Filings and Interactions in the Co-Co Territory .

3.2.1. Ownership of Regulatory Filings. Alnylam will own all INDs, NDAs and related regulatory documentation submitted to any Regulatory Authority in the Co-Co Territory with respect to any Co-Co Licensed Product.

3.2.2. Responsibilities for Regulatory Matters. Pursuant to the Global Development Plan for a Co-Co Licensed Product and, except as otherwise provided in such Global Development Plan, Alnylam will be primarily responsible for all regulatory matters relating to such Co-Co Licensed Product in the Co-Co Territory, including (i) overseeing, monitoring and coordinating all regulatory actions, communications and filings with, and

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submissions to, each Regulatory Authority in the Co-Co Territory with respect to such Co-Co Licensed Product; (ii) interfacing, corresponding and meeting with each Regulatory Authority in the Co-Co Territory with respect to such Co-Co Licensed Product; and (iii) seeking and maintaining all regulatory filings in the Co-Co Territory with respect to such Co-Co Licensed Product; provided , however , that Alnylam and Genzyme may have roles of varying responsibility for such activities in respect of the Co-Co Licensed Products in the Co-Co Territory as is set forth in the applicable Global Development Plan.

3.2.3. Communications with Regulatory Authorities. Alnylam will notify the Genzyme representatives on the PJSC responsible for a Co-Co Licensed Product in writing, including a brief description in English, of the principal issues raised in any material communication with any Regulatory Authority in the Co-Co Territory with respect to such Co-Co Licensed Product within [***] days after receipt of such material communication. Alnylam will allow Genzyme a reasonable opportunity to review and comment on Alnylam’s proposed response to any such material communications in advance of the transmission of any such response, and Alnylam will reasonably consider all comments timely provided by Genzyme in connection therewith. Upon Genzyme’s reasonable request after receiving a notice from Alnylam in accordance with the immediately preceding sentence, Alnylam will provide to Genzyme: (i) at Alnylam’s expense, a summary translation of the applicable material communication in English; (ii) at Alnylam’s expense, complete copies of the original correspondence with the applicable Regulatory Authority in their native language; or (iii) at Genzyme’s expense, a full translation of the applicable material communication in English, in each case (i) through (iii) within a reasonable period of time following such request. For purposes of this Section 3.2.3, “material communication” will include any meetings with Regulatory Authorities, or questions or concerns from Regulatory Authorities, regarding significant issues, such as key product quality attributes ( e.g. , purity), safety findings affecting the platform ( e.g. , Serious Adverse Events, emerging safety signals), clinical or nonclinical findings affecting patient safety, lack of efficacy, or receipt or denial of Regulatory Approval.

3.2.4. Meetings with Regulatory Authorities. Alnylam shall provide Genzyme with reasonable advance notice of all substantive meetings with Regulatory Authorities in the Co-Co Territory pertaining to each Co-Co Licensed Product, or with as much advance notice as practicable under the circumstances. Alnylam shall use Commercially Reasonable Efforts, to the extent reasonably practicable, to permit Genzyme to have, at Genzyme’s expense, mutually acceptable representatives of Genzyme attend the following: (i) solely as non-participating observers, material, substantive meetings (including pre-IND and end of Phase II Study meetings) with Regulatory Authorities in the Co-Co Territory pertaining to such Co-Co Licensed Product, and (ii) any internal Alnylam meetings held in preparation for such material, substantive meetings with Regulatory Authorities in the Co-Co Territory.

3.2.5. Submissions. With respect to each Co-Co Licensed Product, Alnylam will allow Genzyme a reasonable opportunity to review and comment on all regulatory filings and other submissions to Regulatory Authorities or other Governmental Authorities in the Co-Co Territory in advance of the submission of any such filing, and Alnylam will reasonably consider

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all comments timely provided by Genzyme in connection therewith. In addition, Alnylam shall provide Genzyme with prompt written notice of each of the following events (but in any event within [***] days) after the occurrence of such event in the Co-Co Territory: (i) the filing of any IND for such Co-Co Licensed Product; (ii) the submission of any filings or applications for Regulatory Approval (including orphan drug applications and designations) of such Co-Co Licensed Product to any Regulatory Authority; and (iii) receipt or denial of Regulatory Approval for such Co-Co Licensed Product; provided , however , that in all circumstances, Alnylam shall inform Genzyme of such event prior to public disclosure of such event by Alnylam.

3.3. EMA Regulatory Strategy . Within [***] year before the anticipated MAA filing for a Co-Co Licensed Product, the PJSC will determine an EMA regulatory strategy for such Co-Co Licensed Product pursuant to which the PJSC will determine (a) whether Alnylam will seek Regulatory Approval for such Co-Co Licensed Product in the EU using the EMA centralized or a national authorization procedure and (b) whether Genzyme will file a duplicate license with respect to any MAA held by Alnylam in the Co-Co Territory [***]. In determining the EMA regulatory strategy, the Parties agree to reasonably consider in good faith each Party’s interests. In the event that Genzyme files a duplicate license in the Genzyme Territory, Alnylam will coordinate communications with EMA, and provide support to enable Genzyme to efficiently obtain such duplicate license to provide for marketing in Genzyme countries under a separate, Genzyme trade name, to the extent not inconsistent with the Global Commercial Strategy or Global Branding Strategy for such Co-Co Licensed Product.

3.4. Costs of Regulatory Affairs . Except as provided in Sections 2.3 (Joint Responsibilities for Development Activities and Costs) and 3.1.1.2 (Ownership of Regulatory Filings), each Party shall be responsible for all costs and expenses incurred in connection with applying for, obtaining and maintaining Regulatory Approval with respect to Co-Co Licensed Products, and related regulatory affairs activities.

3.5. Right of Reference . Each Party hereby grants to the other Party, and at the request of the other Party will grant to the other Party’s Related Parties, a “Right of Reference,” as that term is defined in 21 C.F.R. § 314.3(b) (or any successor rule or analogous Law recognized outside of the United States), to, and a right to copy, access, and otherwise use, all information and data (including all CMC information as well as data made, collected or otherwise generated in the conduct of any Clinical Studies or Secondary Indication Studies or early access/named patient programs for the Co-Co Licensed Products) included in or used in support of any regulatory filing, Regulatory Approval, drug master file or other regulatory documentation (including orphan drug applications and designations) owned or controlled by such Party or its Related Parties that relates to (a) any Co-Co Licensed Product or (b) with respect to such information and data provided to Genzyme, the siRNA Controlled by Alnylam and known as ALN-TTR01, to the extent necessary or useful to obtain Regulatory Approval of a Co-Co Licensed Product in the Genzyme Territory, and such Party shall provide a signed statement to this effect, if requested by the other Party, in accordance with 21 C.F.R. § 314.50(g)(3) (or any successor or analogous Law outside of the United States). In addition, upon request of either Party (on behalf of itself or a Sublicensee), the other Party shall obtain and

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provide to the requesting Party certificates or other formal or official attestations concerning the regulatory status of the Co-Co Licensed Products in the Genzyme Territory or the Co-Co Territory, as applicable ( e.g. , Certificates of Free Sale, Certificates for Export, Certificates to Foreign Governments). Notwithstanding anything to the contrary in these Co-Co License Terms, neither Party shall withdraw or inactivate any regulatory filing that the other Party references or otherwise uses pursuant to this Section 3.5.

4. COMMERCIALIZATION OF THE LICENSED PRODUCTS

4.1. Responsibility, Cost and Diligence .

4.1.1. Global Commercial Strategy. For each Co-Co Licensed Product, the key Commercialization principles will be set forth in a written summary of the global Commercialization strategy for such Co-Co Licensed Product (each, a “ Global Commercial Strategy ”). Alnylam shall provide the initial draft of such Global Commercial Strategy to the PJSC responsible for the applicable Co-Co Licensed Product within [***] days after the Implementation Date for such Co-Co Licensed Product, and within [***] days after provision, such PJSC shall review, update and approve such Global Commercial Strategy. The PJSC for such Co-Co Licensed Product will update and amend the Global Commercial Strategy not later than the initiation of the first Phase III Study for such Co-Co Licensed Product, and then annually thereafter. Amendments to any Global Commercial Strategy will become effective following review and approval by the applicable PJSC. In no event, however, may any Global Commercial Strategy be amended with the result that it fails to satisfy the requirements for Commercialization of Co-Co Licensed Products set forth in this Section 4.

4.1.2. Co-Co Territory. The PJSC will lead responsibility for all Commercialization activities relating to Co-Co Licensed Products in the Field in the Co-Co Territory. The Parties, under the direction of the PJSC, will participate in the planning and conduct of such Commercialization activities as and to the extent set forth in these Co-Co License Terms, including without limitation, Section 4.2 (Co-Co Territory Commercialization).

4.1.3. Genzyme Territory. Genzyme shall be solely responsible, at its expense, for all Commercialization activities relating to Co-Co Licensed Products in the Field in the Genzyme Territory.

4.1.4. Genzyme Commercial Diligence. Genzyme shall use Commercially Reasonable Efforts to [***].

4.2. Co-Co Territory Commercialization .

4.2.1. Co-Co Territory Commercialization Plan. For each Co-Co Licensed Product, the Commercialization activities that are necessary or useful to be undertaken for such Co-Co Licensed Product in the Co-Co Territory will be set forth in reasonable detail in a written work plan (each, a “ Co-Co Territory Commercialization Plan ”). Each Co-Co Territory Commercialization Plan must, at all times, include a detailed description of the S&M Activities

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to be undertaken in each country in the Co-Co Territory with respect to the applicable Co-Co Licensed Product during the then-current Calendar Year and the next Calendar Year. Each Co-Co Territory Commercialization Plan shall be consistent with the requirements of the applicable Global Commercialization Strategy, as such Global Commercialization Strategy may be updated as reasonably necessary. Any amendment to a Global Commercialization Strategy shall take into account the then-current deployment of resources and time required to realign resources consistent with the Global Commercialization Strategy in a reasonable manner, and with this Section 4.2.1. The Commercialization Activities set forth in each Co-Co Territory Commercialization Plan will at all times be designed to be in compliance with all applicable Laws and in accordance with professional and ethical standards customary in the pharmaceutical industry.

4.2.1.1. ALN-TTRsc Co-Co Territory Commercialization Plan . Within [***] year after the Effective Date, Alnylam will provide a draft of the initial Co-Co Territory Commercialization Plan for ALN-TTRsc to the PJSC, and within [***] days thereafter, the PJSC will review, update and approve such Co-Co Territory Commercialization Plan and it will be attached hereto as Schedule 4.2-1 .

4.2.1.2. ALN-AT3 Co-Co Territory Commercialization Plan . The initial Co-Co Territory Commercialization Plan for ALN-AT3 will be prepared and approved by the PJSC no later than [***] years prior to the anticipated date of the First Commercial Sale of ALN-AT3 in any country in the Co-Co Territory and, upon approval, it will be attached hereto as Schedule 4.2-2 .

4.2.1.3. Allocation of S&M Activities . Promptly following the approval of any Co-Co Territory Commercialization Plan in accordance with this Section 4.2.1 or Section 4.2.4, the Parties shall allocate responsibility for each S&M Activity to be performed in the next Calendar Year between the Parties in an equitable manner mutually agreed by the Parties, which allocation shall be made on an activity-by-activity or S&M FTE-by-S&M FTE basis, as applicable, and subject to the following:

(a) each Party will have the right to provide up to [***] in each country in the Co-Co Territory in such Calendar Year; and

(b) [***]

4.2.2. Diligence. If the PJSC agrees upon the allocation of responsibility for the S&M Activities in a Co-Co Territory Commercialization Plan [***].

4.2.3. Co-Co Territory Commercialization Budget. Each Co-Co Territory Commercialization Plan will contain a budget for the S&M Activities (and no other activities) to be performed during the then-current Calendar Year with respect to the applicable Co-Co Licensed Product in the Co-Co Territory (a “ Co-Co Territory Commercialization Budget ”), which budget will allocate expenditures equitably across the countries in the Co-Co Territory,

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taking into account the allocation of activities described in Section 4.2.1.3 (Allocation of S&M Activities) and the then-current and future commercial opportunities for such Co-Co Licensed Product. Each Co-Co Territory Commercialization Budget will be updated annually by the PJSC responsible for the applicable Co-Co Licensed Product in accordance with Section 4.2.4 (Managing and Amending Co-Co Territory Commercialization Plans and Co-Co Territory Commercialization Budgets). The initial Co-Co Territory Commercialization Budget for a Co-Co Licensed Product, and each update thereto, will be prepared by the PJSC [***]. Alnylam will enter such Co-Co Commercialization Budget in a template that the Parties agree is efficient for both Parties to communicate such information. [***]

4.2.4. Managing and Amending Co-Co Territory Commercialization Plans and Co-Co Territory Commercialization Budgets. For each Co-Co Licensed Product, Alnylam will update and amend, and the PJSC will approve, the applicable Co-Co Territory Commercialization Plan from time-to-time as it deems necessary and, until such time as no further S&M Activities are occurring or expected to occur with respect to such Co-Co Licensed Product, the Co-Co Territory Commercialization Plan will be updated as follows:

(a) No later than [***] of each Calendar Year, Alnylam shall prepare, and the applicable PJSC will approve, an updated draft of the Co-Co Territory Commercialization Plan, which shall contain a proposed Co-Co Territory Commercialization Budget covering the next Calendar Year. The proposed Co-Co Territory Commercialization Budget will satisfy the requirements set forth in Section 4.2.3 (Co-Co Territory Commercialization Budget).

(b) No later than [***] of each Calendar Year, Alnylam shall prepare, and the applicable PJSC will review and tentatively approve an updated Co-Co Territory Commercialization Plan and Co-Co Territory Commercialization Budget for such Co-Co Licensed Product, and such updated Co-Co Territory Commercialization Plan and Co-Co Territory Commercialization Budget will become effective upon such tentative approval by the PJSC, provided that the Parties acknowledge and agree that each Party’s internal process for receiving final approval of such Co-Co Territory Commercialization Plan and Co-Co Territory Commercialization Budget from its Board of Directors may occur after [***] (but, in any event, before [***]) and Co-Co Territory Commercialization Plan and Co-Co Territory Commercialization Budget will not become final unless and until such approvals are obtained. In no event may any Co-Co Territory Commercialization Plan be amended with the result that it fails to satisfy the requirements for Co-Co Territory Commercialization Plans set forth in Section 4.2.1 (Co-Co Territory Commercialization Plan).

4.2.5. Responsibility for Co-Co Territory Commercialization Costs. With respect to each Co-Co Licensed Product, unless otherwise agreed to by the Parties in writing [***]. On the first day of each Calendar Year, the PJSC responsible for a Co-Co Licensed Product will determine the total S&M Costs allocated to each Party for such Calendar Year under the applicable Co-Co Territory Commercialization Budget, which S&M Costs shall be calculated by [***].

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4.2.6. Verification. With respect to each Co-Co Licensed Product, promptly following the end of each Calendar Year, the Head of the Rare Disease Business of Genzyme and an appropriate officer of Alnylam shall certify to one another in writing whether or not such Party has spent the S&M Costs allocated to such Party in the applicable Co-Co Territory Commercialization Budget during such Calendar Year in performing the S&M Activities allocated to such Party in the applicable Co-Co Territory Commercialization Plan. If either Party did not spend all of the S&M Costs or perform all of the S&M Activities allocated to such Party in the applicable Co-Co Territory Commercialization Plan, then such Party shall pay the other Party an amount equal to [***] of the difference between the S&M Costs and S&M Activities allocated to such Party in the applicable Co-Co Territory Commercialization Plan and the S&M Costs and S&M Activities certified as being spent or performed by such Party. The certification mechanism and true-up payment provided for in this Section 4.2.6 shall be in lieu of auditing the Parties’ S&M Costs and S&M Activities for Co-Co Licensed Products in the Co-Co Territory.

