Adverum Biotechnologies, Inc. (Form: 10-Q, Received: 08/09/2016 17:03:02)

Large accelerated filer

Accelerated filer

Non-accelerated filer

o (Do not check if a smaller reporting company)

Smaller reporting company

UNITED STATES

SECURITIES AND EXCHANGE COMMISSION

WASHINGTON , DC 20549

FORM 10-Q

(Mark One)

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

For the quarterly period ended June 30, 2016

o	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: 001-36579

Adverum Biotechnologies, Inc.

(Exact name of registrant as specified in its charter)



Delaware		20-5258327
(State or other jurisdiction of incorporation or organization)		(I.R.S. Employer Identification No.)

1035 O’Brien Drive,

Menlo Park, CA

(Address of principal executive offices)

94025

(Zip Code)

(650) 272-6269

(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 o

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 o

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 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 o No x

As of July 29, 2016 there were 41,348,194 shares of the registrant’s common stock, par value $0.0001 per share, outstanding.

Adverum Biotechnologies, Inc.

(formerly Avalanche Biotechnologies, Inc.)

TABLE OF CONTENTS

		Page

PART I—FINANCIAL INFORMATION		3

Item 1. Unaudited Condensed Consolidated Financial Statements		3
Condensed Consolidated Balance Sheets as of June 30, 2016 and December 31, 2015		3
Condensed Consolidated Statements of Operations and Comprehensive Loss for the three and six months ended June 30, 2016 and 2015		4
Condensed Consolidated Statements of Cash Flows for six months ended June 30, 2016 and 2015		5
Notes to Condensed Consolidated Financial Statements		6
Item 2. Management’s Discussion and Analysis of Financial Condition and Results of Operation		20
Item 3. Quantitative and Qualitative Disclosures About Market Risk		26
Item 4. Controls and Procedures		26

PART II—OTHER INFORMATION		28

Item 1. Legal Proceedings		28
Item 1A. Risk Factors		28
Item 2. Unregistered Sales of Equity Securities and Use of Proceeds		45
Item 3. Defaults Upon Senior Securities		46
Item 4. Mine Safety Disclosures		46
Item 5. Other Information		46
Item 6. Exhibits		46

SIGNATURES		47

EXHIBIT INDEX		48

PART I—FINANCI AL INFORMATION

Item 1.

Unaudited Condensed Consolidated Financial Statements

Adverum Biotechnologies, Inc.

(formerly Avalanche Biotechnologies, Inc.)

Condensed Consolidated Balance Sheets

(Unaudited)

(In thousands except share and per share data)

	June 30,			December 31,
	2016			2015
	(Unaudited)
Assets
Current assets:
Cash and cash equivalents	$	241,302		$	221,348
Marketable securities		—			37,732
Receivable from collaborative partner		1,029			449
Prepaid expenses and other current assets		1,239			1,463
Total current assets		243,570			260,992
Property and equipment, net		3,985			3,187
Intangible assets		16,650			—
Deposit and other long-term assets		140			140
Total assets	$	264,345		$	264,319
Liabilities and stockholders’ equity
Current liabilities:
Accounts payable	$	2,419		$	605
Restructuring liabilities		25			1,013
Accrued expenses and other current liabilities		4,144			4,007
Deferred rent, current portion		81			66
Deferred revenue, current portion		1,228			883
Total current liabilities		7,897			6,574
Long-term liabilities:
Deferred rent, net of current portion		404			447
Deferred revenue, net of current portion		5,936			4,706
Deferred tax liability		2,081			—
Other noncurrent liabilities		373			—
Total liabilities		16,691			11,727
Commitments and contingencies (Note 8)
Stockholders’ equity:
Preferred stock, $0.0001 par value, 5,000,000 shares authorized; no shares issued and outstanding		—			—
Common stock, $0.0001 par value, 300,000,000 shares authorized at June 30, 2016 and December 31, 2015; 41,322,357 and 25,858,722 shares issued and outstanding at June 30, 2016 and December 31, 2015, respectively		4			3
Additional paid-in capital		408,866			336,768
Accumulated other comprehensive income (loss)		4			(11	)
Accumulated deficit		(161,220	)		(84,168	)
Total stockholders’ equity		247,654			252,592
Total liabilities and stockholders’ equity	$	264,345		$	264,319

See accompanying notes to condensed consolidated financial statements

Adverum Biotechnologies, Inc.

(formerly Avalanche Biotechnologies, Inc.)

Condensed Consolidated Statements of Operations and Comprehensive Loss

(Unaudited)

(In thousands except per share data)

	Three Months Ended June 30,						Six Months Ended June 30,
	2016			2015			2016			2015
	(Unaudited)						(Unaudited)
Collaboration revenue	$	307		$	203		$	572		$	406
Operating expenses:
Research and development		7,955			5,126			15,410			10,747
General and administrative		5,114			4,959			13,432			9,102
Goodwill impairment charge		49,120			–			49,120			-
Total operating expenses		62,189			10,085			77,962			19,849
Operating loss		(61,882	)		(9,882	)		(77,390	)		(19,443	)
Other income
Other income, net		222			116			338			168
Total other income, net		222			116			338			168
Net loss	$	(61,660	)	$	(9,766	)	$	(77,052	)	$	(19,275	)
Other comprehensive loss:
Net unrealized gain on marketable securities		—			45			6			10
Foreign currency translation adjustment		(4	)		—			10			(8	)
Comprehensive loss	$	(61,664	)	$	(9,721	)	$	(77,036	)	$	(19,273	)
Net loss per share attributable to common stockholders-basic and diluted	$	(1.76	)	$	(0.38	)	$	(2.50	)	$	(0.76	)
Weighted-average common shares outstanding-basic and diluted		35,044			25,555			30,825			25,223

See accompanying notes to condensed consolidated financial statements

Adverum Biotechnologies, Inc.

(formerly Avalanche Biotechnologies, Inc.)

Condensed Consolidated Statements of Cash Flows

(Unaudited)

(In thousands)

	Six Months Ended June 30,
	2016			2015
	(Unaudited)
Cash flows from operating activities:
Net loss	$	(77,052	)	$	(19,275	)
Adjustments to reconcile net loss to net cash used in operating activities:
Depreciation and amortization		663			265
Stock-based compensation expense		6,903			1,332
Goodwill impairment charge		49,120			—
Amortization of premium on marketable securities		—			317
Changes in operating assets and liabilities:
Receivable from collaborative partner		(580	)		—
Prepaid expenses and other current assets		1,069			(47	)
Deposit and other long-term assets		—			(1	)
Accounts payable		646			534
Accrued expenses and other current liabilities		(1,706	)		59
Restructuring liabilities		(988	)		—
Deferred revenue		1,575			(406	)
Deferred rent		(27	)		230
Net cash used in operating activities		(20,377	)		(16,992	)
Cash flows from investing activities:
Purchases of marketable securities		—			(88,429	)
Maturities of marketable securities		37,738			8,960
Purchases of property and equipment		(1,126	)		(1,485	)
Cash acquired in business acquisition		3,449			—
Net cash provided by (used in) investing activities		40,061			(80,954	)
Cash flows from financing activities:
Proceeds from sales of common stock, net of offering cost		—			138,954
Proceeds from issuance of common stock pursuant to option exercises		349			131
Net cash provided by financing activities		349			139,085
Effect of foreign currency exchange rate on cash and cash equivalents		(79	)		(6	)
Net increase in cash and cash equivalents		19,954			41,133
Cash and cash equivalents at beginning of period		221,348			159,404
Cash and cash equivalents at end of period	$	241,302		$	200,537

Supplemental schedule of noncash investing and financing information
Issuance of common stock and exchange of stock options for business acquisition	$	64,845			—
Fixed assets in accounts payable and accrued expenses and other current liabilities	$	153		$	875

See accompanying notes to condensed consolidated financial statements.

Adverum Biotechnologies, Inc.

(formerly Avalanche Biotechnologies, Inc.)

June 30, 2016

Notes to Condensed Consolidated Financial Statements

(Unaudited)

1. Organization and Basis of Presentation

Adverum Biotechnologies, Inc. (the “Company”, “we” or “us”) was incorporated in Delaware on July 17, 2006 as Avalanche Biotechnologies, Inc. and changed its name to Adverum Biotechnologies, Inc. on May 11, 2016. The Company is headquartered in Menlo Park, California. The Company is a gene therapy company committed to discovering and developing novel medicines that can offer potentially life-changing therapeutic benefit to patients suffering from chronic or debilitating and rare diseases. Since the Company’s inception, it has devoted its efforts principally to performing research and development activities, including conducting preclinical studies, early clinical trials, filing patent applications, obtaining regulatory approvals, hiring personnel, and raising capital to support these activities.

The Company has not generated any revenue from the sale of products since its inception. The Company has experienced net losses since its inception and has an accumulated deficit of $161.2 million as of June 30, 2016. The Company expects to incur losses and have negative net cash flows from operating activities as it expands its portfolio and engages in further research and development activities. The Company believes that it has sufficient funds to continue operations for at least the next 36 months.

On May 11, 2016, the acquisition closing date, the Company completed its previously announced acquisition of all the outstanding shares of Annapurna Therapeutics SAS, a French simplified joint stock company ( Annapurna ), in accordance with the terms of the acquisition agreement (the Agreement ) dated as of January 29, 2016, as amended on April 6, 2016. As a result, Annapurna is now a wholly owned subsidiary of the Company.

Pursuant to the terms of the Agreement, the Company issued 14,087,246 shares of the Company’s common stock, par value $0.0001 per share, for all of the issued and outstanding capital stock of Annapurna. All outstanding options and other rights to purchase capital stock of Annapurna were converted into the Company’s options for common stock. Refer to Note 3 for more details.

Upon completion of the acquisition, the Company changed its name to “Adverum Biotechnologies, Inc.”. The Company’s shares of common stock listed on The NASDAQ Global Market, previously trading through the close of business on Wednesday, May 11, 2016 under the ticker symbol “AAVL,” commenced trading on The NASDAQ Global Market under the ticker symbol “ADVM” on Thursday, May 12, 2016.

Follow-on Offerings —In January 2015, the Company completed a public offering of 2,369,375 shares of its common stock, which included 359,918 shares the Company issued pursuant to the underwriters’ exercise of their option to purchase additional shares. The Company received net proceeds of approximately $130.6 million, after underwriting discounts, commissions and offering expenses.

In March 2015, (i) the Company received net proceeds of approximately $8.3 million, after discounts and other issuance costs, which resulted from the sale of 230,000 common shares, and (ii) the Company issued 230,000 common shares to a shareholder that exercised warrants prior to the initial public offering.

The accompanying unaudited condensed consolidated financial statements have been prepared in accordance with U.S. generally accepted accounting principles (U.S. GAAP) and following the requirements of the Securities and Exchange Commission (SEC) for interim reporting. As permitted under those rules, certain footnotes or other financial information that are normally required by U.S. GAAP can be condensed or omitted. These condensed consolidated financial statements have been prepared on the same basis as the Company’s annual consolidated financial statements and, in the opinion of management, reflect all adjustments, consisting only of normal recurring adjustments, which are necessary for a fair statement of the Company’s consolidated financial information. The results of operations for the six month period ended June 30, 2016 are not necessarily indicative of the results to be expected for the full year or any other future period. The balance sheet as of December 31, 2015 has been derived from audited consolidated financial statements at that date but does not include all of the information required by U.S. GAAP for complete consolidated financial statements.

The accompanying condensed consolidated financial statements and related financial information should be read in conjunction with the audited consolidated financial statements and the related notes thereto included in the Company’s Annual Report on Form 10-K for the year ended December 31, 2015 filed with the SEC.

2. Summary of Significant Accounting Policies

The accounting policies followed in the preparation of the interim condensed consolidated financial statements are consistent in all material respects with those presented in Note 2 to the consolidated financial statements included in the Company’s Annual Report on Form 10-K for the year ended December 31, 2015. The Company added significant accounting policy below as a result of Annapurna acquisition.

Valuation of Long‑Lived Assets and Purchased Intangible Assets

The Company evaluates the carrying value of amortizable long‑lived assets, whenever events, changes in business circumstances or planned use of long‑lived assets indicate that their carrying amounts may not be fully recoverable or that their useful lives are no longer appropriate. If these facts and circumstances exist, the Company assesses for recovery by comparing the carrying values of long‑lived assets with their future undiscounted net cash flows. If the comparison indicates that impairment exists, long‑lived assets are written down to their respective fair value based on discounted cash flows. Significant management judgment is required in the forecast of future operating results that is used in the preparation of expected undiscounted cash flows. No impairment indicators were noted for the Company’s long-lived assets, fixed assets, in the periods presented.

The Company also evaluates the carrying value of intangible assets (not subject to amortization) related to in‑process research and development (“IPR&D”) assets, which are considered to be indefinite‑lived until the completion or abandonment of the associated research and development efforts. Accordingly, amortization of the IPR&D assets will not occur until the product reaches commercialization. During the period the assets are considered indefinite‑lived, they will be tested for impairment on an annual basis, as well as between annual tests if the Company become aware of any events occurring or changes in circumstances that would indicate that the fair values of the IPR&D assets are less than their carrying amounts. If and when development is complete, which generally occurs when regulatory approval to market the product is obtained, the associated IPR&D assets would be deemed definite‑lived and would then be amortized based on their estimated useful lives at that point in time. If the related project is terminated or abandoned, the Company may have an impairment related to the IPR&D asset, calculated as the excess of their carrying value over fair value. The Company estimated fair value of IPR&D assets acquired in Annapurna transaction at the acquisition closing date, May 11, 2016. No impairment was recorded at June 30, 2016, as there were no changes in the fair value of IPR&D assets between May 11 and June 30, 2016.

Recently Issued Accounting Pronouncements — In May 2014, the Financial Accounting Standards Board ( FASB) issued Accounting Standard Update (ASU) No. 2014-09, Revenue from Contracts with Customers (Topic 606), which supersedes the revenue recognition requirements in Accounting Standard Codification (ASC) 605 , Revenue Recognition . This ASU is based on the principle that revenue is recognized to depict the transfer of goods or services to customers in an amount that reflects the consideration to which the entity expects to be entitled in exchange for those goods or services. The ASU also requires additional disclosure about the nature, amount, timing and uncertainty of revenue and cash flows arising from customer contracts, including significant judgments and changes in judgments and assets recognized from costs incurred to obtain or fulfill a contract. Companies may adopt ASU 2014-09 using a full retrospective approach or report the cumulative effect as of the date of adoption. In July 2015, the FASB voted to approve a one-year deferral of the effective date to December 15, 2017 for interim and annual reporting periods beginning after that date and permitted early adoption of the standard, but not before the original effective date of December 15, 2016 . The Company is evaluating the application of this ASU and method of adoption, but has not yet determined the potential effects it may have on the Company’s consolidated financial statements.

In August 2014, the FASB issued ASU 2014-15, Presentation of Financial Statements—Going Concern (Subtopic 205-40): Disclosure of Uncertainties about an Entity’s Ability to Continue as a Going Concern , requiring management to evaluate whether events or conditions could impact an entity’s ability to continue as a going concern and to provide disclosures if necessary. Management will be required to perform the evaluation within one year after the date that the financial statements are issued. Disclosures will be required if conditions give rise to substantial doubt and the type of disclosure will be determined based on whether management’s plans will be able to alleviate the substantial doubt. The accounting standards update will be effective for the first annual period ending after December 15, 2016, and for annual periods and interim periods thereafter with early application permitted. The adoption of this ASU is not expected to impact the Company’s financial position or results of operations.

In February 2016, the FASB issued ASU No. 2016-2, Leases . ASU 2016-2 is aimed at making leasing activities more transparent and comparable, and requires substantially all leases be recognized by lessees on their balance sheet as a right-of-use asset and corresponding lease liability, including leases currently accounted for as operating leases. The new standard is effective for fiscal years and interim periods within those fiscal years beginning after December 15, 2018, with early adoption permitted. The Company has not yet determined the method of adoption and the potential effect the new standard will have on the Company’s consolidated financial statements.

In March 2016, the FASB issued ASU No. 2016-9, Compensation-Stock Compensation: Improvements to Employee Share-Based Payment Accounting . ASU 2016-9 simplifies several aspects of the accounting for share-based payment award transactions, including: (1) the income tax consequences, (2) cl assification of awards as either equity or liabilities, and (3) classification in the consolidated statement of cash flows. The new standard is effective for fiscal years and interim periods within those fiscal years beginning after December 15, 2016 , with early adoption permitted. The Company has not yet determined the method of adoption and the potential effect the new standard will have on the Company’s consolidated financial statements.

The Company has reviewed other recent accounting pronouncements and concluded they are either not applicable to the business or no material effect is expected on the consolidated financial statements as a result of future adoption.

3. Acquisition of Annapurna

(a)

Purchase Price Allocation

On May 11, 2016, the Company completed the acquisition of all outstanding equity interests of Annapurna. Annapurna is a privately held French limited liability company and has two wholly-owned subsidiaries, Annapurna, Inc. in the U.S. and Annapurna Therapeutics Limited in Ireland. Annapurna is a biopharmaceutical company focused on discovering and developing new gene therapy products for people living with severe diseases. The primary reasons for the acquisition were to diversify the technology platforms within the Company’s research and development portfolio and to apply the Company’s resources and expertise in gene vectors development to advance Annapurna programs through development and clinical trials. Annapurna’s results of operations and fair value of assets acquired and liabilities assumed are included in the Company’s condensed consolidated financial statements from the date of acquisition.

The purchase price consideration was estimated to be $64.8 million, which was based on the Company’s common stock closing price on NASDAQ on the acquisition closing date of $4.14 per share. A total of 14,087,246 shares of the Company’s common stock were issued to shareholders of Annapurna in exchange for all common and preferred stock outstanding at the closing date. Annapurna stockholders did not receive any fractional shares of the Company’s common stock in connection with the acquisition. Instead of receiving any fractional shares, each Annapurna stockholders were paid an amount in cash (without interest) equal to such fraction amount multiplied by the average 10 business days sale price of the Company’s common stock on NASDAQ from the acquisition date. Annapurna Series O preferred shares issued to founders were canceled prior to the acquisition date and were not included in the purchase price consideration. Vesting of certain of Annapurna’s options and unvested common stock shares was accelerated at the closing date. The fair value of awards related to accelerated vesting of options and shares of $0.9 million was excluded from the purchase price consideration and included in the Company’s operating expenses post acquisition. A portion of the purchase price has been attributed to the exchange of Annapurna’s options and other rights to purchase capital stock outstanding at the acquisition closing date for corresponding common stock options of the Company at an exchange ratio of 9.54655.

The Company reserved 3,673,940 shares for the future exercise of the Company’s stock options. The total fair value of assumed Annapurna’s stock options and stock-based awards was estimated at $14.7 million on the acquisition date, using the Black-Scholes pricing model, assuming no dividends, expected volatilities of 80% and 89%, risk-free interest rates of 1.4% and 1.1%, and expected lives of six and ten years for employees and non-employees awards, respectively. Of the total fair value, $7.4 million has been attributed as pre-combination service and included as part of the total purchase price consideration. The post-combination attribution of $7.2 million will be recognized as compensation expense over the remaining requisite service period. The Company has included $1.1 million in stock-based compensation expense related to the vesting of exchanged stock options and day-one post combination compensation expenses related to accelerated vesting of options and shares in its condensed consolidated statement of operations during the second quarter 2016.

Total purchase price consideration was as follows (in thousands):

Fair value of common shares issued	$	58,321
Fair value of the Company's common share options exchanged for Annapurna stock options and other awards attributable to pre-combination services		7,422
Less: value of common stock and options accelerated vesting at the closing date		(898	)
Total purchase price consideration	$	64,845

The transaction has been accounted for using the acquisition method based on ASC 805, Business Combinations, with Adverum identified as the acquirer, based on the existence of a controlling financial interest of the combined entities. Under the acquisition method, assets acquired and liabilities assumed were recorded at their estimated fair values as of the May 11, 2016. Goodwill, as well as intangible assets that do not qualify for separate recognition, is measured as of the acquisition date as the excess of consideration transferred, which is also measured at fair value, and the net of the fair values of the as sets acquired and the liabilities assumed as of the acquisition closing date. Acquisition costs were expensed as incurred and recorded as general and administrative expenses. The Company recorded $0.6 million and $ 2.5 million of acquisition costs for the t hree-months and six-months ended June 30, 2016 , respectively .

Valuing certain components of the acquisition, primarily intangible assets acquired, deferred taxes, uncertain tax positions and accrued liabilities required us to make significant estimates that may be adjusted in the future; consequently, the fair value of identifiable assets acquired and liabilities assumed are considered preliminary. Final determination of these estimates could result in an adjustment to the preliminary purchase price allocation, with an offsetting adjustment to goodwill. Preliminary allocation of total purchase price consideration is as follows (in thousands):

Cash	$	3,449
Prepaid expenses and other assets		865
Property and equipment		185
Acquired intangible assets		16,650
Goodwill		49,120
Accounts payable		(1,118	)
Accrued liabilities		(1,848	)
Other noncurrent liabilities		(377	)
Deferred tax liabilities		(2,081	)
Total purchase price allocation	$	64,845

The identifiable intangible assets acquired consist of in-process research and development (IPR&D) assets related to products in development, as summarized in the table below (in thousands):

IPR&D - Alpha-1 antitrypsin deficiency	$	12,150
IPR&D - Hereditary angioedema		4,500
Total acquired intangible assets	$	16,650

The fair value of each IPR&D asset is estimated using the income approach and calculated using cash flow projections adjusted for inherent risks regarding regulatory approval, promotion, and distribution, discounted at a rate of approximately 11.0%. The Company acquired two additional intangible assets relating to the Friedreich’s Ataxia (FA) and severe allergy programs but the fair value of each of these assets was determined to be nominal and is not included in the total acquired intangible assets. All IPR&D intangible assets acquired are currently classified as indefinite-lived and are not currently being amortized. IPR&D asset becomes definite-lived upon the completion or abandonment of the associated research and development efforts, and will be amortized from that time over an estimated useful life based on respective patent terms. The fair value of each IPR&D asset will continue to be evaluated for impairment on an annual basis or more often if the Company identifies impairment indicators that would require earlier testing. Based on the preliminary fair values above, an amount of $49.1 million has been allocated to goodwill, which represents the excess of the purchase price over the fair values assigned to the net assets acquired. The full amount of the preliminary value of goodwill has been assigned to the entire Company, since management has determined that the Company has only one reporting unit. The goodwill is not deductible for tax purposes.

The amount of net loss of Annapurna included in the consolidated statements of operations from the acquisition date, through the period ended June 30, 2016 was $1.2 million. Annapurna did not generate any revenues prior or post acquisition.

The following table presents the unaudited pro forma results for the three and six months ended June 30, 2016 and 2015. The pro forma financial information combines the results of operations of Adv erum and Annapurna as though the businesses had been combined as of the beginning of fiscal 2015. The pro forma financial information is presented for informational purposes only, and is not indicative of the results of operations that would have been achi eved in the current or any future periods.

	Three Months Ended June 30,						Six Months Ended June 30,
	2016			2015			2016			2015
Pro forma information
Collaboration revenue	$	307		$	203		$	572		$	406
Net loss	$	(62,572	)	$	(10,533	)	$	(80,846	)	$	(21,956	)
Basic and diluted loss per share	$	(1.52	)	$	(0.27	)	$	(1.97	)	$	(0.56	)

Pro-forma adjustments included the following:

Actual acquisition-related transaction costs of $0.6 million and $2.5 million for three and six months ended June 2016 were excluded from the 2016 pro forma results above. As these expenses were incurred prior to the closing of the acquisition, they were not included in the 2015 pro forma results.

Stock-based compensation expense related to accelerated vesting associated with the acquisition of $0.9 million was excluded from the 2016 pro forma results and was recorded in the six months ended June 30, 2015.

Stock-based compensation expense related to options granted to executives upon the acquisition closing of $0.1 million and $0.2 million was included in the 2016 and 2015 pro forma results above.

Interest expense related to convertible notes and changes in fair value of preferred stock warrants of $0.5 million for the three and six month periods ended June 30, 2015, $0.5 million for the three month period ended June 30, 2016, and $1.0 million for the six month period ended June 30, 2016, were excluded form 2015 and 2016 pro-forma results above, as the convertible notes and warrants were settled prior to the acquisition closing.

Bonuses paid in connection with closing of the acquisition in May 2016 of $0.4 million were excluded from the 2016 pro forma results and were recorded in the six months ended June 30, 2015.

The unaudited condensed pro forma information does not include any anticipated synergies that may be achievable subsequent to the date of acquisition.

Impairment evaluation for intangible assets and goodwill

As the Company recorded goodwill and IPR&D intangible assets upon the acquisition of Annapurna, the Company is required to test goodwill and indefinite lived intangible assets for impairment on an annual basis or more frequently if indicators of impairment exist. The Company operates as one reporting unit and goodwill was recorded to this reporting unit.

During the second quarter the Company noted a continuing decrease in its stock price that resulted in the market capitalization being less than the carrying value of the Company’s net assets as of June 30, 2016. As the operating losses are expected to increase significantly in the following years due to continuing pre-clinical and expected clinical trials, the Company concluded that it is more likely than not that the fair value of the Company’s one reporting unit is less than its carrying value and as a result performed a step one goodwill impairment analysis.

In performing the step one analysis, the Company determined the fair value of the reporting unit using a market-based approach. The Company multiplied the stock price of $3.16 on June 30, 2016 by the 41.3 million common shares outstanding and applied a control premium to estimate the common equity value on a controlling basis. As the fair value was less than the carrying value of the Company’s net assets, the Company proceeded to step two of the impairment analysis.

The second step of the analysis includes allocating the calculated fair value (determined in the step one analysis) of the reporting unit to its assets and liabilities to determine an implied fair value of goodwill. The implied fair value of goodwill was determined in the same manner as the amount of goodwill recognized in an acquisition. That is, the estimated fair value of the reporting unit was

allocated to all of the assets and liabiliti es as if the Company had been acquired and the estimated fair value was the purchase price paid. As part of this assessment the Company considered preliminary valuation of Annapurna net assets acquired, excluding goodwill, as their fair value from May 11, 2016, the acquisition closing date, to June 30, 2016 did not change . The Company also noted that the fair value of current assets and liabilities approximates their carrying value due to their short-term nature, the Company’s cash and cash equivalent balan ce is higher than the fair value estimated in the step one analysis, and the fair value of fixed assets approximates their recorded value as most of the Company’s fixed assets are acquired in the last couple of years. Based on this analysis, the implied fa ir value of the goodwill was zero. Accordingly, the Company recorded a goodwill impairment charge of $49.1 million in the condensed consolidated statements of operations and comprehensive loss for the period ended June 30, 2016.

As the Annapurna purchase price allocation is preliminary and the amount of goodwill might change during the measurement period, the recorded impairment charge reflects the Company’s best estimate as of June 30, 2016.

We did not impair recorded IPR&D intangible assets, as their carrying value at June 30, 2016 approximated their fair value. We noted no significant changes in IPR&D intangible assets fair values from May 11, 2016, the acquisition closing date, to June 30, 2016.

4. Cash Equivalents and Marketable Securities

The Company did not hold any marketable securities as of June 30, 2016, all investments were held in money market funds and are treated as cash equivalents. .

The following is a summary of the cash equivalents and marketable securities as of December 31, 2015:

	December 31, 2015
	Amortized Cost Basis			Unrealized Gains		Unrealized Loses			Estimated Fair Value
Money Market Funds	$	208,588		$	—	$	—		$	208,588
Certificates of Deposit		1,680			—		—			1,680
U.S. Treasury Securities		15,046			—		(4	)		15,042
U.S. Government Agency Securities		21,012			—		(2	)		21,010
		246,326			—		(6	)		246,320
Less: Cash Equivalents		(208,588	)		—		—			(208,588	)
Total Marketable Securities	$	37,738		$	—	$	(6	)	$	37,732

As of December 31, 2015, the contractual maturities of the Company’s marketable securities were less than one year. The Company has not sold any securities prior to their maturities and so does not consider any losses on these investment to be other-than-temporarily impaired. There were no sales of available-for-sale securities in any of the periods presented.

5. Fair Value Measurements and Fair Value of Financial Instruments

The authoritative guidance on fair value measurements establishes a three-tier fair value hierarchy for disclosure of fair value measurements as follows:

Level 1 : Quoted prices in active markets for identical assets or liabilities.

Level 2 : Observable inputs other than Level 1 prices, such as quoted prices for similar assets or liabilities, quoted prices in markets that are not active, or other inputs that are observable or can be corroborated by observable market data for substantially the full term of the assets or liabilities.

Level 3 : Unobservable inputs that are supported by little or no market activity and that are significant to the fair value of the assets or liabilities.

Assets and liabilities measured at fair value are classified in their entirety based on the lowest level of input that is significant to the fair value measurement. The Company’s assessment of the significance of a particular input to the fair value measurement in its entirety requires management to make judgments and consider factors specific to the asset or liability.

The fair value of Level 1 securities are determined using quoted prices in active markets for identical assets. Level 1 securities consist of highly liquid money market funds. Financial assets and liabilities are considered Level 2 when their fair values are determined using inputs that are observable in the market or can be derived principally from or corroborated by observable market data such as pricing for similar securities, recently executed transactions, cash flow models with yield curves, and benchmark securities. In

addition, Level 2 financial instruments are valued using comparisons to like-kind financial instruments and models that use readily observable market data as thei r basis. U.S. Treasury securities, U.S. government agency securities and certificate of deposit are valued primarily using market prices of comparable securities, bid/ask quotes, interest rate yields and prepayment spreads and are included in Level 2.

There were no transfers within the hierarchy during the six months ended June 30, 2016 and the year ended December 31, 2015. As of June 30, 2016 and December 31, 2015, the Company had no Level 3 assets or liabilities.

The following table summarizes, for assets recorded at fair value on a recurring basis, the respective fair value and the classification by level of input within the fair value hierarchy as described above (in thousands):

			Quoted Prices		Significant Other		Significant
	Total		In Active Markets		Observable Inputs		Unobservable Inputs
	Carrying Value		(Level 1)		(Level 2)		(Level 3)
June 30, 2016
Assets:
Money Market Funds - cash equivalent	$	236,821	$	236,821	$	—	$	—
Total Cash Equivalents	$	236,821	$	236,821	$	—	$	—
December 31, 2015
Assets:
Money Market Funds - cash equivalent	$	208,588	$	208,588	$	—	$	—
Certificates of Deposit		1,680		—		1,680		—
U.S. Treasury Securities		15,042		—		15,042		—
U.S. Government Agency Securities		21,010		—		21,010		—
Total Cash Equivalents and Marketable Securities	$	246,320	$	208,588	$	37,732	$	—

Non-financial and financial assets such as intangible assets, property, plant, and equipment are evaluated for impairment and adjusted to their fair value using Level 3 inputs, only when impairment is recognized. Fair values are considered Level 3 when management makes significant assumptions in developing a discounted cash flow model based upon a number of considerations including projections of revenues, earnings and a discount rate. In addition, in evaluating the fair value of goodwill impairment, further corroboration is obtained using our market capitalization.

6. Significant Agreements

Regeneron

In May 2014, the Company entered into a research collaboration and license agreement with Regeneron to discover, develop and commercialize novel gene therapy products for the treatment of ophthalmologic diseases. The collaboration covers up to eight distinct therapeutic targets (collaboration targets). The Company and Regeneron will collaborate during the initial research period of three years that can be extended by Regeneron for up to an additional five years. During the research period, Regeneron has the option to obtain an exclusive worldwide license for a collaboration target’s further development by giving written notice to the Company and paying $2.0 million per target. If Regeneron exercises its option, it will be responsible for all further development and commercialization of the target. The Company is then eligible to receive contingent payments of up to $80.0 million upon achievement of certain development and regulatory milestones for product candidates directed toward each collaboration target, for a combined total of up to $640.0 million in potential milestone payments for product candidates directed toward all eight collaboration targets, plus a royalty in the low- to mid-single-digits on worldwide net sales of collaboration products.

For any two collaboration targets, the Company has an option to share up to 35% of the worldwide product candidate development costs and profits. If the Company exercises this option, the Company will not be eligible for milestone and royalty payments discussed above but rather the Company will share development costs and profits with Regeneron.

The agreement will expire with respect to each collaboration target upon the earlier of the (a) expiration of the research term if the option right has not been triggered by the end of the research term or (b) expiration of the option right if the option right has not been exercised by Regeneron. If the option right has been exercised, the agreement in connection with each collaboration target will expire upon expiration of all payment obligations by Regeneron. In addition, the agreement, or Reg eneron’s rights to any target development under the agreement, may terminate early under the following situations:

Regeneron may terminate the agreement for convenience at any time on a target by target basis or in totality upon a 30-day notice.

Each party can terminate the agreement if another party commits a material breach or material default in performance of its obligations and such breach or default is not cured within 60 days.

The agreement is automatically terminated upon initiation of any bankruptcy proceedings, reorganization or dissolution of either party.

The Company can terminate the agreement upon 30-day notice if Regeneron challenges the validity, scope or enforceability of any Company patent.

University of California

In May 2010, the Company entered into a license agreement, as amended, with the Regents of the University of California (Regents) for exclusive rights in the U.S. to certain patents owned by the Regents. Under the terms of the agreement, the Company paid an upfront license fee of $100,000 and agreed to reimburse the Regents for patent-related expenses. The Company is obligated to pay the Regents royalties on net sales, if any, as well as an annual maintenance fee of $50,000 beginning in the calendar year after the first commercial sale of a licensed product and milestone payments related to the achievement of certain clinical and regulatory goals totaling up to $900,000 for the first indication and $500,000 for each additional indication for up to two additional indications. Through June 30, 2016, none of these goals had been achieved, and no milestones were payable.

Cornell University

In August 2014, as amended in December 2015, Annapurna entered into a master service agreement with Cornell University for assistance in regulatory affairs, overall project management and parameter development. Per the amended agreement, Annapurna will pay Cornell $13.3 million ratably over 4 years for these services, as services will be performed.

In December 2015, Annapurna Therapeutics Limited entered into three licensing agreements with Cornell University, pursuant to which Annapurna will advance its ANN-001, ANN-002 and ANN-004 programs, which were each based on gene-therapy programs initiated at the Department of Genetic Medicine at Weill Cornell.

A1AT Deficiency License Agreement : Under this agreement, Annapurna Therapeutics Limited holds an exclusive license to certain technology related to alpha-1 antitrypsin (“A1AT”) deficiency and rights to an IND application to initiate clinical studies of gene therapy for A1AT.

HAE License Agreement : Under this agreement, Annapurna Therapeutics Limited holds an exclusive license to certain technology related to hereditary angioedema (“HAE”) and a non-exclusive license to certain other intellectual property related to the HAE program.

Allergy License Agreement : Under this agreement, Annapurna Therapeutics Limited holds an exclusive license to certain patents related to allergens and a non-exclusive license to certain other technology related to allergens.

The Company may terminate any of these license agreements for convenience upon ninety days written notice.

Across these three license agreements, Cornell University is entitled to receive aggregate annual maintenance fees ranging from $30,000 to $300,000 per year, up to $16.0 million in aggregate milestone payments and royalties on sales in the low single-digits, subject to adjustments and minimum thresholds. In addition, under a master services agreement with Cornell University, Annapurna will utilize the university to scale production of gene therapies by manufacturing processes that the institution has already used to produce Good Manufacturing Practice (GMP) material for other gene-therapy trials. The Company accrued $0.5 million as of June 30, 2016 and recorded expenses of $0.5 million (post Annapurna’s acquisition) for the period from May 11, 2016 through June 30, 2016, related to Cornell agreements. No milestone payments were probable to achieve and none were recorded as of June 30, 2016.

Dr. Crystal, Chairman of Genetic Medicine, the Bruce Webster Professor of Internal Medicine and a Professor of Genetic Medicine and of Medicine at Weill Cornell, serve d as a consultant to Annapurna since inception and will continue to provid e services to the Company for the annual compensation of $0.3 million. Dr. Crystal also owns common shares of the Company and he does not have significant influence on the Company’s operations.

REGENXBIO

A1AT Deficiency/Allergy License Agreement : In October 2015, Annapurna Therapeutics Limited entered into an exclusive worldwide license to certain intellectual property in order to make, have made, use, import, sell and offer for sale certain licensed products for the treatment of A1AT deficiency. Additionally under this agreement, the Company has an option to be granted an exclusive worldwide license to certain intellectual property related to the treatment of severe allergies. Under this license agreement, REGENXBIO is eligible to receive annual maintenance fees, up to approximately $20.0 million in combined milestone payments and royalties in the mid-to-high single digits.

Friedreich’s Ataxia License Agreement : In April 2014, Annapurna entered into an exclusive worldwide license to certain intellectual property related to the Friedreich’s Ataxia (“FA”) program to make, have made, use, import, sell and offer for sale licensed products using AAVrh10 for FA where the vector is administered by any route except directly to the central nervous system (FA Systemic). Under the terms of this license agreement, Annapurna also has an option to obtain a non-exclusive worldwide license to make, have made, use, import, sell and offer for sale licensed products using a single vector for each of FA where the vector is administered directly to the central nervous system and FA Systemic. Under this license agreement, REGENXBIO is eligible to receive annual maintenance fees, up to $13.85 million in combined milestone fees and royalties in the mid-to-high single digits.

The Company accrued $46,000 as of June 30, 2016 and recorded expenses of $20,000 (post Annapurna’s acquisition) for the period May 11, 2016 through June 30, 2016, related to REGENXBIO agreements. No milestone payments were probable to achieve and none were recorded as of June 30, 2016.

Inserm Transfert

In July 2014, Annapurna entered into an agreement with Inserm Transfert whereby Annapurna holds an exclusive license to certain patents to develop, make, have made, use, import, offer for sale and sell or otherwise distribute products for the treatment of Friedreich’s ataxia and a non-exclusive license to certain other intellectual property related to the FA program. The Agreement was amended in October 2015 to increase the scope of the intellectual property under the licenses. Under this agreement, Inserm Transfert is entitled to receive certain de minimis license payments, certain development milestone payments of up to approximately €2 million in the aggregate and royalties on sales in the low single-digits, subject to adjustments. The Company did not have any accruals relating to Inserim as of June 30, 2016 and nor did the Company record any expenses (post Annapurna’s acquisition) for the period from May 11, 2016 through June 30, 2016, related to this agreement. No milestone payments were probable to achieve and none were recorded as of June 30, 2016.

7. Property and Equipment, Net

Property and equipment, net consists of the following (in thousands):

	June 30, 2016			December 31, 2015
Computer equipment and software	$	259		$	234
Laboratory equipment		3,688			3,041
Furniture and fixtures		552			552
Leasehold improvements		939			351
Construction in progress		201			—
Total property and equipment		5,639			4,178
Less accumulated depreciation and amortization		(1,654	)		(991	)
Property and equipment, net	$	3,985		$	3,187

Depreciation and amortization expense related to property and equipment for the three months ended June 30, 2016 and 2015 was $343,000 and $147,000, respectively. Depreciation and amortization expense related to property and equipment for the six months ended June 30, 2016 and 2015 was $663,000 and $265,000, respectively.

8. Accrued Expenses and Other Current Liabilities

Accrued expenses and other current liabilities consist of the following (in thousands):

	June 30, 2016		December 31, 2015
Employees’ compensation expenses	$	1,608	$	2,047
Accrued professional services		608		1,177
Accrued preclinical costs	$	1,844	$	642
Accrued clinical and process development costs		—		101
Other		84		40
Total accrued expenses and other current liabilities	$	4,144	$	4,007

9. Other liabilities

Due to the innovative nature of Annapurna’s product candidate development programs, Annapurna has benefited from certain sources of financial assistance from Banque Publique d’Investissement (“BPI France”). BPI France provides financial assistance and support to emerging French enterprises to facilitate the development and commercialization of innovative technologies. The funds received by the Company are intended to finance its research and development efforts and the recruitment of specific personnel. The Company has received such funding in the form of conditional advances.

In August 2015, BPI France granted Annapurna a €750,000 interest free conditional advance, of which €500,000 was drawn down as of December 31, 2015. The remaining €250,000 advance was not and is not expected to be drawn down on. Payments are scheduled in equal quarterly amounts of €25,000 from September 30, 2017 to June 30, 2022. This payment schedule will be modified if the Company will receive revenue from license or product sales before advances are paid in full. The Company calculated 7% imputed interest expense on these advances that recorded it as a discount at the issuance date. The discount is amortized as an interest expense over the life of advances. As of June 30, 2016 the carrying value of the conditional advance was $373,000 and the Company recorded $15,000 interest expense from the acquisition closing date to June 30, 2016.

10. Commitments and Contingencies

Collaborations and License Agreements

In August 2014, as amended December 2015, Annapurna entered into a master service agreement with Cornell University for assistance in regulatory affairs, overall project management and parameter development. Per the amended agreement, Annapurna will pay Cornell $13.3 million ratably over 4 years for these services.

The Company is a party to various agreements, principally relating to licensed technology that requires payment of annual maintenance fees and future payments relating to milestones or royalties on future sales of specified products. Refer to Note 6 for further details. The Company expenses the annual maintenance fees on a straight-line basis and accrues the aggregate balances until invoiced or paid. Through June 30, 2016, none of the goals had been achieved under the license agreements and no cash milestones were accrued or payable. Because the achievement of these milestones is not fixed and determinable, such commitments have not been included in the Company’s condensed consolidated balance sheets.

Guarantees and Indemnifications

In the normal course of business, the Company enters into contracts and agreements that contain a variety of representations and warranties and provide for indemnification for certain liabilities. The exposure under these agreements is unknown because it involves claims that may be made against the Company in the future but have not yet been made. To date, the Company has not paid any claims or been required to defend any action related to its indemnification obligations. However, the Company may record charges in the future as a result of these indemnification obligations. The Company also has indemnification obligations to its directors and executive officers for specified events or occurrences, subject to some limits, while they are serving at the Company’s request in such capacities. There have been no claims to date and the Company believes the fair value of these indemnification agreements is minimal. Accordingly, the Company has not recorded any liabilities for these agreements as of June 30, 2016.

Legal Proceedings

From time to time, the Company may become involved in litigation and other legal actions. The Company estimates the range of liability related to any pending litigation where the amount and range of loss can be estimated. The Company records its best estimate

of a loss when the loss is considered probable. Where a liability is probable and there is a range of estimated loss with no best estimate in the range, the Company records a charge equal to at least the minimum estimated liab ility for a loss contingency when both of the following conditions are met: (i) information available prior to issuance of the financial statements indicates that it is probable that a liability had been incurred at the date of the financial statements and (ii) the range of loss can be reasonably estimated.

In July 2015, three putative securities class action lawsuits were filed against the Company and certain of its officers in the United States District Court for the Northern District of California, each on behalf of a purported class of persons and entities who purchased or otherwise acquired its publicly traded securities between July 31, 2014 and June 15, 2015. The lawsuits assert claims under the Securities Exchange Act of 1934 (Exchange Act) and the Securities Act of 1933, as amended (Securities Act) and allege that the defendants made materially false and misleading statements and omitted allegedly material information related to, among other things, the Phase 2a clinical trial for AVA-101 and the prospects of AVA-101. The complaints seek unspecified damages, attorneys’ fees and other costs. An amended consolidated complaint was filed in February 2016, and the Company’s motion to dismiss that consolidated complaint is pending.

In December 2015, a putative securities class action lawsuit was filed against us, our board of directors, underwriters of our January 13, 2015, follow-on public stock offering, and two of our institutional stockholders, in the Superior Court of the State of California for the County of San Mateo. The complaint alleges that, in connection with our follow-on stock offering, the defendants violated the Securities Act in essentially the same manner alleged by the consolidated federal action: by allegedly making materially false and misleading statements and by allegedly omitting material information related to the Phase 2a clinical trial for AVA-101 and the prospects of AVA-101. The complaint seeks unspecified compensatory and rescissory damages, attorneys’ fees and other costs. The plaintiff has dismissed the two institutional stockholder defendants, and the Company’s motion to stay or to dismiss this action is pending.

The Company believes that the claims in the asserted actions are without merit and intend to defend the lawsuits vigorously. The Company expects to incur costs associated with defending the actions. While the Company has various insurance policies related to the risks associated with its business, including directors’ and officers’ liability insurance policies, there is no assurance that the Company will be successful in its defense of the actions, that its insurance coverage, which contains a self-insured retention, will be sufficient, or that its insurance carriers will cover all claims or litigation costs. Due to the inherent uncertainties of litigation, the Company cannot reasonably predict at this time the timing or outcomes of these matters or estimate the amount of losses, or range of losses, if any, or their effect, if any, on its condensed consolidated financial statements.

11. Stock Option Plans

The Company’s 2014 Equity Incentive Award Plan (2014 Plan) permits the issuance of stock options (options), restricted stock units (RSUs) and other types of awards to employees, directors, and consultants.

As of June 30, 2016, a total of 13,162,656 shares of common stock were authorized for issuance and 2,241,693 shares were available for future grants under the 2014 Plan.

In July 2014, the Company’s board of directors and its stockholders approved the establishment of the 2014 Employee Stock Purchase Plan (2014 ESPP). During the six months ended June 30, 2016 32,425 shares were issued under the 2014 ESPP and no shares were issued in the same period for 2015. A total of 675,383 shares of common stock have been reserved for issuance under the 2014 ESPP and 623,381 were available for issuance under the 2014 ESPP as of June 30, 2016.

The following table summarizes option activity under our stock plans and related information:

						WEIGHTED-
	NUMBER OF			WEIGHTED-		AVERAGE REMAINING		AGGREGATE
	SHARE			AVERAGE EXERCISE		CONTRACTUAL LIFE		INTRINSIC VALUE ^(a)
	(IN THOUSANDS)			PRICE		(IN YEARS)		(IN THOUSANDS)
Balance at January 1, 2016		5,494		$	8.75
Options granted		4,975		$	1.25
Options exercised		(1,233	)	$	0.40
Options cancelled		(511	)	$	23.83
Balance at June 30, 2016		8,725		$	4.77		8.9		15,473
Vested and expected to vest as of June 30, 2016		8,622		$	4.72		8.9		15,471
Exercisable as of June 30, 2016		3,760		$	3.62		8.2		8,997

^(a)	The aggregate intrinsic value is calculated as the difference between the option exercise price and the closing price of common stock of $3.16 per share as of June 30, 2016.

Options granted number includes the Company’s stock options for 3,673,940 common stock shares issued in exchange for Annapurna stock options at $0.21 exercise price per share. The weighted-average fair values of options granted and exchanged during the six months ended June 30, 2016 and 2015 were $1.62 and $27.90, respectively. The total intrinsic value of options exercised during the six months ended June 30, 2016 and 2015 were $6.3 million and $10.6 million, respectively.

The Company has recorded aggregate stock-based compensation expense related to the issuance of stock option awards to employees and nonemployees in the condensed consolidated statement of operations and comprehensive loss as follows (in thousands):

	Three Months Ended					Six Months Ended
	June 30,					June 30,
	2016		2015			2016		2015
Research and development	$	1,912	$	(445	)	$	4,140	$	(161	)
General and administrative		914		1,004			2,770		1,493
Total share-based compensation	$	2,826	$	559		$	6,910	$	1,332

Stock-based compensation expense included additional charges of $0.3 million and $1.1 million, recorded in general and administrative expense, and zero and $1.4 million, recorded in research and development expense, related to stock modifications in connection with separation agreements three Company’s executives for the three-months and six-months ended June 30, 2016, respectively.

Restricted Stock Units

Restricted stock units, or RSUs, are share awards that entitle the holder to receive freely tradable shares of our common stock upon vesting. The fair value of RSUs is based upon the closing sales price of our common stock on the grant date. During the six months ended June 30, 2016 and 2015, the Company granted a total of 1,066,283 and 97,000 RSUs, respectively. RSUs granted to employees generally vest over a two-to-four year period.

The following table summarizes the RSUs activity under our stock plans and related information:

	Number of			Weighted-Average
	Shares			Grant-Date
	(in thousands)			Fair Value (in dollars)
Outstanding at December 31, 2015		632		$	13.07
Granted		1,066		$	4.63
Vested and released		(165	)	$	11.60
Forfeited		(342	)	$	7.85
Outstanding at June 30, 2016		1,191		$	6.50

The total fair value of RSUs that vested for the six months ended June 30, 2016 was $ 2.2 million and no shares were vested for the six months ended June 30, 2015 . As of June 30, 2016, there was $ 5. 3 million of unrecognized compensation cost related to unvested RSUs that we expect to recognize over a weighted-average period of 2. 8 years.

Stock Options Granted to Employees

The fair value of each option issued to employees was estimated at the date of grant using the Black-Scholes valuation model with the following weighted-average assumptions:

	Three Months Ended						Six Months Ended
	June 30,						June 30,
	2016			2015			2016			2015
Option grants:
Expected volatility		81	%		76	%		81	%		77	%
Expected term (in years)		5.9			6.0			5.9			6.1
Expected dividend yield		—			—			—			—
Risk-free interest rate		1.3	%		1.6	%		1.3	%		1.6	%

As of June 30, 2016, there was $18.4 million of unrecognized stock-based compensation expense related to employees’ awards that is expected to be recognized over a weighted-average period of 3.0 years.

Stock Options Granted to Non-Employees

Stock-based compensation related to stock options granted to non-employees is measured and recognized as the stock options are earned. The Company believes that the estimated fair value of the stock options is more readily measurable than the fair value of the services rendered. The following weighted-average assumptions were used in estimating non-employees’ stock-based compensation expenses:

	Three Months Ended						Six Months Ended
	June 30,						June 30,
	2016			2015			2016			2015
Option grants:
Expected volatility		84	%		80	%		83	%		80	%
Expected term (in years)		8.0			8.0			7.5			7.8
Expected dividend yield		—			—			—			—
Risk-free interest rate		1.6	%		2.0	%		1.6	%		1.9	%

As of June 30, 2016, there was $2.5 million of unrecognized stock-based compensation expense related to non-employees’ awards that is expected to be recognized over a weighted-average period of 1.3 years.

12. 401(k) Savings Plan

The Company established a defined-contribution savings plan under Section 401(k) of the Code (the 401(k) Plan). The 401(k) Plan covers all employees who meet defined minimum age and service requirements, and allows participants to defer a portion of their annual compensation on a pretax basis. For the three months ended June 30, 2016 and 2015, the Company contributed $0.1 million and $0 to the 401(k) Plan, respectively. For the six months ended June 30, 2016 and 2015, the Company contributed $0.2 million and $0.1 million to the 401(k) Plan, respectively

13. Net Loss Per Share

Basic net loss per share is calculated by dividing the net loss by the weighted-average number of shares of common stock outstanding for the period. Diluted net loss per share attributable is computed by giving effect to all potential dilutive common stock equivalents outstanding for the period. Diluted net loss per share is the same as basic net loss per share for all periods presented, since the effects of potentially dilutive securities are antidilutive.

We have excluded stock options and RSUs to purchase approximately 9.9 million and 5.2 million shares of our common stock that were outstanding as of June 30, 2016 and 2015, respectively, in the computation of diluted net loss per share attributable to common stockholders because their effect was antidilutive.

14. Subsequent Events

In August 2016, the Company entered into a collaboration, option and license agreement with Editas Medicine, Inc. (“ Editas ”) pursuant to which the Company and Editas will collaborate on certain studies using adeno-associated viral vectors in connection with Editas’ genome editing technology and the Company will grant to Editas an exclusive option to obtain certain exclusive rights to use the Company’s proprietary vectors in up to five ophthalmic indications. The Company will receive a $1.0 million non-refundable upfront payment, with a portion of such payment to be credited against Editas’ obligation to fund research costs. Under the terms of the agreement, both the Company and Editas will be subject to exclusivity obligations.

Editas may exercise the option, with respect to a designated initial indication, until the first anniversary of the effective date of the agreement. With respect to the four other Indications, Editas may exercise the option until the third anniversary of the effective date, provided that the option will expire on the second anniversary of the effective date if Editas has not exercised the option with respect to the initial indication or any other indication by such date. Upon each exercise of the option, Editas will pay the Company a $1.0 million fee. If Editas elects to develop a product using certain of the Company’s proprietary vectors, the Company will be eligible to receive additional payments relating to development and commercialization milestone payments for such product, and tiered royalties on net sales of such product, subject to certain adjustments.

Item 2.

Management’s Discussion and Analysis o f Financial Condition and Results of Operation

The interim financial statements included in this Quarterly Report on Form 10-Q and this Management’s Discussion and Analysis of Financial Condition and Results of Operations should be read in conjunction with the financial statements and notes thereto for the year ended December 31, 2015, and the related Management’s Discussion and Analysis of Financial Condition and Results of Operations, contained in our Annual Report on Form 10-K, as filed with the U.S. Securities and Exchange Commission (SEC) on March 4, 2016. In addition to historical information, this discussion and analysis contains forward-looking statements within the meaning of Section 27A of the Securities Act of 1933, as amended (Securities Act), and Section 21E of the Securities Exchange Act of 1934, as amended (Exchange Act). These forward-looking statements are subject to risks and uncertainties, including those discussed in the section titled “Risk Factors,” set forth in Part II – Other Information, Item 1A below and elsewhere in this report that could cause actual results to differ materially from historical results or anticipated results.

Overview

We are a publicly traded gene therapy company committed to discovering and developing novel medicines that can offer potentially life-changing therapeutic benefit to patients who currently have limited or burdensome treatment options. We have leveraged our next-generation adeno-associated virus (AAV)-based directed evolution platform to generate product candidates designed to provide durable efficacy by inducing sustained expression of a therapeutic protein. We have also acquired certain other gene therapy product candidates through our previously announced transaction with Annapurna Therapeutics SAS, a privately-held French gene therapy company (Annapurna), which closed on May 11, 2016. Our core capabilities include clinical development expertise, vector optimization, process development, manufacturing, and assay development.

Prior to the Annapurna transaction, our primary focus had been the development of AVA-101 for the treatment of wet AMD. We conducted a Phase 2a trial for AVA-101 with 32 wet AMD subjects, for which we announced top-line results in June 2015. Overall, we did not observe evidence of a complete and/or durable anti-VEGF response in the majority of subjects treated with AVA-101 as administered in the Phase 2a study. We decided not to move forward with the Phase 2b clinical trial for AVA-101 with the dose and administration procedure that we had planned to initiate in the second half of 2015. Instead, we conducted additional preclinical studies to inform further development of our wet AMD program.

After analyzing promising preclinical data evaluating different anti-VEGF compounds in non-human primate studies, we decided to discontinue development of AVA-101 and AVA-201. Instead, we will move forward with preclinical development of new, anti-VEGF gene therapy candidates focused on intravitreal delivery and utilizing a proprietary vector. The company will provide additional details on its anti-VEGF program at a scientific meeting in the fall of 2016.

In addition to our anti-VEGF program, we are working on developing product candidates targeting diseases with unmet medical need in ophthalmology, rare disease and allergy. Our most advanced program, ANN-001, is for the treatment of alpha 1 antitrypsin deficiency (A1AT). ANN-001 is designed to deliver A1AT protein to patients with A1AT deficiency and will be evaluated using an intraplueral and intravenous route of administration. ANN-001 has an open IND with the FDA, and we expect to initiate clinical studies in the second half of 2016. Our gene therapy program, ANN-002 to treat hereditary angioedema (HAE), is also in preclinical studies, and we expect to initiate clinical studies in 2017. We have a preclinical program targeting cardiomyopathy associated with Friedreich’s ataxia for which we plan to provide a development update in 2017. In addition, we have a program targeting severe allergy which is in early preclinical development.

We also are developing other product candidates for the treatment of ophthalmic diseases, including AVA-311 for the treatment of juvenile X-linked retinoschisis (XLRS) as part of our research collaboration with Regeneron and AVA-322 and AVA-323 for the treatment of color vision deficiency (CVD) commonly known as red-green color blindness.

On May 11, 2016, we completed our previously announced acquisition of all of the outstanding shares of Annapurna and, as a result, Annapurna is now our wholly owned subsidiary. At the closing of the acquisition, we issued 14,087,246 shares of our common stock to the shareholders of Annapurna, and the outstanding options or other rights to purchase capital stock of Annapurna were exchanged for options relating to shares of our common stock.

Upon completion of the Annapurna transaction, we changed our name to “Adverum Biotechnologies, Inc.”.

Financial Overview

Summary

We have not generated positive cash flow or net income from operations since our inception and, at June 30, 2016, we had an accumulated deficit of $161.2 million, primarily as a result of research and development, general and administrative expenses and the goodwill impairment charge.

While we may in the future generate revenue from a variety of sources, including license fees, milestone and research and development payments in connection with strategic partnerships, and potentially revenue from approved product sales, we have not yet generated any revenue from approved therapeutic product candidates.

We entered into our first license and development revenue generating agreement with Regeneron in May 2014. We entered into the collaboration, option and license agreement with Editas in August 2016, that also will be a revenue agreement. Editas agreement is disclosed in Note 14, Subsequent Events , in the condensed consolidated financial statements included in this Form 10-Q.We have no manufacturing facilities, and all of our manufacturing activities are contracted out to third parties. Additionally, we have used third-party clinical research organizations (CROs) to carry out our clinical development and we do not yet have a sales organization.

We expect to incur substantial expenditures in the foreseeable future for the development and potential commercialization of our product candidates. We will need substantial additional funding in the future to support our operating activities as we advance our product candidates through preclinical and clinical development, seek regulatory approval and prepare for and, if approved, proceed to commercialization. Adequate funding may not be available to us on acceptable terms, or at all. If we are unable to raise capital, or to do so on acceptable terms, when needed, or to form additional collaboration partnerships to support our efforts, we could be forced to delay, reduce or eliminate our research and development programs or potential commercialization efforts.

As of June 30, 2016, we had $241.3 million in cash and cash equivalents. We believe that we have sufficient funds to continue operations for at least the next 36 months.

Revenue

To date we have not generated any revenue from the sale of our products. In May 2014, we entered into a multi-year license and development agreement with Regeneron. Under the terms of the agreement, we received initial payments of $8.0 million that included payment for research license fees, prepaid collaboration research costs and the right of first negotiation for a potential license to develop and commercialize AVA-101. As the agreement provides for multiple deliverables, we account for this agreement as a multiple elements revenue arrangement. If deliverables do not appear to have a standalone fair value, they were combined with other deliverables into a unit of accounting with standalone fair value. We allocated the $8.0 million received to the fair values of the two units of accounting identified in the arrangement. We expect to recognize $6.5 million for research licenses and related research and development services ratably over the associated period of performance, which is the maximum research period of eight years. As there is no discernible pattern of performance and/or objectively measurable performance measures do not exist, we will recognize revenue on a straight-line basis over the eight-year performance period. The remaining $1.5 million allocated to the second unit of accounting for the time-limited right of first negotiation for AVA-101 was deferred. On November 2, 2015, Regeneron notified the management that it was not exercising this right of first negotiation and we recognized the entire $1.5 million as revenue in 2015.

The portion of the upfront payment that was applied to the original research budget was fully used in the fourth quarter of 2015, and the Company and Regeneron, through a joint review committee, agree annually on an updated research and development services budget through the research period. The Company invoices Regeneron quarterly for services performed in each prior. These additional research fees are added to the research licenses and related research and development services unit of accounting, recorded as deferred revenue and recognized to revenue over the remaining maximum research term. The Company recognized $307,000 and $203,000 as revenue related to this unit of accounting during the three months ended June 30, 2016 and 2015, respectively, and $572,000 and $406,000 as revenue related to this unit of accounting during the six months ended June 30, 2016 and 2015, respectively. The Company recorded $7.2 million of deferred revenue, including $1.2 million as current deferred revenue, and $1.0 million as a receivable from collaboration partner as of June 30, 2016.

Our ability to generate product revenue and become profitable depends upon our ability to successfully develop and commercialize our product candidates. Because of the numerous risks and uncertainties associated with product development, we are unable to predict the amount or timing of product revenue. Even if we are able to generate revenue from the sale of our products, we may be unable to continue our operations at planned levels and be forced to reduce our operations.

Research and Development Expenses

Conducting a significant amount of research and development is central to our business model. Research and development expenses include certain payroll and personnel expenses, stock-based compensation expense, laboratory supplies, consulting costs, external contract research and development expenses, including expenses incurred under agreements with CROs, the cost of acquiring, developing and manufacturing clinical study materials and overhead expenses, including rent, equipment depreciation, insurance and utilities.

Research and development costs are expensed as incurred. Advance payments for goods or services for future research and development activities are deferred and expensed as the goods are delivered or the related services are performed.

We estimate preclinical study and clinical trial expenses based on the services performed pursuant to contracts with research institutions and CROs that have conducted and managed preclinical studies and clinical trials on our behalf. In accruing service fees, we estimate the time period over which services will be performed and the level of effort to be expended in each period. We estimate the amounts incurred through communications with third party service providers and our estimates of accrued expenses as of each balance sheet date are based on information available at the time. If the actual timing of the performance of services or the level of effort varies from the estimate, we will adjust the accrual accordingly.

At this time, we cannot reasonably estimate the nature, timing or aggregate costs of the efforts that will be necessary to complete the development of any of our product candidates. The successful development and commercialization of a product candidate is highly uncertain, and clinical development timelines, the probability of success and development and commercialization costs can differ materially from expectations.

We received refundable tax credits from the Australian and French tax authorities in connection with certain research costs incurred by our subsidiaries conducting research in Australia and France. These refunds do not depend on our taxable income or tax position and therefore we do not account for them under an income tax accounting model. We recognize such refunds as government grants in the period when qualified expenses are incurred as a reduction of research expenses. We have recorded the reimbursement from the Australian and French tax authorities as a reduction of research and development expense in the consolidated statements of operations and comprehensive loss for the applicable period. The Company recorded tax credits of $20,000 and $65,000 for the three and six-month periods ending June 30, 2016, respectively, and $67,000 and 119,000 for the three and six-month periods ending June 30, 2015, respectively.

General and Administrative Expenses

General and administrative expenses consist principally of personnel-related costs, stock-based compensation, professional fees for legal, consulting, audit and tax services, rent and other general operating expenses not otherwise included in research and development expenses. Our general and administrative expenses may increase in future periods if and to the extent we elect to increase our investment in infrastructure to support continued research and development activities and potential commercialization of our product candidates. We will continue to evaluate the need for such investment in conjunction with ongoing consideration of our pipeline of product candidates. We anticipate increased expenses related to audit, legal and regulatory functions, as well as director and officer insurance premiums and investor relations costs associated with being a public reporting company.

Goodwill Impairment

As the Company recorded goodwill and IPR&D intangible assets upon the acquisition of Annapurna, the Company is required to test goodwill and indefinite-lived intangible assets for impairment on an annual basis or more frequently if indicators of impairment exist. The Company operates as one reporting unit and goodwill was recorded to this reporting unit. The Company recorded goodwill impairment charge of $49.1 million for the three and six months ended June 30, 2016.

Critical Accounting Policies and Significant Judgments and Estimates

Our management’s discussion and analysis of financial condition and results of operations are based upon our unaudited condensed consolidated financial statements, which have been prepared in accordance with U.S. generally accepted accounting principles (U.S. GAAP). The preparation of these condensed consolidated financial statements requires us to make estimates and judgments that affect the reported amounts of assets, liabilities, revenues and expenses. On an on-going basis, we evaluate our critical accounting policies and estimates. We base our estimates on historical experience and on various other assumptions that we believe to be reasonable in the circumstances, the results of which form the basis for making judgments about the carrying values of assets and liabilities that are not readily apparent from other sources. Actual results may differ from these estimates under different assumptions and conditions. Our significant accounting policies are more fully described in Note 2 of the accompanying unaudited

condensed consolidated financial statements and in Note 2 to our audited consolidated financial statements contained in our Annual Report on Form 10-K (Annual Report) as filed with the SEC, on March 4, 2 016.

The Company added critical accounting policy below as a result of Annapurna acquisition.

Valuation of Long‑Lived Assets and Purchased Intangible Assets

The Company also evaluates the carrying value of intangible assets (not subject to amortization) related to in‑process research and development (“IPR&D”) assets, which are considered to be indefinite‑lived until the completion or abandonment of the associated research and development efforts. Accordingly, amortization of the IPR&D assets will not occur until the product reaches commercialization. During the period the assets are considered indefinite‑lived, they will be tested for impairment on an annual basis, as well as between annual tests if the Company becomes aware of any events occurring or changes in circumstances that would indicate that the fair values of the IPR&D assets are less than their carrying amounts. If and when development is complete, which generally occurs when regulatory approval to market the product is obtained, the associated IPR&D assets would be deemed definite‑lived and would then be amortized based on their estimated useful lives at that point in time. If the related project is terminated or abandoned, the Company may have an impairment related to the IPR&D asset, calculated as the excess of their carrying value over fair value. The Company estimated fair value of IPR&D assets acquired in Annapurna transaction at the acquisition closing date, May 11, 2016. No impairment was recorded at June 30, 2016, as there were no changes in the fair value of IPR&D assets between May 11 and June 30, 2016.

Results of Operations

Comparison of the Three and Six Month Periods Ended June30, 2016 and 2015 (in thousands)

	Three Months Ended June 30,									Six Months Ended June 30,
	2016			2015			Change			2016			2015			Change
Collaboration revenue	$	307		$	203		$	104		$	572		$	406		$	166
Operating expenses:
Research and development		7,955			5,126			2,829			15,410			10,747			4,663
General and administrative		5,114			4,959			155			13,432			9,102			4,330
Goodwill impairment charge		49,120			–			49,120			49,120			–			49,120
Total operating expenses		62,189			10,085			52,104			77,962			19,849			58,113
Operating loss		(61,882	)		(9,882	)		(52,000	)		(77,390	)		(19,443	)		(57,947	)
Other income, net		222			116			106			338			168			170
Total other income, net		222			116			106			338			168			170
Net loss	$	(61,660	)	$	(9,766	)	$	(51,894	)	$	(77,052	)	$	(19,275	)	$	(57,777	)

Revenue

Collaboration revenue for the three and six months ended June 30, 2016 increased by $0.1 million and $0.2 million over the prior year period, respectively. Recorded revenue relates to the revenue contract with Regeneron and represents license and research fees that we recognized over the research term.

Research and Development Expense

Research and development expense increased to $8.0 million for the three months ended June 30, 2016 from $5.1 million for the three months ended June 30, 2015, primarily due to a $2.4 million increase in stock-based compensation expenses, including $0.9 million relating to the accelerated vesting of Annapurna option and shares recorded after the acquisition closing, the addition of $1.2 million in incremental expenses relating to Annapurna’s operations incurred since the date of acquisition and $0.3 million increase in facility and deprecation charges relating to build out of the laboratory space, partially offset by a $0.5 million decrease in payroll related expenses and a $0.5 million decrease in material production and clinical expenses.

Research and development expense increased to $15.4 million for the six months ended June 30, 2016 from $10.7 million for the six months ended June 30, 2015, primarily due to a $4.3 million increase in stock-based compensation expenses, including $0.9 million relating to the accelerated vesting of Annapurna options and shares recorded after the acquisition closing, the addition of $1.2 million in incremental expenses relating to Annapurna’s operations incurred since date of acquisition , $0.8 million increase for outside services expense relating to toxicology, $0.6 million increase in facility and deprecation charges relating to build out of the laboratory space, partially offset by $1.7 million decrease in material production and clinical expenses and $0.5 million decrease in payroll related expenses.

For the periods presented, substantially all of our research and development expense related to Adverum development activities for AVA-101, for the treatment of wet AMD, and our other potential product candidates in our development program. Upon completion of the Annapurna acquisition in May 2016, we began incurring expenses related to Annapurna’s four development programs. We expect research and development expenses may increase in future periods as we continue to invest in our pipeline products and preclinical studies relating to our gene therapies program.

General and Administrative Expense

General and administrative expense increased to $5.1 million for the three months ended June 30, 2016 from $5.0 million for the three months ended June 30, 2015. The increase in general and administrative expense was primarily due to $0.6 million increase in professional service fees relating to Annapurna acquisition and $0.2 million increase in facility charges relating to office expansion, off-set by $0.3 million decrease in recruiting and travel expenses, $0.2 million decrease in marketing and investor relations and $0.1 million decrease in stock-based compensation expense relating to the timing of the annual employee and director equity awards in the second quarter of 2015 versus the first quarter of 2016.

General and administrative expense increased to $13.4 million for the six months ended June 30, 2016 from $9.1 million for the six months ended June 30, 2015. The increase in general and administrative expense was primarily due to increases of $2.5 million in consulting and professional service expenses relating to Annapurna acquisition, $1.7 million in compensation and benefits, including $1.3 million in related stock-based compensation expense and $0.4 million increase in payroll-related expense, and $0.3 million in facilities allocation relating to new office space, off-set by $0.2 decrease in travel expenses.

We expect general and administrative expenses may increase in future periods if and to the extent we elect to increase our investment in infrastructure to support continued research and development activities and potential commercialization of our product candidates. We will continue to assess such expenses in conjunction with ongoing consideration of our pipeline of product candidates. We anticipate increased costs in connection with increased professional fees associated with being a public company.

Goodwill Impairment Charge

During the quarter ended June 30, 2016, we noted a continuing decrease in our stock price that resulted in our market capitalization being less than the carrying value of our net assets as of June 30, 2016. As our operating losses are expected to increase in the following years due to continuing pre-clinical and expected clinical trials, we concluded that it is more likely than not that the fair value of the Company’s one reporting unit is less than its’ carrying value and concluded to perform a goodwill impairment analysis. We performed a two-step goodwill impairment analysis and recorded a $49.1 million goodwill impairment charge in our condensed consolidated statements of operations and comprehensive loss for the period ended June 30, 2016.

Other income, Net

Other income, net is comprised mainly of interest income on our cash and investment in marketable securities in 2016 and 2015.

Liquidity and Capital Resources and Plan of Operations

We have not generated positive cash flow or net income from operations since our inception and at June 30, 2016, we had an accumulated deficit of $161.2 million, primarily as a result of research and development and general and administration expenses and the goodwill impairment charge. As of June 30, 2016, we had $241.3 million in cash and cash equivalents and no marketable securities. We believe that our existing cash and cash equivalents as of June 30, 2016 will be sufficient to fund our operations for at least the next 36 months.

We expect to incur substantial expenditures in the foreseeable future for the development and potential commercialization of our product candidates and ongoing internal research and development programs. At this time, we cannot reasonably estimate the nature, timing or aggregate amount of such costs. However, in order to complete our planned preclinical trials and any future clinical trials, and to complete the process of obtaining regulatory approval for our product candidates, as well as to build the sales, marketing and distribution infrastructure that we believe will be necessary to commercialize our product candidates, if approved, we will require substantial additional funding in the future.

If and when we seek additional funding, we will do so through equity or debt financings, collaborative or other arrangements with corporate sources or through other sources of financing. Adequate additional funding may not be available to us on acceptable terms or at all. Our failure to raise capital in the future could have a negative impact on our financial condition and our ability to pursue our business strategies. In order to complete development and commercialization of any of our product candidates, we anticipate that we will need to raise substantial additional capital, the requirements of which will depend on many factors, including:

the initiation, progress, timing, costs and results of preclinical studies and any clinical trials for our product candidates;

the outcome, timing of and costs involved in, seeking and obtaining approvals from the Food and Drug Administration (FDA) and other regulatory authorities, including the potential for the FDA and other regulatory authorities to require that we perform more studies than those that we currently expect;

the ability of our product candidates to progress through clinical development activities successfully;

our need to expand our research and development activities;

the rate of progress and cost of our commercialization of our products;

the cost of preparing to manufacture our products on a larger scale;

the costs of commercialization activities including product sales, marketing, manufacturing and distribution;

the degree and rate of market acceptance of any products launched by us or future partners;

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

our need to implement additional infrastructure and internal systems;

our ability to hire additional personnel;

our ability to enter into additional collaboration, licensing, commercialization or other arrangements and the terms and timing of such arrangements; and

the emergence of competing technologies or other adverse market developments.