4.3. Genzyme Territory Commercialization Plan . No less than [***] months in advance of the reasonably expected first Regulatory Approval in the Genzyme Territory with respect to a Co-Co Licensed Product, and on an annual basis thereafter, Genzyme shall prepare and deliver to the PJSC responsible for such Co-Co Licensed Product for review a reasonable written plan that summarizes the Commercialization activities to be undertaken with respect to such Co-Co Licensed Product in the Genzyme Territory in the next Calendar Year and, to the extent commercially reasonable, Genzyme’s plans to obtain further Regulatory Approvals and Commercialize such Co-Co Licensed Product in countries in the Genzyme Territory in which Genzyme is not then Commercializing such Co-Co Licensed Product, and the dates by which such activities are targeted to be accomplished (the “ Genzyme Territory Commercialization Plan ”). Each Genzyme Territory Commercialization Plan shall be consistent with the requirements of the initial Global Commercialization Strategy approved by the PJSC pursuant to Section 4.1.1 (Global Commercial Strategy) or the most recently approved by the PJSC without the use of tie-break authority pursuant to Section 5.7.3 (Tie-Breaking). The Genzyme Territory Commercialization Plan for a Co-Co Licensed Product shall subsequently be updated and modified by Genzyme, from time to time at its discretion and no less frequently than once per Calendar Year, based upon, among other things, Genzyme’s Commercialization activities with respect to such Co-Co Licensed Product in the Genzyme Territory, a copy of which updated plan Genzyme will provide to the PJSC responsible for such Co-Co Licensed Product. [***].

4.4. Advertising and Promotional Materials .

4.4.1. Global Branding. Alnylam shall have the right, from time to time during the Term, to develop (and thereafter to modify and update) a global branding strategy (including global positioning, colors and other visual branding elements) for each Co-Co Licensed Product for use in the Field throughout the world (the “ Global Branding Strategy ”), which the PJSC responsible for such Co-Co Licensed Product shall, in accordance with Sections 5.6 (PJSC

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Commercialization Responsibilities) and 5.7 (PJSC Decision-Making), review and approve, and which the Parties shall, following such review and approval, implement. Alnylam will submit the Global Branding Strategy for a Co-Co Licensed Product to the PJSC responsible for such Co-Co Licensed Product at least annually (or more frequently if reasonably requested by Genzyme). Alnylam shall consider in good faith any timely comments Genzyme may have with respect to any Global Branding Strategy, but shall have final decision-making authority with respect to such Global Branding Strategy. Notwithstanding the foregoing, Alnylam shall ensure that the Global Branding Strategy complies with applicable Laws in the Genzyme Territory, and that any branding elements selected for inclusion in the Global Branding Strategy do not infringe any Third Party trademarks or other intellectual property rights. If any such Global Branding Strategy infringes Third Party trademarks or other intellectual property rights or otherwise does not comply with applicable Law in the Genzyme Territory, Alnylam shall take action to end such infringement or other noncompliance (including by modifying such Global Branding Strategy) and Genzyme will not be obligated to implement such Global Branding Strategy in the Genzyme Territory pursuant to this Section 4.4.1 unless and until such infringement or noncompliance is ended.

4.4.2. Alnylam A&P. Alnylam will be responsible for the creation, preparation, production, reproduction and filing with the applicable Regulatory Authorities, of relevant written sales, promotion and advertising materials relating to each Co-Co Licensed Product (“ Promotional Materials ”) for use in the Co-Co Territory. All such Promotional Materials will be compliant with applicable Law and, if applicable, consistent in all material respects with the Global Branding Strategy for such Co-Co Licensed Product. Alnylam will submit representative samples of its Promotional Materials developed by it for use in the Co-Co Territory to the PJSC, at least annually (or more frequently if reasonably requested by Genzyme). Alnylam shall consider in good faith any timely comments Genzyme may have with respect to any such Promotional Materials, but shall have final decision-making authority with respect to such Promotional Materials. Notwithstanding the foregoing, Alnylam will incorporate any changes to Promotional Materials requested by Genzyme in a timely fashion in cases where Genzyme indicates that believes in good faith based on the advice of counsel that such change is necessary to enable it to comply with any applicable Law.

4.4.3. Genzyme A&P. Genzyme will be responsible for the creation, preparation, production, reproduction and filing with the applicable Regulatory Authorities, of relevant Promotional Materials relating to each Co-Co Licensed Product for use in the Genzyme Territory. All such Promotional Materials will be compliant with applicable Law, consistent in all material respects with the Genzyme Territory Commercialization Plan and, if applicable, consistent in all material respects with the Global Branding Strategy for such Co-Co Licensed Product. Genzyme will submit representative samples of its Promotional Materials developed by it for use in the Genzyme Territory to the PJSC at least annually thereafter (or more frequently if reasonably requested by Alnylam). Genzyme shall consider in good faith any timely comments Alnylam may have with respect to any such Promotional Materials, but shall have final decision-making authority with respect to such Promotional Materials.

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4.4.4. Reporting Obligations.

4.4.4.1. Genzyme Territory . Genzyme shall report to the PJSC responsible for a Co-Co Licensed Product in writing, by no later than each [***] following the first Regulatory Approval of such Co-Co Licensed Product in the Field in the Genzyme Territory (for the period ending December 31 of the prior Calendar Year), summarizing in reasonable detail Genzyme’s Commercialization activities for such Co-Co Licensed Product in the Genzyme Territory performed to date (or updating such report for activities performed since the last such report was given hereunder, as applicable). In addition, Genzyme shall provide Alnylam with written notice of the First Commercial Sale of each Co-Co Licensed Product in the Genzyme Territory within [***] days after such event; provided , however , that in all circumstances, Genzyme shall inform Alnylam of such event prior to public disclosure of such event by Genzyme. Genzyme shall provide such other information to the PJSC responsible for a Co-Co Licensed Product as Alnylam may reasonably request with respect to Commercialization of such Co-Co Licensed Product and shall keep such PJSC reasonably informed of Genzyme’s Commercialization activities in the Genzyme Territory with respect to such Co-Co Licensed Product.

4.4.4.2. Co-Co Territory . Each Party shall report to the PJSC responsible for a Co-Co Licensed Product in writing, by no later than each [***] following the first Regulatory Approval of such Co-Co Licensed Product in the Field in the Co-Co Territory (for the period ending December 31 of the prior Calendar Year), summarizing in reasonable detail such Party’s Commercialization activities for such Co-Co Licensed Product in the Co-Co Territory performed to date (or updating such report for activities performed since the last such report was given hereunder, as applicable). Each Party shall provide such other information to the PJSC responsible for a Co-Co Licensed Product as the other Party may reasonably request with respect to Commercialization of such Co-Co Licensed Product and shall keep such PJSC reasonably informed of such Party’s Commercialization activities in the Co-Co Territory with respect to such Co-Co Licensed Product.

4.5. Commercialization Reporting Obligations . Each Party and its Related Parties shall be responsible for booking sales in its Territory (for avoidance of doubt, meaning, with respect to the Co-Co Territory, Alnylam, and with respect to the Genzyme Territory, Genzyme). Each Party and its Related Parties may warehouse Co-Co Licensed Products both inside and outside of such Party’s Territory, provided that any sales with respect to such Co-Co Licensed Products are booked in such Party’s Territory. If a Party receives any orders for any Co-Co Licensed Product in the other Party’s Territory, it shall refer such orders to the other Party, to the extent it is not prohibited from doing so under applicable Law. Moreover, each Party and its Related Parties shall be solely responsible for handling all returns of any Co-Co Licensed Product sold in its Territory, as well as all aspects of Co-Co Licensed Product order processing, invoicing and collection, distribution, inventory and receivables of Co-Co Licensed Products sold in its Territory.

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4.6. Recalls, Market Withdrawals or Corrective Actions . In the event that any Regulatory Authority issues or requests a recall or takes a similar action in connection with a Co-Co Licensed Product in the Co-Co Territory or Genzyme Territory, or in the event either Party determines that an event, incident or circumstance has occurred that may result in the need for a recall or market withdrawal of a Co-Co Licensed Product in the Co-Co Territory or Genzyme determines that an event, incident or circumstance has occurred that may result in the need for a recall or market withdrawal of a Co-Co Licensed Product in the Genzyme Territory, the Party notified of such recall or similar action, or the Party that desires such recall or similar action, shall within [***] hours notify the other Party’s CLP Alliance Manager and PJSC representatives thereof by telephone or e-mail. The Parties shall mutually agree whether to conduct a recall of a Co-Co Licensed Product in the Co-Co Territory and the manner in which any such recall shall be conducted (except in the case of a government mandated recall, when the Party subject to such mandate may act without such advance notice but shall notify the other Party as soon as possible). Genzyme shall determine whether to conduct a recall of a Co-Co Licensed Product in the Genzyme Territory and the manner in which any such recall shall be conducted (except in the case of a government mandated recall, when Genzyme may act without such advance notice but shall notify Alnylam as soon as possible). Except as may be otherwise agreed by the Parties, each Party shall share equally the expense of any such recall in the Co-Co Territory and Genzyme shall bear the expense of any such recall in the Genzyme Territory. Each Party will make available all of its pertinent records that may be reasonably requested by the other Party in order to effect a recall of a Co-Co Licensed Product in the Co-Co Territory or Genzyme Territory. The Parties’ rights and obligations under this Section 4.6 shall be subject to the terms of any supply agreement(s) entered into between the Parties and, in the event of any conflict between the provisions of any such supply agreement and this Section 4.6, the provisions of such supply agreement shall govern.

4.7. Export Monitoring .

4.7.1. [***]

4.7.2. [***]

5. COLLABORATION MANAGEMENT

5.1. Product Joint Steering Committee . The Parties shall establish a product joint steering committee (a “ PJSC ”) to facilitate the Co-Co Collaboration with respect to each Co-Co Licensed Product as follows:

5.1.1. Composition of the Product Joint Steering Committee. The Development and Commercialization of each Co-Co Licensed Product pursuant to the Co-Co Collaboration will be conducted under the oversight of a PJSC, which shall be comprised of three (3) representatives of each Party. The PJSC for ALN-TTRsc shall be established as of the

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Effective Date. Each Party shall appoint its respective representatives to each PJSC from time to time following the Implementation Date for ALN-AT3, and may substitute one or more of its representatives on any PJSC, in its sole discretion, effective upon notice to the other Party of such change. Each Party shall have at least one representative on each PJSC who is a senior employee (vice president level or above), and all representatives on each PJSC shall have appropriate expertise, seniority, decision-making authority and ongoing familiarity with the Co-Co Collaboration and the applicable Co-Co Licensed Product. Unless otherwise agreed by the Parties, each Party’s representatives on any PJSC must be employees of such Party or any of its Affiliates. For the avoidance of doubt, the same representatives from each Party may serve on the PJSC for more than one Co-Co Licensed Product. Additional representatives or consultants may from time to time, by mutual consent of the Parties, be invited to attend PJSC meetings, subject to such representatives and consultants undertaking confidentiality obligations, whether in a written agreement or by operation of law, no less stringent than the requirements of Section 7 of the Master Agreement (Confidentiality and Publication).

5.2. Appointment of Subcommittees, Project Teams and CLP Alliance Managers . Each PJSC shall be empowered to create such subcommittees and project teams as it may deem appropriate or necessary, such as for specific oversight of Development, Manufacturing, Commercialization or intellectual property issues relating to the Co-Co Licensed Product for which such PJSC is responsible. Each such project team created by a PJSC shall report to such PJSC, which shall have authority to approve or reject recommendations or actions proposed by such project team, subject to these Co-Co License Terms. For the avoidance of doubt, the same representatives from each Party may serve on the project team for more than one Co-Co Licensed Product. Each Party will designate an alliance manager for each Co-Co Licensed Product (each, a “ CLP Alliance Manager ”) to serve as a primary point of contact for the other Party with respect to all activities under the CLP Collaboration related to such Co-Co Licensed Product. Each CLP Alliance Manager’s responsibilities shall include (a) scheduling meetings of the PJSC at least once per Calendar Quarter, but more frequently if the PJSC determines it necessary; (b) setting agendas for PJSC meetings with solicited input from the CLP Alliance Manager for the other Party and other members of the PJSC; and (c) coordinating the delivery of draft minutes to the PJSC for review and final approval. Beginning with Alnylam’s CLP Alliance Manager, such responsibilities shall alternate between the CLP Alliance Managers from each Party on a meeting-by-meeting basis after each meeting of the applicable committee. Each Party may change any of its CLP Alliance Managers at any time in its sole discretion with written notice to the other Party, provided that each CLP Alliance Manager will be individually identified at all times and will have such experience, authority, responsibility and accountability as is reasonably sufficient to enable such person to fulfill his or her responsibilities as a CLP Alliance Manager under these Co-Co License Terms on behalf of the applicable Party.

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5.3. PJSC Meetings . Each PJSC shall meet in accordance with a schedule established by mutual written agreement of the Parties, but no less frequently than once per Calendar Quarter during the Term, with the location for such meetings alternating between Alnylam and Genzyme facilities (or such other locations as are mutually agreed by the Parties). Alternatively, a PJSC may meet by means of teleconference, videoconference or other similar communications equipment, but at least two (2) meetings of such PJSC per Calendar Year shall be conducted in person. All proceedings for each PJSC shall take place in English. Where the membership of a PJSC for a Co-Co Licensed Product is the same as one or more other PJSCs for the other Co-Co Licensed Product, such PJSCs may have a single meeting to discuss each Co-Co Licensed Product for which they have responsibility. Each Party shall bear its own expenses relating to attendance at such meetings by its representatives.

5.4. PJSC Minutes . A CLP Alliance Manager shall be appointed secretary for each meeting of each PJSC and shall prepare minutes of the meeting, which shall provide a description in reasonable detail of the discussions held at the meeting and a list of any actions, decisions or determinations approved by such PJSC. Within [***] days after each meeting, the drafting CLP Alliance Manager shall provide the draft minutes to the other CLP Alliance Manager for review and comment. The drafting CLP Alliance Manager shall reasonably consider all comments from the other CLP Alliance Manager within [***] days. The drafting CLP Alliance Manager shall prepare and submit revised minutes for approval within [***] days after receipt of such comments or upon expiration of such [***] day period.