If we are unable to raise additional funds when needed, we may be required to delay, reduce or terminate some or all of our development programs and any clinical trials. We may also be required to sell or license other technologies or clinical product candidates or programs that we would prefer to develop and commercialize ourselves.

Cash Flows

	Six Month Periods Ended
	June 30,
	2016			2015
	(in thousands)
Net cash used in operating activities	$	(20,377	)	$	(16,992	)
Net cash provided by (used in) investing activities		40,061			(80,954	)
Net cash provided by financing activities		349			139,085
Net increase in cash and cash equivalents	$	19,954		$	41,133

During the six months ended June 30, 2016, net cash used in operating activities was $20.4 million, primarily as a result of the net loss of $77.1 million offset by the following non-cash charges: $49.1 million goodwill impairment charge, $6.9 million stock-based compensation expense and $0.6 million depreciation and amortization expense. During the six months ended June 30, 2015, net cash used in operating activities was $17.0 million, primarily as a result of the net loss of $19.3 million offset by the following non-cash charges: $1.3 million stock-based compensation expense, $0.3 million amortization of premium on marketable securities and $0.3 million depreciation and amortization expense.

Net cash provided by investing activities for the six months ended June 30, 2016 was $40.1 million and primarily relates to the maturities of marketable securities of $37.7 million, $3.5 million of cash acquired in the acquisition of Annapurna, offset by $1.1 million purchases of property and equipment. Net cash used in investing activities for the six months ended June 30, 2015 was $81.0 million and primarily relates to the purchases marketable securities of $88.4 million and the purchases of property and equipment of $1.5 million, offset by cash received from maturities of marketable securities of $9.0 million. The purchases of property and equipment consisted primarily of acquisition of laboratory equipment to support our research and development activities.

The net cash provided by financing activities during the six month period ended June 30, 2016 of $0.3 million relates to the exercise of options for common shares. The net cash provided by financing activities during the six month period ended June 30, 2015 of $139.1 million was primarily related to $130.6 million net proceeds from our follow-on offering and $8.3 million from sale of common shares.

Contractual Obligations and Commitments

In August 2015, BPI France granted Annapurna a €750,000 interest free conditional advance, of which €500,000 was received as of December 31, 2015. The remaining €250,000 advance was not and is not expected to be drawn down on. Payments are scheduled in equal quarterly amounts of €25,000 from September 30, 2017 to June 30, 2022. This payment schedule will be modified if the Company will receive revenue from license or product sales before advances are paid in full. The Company calculated 7% imputed interest expense on these advances that was recorded as a discount at the issuance date and is amortized as an interest expense over the life of. As of June 30, 2016 the carrying value of the conditional advance was $373,000.

Off-Balance Sheet Arrangements

We do not have any off-balance sheet arrangements.

Item 3.

Quantitative and Qualitative Disclosures about Market Risk

There have not been any material changes to our exposure to market risk during the three-month period ended June 30, 2016. For additional information regarding market risk, refer to the Qualitative and Quantitative Disclosures About Market Risk section of our Annual Report on Form 10-K.

Item 4.

Contro ls and Procedures

Evaluation of disclosure controls and procedures . Management, including our Chief Executive Officer and Chief Financial Officer, evaluated the effectiveness of our disclosure controls and procedures, as defined in Rules 13a-15(e) and 15d-15(e) under the Exchange Act, as of June 30, 2016. The evaluation of our disclosure controls and procedures included a review of our processes and implementation and the effect on the information generated for use in this Quarterly Report on Form 10-Q. In the course of this evaluation, we sought to identify any material weaknesses in our disclosure controls and procedures to determine whether we had identified any acts of fraud involving personnel who have a significant role in our disclosure controls and procedures, and to confirm that necessary corrective action, including process improvements, was taken. This type of evaluation is done quarterly so that our conclusions concerning the effectiveness of these controls can be reported in our periodic reports filed with the SEC. The overall goals of these evaluation activities are to monitor our disclosure controls and procedures and to make modifications as necessary. We intend to maintain these disclosure controls and procedures, modifying them as circumstances warrant.

Based on that evaluation, the Chief Executive Officer and Chief Financial Officer concluded that as of June 30, 2016, the Company’s disclosure controls and procedures were effective to provide reasonable assurance that information required to be disclosed by us in

the reports that we file or submit under the Exchange Act is (i) recorded, processed, summarized and reported as and when required and (ii) accumulated and communicated to our management, including the Chief Executive Officer and Chief Financial Officer, as appropriate to allow timely discussion regarding required disclosure.

Changes in internal control over financial reporting . There have been no changes in our internal control over financial reporting during the three months ended June 30, 2016 that have materially affected or are reasonably likely to materially affect, our internal control over financial reporting.

Inherent Limitations on Controls and Procedures

Our management, including the Chief Executive Officer and the Chief Financial Officer, does not expect that our disclosure controls and procedures and our internal controls will prevent all error and all fraud. A control system, no matter how well designed and operated, can only provide reasonable assurances that the objectives of the control system are met. The design of a control system reflects resource constraints; the benefits of controls must be considered relative to their costs. Because there are inherent limitations in all control systems, no evaluation of controls can provide absolute assurance that all control issues and instances of fraud, if any, within the Company have been or will be detected. As these inherent limitations are known features of the financial reporting process, it is possible to design into the process safeguards to reduce, though not eliminate, these risks. These inherent limitations include the realities that judgments in decision-making can be faulty and that breakdowns occur because of simple error or mistake. Controls can be circumvented by the individual acts of some persons, by collusion of two or more people, or by management override of the control. The design of any system of controls is based in part upon certain assumptions about the likelihood of future events. While our disclosure controls and procedures are designed to provide reasonable assurance of achieving their objectives, there can be no assurance that any design will succeed in achieving its stated goals under all future conditions. Over time, controls may become inadequate because of changes in conditions or deterioration in the degree of compliance with the policies or procedures. Because of the inherent limitations in a cost-effective control system, misstatements due to error or fraud may occur and not be detected.

We intend to review and evaluate the design and effectiveness of our disclosure controls and procedures on an ongoing basis and to improve our controls and procedures over time and to correct any deficiencies that we may discover in the future. While our Chief Executive Officer and Chief Financial Officer have concluded that, as of June 30, 2016, the design of our disclosure controls and procedures, as defined in Rule 13a-15(e) under the Exchange Act, was effective, future events affecting our business may cause us to significantly modify our disclosure controls and procedures.

PART II – OTHE R INFORMATION

Item 1.

Legal Proceedings

In July 2015, three putative securities class action lawsuits were filed against us and certain of our officers in the United States District Court for the Northern District of California, each on behalf of a purported class of persons and entities who purchased or otherwise acquired our publicly traded securities between July 31, 2014 and June 15, 2015. The lawsuits assert claims under the Exchange Act and Securities Act and allege that the defendants made materially false and misleading statements and omitted allegedly material information related to, among other things, the Phase 2a clinical trial for AVA-101 and the prospects of AVA-101. The complaints seek unspecified damages, attorneys’ fees and other costs. An amended consolidated complaint was filed in February 2016, and the Company’s motion to dismiss that consolidated complaint is pending.

We believe that the claims in the asserted actions are without merit and intend to defend the lawsuits vigorously. We expect to incur costs associated with defending the actions. While we have various insurance policies related to the risks associated with our business, including directors’ and officers’ liability insurance policies, there is no assurance that we will be successful in our defense of the actions, that our insurance coverage, which contains a self-insured retention, will be sufficient, or that our insurance carriers will cover all claims or litigation costs. Due to the inherent uncertainties of litigation, we cannot reasonably predict at this time the timing or outcomes of these matters or estimate the amount of losses, or range of losses, if any, or their effect, if any, on our financial statements.

Item 1A.

Risk Factors

Investing in our common stock involves a high degree of risk. Before deciding to invest in our common stock, you should carefully consider each of the risk factors described in “Part I - Item 1A. Risk Factors” in our Annual Report on Form 10-K for the year ended December 31, 2015 and all information set forth in this Quarterly Report on Form 10-Q. Those risks and the risks described in this Quarterly Report on Form 10-Q, including in the section entitled “Management’s Discussion and Analysis of Financial Condition and Results of Operations,” could materially harm our business, financial condition, operating results, cash flow and prospects. If that occurs, the trading price of our common stock could decline, and you may lose all or part of your investment.

There have been no material changes to the Risk Factors described under “Part I - Item 1A. Risk Factors” in our Annual Report on Form 10-K for the year ended December 31, 2015, other than as set forth below. The risk factors below, some of which are new and some of which originally appear in our Annual Report on Form 10-K or our Quarterly Report on Form 10-Q for the period ending March 31, 2016 and have been updated, reflect additional information regarding the transaction with Annapurna and our anti-VEGF program, among other things.

Risks Related to Our Financial Position and Need for Capital

We have incurred significant operating losses since inception, and we expect to incur significant losses for the foreseeable future. We may never become profitable or, if achieved, be able to sustain profitability.

We have incurred significant operating losses since we were founded in 2006 and expect to incur significant losses for the foreseeable future as we continue development of our product candidates. Annapurna has also incurred significant operating losses since inception. As of June 30, 2016 on a pro forma basis, the combined company had an accumulated deficit of $161.2 million. Our losses have resulted primarily from costs incurred in our clinical trials, research and development programs and from our general and administrative expenses.

In the future, we intend to continue to conduct research and development, clinical testing, regulatory compliance activities and, if any of our product candidates is approved, sales and marketing activities that, together with anticipated general and administrative expenses, will likely result in us incurring significant losses for the next several years.

We currently generate no revenue from sales, and we may never be able to commercialize any of our product candidates. We do not currently have the required approvals to market any of our other product candidates, and we may never receive such approvals. We may not be profitable even if we or any of our future development partners succeed in commercializing any of our produc t candidates. Because of the numerous risks and uncertainties associated with developing and commercializing our product candidates, we are unable to predict the extent of any future losses or when we will become profitable, if at all.

While we expect that our cash and cash equivalents will be sufficient to fund our operations for at least 36 months, we will need to obtain additional capital to fund our operations. Failure to obtain capital when needed may force us to delay, limit or terminate our product development efforts or other operations and we will be unable to successfully develop and commercialize our product candidates.

Developing gene therapy products is expensive, and we expect our research and development expenses to increase substantially, particularly if we advance ANN-001, ANN-002, an anti-VEGF candidate or other product candidates into clinical studies.

We expect that our cash and cash equivalents will be sufficient to fund our operations through at least 36 months. However, this estimate is based on a number of assumptions that may prove to be wrong, and changing circumstances beyond our control may cause capital to be consumed more rapidly than currently anticipated. As a result, our operating plan may change due to factors currently unknown to us, and we may need to seek additional funds sooner than planned, through collaboration agreements and public or private financings.

We will require substantial future capital in order to complete the preclinical and clinical development for our product candidates and to potentially commercialize these product candidates. Any future clinical trials of our product candidates would cause an increase in our spending levels, as would other corporate activities. The amount and timing of any expenditure needed to implement our development and commercialization programs will depend on numerous factors, including:

the type, number, scope, progress, expansion costs, results of and timing of any future clinical trials of any of our product candidates which we are pursuing or may choose to pursue in the future;

the need for, and the progress, costs and results of, any additional clinical trials of our product candidates we may initiate based on the results of any clinical trials that we may plan or discussions with the FDA, including any additional trials the FDA or other regulatory agencies may require evaluating the safety of our product candidates;

the costs of obtaining, maintaining and enforcing our patents and other intellectual property rights;

the costs and timing of obtaining or maintaining manufacturing for our product candidates, including commercial manufacturing if any product candidate is approved;

the costs and timing of establishing sales and marketing capabilities and enhanced internal controls over financial reporting;

the terms and timing of establishing collaborations, license agreements and other partnerships;

costs associated with any new product candidates that we may develop, in-license or acquire;

the effect of competing technological and market developments;

our ability to establish and maintain partnering arrangements for development; and

the costs associated with being a public company.

Some of these factors are outside of our control. We do not expect our existing capital resources to be sufficient to enable us to fund the completion of our clinical trials and remaining development program through commercial introduction. We expect that we will need to raise additional funds in the future.

We have not sold any products, and we do not expect to sell or derive revenue from any product sales for the foreseeable future. We may seek additional funding through collaboration agreements and public or private financings. Additional funding may not be available to us on acceptable terms or at all, and given our decision to discontinue development of AVA-101, our ability to obtain funding in the future on favorable terms, or at all, may be substantially impaired. In addition, the terms of any financing may adversely affect the holdings or the rights of our stockholders, and the issuance of additional shares by us, or the possibility of such issuance, may cause the market price of our shares to decline.

If we are unable to obtain funding on a timely basis, we will be unable to complete any future clinica l trials for our product candidates and we may be required to significantly curtail some or all of our activities. We also could be required to seek funds through arrangements with collaborative partners or otherwise that may require us to relinquish right s to our product candidates or some of our technologies or otherwise agree to terms unfavorable to us.

Risks Related to the Discovery and Development of Our Product Candidates

As a result of the transaction with Annapurna, we are transforming from a company developing product candidates for the treatment of eye diseases into a gene therapy company with a diverse pipeline of gene therapy product candidates. We may encounter challenges in implementing this transformation and the integration of Annapurna that could adversely impact our business and operations.

Prior to completion of the transaction with Annapurna, all of our development efforts were focused on developing product candidates for the treatment of eye diseases. The pipeline acquired through the Annapurna transaction includes gene therapy product candidates designed to treat a range of diseases. The most advanced product candidate from the Annapurna pipeline is ANN-001, which is designed to deliver alpha-1 antitrypsin protein, or A1AT, in patients with A1AT, a rare genetic disorder which may result in serious respiratory disease in adults and, less commonly, liver disease at any age. Other product candidates from the Annapurna pipeline are designed to treat patients with hereditary angioedema, Friedreich’s ataxia and severe allergies. We intend to continue to advance both our development programs for the treatment of eye diseases and Annapurna’s development programs. As a result, we are transforming from a company focused solely on gene therapy treatments for eye diseases to a gene therapy company with a diverse pipeline of product candidates.

This transformation into a diversified gene therapy company poses risks relating to implementing a new business and operational strategy, including the following:

the potential disruption of our ongoing development of product candidates for the treatment of eye diseases;

demands on our management and our limited resources related to the increase in number and diversification of our product candidates;

difficulties in coordinating research and development activities;

the establishment of uniform standards, controls, procedures and policies; and

uncertainties in the business relationships with our collaborators and suppliers due to the Annapurna transaction and our transformation into a diversified gene therapy company.

Additionally, there can be no guarantee that we and Annapurna will operate successfully as a combined company. Integration of Annapurna and consolidation of its operations into our organization will require considerable time and attention from management, which could result in the diversion of management resources from other important matters. Moreover, Dr. Salzman is based in Philadelphia and certain Annapurna operations will continue to be based in Paris. Their location outside of our Menlo Park headquarters may make their integration into our organization more challenging.

If we are unable to successfully manage these or other risks and uncertainties relating to the integration of Annapurna’s business into our organization, there will likely be adverse impacts on our business and operations.

Our business to date has depended substantially on the success of AVA-101. In the second quarter of 2016, we decided to discontinue development of AVA-101. As a result, commercialization of our first product candidate may be delayed, and our business may be materially harmed.

We previously focused our advanced development efforts on one product candidate: AVA-101, a recombinant adeno-associated vector type 2 (AAV2) encoding the anti-VEGF protein sFlt-1, and considered successful continued development and ultimate regulatory approval of AVA-101 critical for our future business success.

We expect to initiate clinical studies for our most advanced product candidate, ANN-001, in the second half of 2016. Our other product candidates are in the early stage of development and will require additional preclinical studies, substantial clinical

development and testing, manufacturing bridging studies and process validation and regulatory approval prior to commercialization. As a result of our decision to discontinue AVA-101 and focus on o ur other, preclinical stage product candidates, commercialization of our first product candidate may be delayed, and we may not be able obtain funding in the future on favorable terms, or at all, that will be necessary to continue our business, or generate sufficient revenue to continue our business.

Our decision to discontinue development of AVA-101 and instead focus on development of new, anti-VEGF candidates may delay our commercialization of an anti-VEGF product. As a result, our business may be materially harmed.

In the second quarter of 2016, following analysis of the data generated in our Phase 2a clinical study of AVA-101, additional preclinical studies, and analysis of promising preclinical data evaluating different anti-VEGF compounds in non-human primate studies, we decided to discontinue development of AVA-101 and instead continue pre-clinical development of new anti-VEGF candidates focused on intravitreal delivery and utilizing a proprietary vector. We may conduct additional pre-clinical studies on these product candidates, and, if we decide to pursue clinical development of any of these product candidates, we expect we will be required to restart the clinical development process and conduct a Phase 1 or Phase 2a clinical trial to demonstrate safety and tolerability. This restart could result in a significant development delay for an anti-VEGF product candidate. If our development of an anti-VEGF product candidate is delayed, our competitors may be able to bring products to market before we do, and the commercial viability of our anti-VEGF product candidate could be significantly reduced.

Our business will depend substantially on the success of one or more of our product candidates, which are still in preclinical development. If we are unable to commercialize our product candidates or if we experience significant delays in obtaining regulatory approval for, or commercializing, any or all of our product candidates, our business may be materially harmed.

Our product candidates are in the early stage of development and will require additional preclinical studies, substantial clinical development and testing, manufacturing bridging studies and process validation and regulatory approval prior to commercialization. In the second quarter of 2016, we decided to discontinue development of our one product candidate that had been the focus of advanced development efforts, AVA-101. We expect to initiate clinical studies for our most advanced product candidate, ANN-001, in the second half of 2016, and we are continuing pre-clinical development of our other product candidates. It is critical to our business to successfully develop and obtain ultimate regulatory approval for one or more of these product candidates. Our ability to commercialize our product candidates effectively will depend on several factors, including the following:

successful completion of preclinical studies and clinical trials, including the ability to demonstrate safety and efficacy of our product candidates;

receipt of marketing approvals from the FDA and similar regulatory authorities outside the United States;

establishing commercial manufacturing capabilities, for example, by making arrangements with third-party manufacturers;

successfully launching commercial sales of the product, whether alone or in collaboration with others;

acceptance of the product by patients, the medical community and third-party payers;

establishing market share while competing with other therapies;

a continued acceptable safety profile of our products following regulatory approval;

maintaining compliance with post-approval regulation and other requirements; and

qualifying for, identifying, registering, maintaining, enforcing and defending intellectual property rights and claims covering our product candidates.

If we, or our collaborators, do not achieve one or more of these factors in a timely manner or at all, we could experience significant delays or an inability to commercialize our product candidates, which would materially and adversely affect our business, financial condition and results of operations.

Moreover, of the large number of biologics and drugs in development in the pharmaceutical industry, only a small percentage result in the submission of a Biologics License Application (BLA) to the FDA and even fewer are approved for commercialization. Furthermore, even if we do receive regulatory approval to market any of our product candidates, any such approval may be subject to limitations on the indicated uses for which we may market the product. Accordingly, even if we are able to obtain the requisite financing to continue to fund our development programs, we cannot assure you that any of our product candidates will be successfully developed or commercialized. If we decide to invest in the continued development and potential commercialization of any or all of our product candidates and we or any

of our future development partners are unable to develop, or obtain regulatory approval for, or, if approved, successfully commercialize, such product candidates, we m ay not be able to generate sufficient revenue to continue our business.

We have conducted, and may in the future conduct, clinical trials for product candidates in sites outside the United States and the FDA may not accept data from trials conducted in such locations.

We have conducted, and may in the future choose to conduct, one or more of our clinical trials outside the United States. For example, we conducted a Phase 1/2a trial for AVA-101 with LEI in Australia.

Although the FDA may accept data from clinical trials conducted outside the United States, acceptance of this data is subject to certain conditions imposed by the FDA. For example, the clinical trial must be well designed and conducted and performed by qualified investigators in accordance with ethical principles. The study population must also adequately represent the U.S. population, and the data must be applicable to the U.S. population and U.S. medical practice in ways that the FDA deems clinically meaningful. Generally, the patient population for any clinical studies conducted outside of the United States must be representative of the population for whom we intend to label the product in the United States. In addition, while these clinical trials are subject to the applicable local laws, FDA acceptance of the data will be dependent upon its determination that the studies also complied with all applicable U.S. laws and regulations. There can be no assurance the FDA will accept data from trials conducted outside of the United States. If the FDA does not accept the data from our clinical trials for our product candidates, it would likely result in the need for additional trials, which would be costly and time-consuming and delay or permanently halt our development of our product candidates.

We may not be successful in our efforts to identify or discover additional product candidates.

The success of our business depends primarily upon our ability to identify, develop and commercialize products based on our platform. Our research programs, including those subject to our collaboration with Regeneron, may fail to identify other potential product candidates for clinical development for a number of reasons. Our research methodology may be unsuccessful in identifying potential product candidates or our potential product candidates may be shown to have harmful side effects or may have other characteristics that may make the products unmarketable or unlikely to receive marketing approval.

If any of these events occur, we may be forced to abandon our development efforts for a program or programs, which would have a material adverse effect on our business and could potentially cause us to cease operations. Research programs to identify new product candidates require substantial technical, financial and human resources. We may focus our efforts and resources on potential programs or product candidates that ultimately prove to be unsuccessful.

We have not tested any of our internally-developed viral vectors, or product candidates derived from these viral vectors, in clinical trials.

Drug development has inherent risk. None of our current product candidates has ever been evaluated in human clinical studies, and we may experience unexpected results in the future. We or any of our future development partners will be required to demonstrate through adequate and well-controlled clinical trials that our product candidates containing our proprietary vectors are safe and effective, with a favorable benefit-risk profile, for use in their target indications before we can seek regulatory approvals for their commercial sale. Drug development is a long, expensive and uncertain process, and delay or failure can occur at any stage of development, including after commencement of any of our clinical trials.

The results of preclinical studies and early clinical trials are not always predictive of future results. Any product candidate we or any of our future development partners advance into clinical trials may not have favorable results in later clinical trials, if any, or receive regulatory approval.

If our proprietary vectors are not shown to be safe and effective in targeting retinal tissue, we may not realize the value of our investment in directed evolution technology. In addition, success in early clinical trials does not mean that later clinical trials will be successful, because product candidates in later-stage clinical trials may fail to demonstrate sufficient safety or efficacy despite having progressed through initial clinical testing. Furthermore, any future trials will need to demonstrate sufficient safety and efficacy for approval by regulatory authorities in larger patient populations. Companies frequently suffer significant setbacks in advanced clinical trials, even after earlier clinical trials have shown promising results. For example, following analysis of the data generated in our Phase 2a clinical trial of AVA-101, we concluded that, overall, we did not observe evidence of a complete and/or durable anti-VEGF response in the majority of subjects treated with AVA-101 as administered in the Phase 2a study, and we have discontinued development of AVA-101. In addition, only a small percentage of products under development result in the submission of a BLA to the FDA and even fewer are approved for commercialization.

We cannot be certain that any clinical trials that we plan will be successful, and any safety concerns observed in any one of our clinical trials in our targeted indications could limit the prospects for regulatory approval of our product candidates in those and ot her indications.

If we encounter difficulties enrolling subjects in our clinical trials, our clinical development activities could be delayed or otherwise adversely affected.

We intend to initiate clinical trials for Annapurna’s most advanced product candidate, ANN-001, in the second half of 2016 and accordingly we expect ANN-001 to be our next product candidate to enter clinical development. Identifying and qualifying subjects to participate in clinical studies of ANN-001 and our other product candidates will be critical to our success. The timing of future clinical studies will depend on the speed at which we can recruit subjects to participate in future testing of these product candidates.

Subject enrollment, a significant factor in the timing of clinical trials, is affected by many factors including the size and nature of the patient population, the proximity of patients to clinical sites, the eligibility criteria for the trial, the design of the clinical trial, competing clinical trials and clinicians’ and patients’ perceptions as to the potential advantages of the product candidate being studied in relation to other available therapies, including any new drugs that may be approved for the indications we are investigating. We will be required to identify and enroll a sufficient number of subjects with the relevant disease we are targeting for any future clinical trials for our product candidates. Potential subjects may not be adequately diagnosed or identified with the diseases which we are targeting or may not meet the entry criteria for our studies. We also may encounter difficulties in identifying and enrolling subjects with a stage of disease appropriate for such future clinical trials. We may not be able to identify, recruit and enroll a sufficient number of subjects, or those with required or desired characteristics to achieve diversity in a study.

In particular, each of the conditions for which we plan to evaluate product candidates acquired in the Annapurna transaction are rare genetic disorders with limited patient pools from which to draw for clinical studies. ANN-001 is focused on the treatment of patients with A1AT deficiency. It is estimated that A1AT deficiency affects approximately 100,000 patients in the United States. ANN-002 is focused on the treatment of patients with hereditary angioedema (HAE). The prevalence of HAE is estimated to be 1 in 10,000 to 1 in 50,000, with approximately 10,000 patients diagnosed across major markets. ANN-003 is focused on the treatment of patients with Friedreich’s Ataxia (FA). It is estimated that FA affects approximately 5,000 people in the United States and approximately 5,000 to 10,000 people in Europe. In addition, we and our collaboration partner, Regeneron, are developing AVA-311 for the treatment of X-linked retinoschisis (XLRS), an orphan indication. Enrollment of eligible subjects with orphan diseases may be limited or slower than we anticipate in light of the small subject populations involved. We plan to seek initial marketing approval of these product candidates in the United States and Europe and we may not be able to initiate clinical studies if we cannot enroll a sufficient number of eligible subjects to participate in the clinical studies required by the FDA or the EMA or other regulatory agencies. In addition, the process of finding and diagnosing subjects may prove costly.

Further, if patients are unwilling to participate in our gene therapy studies because of negative publicity from adverse events in the biotechnology or gene therapy industries or inadequate results in our preclinical or clinical studies or for other reasons, including competitive clinical trials for similar patient populations or available approved therapies, our recruitment of subjects, conduct of studies and ability to obtain regulatory approval of our product candidates may be hindered.

Trials using early versions of retroviral vectors, which integrate with, and thereby alter, the host cell’s DNA, have led to several well-publicized adverse events. For example, generalized public backlash developed against gene therapy following the death in September 1999 of an 18-year-old who had volunteered for a gene therapy experiment at the University of Pennsylvania. Researchers at the university had infused the volunteer’s liver with a gene aimed at reversing a rare metabolic disease of the liver. The procedure triggered an extreme immune-system reaction that caused multiple-organ failure in a very short time, leading to the first death to occur as a direct result of a gene therapy experiment. In addition, in 2003, 20 subjects treated for X-linked severe combined immunodeficiency in two gene therapy studies using a murine gamma-retroviral vector showed correction of the disease, but the studies were terminated after five subjects developed leukemia (four of whom were subsequently cured). The cause of these adverse events was shown to be insertional oncogenesis, which is the process whereby the corrected gene inserts near a gene that is important in a critical cellular process like growth or division, and this insertion results in the development of a cancer (often leukemia). Using molecular diagnostic techniques, it was determined that clones from these subjects showed retrovirus insertion in proximity to the promoter of the LMO2 proto-oncogene. Earlier generation retroviruses like the one used in these two studies have been shown to preferentially integrate in regulatory regions of genes that control cell growth.

If we have difficulty enrolling a sufficient number of subjects to conduct clinical studies on our product candidates as planned, we may need to delay, limit or terminate future clinical studies, any of which would have an adverse effect on our business.

We believe we have appropriately accounted for the above factors in our tria ls when determining expected clinical trial timelines, but we cannot assure you that our assumptions are correct or that we will not experience delays in enrollment, which would result in the delay of completion of such trials beyond our expected timelines .

The occurrence of serious complications or side effects in connection with use of our product candidates, either in clinical trials or post-approval, could lead to discontinuation of our clinical development program, refusal of regulatory authorities to approve our product candidates or, post-approval, revocation of marketing authorizations or refusal to approve new indications, which could severely harm our business, prospects, operating results and financial condition.

During the conduct of clinical trials, patients report changes in their health, including illnesses, injuries and discomforts, to their study doctor. Often, it is not possible to determine whether or not the product candidate being studied caused these conditions. Various illnesses, injuries, and discomforts have been reported from time-to-time during clinical trials of our product candidates. It is possible that as we test our product candidates in larger, longer and more extensive clinical programs, or as use of these product candidates becomes more widespread if they receive regulatory approval, illnesses, injuries, discomforts and other adverse events that were observed in earlier trials, as well as conditions that did not occur or went undetected in previous trials, will be reported by subjects. Many times, side effects are only detectable after investigational products are tested in large-scale, Phase 3 clinical trials or, in some cases, after they are made available to patients on a commercial scale after approval. If additional clinical experience indicates that any of our product candidates has side effects or causes serious or life-threatening side effects, the development of the product candidate may fail or be delayed, or, if the product candidate has received regulatory approval, such approval may be revoked, which would severely harm our business, prospects, operating results and financial condition.

Patients given infusions of any protein may develop severe hypersensitivity reactions or infusion reactions. In particular, there are many potential safety concerns associated with significant blockade of VEGF that may limit our ability to successfully develop and/or commercialize our anti-VEGF product candidates. These serious and potentially life-threatening risks, based on clinical and preclinical experience of VEGF inhibitors, include bleeding, intestinal perforation, hypertension, proteinuria, congestive heart failure, heart attack, stroke and geographic atrophy.

In addition, there are risks in treating patients with gene therapy vectors, including adeno-associated virus (AAV), such as inflammation, cytotoxic T-cell response, anti-AAV antibodies and immune response to the AAV capsid, T-cell responses and/or auto-antibodies against the expressed protein.

Furthermore, there are risks inherent in the administration of drugs like our product candidates. For example, we may elect to pursue intravenous or intrapleural administration of ANN-001, and there are known risks associated with both routes of administration. For intravenous administration, such risks include bleeding and swelling at the site of administration, and, for intrapleural administration, such risks include pneumothorax (collapsed lung) and/or bleeding at the site of administration.

There are also risks inherent in the intravitreal administration of drugs like our anti-VEGF product candidates, which can cause injury to the eye and other complications. Such risks include pain, subconjunctival hemorrhage, vitreous hemorrhage, retinal tear, retinal, detachment, cataracts, endophthalmitis and other side effects.

Serious complications or serious, unexpected side effects in connection with the use of our product candidates could materially harm our business, prospects’ operating results and financial condition.

Risks Related to Our Reliance on Third Parties

We and our contract manufacturers are subject to significant regulation with respect to manufacturing our products. The manufacturing facilities on which we rely may not continue to meet regulatory requirements and may have limited capacity.

We currently have relationships with limited number of suppliers for the manufacturing of our viral vectors and product candidates. These suppliers may require licenses to manufacture such components if such processes are not owned by the suppliers or in the public domain and we may be unable to transfer or sublicense the intellectual property rights we may have with respect to such activities. All entities involved in the preparation of therapeutics for clinical studies or commercial sale, including our existing contract manufacturer for our product candidates, are subject to extensive regulation. Components of a finished therapeutic product approved for commercial sale or used in late-stage clinical studies must be manufactured in accordance with current Good Manufacturing Practice (cGMP). These regulations govern manufacturing processes and procedures (including record keeping) and the implementation and operation of quality systems to control and assure the quality of investigational products and products approved for sale. Poor control of production processes can lead to the introduction of adventitious agents or other contaminants, or to inadvertent changes in the properties or stability of our product candidates that may not be detectable in final product testing. We or

our contract manufacturers must supply all necessary documentation in support of a BLA on a timely basis and must adhere to the FDA’s current Good Laboratory Practice regulations and cGMP regulations enforced by the FDA through its facilities inspection program. Our contract manufacturers have not produced a commercially-approved product and therefore have not obtained the requisite FDA approvals to do so. Our facilities and quality systems and the facilities and quality systems of some or all of our third-party contractors must pass a pre-approval inspection for compliance with the applicable regulations as a condition of regulatory approval of our product candidates or any of our other potential products. In addition, t he regulatory authorities may, at any time, audit or inspect our manufacturing facilities or those of our third-party contractors involved with the preparation of our product candidates or our other potential products or the associated quality systems for compliance with the regulations applicable to the activities being conducted. If the facility does not pass a pre-approval plant inspection, FDA approval of the products will not be granted.

The regulatory authorities also may, at any time following approval of a product for sale, audit our manufacturing facilities or those of our third-party contractors. If any such inspection or audit identifies a failure to comply with applicable regulations or if a violation of our product specifications or applicable regulations occurs independent of such an inspection or audit, we or the relevant regulatory authority may require remedial measures that may be costly and/or time-consuming for us or a third party to implement and that may include the temporary or permanent suspension of a clinical study or commercial sales or the temporary or permanent closure of a facility. Such violations could also result in civil and/or criminal penalties. Any such remedial measures or other civil and/or criminal penalties imposed upon us or third parties with whom we contract could materially harm our business.

If we or our third-party manufacturers fail to maintain regulatory compliance, the FDA can impose regulatory sanctions including, among other things, refusal to approve a pending application for a new drug product or biologic product, revocation of a pre-existing approval, other civil or criminal penalties or closing one or more manufacturing facilities. As a result, our business, financial condition and results of operations may be materially harmed.

Additionally, if supply from an approved manufacturer is interrupted, there could be a significant disruption in commercial supply. An alternative manufacturer would need to be qualified through a BLA supplement which could result in further delay. The regulatory agencies may also require additional studies if a new manufacturer is relied upon for commercial production. Switching manufacturers may involve substantial costs and is likely to result in a delay in our desired clinical and commercial timelines.

These factors could cause the delay of clinical studies, regulatory submissions, required approvals or commercialization of our product candidates, cause us to incur higher costs and prevent us from commercializing our products successfully. Furthermore, if our suppliers fail to meet contractual requirements, and we are unable to secure one or more replacement suppliers capable of production at a substantially equivalent cost, our clinical studies may be delayed or we could lose potential revenue.

Annapurna’s collaboration with Weill Cornell Medicine is crucial to our business. If we are unable to maintain this collaboration, or if this collaboration is not successful, our business could be adversely affected.

Our most advanced product candidate, ANN-001, and two other product candidates acquired in the Annapurna transaction, ANN-002, and ANN-004, are licensed from Weill Cornell Medicine (Weill Cornell). In addition, Annapurna and we rely on Weill Cornell to conduct preclinical development for these product candidates pursuant to a master services agreement. If Annapurna were to fail to comply with its obligations under any of these agreements and Weill Cornell were to terminate these licenses and/or its preclinical development services, then our pipeline of product candidates would be adversely affected.

Furthermore, Weill Cornell may fail to properly maintain or defend the intellectual property Annapurna has licensed from them, leading to the potential invalidation of Annapurna’s intellectual property or subjecting Annapurna or us to litigation or arbitration, any of which would be time-consuming and expensive. Additionally, in the event that Weill Cornell commits a material breach of any of these license or master service agreements, Annapurna’s only recourse is to terminate the agreement. If Annapurna terminates its collaboration with Weill Cornell, especially during its preclinical development phase, the development of the product candidates subject to the Weill Cornell collaboration would be materially delayed or harmed.

If disputes with Weill Cornell prevent or impair Annapurna’s ability to maintain its current licensing and preclinical development arrangements on acceptable terms, we may be unable to successfully develop and commercialize the affected product candidates, and our business could be materially harmed.

Risks Related to Commercialization of Our Product Candidates

Any termination or suspension of, or delays in the commencement or completion of, clinical trials for our product candidates could result in increased costs to us, delay or limit our ability to generate revenue and adversely affect our commercial prospects.

Before we can initiate clinical trials in the United States for our product candidates, we need to submit the results of preclinical testing to the FDA, along with other information including information about product candidate chemistry, manufacturing and controls and our proposed clinical trial protocol, as part of an IND. We may rely in part on preclinical, clinical and quality data generated by CROs and other third parties for regulatory submissions for our product candidates. If these third parties do not make timely regulatory submissions for our product candidates, it will delay our plans for our clinical trials. If those third parties do not make this data available to us, we will likely have to develop all necessary preclinical and clinical data on our own, which will lead to significant delays and increase development costs of the product candidate. In addition, the FDA may require us to conduct additional preclinical testing for any product candidate before it allows us to initiate clinical testing under any IND, which may lead to additional delays and increase the costs of our preclinical development. Delays in the commencement or completion of any clinical trials that we plan for our product candidates could significantly affect our product development costs. We do not know whether any trials that we plan will begin on time or be completed on schedule, if at all. The commencement and completion of clinical trials can be delayed for a number of reasons, including delays related to:

the FDA failing to grant permission to proceed or placing the clinical trial on hold;

subjects failing to enroll or remain in our trial at the rate we expect;

subjects choosing an alternative treatment for the indication for which we are developing our product candidates, or participating in competing clinical trials;

lack of adequate funding to continue the clinical trial;

subjects experiencing severe or unexpected drug-related adverse effects;

a facility manufacturing any of our product candidates or any of their components being ordered by the FDA or other government or regulatory authorities to temporarily or permanently shut down due to violations of cGMP or other applicable requirements, or infections or cross-contaminations of product candidates in the manufacturing process;

any changes to our manufacturing process that may be necessary or desired;

third-party clinical investigators losing the licenses or permits necessary to perform our clinical trials, not performing our clinical trials on our anticipated schedule or consistent with the clinical trial protocol, Good Clinical Practice or regulatory requirements or other third parties not performing data collection or analysis in a timely or accurate manner;

insp3ections of clinical trial sites by the FDA or the finding of regulatory violations by the FDA or an IRB that require us to undertake corrective action, result in suspension or termination of one or more sites or the imposition of a clinical hold on the entire trial or that prohibit us from using some or all of the data in support of our marketing applications;

third-party contractors becoming debarred or suspended or otherwise penalized by the FDA or other government or regulatory authorities for violations of regulatory requirements, in which case we may need to find a substitute contractor, and we may not be able to use some or all of the data produced by such contractors in support of our marketing applications; or

one or more IRBs refusing to approve, suspending or terminating the trial at an investigational site, precluding enrollment of additional subjects, or withdrawing its approval of the trial.

Product development costs will increase if we have delays in testing or approval of any of our product candidates, or if we need to perform more or larger clinical trials than planned. Additionally, changes in regulatory requirements and policies may occur, and we may need to amend clinical trial protocols to reflect these changes. Amendments may require us to resubmit our clinical trial protocols to IRBs for reexamination, which may impact the costs, timing or successful completion of a clinical trial. If we experience delays in completion of our clinical trials, or if we, the FDA or other regulatory authorities, the IRB, other reviewing entities, or any of our clinical trial sites suspend or terminate any of our clinical trials, the commercial prospects for a product candidate may be harmed and our ability to generate product revenue will be delayed. In addition, many of the factors that cause, or lead to, termination or suspension of, or a delay in the commencement or completion of, clinical trials may also ultimately lead to the denial of regulatory approval of a product candidate. For example, if we make manufacturing or formulation changes to our product candidates, we may need to conduct additional studies to bridge our modified product candidates to earlier versions. Further, if one or more clinical trials are delayed, our competitors may be able to bring products to market before we do, and the commercial viability of our product candidates could be significantly reduced.

If the market opportunities for our pro duct candidates are smaller than we believe they are, our future revenues may be adversely affected, and our business may suffer.

If the size of the markets for our target diseases are smaller than we anticipate, we may not be able to achieve profitability and growth. Our projections of the number of people who have these diseases, as well as the subset of people with these diseases who have the potential to benefit from treatment with our product candidates, are based on estimates. These estimates have been derived from a variety of sources, including the scientific literature, surveys of clinics, patient foundations and market research and may prove to be incorrect. Further, new studies may change the estimated incidence or prevalence of these diseases. The number of patients may turn out to be lower than expected. The effort to identify patients with diseases we seek to treat is in early stages, and we cannot accurately predict the number of patients for whom treatment might be possible. Additionally, the potentially addressable patient populations may be limited or may not be amenable to treatment with our product candidates, and new patients may become increasingly difficult to identify or gain access to, which would adversely affect our results of operations and our business. Further, even if we obtain significant market share for our product candidates, because the potential target populations are very small, we may never achieve profitability despite obtaining such significant market share.

Because the target patient populations of the product candidates acquired in the Annapurna transaction are relatively small, we must be able to successfully identify patients and achieve a significant market share to maintain profitability and growth. If the market opportunities for these product candidates are smaller than we believe they are, our future revenue may be adversely affected, and our business may suffer.

ANN-001 and the other product candidates acquired in the Annapurna transaction are designed to treat rare genetic and orphan diseases. Our projections of both the number of people who have these diseases, as well as the subset of people with these diseases who have the potential to benefit from treatment with these product candidates, are based on estimates. These estimates may prove to be incorrect and new studies may change the estimated incidence or prevalence of these diseases. The number of patients in the United States, Europe and elsewhere may turn out to be lower than expected, may not be otherwise amenable to treatment with these products, or new patients may become increasingly difficult to identify or gain access to, all of which would adversely affect our results of operations and our business.

Additionally, because the target patient populations for these product candidates are relatively small, the pricing and reimbursement of these product candidates, if approved, must be adequate to support commercial infrastructure. If we are unable to obtain adequate levels of reimbursement, our ability to successfully market and sell these product candidates will be adversely affected. The manner and level at which reimbursement is provided for services related to these product candidates (e.g., for administration of such product to patients) is also important. Inadequate reimbursement for such services may lead to physician resistance and adversely affect our ability to market or sell these products.

Coverage and reimbursement may be limited or unavailable in certain market segments for our product candidates, which could make it difficult for us to sell our product candidates profitably.

Market acceptance and sales of our product candidates will depend significantly on the availability of adequate coverage and reimbursement from third-party payers for any of our product candidates and may be affected by existing and future health care reform measures. Government authorities and third-party payers, such as private health insurers and health maintenance organizations, decide which drugs they will pay for and establish reimbursement levels. Reimbursement by a third-party payer may depend upon a number of factors including the third-party payer’s determination that use of a product candidate is:

a covered benefit under its health plan;

safe, effective and medically necessary;

appropriate for the specific patient;

cost-effective; and

neither experimental nor investigational.

Obtaining coverage and reimbursement approval for a product candidate from a government or other third-party payer is a time-consuming and costly process that could require us to provide supporting scientific, clinical and cost effectiveness data for the use of the applicable product candidate to the payer. We may not be able to provide data sufficient to gain acceptance with respect to coverage and reimbursement. We cannot be sure that coverage or adequate reimbursement will be available for any of our product candidates. Further, reimbursement amounts may reduce the demand for, or the price of, our product candidates. If reimbursement is not available or is available only in limited levels, we may not be able to commercialize certain of our product candidates profitably, or at all, even if approved.

As a result of legislative proposals and the trend toward managed health care in the Un ited States, third-party payers are increasingly attempting to contain health care costs by limiting both coverage and the level of reimbursement of new drugs. By way of example, the Medicare Prescription Drug Improvement and Modernization Act of 2003 (MMA ) changed the way Medicare covers and pays for pharmaceutical products. The legislation expanded Medicare coverage for outpatient drug purchases by those covered by Medicare under a new Part D and introduced a new reimbursement methodology based on average sales prices for Medicare Part B physician-administered drugs, including anti-VEGF therapies currently on the market used by physicians and likely our anti-VEGF product candidate, if approved. As a result of this legislation and the expansion of federal c overage of drug products, there is additional pressure to contain and reduce costs. While the MMA applies only to drug benefits for Medicare beneficiaries, private payers often follow Medicare coverage policy and payment limitations in setting their own re imbursement rates, and any reduction in reimbursement that results from the MMA may result in a similar reduction in payments from private payers. These cost reduction initiatives and other provisions of the MMA could decrease the coverage and reimbursemen t that we receive for any approved products, and could seriously harm our business.

In March 2010, the Patient Protection and Affordable Care Act, as amended by the Health Care and Education Reconciliation Act, collectively referred to as the Affordable Care Act, was enacted with a goal of reducing the cost of healthcare and substantially changing the way healthcare is financed by both government and private insurers. The Affordable Care Act, among other things, addressed a new methodology by which rebates owed by manufacturers under the Medicaid Drug Rebate Program are calculated for drugs that are inhaled, infused, instilled, implanted or injected, increased the minimum Medicaid rebates owed by manufacturers under the Medicaid Drug Rebate Program, extended the rebate program to individuals enrolled in Medicaid managed care organizations and established annual fees and taxes on manufacturers of certain prescription drugs.

Other legislative changes have also been proposed and adopted in the U.S. since the Affordable Care Act was enacted. On August 2, 2011, the Budget Control Act of 2011 created measures for spending reductions by Congress. A Joint Select Committee on Deficit Reduction, tasked with recommending a targeted deficit reduction of at least $1.2 trillion for the years 2013 through 2021, was unable to reach required goals, thereby triggering the legislation’s automatic reduction to several government programs. This included aggregate reductions of Medicare payments to providers of 2% per fiscal year, which went into effect on April 1, 2013 and will stay in effect through 2024 unless additional Congressional action is taken.

We expect that additional healthcare reform measures will be adopted in the future, any of which could limit the amounts that federal, state and foreign governments will pay for healthcare products and services, which could result in reduced demand for our products, if approved, or additional pricing pressures.

The continuing efforts of the government, insurance companies, managed care organizations and other payers of healthcare services to contain or reduce costs of health care may adversely affect:

the demand for any product candidates for which we may obtain regulatory approval;

our ability to set a price that we believe is fair for our product candidates;

our ability to generate revenue and achieve or maintain profitability;

the level of taxes that we are required to pay; and

the availability of capital.

We are subject to many manufacturing risks, any of which could substantially increase our costs and limit supply of our products.

The process of manufacturing our products is complex, highly regulated and subject to several risks, including:

The manufacturing of biologics is extremely susceptible to product loss due to contamination, equipment failure, improper installation or operation of equipment or vendor or operator error. Even minor deviations from normal manufacturing processes could result in reduced production yields, product defects and other supply disruptions. If microbial, viral or other contaminations are discovered in our products or in the manufacturing facility in which our products are made, such manufacturing facility may need to be closed for an extended period of time to investigate and remedy the contamination.

The manufacturing facilities in which our products are made could be adversely affected by equipment failures, labor shortages, contaminants, raw materials shortages, natural disasters, power failures and numerous other factors.

We and our [contract manufa cturer] must comply with the FDA’s cGMP regulations and guidelines. We and our [contract manufacturer] may encounter difficulties in achieving quality control and quality assurance and may experience shortages in qualified personnel. We and our [contract m anufacturer] are subject to inspections by the FDA and comparable agencies in other jurisdictions to confirm compliance with applicable regulatory requirements. Any failure to follow cGMP or other regulatory requirements or any delay, interruption or other issues that arise in the manufacture, fill-finish, packaging or storage of our products as a result of a failure of our facilities or the facilities or operations of third parties to comply with regulatory requirements or pass any regulatory authority ins pection could significantly impair our ability to develop and commercialize our products. This may lead to significant delays in the availability of products for our clinical studies or the termination or hold on a clinical study, or the delay or preventio n of a filing or approval of marketing applications for our product candidates. Significant noncompliance could also result in the imposition of sanctions, including fines, injunctions, civil penalties, failure of regulatory authorities to grant marketing approvals for our product candidates, delays, suspension or withdrawal of approvals, license revocation, seizures or recalls of products, operating restrictions and criminal prosecutions, any of which could be costly and damage our reputation. If we are no t able to maintain regulatory compliance, we may not be permitted to market our products and/or may be subject to product recalls, seizures, injunctions or criminal prosecution.

Our product candidates are biologics and require processing steps that are more complex than those required for most chemical pharmaceuticals. Moreover, unlike chemical pharmaceuticals, the physical and chemical properties of a biologic such as our product candidates generally cannot be adequately characterized prior to manufacturing the final product. As a result, an assay of the finished product is not sufficient to ensure that the product will perform in the intended manner. Accordingly, we expect to employ multiple steps to attempt to control our manufacturing process to assure that the process works and the product or product candidate is made strictly and consistently in compliance with the process.

Problems with the manufacturing process, even minor deviations from the normal process, could result in product defects or manufacturing failures that result in lot failures, product recalls, product liability claims and insufficient inventory.

Some of the raw materials required in our manufacturing process are derived from biological sources. Such raw materials are difficult to procure and may also be subject to contamination or recall. A material shortage, contamination, recall or restriction on the use of biologically derived substances in the manufacture of our product candidates could adversely impact or disrupt commercialization.

Any adverse developments affecting manufacturing operations for our products may result in shipment delays, inventory shortages, lot failures, product withdrawals or recalls, or other interruptions in the supply of our products. We may also have to take inventory write-offs and incur other charges and expenses for products that fail to meet specifications, undertake costly remediation efforts or seek more costly manufacturing alternatives. We may encounter problems achieving adequate or clinical-grade materials that meet FDA, EMA or other applicable standards or specifications with consistent and acceptable production yields and costs.

If our competitors develop treatments for the target indications of our product candidates that are approved more quickly than ours, marketed more successfully or demonstrated to be safer or more effective than our product candidates, our commercial opportunity will be reduced or eliminated.

We operate in highly competitive segments of the biopharmaceutical markets. We face competition from many different sources, including larger and better-funded pharmaceutical, specialty pharmaceutical and biotechnology companies, as well as from academic institutions, government agencies and private and public research institutions. Our product candidates, if successfully developed and approved, will compete with established therapies as well as with new treatments that may be introduced by our competitors. There are a variety of drug candidates in development for the indications that we intend to test. Many of our competitors have significantly greater financial, product candidate development, manufacturing and marketing resources than we do. Large pharmaceutical and biotechnology companies have extensive experience in clinical testing and obtaining regulatory approval for drugs. In addition, universities and private and public research institutes may be active in our target disease areas, and some could be in direct competition with us. We also may compete with these organizations to recruit management, scientists and clinical development personnel. We will also face competition from these third parties in establishing clinical trial sites, registering subjects for clinical trials and in identifying and in-licensing new product candidates. Smaller or early-stage companies may also prove to be significant competitors, particularly through collaborative arrangements with large and established companies.

New developments, including the development of other pharmaceutical technologies and methods of treating disease, occur in the pharmaceutical and life sciences industries at a rapid pace. Developments by competitors may render our product candidates obsolete or noncompetitive. Competition in drug development is intense. We anticipate that we will face intense and increasing competition as new treatments enter the market and advanced technologies become available.

Even if we obtain regulatory approval for our product candidates, the availability and price of our competitors’ products could limit th e demand, and the price we are able to charge, for our product candidates. For example, EYLEA® is currently available in the United States for treatment of wet AMD and macular edema following central retinal vein occlusion (CRVO), and in the United Kingdom , Germany, Switzerland, Australia, Japan and certain other countries for the treatment of wet AMD. Additionally, marketing approval has been obtained in the EU for EYLEA® for the treatment of visual impairment due to macular edema secondary to CRVO. We wil l not achieve our business plan if the acceptance of our product candidates is inhibited by price competition or the reluctance of physicians to switch from existing methods of treatment to our product candidates, or if physicians switch to other new drug products or choose to reserve our product candidates for use in limited circumstances. Our inability to compete with existing or subsequently introduced drug products would have a material adverse impact on our business, prospects, financial condition and results of operations.

Our potential competitors in these diseases may be developing novel immune modulating therapies that may be safer or more effective than our product candidates. For example, if we seek to commercialize an anti-VEGF product candidate, it will compete with a variety of anti-VEGF therapies currently marketed and in development, using therapeutic modalities such as biologics, small molecules and gene therapy. Lucentis®, EYLEA® and Avastin® are anti-VEGF therapies that are well established and widely accepted by physicians, patients and third-party payers. There are also several other companies with marketed anti products or products in development for the treatment of wet AMD, including Allergan, Iconic Therapeutics, Inc., Novartis AG, Ocular Therapeutix, Inc., Ophthotech Corporation, Hoffmann-La Roche Ltd., Neurotech Pharmaceuticals, Inc., Regeneron, Santen Pharmaceuticals Co., Ltd., Valeant Pharmaceuticals North America LLC, R Biosciences LLC, Applied Genetic Technologies Corporation, Oxford Biomedica plc, Ohr Pharmaceuticals, Inc. and Mesoblast Limited.

Our preclinical product candidates are being developed for the treatment of diseases with unmet medical need in ophthalmology, rare disease and allergy, such as the prevention of wet AMD and the treatment of alpha 1 antitrypsin deficiency (A1AT).. However, there are multiple companies developing gene therapies for ophthalmic diseases, including Applied Genetic Technologies Corporation, Asklepios BioPharmaceutical Inc., Eos Neuroscience, Inc., ReGenX Biosciences LLC, GenSight Biologics, Genzyme Corporation, Hemera Biosciences, Inc., RetroSense Therapeutics, LLC, Spark Therapeutics, Inc., Oxford Biomedica plc, Sanofi-Aventis S.A., NightStaRx Limited and 4D Molecular Therapeutics, LLC and Benitec Biopharma Limited.

Risks Related to Our Business Operations

We are dependent on the services of our key executives and scientific staff, and if we are not able to retain these members of our management or recruit additional management, clinical and scientific personnel, our business will suffer.

We are dependent on the principal members of our management and scientific staff. The loss of service of any of our management could harm our business. In addition, we are dependent on our continued ability to attract, retain and motivate highly qualified additional management, clinical and scientific personnel. If we are not able to retain our management, and to attract, on acceptable terms, additional qualified personnel necessary for the continued development of our business, we may not be able to sustain our operations or grow. Although we have executed employment agreements with each member of our current executive management team, these agreements are terminable at will with or without notice and, therefore, we may not be able to retain their services as expected.

We will need to expand and effectively manage our managerial, operational, financial, and other resources in order to successfully pursue our development and commercialization efforts. Our success also depends on our continued ability to attract, retain and motivate highly qualified management and scientific personnel. We may not be able to attract or retain qualified management and scientific and clinical personnel in the future due to the intense competition for qualified personnel among biotechnology, pharmaceutical and other businesses, particularly in the San Francisco Bay Area. Our industry has experienced a high rate of turnover of management and scientific personnel in recent years. If we are not able to attract, retain and motivate necessary personnel to accomplish our business objectives, we may experience constraints that will significantly impede the achievement of our development objectives, our ability to raise additional capital and our ability to implement our business strategy.

Paul B. Cleveland joined as our President and Chief Executive Officer in December 2015. Upon the completion of the transaction with Annapurna in May 2016, Amber Salzman, Ph.D. joined us as our President, with Mr. Cleveland continuing to serve as our Chief Executive Officer. In addition, Leone Patterson joined us as our Chief Financial Officer in June 2016. Our future performance will depend, in part, on our ability to successfully integrate newly hired executive officers, including Mr. Cleveland, Dr. Salzman and Ms. Patterson, into our management team and our ability to develop an effective working relationship among senior management. Our failure to integrate these individuals and create effective working relationships among them and other members of management could result in inefficiencies in the development and commercialization of our product candidates, harming future regulatory approvals, sales of our product candidates and our results of operations. Moreover, Dr. Salzman is based in Philadelphia, and her location outside of our Menlo Park headquarters may make her integration into our organization more challenging.

Additionally, we do not currently maintain “key person” life insurance on the lives of our executives or any of our em ployees. This lack of insurance means that we may not have adequate compensation for the loss of the services of these individuals.

If we fail to effectively integrate our new executive officers into our organization, the future development and commercialization of our product candidates may suffer, harming future regulatory approvals, sales of our product candidates or our results of operations.

Our current management team has only been working together for a relatively short period of time and some of our current management team, including Chief Executive Officer Paul B. Cleveland, President Amber Salzman, Ph.D., and Chief Financial Officer Leone Patterson, have been employed by us for less than a year. In addition, we may continue to expand our management team in the future. Our future performance will depend, in part, on our ability to successfully integrate recently and subsequently hired executive officers into our management team and their ability to develop and maintain an effective working relationship. Our failure to integrate these individuals with other members of management could result in inefficiencies in the development and commercialization of our product candidates, harming future regulatory approvals, sales of our product candidates and our results of operations. Moreover, Dr. Salzman is based in Philadelphia, and her location outside of our Menlo Park headquarters may make her integration into our organization more challenging. In addition to the competition for personnel, the San Francisco Bay Area in particular is characterized by a high cost of living. As such, we could have difficulty attracting experienced personnel to our company and may be required to expend significant financial resources in our employee recruitment and retention efforts.

Risks Relating to Our Intellectual Property

Our rights to develop and commercialize our product candidates are subject in part to the terms and conditions of licenses granted to us by other companies and universities.

We currently are heavily reliant upon licenses of certain patent rights and proprietary technology from third parties that is important or necessary to the development of our technology and products, including technology related to our manufacturing process and our gene therapy product candidates. These and other licenses may not provide adequate rights to use such intellectual property and technology in all relevant fields of use and in all territories in which we may wish to develop or commercialize our technology and products in the future. For example, the license granted to us by the Regents to make, have made, use, offer for sale, import, export and sell products covered by certain patent rights licensed to us under our agreement with the Regents is limited to the United States. The license is also limited to the Regents’ interest in the licensed patent rights which are co-owned by Chiron Corporation (Chiron). As a result, we may not be able to prevent competitors from developing and commercializing competitive products in territories not included in our licenses to patents.

Licenses to additional third-party technology that may be required for our development programs may not be available in the future or may not be available on commercially reasonable terms, which could have a material adverse effect on our business and financial condition.

In some circumstances, we may not have the right to control the preparation, filing and prosecution of patent applications, or to maintain the patents, covering technology that we license from third parties. In addition, we must obtain consent from the Regents before we can enforce patent rights licensed to us by the Regents. While such consent may not be unreasonably withheld, the Regents may withhold such consent or may not provide it on a timely basis. Therefore, we cannot be certain that these patents and applications will be prosecuted and enforced in a manner consistent with the best interests of our business. In addition, if third parties who license patents to us fail to maintain such patents, or lose rights to those patents, the rights we have licensed may be reduced or eliminated.

Our success depends on our ability to protect our intellectual property and our proprietary technologies.

Our commercial success depends in part on our ability to obtain and maintain patent protection and trade secret protection for our product candidates, proprietary technologies, and their uses as well as our ability to operate without infringing upon the proprietary rights of others. There can be no assurance that our patent applications or those of our licensors will result in additional patents being issued or that issued patents will afford sufficient protection against competitors with similar technology, nor can there be any assurance that the patents issued will not be infringed, designed around or invalidated by third parties. Even issued patents may later be found unenforceable or may be modified or revoked in proceedings instituted by third parties before various patent offices or in courts. The degree of future protection for our proprietary rights is uncertain. Only limited protection may be available and may not adequately protect our rights or permit us to gain or keep any competitive advantage. This failure to properly protect the intellectual property rights relating to our product candidates could have a material adverse effect on our financial condition and results of operations.

Composition-of-matter patents on the biological or chemical active pharmaceutical ingredient are generally considered to be the strongest form of intellectual property protection for pharmaceutical products, as such patents provide protection without regard to any method of use. We cannot be certain that the claims in our patent applications covering composition-of-matter of a ny of our product candidates will be considered patentable by the United States Patent and Trademark Office (USPTO) and courts in the United States or by the patent offices and courts in foreign countries, nor can we be certain that the claims in our issue d composition-of-matter patents will not be found invalid or unenforceable if challenged.

Method-of-use patents protect the use of a product for the specified method or for treatment of a particular indication. However, this type of patent does not prevent a competitor from making and marketing a product that is identical to our product for an indication that is outside the scope of the patented method. Moreover, even if competitors do not actively promote their product for our targeted indications, physicians may prescribe these products “off-label.” Although off-label prescriptions may infringe or contribute to the infringement of method-of-use patents, the practice is common and such infringement is difficult to prevent or prosecute.

The patent application process is subject to numerous risks and uncertainties, and there can be no assurance that we or any of our future development partners will be successful in protecting our product candidates by obtaining and defending patents. These risks and uncertainties include the following:

the USPTO and various foreign governmental patent agencies require compliance with a number of procedural, documentary, fee payment and other provisions during the patent process. There are situations in which noncompliance can result in abandonment or lapse of a patent or patent application, resulting in partial or complete loss of patent rights in the relevant jurisdiction. In such an event, competitors might be able to enter the market earlier than would otherwise have been the case;

patent applications may not result in any patents being issued;

patents that may be issued or in-licensed may be challenged, invalidated, modified, revoked, circumvented, found to be unenforceable or otherwise may not provide any competitive advantage;

our competitors, many of whom have substantially greater resources than we do and many of whom have made significant investments in competing technologies, may seek or may have already obtained patents that will limit, interfere with or eliminate our ability to make, use, and sell our potential product candidates;

there may be significant pressure on the U.S. government and international governmental bodies to limit the scope of patent protection both inside and outside the United States for disease treatments that prove successful, as a matter of public policy regarding worldwide health concerns; and

countries other than the United States may have patent laws less favorable to patentees than those upheld by United States courts, allowing foreign competitors a better opportunity to create, develop and market competing product candidates.

In addition, we rely on the protection of our trade secrets and proprietary know-how. Although we have taken steps to protect our trade secrets and unpatented know-how, including entering into confidentiality agreements with third parties, and confidential information and inventions agreements with employees, consultants and advisors, we cannot provide any assurances that all such agreements have been duly executed, and third parties may still obtain this information or may come upon this or similar information independently.

Additionally, if the steps taken to maintain our trade secrets are deemed inadequate, we may have insufficient recourse against third parties for misappropriating our trade secrets. If any of these events occurs or if we otherwise lose protection for our trade secrets or proprietary know-how, the value of this information may be greatly reduced.

We may not be able to protect our intellectual property rights throughout the world.

While we have pending patent applications directed at certain of our product candidates in the United States and other countries, filing, prosecuting and defending patents on our product candidates in all countries throughout the world would be prohibitively expensive, and our intellectual property rights in some countries outside the United States can be less extensive than those in the United States. In addition, the laws of some foreign countries do not protect intellectual property rights to the same extent as federal and state laws in the United States. Consequently, we may not be able to prevent third parties from practicing our inventions in all countries outside the United States, or from selling or importing products made using our inventions in and into the United States or other jurisdictions. Competitors may use our technologies in jurisdictions where we have not obtained patent protection to develop their own products and, further, may export otherwise infringing products to territories where we have patent protection but enforcement is not as strong as that in the United States. These products may compete with our product candidates, and our patents or other intellectual property rights may not be effective or sufficient to prevent them from competing.

Many companies have encountered significant problems in protecting and defending intellectual property rights in foreign jurisdictions. The legal systems of certain countries, particularly certain developing countri es, do not favor the enforcement of patents and other intellectual property protection, particularly those relating to biopharmaceuticals, which could make it difficult for us to stop the infringement of our patents or marketing of competing products in vi olation of our proprietary rights generally. Proceedings to enforce our patent rights in foreign jurisdictions could result in substantial costs and divert our efforts and attention from other aspects of our business, could put our patents at risk of being invalidated or interpreted narrowly and our patent applications at risk of not issuing and could provoke third parties to assert claims against us. We may not prevail in any lawsuits that we initiate, and the damages or other remedies awarded, if any, may not be commercially meaningful. Accordingly, our efforts to enforce our intellectual property rights around the world may be inadequate to obtain a significant commercial advantage from the intellectual property that we develop or license.

Known third party patent rights could delay or otherwise adversely affect our planned development and sale of a new anti-VEGF product candidate.

We are aware of patent rights held by third parties that may cover certain compositions within our new anti-VEGF product candidates. A patent holder has the right to prevent others from making, using, or selling a drug that incorporates the patented compositions while the patent remains in force. While we believe that third party patent rights will not affect our planned development, regulatory clearance, and eventual marketing, commercial production, and sale of an anti-VEGF product candidate, there can be no assurance that this will be the case. In each case, the relevant patent expires before we expect to commercially introduce an anti-VEGF product candidate. In addition, the Hatch-Waxman exemption to U.S. patent law permits all uses of compounds in clinical trials and for other purposes reasonably related to obtaining FDA clearance of drugs that will be sold only after patent expiration, so our use of our product candidates in those FDA-related activities does not infringe any patent holder’s rights. However, were a patent holder to assert its rights against us before expiration of such patent holder’s patent for activities unrelated to FDA clearance, the development and ultimate sale of our anti-VEGF product could be significantly delayed, and we could incur the expense of defending a patent infringement suit and potential liability for damages for periods prior to the patent’s expiration.

Risks Related to Our Financial Results

We recognized an impairment in the carrying value of goodwill booked in connection with the Annapurna transaction. Any impairment of our intangible assets in the future could negatively affect our operating results and financial condition.

We recorded goodwill and intangible assets, consisting of in-process research and development (IPR&D) assets related to Annapurna products in development, upon the acquisition of Annapurna. During the second quarter, we noted a continuing decrease in our stock price that resulted in our market capitalization being less than the carrying value of our net assets and less than our cash and cash equivalents balance as of June 30, 2016. As a result, we are conducting a two-step impairment analysis and, based on the work performed as of the filing date, we recorded a goodwill impairment charge of $49.1 million in our condensed consolidated statements of operations and comprehensive loss for the period ended June 30, 2016.

We will continue to conduct impairment analyses of the IPR&D assets on a regular basis, and we would be required to take impairment charges in the future if any assessments thereof reflect estimated fair values which are less than our recorded values, and such charges could be significant. Any impairment charges with respect to the IPR&D assets could negatively affect our operating results and financial condition.

The purchase price allocation for the Annapurna transaction has not been finalized, and any final adjustment to the valuation could have a material change on what is reported as the fair value assigned to the assets and liabilities .

The final purchase price allocation for the Annapurna transaction depends upon the finalization of asset and liability valuations, among other things. Valuing certain components of the acquisition, primarily intangible assets acquired, deferred taxes and accrued liabilities required us to make significant estimates that may be adjusted in the future; consequently, the fair value of identifiable assets acquired and liabilities assumed are considered preliminary. Final determination of these estimates could result in an adjustment to the preliminary purchase price allocation, with an offsetting adjustment to goodwill. Any resulting change to our condensed consolidated financial statements could be material.

Risks Related to Our Common Stock

The trading price of the shares of our common stock has been and could continue to be highly volatile, and purchasers of our common stock could incur substantial losses.

Our stock price has been and is likely to continue to be volatile. The stock market in general and the market for biotechnology companies in particular have experienced extreme volatility that has often been unrelated to the operating performance of particular companies. The market price for our common stock may be influenced by many factors, including those discussed in this “Risk Factors” section of this Quarterly Report on Form 10-Q and others such as:

our plans regarding development of ANN-001, ANN-002, a new anti-VEGF product candidate or our other product candidates;

our ability to enroll subjects in any clinical trials that we plan in the future;

results of any clinical trials, and the results of trials of our competitors or those of other companies in our market sector;

regulatory developments in the United States and foreign countries;

our ability to obtain regulatory approvals for our product candidates, and delays or failures to obtain such approvals;

failure of any of our product candidates, if approved, to be reimbursed or achieve commercial success;

variations in our financial results or those of companies that are perceived to be similar to us;

changes in the structure of healthcare payment systems, especially in light of current reforms to the U.S. healthcare

system;

announcements by us or our competitors of significant acquisitions, strategic partnerships, joint ventures or capital commitments;

failure to maintain our existing third-party license and supply agreements;

failure by our or our licensors to prosecute, maintain or enforce its intellectual property rights;

any inability to obtain adequate supply of our product candidates or the inability to do so at acceptable prices;

the introduction of new products, services or technologies by our competitors;

announcements of significant acquisitions, strategic partnerships, joint ventures or capital commitments by us or our competitors;

announcements by commercial partners or competitors of new commercial products, clinical progress or the lack thereof, significant contracts, commercial relationships or capital commitments;

the introduction of technological innovations or new therapies that compete with our potential products;

adverse publicity relating to the gene therapy market generally, including with respect to other products and potential products in such markets;

market conditions in the pharmaceutical and biotechnology sectors and issuance of securities analysts’ reports or recommendations;

failure to meet or exceed the expectations of financial or industry analysts;

failure to achieve the perceived benefits of the transaction with Annapurna as rapidly or to the extent anticipated by financial or industry analysts;

sales of our stock by insiders and stockholders;

trading volume of our common stock;

period-to-period fluctuations in our financial results;

general economic, industry and market conditions other events or factors, many of which are beyond our control;

additions or departures of key personnel; and

intellectual property, product liability or other litigation against us.

In addition, in the past, stockholders have initiated class action lawsuits against biotechnology and pharmaceutical companies following periods of volatility in th e market prices of these companies’ stock, and similar litigation has been instituted against us. Such litigation could cause us to incur substantial costs and divert management’s attention and resources, which could have a material adverse effect on our b usiness, financial condition and results of operations.

Our quarterly operating results may fluctuate significantly.

We expect our operating results to be subject to quarterly fluctuations. Our net loss and other operating results will be affected by numerous factors, including:

variations in the level of expenses related to our clinical trial and development programs;

addition or termination of clinical trials;

any intellectual property infringement lawsuit in which we may become involved;

regulatory developments affecting our product candidates;

our execution of any collaborative, licensing or similar arrangements and the timing of payments we may make or receive under these arrangements;

nature and terms of stock-based compensation grants; and

derivative instruments recorded at fair value.

If our quarterly operating results fall below the expectations of investors or securities analysts, the price of our common stock could decline substantially. Furthermore, any quarterly fluctuations in our operating results may, in turn, cause the price of our stock to fluctuate substantially.

If we sell shares of our common stock in future financings or acquisitions, stockholders may experience immediate dilution and, as a result, our stock price may decline.

We may from time to time issue additional shares of common stock at a discount from the current trading price of our common stock. As a result, our stockholders would experience immediate dilution upon the purchase of any shares of our common stock sold at such discount. In addition, as opportunities present themselves, we may enter into financing or similar arrangements in the future, including the issuance of debt securities, preferred stock or common stock. Furthermore, we may issue common stock as consideration in acquisitions. For example, in May 2016, we issued 14,087,246 shares of our common stock to Annapurna’s shareholders as consideration for all of the outstanding shares of Annapurna. If we issue common stock or securities convertible into common stock, our common stockholders would experience additional dilution and, as a result, our stock price may decline.

Our ability to use Annapurna’s net operating loss carryforwards may be limited.

Annapurna has incurred net operating losses in France every year since its inception in 2014, has never generated revenue from product sales, and may never be profitable. To the extent that Annapurna continues to generate taxable losses, unused losses will carry forward to offset future taxable income in France, if any, unless such losses expire. Such losses may expire under certain conditions if, in particular, Annapurna’s activity, assets, revenues or staff change substantially, or if Annapurna becomes a party to certain forms of reorganizations. In any event, Annapurna’s ability to use these losses to offset future income in any given year is limited under current French tax law.

Item 2.

Unregistered Sales of Equity Securities and Use of Proceeds

Unregistered Sales of Equity Securities

On May 11, 2016, in connection with the closing of our transaction with Annapurna, we issued 14,087,246 shares of our common stock (the New Shares) to Annapurna’s shareholders in consideration for all of the outstanding shares of Annapurna’s capital stock. The sale and issuance of the New Shares were not registered under the Securities Act in reliance upon the exemption from registration provided by Section 4(a)(2) of the Securities Act, since, among other things, the sale and issuance of the New Shares did not involve a public offering and were acquired by the Annapurna shareholders not with a view to the distribution thereof. The Annapurna shareholders have certain demand and “piggyback” registration rights under the Securities Act with respect to these shares, subject to certain limitations, pursuant to our Amended and Restated Investor Rights Agreement.

Use of Proceeds

On August 5, 2014, we closed our IPO and issued 6,900,000 shares of our common stock at an initial offering price of $17.00 per share. The offer and sale of all of the shares in the IPO were registered under the Securities Act pursuant to a registration statement on Form S-1, as amended (File Nos. 333-197133 and 333-197739), which was declared effective by the SEC on July 30, 2014. The joint book-running managers for the IPO were Jefferies LLC, Cowen and Company, LLC and Piper Jaffray & Co. The aggregate offering price to the public for the shares sold in the IPO was $117.3 million. We received net proceeds from the IPO of approximately $106.5 million, after deducting underwriting discounts and commissions of approximately $8.2 million and expenses of approximately $2.6 million payable by us. None of the expenses associated with the IPO were paid to directors, officers, persons owning 10% or more of any class of equity securities, or to their associates, or to our affiliates.

We invested the funds received in short-term, interest-bearing investment-grade securities and government securities.