5.5. PJSC Development Responsibilities . Each PJSC shall have the following responsibilities with respect to the Development of the Co-Co Licensed Product for which it is responsible:

5.5.1. reviewing, commenting on and approving updates and amendments to the Global Development Strategy for such Co-Co Licensed Product in accordance with Section 2.2.2.3 (Managing and Amending Global Development Plans and Global Development Budgets);

5.5.2. reviewing, commenting on and approving updates and amendments to the Global Development Plan for such Co-Co Licensed Product in accordance with Section 2.2.2.3 (Managing and Amending Global Development Plans and Global Development Budgets);

5.5.3. monitoring the implementation of the Global Development Plan for such Co-Co Licensed Product, including the Global Development Activities set forth in such Global Development Plan;

5.5.4. reviewing, commenting on and approving the design of any Phase III Study for such Co-Co Licensed Product;

5.5.5. monitoring any Clinical Study included in such Global Development Activities (a “ Global Clinical Study ”) performed by a CRO retained by a Party to perform such Global Clinical Study, against the criteria and timelines in such Global Development Plan;

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5.5.6. reviewing, commenting on and approving the initial Genzyme Territory Development Plan for such Co-Co Licensed Product in accordance with Section 2.2.3 (Genzyme Territory Development Plan);

5.5.7. reviewing, commenting on and approving updates and amendments to the Genzyme Territory Development Plan in accordance with Section 2.2.3 (Genzyme Territory Development Plan), and providing Genzyme with feedback regarding the same;

5.5.8. reviewing and discussing updates provided by each Party regarding the Development of such Co-Co Licensed Product in either Territory in accordance with Section 2.5.1 (Development Activities Reports), and providing each Party with feedback regarding the same;

5.5.9. monitoring and coordinating Development activities in the Genzyme Territory and the Co-Co Territory for such Co-Co Licensed Product, and regulatory and pharmacovigilance requirements and matters;

5.5.10. reviewing and discussing updates provided by each Party regarding any Global Development Activities in accordance with the Global Development Plan for such Co-Co Licensed Product (including the Global Development Budget);

5.5.11. overseeing any manufacturing and supply relationship between the Parties with respect to the Manufacture of such Co-Co Licensed Product for Development activities (subject to the provisions of the CLP Clinical Supply Agreement);

5.5.12. approving a global list of clinical sites for each Global Clinical Study for such Co-Co Licensed Product;

5.5.13. approving the appointment of the global CRO to manage any Phase II Study or Phase III Study for such Co-Co Licensed Product; and

5.5.14. performing such other activities as the Parties agree in writing shall be the responsibility of such PJSC or that are otherwise assigned to such PJSC under these Co-Co License Terms.

5.6. PJSC Commercialization Responsibilities . Each PJSC shall have the following responsibilities with respect to the Commercialization of the Co-Co Licensed Product for which it is responsible, to the extent permissible under applicable Laws:

5.6.1. reviewing, commenting on and approving updates and amendments to the Global Commercial Strategy for such Co-Co Licensed Product in accordance with Section 4.1.1 (Global Commercial Strategy);

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5.6.2. reviewing and discussing reports and information provided by each Party regarding the Commercialization of such Co-Co Licensed Product in both Territories in accordance with Section 4.5 (Commercialization Reporting Obligations);

5.6.3. reviewing, commenting on and approving any Global Branding Strategy developed by Alnylam for such Co-Co Licensed Product in accordance with Section 4.4.1 (Global Branding);

5.6.4. reviewing, commenting on and approving the Genzyme Territory Commercialization Plan for such Co-Co Licensed Product and updates thereto provided by Genzyme to the extent provided in Section 4.3 (Genzyme Territory Commercialization Plan);

5.6.5. reviewing, commenting on and approving the Co-Co Territory Commercialization Plan for such Co-Co Licensed Product and updates thereto provided by Genzyme to the extent provided in Section 4.2 (Co-Co Territory Commercialization Plan);

5.6.6. reviewing, commenting on and discussing Promotional Material for such Co-Co Licensed Product of both Parties in accordance with Sections 4.4.2 (Alnylam A&P) and 4.4.3 (Genzyme A&P);

5.6.7. providing a forum for the Parties to discuss the Commercialization of such Co-Co Licensed Product in the Field worldwide, including coordination regarding Co-Co Licensed Product positioning and messaging, key opinion leader relationship management, medical affairs, and marketing and selling materials;

5.6.8. providing a forum for the Parties to discuss collaborating on commercial activities with respect to such Co-Co Licensed Product that can be leveraged for both Territories and how the Parties would share the costs of such mutually agreed joint Commercialization activities;

5.6.9. overseeing any manufacturing and supply relationship between the Parties with respect to the Manufacture of such Co-Co Licensed Product for Commercialization activities (subject to the provisions of the CLP Commercial Supply Agreement); and

5.6.10. performing such other activities as the Parties agree in writing shall be the responsibility of such PJSC or that are otherwise assigned to such PJSC under these Co-Co License Terms.

5.7. PJSC Decision-Making .

5.7.1. PJSC Decisions. With respect to decisions of each PJSC, the representatives of each Party on such PJSC shall have collectively one vote on behalf of such Party. For each meeting of a PJSC, at least two (2) representatives of each Party shall constitute a quorum. Action on any matter may be taken at a meeting, by teleconference, videoconference or by written agreement. Each PJSC shall attempt to resolve any and all disputes before it for decision by consensus. [***]. For the avoidance of doubt, the phrase “approval by the PJSC” and similar phrases used in these Co-Co License Terms shall mean approval in accordance with this Section 5.7 (PJSC Decision-Making), including [***]

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5.7.2. Escalation. If a PJSC is unable to reach a consensus with respect to any dispute for a period in excess of [***] days, then the dispute shall be submitted to the AJSC (as defined in the Master Agreement) at a meeting or meetings (whether in-person or by teleconference or videoconference). During such meeting(s), each Party shall provide analysis to support its position with respect to such dispute. If the dispute is still unresolved after a further [***] days, such dispute shall be [***].

5.7.3. [***] . If a PJSC dispute cannot be resolved under Section 5.7.2 (Escalation), then, subject to Sections 5.7.4 ([***]) and 5.7.5 (No Deciding Vote):

5.7.3.1. [***]

5.7.3.2. [***]

5.7.3.3. [***]

[***]

5.7.4. [***]

5.7.4.1. [***]r

5.7.4.2. [***]

[***]

5.7.5. [***]

5.7.5.1. [***]

5.7.5.2. [***]

5.7.5.3. [***]

5.7.5.4. [***]

5.7.5.5. [***]

5.8. Term of PJSC . With respect to each Co-Co Licensed Product, after the [***] of the Implementation Date for such Co-Co Licensed Product, Alnylam shall have the right, but not the obligation, to continue its participation on the PJSC responsible for such Co-Co Licensed Product.

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6. MANUFACTURE AND SUPPLY OF CO-CO LICENSED PRODUCTS

6.1. Supply Agreements . The Manufacturing of each Co-Co Licensed Product, including ALN-TTRsc, will be addressed in the Master Agreement and breach of such Manufacturing terms as applied to a Co-Co Licensed Product shall be treated as a breach under this Agreement, and not under the Master Agreement.

7. LICENSES

7.1. License Grants to Genzyme .

7.1.1. Development License. On a Co-Co Licensed Product-by-Co-Co Licensed Product basis, subject to the provisions of these Co-Co License Terms (including Section 10.4.1.4 (Exception to Exclusivity)), and any Co-Co Clinical Supply Agreement, effective upon the Implementation Date for such Co-Co Licensed Product, Alnylam hereby grants Genzyme (i) a non-transferable (except as provided in Section 13.1 of the Master Agreement (Assignment)), sublicensable (subject to Section 7.1.4 (Sublicensing Terms)), exclusive (even as to Alnylam) license under Alnylam Technology to Develop such Co-Co Licensed Product in the Field in the Genzyme Territory and Co-Co Territory, in each case (x) solely as and to the extent provided in any approved Genzyme Territory Development Plan or any Global Development Plan and (y) solely for Regulatory Approval and Commercialization in the Genzyme Territory; and (ii) a non-transferable, non-sublicensable, co-exclusive (with Alnylam) license under Alnylam Technology to Develop such Co-Co Licensed Product in the Field for Regulatory Approval and Commercialization in the Co-Co Territory, solely as and to the extent provided in any approved Global Development Plan. Notwithstanding the foregoing: (a) Alnylam retains the right under the Alnylam Technology to Develop each Co-Co Licensed Product in the Field anywhere in the world for Regulatory Approval and Commercialization by Genzyme in the Genzyme Territory, in accordance with the Global Development Plan for such Co-Co Licensed Product and (b) Alnylam retains the co-exclusive right (with Genzyme) under the Alnylam Technology to Develop such Co-Co Licensed Product anywhere in the world for Commercialization in the Co-Co Territory.

7.1.2. Commercialization License. On a Co-Co Licensed Product-by-Co-Co Licensed Product basis, subject to the provisions of these Co-Co License Terms (including Section 10.4.1.4 (Exception to Exclusivity)), and any Co-Co Commercial Supply Agreement, effective upon the Implementation Date for such Co-Co Licensed Product, Alnylam hereby grants Genzyme (i) a non-transferable (except as provided in Section 13.1 of the Master Agreement (Assignment)), sublicensable (subject to Section 7.1.4 (Sublicensing Terms)), exclusive (even as to Alnylam) license under Alnylam Technology to Commercialize such Co-Co Licensed Products in the Field in the Genzyme Territory and (ii) a non-transferable, non-sublicensable, co-exclusive (with Alnylam) license under Alnylam Technology to Commercialize such Co-Co Licensed Product in the Field in the Co-Co Territory.

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The license granted under the foregoing clause (i) shall be royalty-bearing for the Royalty Term applicable to each Co-Co Licensed Product in each country in the Genzyme Territory, and, after the Royalty Term applicable to such Co-Co Licensed Product in such country, shall convert to a fully-paid, exclusive, perpetual license to Commercialize such Co-Co Licensed Product in the Field in such country in the Genzyme Territory.

7.1.3. Manufacturing Licenses. On a Co-Co Licensed Product-by-Co-Co Licensed Product basis, subject to the provisions of these Co-Co License Terms (including Section 10.4.1.4 (Exception to Exclusivity)), and any Co-Co Clinical Supply Agreement and Co-Co Commercial Supply Agreement, effective upon the Implementation Date for such Co-Co Licensed Product, Alnylam hereby grants Genzyme (i) a non-transferable (except as provided in Section 13.1 of the Master Agreement (Assignment)), sublicensable (subject to Section 7.1.4 (Sublicensing Terms)), worldwide, non-exclusive license under Alnylam Technology to Manufacture such Co-Co Licensed Product inside or outside the Genzyme Territory solely for Development or Commercialization in the Genzyme Territory and, to the extent permitted pursuant to Section 2.3.2 (Genzyme Development), for Development in the Co-Co Territory for the purpose of obtaining Regulatory Approval and Commercialization in the Genzyme Territory and (ii) a non-transferable, non-sublicensable, non-exclusive license under Alnylam Technology to Manufacture such Co-Co Licensed Product inside or outside the Genzyme Territory for Development and Commercialization in the Co-Co Territory solely as and to the extent required for Genzyme to act as a second source Manufacturer as described in Section 6 of the Master Agreement (Manufacture and Supply of the Collaboration Products) or to Manufacture Co-Co Licensed Products on the terms and conditions set forth in the Co-Co Supply Agreements. Notwithstanding the foregoing exclusive license: Alnylam retains the exclusive right under the Alnylam Technology, with the right to grant licenses through multiple tiers without restriction, to Manufacture Co-Co Licensed Products anywhere in the world (a) for Development and Commercialization in the Co-Co Territory and, to the extent permitted pursuant to Section 2 (Development Collaboration) for Development in the Genzyme Territory, and (b) to supply Genzyme pursuant to the Co-Co Supply Agreements to be agreed by the Parties pursuant to Section 6.1 (Supply Agreements).

7.1.4. Sublicensing Terms.

(a) Genzyme shall have the right to sublicense any of its rights under (i) Section 7.1.1 (Development License), (ii) the license granted in clause (i) (but not clause (ii)) of Section 7.1.2 (Commercialization License), and (iii) Section 7.1.3 (Manufacturing License) to any of its Affiliates or to any Third Party (which sublicensed rights may be further sublicensable through multiple tiers) without the prior consent of Alnylam, subject to the requirements of this Section 7.1.4. [***]

(b) Each sublicense granted by Genzyme pursuant to this Section 7.1.4 shall be subject and subordinate to the provisions of these Co-Co License Terms and shall contain terms and conditions consistent with those in these Co-Co License Terms. Genzyme shall promptly provide Alnylam with a copy of the fully executed sublicense

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agreement covering any sublicense granted hereunder (which copy may be redacted to remove terms and conditions which are not necessary to monitor compliance with this Section 7.1.4), and each such sublicense agreement shall contain the following provisions: (i) a requirement that the Sublicensee comply with the confidentiality and non-use provisions of Section 7 of the Master Agreement (Confidentiality and Publication) with respect to Alnylam’s Confidential Information; (ii) if such sublicense agreement contains a sublicense of Co-Co Licensed Product Commercialization rights, such sublicense agreement shall also contain the following provisions: (x) a requirement that the Sublicensee submit applicable sales or other reports to Genzyme to the extent necessary or relevant to the reports required to be made or records required to be maintained under these Co-Co License Terms; and (y) the audit requirement set forth in Section 9.2 of the Master Agreement (Audits); and (iii) a requirement that the Sublicensee comply with the applicable provisions under any Alnylam In-License.

(c) If Genzyme becomes aware of a material breach of the terms of any sublicense by any Genzyme Sublicensee, compliance with which is necessary for Genzyme’s compliance with the provisions of these Co-Co License Terms, Genzyme shall promptly notify Alnylam of the particulars of the same and use Commercially Reasonable Efforts to cause the Sublicensee to comply with all the terms of the sublicense necessary for Genzyme’s compliance with the provisions of these Co-Co License Terms. [***] Notwithstanding any sublicense, Genzyme shall remain primarily liable to Alnylam for the performance of all of Genzyme’s obligations under, and Genzyme’s compliance with all provisions of, these Co-Co License Terms.

7.1.5. Back-Up Products. Subject to Sections 13.2 (Future Acquisition of a Party or its Business), 13.3.1 (Acquired Programs) and 13.3.2 (Acquired Programs), Alnylam hereby grants to Genzyme a series of exclusive options (each, a “ Back-Up Option ”), under each of which Genzyme shall have the right, but not the obligation, to take a license on the terms set forth in these Co-Co License Terms, to any siRNA that targets the same Licensed Target as a Co-Co Licensed Product (a “ Back-Up Product ”) and for which Alnylam has determined the GLP toxicology studies will be conducted during the Back-Up Option Period. Genzyme may exercise the Back-Up Option with respect to such Back-Up Product by delivering written notice to Alnylam at any time during the Back-Up Option Period (the “ Back-Up Option Exercise Notice ”). Upon delivery of the Back-Up Option Exercise Notice to Alnylam, the applicable Back-Up Product shall automatically be deemed to be a Co-Co Licensed Product for all purposes under the Collaboration Agreement and the license from Alnylam to Genzyme for such Co-Co Licensed Product shall automatically, with no further action by any Party, go into full force and effect and all obligations of Alnylam and Genzyme set forth in these Co-Co License Terms, including the payment obligations set forth herein, shall become the binding obligations of the applicable Party in respect of such Co-Co Licensed Product. Upon the expiration of the Back-Up Option Period, all Back-Up Options not previously exercised shall automatically terminate.

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7.2. License Grants to Alnylam .

7.2.1. Commercialization License in the Co-Co Territory. Genzyme hereby grants Alnylam a non-transferable (except as provided in Section 13.1 of the Master Agreement (Assignment)), sublicensable (subject to Section 7.2.4 (Sublicensing Terms)), non-exclusive, royalty-free license under Genzyme Collaboration IP to Develop and Commercialize Co-Co Licensed Products in the Field in the Co-Co Territory.