We have discontinued development of AVA-101, and so we will not use approximately $20 million of our net proceeds from the IPO to fund Phase 3 research and development startup activities for our AVA-101 study, as we had described in our final prospectus filed with the SEC on July 31, 2014 pursuant to Rule 424(b) of the Securities Act. Instead, we plan to reallocate such proceeds to fund research and development expenses for other product candidates in our pipeline.

Item 3.

Defaults Upon Senior Securities

None.

Item 4.

Mine Safety Disclosures

Not applicable.

Item 5.

Other Information

On August 4, 2016, our Board of Directors appointed Leone Patterson, our Chief Financial Officer, to also serve as our Principal Accounting Officer. In connection with Ms. Patterson’s appointment, Michael Swartzburg will no longer serve as our Principal Accounting Officer.

Item 6.

Exhibits

See the Exhibit Index on the page immediately preceding the exhibits for a list of exhibits filed as part of this Quarterly Report on Form 10-Q, which Exhibit Index is incorporated herein by reference.

SIGNA TURES

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.

Date: August 09, 2016	ADVERUM BIOTECHNOLOGIES, INC.

	By:	/s/ Paul B. Cleveland
		Paul B. Cleveland
		Chief Executive Officer

EXHIBIT INDEX

EXHIBIT NUMBER		DESCRIPTION

2.2		Amendment No. 1 to Acquisition Agreement, dated as of April 6, 2016, by and among Avalanche Biotechnologies, Inc., Annapurna Therapeutics SAS and the Contributors (filed as Exhibit 2.1 to the Company’s Current Report on Form 8-K filed on April 7, 2016, and incorporated herein by reference).

3.1		Certificate of Amendment to Amended and Restated Certificate of Incorporation of Avalanche Biotechnologies, Inc., filed with the Secretary of State of the State of Delaware on May 11, 2016 (filed as Exhibit 3.1 to the Company’s Current Report on Form 8-K filed on May 12, 2016, and incorporated herein by reference).

3.2		Amended and Restated Bylaws of Adverum Biotechnologies, Inc. (filed as Exhibit 3.2 to the Company’s Current Report on Form 8-K filed on May 12, 2016, and incorporated herein by reference).

4.1		Second Amended and Restated Investor Rights Agreement, dated as of May 11, 2016, by and among Avalanche Biotechnologies, Inc. and certain of its stockholders (filed as Exhibit 4.1 to the Company’s Current Report on Form 8-K filed on May 12, 2016, and incorporated herein by reference).

10.1		Offer Letter, dated June 10, 2016, by and between Adverum Biotechnologies, Inc. and Leone Patterson (filed as Exhibit 10.1 to the Company’s Current Report on Form 8-K filed on June 13, 2016, and incorporated herein by reference).

10.2		Change in Control and Severance Agreement, dated June 10, 2016, by and between Adverum Biotechnologies, Inc. and Leone Patterson (filed as Exhibit 10.2 to the Company’s Current Report on Form 8-K filed on June 13, 2016, and incorporated herein by reference).

10.3‡		Amended and Restated Master Service Agreement by and between Annapurna Therapeutics SAS and Cornell University, effective July 15, 2014.

10.4‡		A1AT Deficiency License Agreement between Annapurna Therapeutics Limited and Cornell University, dated December 15, 2015.

10.5‡		HAE License Agreement between Annapurna Therapeutics Limited and Cornell University, dated December 15, 2015.

10.6‡		Allergy License Agreement between Annapurna Therapeutics Limited and Cornell University, dated December 15, 2015.

10.7‡		License Agreement between Annapurna Therapeutics Limited and REGENXBIO Inc., dated October 20, 2015.

10.8‡		License Agreement between AAVLife and REGENXBIO Inc., dated April 10, 2014.

10.9‡		License Agreement between AAVLife and Inserm Transfert, dated July 4, 2014.

10.10‡		Amendment No. 1 to License Agreement between AAVLife and Inserm Transfert, dated October 5, 2015.

31.1		Certification of Chief Executive Officer, as required Under Rule 13a-14(a) and 15d-14(a) of the Securities Exchange Act of 1934, as amended.

31.2		Certification of Chief Financial Officer, as required Under Rule 13a-14(a) and 15d-14(a) of the Securities Exchange Act of 1934, as amended.

32.1		Certification of Chief Executive Officer and Chief Financial Officer, as required Under Rule 13a-14(b) of the Securities Exchange Act of 1934, as amended, and 18 U.S.C. §1350.

101		The following materials from Registrant’s Quarterly Report on Form 10-Q for the quarter ended June 30, 2016, formatted in eXtensible Business Reporting Language (XBRL) includes: (i) Condensed Consolidated Balance Sheets at June 30, 2016 (unaudited) and December 31, 2015, (ii) Condensed Consolidated Statements of Operations and Comprehensive Loss (unaudited) for the three months ended June 30, 2016 and 2015, (iii) Condensed Consolidated Statements of Cash Flows (unaudited) for the three months ended June 30, 2016 and 2015, and (iv) Notes to the Condensed Consolidated Financial Statements.

‡Portions of the exhibit have been omitted pursuant to a request for confidential treatment. The omitted information has been filed separately with the Securities and Exchange Commission.

Exhibit 10.3

[***] Certain information in this document has been omitted and filed separately with the Securities and Exchange Commission. Confidential treatment has been requested with respect to the omitted portions.

Amended and Restated Master Services Agreement

This Amended and Restated Master Services Agreement (together with its Schedules, this “ Agreement ”) is made effective from July 15 2014 (the “ Effective Date ”) and amends and restates in its entirety that certain Master Services Agreement effective July 15 ^th , 2014 between Annapurna Therapeutics, SAS (formerly AAVLife), a French simplified joint stock company ( societe par actions simplifiee ) (“ Annapurna ”), and Cornell University, for and on behalf of its Joan and Sanford I. Weill Medical College, a New York education corporation (“ Cornell ”). Each of Annapurna and Cornell may be referred to herein as a “ Party ” or, collectively, as the “ Parties .”

The Parties hereby agree that the following provisions shall govern with respect to each set of Services (as defined below):

ARTICLE I

Performance of Services

Section 1.01 Services . Cornell shall render services to Annapurna (collectively, the “ Services ” ), as set forth in Schedule A through D hereto and any additional Schedule(s) executed pursuant to this Agreement (collectively, the “ Schedules ” ). In the event of any conflict between the provisions of a Schedule and the provisions of this Agreement, the provisions of this Agreement shall govern, except to the extent expressly set forth in such Schedule.

All Services will be performed in accordance with the terms of this Agreement. Any change or modification to this Agreement must be made in accordance with Section 9.07 below.

Cornell shall provide the Services (a) at such times and at such places as Annapurna may reasonably request; and (b) within the time period specified in the relevant and mutually agreed to Schedule.

Cornell will designate one of its employees as “ Project Leader ,” who will be available for frequent communications with Annapurna regarding the Services.

Section 1.02 Subcontracting . With Annapurna’s prior written consent, Cornell may subcontract the performance of certain of its obligations under this Agreement to qualified affiliates or Third Parties (as defined below), provided that:

(a) Except as otherwise permitted under this Agreement, Cornell will not transfer Annapurna Materials or use any of its affiliates’ or any Third Party’s facilities or intellectual property in performing the Services, without Annapurna’s prior written consent,

(b) Cornell notifies Annapurna of the proposed subcontractor and identifies the specific Services to be performed by the subcontractor,

(c) the subcontractor performs those Services in a manner consistent with the terms and conditions of this Agreement, and

(d) Cornell remains liable for the performance of the subcontractor.

ARTICLE II

Representations

Cornell represents and warrants to Annapurna that (a) Cornell is under no contractual or other obligation or restriction that is inconsistent with Cornell’s execution or performance of this Agreement. Cornell will not enter into any agreement, either written or oral, that could conflict with Cornell’s responsibilities or obligations under this Agreement; (b) Cornell’s employees, subcontractors and/or consultants providing the Services (“ Cornell Personnel ”) have the proper skill, training and experience to provide the Services; (c) Cornell will be solely responsible for paying Cornell Personnel and providing any employee benefits that they are owed; (d) each of the Cornell Personnel performing Services is subject to confidentiality obligations no less stringent than described in this Agreement; (e) Cornell Personnel are obligated to assign to Cornell all right, title and interest in and to the Deliverables and Cornell Materials and the intellectual property rights therein; (f) Cornell will comply with all laws, regulations and orders applicable to the provision of the Services; in addition, Cornell will comply with the terms of this Agreement;; (g) Cornell’s provision of, and Annapurna’s use of, the Services and the Deliverables (as defined below) in accordance with this Agreement will not, to the best of Cornell’s knowledge, violate any patent, trade secret or other proprietary or intellectual property right of any Third Party; and (h) neither Cornell nor any of the Cornell Personnel performing Services under this Agreement have been debarred, and to the best of Cornell’s knowledge, are not under consideration to be debarred, by the United States Food and Drug Administration (“ FDA ”) or any other governmental authority from working in or providing services to any pharmaceutical or biotechnology company under the Generic Drug Enforcement Act of 1992.

ARTICLE III

Inspections; Records

Section 3.01 Inspections by Annapurna . Annapurna, or a Third Party designated by Annapurna, during Cornell’s regular hours of business, may request reasonable access to Cornell’s facility to perform quality assurance inspections at mutually convenient times, subject to Cornell’s consent, which shall not be unreasonable withheld. Cornell shall reasonably cooperate with such inspectors and shall provide copies of all documents reasonably required by them to properly perform such inspections.

Section 3.02 Inspections by Regulatory Authorities . Cornell shall promptly notify Annapurna of any inspection of its facility conducted by any regulatory authority, including the FDA, that is directly related to the Services. Cornell shall promptly provide copies of all reports, citation, violations, warnings and notices of deficiency received by Cornell in connection with each such inspection.

Section 3.03 Records .

(a) Cornell will maintain all materials, data and documentation obtained or generated by Cornell in the course of providing the Services, including all electronic or computerized records and files (collectively, the “ Records ”), in a secure area protected from destruction.

(b) Cornell shall retain all Records for a period of five (5) years from the termination or expiration of this Agreement, or as otherwise required by applicable law or regulation. Upon written request of Annapurna, all Records will, at Annapurna’s option, either be delivered to Annapurna or to Annapurna’s designee, at Annapurna’s expense.

(c) In no event will Cornell dispose of any such Records without first giving Annapurna sixty (60) days’ prior written notice of its intent to do so. Cornell may, however, retain copies of any Records as are reasonably necessary for regulatory or insurance purposes, subject to Cornell’s obligation of confidentiality.

ARTICLE IV

Compensation

As full consideration for the Services, Annapurna will pay Cornell as set forth in the applicable Schedule.

ARTICLE V

Proprietary Rights

Section 5.01 Materials . All documentation, information and data, as well as all biological, chemical or other materials, controlled by Annapurna and furnished to Cornell in connection with this Agreement and/or the Services (including all samples and all Annapurna’s Confidential Information), and all reports, communications, or analyses provide by Annapurna in connection with the Services (collectively, “ Annapurna Materials ” ), are and shall remain the exclusive property of Annapurna. Cornell shall keep all Annapurna Materials in its custody and control, and Cornell shall deliver to Annapurna any Annapurna Materials upon termination of this Agreement or otherwise upon Annapurna’s request. All documentation, information, data and other materials created, controlled or provided by Cornell in connection with this Agreement and/or the Services (including all samples and all Cornell’s Confidential Information), and all reports, communications, or analyses provided by Cornell in connection with the Services (collectively, “ Cornell Materials ” ;), are and shall remain the exclusive property of Cornell, subject to the rights expressly granted to Annapurna hereunder.. Each of the Annapurna Materials and Cornell Materials are “ Materials ” .

Section 5.02 Disclosure . Any Deliverables or Cornell Materials produced in connection with this Agreement shall be promptly and fully disclosed to Annapurna in accordance with the terms of this Agreement.

Section 5.03 Deliverables . With respect to (a) all Cornell Materials and (b) all information, data, documentation, reports, results and other products of the Services (collectively, the “ Deliverables ” ):

(a) With respect to Deliverables arising from Services delivered to Annapurna for research, development or manufacture of Licensed Products as defined in the relevant license agreement effective December 15, 2015 between Cornell and Annapurna for each of the following Cornell inventions:

[***]

(each a “ License Agreement ” and together, the “ License Agreements ”) the terms of the relevant License Agreement will govern Annapurna’s rights to use such Deliverables.

(b) With respect to Deliverables arising from Services not directed to research, developing or manufacturing Licensed Products, subject to the terms and conditions set forth herein Cornell hereby grants to Annapurna a non-exclusive, worldwide, perpetual, royalty-free, non-transferable (except in accordance with Section 9.05), sub-licensable license to use, copy, disclose, modify and distribute in any manner, all or any part of such Deliverables. Annapurna will promptly inform Cornell of such sublicense(s), and provide a copy of each such sublicense and each amendment made to any sublicense(s) to Cornell. All such sublicenses issued by Annapurna will protect Cornell’s rights in Deliverables, and ensure that sub-licensees are subject to obligations to Cornell similar to obligations described in this Agreement. Any such sublicense granted herein is not further sub-licensable.

Section 5.04 Grant-back License to Cornell for Manufacturing Process Improvements to the Deliverables . Annapurna hereby grants to Cornell, a fully-paid and royalty free, non-exclusive, non-transferable and non-sublicensable, worldwide license to use any inventions or discoveries made by Annapurna which are manufacturing process improvements pertaining specifically to the process for manufacture of AAV vectors which are improvements to or are based upon or incorporate any of the Deliverables provided hereunder (the “ Annapurna Manufacturing Process Improvements ” ), solely for Cornell to provide vector manufacturing process services to any for-profit, non-profit or commercial third party, but not to transfer or sublicense any such Annapurna Manufacturing Process Improvements to any third party Any sublicense granted herein is not further sub-licensable.

ARTICLE VI

Confidential Information

Section 6.01 “ Confidential Information ” means all information disclosed by one Party to the other Party, that is treated as confidential and proprietary by the disclosing Party, including the disclosing Party’s Materials, whether or not labeled “Confidential”, and any information developed by either Party as a result of work in connection with this Agreement, including the Records, the Deliverables and the Materials; provided that “Confidential Information” does not include information that prior or subsequent to the time of such disclosure:

(a) is known to the receiving Party other than in connection with this Agreement and is and was not subject to another confidentiality obligation to the disclosing Party;

(b) is publicly known, or becomes publicly known, under circumstances involving no breach of this Agreement;

(c) is lawfully and in good faith disclosed to the receiving Party other than in connection with this Agreement by a Third Party (as defined in Section 9.12 of this Agreement), who is not subject to a confidentiality obligation to the disclosing Party;

(d) is independently developed by the receiving Party other than in connection with this Agreement and without reference to the other Party’s Confidential Information, as evidenced by its contemporaneous written records; or

(e) is released from confidential status pursuant to a written agreement between the Parties.

For the purposes of clarity Parties agree that results of Services and supporting data published by Cornell and Cornell Project Leader are not Confidential Information.

Section 6.02 Obligations . Both Parties acknowledge that the disclosing Party is and will remain the sole owner of all of such disclosing Party’s Confidential Information. During the term of this Agreement and for a period of five (5) years thereafter, the receiving Party will take all commercially reasonable precautions to protect the confidentiality of the disclosing Party’s Confidential Information, and will not disclose or use any such Confidential Information except, with disclosing Party’s consent.

Section 6.03 Permitted Disclosure . The Parties may disclose Confidential Information to their Personnel who need to know such Confidential Information in order to provide the Services and who are obligated, in writing, to protect the confidentiality of such Confidential Information under terms no less stringent than those set forth in this Article VI. If required by law, the receiving Party may disclose Confidential Information to a governmental authority, provided that, to the extent possible, reasonable advance notice is given to the disclosing Party and the receiving Party reasonably cooperates with the disclosing Party to obtain confidentiality protection of such information. In addition, Annapurna may disclose Cornell’s Confidential Information in exercising its rights under Section 5.03 or 5.04 or to an actual or bona fide potential acquirer, collaborator, contractor, investor or financing source for purposes of an acquisition, investment, financing transaction or the research, development, manufacturing and/or commercialization of products for rare diseases and conditions, including, without limitation, Friedreich ataxia.

Section 6.04 PHI . Both Parties shall hold all individually identifiable Protected Health Information (as is defined under the Health Insurance Portability and Accountability Act of 1996) or comparable information under the law of any other jurisdiction (collectively, “ PHI ” ) that is obtained pursuant to this Agreement strictly confidential in accordance with applicable law and provide all reasonable protections to prevent the unauthorized disclosure of such PHI.

ARTICLE VII

Indemnification and Insurance

Section 7.01 Indemnification of Annapurna . Cornell agrees to defend, indemnify and hold harmless Annapurna and its employees, directors, independent contractors and agents from and against any and all liabilities, obligations, losses, damages, penalties, claims, costs, expenses and disbursements of any kind or nature whatsoever (including attorney fees) (collectively “ Liabilities ” ) in connection with any action, proceeding or claim commenced or threatened by any Third Party (each, a “ Claim ” ), to the extent arising out of Cornell’s performance of the Services or material breach by Cornell of this Agreement, in each case except to the extent such Claim arises from negligence or intentional misconduct of Annapurna or breach of this Agreement by Annapurna.

As a condition of this indemnification obligation, Annapurna must promptly notify Cornell of such Claim, must tender to Cornell (and/or its insurer) full authority to defend or settle such Claim and must reasonably cooperate with the defense of such Claim. Cornell shall not settle such Claim without Annapurna’s prior written consent, such consent not to be unreasonably withheld.

Section 7.02 Indemnification of Cornell . Annapurna agrees to defend, indemnify and hold harmless Cornell and the Cornell Personnel from and against any and all Liabilities in connection with any Claim to the extent relating to or arising out of (a) Annapurna’s negligence or willful misconduct in connection with this Agreement, (b) Annapurna’s breach of this Agreement, or (c) Annapurna’s use or sale of the Annapurna Materials or the Deliverables, in each case except to the extent such Claim arises out of or results from a material breach by Cornell of this Agreement or from the gross negligence or willful misconduct of Cornell or any of the Cornell Personnel, or to the extent provided in Section 7.01.

As a condition of such indemnification obligation, Cornell must promptly notify Annapurna of such Claim, must tender to Annapurna (and/or its insurer) full authority to defend or settle such Claim and must reasonably cooperate with the defense of such Claim. Annapurna shall not settle any such Claim without Cornell’s prior written consent, such consent not to be unreasonably withheld.

ARTICLE VIII

Expiration and Termination

Section 8.01 Term . This Agreement will be in effect starting on the Effective Date and continuing until the second (2nd) anniversary of the Effective Date, as may be extended by mutual agreement; provided that this Agreement shall remain in effect, unless earlier terminated in accordance with Section 8.02, until the termination, or completion of performance of the Services under any Schedule in effect as of the date of expiration of this Agreement.

Section 8.02 Termination . Either Party may terminate this Agreement or any Schedule:

(i) upon thirty (30) days’ prior written notice to the other Party, if such other Party breaches this Agreement and fails to cure the breach during such notice period.

Section 8.03 Effects of Termination . Upon termination or expiration of this Agreement, (a) Cornell will terminate all Services in progress in an orderly manner as soon as practical and in accordance with a schedule agreed to by the Parties, (b) Cornell will deliver to Annapurna any Materials and Deliverables, (c) Annapurna will pay Cornell any monies due and owing Cornell, up to the time of termination or expiration, for Services actually and properly performed (not to exceed the amount set forth in the relevant Schedule) and all authorized expenses actually incurred, (d) receiving Parties will immediately return to the disclosing Parties all of such disclosing Party’s Confidential Information and copies thereof provided to the receiving Party under this Agreement (except for (i) one (1) copy which the receiving Party may retain solely to monitor its surviving obligations of confidentiality under this Agreement and (ii) to exercise its rights that survive expiration or termination of this Agreement), and (e) the provisions of Articles III, V, VI, VII and IX, and this Section 8.03 will survive the expiration or any termination of this Agreement.

ARTICLE IX

Miscellaneous

Section 9.01 Independent Contractor . All Services will be rendered by Cornell as an independent contractor and this Agreement does not create an employer-employee relationship between the Parties. Cornell and Cornell Personnel will have no rights to receive any employee benefits, including health and accident insurance, sick leave or vacation, which are accorded to Annapurna employees. Cornell will not in any way represent itself to be an employee, partner, joint venturer or agent of Annapurna.

Section 9.02 Taxes . Cornell will pay all required taxes on Cornell’s income from Annapurna under this Agreement. Cornell will provide Annapurna with Cornell’s taxpayer identification number.

Section 9.03 Publicity . Except as otherwise stated in this Agreement, neither Party may use the name of the other Party in any advertising or other form of publicity, without the written permission of such other Party; it being noted that the publication of scholarly articles, disclosures required by law, shall not be considered publicity.

Section 9.04 Notices . All notices delivered pursuant to this Agreement must be written and sent to the following addresses (or such other address as is provided in accordance with this Section 9.4) and otherwise in accordance of this section 9.04:

If to Annapurna:

Annapurna Therapeutics

183 Avenue de Choisy

Paris, France 75013

Attn: Amber Salzman

If to Cornell:

Weill Cornell Medicine

1300 York Avenue, Box 89

New York, New York 10065

Attn: Office of Sponsored Research Administration

With a copy to:

Weill Cornell Medicine

1300 York Avenue,

New York, NY 10065

Attn: Dr. Ronald Crystal

All notices will be effective upon receipt and must be delivered: (a) by personal delivery, with receipt acknowledged; (b) by facsimile, by electronic mail in portable document format (.pdf) form, or by any other electronic means intended to preserve the originals graphic and pictorial appearance of a document; (c) by prepaid certified or registered mail, return receipt requested; or (d) by prepaid recognized next business day delivery service.

Section 9.05 Assignment .

(a) This Agreement is a personal services agreement, and the rights and obligations hereunder may not be assigned or transferred by either Party without the other Party’s prior written consent, except as, otherwise, set forth in this Section 9.05.

(b) Annapurna may assign this Agreement without the consent of Cornell, in whole or in part, to an affiliate, or in connection with a merger, consolidation, acquisition or sale or transfer of all or substantially all assets to which this Agreement relates.

Section 9.06 Entire Agreement . This Agreement constitutes the entire agreement of the Parties with regard to its subject matter, and supersedes all previous written or oral representations, agreements and understandings between Annapurna and Cornell with respect to its subject matter.

Section 9.07 Amendment . The provisions of this Agreement may be changed only by a written agreement signed by authorized representatives of both Parties.

Section 9.08 Severability . Each provision in this Agreement is independent and severable from the others, and no provision will be rendered unenforceable as a result of any other provision(s) being held to be invalid or unenforceable in whole or in part. If any provision of this Agreement is determined to be invalid or unenforceable, that provision shall be appropriately limited and revised to the extent permitted by applicable law.

Section 9.09 Governing Law . This Agreement will be construed and interpreted and its performance governed by the laws of the State of New York, without giving effect to the doctrine of conflict of laws.

Section 9.10 Waiver . No waiver of any term, provision or condition of this Agreement (whether by conduct or otherwise) in any one or more instances will be deemed to be or construed as a further or continuing waiver of any such term, provision or condition of this Agreement.

Section 9.11 Counterparts and Signatures . This Agreement may be executed in one or more counterparts, each of which will be deemed an original, and all of which together will be deemed to be one and the same instrument. Signatures to this Agreement transmitted by facsimile transmission, by electronic mail in portable document format (.pdf) form, or by any other electronic means intended to preserve the originals graphic and pictorial appearance of a document, will have the same effect as physical delivery of the paper document bearing the original signatures, and shall be deemed original signatures by both Parties.

Section 9.12 Construction . In construing this Agreement, unless expressly specified otherwise, (a) except where the context otherwise requires, use of any gender includes any other gender, and use of the singular includes the plural and vice versa; (b) any list or examples following the word “including” shall be interpreted without limitation to the generality of the preceding words; (c) all references to “ dollars ” or “ $ ” herein shall mean U.S. Dollars; (d) “ Third Party ” means any person or entity other than a Party or an affiliate of a Party; (e) headings are only for convenience and the headings do not constitute or form a part of this Agreement, and should not be used in the construction of this Agreement; and (f) each Party represents that it has been represented by legal counsel in connection with this Agreement and acknowledges that it has participated in the drafting hereof, and that in interpreting and applying the terms and provisions of this Agreement, no presumption shall apply against the Party that originally drafted such terms and provisions.

[ Signature Page Follows ]

The Parties to this Agreement hereby indicate their acceptance of the terms of this Agreement by the signatures set forth below. Each individual signing on behalf of a corporate entity hereby personally represents and warrants his or her legal authority to legally bind that entity.

Annapurna

By:
	Name:
	Title:

Cornell University , for and on behalf of its Joan and Sanford I. Weill Medical College

By:
	Name:	Amy A. Lane, MBA
	Title:	Assistant Director, Office of Sponsored Research Administration

SIGNATURE PAGE TO MASTER SERVICES AGREEMENT

A [Do not delete - this paragraph generates the automatic page number]

Schedule A

Services and Compensation

This Schedule (“ Schedule ”) is made effective as of July 15, 2014 (the “ Schedule Effective Date ”) between AAVLife, a French simplified joint stock company ( societe par actions simplifee ) (“ AAVLife ”) and Cornell University, for and on behalf of its Joan and Sanford I. Weill Medical College, a New York education corporation (“ Cornell ”), and upon execution will be incorporated into the Master Services Agreement between AAVLife and Cornell dated July 15, 2014 (the “ Agreement ”).

In the event of any conflict between the provisions of this Schedule and the provisions of the Agreement, the provisions of the Agreement shall govern, except to the extent expressly set forth in this Schedule. Capitalized terms defined in the Agreement and not otherwise defined in this Schedule shall have the meanings ascribed to such capitalized terms in the Agreement.

1. Services; Materials.

Cornell will render to AAVLife the Services set forth below. Any Deliverables will be provided to AAVLife in a mutually agreeable format.

[***]

2. Cornell Project Leader.

The project leader for the Services set forth above shall be:


Name:	Dr. Dolan Sondhi
Title:	Associate Research Professor
Phone:	(212)746-5609
Email:	dos2011@med.cornell.edu

3. Compensation.

As full compensation for Services performed pursuant to this Schedule, AAVLife will pay Cornell in accordance with the budget attached hereto as Annex A and incorporated herein by reference.

If paying for travel/expenses: AAVLife will reimburse Cornell for all reasonable travel and other expenses incurred by Cornell in rendering the Services, provided that such expenses are agreed upon in writing in advance, and are confirmed by appropriate written expense statements and other supporting documentation. The total amount paid to Cornell by AAVLife for both compensation and expenses shall not exceed [***] without AAVLife’s prior written consent.

[Schedule ___]

On the last day of each calendar month, Cornell shall invoice AAVLife for Services rendered and expenses incurred during the preceding month. All invoices will be sent to:

AAVLife

183 Avenue de Choisy

Paris, France 75013

Attn: Amber Salzman

and shall reference Schedule A.

AAVLife will remit payment within thirty (30) days of AAVLife’s receipt of invoice to the following address:


Payable To:		Weill Medical College of Cornell University
Tax ID #:		13-1623978
Address:		1305 York Avenue, 13th Floor, New York, NY 10021
Attention:		Dr. Dolan Sondhi
Phone:		(212) 746-5609

4. Completion.

The Parties agree that the estimated time for completion of the Services is [***] from the Schedule Effective Date.

5. Counterparts and Signatures.

This Schedule may be executed in one or more counterparts, each of which will be deemed an original, and all of which together will be deemed to be one and the same instrument. Signatures to this Schedule transmitted by facsimile transmission, by electronic mail in portable document format (.pdf) form, or by any other electronic means intended to preserve the originals graphic and pictorial appearance of a document, will have the same effect as physical delivery of the paper document bearing the original signatures, and shall be deemed original signatures by both Parties.

* * *

[Schedule ___]

The Parties to this Schedule hereby indicate their acceptance of the terms of this Schedule by the signatures set forth below. Each individual signing on behalf of a corporate entity hereby personally represents and warrants his or her legal authority to legally bind that entity.

AAVLife

By:
	Name:
	Title:

Cornell University , for and on behalf of its Joan and Sаnford I. Weill Medical College

By:
	Name:	Michelle A. Lewis, M.S.
	Title:	Director, Office of Sponsored Research Administration

Read and Acknowledged:

By:
	Name:	Dr. Dolan Sondhi

[Schedule ___]

Annex A

Budget

The following amounts are based on completion of Services covered by this Schedule within [***] of the Schedule Effective Date; to be invoiced based on the actual amount of time the relevant individual spends in providing the Services.

[***]

B [Do not delete - this paragraph generates the automatic page number]

Schedule B

Services and Compensation

This Schedule (“ Schedule B ”) is made effective as of Nov 6, 2014 (the “ Schedule B Effective Date ”) between AAVLife, a French simplified joint stock company (societe par actions simplifiее) (“ AAVLife ”) and Cornell University, for and on behalf of its Joan and Sanford I. Weill Medical College, a New York education corporation (“ Cornell ”), and upon execution will be incorporated into the Master Services Agreement between AAVLife and Cornell dated July 15. 2014 (the “ Agreement ”).

1. Services; Materials.

Cornell will render to AAVLife the Services set forth below. Any Deliverables will be provided to AAVLife in a mutually agreeable format.

[***]

2. Cornell Project Leader.

The project leader for the Services set forth above shall be:


Name:	Dr. Dolan Sondhi
Title:	Associate Research Professor
Phone:	(212)746-5609
Email:	dos2011@med.еdu

3. Compensation.

AAVLife will pay to Cornell die lump sum of [***] plus [***] in indirects to cover services performed by Benjamin Van de Graaf, and AAVLife will pay to Cornell the lump sum of [***] plus [***] in indirects for [***] services provided. Cornell shall invoice AAVLife for Services rendered and expenses.

This would be at a cost of [***] in direct costs with indirect costs being[***] so therefore total cost would be [***]

[Schedule ___]

All invoices will be sent to:

AAVLife

183 Avenue de Choisy

Paris, France 75013

Attn: Amber Salzman

and shall reference Schedule B.

AAVLife will remit payment within thirty (30) days of AAVLife’s receipt of invoice to the following address:


Payable To:		Weill Medical College of Cornell University
Tax ID #:		13-1623978
Address:		1300 York Avenue, Box 164. New York, NY 10065
Attention:		Eduardo Betancourt. Department Administrator
Phone:		646-962-5561

4. Completion.

The Parties agree that the estimated time for completion of the Services is [***] from the Schedule Effective Date.

5. Counterparts and Signatures.

* * * * *

[Schedule ___]

AAVLife

By:
	Name:
	Title:

Cornell University , for and on behalf of its Joan and Sаnford I. Weill Medical College

By:
	Name:	Michelle A. Lewis, M.S.
	Title:	Director, Office of Sponsored Research Administration

Read and Acknowledged:

By:
	Name:	Dr. Dolan Sondhi

[Schedule ___]

C [Do not delete - this paragraph generates the automatic page number]

Schedule C

Services and Compensation

This Schedule (“ Schedule C ”) is made effective as of June 8, 2015 (the “ Schedule C Effective Date ”) between AAVLife, a French simplified joint stock company ( societe par actions simplifiee ) (“ AAVLife ”) and Cornell University, for and on behalf of its Joan and Sanford I. Weill Medical College, a New York education corporation (“ Cornell ”), and upon execution will be incorporated into the Master Services Agreement between AAVLife and Cornell dated July 15, 2014 (the “ Agreement ”).

1. Services; Materials.

Cornell will render to AAVLife the Services set forth below. Any Deliverables will be provided to AAVLife in a mutually agreeable format.

[***]

Direct costs: [***] and indirect costs [***]: [***] come to a total of [***]

2. Cornell Project Leader.

The project leader for the Services set forth above shall be:


Name:	Dr. Dolan Sondhi
Title:	Associate Research Professor
Phone:	(212)746-5609
Email:	dos2011@med.cornell.edu

3. Compensation.

AAVLife will pay to Cornell the amount of [***] for these Services. On the last day of each calendar month, Cornell shall invoice AAVLife for Services rendered and expenses incurred during the preceding month.

[Schedule ___]

All invoices will be sent to:

AAVLife

183 Avenue de Choisy

Paris, France 75013

Attn: Amber Salzman

and shall reference Schedule A.

AAVLife will remit payment within thirty (30) days of AAVLife’s receipt of invoice to the following address:


Payable To:		Weill Medical College of Cornell University
Tax ID #:		13-1623978
Address:		1305 York Avenue, 13 ^th Floor, New York, NY 10021
Attention:		Dr. Dolan Sondhi
Phone:		(212) 746-5609

4. Completion.

The Parties agree that the estimated time for completion of the Services is [***] from the Schedule Effective Date.

5. Counterparts and Signatures.

* * *

[Schedule ___]

AAVLife

By:
	Name:	Amber Salzman, PhD
	Title:	CEO

Cornell University , for and on behalf of its Joan and Sаnford I. Weill Medical College

By:
	Name:	Amy A. Lane, MBA
	Title:	Assistant Director, Office of Sponsored Research Administration

Read and Acknowledged:

By:
	Name:	Dr. Dolan Sondhi

[Schedule ___]

D [Do not delete - this paragraph generates the automatic page number]

Schedule D

WorkPlan for the Services, Deliverables, Budget and Compensation

This Schedule (“ Schedule D ”) is made effective as of December 1, 2015 (the “ Schedule D Effective Date ”) between Annapurna Therapeutics, SAS, a French simplified joint stock company ( societe par actions simplifiee ) (“ Annapurna ”) and Cornell University, for and on behalf of its Joan and Sanford I. Weill Medical College, a New York education corporation (“ Cornell ”), and upon execution will be incorporated into the Amended and Restated Master Services Agreement between Annapurna and Cornell effective from July 15, 2014 (the “ Agreement ”). The WorkPlan under this Schedule D shall cover a term of [***] (the “ Term ”). In the event of any conflict between the provisions of this Schedule and the provisions of the Agreement, the provisions of this Schedule shall govern. Capitalized terms defined in the Agreement and not otherwise defined in this Schedule shall have the meanings ascribed to such capitalized terms in the Agreement.

1. Services under the WorkPlan; Deliverables; and Budget.

This Schedule D shall be understood to describe the scope to apply for [***] of the WorkPlan hereunder, with the general parameters for each [***] (other than [***]) to be agreed upon no later than 60 days prior to [***] of this Schedule D. Annapurna shall not under this Agreement be obligated to pay any rates or costs for any Services to be conducted or Deliverables to be provided by Cornell at rates or costs that are not materially consistent with those charged by comparable university research institutions similarly situated. The WorkPlan and Budget shall set forth a detailed and full description of all of the work and services to be included within the Services to be provided hereunder. The Parties shall meet at least once per calendar quarter (or more frequently if requested in writing by Annapurna from time to time), to review and update each WorkPlan and the Budget to reflect the desired scope of work and services requested by Annapurna to be provided by Cornell (each, a “ Quarterly WorkPlan Review ”). For clarity, Annapurna shall not have any obligation to pay for any Services or Deliverables unless such Services or Deliverables were agreed in advance by the Parties in writing as documented as a result of the most recent Quarterly Workplan Review, as reflected in the latest updated WorkPlan and Budget. The failure by the parties to agree on a WorkPlan for any calendar quarter shall not ever give rise to any right of termination by Annapurna. If no agreement can be reached on the WorkPlan as the result of any Quarterly WorkPlan Review, then Annapurna will work in good faith with Cornell to define Services that are in the best interest of Annapurna’s business and within Cornell’s ability to deliver. Services will relate to gene therapy with adeno-associated virus vectors.

Cornell will render to Annapurna the Services set forth pursuant to the WorkPlan for [***] as described below and in accordance with the Budget as described in “ Annex A ” which is attached hereto and is hereby incorporated by reference and only shall be amended by the parties in good faith discussions from time to time. The WorkPlan for [***] shall be as follows, and any Deliverables will be provided to Annapurna in a mutually agreeable format.

[***]

Schedule D-1

2. Cornell Project Leader/Changes to Project Leader or Types of Services.

The Project Leader for the Services and Deliverables under this WorkPlan as set forth above shall be Dr. Ronald G. Crystal. In the event that Dr. Crystal is no longer able to serve as the Cornell Project Leader for the Services under the WorkPlan, Annapurna shall have the right to terminate the Agreement upon thirty (30) days written notice to Cornell. Further, Annapurna shall have the right to terminate the Agreement upon thirty (30) days written notice to Cornell if Cornell is otherwise unable to continue to provide the types of services as outlined in the WorkPlan for [***] in a similar or comparable fashion for [***], or if Cornell or the Cornell Project Leader has failed to cure a material breach in accordance with Section 8.02 of the Agreement.

3. Compensation.

(i)

For [***] and any subsequent [***], unless Annapurna raises financing after the Effective Date as set forth in subparts (ii) or (iii) below, Annapurna will pay to Cornell, in accordance with the details of the Budget as set forth in “ Annex A ”, the total aggregate amount of [***] as fully-inclusive for [***], such total (i) to be fully-inclusive of all direct and indirect costs of all types (such indirect costs at a rate not to exceed [***]), (ii) to be paid upon the delivery of the Deliverables in quarterly installments, (iii) to include all costs for [***], and (iv) to be fully inclusive for all of the Services as set forth herein for [***] and for the delivery of the resulting Deliverables and for the rights granted to Annapurna under the Agreement for the use of all the Deliverables.

(ii)

In the event that Annapurna and its affiliates raise, in total, an additional [***] in financing after the Effective Date of this Schedule D, through investors or Annapurna or one of its affiliates engages in a business transaction such as a merger with or acquisition by a third party wherein the surviving entity in the merger or the parent company or affiliate in the acquisition has at least [***], Annapurna will pay to Cornell, in accordance with the details of the Budget as set forth in “ Annex A ”, the total aggregate amount of [***] as fully-inclusive for [***] and each of the following [***], such total (i) to be fully-inclusive of all direct and indirect costs of all types (such indirect costs at a rate not to exceed [***]) , (ii) to be paid upon the delivery of the Deliverables in quarterly installments, (iii) to include all costs for [***], and (iv) to be fully inclusive for all of the Services as set forth herein for [***] and as agreed to for each of the following [***] and for the delivery of the resulting Deliverables and for the rights granted to Annapurna under the Agreement for the use of all the Deliverables.

(iii)

forth in “Annex A”, the total aggregate amount of [***] as fully-inclusive for [***] and each of the following [***], such total (i) to be fully-inclusive of all direct and indirect costs of all types (such indirect costs at a rate not to exceed [***]) , (ii) to be paid upon the delivery of the Deliverables in quarterly installments, (iii) to include all costs for [***], and (iv) to be fully inclusive for all of the Services as set forth herein for [***] and as agreed to for each of the following [***] and for the delivery of the resulting Deliverables and for the rights granted to Annapurna under the Agreement for the use of all the Deliverables.

For clarity, the amounts to be paid by Annapurna under the Budget as shown in subparts (i), (ii) and (iii) above are not to be taken as cumulative, and instead, only the highest amount that is applicable will apply. In each [***] of the Term prior to the consummation of the financings referred to above, Annapurna will be required to pay not less than the minimum amount required above. Upon consummation of the financing, Annapurna will be required to pay not less than [***] per [***] plus any shortfall from prior [***] so that at the end of the Term Annapurna shall have paid [***].

For example, for [***], if the total of [***] in additional revenue has been raised after the Effective Date during [***] as described in subpart (iii) above, [***] total shall be spent on the following:

[***]

Invoices should be generated quarterly in the amounts specified under the Budget, based on the updated WorkPlan resulting from the most recent Quarterly WorkPlan Review, provided that the WorkPlan is being conducted diligently and in good faith to provide the Deliverables as set forth therein.

On the last day of each calendar quarter, Cornell shall invoice Annapurna for Services rendered and expenses incurred during the preceding quarter, as described in the Agreement and of this Schedule D.

Notwithstanding any provision or interpretation of the Agreement or of this Schedule D to the contrary, in the event that either (i) Cornell is not charging in any material respect competitive market-based prices for each element of the Deliverables or Services under the WorkPlan (as updated by the Quarterly WorkPlan Review), or (ii) Cornell has failed to provide any of the Deliverables or Services in accordance with the requisite timing stated for any Deliverables or Services under the WorkPlan (as updated by the Quarterly WorkPlan Review), or (iii) is not providing Deliverables or Services of the requisite quality, quantity or technical specifications as is set forth in the WorkPlan for the Deliverables or Services (as updated by the Quarterly WorkPlan Review), then, in either case of (i), (ii) or (iii), Annapurna shall have no obligation to make any payments on account of any such specific Deliverables or Services that materially fail to meet any of such parameters Under all circumstances Annapurna shall be obligated to discuss in good faith with Cornell details of such problems to facilitate resolution.

If paying for travel/expenses: Annapurna will reimburse Cornell for all reasonable travel and other expenses incurred by Cornell in rendering the Services, provided that such expenses are agreed upon in writing in advance (with such consent not to be unreasonably withheld) , and are confirmed by appropriate written expense statements and other supporting documentation.

All invoices will be sent to:

Annapurna Therapeutics, SAS

183 Avenue de Choisy

Paris, France 75013

Attn: Amber Salzman

and shall reference Schedule D.

Annapurna will remit payment within thirty (30) days of Annapurna’s receipt of invoice to the following address:


Payable To:		Weill Medical College of Cornell University
Tax ID #:		_13-1623978_
Address:		1305 York Avenue, 13 ^th Floor, New York, NY 10021
Attention:		Dr. Ronald G. Crystal
Phone:		(646) 962-4363

4. Completion.

The Parties agree that the estimated time for completion of [***] under the WorkPlan for the performance of the Services is [***] from the Schedule Effective Date, which, subject to the terms and conditions of this Schedule D and of the Agreement, shall run for a term [***] for a total of [***] as described under the terms and conditions herein.

5. Counterparts and Signatures.

* * *

Annapurna Therapeutics, SAS

By:
	Name:	Amber Salzman, PhD
	Title:	CEO

Cornell University , for and on behalf of its Joan and Sаnford I. Weill Medical College

By:
	Name:	Amy A. Lane, MBA
	Title:	Assistant Director, Office of Sponsored Research Administration

Read and Acknowledged:

By:
	Name:	Dr. Ronald G. Crystal

[***] THIS PAGE HAS BEEN OMITTED AND FILED SEPARATELY WITH THE U.S. SECURITIES AND EXCHANGE COMMISSION PURSUANT TO A REQUEST FOR CONFIDENTIAL TREATMENT.

Exhibit 10.4

LICENSE AGREEMENT

BETWEEN

ANNAPURNA THERAPEUTICS LIMITED

AND

CORNELL UNIVERSITY

FOR

[***]

CTL CONTRACT NO. C2016-11-10546

Exhibit 10.4

TABLE OF CONTENTS

ARTICLE 1. DEFINITIONS		1
ARTICLE 2. GRANTS		4
ARTICLE 3. CONSIDERATION		5
ARTICLE 4. REPORTS, RECORDS AND PAYMENTS		9
ARTICLE 5. INTELLECTUAL PROPERTY MATTERS		12
ARTICLE 6. GOVERNMENTAL MATTERS		13
ARTICLE 7. TERMINATION OF THE AGREEMENT		13
ARTICLE 8. LIMITED WARRANTY AND INDEMNIFICATION		14
ARTICLE 9. USE OF NAMES AND TRADEMARKS		16
ARTICLE 10. MISCELLANEOUS PROVISIONS		17
Appendix A : Original Material		22
Appendix B : Convertible Note		23
Appendix C : Development Report		30
Appendix D : Commercialization Report		34
Appendix E : Business Plan		37

LICENSE AGREEMENT

This agreement ("Agreement") is made by and between Annapurna Therapeutics Limited, an Irish corporation having an address at 9 Upper Pembroke Street, Dublin 2 ("LICENSEE") and Cornell University (“Cornell”) as represented by its Center for Technology Licensing ("CTL") at Cornell University at 395 Pine Tree Road, Ithaca, NY 14850.

This Agreement is effective on the December 15, 2015 (“Effective Date”).

RECITALS

WHEREAS , the inventions disclosed in [***] ("Invention") were made in the course of research at Cornell by Dr. Ronald Crystal and his associates (hereinafter and collectively, the "Inventors") and associated Technology (as defined herein);

WHEREAS , the Inventors are employees of Cornell, and they are obligated to assign all of their right, title and interest in the Invention to Cornell and have done so;

WHEREAS , CTL is the officially authorized unit at Cornell to manage Invention and to grant rights subsisting therein for Cornell;

WHEREAS , Cornell desires that the Invention be developed and utilized to the fullest possible extent so that its benefits can be enjoyed by the general public;

WHEREAS , LICENSEE has provided CTL a brief business plan, a copy of which is attached herein as Appendix E, for the purpose of obtaining certain rights from Cornell for the commercialization of the Inventions under this Agreement; and

WHEREAS , LICENSEE understands that Cornell may publish or otherwise disseminate information concerning the Invention and Technology (as defined below) at any time and that LICENSEE is paying consideration hereunder for its early access to the Invention, the associated intellectual property rights and Technology, not continued secrecy therein.

NOW, THEREFORE , the parties agree:

ARTICLE 1. DEFINITIONS

The terms, as defined herein, shall have the same meanings in both their singular and plural forms.

1.1

(20%) of the outstanding stock, units of membership, or other voting rights entitled to elect directors or officers; but in any country where the local law does not permit foreign equity participation of at least twenty percent (20%), then an "Affiliate" includes any company in which LICENSEE owns or controls or is owned or controlled by, directly or indirectly, the maximum percentage of outstanding stock, units of membership, or voting rights permitted by local law.

1.2

"Sublicense" means an agreement into which LICENSEE enters with a third party that is not an Affiliate for the purpose of (i) granting certain rights; (ii) granting an option to certain rights; or (iii) forbearing the exercise of any rights, granted to LICENSEE under this Agreement after Effective Date. For clarity, a “Sublicense” will not include any such agreement entered into with LICENEE’s successor, assignee or transferee in the context of or as a result of any merger, acquisition, sale or change of control of LICENSEE. "Sublicensee" means a third party with whom LICENSEE enters into a Sublicense.

1.3	"Field" means all fields.

1.4	"Territory" means [***].

1.5

"Term" means, on a country-by-country and Licensed Product-by-Licensed Product basis, the period of time beginning on Effective Date and ending on the later of (i) the date of the twelfth (12 ^th ) anniversary of the first commercial sale of the applicable Licensed Product ; or (ii) the expiration date for orphan drug exclusivity or for other regulatory-based marketing exclusivity rights obtained by LICENSEE or by any Sublicensee expire for the applicable Licensed Product in that country; or (iii) the introduction of any generic, biosimilar or other directly competing product.

1.6	[this paragraph left intentionally blank]

1.7

"Technology" means Materials and technical information and know-how relating to the IND and/or the Invention that Cornell or the Inventor provide or disclose to LICENSEE prior to the Effective Date or during the Term of this Agreement for the purpose of researching, developing or manufacturing Licensed Products, and the first-mover advantage imparted to LICENSEE by those provisions and by the assignment and transfer of the IND to LICENSEE as provided in Paragraph 5.4(d) hereof.

1.8	[This paragraph left intentionally blank.]

1.9	"Licensed Method" means any method that uses Technology, the use of which would constitute, but for the license granted to LICENSEE under this Agreement, misappropriation of Technology.

1.10

"Licensed Product" means any service, composition or product that uses Technology, or that is produced or enabled by Licensed Method, or the manufacture, use, sale, offer for sale, or importation of which would constitute, but for the license granted to LICENSEE under this Agreement, misappropriation of Technology.

1.11

"Net Sales" means the total of the gross invoice prices of Licensed Products sold or leased by LICENSEE, Sublicensee, Affiliate, or any combination thereof, less the sum of the following actual and customary deductions where applicable and separately listed: cash, trade, or quantity discounts; sales, use, tariff, import/export duties or other excise taxes imposed on particular sales (except for value-added and income taxes imposed on the sales of Licensed Product in foreign countries); transportation charges; or credits to customers because of rejections or returns. For purposes of calculating Net Sales, transfers to a Sublicensee or an Affiliate of Licensed Product under this Agreement for (i) end use (but not resale) by the Sublicensee or Affiliate shall be treated as sales by LICENSEE at the invoiced price of LICENSEE in an arm-length transaction, or (ii) resale by a Sublicensee or an Affiliate shall be treated as sales at the list price of the Sublicensee or Affiliate, but in no event shall both (i) and (ii) be considered in cumulative fashion. In addition any “compassionate use” sales or other similar private benefit sales of Licensed Product permitted by law in the relevant country before commercial launch in such country shall not be deemed to be included within Net Sales hereunder for any such Licensed Product that is transferred or sold at or below the cost of goods for producing such Licensed Product and without any profit on the basis of such Net Sales with the proviso that should LICENSEE include overhead or other non-customary costs in such compassionate use sales then such overhead or other non-customary costs will be treated as “Net Sales” and will be subject to the earned royalty provision in Paragraph 3.1(d).

1.12	[This paragraph left intentionally blank.]

1.13

"Materials" shall mean Original Material, Progeny, and Unmodified Derivatives, and Modifications as defined in this Paragraph 1.13. Materials shall not include any other substances created by the LICENSEE through the use of the Materials which are not Modifications, Progeny, or Unmodified Derivatives.

(a) "Original Material" shall mean the material described in Appendix A, as provided to LICENSEE by Inventor under this Agreement.

(b) "Progeny" shall mean unmodified descendant from the Original Material, such as virus from virus, cell from cell, or organism from organism.

(c) "Unmodified Derivatives" shall mean substances created by or at the behest of LICENSEE, a Sublicensee, or an Affiliate, which constitute an unmodified functional subunit or product expressed by the Original Material or its Progeny. Some examples include: subclones of unmodified cell lines, purified or fractionated subsets of the Original Material or Progeny, proteins expressed by DNA/RNA, monoclonal antibodies secreted by a hybridoma cell line, or purified proteins expressed or secreted by a cell line, or cells or other material extracted from a model organism.

(d) "Modifications" shall mean substances created by or at the behest of LICENSEE, a Sublicensee, or an Affiliate which contain or incorporate, in whole or in part, the Original Material, Progeny, and/or Unmodified Derivatives.

1.14	"IND" Shall mean the Investigational New Drug Application No [***].

1.15	“Major Market Region" shall mean any of the following countries or regions: [***].

ARTICLE 2. GRANTS

2.1 License. Subject to the limitations set forth in this Agreement, Cornell hereby grants to LICENSEE, and LICENSEE hereby accepts, a license to use Technology to make and have made, to use and have used, to sell and have sold, to offer for sale, and to import and have imported Licensed Products and to practice Licensed Methods, in the Field within the Territory and during the Term.

The license granted herein is exclusive for Technology.

Upon the expiration of the Term, the license granted herein shall be considered a fully-paid, perpetual and royalty-free license.

LICENSEE may extend the rights granted above to its Affiliates provided that LICENSEE shall first provide to Cornell a written assurance from each of its Affiliates to comply with all applicable terms, conditions and obligations to Cornell.

2.2 Sublicense.

(a) The license granted in Paragraph 2.1 includes the right of LICENSEE to grant Sublicenses (including through multiple tiers) to third parties during the Term.

(b) With respect to Sublicense granted pursuant to Paragraph 2.2(a), LICENSEE shall:

(i) not receive, or agree to receive, anything of value in lieu of cash as consideration from a third party under a Sublicense granted pursuant to Paragraph 2.2(a) without the prior written consent of Cornell, such consent not to be unreasonably refused; provided, however, that in the event that, prior to the execution of any such Sublicense, LICENSEE and Cornell discuss and agree in good faith on the treatment of any such non-cash consideration and how to apply an appropriate percentage of such non-cash consideration or the revenue resulting to LICENSEE attributable to any such non-cash consideration in percentages equal to the percentages as set forth below for Sublicense fees, then the requirement to obtain the consent of Cornell under this subsection 2.2b(i) shall not apply;

(ii) to the extent applicable, include all of the rights of and obligations due to Cornell (and, if applicable, the Sponsor's Rights) and contained in this Agreement;

(iii) promptly provide Cornell with a copy of each Sublicense issued and any amendment made to any Sublicense; and

(iv) collect and guarantee payment of all payments due, directly or indirectly, to Cornell from Sublicensees and summarize and deliver all reports due, directly or indirectly, to Cornell from Sublicensees.

(c) Unless a Sublicense receives written consent from Cornell prior to its issuance by LICENSEE to the Sublicensee and becomes effective, upon termination of this Agreement for any reason, Cornell, at its sole discretion, shall determine whether LICENSEE shall cancel or assign to Cornell said Sublicense.

2.3 Reservation of Rights. Cornell reserves the right to:

(a) use the Invention and Technology solely for its own educational and academic research purposes, but not in the context of any third-party commercially-sponsored research or with or for the benefit of any third-party for-profit or third-party commercial entity;

(b) publish or otherwise disseminate any information about the Invention and Technology at any time; and

(c) allow other nonprofit academic institutions to use the Invention and Technology solely for their own educational and academic research purposes, provided, however, that Cornell shall not grant affirmative rights to such nonprofit institutions to use any Invention or Technology for use in the context of any commercially-sponsored research or with or for the benefit of any for-profit or commercial entity.

ARTICLE 3. CONSIDERATION

3.1 Fees and Royalties. The parties hereto understand that the fees and royalties payable by LICENSEE to Cornell under this Agreement are partial consideration for the license granted herein to LICENSEE under the Technology and for the assignment and transfer of ownership and sponsorship of the IND to LICENSEE pursuant to the terms and conditions of Section 5.4(d). LICENSEE shall pay Cornell:

(a) in recognition of LICENSEE being a new start-up business, a license issue fee and an assignment fee to have the IND assigned and transferred in the amount of [***], of which [***] shall be paid in cash within thirty (30) days of Effective Date, and [***] shall be paid in cash upon the first anniversary of the Effective Date, and the remaining [***] shall be paid in the form of a convertible promissory note attached herein as Appendix B and issued by LICENSEE to Cornell contemporaneously with the execution of this Agreement which shall be convertible into either cash or shares of stock in LICENSEE (at Cornell’s election) upon either the completion of a Series B round of financing by LICENSEE which raises at least at [***] or one year from the Effective Date, whichever shall occur sooner.

(b) license maintenance fees payable on each anniversary of the Effective Date according to the following schedule; provided however, that LICENSEE's obligation to pay this fee shall end on the date when LICENSEE is commercially selling the first Licensed Product in the first Major Market Region of the Territory, and the license maintenance fee payable shall be pro-rated for the number of months remaining in that license year.


Fee payable to Cornell	Date
[***]	1st - 3rd anniversaries of Effective Date
[***]	4th anniversary of Effective Date
[***]	5th anniversary of Effective Date
[***]	6th anniversary of Effective Date and each subsequent anniversary thereafter, until the date of first commercial sale of a Licensed Product in the first Major Market Region


Amount	Date or Event
[***]	Completion of a Phase II clinical trial
[***]	Completion of a Phase III clinical trial
[***]	Marketing approval from the US FDA for first indication
[***]	Marketing approval in each non-US Major Market Region for first indication
[***]	Marketing approval from the US FDA for additional indications
[***]	Marketing approval in each non-US Major Market Region for each additional indication

(d) an earned royalty

(i) of [***] on Net Sales of Licensed Products by LICENSEE and/or its Affiliate(s) from the date of first commercial sale of the applicable Licensed Product in the country of sale until the expiration of the Term, which is not subject to any anti-stacking relief for royalty payments owed by LICENSEE to a third party.

(ii) For clarity, in the event that a royalty obligation would apply to a Licensed Product under this Agreement as well as under any other license agreement entered into between LICENSEE and Cornell or any of its Affiliates, then only one royalty rate shall apply for such Licensed Product and the royalty rates shall not be stacked or otherwise considered cumulative or additive upon any such Licensed Product, and only the highest royalty rate applicable under any such agreement between the Parties shall apply to Net Sales of such Licensed Product.

(e) a percentage of all Sublicense fees received by LICENSEE from its Sublicensees that are not earned royalties according to the following schedule;


Percentage of the Sublicense fees to be shared with and payable to Cornell	Events achieved by LICENSEE related to the timing of the issuance of each Sublicense by LICENSEE
[***]	After filing an IND but before completion of the first human study
[***]	After completion of first human study but prior to submitting a BLA for approval in a Major Market

(f) on each and every Sublicense royalty payment received by LICENSEE from its Sublicensees on sales of Licensed Product by Sublicensee, the higher of (i) the relevant percentage described in Paragraph 3.1(e) of the royalties received by LICENSEE; or the (ii) royalties based on the royalty rate in Paragraph 3.1(d) as applied to Net Sales of Sublicensee; provided, however that, for clarity, in the event that a Sublicense fee or Sublicense royalty would apply to a Licensed Product under this Agreement as well as under any other license agreement entered into between LICENSEE and Cornell or any of its Affiliates, then only one Sublicense fee or Sublicense royalty rate shall apply for such Licensed Product and the Sublicense fees or Sublicense royalties shall not be stacked or otherwise considered cumulative or additive upon any such Licensed Product, and only the highest Sublicense fee or Sublicense royalty rate applicable under any such agreement between the Parties shall apply to Net Sales of such Licensed Product by any Sublicensee.

(g) beginning the calendar year of commercial sales of the first License Product by LICENSEE, its Sublicensee, or an Affiliate and if the total earned royalties paid by LICENSEE under Paragraphs 3.1(d) and (f) to Cornell in any such year cumulatively are less than the amount (“ minimum annual royalty ”) illustrated below:


Year of Commercial Sale	Minimum Annual Royalty
First	[***]
Second	[***]
Third and each year thereafter	[***]

LICENSEE shall pay to Cornell on or before February 28 following the last quarter of such year the difference between amount noted above and the total earned royalty paid by LICENSEE for such year under Paragraphs 3.1(d) and (f); provided, however, that for the year of commercial sales of the first Licensed Product, the amount of minimum annual royalty payable shall be pro-rated for the number of months remaining in that calendar year.

All fees and royalty payments specified in Paragraphs 3.1(a) through 3.1(g) above shall be paid by LICENSEE pursuant to Paragraph 4.3 and shall be delivered by LICENSEE to Cornell as

noted in Paragraph 10.1. At Cornell’s election, all fees and payments specified in Paragraphs 3.1(b), (c), and (g) shall be adjusted to reflect any increase in the Consumer Price Index as announced by the Bureau of Labor Statistics of the United States Department of Labor.

3.2 [paragraph left intentionally blank]

3.3 Due Diligence.

(a) LICENSEE shall, either directly or through its Affiliate(s) or Sublicensee(s):

(i) use commercially reasonable diligent efforts to proceed with the development, and commercialization of at least one Licensed Product in the Field and in at least one Major Market Region;

(ii) raise [***] within [***] of the Effective Date and a further [***] within [***] of the Effective Date.

(iii) raise a total of [***] within [***] of the Effective Date. For clarity, any portion or all of such amount shall be counted toward the [***] total required regardless of whether any of such amounts are obtained from existing investors in LICENSEE as of the Effective Date or from new investors, or whether such amount represents the cash funds existing and available to any successor to LICENSEE in the event of a merger, acquisition, consolidation or other business combination.

(iv) file an Investigational New Drug Application for a first Licensed Product within [***] of the Effective Date.

(v) commence human testing of a Licensed Product within [***] of the Effective Date.

(vi) commence a clinical trial intended to provide safety and efficacy data for a Biologics License Application or its foreign equivalent to the FDA or its foreign equivalent for a Licensed Product within [***] of the Effective Date.

(vii) submit a Biologics License Application for a Licensed Product to the United States FDA within [***] of the Effective Date;

(viii) submit the equivalent of a Biologics License Application to the equivalent of the FDA in a Major Market other than the US for a Licensed Product within [***] of the Effective Date;

(ix) market Licensed Products in each country within the Territory within nine (9)months of receiving regulatory approval to market such Licensed Products in said country;

(x) reasonably fill the market demand for Licensed Products following commencement of marketing at any time during the term of this Agreement; and

(xi) obtain and maintain all necessary governmental approvals and permits for the manufacture, use and sale of Licensed Products.

(b) If LICENSEE fails to perform any of its obligations specified in Paragraphs 3.3(a)(i)-(xi), then Cornell shall issue a Notice of Default to LICENSEE and the Parties shall discuss in good faith the key reasons for any such delay, and where any such delay or failure to meet the goals set forth above is due to any key scientific or technical challenges or complexities, or unexpected development costs, challenges or complexities or safety issues, manufacturing challenges or hurdles, commercial factors, IP issues or any other key aspects of development and commercialization, the Parties shall discuss the matter in good faith and within sixty (60) days of such Notice of Default, LICENSEE shall propose in good faith a modified development plan in order to remedy or overcome any such challenges. If in Cornell’s reasonable judgment, said plan is made in good faith then, Cornell shall accept such modified development plan in good faith; provided, however, that in the event that after LICENSEE initiates such modified development plan, Cornell does not believe that LICENSEE or its Sublicensee is applying its good faith diligent efforts towards the objectives, Cornell shall have the right and option to either terminate this Agreement or change LICENSEE's exclusive license to a nonexclusive license. This right, if exercised by Cornell, supersedes the rights granted in Article 2.

(c) If at any time during the Term, LICENSEE has not begun a genuine product research and development or business development program for a specific Licensed Product in any country within the Territory and Cornell receives one ore more earnest inquiries to license Technology for the commercialization of said specific Licensed Product in said country, Cornell shall refer such offers to LICENSE. If LICENSEE fails to satisfy the market demand in said country of the specific Licensed Product or fails to grant Sublicenses to the inquirers to satisfy such market demand, Cornell may then exclude said country from the Territory and license such rights to one or more third parties.

ARTICLE 4. REPORTS, RECORDS AND PAYMENTS

4.1 Reports.

(a) Development Reports . Beginning six months after Effective Date and ending on the date of first commercial sale of a Licensed Product in the United States, LICENSEE shall report to Cornell progress covering LICENSEE's (and Affiliate's and Sublicensee's) activities and efforts in the development of rights granted to LICENSEE under this Agreement for the preceding six months. The report shall include, but not be limited to, activities and efforts to develop and test all Licensed Products and obtain governmental approvals necessary for marketing the same. Such semi-annual reports shall be due within sixty days (60) of the reporting period and shall use the form as provided herein as Appendix C.

(b) Commercialization Reports. After the first commercial sale of a Licensed Product anywhere in the world, LICENSEE shall submit to Cornell semi-annual reports on or before each February 28 and August 31 of each year. Each report shall cover LICENSEE's (and each Affiliate's and Sublicensee's) most recently completed calendar half and shall show:

(i) the gross sales and Net Sales (as defined in Paragraph 1.11) during the most recently completed calendar quarter and the royalties, in US dollars, payable with respect thereto;

(ii) the number of each type of Licensed Product sold;

(iii) Sublicense fees and royalties received during the most recently completed calendar half in US dollars, payable with respect thereto;

(iv) the method used to calculate the royalties;

(v) the exchange rates used;

(vi) relevant business and corporate development efforts relating to the rights granted in this Agreement.

LICENSEE shall provide the above information using the form as shown in Appendix D and include information on the date of the first commercial sale of each additional Licensed Product or in each additional country.

If no sales of Licensed Products have been made and no Sublicense revenue has been received by LICENSEE during any reporting period, LICENSEE shall so report.

4.2 Records & Audits.

(a) LICENSEE shall keep, and shall require its Affiliates and Sublicensees to keep, accurate and correct records of all Licensed Products manufactured, used, and sold, and Sublicense fees received under this Agreement. Such records shall be retained by LICENSEE for at least five (5) years following a given reporting period.

(b) All records shall be available during normal business hours for inspection at the expense of Cornell by Cornell’s Internal Audit Department or by a Certified Public Accountant selected by Cornell and in compliance with the other terms of this Agreement for the sole purpose of verifying reports and payments or other compliance issues. Such inspector shall not disclose to Cornell any information other than information relating to the accuracy of reports and payments made under this Agreement or other compliance issues. In the event that any such inspection shows an under reporting and underpayment in excess of five percent (5%) for any twelve-month (12-month) period, then LICENSEE shall pay the cost of the audit as well as any additional sum that would have been payable to Cornell had the LICENSEE reported correctly, plus an interest charge at a rate of [***] per year. Such interest shall be calculated from the date the correct payment was due to Cornell up to the date when such payment is actually made by

LICENSEE. For underpayment not in excess of five percent (5%) for any twelve-month (12-month) period, LICENSEE shall pay the difference within thirty (30) days without inspection cost but with interest charge per the provisions of Paragraph 4.3(c).

4.3 Payments .

(a) All fees, reimbursements and royalties due Cornell shall be paid in United States dollars and all checks shall be made payable to "Cornell University", referencing Cornell's taxpayer identification number, 15-0532082, and sent to Cornell according to Paragraph 10.1 (Correspondence). When Licensed Products are sold in currencies other than United States dollars, LICENSEE shall first determine the earned royalty in the currency of the country in which Licensed Products were sold and then convert the amount into equivalent United States funds, using the exchange rate quoted in the Wall Street Journal on the last business day of the applicable reporting period.

(b) Royalty Payments.

(i) Royalties shall accrue when Licensed Products are invoiced, or if not invoiced, when delivered to a third party or Affiliate.

(ii) LICENSEE shall pay earned royalties semi-annually on or before February 28 and August 31 of each calendar year. Each such payment shall be for earned royalties accrued within LICENSEE's most recently completed calendar half.

(iii) Royalties earned on sales occurring or under Sublicense granted pursuant to this Agreement in any country outside the United States shall not be reduced by LICENSEE for any taxes, fees, or other charges imposed by the government of such country on the payment of royalty income, except that all payments made by LICENSEE in fulfillment of Cornell's tax liability in any particular country may be credited against earned royalties or fees due Cornell for that country. LICENSEE shall pay all bank charges resulting from the transfer of such royalty payments.

(iv) If at any time legal restrictions prevent the prompt remittance of part or all royalties by LICENSEE with respect to any country where a Licensed Product is sold or a Sublicense is granted pursuant to this Agreement, LICENSEE shall convert the amount owed to Cornell into US currency and shall pay Cornell directly from its US sources of fund for as long as the legal restrictions apply.

(c) Late Payments. In the event royalty, reimbursement and/or fee payments are not received by Cornell when due, LICENSEE shall pay to Cornell interest charges at a rate of [***] per year. Such interest shall be calculated from the date payment was due until actually received by Cornell.

ARTICLE 5. INTELLECTUAL PROPERTY MATTERS

5.1 [This paragraph left intentionally blank.]

5.2 [This paragraph left intentionally blank.]

5.3 [This paragraph left intentionally blank.]

5.4 Ownership of Technology

(a) Cornell retains ownership of Technology, with the exception of the IND, which shall be assigned to LICENSEE and LICENSEE shall be the sole owner thereof, in accordance with the terms and conditions of Section 5.4(d).

(b) LICENSEE shall make no use of Technology outside the scope of this Agreement and the licenses granted hereunder. Any such use shall be a material breach of this Agreement.

(c) LICENSEE shall notify Cornell in writing promptly after generating any Modification and such notice shall include a reasonably complete description of each Modification and its use. Upon written request from Cornell, LICENSEE shall promptly provide Cornell or Inventors with each Modification, in an amount and form reasonably usable by Inventors under Paragraph 2.3.

(d) Subject to LICENSEE raising no less than [***] in financing, the achievement of such event LICENSEE will confirm by providing financial statements to Cornell, within thirty (30) days from the date of such event, Cornell and Inventor each agree to assign and does hereby assign, conditional upon the achievement of such event, all of their right, title and interest in and to the IND to LICENSEE as the sole owner thereof, and each of Cornell and Inventor will execute the assignment and will transfer the sponsorship of the IND to LICENSEE upon the achievement of such event. Cornell and Inventor shall each cooperate with LICENSEE to execute all documents and take all such actions as are reasonably necessary to perfect the assignment and transfer of ownership of the IND to and in the name of LICENSEE as the sole owner thereof, and to have sponsorship of the IND transferred and assigned to LICENSEE throughout the Territory.

ARTICLE 6. GOVERNMENTAL MATTERS

6.1 Governmental Approval or Registration. If this Agreement or any associated transaction is required by the law of any nation to be either approved or registered with any governmental agency, LICENSEE shall assume all legal obligations to do so. LICENSEE shall notify Cornell if it becomes aware that this Agreement is subject to a United States or foreign government reporting or approval requirement. LICENSEE shall make all necessary filings and pay all costs including fees, penalties, and all other out-of-pocket costs associated with such reporting or approval process.

6.2 Export Control Laws. LICENSEE shall observe all applicable United States and foreign laws with respect to the transfer of Licensed Products and related technical data to foreign countries, including, without limitation, the International Traffic in Arms Regulations and the Export Administration Regulations.

ARTICLE 7. TERMINATION OF THE AGREEMENT

7.1 Termination by Cornell.

(a) If LICENSEE fails to perform or violates any term of this Agreement, then Cornell may give written notice of default ("Notice of Default") to LICENSEE. If LICENSEE fails to cure the default within forty five (45) days of the Notice of Default, Cornell may terminate this Agreement and the license granted herein by a second written notice ("Notice of Termination") to LICENSEE. If a Notice of Termination is sent to LICENSEE, this Agreement shall automatically terminate on the effective date of that notice. Termination shall not relieve LICENSEE of its obligation to pay any fees owed at the time of termination and shall not impair any accrued right of Cornell. Upon termination, LICENSEE shall immediately transfer the IND back to Cornell.

(b) [This paragraph left intentionally blank.]

7.2 Termination by LICENSEE.

(a) LICENSEE shall have the right at any time and for any reason, or merely for convenience, to terminate this Agreement upon a ninety (90) day written notice to Cornell. Said notice shall state LICENSEE’s reason for terminating this Agreement.

(b) Any termination under Paragraph 7.2(a) shall not relieve LICENSEE of any obligation or liability accrued under this Agreement prior to termination or rescind any payment made to Cornell or action by LICENSEE prior to the time termination becomes effective. Termination shall not affect in any manner any rights of Cornell arising under this Agreement prior to termination.

7.3 Survival on Termination. The following Paragraphs and Articles shall survive the termination of this Agreement:

(a)

Article 4 (REPORTS, RECORDS AND PAYMENTS);

(b)

Paragraph 7.4 (Disposition of Licensed Products on Hand);

(c)

Paragraph 8.2 (Indemnification);

(d)

Article 9 (USE OF NAMES AND TRADEMARKS);

(e)

Paragraph 10.2 hereof (Secrecy); and

(f)

Paragraph 10.5 (Failure to Perform).

7.4 Disposition of Licensed Products on Hand. Upon termination of this Agreement, LICENSEE may dispose of all previously made or partially made Licensed Product within a period of one hundred and twenty (120) days of the effective date of such termination provided that the sale of such Licensed Product by LICENSEE, its Sublicensees, or Affiliates shall be subject to the terms of this Agreement, including but not limited to the rendering of reports and payment of royalties required under this Agreement. At the end of such period, LICENSEE shall no longer have rights to use Technology, and LICENSEE will promptly transfer sponsorship of the IND to Cornell.

ARTICLE 8. LIMITED WARRANTY AND INDEMNIFICATION

8.1 Limited Warranty.

(a) Cornell warrants that, without conducting any investigation or any inquiry, it has the lawful right to grant this license, and that, as of the Effective Date, its Center for Technology Licensing, has not received written notice from any third party of any pending or threatened legal action or suit asserting that the use of the Technology as contemplated hereunder for the development and commercialization of any Licensed Product would infringe or misappropriate the patent rights or intellectual property rights of any third party.

(b) T he license granted herein is provided “AS IS” and without WARRANTY OF MERCHANTABILITY or WARRANTY OF FITNESS FOR A PARTICULAR PURPOSE or any other warranty, express or implied. Other than as expressly stated in paragraph (a) above, Cornell makes no representation or warranty that the Licensed Product, Licensed Method or the use of Technology will not infringe any other patent or other proprietary rights.