7.2.2. License to Improvement Manufacturing Patent Rights. Subject to the provisions of these Co-Co License Terms, Genzyme hereby grants Alnylam a non-transferable (except as provided in Section 13.1 of the Master Agreement (Assignment)), sublicensable (subject to Section 7.2.4 (Sublicensing Terms)), worldwide, non-exclusive license under the Improvement Manufacturing Patent Rights, to Manufacture (a) Alnylam Developed siRNA Products targeting any human gene; and (b) Co-Co Licensed Products for Commercialization in the Co-Co Territory, Development in either the Co-Co Territory or Genzyme Territory in accordance with the Global Development Plan for such Co-Co Licensed Product, and for sale to Genzyme under any Co-Co Clinical Supply Agreement or Co-Co Commercial Supply Agreement.

7.2.3. License to Genzyme Disclosed Manufacturing Know-How. Subject to the provisions of these Co-Co License Terms, Genzyme hereby grants Alnylam a non-transferable (except as provided in Section 13.1 of the Master Agreement (Assignment)), sublicensable (subject to Section 7.2.4 (Sublicensing Terms)), worldwide, non-exclusive license under the Genzyme Disclosed Manufacturing Know-How to Manufacture Co-Co Licensed Products for Commercialization in the Co-Co Territory, Development in either the Co-Co Territory or Genzyme Territory in accordance with the Global Development Plan for such Co-Co Licensed Product, and for sale to Genzyme under any Co-Co Clinical Supply Agreement or Co-Co Commercial Supply Agreement.

7.2.4. Sublicensing Terms.

(a) Alnylam shall have the right to sublicense any of its rights under Section 7.2.1 (Commercialization License in the Co-Co Territory), 7.2.2 (License to Improvement Manufacturing Patent Rights) and 7.2.3 (License to Genzyme Disclosed Manufacturing Know-How) to [***].

(b) Each sublicense granted by Alnylam pursuant to this Section 7.2.4 shall be subject and subordinate to the provisions of these Co-Co License Terms and shall contain terms and conditions consistent with those in these Co-Co License Terms. Alnylam shall promptly provide Genzyme with a copy of the fully executed sublicense agreement covering any sublicense granted hereunder (which copy may be redacted to remove terms and conditions which are not necessary to monitor compliance with this Section 7.2.4), and each such sublicense agreement shall contain the following provisions: (i) a requirement that the Sublicensee comply with the confidentiality and non-use provisions of Section 7 of the Master Agreement (Confidentiality and Publication) with respect to Genzyme’s Confidential Information and (ii) a requirement that the Sublicensee comply with the applicable provisions under any Genzyme In-License.

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(c) If Alnylam becomes aware of a material breach of any sublicense by any Alnylam Sublicensee, compliance with which is necessary for Alnylam’s compliance with the provisions of these Co-Co License Terms, Alnylam shall promptly notify Genzyme of the particulars of the same and use Commercially Reasonable Efforts to cause the Sublicensee to comply with all the terms of the sublicense necessary for Alnylam’s compliance with the provisions of these Co-Co License Terms. [***] Notwithstanding any sublicense, Alnylam shall remain primarily liable to Genzyme for the performance of all of Alnylam’s obligations under, and Alnylam’s compliance with all terms and conditions of, these Co-Co License Terms.

7.3. Joint Collaboration IP . Subject to the rights and licenses granted to, and the obligations (including royalty obligations) of, each Party under these Co-Co License Terms, either Party is entitled to practice Joint Collaboration IP for all purposes on a worldwide basis and license Joint Collaboration IP without consent of and without a duty of accounting to the other Party. Each Party will grant and hereby does grant all permissions, consents and waivers with respect to, and all licenses under, the Joint Collaboration IP, throughout the world, necessary to provide the other Party with such rights of use and exploitation of the Joint Collaboration IP, and will execute documents as necessary to accomplish the foregoing.

7.4. In-Licenses .

All licenses and other rights granted to Genzyme under this Section 7 are subject to the rights and obligations of Alnylam under the Alnylam In-Licenses. All licenses and other rights granted to Alnylam under this Section 7 are subject to the rights and obligations of Genzyme under the Genzyme In-Licenses. Each Party shall comply with all applicable terms and conditions of the In-Licenses, and shall perform and take such actions as may be required to allow the Party that is party to such In-License to comply with its obligations thereunder, including obligations relating to sublicensing, patent matters, confidentiality, reporting, audit rights, indemnification and diligence. Without limiting the foregoing, each Party shall prepare and deliver to the other Party any additional reports required under the applicable In-Licenses and requested by such other Party, in each case sufficiently in advance to enable the Party that is party to such In-License to comply with its obligations under the applicable In-Licenses. Each Party agrees, upon the other Party’s request, to provide the other Party with copies of any In-Licenses to which it is a party. Confidential Information of the providing Party or its counterparty may be redacted from such copies, except to the extent that such information is required in order to enable the other Party to comply with its obligations to the providing Party under these Co-Co License Terms with respect to such In-License or in order to enable the providing Party to ascertain compliance with the provisions of these Co-Co License Terms.

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7.5. Bankruptcy . All rights and licenses granted under or pursuant to these Co-Co License Terms by a Party to the other, including those set forth in Sections 7.1 (License Grants to Genzyme), 7.2 (License Grants to Alnylam), and 3.5 (Right of Reference), are and shall otherwise be deemed to be, for purposes of Section 365(n) of the U.S. Bankruptcy Code, licenses of rights to “intellectual property” as defined under Section 101 of the U.S. Bankruptcy Code. The Parties agree that the Parties and their respective Sublicensees, as sublicensees of such rights under these Co-Co License Terms, shall retain and may fully exercise all of their rights and elections under the U.S. Bankruptcy Code and any foreign counterpart thereto. The Parties further agree that upon commencement of a bankruptcy proceeding by or against a Party (the “ Bankrupt Party ”) under the Bankruptcy Code, the other Party (the “ Non-Bankrupt Party ”) will be entitled to a complete duplicate of, or complete access to (as the Non-Bankrupt Party deems appropriate), all such intellectual property and all embodiments of such intellectual property. Such intellectual property and all embodiments of such intellectual property will be promptly delivered to the Non-Bankrupt Party (a) upon any such commencement of a bankruptcy proceeding and upon written request by the Non-Bankrupt Party, unless the Bankrupt Party elects to continue to perform all of its obligations under these Co-Co License Terms, or (b) if not delivered under (a) above, upon the rejection of these Co-Co License Terms by or on behalf of the Bankrupt Party and upon written request by the Non-Bankrupt Party. Without limiting the foregoing, Alnylam hereby grants to Genzyme a right of access to and to obtain possession of (i) copies of research data, (ii) laboratory samples, (iii) samples of Co-Co Licensed Product, (iv) formulas, (v) laboratory notes and notebooks, (vi) data and results related to clinical trials, (vii) regulatory filings and approvals, (viii) rights of reference in respect of regulatory filings and approvals, (ix) pre-clinical research data and results, and (x) marketing, advertising and promotional materials, all of which (in clauses (i) through (x)) constitute “embodiments” of intellectual property pursuant to Section 365(n) of the Bankruptcy Code and (xi) all other embodiments of such intellectual property, and in respect of each of the foregoing clauses (i) through (xi), solely for the purpose of the exercise of Genzyme’s rights and licenses under these Co-Co License Terms, whether any of the foregoing are in Alnylam’s possession or control or in the possession and control of Third Parties. The Bankrupt Party (in any capacity, including debtor-in-possession) and its successors and assigns (including any trustee) agree not to interfere with the exercise by the Non-Bankrupt Party or its Related Parties of its rights and licenses to such intellectual property and such embodiments of intellectual property in accordance with these Co-Co License Terms, and agrees to assist the Non-Bankrupt Party and its Related Parties in obtaining such intellectual property and such embodiments of intellectual property in the possession or control of Third Parties as are reasonably necessary or desirable for the Non-Bankrupt Party to exercise such rights and licenses in accordance with these Co-Co License Terms. The foregoing provisions are without prejudice to any rights the Non-Bankrupt Party may have arising under the Bankruptcy Code or other Laws.

7.6. No Other Rights . Except as otherwise expressly provided in these Co-Co License Terms, under no circumstances shall a Party, as a result of these Co-Co License Terms, obtain any ownership interest or other right in any Know-How, Patent Rights or other intellectual property rights of the other Party, including items owned, controlled or developed by the other Party, or provided by the other Party to the receiving Party at any time pursuant to these Co-Co License Terms.

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8. FINANCIAL TERMS FOR GENZYME TERRITORY

8.1. Development Milestone Fees . Genzyme shall provide Alnylam with written notice of the achievement by Genzyme or any of its Related Parties of any development milestone event set forth below in this Section 8.1 and Alnylam shall provide Genzyme with written notice of the achievement by Alnylam or any of its Related Parties of any development milestone event set forth below in this Section 8.1, in each case within [***] days after such event has occurred; provided , however , that the notifying Party shall inform the other Party of such event prior to any public disclosure of such event by the notifying Party. Alnylam shall invoice Genzyme within [***] days of receipt of such written notice by either Party, and Genzyme shall remit the associated development milestone payment within [***] days of the receipt of such invoice. Each development milestone payment by Genzyme to Alnylam hereunder shall be payable only once with respect to each Co-Co Licensed Product, regardless of the number of times a development milestone event is achieved with respect to such Co-Co Licensed Product.

8.1.1. Development Milestones for ALN-TTRsc. Genzyme shall pay Alnylam the following amounts upon achievement of the following development milestone events with respect to ALN-TTRsc:


Development Milestone Event	Development Milestone Payment
[***]		[***]
[***]		[***]
[***]		[***]
[***]		[***]
[***]		[***]

8.1.2. Development Milestones for ALN-AT3. Genzyme shall pay Alnylam the following amounts upon achievement of the following development milestone events with respect to ALN-AT3:


Development Milestone Event	Development Milestone Payment
[***]		[***]
[***]		[***]
[***]		[***]
[***]		[***]
[***]		[***]

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8.2. Royalties .

8.2.1. Royalties Payable on Co-Co Licensed Products. Subject to the provisions these Co-Co License Terms, Genzyme shall pay to Alnylam royalties on annual Net Sales by Genzyme and its Related Parties of each Co-Co Licensed Product in the Genzyme Territory, as follows:


Calendar Year Net Sales of a Co-Co Licensed Product in the Genzyme Territory	Royalty (as a percentage of Net Sales of such Co-Co Licensed Product)
[***]		[***]
[***]		[***]
[***]		[***]
[***]		[***]
[***]		[***]

[***]

Royalties on annual Net Sales of a Co-Co Licensed Product shall be paid at the rate applicable to the portion of Net Sales within each of the Net Sales levels above during such Calendar Year.

8.2.2. Royalty Term. Subject to Section 8.2.6 (Royalty Floor), the period during which the royalties set forth in Section 8.2.1 (Royalties Payable on Co-Co Licensed Products) shall be payable, on a Co-Co Licensed Product-by-Co-Co Licensed Product and country-by-country basis, shall commence with the First Commercial Sale of a Co-Co Licensed Product in a country and continue until the latest of (a) the expiration of the last Valid Claim of [***] in the country of sale; (b) the expiration of Regulatory Exclusivity for such Co-Co Licensed Product in such country; or (c) subject to the last sentence of this Section 8.2.2, the [***] anniversary of the First Commercial Sale of such Co-Co Licensed Product in such country (each such period, a “ Royalty Term ”). [***].

8.2.3. Third Party Royalty Offsets. Genzyme shall be permitted to reduce any royalties payable under Section 8.2.1 (Royalties Payable on Co-Co Licensed Products) for a Co-Co Licensed Product by [***].

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8.2.4. [***].

8.2.5. [***].

8.2.6. Royalty Floor. Anything in these Co-Co License Terms to the contrary notwithstanding, in no event during the applicable Royalty Term for a Co-Co Licensed Product in a country of the Genzyme Territory shall the royalties payable to Alnylam hereunder for such Co-Co Licensed Product in such country for any Calendar Quarter be reduced [***] In-Licenses).

8.2.7. Validation Information. At Genzyme’s request, Alnylam will provide Genzyme with such information as Genzyme may reasonably request to validate the amount of the royalty floor described in Section 8.2.6 (Royalty Floor).

9. FINANCIAL TERMS FOR CO-CO TERRITORY

9.1. [***].

9.2. Third Party License Payments Paid By Genzyme . Genzyme shall provide Alnylam with written notice of any Third Party License Payments made by Genzyme with respect to a Co-Co Licensed Product in the Co-Co Territory. [***].

10. REPRESENTATIONS, WARRANTIES AND COVENANTS

10.1. Representations and Warranties of Alnylam . Except as provided in the Disclosure Schedule to this Section 10.1 (which Disclosure Schedule with respect to ALN-TTRsc is attached hereto as Schedule 10.1- 1 and with respect to ALN-AT3 will be provided by Alnylam to Genzyme as part of the Option Data Package for ALN-AT3), Alnylam represents and warrants to Genzyme that, with respect to ALN-AT3, as of the Implementation Date, and, with respect to ALN-TTRsc, as of the Execution Date:

10.1.1. Alnylam is the sole and exclusive owner of, or otherwise Controls pursuant to an Alnylam In-License, the Alnylam Technology, and all of the Alnylam Technology licensed to Genzyme hereunder in the Genzyme Territory and the Co-Co Territory that is solely and exclusively owned by Alnylam is free and clear of liens, charges or encumbrances other than licenses granted to Third Parties that are not inconsistent with the rights and licenses granted to Genzyme under these Co-Co License Terms.

10.1.2. Alnylam has sufficient legal and/or beneficial title and ownership of, or sufficient license rights under, the Alnylam Technology to grant the licenses to such Alnylam Technology granted to Genzyme pursuant to these Co-Co License Terms.

10.1.3. (a) Schedule 1.2.14 and Schedule 1.2.19 collectively set forth a complete and accurate list of the Alnylam Patents owned, either solely or jointly, by Alnylam, and to Alnylam’s knowledge, Schedule 1.2.14 and Schedule 1.2.19 collectively set forth a complete and accurate list of the Alnylam Patents licensed, either exclusively or nonexclusively, to Alnylam, (b) to Alnylam’s knowledge, each issued Alnylam Patent remains in full force and effect and

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(c) Alnylam or its Affiliates have timely paid all filing and renewal fees payable with respect to such Alnylam Patents for which Alnylam controls prosecution and maintenance. Schedule 1.2.14 and Schedule 1.2.19 indicate whether each Alnylam Patent is owned exclusively by Alnylam, is owned jointly by Alnylam and one or more Third Parties, or is licensed to Alnylam. For each Alnylam Patent that is owned, but not owned exclusively, by Alnylam, or that is licensed to Alnylam, Schedule 1.2.14 and Schedule 1.2.19 identify the Third Party owner(s) and, if applicable, the Alnylam In-License pursuant to which Alnylam Controls such Alnylam Patent. For each Alnylam Product-Specific Patent that is licensed, but not exclusively licensed, to Alnylam, Schedule 1.2.19 indicates the non-exclusive nature of the license. For each Alnylam Core Technology Patent family (other than Patent Rights licensed from Isis Pharmaceuticals, Inc.) that is licensed, but not exclusively licensed, to Alnylam, Schedule 1.2.14 indicates the non-exclusive nature of the license. Alnylam is the sole and exclusive owner of all Patent Rights identified in Schedule 1.2.14 and Schedule 1.2.19 as being owned exclusively by Alnylam and Controls all other Patent Rights identified on such schedules.