(c) In no event shall Cornell be liable for any incidental, special or consequential damages resulting from exercise of the license granted herein or the use of the Invention, Licensed Product, Licensed Method or Technology.

(d) Nothing in this Agreement shall be construed as:

(i) a warranty or representation that anything made, used, sold or otherwise disposed of under any license granted in this Agreement is or shall be free from infringement of patents of third parties;

(ii) conferring by implication, estoppel or otherwise any license or rights under any patents of Cornell Research Foundation, Inc. or Cornell other than as defined in this Agreement; or

(iii) an obligation to furnish any know-how not provided in Technology; or

(iv) an obligation to update Technology.

8.2 Indemnification.

(a) LICENSEE shall indemnify, hold harmless and defend Cornell, its officers, employees, and agents; the sponsors of the research that led to the Invention; and the Inventors of the Technology and their employers (the “Cornell Indemnitees”) against any and all claims, suits, losses, damage, costs, fees, and expenses (“Claims”) resulting from or arising out of exercise of this license by LICENSEE or any of its Affiliates or any Sublicense by any Sublicensee. This indemnification shall include, but not be limited to, any product liability Claims, but shall expressly exclude any Claims to the extent attributable to (i) the willful misconduct or gross negligence of any of the Cornell Indemnitees, or (ii) the breach by Cornell or any of the Cornell Indemnitees of any provision of this Agreement or of any representation, warranty or covenant made by Cornell hereunder.

(b) LICENSEE, at its sole cost and expense, shall insure its activities in connection with the work under this Agreement and obtain, keep in force and maintain insurance or an equivalent program of self insurance as follows:

(i) Prior to the first “in human” test of a Licensed Product: comprehensive or commercial general liability insurance (contractual liability included) with limits of at least: (A) each occurrence, one million dollars (US$1,000,000); (B) products/completed operations aggregate, five million dollars (US$5,000,000); (C) personal and advertising injury, one million dollars (US$1,000,000); and (D) general aggregate (commercial form only), five million dollars (US$5,000,000); and

(ii) Commencing upon the first “in human” test of a Licensed Product: comprehensive or commercial general liability insurance (contractual liability included) with limits of at least: (A) each occurrence, five million dollars (US$5,000,000); (B) products/completed operations aggregate, ten million dollars (US$10,000,000); (C) personal and advertising injury, five million dollars (US$5,000,000); and (D) general aggregate (commercial form only), ten million dollars (US$10,000,000); and

(ii) the coverage and limits referred to above shall not in any way limit the liability of LICENSEE.

(c) LICENSEE shall, within ninety (90) days of Effective Date and annually thereafter on anniversary of Effective Date for the life of the Agreement, furnish Cornell with certificates of insurance showing compliance with all requirements. Such certificates shall: (i) provide for seven (7) day advance written notice to Cornell of any modification; (ii) indicate that Cornell has been endorsed as an additionally insured party under the coverage referred to above; and (iii) include a provision that the coverage shall be primary and shall not participate with nor shall be excess over any valid and collectable insurance or program of self-insurance carried or maintained by Cornell.

(d) Cornell shall notify LICENSEE in writing of any claim or suit brought against Cornell in respect of which Cornell intends to invoke the provisions of this Article. LICENSEE shall keep Cornell informed on a current basis of its defense of any claims under this Article.

ARTICLE 9. USE OF NAMES AND TRADEMARKS

9.1 Nothing contained in this Agreement confers any right to use in advertising, publicity, or other promotional activities any name, trade name, trademark, or other designation of either party hereto (including contraction, abbreviation or simulation of any of the foregoing). Unless required by law, the use by LICENSEE of the name, "Cornell University" is prohibited, without the express written consent of Cornell.

9.2 Cornell may disclose to the Inventors the terms and conditions of this Agreement upon their request. If such disclosure is made, Cornell shall request the Inventors not disclose such terms and conditions to others, and all such Inventors shall be required to maintain such information as Confidential Information, subject to the obligations of confidentiality and non-use set forth in Section 10.2.

9.3 Cornell may acknowledge the existence of this Agreement and the extent of the grant in Article 2 to third parties, but Cornell shall not disclose the financial terms of this Agreement to third parties, except where Cornell is required by law or the order of a court of competent jurisdiction to do so.

9.4 LICENSEE may acknowledge or make press releases regarding the existence of this Agreement and the extent of the grant in Article 2 but LICENSEE shall not disclose the financial terms of this Agreement, except where LICENSEE is required by law or by the order of a court of competent jurisdiction to do so, or as is reasonably necessary to be disclosed to any of LICENSEEs existing or bona fide potential investors, acquirers, or collaborators. To the extent LICENSEE makes any forward-looking statement in its press releases mentioning Cornell, LICENSEE shall receive prior consent of Cornell which shall not be unreasonably withheld.

ARTICLE 10. MISCELLANEOUS PROVISIONS

10.1 Correspondence. Any notice, invoice or payment required to be given to either party under this Agreement shall be deemed to have been properly given and effective:

(a) on the date of delivery if delivered in person;

(b) on the date of successful transmission if sent by facsimile,

(d) five (5) days after mailing if mailed by first-class or certified mail, postage paid, to the respective addresses given below, or to such other address as is designated by written notice given to the other party.

If sent to LICENSEE :

Reports and Notices Contact:

Annapurna Therapeutics

3711 Market Street, Suite 800

Philadelphia, PA 19104

Attention: Amber Salzman

Tel: [***]

email: amber@annapurnatx.com

Accounts Payable Contact:

Annapurna Therapeutics

3711 Market Street, Suite 800

Philadelphia, PA 19104

Attention: Amber Salzman

Tel: [***]

email: amber@annapurnatx.com

Intellectual Property Contact:

Annapurna Therapeutics

3711 Market Street, Suite 800

Philadelphia, PA 19104

Attention: Amber Salzman

Tel: [***]

email: amber@annapurnatx.com

If sent to Cornell:

For all correspondence except payments -

Center for Technology Licensing at Cornell University

Attention: Executive Director

395 Pine Tree Road, Suite 310

Ithaca, NY 14850

FAX: 607-254-5454

TEL: 607-254-5236

EMAIL: ctl-contracts@cornell.edu

For all payments -

If sent by mail :

Center for Technology Licensing at Cornell University

PO Box 6899

Ithaca, NY 14851-6899

If remitted by electronic payments via ACH or Fed Wire :


Receiving bank name:	[***]
Bank account no.:	[***]
Bank routing (ABA) no.: SWIFT code:	[*] [*]
Bank account name:	[***]
Bank ACH format code:	[***]
Bank address:	[***]
Additional information:	[*] [*]

An email or FAX copy of the wire transfer transaction receipt shall be sent to Director for Finance and Operations at ctl-contracts@cornell.edu or 607-254-5454, respectively. LICENSEE is responsible for all bank charges of wire transfer of funds for payments. The bank charges shall not be deducted from total amount due to Cornell.

10.2 Secrecy.

(a) "Confidential Information" shall mean information, including Technology, relating to the Invention and disclosed by Cornell to LICENSEE during the term of this Agreement, which if disclosed in writing shall be marked "Confidential", or if first disclosed otherwise, shall within thirty (30) days of such disclosure be reduced to writing by Cornell and sent to LICENSEE:

(b) Licensee shall:

(i) use the Confidential Information for the sole purpose of performing under the terms of this Agreement;

(ii) safeguard Confidential Information against disclosure to others with the same degree of care as it exercises with its own data of a similar nature;

(iii) not disclose Confidential Information to others (except to its employees, agents or consultants who are bound to LICENSEE by a like obligation of confidentiality) without the express written permission of Cornell, except that LICENSEE shall not be prevented from using or disclosing any of the Confidential Information that:

(A)

LICENSEE can demonstrate by written records was previously known to it;

(B)

is now, or becomes in the future, public knowledge other than through acts or omissions of LICENSEE;

(C)

is lawfully obtained by LICENSEE from sources independent of Cornell; or

(D)

is required to be disclosed by law or a court of competent jurisdiction; and

(c) The secrecy obligations of LICENSEE with respect to Confidential Information shall continue for a period ending five (5) years from the termination date of this Agreement.

Cornell shall be considered reasonable for a proposed assignment by LICENSEE to a third party which does not have the necessary resources to commercially develop the Licensed Product, which is in active litigation, arbitration proceedings or other contractual dispute with Cornell at the time of assignment, which is associated with or is controlled by one or more organizations known to be affiliated with countries that are considered by the U.S. government as rogue, which is considered as a business that does not seek to actively make technology available to the public in commerce, which is engaged in “patent troll” activities, or whose association with Cornell will materially negatively impact Cornell’s reputation as an academic institution. In all cases of permitted assignment the assignee must have agreed in writing to assume and comply with LICENSEE’s obligations (or Cornell’s obligations if Cornell is assigning this Agreement) under, and to be bound by, this Agreement.

10.4 No Waiver. No waiver by either party of any breach or default of any covenant or agreement set forth in this Agreement shall be deemed a waiver as to any subsequent and/or similar breach or default.

10.5 Failure to Perform. In the event of a failure of performance due under this Agreement and if it becomes necessary for either party to undertake legal action against the other on account thereof, then the prevailing party shall be entitled to reasonable attorney's fees in addition to costs and necessary disbursements.

10.6 Governing Laws. THIS AGREEMENT SHALL BE INTERPRETED AND CONSTRUED IN ACCORDANCE WITH THE LAWS OF THE STATE OF NEW YORK.

10.7 Force Majeure. A party to this Agreement may be excused from any performance required herein if such performance is rendered impossible or unfeasible due to any catastrophe or other major event beyond its reasonable control, including, without limitation, war, riot, and insurrection; laws, proclamations, edicts, ordinances, or regulations; strikes, lockouts, or other serious labor disputes; and floods, fires, explosions, or other natural disasters. When such events have abated, the non-performing party's obligations herein shall resume.

10.8 Headings. The headings of the several sections are inserted for convenience of reference only and are not intended to be a part of or to affect the meaning or interpretation of this Agreement.

10.9 Entire Agreement. This Agreement embodies the entire understanding of the parties and supersedes all previous communications, representations or understandings, either oral or written, between the parties relating to the subject matter hereof.

10.10 Amendments. No amendment or modification of this Agreement shall be valid or binding on the parties unless made in writing and signed on behalf of each party.

10.11 Severability. In the event that any of the provisions contained in this Agreement is held to be invalid, illegal, or unenforceable in any respect, such invalidity, illegality or unenforceability shall not affect any other provisions of this Agreement, and this Agreement shall be construed as if the invalid, illegal, or unenforceable provisions had never been contained in it.

IN WITNESS WHEREOF , both Cornell and LICENSEE have executed this Agreement, in duplicate originals, by their respective and duly authorized officers on the day and year written.


ANNAPURNA THERAPEUTICS LIMITED	CORNELL UNIVERSITY

By: ________________________	By: ________________________
(Signature of an authorized officer)	(Signature of an authorized officer)
Name: Amber Salzman, PhD	Name: Brian J. Kelly, PhD
Title: CEO	Title: Director, Technology Licensing
Date:________________________	Date:_________________________

Appendix A : Original Material

[***]

Appendix B : Convertible Note

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 SUCH ACT OR AN OPINION OF COUNSEL SATISFACTORY TO THE COMPANY THAT SUCH REGISTRATION IS NOT REQUIRED OR UNLESS SOLD PURSUANT TO RULE 144 OF SUCH ACT.

Annapurna Therapeutics Limited

CONVERTIBLE PROMISSORY NOTE

[***]

December 15, 2015

Annapurna Therapeutics Limited, a registered business in Ireland, (the "Company"), the principal office of which is located at 9 Upper Pembroke Street, Dublin 2 for value received hereby and/or as partial consideration of an intellectual property license (or an amendment to an intellectual property license) entered into by and between the parties on December 15, 2015 (the "Agreement:"), promises to pay, at the time and in the manner set forth below, with interest at the rate set forth below, to the order of Cornell University or its registered assigns (the "Holder"), the principal sum of [***] plus interest or at the election of the Holder, the equivalent value in Stock (as later defined).

The following is a statement of the obligations of the Company and the rights of the Holder of this Note and the conditions to which this Note is subject, and to which the Holder hereof, by the acceptance of this Note, and to which the Company, by the issuance of this Note, mutually agree:

i) Principal and Interest. Interest will accrue on the principal amount of this Note at the rate of eight percent (8%) per annum and compounded annually. The principal balance and all accrued interest thereon are due and payable to Holder in Company's stock or in cash on the Maturity Date and at the sole discretion of the Holder. Maturity Date shall be the sooner of:

(a) The date that is twelve (12) months from the date of this Note; or

(b) when Annapurna Therapeutics SAS, a French société par actions simplifiée (RCS Paris No. 799 863 873) (the “Parent”) receives a bona fide equity investment offers from one or more third parties that, cumulatively with all other equity investments received by the Parent after the date hereof, equals no less than [***] in one or more arm-length transactions. An arm-length transaction shall mean the sale of stock by company to one or more shareholders who, prior to the sale of the Parent’s stock, do not control or are not controlled by, the Parent.

For the purpose of sub-paragraph (a) above, the principal balance and all accrued interest shall be paid in cash within thirty (30) days of the Maturity Date.

For the purpose of sub-paragraph (b) above, the principal balance and all accrued interest shall be paid, at the sole discretion of the Holder, either in cash, in the Parent’s stock, or in any combination thereof. In the event of a payment in the Parent’s stock, the conversion per share value and the stock class shall be the share price, discounted at a rate of [***] , and class of the stock issued by the Parent in the equity financing that results in the cumulative sum cited in (b) above being satisfied (the "Stock").

ii) Events of Default. If any of the events specified in this Section 2 herein below shall occur (individually referred to as an "Event of Default" hereinafter), the Holder of the Note may, so long as such condition exists, declare the entire principal and unpaid accrued interest hereon immediately due and payable, by notice in writing to the Company:

(i) Default in the payment of the principal and unpaid accrued interest of this Note when due and payable if such default is not cured by the Company within twenty (20) days after the Holder has given the Company written notice of such default; or

(ii) The institution by the Company of proceedings to be adjudicated as bankrupt or insolvent, or the consent by it to institution of bankruptcy or insolvency proceedings against it or the filing by it of a petition or answer or consent seeking reorganization or release under the federal Bankruptcy Act, or any other applicable federal or state law, or the consent by it to the filing of any such petition or the appointment of a receiver, liquidator, assignee, trustee or other similar official of the Company, or of any substantial part of its property, or the making by it of an assignment for the benefit of creditors, or the taking of corporate action by the Company in furtherance of any such action; or

(iii) If, within sixty (60) days after the commencement of an action against the Company (and service of process in connection therewith on the Company) seeking any bankruptcy, insolvency, reorganization, liquidation, dissolution or similar relief under any present or future statute, law or regulation, such action shall not have been resolved in favor of the Company or all orders or proceedings thereunder affecting the operations or the business of the Company stayed, or if the stay of any such order or proceeding shall thereafter be set aside, or if, within sixty (60) days after the appointment without the consent or acquiescence of the Company of any trustee, receiver or liquidator of the Company or of all or any substantial part of the properties of the Company, such appointment shall not have been vacated; or

(iv) Any material change in the Business Plan provided to CTL for the purpose of negotiating the Agreement and attached the Agreement as Appendix E, to the extent not approved by CTL.

iii) Prepayment (cash). The Company may, at its option, at any time, prepay, in whole or part, the principal and interest due under this Note.

iv) Conversion . In the event the Holder wishes to convert this Note into fully paid and shares of Stock of the Parent (the "Stock") the following articles shall apply:

(i) Information Exchange and Conversion Procedure. Upon the Holder's expression of an interest to convert this Note, in whole or in part, into shares of Stock under the provision in paragraph 1(b) above, Company shall promptly provide the Holders all relevant information regarding the Parent’s private equity financing details, including but not limited to the share price and class of the Stock. If the Holder, after evaluating the Stock offer elects to convert any portion of this Note into Stock, the Holder shall surrender this Note, duly endorsed, at the principal office of the Company and shall give written notice (Exhibit A) by mail, postage prepaid, to the Company at its principal corporate office, of the election to convert the same pursuant to this Section 5, and shall state therein the portion of the Note to be paid in cash and the portion of the Note to be converted into Stock with the name or names in which the certificate or certificates for shares of the Stock are to be issued. Such conversion shall be deemed to have been made immediately prior to the close of business on the date of such surrender of this Note, and the person or persons entitled to receive the shares of Stock issuable upon such conversion shall be treated for all purposes as the record holder or holders of such shares of Stock as of such date.

(ii) Rights of the Holder . Upon the conversion of this Note into the Stock, the Parent shall issue to the Holder the same type or security, upon the same terms and subject to the same contractual rights, including, without limitation, redemption rights, co-sale rights, registration rights, and the Holder shall execute any documents executed by the investors purchasing the Stock; provided, however, that the Holder will not be required to: (A) indemnify the Parent, the Company or any third party; (B) enter into a voting agreement or otherwise grant a proxy or power of attorney to any individual or entity; or (C) agree to any other provision that is inconsistent with Cornell University’s charter, non-profit status or charitable purpose or in contradiction with Cornell University’s role as a non-profit educational and research institution. Furthermore, in connection with such conversion, the Company shall grant to the Holder in writing the following participation rights:

“ Participation Rights . If the Company proposes to sell any equity securities or securities that are convertible into equity securities of the Company, to investors in a financing (excluding any strategic, business partnership or similar transaction), then Cornell University and/or its Assignee (as defined below) will have the right to purchase up to that portion of the securities issued in each offering that equals Cornell University’s then-current, fully diluted percentage ownership of the Company on the same terms and conditions as are offered to the others in each such financing. The Company shall provide Cornell University, and any Assignee of which the Company has notice, with thirty (30) days’ advance written notice of each such financing, including reasonable detail regarding the terms and purchasers in the financing. The term “Assignee” means (a) any entity that is controlled by Cornell University, or (b) any entity to which Cornell University’s participation rights under this Section have been assigned either by Cornell University or another entity.” These rights will terminate immediately prior to an initial public offering or sale of the Company. Cornell University agrees to work with the Company to conform these participation rights to applicable law and any existing agreements that the

Company may have with other investors, so as to ensure that Cornell University's participation rights are neither more nor less favorable than those of the Company's other similarly situated investors.

(iii) Delivery of Certificates. As promptly as practicable after the conversion of this Note, the Parent at its expense will issue and deliver to the Holder of this Note a certificate or certificates for the number of full shares of the Stock issuable upon such conversion (bearing such legends as are required by applicable state and federal securities laws in the opinion of counsel to the Parent), together with any other securities and property to which the Holder is entitled upon such conversion under the terms of this Note, including a check payable to the Holder for any cash amounts payable due to the election of the Holder or of residual value as described in (iii) below.

(iv) Fractional Shares; Effect of Conversion. No fractional shares of the Stock shall be issued upon conversion of this Note. In lieu of the Parent issuing any fractional shares to the Holder upon the conversion of this Note, the Company shall pay to the Holder the amount of outstanding principal that is not so converted. Upon conversion and/or payout in cash of the entire principal balance of this Note, the Company shall be forever released from all its obligations and liabilities under this Note, except that the Company shall be obligated to pay the Holder, within ten (10) days after the date of such conversion, any interest accrued and unpaid or unconverted to and including the date of such conversion, and no more.

6. Notices of Record Date, etc. In the event of:

(i) Any taking by the Company of a record of the holders of any class of securities of the Company for the purpose of determining the holders thereof who are entitled to receive any dividend (other than a cash dividend payable out of earned surplus at the same rate as that of the last such cash dividend theretofore paid) or other distribution, or any right to subscribe for, purchase or otherwise acquire any shares of stock of any class or any other securities or property, or to receive any other right; or

(ii) Any capital reorganization of the Company, any reclassification or recapitalization of the capital stock of the Company or any transfer of all or substantially all of the assets of the Company to any other person or any consolidation or merger involving the Company; or

(iii) Any voluntary or involuntary dissolution, liquidation or winding ‑up of the Company, the Company will mail to the holder of this Note at least ten (10) days prior to the earliest date specified therein, a notice specifying:

(a) The date on which any such record is to be taken for the purpose of such dividend, distribution or right, and the amount and character of such dividend, distribution or right; and

(b) The date on which any such reorganization, reclassification, transfer, consolidation, merger, dissolution, liquidation or winding ‑up is expected to become effective and the record date for determining stockholders entitled to vote thereon.

7. Reservation of Stock Issuable Upon Conversion. The Parent shall at all times reserve and keep available out of its authorized but unissued shares of the proper class of the Stock, solely for the purpose of effecting the conversion of the Note, such number of its shares of the Stock as shall from time to time be sufficient to effect the conversion of the Note; and if at any time the number of authorized but unissued shares of the proper class of the Stock shall not be sufficient to effect the conversion of the entire outstanding principal amount of the Note, in addition to such other remedies as shall be available to the holder of this Note, the Parent will use its best efforts to take such corporate action as may, in the opinion of its counsel, be necessary to increase its authorized but unissued shares of the proper class of the Stock to such number of shares as shall be sufficient for such purposes. The Company shall cause the Parent to take all actions required of the Parent pursuant to this Note.

8. Assignment. The rights and obligations of the Company are binding and personal and may only be assigned or transferred with the written consent by the Holder, which consent shall not be unreasonably withheld. The rights and obligations of the Holder of this Note shall be binding and the benefit be inured, at the discretion of the Holder and in whole or in part, to its successors, assigns, heirs, administrators and transferees.

9. Waiver and Amendment. Any provision of this Note may be amended, waived or modified only upon the written consent of the Company and the Holder of this Note.

10. Transfer of this Note or Securities Issuable on Conversion Hereof. With respect to any offer, sale or other disposition of this Notes or securities into which such Note may be converted, the Holder will give written notice to the Company prior thereto.

11. Treatment of Note. To the extent permitted by generally accepted accounting principles, the Company will treat, account and report the Note as debt and not equity for accounting purposes and with respect to any returns filed with federal, state or local tax authorities.

set forth herein. Any party hereto may by notice so given change its address for future notice hereunder. Notice shall conclusively be deemed to have been given when personally delivered or when deposited in the mail or telegraphed in the manner set forth above and shall be deemed to have been received when delivered.

13. No Stockholder Rights. Unless an election under the provision in sub-paragraph 1(b) has been made by the Holder according to paragraph 5, nothing contained in this Note shall be construed as conferring upon the Holder or any other person the right to vote or to consent or to receive notice as a stockholder in respect of meetings of stockholders for the election of directors of the Parent or any other matters or any rights whatsoever as a stockholder of the Parent; and no dividends shall be payable or accrued in respect of this Note.

14. Governing law. This Agreement shall be governed by and construed in accordance with the laws of the State of New York, excluding that body of law relating to conflict of laws.

15. Heading; References. All headings used herein are used for convenience only and shall not be used to construe or interpret this Note. Except where otherwise indicated, all returns herein to Sections refer to Sections hereof.

IN WITNESS WHEREOF, the Company has caused this Note be issued this fifteenth day of December, 2015.


Annapurna Therapeutics Limited

By:

Its:


Name of Holder:		Cornell University
Address:		c/o Center for Technology Licensing at Cornell University
		395 Pine Tree Road, Suite 310
		Ithaca, New York 14850

Exhibit A

NOTICE OF CONVERSION

(To Be Signed Only Upon Conversion of Note)

TO: Annapurna Therapeutics Limited

The undersigned, the holder of the foregoing Note, hereby surrenders such Note for conversion into __________ shares of _ (class) ______________ Stock to the extent the amount of $____________ unpaid principal amount of such Note, and requests that the certificates for such shares be issued in the name of, and delivered to, __________________________ , whose address is ____________________________.

Dated:
			(Signature must conform in all respects to name of holder as specified on the face of the Note)

			(Address)

Appendix C : Development Report

Company Name

CTL Agreement No

Your Reference No

Reporting Period ( mm / dd / yyyy )

From ______ / ______ / ______ Through _____ / ______ / _____

Expected Date of first sale of

Licensed Product(s)

( mm / dd / yyyy ) ______ / ______ / ______

Please Check One

Your Company Has: o less than 500 employees worldwide o 500 or more employees worldwide

For the reporting period prescribed in the agreement, please provide detailed answers to the questions listed below. Please attach a separate report to this sheet if necessary.

1. Listing of milestones / performance requirements accomplished during the reporting period

Done

Completed

Date

In Progress

Anticipated

Date

Not Done

Anticipated

Date


2. List of Products being developed under this agreement
Product Name	Brief Description	Status
Product Name	Brief Description	Status
Product Name	Brief Description	Status
Product Name	Brief Description	Status
Product Name	Brief Description	Status

3. Total expenditure spent in the reporting period (under this agreement)

4.Sublicense Activity (if applicable)
List of Sublicenses granted during reporting period			List of sublicenses terminated during reporting period





Total Number of active sublicenses during reporting period

Information reported below will only be used in an aggregated manner. Information related to individual licensee will not be released.

5. Jobs and Payroll Information
Number of Full Time Employee equivalents currently employed by company (do not count consultants or contractors hired as independent agents)
Total current company payroll for preceding 12 months

6. Financial Information
Amount of equity investment received :
a)For preceding 12 months
b)Cumulative total
Amount of investment received using other financial instrument to date excluding equity investment above (e.g. loan, warrant, convertible note etc.)
a) For preceding 12 months
b) Cumulative total
Amount of grants and awards received to date. (e.g. Federal grants, Small business, Foundation grants, Competition awards) Please list source, amount and years if applicable.
a) For preceding 12 months




b) Cumulative total




Estimated market value (private) or market capitalization (public) of company

Report Prepared & Approved By

Name ( Please Print )

Title

Signature

Date ( mm / dd / yyyy )

_______ / _______ / ___________

Please submit completed report either via mail or email at address below:

Center for Technology Licensing

At Cornell University

395 Pine Tree Rd., Suite 310

Ithaca, NY 14850

ctl-contracts@cornell.edu

Appendix D: Commercialization Report

Company Name

CTL Agreement No

Your Reference No

Reporting Period ( mm / dd / yyyy )

From _______ / _______ / _____________ Through _______ / _______ / ______________

Date of first sale of

Licensed Product(s)

( mm / dd / yyyy ) ________ / ________ / _____________

Please list all trade names for product(s) incorporating licensed rights whether or not you had sales during this reporting period.
Product Name		Licensed Invention or Patent Rights (No.) used if known or Docket No	Country	Number of Units Sold	Gross Sales	Net Sales ( A )		Royalty Rate ¹ ( B )	Total Royalties ( A * B )









	1 Please refer to the license agreement for: · applicable royalty rate, please provide as decimal; · how Net Sales should be calculated; · applicable share of sublicense fees; · application of minimum royalty rate · If sales were in a currency other than United States Dollars, please specify exchange rate used 2 Subtract minimum royalty already paid from royalty subtotal for Total Royalty Owed						Royalty Subtotal
							Minimum Royalty already paid*
							Total Royalty Owed ²
							Total Sublicense Fees* (if applicable)
							Total Payment

Sublicense Activity (if applicable)
List of sublicenses granted during the reporting period			List of sublicenses terminated or expired during the reporting period





Total Number of active sublicenses during reporting period

List of Products being developed under this agreement
Product Name	Brief Description	Status
Product Name	Brief Description	Status
Product Name	Brief Description	Status
Product Name	Brief Description	Status
Product Name	Brief Description	Status

List of Licensed Product(s) Not Manufactured in the US
Product Name
Product Name
Product Name
Product Name

Jobs and Payroll Information
Number of Full Time Employee equivalents currently employed by company (do not count consultants or contractors hired as independent agents)
Total current company payroll for preceding 12 months


Financial Information
Amount of equity investment received :
c)For preceding 12 months
d)Cumulative total
Amount of investment received using other financial instrument to date excluding equity investment above (e.g. loan, warrant, convertible note etc.)
a) For preceding 12 months
c) Cumulative total
Amount of grants and awards received to date. (e.g. Federal Agency, Small business, NSF grants) Please list source, amount and years if applicable.
a) For preceding 12 months



b) Cumulative total



Estimated market value of company (best guess)

Report Prepared & Approved By

Name ( Please Print )

Title

Signature

Date ( mm / dd / yyyy )

_________ / _________ / ______________

Appendix E: Business Plan

[***]

THE REMAINDER OF THIS PAGE AND THE FOLLOWING 40 PAGES HAVE BEEN OMITTED AND FILED SEPARATELY WITH THE U.S. SECURITIES AND EXCHANGE COMMISSION PURSUANT TO A REQUEST FOR CONFIDENTIAL TREATMENT.

Exhibit 10.5

LICENSE AGREEMENT

BETWEEN

ANNAPURNA THERAPEUTICS LIMITED

AND

CORNELL UNIVERSITY

FOR

[***]

CTL CONTRACT NO. C2016-11-10547

TABLE OF CONTENTS

RECITALS		1
ARTICLE 1.	DEFINITIONS	1
ARTICLE 2.	GRANTS	4
ARTICLE 3.	CONSIDERATION	6
ARTICLE 4.	REPORTS, RECORDS AND PAYMENTS	10
ARTICLE 5.	INTELLECTUAL PROPERTY MATTERS	12
ARTICLE 6.	GOVERNMENTAL MATTERS	14
ARTICLE 7.	TERMINATION OF THE AGREEMENT	15
ARTICLE 8.	LIMITED WARRANTY AND INDEMNIFICATION	16
ARTICLE 9.	USE OF NAMES AND TRADEMARKS	18
ARTICLE 10.	MISCELLANEOUS PROVISIONS	18
Appendix A:	Original Material	23
Appendix B:	Convertible Note	24
Appendix C:	Development Report	31
Appendix D:	Commercialization Report	34
Appendix E:	Business Plan	37

LICENSE AGREEMENT

This Agreement is effective on December 15, 2015 (“Effective Date”).

RECITALS

WHEREAS , the Inventors are employees of Cornell, and they are obligated to assign all of their right, title and interest in the Invention to Cornell and have done so;

WHEREAS , CTL is the officially authorized unit at Cornell to manage Invention and to grant rights subsisting therein for Cornell;

WHEREAS , Cornell desires that the Invention be developed and utilized to the fullest possible extent so that its benefits can be enjoyed by the general public;

NOW, THEREFORE , the parties agree:

ARTICLE 1. DEFINITIONS

The terms, as defined herein, shall have the same meanings in both their singular and plural forms.

1.1

"Affiliate" means any corporation or other business entity in which LICENSEE owns or controls, directly or indirectly, at least twenty percent (20%) of the outstanding stock, units of membership, or other voting rights entitled to elect directors or officers, or in which LICENSEE is owned or controlled directly or indirectly by at least twenty percent (20%) of the outstanding stock, units of membership, or other voting rights entitled to elect directors or officers; but in any country where the local law does not permit foreign

equity participation of at least twenty percent (20%), then an "Affiliate" includes any company in which LICENSEE owns or controls or is owned or controlled by, directly or indirectly, the maximum percentage of outstanding stock, units of membership, or voting rights permitted by local law.

1.2

1.3	"Field" means all fields.

1.4	"Territory" means [***].

1.5

"Term" means, on a country-by-country and Licensed Product-by-Licensed Product basis, the period of time beginning on Effective Date and ending on the later of (i) the expiration date of the last to expire Valid Claim within the Patent Rights which covers the manufacture, use or sale of the Licensed Product in the country of sale; or (ii) the expiration date for orphan drug exclusivity or for other regulatory exclusivity rights obtained by LICENSEE or by any Sublicensee expire for the Licensed Product in that country; or (iii) the introduction of any generic, biosimilar or other directly competing product.

1.6

"Patent Rights" means Cornell’s right in any of the following: the US patent application (serial number [***], titled [***]), disclosing and claiming the Invention, filed by Inventors and assigned to Cornell and applications which claim priority thereto, and continuing applications thereof including divisions, substitutions, and continuations-in-part (but only to extent the claims thereof are enabled by disclosure of the parent application); any patents issuing on said applications including reissues, reexaminations and extensions; and any corresponding foreign applications or patents, existing anywhere in the world.

1.7

"Technology" means Materials and technical information relating to any of the Inventions that Cornell or the Inventor provide or disclose to LICENSEE prior to the Effective Date or during the Term of this Agreement for the purpose of researching, developing or manufacturing Licensed Products, and the first-mover advantage imparted to LICENSEE by those provisions to LICENSEE.

1.8	[This paragraph left intentionally blank.]

1.9

"Licensed Method" means any method that uses Technology, or is claimed by a Valid Claim within the Patent Rights the use of which would constitute, but for the license granted to LICENSEE under this Agreement, misappropriation of Technology or an infringement, an inducement to infringe or contributory infringement, of any pending or issued Valid Claim within Patent Rights.

1.10

"Licensed Product" means any service, composition or product that uses Technology, or is claimed by a Valid Claim within the Patent Rights, or that is produced or enabled by Licensed Method, or the manufacture, use, sale, offer for sale, or importation of which would constitute, but for the license granted to LICENSEE under this Agreement, misappropriation of Technology or an infringement, an inducement to infringe or contributory infringement, of any pending or issued Valid Claim within the Patent Rights.

1.11

1.12

“Patent Costs” means all reasonable and documented expenses for the preparation, filing, prosecution, and maintenance of all United States and foreign patents included in Patent Rights. Patent Costs shall also include reasonable and documented out-of-pocket expenses for patentability opinions, inventorship review and determination, preparation and prosecution of patent application, re-examination, re-issue, interference, opposition activities related to patents or applications in Patent Rights.

1.13

(a) "Original Material" shall mean the material described in Appendix A, as provided to LICENSEE by Inventor under this Agreement.

(b) "Progeny" shall mean unmodified descendant from the Original Material, such as virus from virus, cell from cell, or organism from organism.

1.14	"Major Market Region" shall mean any of the following countries or regions: [***].

1.15

“Valid Claim” shall mean in the applicable country any claim of: (a) a pending application within the Patent Rights which has not been pending for more than seven (7) years from the earliest priority date claimed; and/or (b) an issued and unexpired patent included in the Patent Rights that has not been abandoned, lapsed, disclaimed, or held unenforceable, unpatentable or invalid by a decision of a court or tribunal of competent jurisdiction, that is unappealable or unappealed within the time allowed for appeal.

ARTICLE 2. GRANTS

2.1 License. Subject to Article 5.1 ("patent costs reimbursement obligations") and to the limitations set forth in this Agreement, Cornell hereby grants to LICENSEE, and LICENSEE hereby accepts, an exclusive license under Patent Rights to make and have made, to use and have used, to sell and have sold, to offer for sale, and to import and have imported Licensed Products and to practice Licensed Methods and to use Technology, in the Field within the Territory and during the Term.

The license granted herein is exclusive for Patent Rights and is non-exclusive for Technology. Cornell hereby undertakes and covenants not to grant any license with respect to Technology to any third party to use any of the Technology within the Field during the Term. Upon the expiration of the Term, the license granted herein shall be considered a fully-paid, perpetual and royalty-free license.

2.2 Sublicense.

(a) The license granted in Paragraph 2.1 includes the right of LICENSEE to grant Sublicenses (including through multiple tiers) to third parties during the Term.

(b) With respect to Sublicense granted pursuant to Paragraph 2.2(a), LICENSEE shall:

(ii) to the extent applicable, include all of the rights of and obligations due to Cornell (and, if applicable, the Sponsor's Rights) and contained in this Agreement;

(iii) promptly provide Cornell with a copy of each Sublicense issued and any amendment made to any Sublicense; and

2.3 Reservation of Rights. Cornell reserves the right to:

(a) use the Invention, Technology and Patent Rights solely for its own educational and academic research purposes, but not in the context of any third-party commercially-sponsored research or with or for the benefit of any third-party for-profit or third-party commercial entity;

(b) publish or otherwise disseminate any information about the Invention and Technology at any time subject to the applicable publication provisions under the related Sponsored Research Agreement referenced in Paragraph 3.4; and

(c) allow other nonprofit academic institutions to use Invention, Technology and Patent Rights solely for their own educational and academic research purposes, provided, however, that Cornell shall not grant affirmative rights to such nonprofit institutions to use any Invention, Technology or Patent Rights for use in the context of any commercially-sponsored research or with or for the benefit of any for-profit or commercial entity.