10.1.4. To Alnylam’s knowledge, the Alnylam Product-Specific Patents, are, or, upon issuance, will be, valid and enforceable patents and no Third Party has challenged or threatened to challenge the scope, validity or enforceability of any Alnylam Product-Specific Patent (including, by way of example, through opposition or the institution or written threat of institution of interference, nullity or similar invalidity proceedings before the United States Patent and Trademark Office or any analogous foreign Governmental Authority).

10.1.5. Alnylam has complied with all applicable Laws, including any duties of candor to applicable patent offices, in connection with the filing, prosecution and maintenance of the Alnylam Patent Rights.

10.1.6. Alnylam owns or Controls all Know-How that is or has been used by Alnylam in the Development and Manufacture of such Co-Co Licensed Product, and has sufficient legal or beneficial title and ownership of, or sufficient license rights under such Know-How to transfer Know-How to Genzyme as provided in Section 6.4 of the Master Agreement (Transfer of Manufacturing Know-How).

10.1.7. Alnylam Controls all Know-How and Patent Rights licensed to Alnylam under the Existing Alnylam In-Licenses that is necessary or useful for Genzyme to Develop, Manufacture and/or Commercialize such Co-Co Licensed Product in the Field in the Genzyme Territory and the Co-Co Territory. Without limiting the generality of the foregoing, Alnylam has obtained all necessary consents and fulfilled all necessary conditions, if any, to sublicense to Genzyme under these Co-Co License Terms such Know-How and Patent Rights licensed to Alnylam under Existing Alnylam In-Licenses.

10.1.8. To Alnylam’s knowledge, neither Alnylam nor its Affiliates are in breach or default under any existing Alnylam In-License, and neither Alnylam nor its Affiliates have received any written notice of breach or default with respect to any existing Alnylam In-License.

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10.1.9. Alnylam has obtained from all inventors of Alnylam Technology owned by Alnylam valid and enforceable agreements assigning to Alnylam each such inventor’s entire right, title and interest in and to all such Alnylam Technology.

10.1.10. To Alnylam’s knowledge, the use, Development, Manufacture or Commercialization by Alnylam or Genzyme (or their respective Related Parties) of such Co-Co Licensed Product as formulated and manufactured as of the Effective Date, or as intended to be formulated and manufactured as of the Effective Date (a) does not and will not infringe any issued patent of any Third Party and (b) will not infringe the claims of any published Third Party patent application when and if such claims were to issue in their current form.

10.1.11. There is no (a) claim, demand, suit, proceeding, arbitration, inquiry, investigation or other legal action of any nature, civil, criminal, regulatory or otherwise, pending or, to Alnylam’s knowledge, threatened against Alnylam or any of its Affiliates or (b) judgment or settlement against or owed by Alnylam or any of its Affiliates, in each case in connection with the Alnylam Technology or such Co-Co Licensed Product.

10.1.12. For each Co-Co Licensed Product, other than ALN-TTRsc, Schedule 10.1.12(a) (Existing Alnylam In-Licenses) sets forth a complete and accurate list of all agreements between Alnylam and a Third Party entered into prior to the Implementation Date for a Co-Co Licensed Product pursuant to which Alnylam Controls Know-How or Patent Rights that are necessary or useful to Develop, Manufacture or Commercialize such Co-Co Licensed Product in the Field other than Additional Alnylam In-Licenses. [***]. For the sake of clarity, representations and warranties similar to those made pursuant to this Section 10.1.12 with respect to Regional Licensed Products other than ALN-TTRsc are made with respect to ALN-TTRsc in the Master Agreement.

10.2. Representations and Warranties of Genzyme . Except as disclosed in Genzyme’s Option Exercise Notice for a Co-Co Licensed Product, Genzyme represents and warrants to Alnylam as of the Implementation Date that it is not a party to any agreement with a Third Party under which it Controls Know-How or Patent Rights that are sublicensed to Alnylam under these Co-Co License Terms with respect to such Co-Co Licensed Product.

10.3. Warranty Disclaimer . EXCEPT AS OTHERWISE EXPRESSLY PROVIDED IN THESE CO-CO LICENSE TERMS, NEITHER PARTY MAKES ANY REPRESENTATION OR EXTENDS ANY WARRANTY OF ANY KIND, EITHER EXPRESS OR IMPLIED, TO THE OTHER PARTY WITH RESPECT TO ANY TECHNOLOGY, CO-CO LICENSED PRODUCT, GOODS, SERVICES, RIGHTS OR OTHER SUBJECT MATTER OF THESE CO-CO LICENSE TERMS AND HEREBY DISCLAIMS ALL IMPLIED WARRANTIES OF MERCHANTABILITY, FITNESS FOR A PARTICULAR PURPOSE AND NON-INFRINGEMENT WITH RESPECT TO ANY AND ALL OF THE FOREGOING. EACH PARTY HEREBY DISCLAIMS ANY REPRESENTATION OR WARRANTY THAT THE DEVELOPMENT, MANUFACTURE OR COMMERCIALIZATION OF ANY CO-CO LICENSED PRODUCT PURSUANT TO THESE CO-CO LICENSE TERMS WILL BE SUCCESSFUL OR THAT ANY PARTICULAR SALES LEVEL WITH RESPECT TO ANY CO-CO LICENSED PRODUCT WILL BE ACHIEVED.

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10.4. Certain Covenants.

10.4.1. [***] .

10.4.1.1. [***]

(i)

[***]

(ii)

[***]

(iii)

[***]

10.4.1.2. [***]

(i)

[***]

(ii)

[***]

(iii)

[***]

10.4.1.3. [***]

(i)

[***]

(ii)

[***]

(iii)

[***]

10.4.1.4. [***]

10.4.2. No Third Party Collaboration Agreements in the Co-Co Territory. During the Term, Alnylam shall not enter into any agreement with any Third Party granting it rights to Develop or Commercialize any Co-Co Licensed Product in the Field in any portion of the Co-Co Territory except for the benefit, and at the direction, of Alnylam.

10.4.3. Compliance. Each Party and its Related Parties shall conduct the Co-Co Collaboration and the Development, Manufacture and Commercialization of the Co-Co Licensed Products in accordance with all Laws, including current governmental regulations concerning Good Laboratory Practices (as defined in the Master Agreement), good clinical practices and good manufacturing practices. In addition, if either Party is or becomes subject to a legal obligation to a Regulatory Authority or other Governmental Authority (such as a corporate integrity agreement or settlement agreement with a Governmental Authority), then the other Party shall perform such activities as may be reasonably requested by the obligated Party to enable the obligated Party to comply with its legal obligation to such Regulatory Authority with respect to the Co-Co Licensed Products.

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10.4.4. Conflicting Transactions. During the Term, Alnylam shall not (a) transfer or assign any of its rights, title or interests in the Alnylam Technology other than as part of a transaction pursuant to which these Co-Co License Terms are also assigned and assumed in accordance with Section 13.1 of the Master Agreement (Assignment), or (b) enter into any agreement granting a license or other right under the Alnylam Technology that is inconsistent with the provisions of these Co-Co License Terms.

10.4.5. Governmental Authority. If any of the Alnylam Technology is subject to any funding arrangement with any Governmental Authority, at Genzyme’s reasonable request, Alnylam will reasonably cooperate in seeking a waiver or other modification to such funding arrangement with respect to such Alnylam Technology.

11. INTELLECTUAL PROPERTY OWNERSHIP, PROTECTION AND RELATED MATTERS

11.1. Inventorship . Inventorship for inventions and discoveries first made during the course of the performance of activities pursuant to these Co-Co License Terms shall be determined in accordance with United States patent Laws for determining inventorship.

11.2. Ownership . Alnylam shall own the entire right, title and interest in and to all inventions and discoveries (and Patent Rights claiming patentable inventions therein) first made or discovered solely by employees or consultants of Alnylam or acquired solely by Alnylam in the course of conducting the Collaboration. Genzyme shall own the entire right, title and interest in and to all inventions and discoveries (and Patent Rights claiming patentable inventions therein) first made or discovered solely by employees or consultants of Genzyme or acquired solely by Genzyme in the course of conducting the Collaboration. The Parties shall jointly own any inventions and discoveries (and Patent Rights claiming patentable inventions therein) first made or discovered jointly in the course of conducting the Collaboration.

11.3. Prosecution and Maintenance of Patent Rights .

11.3.1. IP Committee. The Parties agree that the IP Committee created pursuant to Section 5.3 of the Master Agreement (IP Committee) shall be responsible for overseeing and effecting the information sharing and consulting provisions under this Section 11.3.

11.3.2. Genzyme Technology.

(a) Subject to Section 11.3.2(b) below, Genzyme has the sole responsibility to, at Genzyme’s discretion and at Genzyme’s sole cost and expense, file, prosecute, and maintain (including the defense of any interference or opposition proceedings), all Patent Rights comprising Genzyme Technology (other than Joint Collaboration IP), in Genzyme’s name.

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(b) In the event that Genzyme elects not to seek or continue to seek or maintain patent protection on any Genzyme Collaboration IP in the Co-Co Territory, Genzyme shall notify Alnylam at least [***] days before any such Patent Rights would become abandoned, no longer available or otherwise forfeited, and subject to the terms and conditions of any applicable Genzyme In-License, Alnylam shall have the right (but not the obligation), at its sole cost and expense, to seek, prosecute and maintain in any country patent protection on such Genzyme Collaboration IP in the name of Genzyme. Genzyme shall use Commercially Reasonable Efforts to make available to Alnylam its authorized attorneys, agents or representatives, and/or such of its employees as are reasonably necessary to assist Alnylam in obtaining and maintaining the patent protection described under this Section 11.3.2(b). Genzyme shall sign or use Commercially Reasonable Efforts to have signed all legal documents as are reasonably necessary to file and prosecute such patent applications or to obtain or maintain such patents.

11.3.3. Alnylam Technology. The following will apply with respect to Alnylam Patent Rights during the Term, [***].

(a) Subject to Section 11.3.3(c) below, Alnylam has the sole responsibility to, at Alnylam’s discretion and at Alnylam’s sole cost and expense, file, conduct prosecution, and maintain (including the defense of any interference or opposition proceedings), all Patent Rights comprising Alnylam Technology (other than Joint Collaboration IP), in Alnylam’s name. Notwithstanding the foregoing, Alnylam shall file such Alnylam Product-Specific Patents in the Genzyme Patent Jurisdictions (as defined in the Master Agreement) and shall use commercially reasonable efforts to prosecute and maintain such Patent Rights in the Genzyme Patent Jurisdictions and shall timely pay all filing and renewal fees payable with respect thereto.

(b) Notwithstanding the foregoing Section 11.3.3(a), Alnylam shall consult with Genzyme, including through the IP Committee, on its strategy for the preparation, filing, prosecution, and maintenance of all Alnylam Product-Specific Patents in the Genzyme Territory and the Co-Co Territory. Alnylam shall furnish to Genzyme, via electronic mail or such other method as mutually agreed by the Parties, copies of proposed filings and documents received from outside counsel in the course of such filing, prosecution or maintenance of and/or copies of documents filed with the relevant patent offices with respect to Alnylam Product-Specific Patents and such other documents directly related to the prosecution and maintenance of Alnylam Product-Specific Patents reasonably necessary for Genzyme to exercise its rights under this Section 11.3.3(b), and as applicable in sufficient time prior to filing such document or making any payment due thereunder to allow for review and comment by Genzyme and shall consider in good faith timely comments from Genzyme thereon. Alnylam shall furnish to Genzyme, via electronic mail or such other method as mutually agreed by the Parties, copies of documents received from outside counsel in the course of filing, prosecution or maintenance of and/or copies of documents filed with the relevant national patent offices with respect to the filing, prosecution, and maintenance of Alnylam Core Technology Patents within a reasonable period of time after the receipt and/or filing of such documents.

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(c) In the event that Alnylam elects not to seek or continue to seek or maintain patent protection on any Alnylam Product-Specific Patent in the Genzyme Territory or the Co-Co Territory, Alnylam shall notify Genzyme at least [***] days before any such Patent Rights would become abandoned, no longer available or otherwise forfeited, and subject to the provisions of any applicable Alnylam In-License, Genzyme shall have the right (but not the obligation), at its sole cost and expense, to seek, prosecute and maintain in any country patent protection on such Alnylam Product-Specific Patent in the Genzyme Territory. If Genzyme exercises such right, Alnylam shall thereafter and hereby does assign all right, title and interest in and to such Alnylam Product-Specific Patent Rights to Genzyme. Alnylam shall use Commercially Reasonable Efforts to make available to Genzyme its authorized attorneys, agents or representatives, and/or such of its employees as are reasonably necessary to assist Genzyme in obtaining and maintaining the patent protection described under this Section 11.3.3(c). Alnylam shall sign or use Commercially Reasonable Efforts to have signed all legal documents as are reasonably necessary to file and prosecute such patent applications or to obtain or maintain such patents.

(d) [***]

11.3.4. Joint Collaboration IP.

(a) [***]shall have the first right to, at [***]discretion, file, prosecute and maintain (including the defense of any interference or opposition proceedings), all Patent Rights comprising Joint Collaboration IP, in the names of both Alnylam and Genzyme. [***]shall consult with [***] on the filing, prosecution and maintenance of all such Patent Rights. Each Party shall sign, or use Commercially Reasonable Efforts to have signed, all legal documents as are reasonably necessary to file and prosecute patent applications or to obtain or maintain patents in respect of such Joint Collaboration IP, at its own cost.

(b) [***] shall furnish [***], via electronic mail or such other method as mutually agreed by the Parties, copies of documents received from outside counsel in the course of such filing, prosecution or maintenance of Joint Collaboration IP and/or copies of documents relevant to such preparation, filing, prosecution, and maintenance in sufficient time prior to filing such document or making any payment due thereunder to allow for review and comment by [***] and shall consider in good faith timely comments from [***] thereon. Alnylam shall furnish to[***], via electronic mail or such other method as mutually agreed by the Parties, copies of such documents as filed in the relevant patent offices.

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(c) In the event that [***] elects not to file or continue to prosecute or maintain patent protection on any Joint Collaboration IP, [***] shall have the right (but not the obligation) to file, prosecute and maintain Patent Rights comprising Joint Collaboration IP in the names of both Alnylam and Genzyme. If Genzyme exercises such right, [***] shall use Commercially Reasonable Efforts to make available to [***] its authorized attorneys, agents or representatives, and/or such of its employees as are reasonably necessary to assist [***] in obtaining and maintaining the patent protection described under this Section 11.3.4(c). [***] shall sign or use Commercially Reasonable Efforts to have signed all legal documents as are reasonably necessary to file and prosecute such patent applications or to obtain or maintain such patents.

(d) The Parties shall share equally the out-of-pocket patent filing, prosecution and maintenance expenses incurred with respect to Patent Rights comprising Joint Collaboration IP.

11.3.5. Patent Miscellaneous. Each Party hereby agrees: (a) to make its employees, agents and consultants reasonably available to the other Party (or to the other Party’s authorized attorneys, agents or representatives), to the extent reasonably necessary to enable such Party to undertake patent prosecution; (b) to provide the other Party with copies of all material correspondence pertaining to prosecution with the patent offices; (c) to cooperate, if necessary and appropriate, with the other Party in gaining patent term extensions wherever applicable to Patent Rights licensed under these Co-Co License Terms; and (d) to endeavor in good faith to coordinate its efforts with the other Party to minimize or avoid interference with the prosecution and maintenance of the other Party’s patent applications.

11.3.6. [***] .

11.3.6.1. [***]

11.3.6.2. [***]

11.3.6.3. [***]

11.4. Third Party Infringement .

11.4.1. Notices. Each Party shall promptly report in writing to the other Party any (a) known or suspected infringement of any Alnylam Technology, Genzyme Technology or Joint Collaboration IP or (b) unauthorized use or misappropriation of any Confidential Information or Know-How of a Party by a Third Party of which it becomes aware, in each case to the extent such infringing, unauthorized or misappropriating activities involve, as to a Co-Co Licensed Product, a competing product in the Field (a “Competitive Infringement ”), and shall provide the other Party with all available evidence of such infringement, unauthorized use or misappropriation.

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11.4.2. Rights to Enforce.

(a) Genzyme Technology . Subject to the provisions of any In-License, Genzyme shall have the sole and exclusive right to initiate an infringement or other appropriate suit (an “ Infringement Action ”) anywhere in the world against any Third Party as to any infringement, or suspected infringement, of any Patent Rights, or as to any use or suspected use without proper authorization of any Know-How comprising Genzyme Patent Rights, Genzyme Know-How or Genzyme Collaboration IP. Genzyme will consider in good faith any request from Alnylam to initiate an Infringement Action against any Third Party with respect to Competitive Infringement in the Co-Co Territory of Genzyme Patent Rights, Genzyme Know-How or Genzyme Collaboration IP licensed to Alnylam under Section 7 (Licenses); provided , however , that Genzyme shall not be required to initiate any such Infringement Action or permit Alnylam to initiate any such Infringement Action.

(b) Alnylam Technology .

(i)

Genzyme Territory. Subject to the provisions of any In-License, Genzyme shall have the first right to initiate an Infringement Action anywhere in the world against any Third Party with respect to any Competitive Infringement in the Genzyme Territory of any Alnylam Product-Specific Patent, Joint Collaboration IP or Alnylam Collaboration IP, or, with Alnylam’s prior written consent, Alnylam Core Technology Patent or Alnylam Know-How. Alnylam will consider in good faith any request from Genzyme to initiate an Infringement Action against any Third Party with respect to a Competitive Infringement in the Genzyme Territory of any Alnylam Core Technology Patent Right or Alnylam Know-How; provided , however , that Alnylam shall not be required to initiate any such Infringement Action or permit Genzyme to initiate any such Infringement Action.

(ii)

Co-Co Territory . Subject to the provisions of any In-License, Alnylam shall have the first right to initiate an Infringement Action anywhere in the world against any Third Party with respect to any Competitive Infringement in the Co-Co Territory of any Alnylam Product-Specific Patent, Joint Collaboration IP, Alnylam Collaboration IP, Alnylam Core Technology Patent or Alnylam Know-How. Alnylam will consider in good faith any request from Genzyme to initiate an Infringement Action against any Third Party with respect to such Competitive Infringement in the Co-Co Territory; provided , however , that Alnylam shall not be required to initiate any such Infringement Action.

(c)

Step-In Rights .

(i)

Alnylam Step-In Right for Alnylam Technology in Genzyme Territory . If within [***] days (or such shorter period of time as required by applicable Law to avoid loss of material enforcement rights) after Genzyme’s receipt

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of a notice of a Competitive Infringement with respect to any Alnylam Product-Specific Patent or Joint Collaboration IP, Genzyme does not initiate any Infringement Action against such Competitive Infringement in the Genzyme Territory, Alnylam may in its sole discretion, bring and control any Infringement Action in connection therewith at its sole cost and expense.

(ii)

Genzyme Step-In Right for Alnylam Technology in Co-Co Territory . If within [***] days (or such shorter period of time as required by applicable Law to avoid loss of material enforcement rights) after Alnylam’s receipt of a notice of a Competitive Infringement with respect to any Alnylam Product-Specific Patent, Joint Collaboration IP or Alnylam Collaboration IP, Alnylam does not initiate any Infringement Action against such Competitive Infringement in the Co-Co Territory, Genzyme may in its sole discretion, bring and control any Infringement Action in connection therewith at its sole cost and expense.

(iii)

[***]

11.4.3. Procedures; Expenses and Recoveries. The Party having the right to initiate any Infringement Action under Section 11.4.2 (Rights to Enforce) above shall have the sole and exclusive right to select counsel for any such Infringement Action and shall pay all expenses of the suit, including attorneys’ fees and court costs and reimbursement of the other Party’s reasonable Co-Co Out-of-Pocket Costs in rendering assistance requested by the initiating Party. If required under applicable Law in order for the initiating Party to initiate and/or maintain such Infringement Action, or if either Party is unable to initiate or prosecute such Infringement Action solely in its own name or it is otherwise advisable to obtain an effective legal remedy, in each case, the other Party shall join as a party to the Infringement Action and will execute and cause its Affiliates to execute all documents necessary for the initiating Party to initiate litigation to prosecute and maintain such action. In addition, at the initiating Party’s request, the other Party shall provide reasonable assistance to the initiating Party in connection with an Infringement Action at no charge to the initiating Party except for reimbursement by the initiating Party of reasonable Co-Co Out-of-Pocket Costs incurred in rendering such assistance. The non-initiating Party shall have the right to participate and be represented in any such Infringement Action by its own counsel at its own expense. If the Parties obtain from a Third Party, in connection with such Infringement Action, any damages, license fees, royalties or other compensation (including any amount received in settlement of such litigation), after payment of any amounts required under any In-Licenses, the remaining amounts shall be allocated in all cases as follows:

(a) first, to reimburse each Party for all expenses of the Infringement Action incurred by the Parties, including attorneys’ fees and disbursements, court costs and other litigation expenses;

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(b) second, [***] of the balance to be paid to the Party initiating the Infringement Action, with respect to Infringement Actions in the Genzyme Territory, and [***] of the balance to be paid to the Party initiating the Infringement Action, with respect to Infringement Actions in the Co-Co Territory; and

Notwithstanding the foregoing, in the event that Alnylam elects to itself assert an Alnylam Core Technology Patent against a Competitive Infringement in the Genzyme Territory, the Parties shall each be entitled to [***] of the balance of any recovery therefrom after reimbursement of expenses as described in clause (i) above. In addition, with respect to Infringement Actions brought in the Co-Co Territory, the Parties shall share evenly the expenses of the suit, including attorneys’ fees of each Party, court costs, and both Parties’ reasonable Co-Co Out-of-Pocket expenses in rendering assistance related to the Infringement Action (“ Litigation Expenses ”). For such Infringement Actions brought in the Co-Co Territory, Litigation Expenses shall initially be borne by the Party incurring the expense. Each Party will calculate and maintain records of Litigation Expenses incurred by it and its Affiliates with respect to any such Infringement Action, and, within thirty (30) days following the end of each Calendar Quarter, each Party shall submit to the other a report detailing the Litigation Expenses incurred by it and its Affiliates during such Calendar Quarter. Unless otherwise agreed by the Parties, the Party that incurs more than its share of the total Litigation Expenses with respect to such an Infringement Action in the Co-Co Territory during any Calendar Quarter shall be paid by the other Party an amount of cash sufficient to reconcile to its fifty percent (50%) share of Litigation Expenses.

11.5. Patent Term Extensions .

11.5.1. Retained Alnylam Product-Specific Patent Rights. Subject to the provisions of any Alnylam In-License, Alnylam shall use Commercially Reasonable Efforts to obtain all available supplementary protection certificates (“ SPCs ”) and other extensions of Alnylam Product-Specific Patents in the Genzyme Territory[***]. If more than one Alnylam Product-Specific Patent is eligible for extension or patent term restoration in the Genzyme Territory, Genzyme will determine, in its sole discretion, a strategy that will be designed to maximize patent protection and commercial value for the Co-Co Licensed Product, and the Parties, subject to the provisions of any In-License, will seek patent term extensions, restorations and SPCs for Alnylam Product-Specific Patents in the Genzyme Territory in accordance with that strategy. Where required under national law, and subject to the other requirements of this Section 11.5, Alnylam will make the filings for such extensions, restorations and SPCs for Alnylam Product-Specific Patents in the Genzyme Territory as directed by Genzyme.

11.5.2. Further Assurances for SPCs. Each Party will execute such authorizations and other documents and take such other actions as may be reasonably requested by the other Party to obtain any such extensions, restorations and SPCs for Alnylam Product-Specific Patents in the Genzyme Territory, in accordance with this Section 11.5.

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11.6. Common Interest . All information exchanged between the Parties’ representatives regarding the preparation, filing, prosecution, maintenance, or enforcement of the Patent Rights under this Section 11 will be deemed Confidential Information. In addition, the Parties acknowledge and agree that, with regard to such preparation, filing, prosecution, maintenance, and enforcement of the Patents Rights under this Section 11, the interests of the Parties as collaborators and licensor and licensee are to obtain the strongest patent protection possible, and as such, are aligned and are legal in nature. The Parties agree and acknowledge that they have not waived, and nothing in these Co-Co License Terms constitutes a waiver of, any legal privilege concerning the Patents Rights under this Section 11, including privilege under the common interest doctrine and similar or related doctrines.

11.7. Trademarks .

(a) Each Party has the right to use any trademark it owns or controls for Co-Co Licensed Products in its Territory at its sole discretion, and each Party and its Affiliates shall retain all right, title and interest in and to its and their respective corporate names and logos.

(b) Genzyme will develop and propose, and the PJSC shall review and comment on, one or more Product Trademark(s) for use by Genzyme and its Related Parties throughout the Genzyme Territory. Such Product Trademark(s) considered by the PJSC may include, in Genzyme’s sole discretion, the Product Trademark(s) developed and/or used by Alnylam with respect to the Commercialization of Co-Co Licensed Products in the Co-Co Territory (the “ Alnylam Trademarks ”), but may not include other trademarks owned or controlled by Alnylam. Any Product Trademark(s) (other than the Alnylam Trademarks) that are used by Genzyme to promote and sell Co-Co Licensed Products in the Genzyme Territory are hereinafter referred to as the “ Genzyme Trademarks .” Alnylam (or its Related Parties, as appropriate) shall own all rights to Alnylam Trademarks, and all goodwill associated therewith, throughout the Co-Co Territory and the Genzyme Territory. Genzyme (or its Related Parties, as appropriate) shall own all rights to Genzyme Trademarks and all goodwill associated therewith, throughout the Genzyme Territory. Alnylam shall also own rights to any Internet domain names incorporating the applicable Alnylam Trademarks or any variation or part of such Alnylam Trademarks used as its URL address or any part of such address; and Genzyme shall also own rights to any Internet domain names incorporating the applicable Genzyme Trademarks or any variation or part of such Genzyme Trademarks used as its URL address or any part of such address.

(c) If Genzyme determines to use Alnylam Trademarks to promote and sell any Co-Co Licensed Product in the Genzyme Territory, then Alnylam and Genzyme shall enter into a separate trademark license agreement containing commercially reasonable and customary terms pursuant to which Alnylam will grant Genzyme an exclusive, royalty-free license to use the applicable Alnylam Trademark(s) to Commercialize Co-Co Licensed Products in the Genzyme Territory.

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11.8. Cooperative Research and Technology (CREATE) Act Acknowledgment . It is the intention of the Parties that these Co-Co License Terms are a “joint research agreement” as that phrase is defined in Section 35 U.S.C. 103(c).

12. TERM AND TERMINATION

12.1. Term . These Co-Co License Terms shall be effective as of the Effective Date and, unless terminated earlier pursuant to Section 12.2 (Termination Rights), these Co-Co License Terms shall continue in effect on a Co-Co Licensed Product-by-Co-Co Licensed Product and country-by-country basis until no further payments are due under Section 8 (Financial Terms for Genzyme Territory) or Section 9 (Financial Terms for Co-Co Territory) of these Co-Co License Terms (“ Term ”). Upon expiration of the Royalty Term for any particular Co-Co Licensed Product, all licenses of the Parties under Section 7 (Licenses) with respect to such Co-Co Licensed Product then in effect shall become fully paid-up, perpetual licenses.

12.2. Termination Rights . These Co-Co License Terms may be terminated by the Parties only as set forth in this Section 12.2.

12.2.1. Termination for Convenience. Subject to the remainder of this Article 12, Genzyme shall have the right to terminate these Co-Co License Terms with respect to any particular Co-Co Licensed Product as follows:

(a) After initiation of the first Phase II Study for such Co-Co Licensed Product and prior to completion of such Phase II Study for such Co-Co Licensed Product, Genzyme shall have the right to terminate these Co-Co License Terms with respect to such Co-Co Licensed Product upon sixty (60) days prior written notice in the event that a Safety Concern occurs, provided that in the event of such termination Genzyme shall pay to Alnylam [***] of the Global R&D Costs and Global Regulatory Costs incurred through the effective date of termination (not to exceed [***]) to wind down any ongoing Phase II Studies with respect to such Co-Co Licensed Product in an efficient manner consistent with patient safety, applicable Law and ethical standards.

(b) After initiation of the first Phase II Study for such Co-Co Licensed Product and prior to completion of such Phase II Study for such Co-Co Licensed Product, Genzyme shall have the right to terminate these Co-Co License Terms with respect to

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such Co-Co Licensed Product for any reason upon written notice (in which case, such termination shall become effective immediately upon Alnylam’s receipt of notice of such termination), provided that in the event of such termination Genzyme shall pay to Alnylam [***] of the Global R&D Costs and Global Regulatory Costs incurred in any ongoing Phase II Studies for such Co-Co Licensed Product (not to exceed [***].

(c) Within sixty (60) days of Genzyme’s receipt of the Phase 3 Budget and End of Phase II Package, Genzyme shall have the right to terminate these Co-Co License Terms with respect to such Co-Co Licensed Product upon written notice to Alnylam (in which case, such termination shall become effective immediately upon Alnylam’s receipt of notice of such termination), provided that in the event of such termination Genzyme shall pay to Alnylam [***] of the Global R&D Costs and Global Regulatory Costs incurred through the effective date of termination (not to exceed [***].

(d) After initiation of the first Phase III Study for such Co-Co Licensed Product and prior to completion of such Phase III Study for such Co-Co Licensed Product, Genzyme shall have the right to terminate these Co-Co License Terms with respect to such Co-Co Licensed Product upon sixty (60) days prior written notice in the event that a Safety Concern occurs, provided that in the event of such termination Genzyme shall pay to Alnylam [***] of the Global R&D Costs and Global Regulatory Costs incurred through the effective date of termination (not to exceed [***]) to wind down any ongoing Clinical Studies with respect to such Co-Co Licensed Product in an efficient manner consistent with patient safety, applicable Law and ethical standards.

(e) After initiation of the first Phase III Study for such Co-Co Licensed Product and Genzyme’s payment of the Phase III Study initiation milestone payment described in Section 8.1.1(i) (Development Milestones for ALN-TTRsc) or 8.1.2(i) (Development Milestones for ALN-AT3), Genzyme shall have the right to terminate these Co-Co License Terms with respect to such Co-Co Licensed Product at any time upon sixty (60) days prior written notice to Alnylam, provided that in the event of such termination Genzyme shall pay to Alnylam [***] of the Global R&D Costs and Global Regulatory Costs incurred in conducting any ongoing Phase III Study with respect to such Co-Co Licensed Product through filing of the first NDA with respect to such Co-Co Licensed Product (not to[***]).

(f) After completion of the first Phase III Study for such Co-Co Licensed Product, Genzyme shall have the right to terminate these Co-Co License Terms with respect to such Co-Co Licensed Product at any time upon sixty (60) days prior written notice to Alnylam.

12.2.2. Termination for Cause. These Co-Co License Terms may be terminated with respect to any particular Co-Co Licensed Product at any time during the Term upon written notice by either Party if (a) the other Party is in material breach of its obligations hereunder with respect to such Co-Co Licensed Product and (b) the other Party has not cured such breach within thirty (30) days in the case of a payment breach, or within ninety (90) days in the case of all

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other breaches, after notice requesting cure of the breach; provided , however , that if any breach other than a payment breach is not reasonably curable within ninety (90) days and if a Party is making a bona fide effort to cure such breach, such termination shall be delayed for a time period to be agreed by both Parties, not to exceed an additional ninety (90) days, in order to permit such Party a reasonable period of time to cure such breach; and provided , further , that in the event that the breach relates to a dispute between the Parties regarding Genzyme’s obligations to use Commercially Reasonable Efforts in Developing or Commercializing such Co-Co Licensed Product and Genzyme disputes whether it has breached such obligation or whether such breach gives Alnylam the right to terminate these Co-Co License Terms with respect to such Co-Co Licensed Product and initiates a legal action against Alnylam to resolve such dispute within the foregoing sixty (60) day cure period, then these Co-Co License Terms shall not terminate during the pendency of such legal action, provided that if (i) Genzyme is found, in an unappealable decision by a court of competent jurisdiction or an appealable decision of a court of competent jurisdiction that has not been appealed in the time allowed for an appeal in such legal action, to have materially breached these Co-Co License Terms with respect to such Co-Co Licensed Product, or (ii) Genzyme admits in such legal action or settlement thereof that it has materially breached these Co-Co License Terms with respect to such Co-Co Licensed Product, then these Co-Co License Terms shall terminate immediately with respect to such Co-Co Licensed Product following the Parties’ receipt of such decision or immediately following such admission, as applicable.

12.2.3. Challenges of Patent Rights. If, during the Term, Genzyme or any of its Affiliates (a) commences or participates in any action or proceeding (including any patent opposition or re-examination proceeding), or otherwise asserts any claim, challenging or denying the validity or enforceability of any Alnylam Product-Specific Patent or any claim thereof or (b) actively assists any other Person or entity in bringing or prosecuting any action or proceeding (including any patent opposition or re-examination proceeding) challenging or denying the validity or enforceability of any Alnylam Product-Specific Patent for a Co-Co Licensed Product or any claim thereof (each of (a) and (b), a “ Patent Challenge ”), then, to the extent permitted by the applicable Laws, Alnylam shall have the right, exercisable within sixty (60) days following receipt of notice regarding such Patent Challenge, in its sole discretion, to give notice to Genzyme that Alnylam may terminate these Co-Co Licensed Terms with respect to the Co-Co Licensed Product Covered by the Alnylam Product-Specific Patent that is the subject of the Patent Challenge (which termination will be effective ninety (90) days following such notice (or such longer period as Alnylam may designate in such notice)), and, unless Genzyme or such Affiliate withdraws or causes to be withdrawn all such challenge(s) (or in the case of ex-parte proceedings, multi-party proceedings, or other Patent Challenges that Genzyme or Genzyme’s Affiliates do not have the power to unilaterally withdraw or cause to be withdrawn, Genzyme and Genzyme’s Affiliates cease actively assisting any other party to such Patent Challenge and, to the extent Genzyme or a Genzyme Affiliate is a party to such Patent Challenge, it withdraws from such Patent Challenge) within such ninety (90)-day period, Alnylam will have the right to terminate these Co-Co License Terms with respect to such Co-Co Licensed Product by providing written notice thereof to Genzyme. The foregoing sentence shall not apply with respect to (i) any Alnylam Product-Specific Patent that Alnylam first asserts against Genzyme or any of its

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Affiliates where the Patent Challenge is made in defense of such assertion or (ii) any Patent Challenge commenced by a Third Party that, after the Effective Date, acquires or is acquired by Genzyme or its Affiliates or its or their business or assets, whether by stock purchase, merger, asset purchase or otherwise, but only with respect to Patent Challenges commenced prior to the closing of such acquisition.

12.2.4. Abandonment of Development. At any time on or after [***], either Party may terminate these Co-Co License Terms in their entirety ( i.e. , with respect to all Co-Co Licensed Products) if (a) no Co-Co Licensed Product has received Regulatory Approval anywhere in the Genzyme Territory, (b) no Co-Co Licensed Product is being Developed for the Genzyme Territory, (c) no Global Development Plan or Genzyme Territory Development Plan is in effect for any Co-Co Licensed Product, provided that if Genzyme provides Alnylam with a good faith Genzyme Territory Development Plan pursuant to Section 2.2.3 (Genzyme Territory Development Plan) during the termination notice period set forth below in this Section 12.2.4, then the condition set forth in this clause (c) shall be deemed not satisfied at such time and the applicable termination notice shall be deemed not to have effect, and (d) the absence of Development in the Genzyme Territory or a good faith Genzyme Territory Development Plan is not the result of a breach by the Party seeking to terminate these Co-Co License Terms of its obligations under Section 2.4 (Diligence). In order to terminate these Co-Co License Terms pursuant to this Section 12.2.4, the terminating Party must provide at least six (6) months’ prior written notice to the other Party referencing this Section 12.2.4 and specifying a termination date on or after [***], provided that, with respect to any such termination by Alnylam, such notice must also include an update regarding the current status of Alnylam’s Development activities with respect to Co-Co Licensed Products.

12.3. Effect of Termination .

12.3.1. Effects of Termination by Genzyme for Cause. Without limiting any other legal or equitable remedies that either Party may have, if these Co-Co License Terms are terminated by Genzyme with respect to any particular Co-Co Licensed Product pursuant to Section 12.2.2 (Termination for Cause), then:

(a) these Co-Co License Terms shall continue to survive in all respects with respect to all Co-Co Licensed Products other than the terminated Co-Co Licensed Product;

(b) all license grants in these Co-Co License Terms with respect to the terminated Co-Co Licensed Product from either Party to the other shall immediately terminate;

(c) the Back-Up Option shall terminate with respect to all Back-Up Products for the terminated Co-Co Licensed Product; provided , however , that such Back-Up Products shall, as of such date, be considered Option Products for the purposes of the Master Agreement, and the Options granted under the Master Agreement to siRNA that targets the same gene as the terminated Co-Co Licensed Product shall again apply in accordance with the terms and conditions set forth in the Master Agreement;

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(d) Genzyme shall as promptly as practicable transfer to Alnylam or Alnylam’s designee (i) possession and ownership of all Regulatory Approvals and pricing and reimbursement approvals relating to the Development, Manufacture or Commercialization of the terminated Co-Co Licensed Product, and (ii) copies of all non-clinical and clinical data and material regulatory correspondence relating to the terminated Co-Co Licensed Product, provided that Alnylam shall reimburse Genzyme for any reasonable out-of-pocket expenses incurred by Genzyme in connection with such transfer;

(e) Genzyme will assign and transfer to Alnylam all rights, title and interests in and to any Alnylam Product-Specific Patents that relate solely to the terminated Co-Co Licensed Product that were assigned to Genzyme pursuant to Section 11.3.6 (Assignment of Alnylam Product-Specific Patents to Genzyme), provided that Alnylam shall reimburse Genzyme for any reasonable out-of-pocket expenses incurred by Genzyme in connection with such assignment and transfer. In such event, Genzyme will execute and deliver a patent assignment relating to such Alnylam Product-Specific Patents in the same form used to assign such Patent Rights to Genzyme; and

(f) each Party shall promptly pay any amounts owed to the other Party as of the effective date of such termination.

12.3.2. Effects of Termination by Alnylam for Cause or by Genzyme for Convenience. Without limiting any other legal or equitable remedies that either Party may have, if these Co-Co License Terms are terminated with respect to any particular Co-Co Licensed Product by Genzyme pursuant to Section 12.2.1 (Termination for Convenience) or by Alnylam under Section 12.2.2 (Termination for Cause) or Section 12.2.3 (Challenges of Patent Rights), then:

(a) these Co-Co License Terms shall continue to survive in all respects with respect to all Co-Co Licensed Products other than the terminated Co-Co Licensed Product;

(b) all licenses granted by Alnylam to Genzyme in these Co-Co License Terms with respect to the terminated Co-Co Licensed Product shall immediately terminate;

(c) the Back-Up Option shall terminate with respect to all Back-Up Products for the terminated Co-Co Licensed Product and such Back-Up Products shall be treated as Option Products for which Genzyme has not exercised an Option for purposes of Section 3.5 of the Master Agreement;

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(d) Genzyme will assign and transfer to Alnylam, all rights, title and interests in and to any Alnylam Product Specific Patents that relate solely to the terminated Co-Co Licensed Product that were assigned to Genzyme pursuant to Section 11.3.6 (Assignment of Alnylam Product-Specific Patents to Genzyme). In such event, Genzyme will execute and deliver a patent assignment relating to such Alnylam Product-Specific Patents in the same form used to assign such Patent Rights to Genzyme;

(e) Genzyme will grant to Alnylam, effective upon the effective date of termination and subject to the provisions of any applicable Genzyme In-License, a non-transferable, sublicensable (on terms consistent with Section 7.2.4 (Sublicensing Terms)), worldwide, non-exclusive, royalty-free license under any Genzyme Collaboration IP and Genzyme Patent Rights that Cover the terminated Co-Co Licensed Product, in the form that such terminated Co-Co Licensed Product exists on the effective date of termination (the “ Reverted Co-Co Licensed Product ”), solely to the extent necessary to Develop and Commercialize the Reverted Co-Co Licensed Product in the Field in the Genzyme Territory. Notwithstanding the foregoing, if (i) any Patent Rights that Cover the Reverted Co-Co Licensed Product are Controlled by Genzyme pursuant to a Genzyme In-License and (ii) such Genzyme In-License cannot be assigned to Alnylam or does not relate exclusively to the Reverted Co-Co Licensed Product, Genzyme shall promptly disclose any payment obligations under such Genzyme In-License to Alnylam and such Genzyme Patent Rights shall be subject to the license granted in this Section 12.3.2(e) only if Alnylam agrees in writing to (A) reimburse Genzyme for one hundred percent (100%) of any amounts that become payable under such Genzyme In-License as a result of Alnylam’s exercise of the license granted in this Section 12.3.2(e), (B) comply with all applicable terms and conditions of such Genzyme In-License and (C) perform and take such actions as may be required to allow Genzyme to comply with its obligations under such Genzyme In-License.

(f) The license grants to Alnylam in Section 7.2 (License Grants to Alnylam) shall survive and shall be expanded to include the Genzyme Territory with respect to the Reverted Co-Co Licensed Product.

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months after the effective date of termination with respect to such Reverted Co-Co Licensed Product, Genzyme shall use Commercially Reasonable Efforts to obtain for Alnylam the right to access all such data, reports, records, materials, and other sales and marketing related information related to the Reverted Co-Co Licensed Product, and (iii) all records and materials in Genzyme’s possession or Control containing Confidential Information of Alnylam solely relating to the Reverted Co-Co Licensed Product. In addition, Genzyme shall appoint Alnylam as Genzyme’s and/or Genzyme’s Related Parties’ agent for all matters related to the Reverted Co-Co Licensed Product involving Regulatory Authorities in the Genzyme Territory until all Regulatory Approvals and other regulatory filings have been transferred to Alnylam or its designee.

(h) If the effective date of termination is after First Commercial Sale of the Reverted Co-Co Licensed Product, then Genzyme shall appoint Alnylam as its exclusive distributor of the Reverted Co-Co Licensed Product in the Genzyme Territory and grant Alnylam the right to appoint sub-distributors, until such time as all Regulatory Approvals in the Genzyme Territory have been transferred to Alnylam or its designee.

(i) If Genzyme or its Related Parties are Manufacturing finished product with respect to the Reverted Co-Co Licensed Product on the effective date of termination, at Alnylam’s option, Genzyme or its Related Parties shall supply such finished product to Alnylam in the Genzyme Territory on terms no less favorable than those on which Genzyme supplied such finished product prior to such termination to its most favored distributor in the Genzyme Territory, until the earlier of (i) such time as all Regulatory Approvals in the Genzyme Territory solely related to the Reverted Co-Co Licensed Product have been transferred to Alnylam or its designee, Alnylam has obtained all necessary manufacturing approvals and Alnylam has procured or developed its own source of such finished product supply or (ii) [***] months following the effective date of such termination.

(j) If Alnylam so requests, and to the extent permitted under Genzyme’s obligations to Third Parties on the effective date of termination, Genzyme shall transfer to Alnylam any Third Party agreements relating solely and exclusively to the Development, Manufacture or Commercialization of the Reverted Co-Co Licensed Product to which Genzyme is a party (including any Genzyme In-License), subject to any required consents of such Third Party, which Genzyme shall use Commercially Reasonable Efforts to obtain promptly.

(k) Genzyme shall promptly transfer and assign to Alnylam all of Genzyme’s and its Affiliates’ rights, title and interests in and to the Genzyme Trademark(s) (but not any Genzyme house marks or any trademark containing the word “Genzyme” owned by Genzyme and used for the Reverted Co-Co Licensed Product in the Field in the Genzyme Territory) owned by Genzyme and used solely and exclusively for the Reverted Co-Co Licensed Product in the Field in the Genzyme Territory.

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(l) Genzyme shall transfer to Alnylam any inventory of the Reverted Co-Co Licensed Products Controlled by Genzyme or its Affiliates as of the termination date at the actual price paid by Genzyme for such supply.

(m) Genzyme shall provide any other assistance reasonably requested by Alnylam for the purpose of allowing Alnylam or its designee to proceed expeditiously with the Development, Manufacture and Commercialization of the Reverted Co-Co Licensed Product in the Genzyme Territory, provided that Genzyme’s obligations under this clause (m) of Section 12.3.2 shall expire [***] months after the effective date of termination of such Reverted Co-Co Licensed Product.

(n) Genzyme shall execute all documents and take all such further actions as may be reasonably requested by Alnylam in order to give effect to the foregoing clauses.

12.3.3. Effects of Termination for Abandonment of Development. If these Co-Co License Terms are terminated in their entirety ( i.e. , with respect to all Co-Co Licensed Products) by either Party pursuant to Section 12.2.4 (Abandonment of Development), then the license granted to Alnylam under Section 7.2.2 (License to Improvement Manufacturing Patent Rights) shall survive and all other licenses granted in these Co-Co License Terms from either Party to the other shall immediately terminate and:

(a) the Back-Up Option shall terminate with respect to all Back-Up Products for the terminated Co-Co Licensed Products ;

(b) Genzyme shall as promptly as practicable transfer to Alnylam or Alnylam’s designee (i) possession and ownership of all Regulatory Approvals and pricing and reimbursement approvals relating to the Development, Manufacture or Commercialization of the terminated Co-Co Licensed Product, and (ii) copies of all non-clinical and clinical data and material regulatory correspondence relating to the terminated Co-Co Licensed Product;

(c) Genzyme will assign and transfer to Alnylam, all rights, title and interests in and to any Alnylam Product Specific Patents that relate solely to the terminated Co-Co Licensed Product that were assigned to Genzyme pursuant to Section 11.3.6 (Assignment of Alnylam Product-Specific Patents to Genzyme). In such event, Genzyme will execute and deliver a patent assignment relating to such Alnylam Product-Specific Patents in the same form used to assign such Patent Rights to Genzyme; and

(d) each Party shall promptly pay any amounts owed to the other Party as of the effective date of such termination.

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12.4. Fundamental Breach of Alnylam’s Development Obligations . Without limiting Genzyme’s rights under Section 12.2.2 (Termination for Cause) with respect to other material breaches, in the event that Alnylam commits a Fundamental Breach of its Development obligations under Section 2.4.2 (Alnylam Diligence) with respect to any particular Co-Co Licensed Product, and Genzyme does not terminate these Co-Co License Terms in their entirety ( i.e. , with respect to all Co-Co Licensed Products) or with respect to such Co-Co Licensed Product for cause pursuant to Section 12.2.2 (Termination for Cause), then Genzyme may elect to receive the following remedies for such Fundamental Breach:

12.4.1. Genzyme’s obligation to pay development milestone fees under Section 8.1 (Development Milestone Fees) with respect to such Co-Co Licensed Product shall automatically terminate;

12.4.2. Genzyme will receive a credit, which Genzyme may offset against royalties and other amounts payable under these Co-Co License Terms due to Alnylam with respect to such Co-Co Licensed Product pursuant to Section 8 (Financial Terms for Genzyme Territory), in an amount equal to one hundred fifty percent (150%) of all costs and expenses (i) incurred by Genzyme to Develop such Co-Co Licensed Product for the Genzyme Territory that are in excess of the costs budgeted by Genzyme in connection with the Genzyme Territory Development Plan for such Co-Co Licensed Product in effect at the time of Alnylam’s Fundamental Breach of Section 2.4.2 (Alnylam Diligence) with respect to such Co-Co Licensed Product and (ii) are incurred by Genzyme as a direct consequence of Alnylam’s Fundamental Breach of Section 2.4.2 (Alnylam Diligence) with respect to such Co-Co Licensed Product;

12.4.3. Genzyme may, in its discretion, terminate any or all of the following provisions of these Co-Co License Terms (or any subsection thereof) with respect to such Co-Co Licensed Product: Section 3.1.4 (Meetings with Regulatory Authorities), Section 4.1.2 (Co-Co Territory), Section 4.2.1 (Co-Co Territory Commercialization Plan), Section 4.3 (Genzyme Territory Commercialization Plan), Section 4.4 (Advertising and Promotional Materials), Section 4.5 (Commercialization Reporting Obligations) and Section 5 (Collaboration Management); and

12.4.4. Without limiting Genzyme’s remedies under these Co-Co License Terms or otherwise with respect to breaches of Alnylam’s Development obligations under clause (a) of Section 2.4.2 (Alnylam Diligence) other than Fundamental Breaches, if Genzyme elects to receive the remedies set forth in this Section 12.4 with respect to a Fundamental Breach of its Development obligations under clause (a) of Section 2.4.2 (Alnylam Diligence) with respect to any Co-Co Licensed Product, such remedies shall be Genzyme’s sole and exclusive remedies with respect to such Fundamental Breach and Genzyme shall have no right to seek any further remedies or damages against Alnylam and its Affiliates with respect to such Fundamental Breach by Alnylam of clause (a) of Section 2.4.2 (Alnylam Diligence).

12.5. Effect of Expiration or Termination; Survival . Any expiration or termination of these Co-Co License Terms (a) shall not relieve the Parties of any obligation accruing prior to such expiration or termination and (b) shall be without prejudice to the rights of either Party against the other accrued or accruing under these Co-Co License Terms prior to expiration or termination, including the obligation to pay royalties for any Co-Co Licensed Product sold prior to such expiration or termination. The following provisions shall survive any expiration or

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termination of these Co-Co License Terms in their entirety ( i.e. , with respect to all Co-Co Licensed Products) and, if these Co-Co License Terms expire or are terminated with respect to any particular Co-Co Licensed Product, shall survive with respect to such Co-Co Licensed Product: (a) Sections 1 (Definitions), 9 (Financial Terms for Co-Co Territory), 10.3 (Warranty Disclaimer), 11.1 (Inventorship), 11.2 (Ownership), 12.3 (Effect of Termination), 12.5 (Effect of Termination or Expiration; Survival), Section 13 (Performance by Affiliates) of these Co-Co License Terms and (b) Sections 1 (Definitions), 7 (Confidentiality and Publication), 10 (Indemnification; Limitation of Liability; Insurance), 12 (Term and Termination) and 13 (Miscellaneous) of the Master Agreement. Section 8.2.6 (Royalty Floor) shall survive any termination or expiration of these Co-Co License Terms with respect to any Co-Co Licensed Product for royalties accruing prior to such termination or expiration. Section 9 of the Master Agreement (Royalty Reports; Payments; Audit) will survive for so long as any royalties are due under these Co-Co License Terms plus three (3) years. Except as otherwise set forth in this Section 12 or elsewhere in these Co-Co License Terms, upon termination or expiration of these Co-Co License Terms in their entirety, all rights and obligations of the Parties under these Co-Co License Terms shall cease, but, for clarity, expiration or termination of these Co-Co License Terms in their entirety ( i.e. , with respect to all Co-Co Licensed Products) shall not result in the termination or expiration of the Master Agreement or any other License Terms. Upon termination or expiration of these Co-Co License Terms with respect to any particular Co-Co Licensed Product, all rights and obligations of the Parties under these Co-Co License Terms with respect to such Co-Co Licensed Product shall cease except as otherwise set forth in this Section 12 or elsewhere in these Co-Co License Terms, but, for clarity, such termination or expiration shall not affect the Parties’ rights and obligations under these Co-Co License Terms with respect to the other Co-Co Licensed Product.

13. PERFORMANCE BY AFFILIATES

13.1. Use of Affiliates . Each Party acknowledges and accepts that the other Party may exercise its rights and perform its obligations under these Co-Co License Terms either directly or through one or more of its Affiliates. A Party’s Affiliates will have the benefit of all rights (including all licenses) of such Party under these Co-Co License Terms. Accordingly, in these Co-Co License Terms “Genzyme” will be interpreted to mean “Genzyme and/or its Affiliates” and “Alnylam” will be interpreted to mean “Alnylam and/or its Affiliates” where necessary to give each Party’s Affiliates the benefit of the rights provided to such Party in these Co-Co License Terms; provided , however , that in any event each Party will remain responsible for the acts and omissions, including financial liabilities, of its Affiliates.

13.2. Future Acquisition of a Party or its Business . [***]

13.3. Acquired Programs .

13.3.1. [***]

13.3.2. [***]

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13.3.3. For clarity, upon the closing of the acquisition of the stock and/or assets of Sirna Therapeutics, Inc. by Alnylam from Merck Sharpe & Dohme Corp., all relevant acquired intellectual property rights acquired in such transaction that may be Controlled by Alnylam (without any further action by Alnylam or Sirna Therapeutics, Inc.) shall become Controlled by Alnylam for the purposes of these Co-Co License Terms.

[THE REMAINDER OF THIS PAGE HAS BEEN LEFT INTENTIONALLY BLANK]

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Schedule 1.2.14-1

ALNYLAM CORE TECHNOLOGY PATENTS FOR ALN-TTRsc

See attached.

[***]

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Schedule 1.2.19-1

ALNYLAM PRODUCT-SPECIFIC PATENTS FOR ALN-TTRsc

See attached.

[***]

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Schedule 2.2.2.1-1

GLOBAL DEVELOPMENT STRATEGY FOR ALN-TTRsc

(To be attached when developed pursuant to Section 2.2.2.1.)

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Schedule 2.2.2-1

GLOBAL DEVELOPMENT PLAN FOR ALN-TTRsc

(To be attached when developed pursuant to Section 2.2.2.)

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Schedule 2.2.3-1

GENZYME TERRITORY DEVELOPMENT PLAN FOR ALN-TTRsc

(To be attached when developed pursuant to Section 2.2.3.)

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Schedule 2.7

TTRSC/02 ARBITRATION CRITERIA

Confidential Materials omitted and filed separately with the Securities and Exchange Commission. A total of 1 page was omitted.

[***]

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Schedule 4.2-1

CO-CO TERRITORY COMMERCIALIZATION PLAN FOR ALN-TTRsc

(To be attached when developed pursuant to Section 4.2.)

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Schedule 10.1-1

DISCLOSURE SCHEDULE

See attached.

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Confidential Materials omitted and filed separately with the Securities and Exchange Commission. A total of 2 pages were omitted.

[***]

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Schedule 10.1.12

(A) EXISTING ALNYLAM IN-LICENSES

(To be attached)

(B) ADDITIONAL ALNYLAM IN-LICENSES

(To be attached)

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Schedule 10.4.1.4

EXCEPTIONS TO EXCLUSIVITY

Confidential Materials omitted and filed separately with the Securities and Exchange Commission. A total of 1 page was omitted.

[***]

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Exhibit 12

STATEMENT REGARDING COMPUTATION OF CONSOLIDATED RATIOS OF EARNINGS/DEFICIENCIES TO FIXED CHARGES

(dollars in thousands)


	Three Months ended March 31,			Fiscal Year Ended December 31,
	2014			2013			2012			2011			2010			2009
Earnings (loss):
Pre-tax loss from continuing operations before adjustment for loss from equity investee	$	(268,813	)	$	(91,920	)	$	(112,064	)	$	(54,144	)	$	(35,362	)	$	(42,098	)
add: Fixed charges (see below)		228			678			1,188			1,207			1,207			712

Pre-tax loss from continuing operations before adjustment for income/loss from equity investees plus fixed charges	$	(268,585	)	$	(91,242	)	$	(110,876	)	$	(52,937	)	$	(34,155	)	$	(41,386	)
Fixed charges:
Interest expense on portion of rent expense representative of interest	$	228		$	678		$	1,188		$	1,207		$	1,207		$	712

Total fixed charges	$	228		$	678		$	1,188		$	1,207		$	1,207		$	712

Ratio of earnings to fixed charges		—			—			—			—			—			—

Deficiency of earnings available to cover fixed charges	$	(268,813	)	$	(91,920	)	$	(112,064	)	$	(54,144	)	$	(35,362	)	$	(42,098	)

EXHIBIT 31.1

CERTIFICATION

I, John M. Maraganore, Ph.D., certify that:

I have reviewed this Quarterly Report on Form 10-Q of Alnylam Pharmaceuticals, Inc.;

Based on my knowledge, this report does not contain any untrue statement of a material fact or omit to state a material fact necessary to make the statements made, in light of the circumstances under which such statements were made, not misleading with respect to the period covered by this report;

Based on my knowledge, the financial statements, and other financial information included in this report, fairly present in all material respects the financial condition, results of operations and cash flows of the registrant as of, and for, the periods presented in this report;

The registrant’s other certifying officer and I are responsible for establishing and maintaining disclosure controls and procedures (as defined in Exchange Act Rules 13a-15(e) and 15d-15(e)) and internal control over financial reporting (as defined in Exchange Act Rules 13a-15(f) and 15d-15(f)) for the registrant and have:

Designed such disclosure controls and procedures, or caused such disclosure controls and procedures to be designed under our supervision, to ensure that material information relating to the registrant, including its consolidated subsidiaries, is made known to us by others within those entities, particularly during the period in which this report is being prepared;

Designed such internal control over financial reporting, or caused such internal control over financial reporting to be designed under our supervision, to provide reasonable assurance regarding the reliability of financial reporting and the preparation of financial statements for external purposes in accordance with generally accepted accounting principles;

Evaluated the effectiveness of the registrant’s disclosure controls and procedures and presented in this report our conclusions about the effectiveness of the disclosure controls and procedures, as of the end of the period covered by this report based on such evaluation; and

Disclosed in this report any change in the registrant’s internal control over financial reporting that occurred during the registrant’s most recent fiscal quarter (the registrant’s fourth fiscal quarter in the case of an annual report) that has materially affected, or is reasonably likely to materially affect, the registrant’s internal control over financial reporting; and

The registrant’s other certifying officer and I have disclosed, based on our most recent evaluation of internal control over financial reporting, to the registrant’s auditors and the audit committee of the registrant’s board of directors (or persons performing the equivalent functions):

All significant deficiencies and material weaknesses in the design or operation of internal control over financial reporting which are reasonably likely to adversely affect the registrant’s ability to record, process, summarize and report financial information; and

Any fraud, whether or not material, that involves management or other employees who have a significant role in the registrant’s internal control over financial reporting.


Date: May 9, 2014				/s/ John M. Maraganore
				John M. Maraganore, Ph.D.
				Chief Executive Officer

EXHIBIT 31.2

CERTIFICATION

I, Michael P. Mason, certify that:

I have reviewed this Quarterly Report on Form 10-Q of Alnylam Pharmaceuticals, Inc.;

Any fraud, whether or not material, that involves management or other employees who have a significant role in the registrant’s internal control over financial reporting.


Date: May 9, 2014				/s/ Michael P. Mason
				Michael P. Mason
				Vice President of Finance and Treasurer

EXHIBIT 32.1

CERTIFICATION PURSUANT TO 18 U.S.C. SECTION 1350, AS ADOPTED PURSUANT

TO SECTION 906 OF THE SARBANES-OXLEY ACT OF 2002

In connection with the Quarterly Report on Form 10-Q of Alnylam Pharmaceuticals, Inc. (the “Company”) for the quarter ended March 31, 2014 as filed with the Securities and Exchange Commission on the date hereof (the “Report”), the undersigned, John M. Maraganore, Ph.D., Chief Executive Officer of the Company, hereby certifies, pursuant to Section 1350 of Chapter 63 of Title 18, United States Code, that to his knowledge:

(1)

The Report fully complies with the requirements of Section 13(a) or 15(d) of the Securities Exchange Act of 1934; and

(2)

The information contained in the Report fairly presents, in all material respects, the financial condition and results of operations of the Company.


Dated: May 9, 2014				/s/ John M. Maraganore
				John M. Maraganore, Ph.D.
				Chief Executive Officer

A signed original of this written statement required by Section 906 has been provided to the Company and will be retained by the Company and furnished to the Securities and Exchange Commission or its staff upon request.

EXHIBIT 32.2

CERTIFICATION PURSUANT TO 18 U.S.C. SECTION 1350, AS ADOPTED PURSUANT

TO SECTION 906 OF THE SARBANES-OXLEY ACT OF 2002

In connection with the Quarterly Report on Form 10-Q of Alnylam Pharmaceuticals, Inc. (the “Company”) for the quarter ended March 31, 2014 as filed with the Securities and Exchange Commission on the date hereof (the “Report”), the undersigned, Michael P. Mason, Vice President of Finance and Treasurer of the Company, hereby certifies, pursuant to Section 1350 of Chapter 63 of Title 18, United States Code, that to his knowledge:

(1)

the Report fully complies with the requirements of Section 13(a) or 15(d) of the Securities Exchange Act of 1934; and

(2)

the information contained in the Report fairly presents, in all material respects, the financial condition and results of operations of the Company.


Dated: May 9, 2014				/s/ Michael P. Mason
				Michael P. Mason
				Vice President of Finance and Treasurer