ARTICLE 3. CONSIDERATION

(a) in recognition of LICENSEE being a new start-up business, a license issue fee of [***], of which [***] shall be paid in cash within thirty (30) days of Effective Date and [***] shall be paid in the form of a convertible promissory note attached herein as Appendix B and issued by LICENSEE to Cornell contemporaneously with the execution of this Agreement which shall be convertible into cash or shares of stock in LICENSEE upon either the completion of a Series B round of financing by LICENSEE which raises at least at [***] or one year from the Effective Date, whichever shall occur sooner.

(b) license maintenance fees payable on each anniversary of the Effective Date according to the following schedule; provided however, that LICENSEE's obligation to pay this fee shall end on the date when LICENSEE is commercially selling a Licensed Product in the first country of the Territory, and the license maintenance fee payable shall be pro-rated for the number of months remaining in that license year.


Fee payable to Cornell	Date
[***]	1st - 3rd anniversaries of Effective Date
[***]	4th anniversary of Effective Date
[***]	5th anniversary of Effective Date
[***]	6th anniversary of Effective Date and each subsequent anniversary thereafter, until the date of first commercial sale of a Licensed Product in the first country of sale


Amount	Date or Event
[***]	Filing of an IND
[***]	Completion of a Phase II clinical trial
[***]	Completion of a Phase III clinical trial
[***]	Marketing approval from the US FDA for first indication
[***]	Marketing approval in each non-US Major Market Region for first indication
[***]	Marketing approval from the US FDA for additional indications
[***]	Marketing approval in each non-US Major Market Region for each additional indication

(d) an earned royalty

(i) of [***] on Net Sales of Licensed Products by LICENSEE and/or its Affiliate(s) in countries where the manufacture, use or sale of the Licensed Product is covered by a Valid Claim within the Patent Rights that exists in the country of sale and at the time of sale, subject to the anti-stacking provisions set forth in sub-paragraph (iii) below but provided, however, that in no event shall the amount payable to Cornell under this sub-paragraph 3.1(d)(i) be less than [***] of Net Sales.

(ii) of [***] on Net Sales of Licensed Products by LICENSEE and/or its Affiliate(s) in countries where a Valid Claim within the Patent Rights which covers the manufacture, use or sale of the Licensed Product does not exist at the time of sale, until the expiration of the Term, which is not subject to the anti-stacking provisions set forth in sub-paragraph (iii) below.

(iii) In the event LICENSEE is required to pay royalties to one or more third parties for patent rights necessary to manufacture, use or sell any Licensed Products, and the total royalties payable by LICENSEE would exceed [***] of Net Sales, then LICENSEE may deduct [***] from the earned royalties payable to Cornell for every [***] LICENSEE actually pays to said third parties of the amount LICENSEE pays above the [***] of Net Sales, but the said deduction shall not be applicable once the royalties paid to Cornell are lowered to [***] of Net Sales as described above in 3.1(d)(i).

(iv) For clarity, in the event that a royalty obligation would apply to a Licensed Product under this Agreement as well as under any other license agreement entered into between LICENSEE and Cornell or any of its Affiliates, then only one royalty rate shall apply for such Licensed Product and the royalty rates shall not be stacked or otherwise considered cumulative or additive upon any such Licensed Product, and only the highest royalty rate applicable under any such agreement between the Parties shall apply to Net Sales of such Licensed Product.

(e) a percentage of all Sublicense fees received by LICENSEE from its Sublicensees that are not earned royalties according to the following schedule;


Percentage of the Sublicense fees to be shared with and payable to Cornell	Events achieved by LICENSEE related to the timing of the issuance of each Sublicense by LICENSEE
[***]	Prior to filing an IND
[***]	After filing an IND but before completion of the first human studies
[***]	After completion of first human studies but prior to submitting a BLA for approval in a Major Market

royalties based on the royalty rate in Paragraph 3.1(d) as applied to Net Sales of Sublicensee; provided, however that, for clarity, in the event that a Sublicense fee or Sublicense royalty would apply to a Licensed Product under this Agreement as well as under any other license agreement entered into between LICENSEE and Cornell or any of its Affiliates, then only one Sublicense fee or Sublicense royalty rate shall apply for such Licensed Product and the Sublicense fees or Sublicense royalties shall not be stacked or otherwise considered cumulative or additive upon any such Licensed Product, and only the highest Sublicense fee or Sublicense royalty rate applicable under any such agreement between the Parties shall apply to Net Sales of such Licensed Product by any Sublicensee.


Year of Commercial Sale	Minimum Annual Royalty
First	[***]
Second	[***]
Third and each year thereafter	[***]

All fees and royalty payments specified in Paragraphs 3.1(a) through 3.1(g) above shall be paid by LICENSEE pursuant to Paragraph 4.3 and shall be delivered by LICENSEE to Cornell as noted in Paragraph 10.1. At Cornell’s election, all fees and payments specified in Paragraphs 3.1(b), (c), and (g) shall be adjusted to reflect any increase in the Consumer Price Index as announced by the Bureau of Labor Statistics of the United States Department of Labor.

3.2 Patent Costs. LICENSEE shall reimburse Cornell all Patent Costs within thirty (30) days following the date an itemized invoice is sent from Cornell to LICENSEE.

3.3 Due Diligence.

(a) LICENSEE shall, either directly or through its Affiliate(s) or Sublicensee(s):

(i) use commercially reasonable diligent efforts to proceed with the development, and commercialization of at least one Licensed Product in the Field and in at least one Major Market Region;

(ii) raise [***] within [***] of the Effective Date and a further [***] within [***] of the Effective Date.

(iv) file an Investigational New Drug Application for a first Licensed Product within [***] of the Effective Date

(v) commence human testing of a Licensed Product within [***] of the Effective Date.

(vii) submit a Biologics License Application for a Licensed Product to the United States FDA within [***] of the Effective Date;

(viii) submit the equivalent of a Biologics License Application to the equivalent of the FDA in a Major Market other than the US for a Licensed Product within [***] of the Effective Date;

(ix) market Licensed Products in each country within the Territory within nine (9) months of receiving regulatory approval to market such Licensed Products in said country;

(x) reasonably fill the market demand for Licensed Products following commencement of marketing at any time during the term of this Agreement; and

(xi) obtain and maintain all necessary governmental approvals and permits for the manufacture, use and sale of Licensed Products.

3.4 Research Support. LICENSEE agrees to provide research support to Inventor to further develop Invention at Cornell in the amount of [***] total costs per year for four years under a Sponsored Research Agreement for research relating to the further development of the Technology and the Patent Rights licensed under this Agreement, to be negotiated by LICENSEE with the relevant office at Weill Cornell Medical College.

ARTICLE 4. REPORTS, RECORDS AND PAYMENTS

4.1 Reports.

(i) the gross sales and Net Sales (as defined in Paragraph 1.11) during the most recently completed calendar quarter and the royalties, in US dollars, payable with respect thereto;

(ii) the number of each type of Licensed Product sold;

(iii) Sublicense fees and royalties received during the most recently completed calendar half in US dollars, payable with respect thereto;

(iv) the method used to calculate the royalties;

(v) the exchange rates used;

(vi) relevant business and corporate development efforts relating to the rights granted in this Agreement.

If no sales of Licensed Products have been made and no Sublicense revenue has been received by LICENSEE during any reporting period, LICENSEE shall so report.

4.2 Records & Audits.

4.3 Payments .

(b) Royalty Payments.

(i) Royalties shall accrue when Licensed Products are invoiced, or if not invoiced, when delivered to a third party or Affiliate.

(v) In the event that any patent or patent claim within Patent Rights is held invalid in a final decision by a patent office from which no appeal or additional patent prosecution has been or can be taken, or by a court of competent jurisdiction and last resort and from which no appeal has or can be taken, all obligation to pay royalties based solely on that patent or claim or any claim patentably indistinct therefrom shall cease as of the date of such final decision. LICENSEE shall not, however, be relieved from paying any royalties that accrued before the date of such final decision, or that are based on another patent or claim not involved in such final decision, or that are based on the use of Technology.

ARTICLE 5. INTELLECTUAL PROPERTY MATTERS

5.1 Patent Prosecution and Maintenance .

from Cornell, and all patents and patent applications in Patent Rights shall be assigned solely to Cornell; provided, however, that LICENSEE shall have the right to provide timely and meaningful input and comments to Cornell and its selected counsel on the content of any proposed patent application filings and for all material correspondence with the relevant patent offices throughout the world for prosecution of the Patent Rights. In the event that Cornell declines to file any patent applications within the Patent Rights, Cornell shall notify LICENSEE in writing at least forty-five days prior to the relevant filing deadlines, and LICENSEE shall have the right, but not the obligation, to step-in and diligently prosecute and maintain the United States and, if available, foreign patents, and applications for such Patent Rights using counsel of its choice.

(b) Cornell shall consider amending any patent application in Patent Rights to include claims reasonably requested by LICENSEE to protect the products contemplated to be sold as Licensed Products by LICENSEE under this Agreement.

(c) LICENSEE may elect to terminate its reimbursement obligations with respect to any patent application or patent in Patent Rights upon ninety (90) days written notice to Cornell. Cornell shall use reasonable efforts to curtail or avoid any further Patent Costs for such application or patent when such notice of termination is received from LICENSEE. Cornell, in its sole discretion and at its sole expense, may continue prosecution and maintenance of said application or patent, and LICENSEE shall have no further license with respect thereto. Non-payment of any portion of Patent Costs with respect to any application or patent may be deemed by Cornell as an election by LICENSEE to terminate its reimbursement obligations with respect to such application or patent. Cornell is not obligated to file, prosecute, or maintain Patent Rights outside of the territory at any time or to file, prosecute, or maintain Patent Rights to which Licensee has terminated its License hereunder.

(d) LICENSEE shall apply for an extension of the term of any patent in Patent Rights if appropriate under the Drug Price Competition and Patent Term Restoration Act of 1984 and/or European, Japanese and other foreign counterparts of this law. LICENSEE shall prepare all documents for such application, and Cornell shall execute such documents and to take any other additional action as LICENSEE reasonably requests in connection therewith.

5.2 Patent Infringement.

(a) If either party learns of any substantial infringement of Patent Rights, the party which first became aware of such infringement shall so inform the other party and provide the other party with reasonable evidence of the infringement. Neither party shall notify a third party of the infringement of Patent Rights without the consent of the other party. Both parties shall use reasonable efforts and cooperation to terminate infringement without litigation.

receiving notice of such request from LICENSEE. LICENSEE may thereafter bring suit for patent infringement at its own expense, if and only if Cornell elects not to commence suit and the infringement occurred in a jurisdiction where LICENSEE has an exclusive license under this Agreement for the infringing activity. If LICENSEE elects to bring suit, Cornell and/or CRF may join that suit at its own expense.

(c) Any recovery or settlement received in connection with any suit will (i) first be shared by Cornell and LICENSEE equally until the actual out-of-pocket litigation costs of one of the parties are fully recovered; (ii) thereafter, it shall be provided to the party that has not yet fully recovered its actual out-of-pocket litigation costs until all such costs are fully recovered; and (iii) finally, any remaining amount shall then be shared between Cornell and LICENSEE in a ratio that is proportionate to the actual out-of-pocket litigation costs incurred by the parties. If, however, Cornell has no out of pocket costs, Cornell's share of any remaining amount shall be governed by Paragraph 3.1(f) as sublicense royalty. Cornell and LICENSEE agree to be bound by all determinations of patent infringement, validity, and enforceability (but no other issue) resolved by any adjudicated judgment in a suit brought in compliance with this Section 5.2.

(d) Not withstanding 5.2 (c), a ny agreement made by LICENSEE for purposes of settling litigation or other dispute shall comply with the requirements of Section 2.2 (Sublicenses) of this Agreement.

(e) Each party shall cooperate with the other in litigation proceedings at the expense of the party bringing suit. Litigation shall be controlled by the party bringing the suit, except that CRF and/or Cornell may be represented by counsel of its choice in any suit brought by LICENSEE.

5.3 Patent Marking. LICENSEE shall mark all Licensed Products made, used or sold under the terms of this Agreement, or their containers, in accordance with the applicable patent marking laws.

5.4 Ownership of Technology

(a) Cornell retains ownership of Technology.

(b) LICENSEE shall make no use of Technology outside the scope of this Agreement and the licenses granted hereunder. Any such use shall be a material breach of this Agreement.

ARTICLE 6. GOVERNMENTAL MATTERS

ARTICLE 7. TERMINATION OF THE AGREEMENT

7.1 Termination by Cornell.

(b) This Agreement will terminate immediately, without the obligation to provide written notices as set forth in Paragraph 7.1(a), if LICENSEE initiates a legal proceeding and files a written claim including in any way the assertion that any portion of Cornell’s Patent Rights is invalid or unenforceable where the filing is by the LICENSEE, a third party on behalf of the LICENSEE, or a third party at the written urging of the LICENSEE.

7.2 Termination by LICENSEE.

7.3 Survival on Termination. The following Paragraphs and Articles shall survive the termination of this Agreement:

(a) Article 4 (REPORTS, RECORDS AND PAYMENTS);

(b) Paragraph 7.4 (Disposition of Licensed Products on Hand);

(d) Article 9 (USE OF NAMES AND TRADEMARKS);

(e) Paragraph 10.2 hereof (Secrecy); and

(f) Paragraph 10.5 (Failure to Perform).

ARTICLE 8. LIMITED WARRANTY AND INDEMNIFICATION

8.1 Limited Warranty.

(a) Cornell warrants that, without conducting any investigation or any inquiry, it has the lawful right to grant this license, and that, as of the Effective Date, its Center for Technology Licensing, has not received written notice from any third party of any pending or threatened legal action or suit asserting that the use of the Patent Rights or the Technology as contemplated hereunder for the development and commercialization of any Licensed Product would infringe or misappropriate the patent rights or intellectual property rights of any third party.

(b) T he license granted herein is provided “AS IS” and without WARRANTY OF MERCHANTABILITY or WARRANTY OF FITNESS FOR A PARTICULAR PURPOSE or any other warranty, express or implied. Other than as expressly stated in paragraph (a) above, Cornell makes no representation or warranty that the Licensed Product, Licensed Method or the use of Patent Rights or Technology will not infringe any other patent or other proprietary rights.

(d) Nothing in this Agreement shall be construed as:

(i) a warranty or representation by Cornell as to the validity or scope of any Patent Rights;

(ii) a warranty or representation that anything made, used, sold or otherwise disposed of under any license granted in this Agreement is or shall be free from infringement of patents of third parties;

(iii) an obligation to bring or prosecute actions or suits against third parties for patent infringement except as provided in Paragraph 5.2 hereof;

(iv) conferring by implication, estoppel or otherwise any license or rights under any patents of Cornell Research Foundation, Inc. or Cornell other than Patent Rights as defined in this Agreement; or

(v) an obligation to furnish any know-how not provided in Patent Rights or Technology; or

(vi) an obligation to update Technology.

8.2 Indemnification.

(a) LICENSEE shall indemnify, hold harmless and defend Cornell, its officers, employees, and agents; the sponsors of the research that led to the Invention; and the Inventors of the patents and patent applications in Patent Rights and their employers (the “Cornell Indemnitees”) against any and all claims, suits, losses, damage, costs, fees, and expenses (“Claims”) resulting from or arising out of exercise of this license by LICENSEE or any of its Affiliates or any Sublicense by any Sublicensee. This indemnification shall include, but not be limited to, any product liability Claims, but shall expressly exclude any Claims to the extent attributable to (i) the willful misconduct or gross negligence of any of the Cornell Indemnitees, or (ii) the breach by Cornell or any of the Cornell Indemnitees of any provision of this Agreement or of any representation, warranty or covenant made by Cornell hereunder.

(ii) the coverage and limits referred to above shall not in any way limit the liability of LICENSEE.

and (iii) include a provision that the coverage shall be primary and shall not participate with nor shall be excess over any valid and collectable insurance or program of self-insurance carried or maintained by Cornell.

ARTICLE 9. USE OF NAMES AND TRADEMARKS

ARTICLE 10. MISCELLANEOUS PROVISIONS

10.1 Correspondence. Any notice, invoice or payment required to be given to either party under this Agreement shall be deemed to have been properly given and effective:

(a) on the date of delivery if delivered in person;

(b) on the date of successful transmission if sent by facsimile,

If sent to LICENSEE :

Reports and Notices Contact:

Annapurna Therapeutics

3711 Market Street, Suite 800

Philadelphia, PA 19104

Attention: Amber Salzman

Tel: [***]

email: amber@annapurnatx.com

Accounts Payable Contact:

Annapurna Therapeutics

3711 Market Street, Suite 800

Philadelphia, PA 19104

Attention: Amber Salzman

Tel: [***]

email: amber@annapurnatx.com

Intellectual Property Contact:

Annapurna Therapeutics

3711 Market Street, Suite 800

Philadelphia, PA 19104

Attention: Amber Salzman

Tel: [***]

email: amber@annapurnatx.com

If sent to Cornell:

For all correspondence except payments -

Center for Technology Licensing at Cornell University

Attention: Executive Director

395 Pine Tree Road, Suite 310

Ithaca, NY 14850

FAX: 607-254-5454

TEL: 607-254-5236

EMAIL: ctl-contracts@cornell.edu

For all payments -

If sent by mail:

Center for Technology Licensing at Cornell University

PO Box 6899

Ithaca, NY 14851-6899

If remitted by electronic payments via ACH or Fed Wire :


Receiving bank name:	[***]
Bank account no.:	[***]
Bank routing (ABA) no.: SWIFT code:	[*] [*]
Bank account name:	[***]
Bank ACH format code:	[***]
Bank address:	[***]
Additional information:	[*] [*]

10.2 Secrecy.

(b) Licensee shall:

(i) use the Confidential Information for the sole purpose of performing under the terms of this Agreement;

(ii) safeguard Confidential Information against disclosure to others with the same degree of care as it exercises with its own data of a similar nature;

(A) LICENSEE can demonstrate by written records was previously known to it;

(B) is now, or becomes in the future, public knowledge other than through acts or omissions of LICENSEE;

(D) is required to be disclosed by law or a court of competent jurisdiction; and

(c) The secrecy obligations of LICENSEE with respect to Confidential Information shall continue for a period ending five (5) years from the termination date of this Agreement.

10.3 Assignability. This Agreement may be assigned by Cornell, but is personal to LICENSEE and assignable by LICENSEE only with the written consent of Cornell, such consent not to be unreasonably withheld; provided, however, that LICENSEE shall, subject to an assignment fee payment of [***] paid in advance of the assignment date by LICENSEE to Cornell, have the right to assign this Agreement and any of its obligations hereunder, without the consent of Cornell, to any of its Affiliates or to any successor or transferee in connection with a merger, acquisition, consolidation or other business combination or sale or other disposition of all or substantially all of LICENSEE’s business or assets relating to the subject matter hereof so long as such of its Affiliates, or any successor or transferee do not have any of the qualities or statuses set forth in the following sentence and further provided that LICENSEE is in good standing with respect to this Agreement. As illustrative examples, withholding of consent by Cornell shall be considered reasonable for a proposed assignment by LICENSEE to a third party which does not have the necessary resources to commercially develop the licensed Patent Rights, which is in active litigation, arbitration proceedings or other contractual dispute with Cornell at the time of assignment , which is associated with or is controlled by one or more organizations known to be affiliated with countries that are considered by the U.S. government as rogue, which is considered as a business that does not seek to actively make technology available to the public in commerce, which is engaged in “patent troll” activities, or whose association with Cornell will materially negatively impact Cornell’s reputation as an academic institution. In all cases of permitted assignment the assignee must have agreed in writing to assume and comply with LICENSEE’s obligations (or Cornell’s obligations if Cornell is assigning this Agreement) under, and to be bound by, this Agreement.

10.6 Governing Laws. THIS AGREEMENT SHALL BE INTERPRETED AND CONSTRUED IN ACCORDANCE WITH THE LAWS OF THE STATE OF NEW YORK, but the scope and validity of any patent or patent application shall be governed by the applicable laws of the country of the patent or patent application.

10.8 Headings. The headings of the several sections are inserted for convenience of reference only and are not intended to be a part of or to affect the meaning or interpretation of this Agreement.

10.10 Amendments. No amendment or modification of this Agreement shall be valid or binding on the parties unless made in writing and signed on behalf of each party.

IN WITNESS WHEREOF , both Cornell and LICENSEE have executed this Agreement, in duplicate originals, by their respective and duly authorized officers on the day and year written.


ANNAPURNA THERAPEUTICS LIMITED	CORNELL UNIVERSITY

By: ________________________	By: ________________________
(Signature of an authorized officer)	(Signature of an authorized officer)
Name: Amber Salzman, PhD	Name: Brian J. Kelly, PhD
Title: CEO	Title: Director, Technology Licensing
Date:________________________	Date:_________________________

Appendix A : Original Material

[***]

Appendix B : Convertible Note

Annapurna Therapeutics Limited

CONVERTIBLE PROMISSORY NOTE

[***]

December 15, 2015

(a) The date that is twelve (12) months from the date of this Note; or

For the purpose of sub-paragraph (a) above, the principal balance and all accrued interest shall be paid in cash within thirty (30) days of the Maturity Date.

For the purpose of sub-paragraph (b) above, the principal balance and all accrued interest shall be paid, at the sole discretion of the Holder, either in cash, in the Parent’s stock, or in any

combination thereof. In the event of a payment in the Parent’s stock, the conversion per share value and the stock class shall be the share price, discounted at a rate of [***] , and class of the stock issued by the Parent in the equity financing that results in the cumulative sum cited in (b) above being satisfied (the "Stock").

(iv) Any material change in the Business Plan provided to CTL for the purpose of negotiating the Agreement and attached the Agreement as Appendix E, to the extent not approved by CTL.

iii) Prepayment (cash). The Company may, at its option, at any time, prepay, in whole or part, the principal and interest due under this Note.

iv) Conversion. In the event the Holder wishes to convert this Note into fully paid and shares of Stock of the Parent (the "Stock") the following articles shall apply:

convert any portion of this Note into Stock, the Holder shall surrender this Note, duly endorsed, at the principal office of the Company and shall give written notice (Exhibit A) by mail, postage prepaid, to the Company at its principal corporate office, of the election to convert the same pursuant to this Section 5, and shall state therein the portion of the Note to be paid in cash and the portion of the Note to be converted into Stock with the name or names in which the certificate or certificates for shares of the Stock are to be issued. Such conversion shall be deemed to have been made immediately prior to the close of business on the date of such surrender of this Note, and the person or persons entitled to receive the shares of Stock issuable upon such conversion shall be treated for all purposes as the record holder or holders of such shares of Stock as of such date.

(iii) Delivery of Certificates . As promptly as practicable after the conversion of this Note, the Parent at its expense will issue and deliver to the Holder of this Note a certificate or certificates for the number of full shares of the Stock issuable upon such conversion (bearing such legends as are required by applicable state and federal securities laws in the opinion of counsel to the Parent), together with any other securities and property to which the Holder is entitled upon such conversion under the terms of this Note, including a check payable to the Holder for any cash amounts payable due to the election of the Holder or of residual value as described in (iii) below.

6. Notices of Record Date, etc. In the event of:

(a) The date on which any such record is to be taken for the purpose of such dividend, distribution or right, and the amount and character of such dividend, distribution or right; and

any time the number of authorized but unissued shares of the proper class of the Stock shall not be sufficient to effect the conversion of the entire outstanding principal amount of the Note, in addition to such other remedies as shall be available to the holder of this Note, the Parent will use its best efforts to take such corporate action as may, in the opinion of its counsel, be necessary to increase its authorized but unissued shares of the proper class of the Stock to such number of shares as shall be sufficient for such purposes. The Company shall cause the Parent to take all actions required of the Parent pursuant to this Note.

9. Waiver and Amendment. Any provision of this Note may be amended, waived or modified only upon the written consent of the Company and the Holder of this Note.

12. Notices. Any notice, request or other communication required or permitted hereunder shall be in writing and shall be deemed to have been duly given if personally delivered or mailed registered or certified mail, postage prepaid, at the respective address of the parties as set forth herein. Any party hereto may by notice so given change its address for future notice hereunder. Notice shall conclusively be deemed to have been given when personally delivered or when deposited in the mail or telegraphed in the manner set forth above and shall be deemed to have been received when delivered.

14. Governing law. This Agreement shall be governed by and construed in accordance with the laws of the State of New York, excluding that body of law relating to conflict of laws.

IN WITNESS WHEREOF, the Company has caused this Note be issued this fifteenth day of December, 2015.

Annapurna Therapeutics Limited

By:

Its:

Name of Holder:		Cornell University
Address:		c/o Center for Technology Licensing at Cornell University
		395 Pine Tree Road, Suite 310
		Ithaca, New York 14850

Exhibit A

NOTICE OF CONVERSION

(To Be Signed Only Upon Conversion of Note)

TO: Annapurna Therapeutics Limited

Dated: _____________________

(Signature must conform in all respects to name of holder as specified on the face of the Note)

(Address)

Appendix C : Development Report

Company Name

CTL Agreement No

Your Reference No

Reporting Period ( mm / dd / yyyy )

From ______ / ______ / ______ Through _____ / ______ / _____

Expected Date of first sale of

Licensed Product(s)

( mm / dd / yyyy ) ______ / ______ / ______

Please Check One

Your Company Has: o less than 500 employees worldwide o 500 or more employees worldwide

For the reporting period prescribed in the agreement, please provide detailed answers to the questions listed below. Please attach a separate report to this sheet if necessary.

1. Listing of milestones / performance requirements accomplished during the reporting period

Done

Completed

Date

In Progress

Anticipated

Date

Not Done

Anticipated

Date


2. List of Products being developed under this agreement
Product Name	Brief Description	Status
Product Name	Brief Description	Status
Product Name	Brief Description	Status
Product Name	Brief Description	Status
Product Name	Brief Description	Status

3. Total expenditure spent in the reporting period (under this agreement)

4.Sublicense Activity (if applicable)
List of Sublicenses granted during reporting period			List of sublicenses terminated during reporting period





Total Number of active sublicenses during reporting period

Information reported below will only be used in an aggregated manner. Information related to individual licensee will not be released.

5. Jobs and Payroll Information
Number of Full Time Employee equivalents currently employed by company (do not count consultants or contractors hired as independent agents)
Total current company payroll for preceding 12 months

6. Financial Information
Amount of equity investment received :
a)For preceding 12 months
b)Cumulative total
Amount of investment received using other financial instrument to date excluding equity investment above (e.g. loan, warrant, convertible note etc.)
a) For preceding 12 months
b) Cumulative total
Amount of grants and awards received to date. (e.g. Federal grants, Small business, Foundation grants, Competition awards) Please list source, amount and years if applicable.
a) For preceding 12 months




b) Cumulative total




Estimated market value (private) or market capitalization (public) of company

Report Prepared & Approved By

Name ( Please Print )

Title

Signature

Date ( mm / dd / yyyy )

_______ / _______ / ___________

Please submit completed report either via mail or email at address below:

Center for Technology Licensing

At Cornell University

395 Pine Tree Rd., Suite 310

Ithaca, NY 14850

ctl-contracts@cornell.edu

Appendix D: Commercialization Report

Company Name

CTL Agreement No

Your Reference No

Reporting Period ( mm / dd / yyyy )

From _______ / _______ / _____________ Through _______ / _______ / ______________

Date of first sale of

Licensed Product(s)

( mm / dd / yyyy ) ________ / ________ / _____________

Please list all trade names for product(s) incorporating licensed rights whether or not you had sales during this reporting period.
Product Name		Licensed Invention or Patent Rights (No.) used if known or Docket No	Country	Number of Units Sold	Gross Sales	Net Sales ( A )		Royalty Rate ¹ ( B )	Total Royalties ( A * B )









	1 Please refer to the license agreement for: · applicable royalty rate, please provide as decimal; · how Net Sales should be calculated; · applicable share of sublicense fees; · application of minimum royalty rate · If sales were in a currency other than United States Dollars, please specify exchange rate used 2 Subtract minimum royalty already paid from royalty subtotal for Total Royalty Owed						Royalty Subtotal
							Minimum Royalty already paid*
							Total Royalty Owed ²
							Total Sublicense Fees* (if applicable)
							Total Payment

Sublicense Activity (if applicable)
List of sublicenses granted during the reporting period			List of sublicenses terminated or expired during the reporting period





Total Number of active sublicenses during reporting period

List of Products being developed under this agreement
Product Name	Brief Description	Status
Product Name	Brief Description	Status
Product Name	Brief Description	Status
Product Name	Brief Description	Status
Product Name	Brief Description	Status

List of Licensed Product(s) Not Manufactured in the US
Product Name
Product Name
Product Name
Product Name

Jobs and Payroll Information
Number of Full Time Employee equivalents currently employed by company (do not count consultants or contractors hired as independent agents)
Total current company payroll for preceding 12 months

Financial Information
Amount of equity investment received :
c)For preceding 12 months
d)Cumulative total
Amount of investment received using other financial instrument to date excluding equity investment above (e.g. loan, warrant, convertible note etc.)
a) For preceding 12 months
c) Cumulative total
Amount of grants and awards received to date. (e.g. Federal Agency, Small business, NSF grants) Please list source, amount and years if applicable.
a) For preceding 12 months



b) Cumulative total



Estimated market value of company (best guess)

Report Prepared & Approved By

Name ( Please Print )

Title

Signature

Date ( mm / dd / yyyy )

_________ / _________ / ______________

Appendix E: Business Plan

[***]

THE REMAINDER OF THIS PAGE AND THE FOLLOWING 41 PAGES HAVE BEEN OMITTED AND FILED SEPARATELY WITH THE U.S. SECURITIES AND EXCHANGE COMMISSION PURSUANT TO A REQUEST FOR CONFIDENTIAL TREATMENT.

Exhibit 10.6

LICENSE AGREEMENT

BETWEEN

ANNAPURNA THERAPEUTICS LIMITED

AND

CORNELL UNIVERSITY

FOR

[***]

CTL CONTRACT NO. C2016-11-10548

TABLE OF CONTENTS

RECITALS		1

ARTICLE 1.	DEFINITIONS	1

ARTICLE 2.	GRANTS	4

ARTICLE 3.	CONSIDERATION	6

ARTICLE 4.	REPORTS, RECORDS AND PAYMENTS	10

ARTICLE 5.	INTELLECTUAL PROPERTY MATTERS	12

ARTICLE 6.	GOVERNMENTAL MATTERS	14

ARTICLE 7.	TERMINATION OF THE AGREEMENT	15

ARTICLE 8.	LIMITED WARRANTY AND INDEMNIFICATION	16

ARTICLE 9.	USE OF NAMES AND TRADEMARKS	18

ARTICLE 10.	MISCELLANEOUS PROVISIONS	18

Appendix A :	Original Material	23

Appendix B :	Convertible Note	24

Appendix C :	Development Report	31

Appendix D:	Commercialization Report	34

Appendix E:	Business Plan	37

LICENSE AGREEMENT

This Agreement is effective on December 15, 2015 (“Effective Date”).

RECITALS

WHEREAS , the Inventors are employees of Cornell, and they are obligated to assign all of their right, title and interest in the Invention to Cornell and have done so;

WHEREAS , CTL is the officially authorized unit at Cornell to manage Invention and to grant rights subsisting therein for Cornell;

WHEREAS , Cornell desires that the Invention be developed and utilized to the fullest possible extent so that its benefits can be enjoyed by the general public;

NOW, THEREFORE , the parties agree:

ARTICLE 1. DEFINITIONS

The terms, as defined herein, shall have the same meanings in both their singular and plural forms.

1.1

permit foreign equity participation of at least twenty percent ( 20 %) , then an "Affiliate" includes any company in which LICENSEE owns or controls or is owned or controlled by, directly or indirectly, the maximum percentage of outstanding stock , units of membership, or voting rights permitted by local law.

1.2

1.3	"Field" means all fields.

1.4	"Territory" means [***].

1.5

1.6

"Patent Rights" means Cornell’s right in any of the following: the US patent application (serial number [***] titled [***]) disclosing and claiming the Invention, filed by Inventors and assigned to Cornell and applications which claim priority thereto, and continuing applications thereof including divisions, substitutions, and continuations-in-part (but only to extent the claims thereof are enabled by disclosure of the parent application); any patents issuing on said applications including reissues, reexaminations and extensions; and any corresponding foreign applications or patents, existing anywhere in the world.

1.7

1.8	[This paragraph left intentionally blank.]

1.9

1.10

"Licensed Product" means any service, composition or product that uses Technology, or is claimed by a Valid Claim with in the Patent Rights, or that is produced or enabled by Licensed Method, or the manufacture, use, sale, offer for sale, or importation of which would constitute, but for the license granted to LICENSEE under this Agreement, misappropriation of Technology or an infringement, an inducement to infringe or contributory infringement, of any pending or issued Valid C laim within the Patent Rights .

1.11

1.12

1.13

(a)

"Original Material" shall mean the material described in Appendix A, as provided to LICENSEE by Inventor under this Agreement.

(b)

"Progeny" shall mean unmodified descendant from the Original Material, such as virus from virus, cell from cell, or organism from organism.

(c)

"Unmodified Derivatives" shall mean substances created by or at the behest of LICENSEE , a Sublicensee, or an Affiliate, which constitute an unmodified functional subunit or product expressed by the Original Material or its Progeny. Some examples include: subclones of unmodified cell lines, purified or fractionated subsets of the Original Material or Progeny, proteins expressed by DNA/RNA, monoclonal antibodies secreted by a hybridoma cell line, or purified proteins expressed or secreted by a cell line, or cells or other material extracted from a model organism.

(d)

"Modifications" shall mean substances created by or at the behest of LICENSEE, a Sublicensee, or an Affiliate which contain or incorporate, in whole or in part, the Original Material, Progeny, and/or Unmodified Derivatives.

1.14	"Major Market Region" shall mean any of the following countries or regions: [***].

1.15

ARTICLE 2. GRANTS

2.2 Sublicense.

(a) The license granted in Paragraph 2.1 includes the right of LICENSEE to grant Sublicenses (including through multiple tiers) to third parties during the Term but only for as long as, and only in parts of the Field, for which the license for Patent Rights is exclusive.

(b) With respect to Sublicense granted pursuant to Paragraph 2.2(a), LICENSEE shall:

(ii) to the extent applicable, include all of the rights of and obligations due to Cornell (and, if applicable, the Sponsor's Rights) and contained in this Agreement;

(iii) promptly provide Cornell with a copy of each Sublicense issued and any amendment made to any Sublicense; and

2.3 Reservation of Rights. Cornell reserves the right to:

ARTICLE 3. CONSIDERATION

(b) license maintenance fees payable on each anniversary of the Effective Date according to the following schedule; provided however, that LICENSEE's obligation to pay this fee shall end on the date when LICENSEE is commercially selling a Licensed Product in the first country of the Territory, and the license maintenance fee payable shall be pro-rated for the number of months remaining in that license year.


Fee payable to Cornell	Date
[***]	1st - 3rd anniversaries of Effective Date
[***]	4th anniversary of Effective Date
[***]	5th anniversary of Effective Date
[***]	6th anniversary of Effective Date and each subsequent anniversary thereafter, until the date of first commercial sale of a Licensed Product in the first country of sale


Amount	Date or Event
[***]	Filing of an IND
[***]	Completion of a Phase II clinical trial
[***]	Completion of a Phase III clinical trial
[***]	Marketing approval from the US FDA for first indication
[***]	Marketing approval in each non-US Major Market Region for first indication
[***]	Marketing approval from the US FDA for additional indications
[***]	Marketing approval in each non-US Major Market Region for each additional indication

(d) an earned royalty

(ii) [***] on Net Sales of Licensed Products by LICENSEE and/or its Affiliate(s) in countries where a Valid Claim within the Patent Rights which covers the manufacture, use or sale of the Licensed Product does not exist at the time of sale, until the expiration of the Term, which is not subject to the anti-stacking provisions set forth in sub-paragraph (iii) below.

(e) a percentage of all Sublicense fees received by LICENSEE from its Sublicensees that are not earned royalties according to the following schedule;


Percentage of the Sublicense fees to be shared with and payable to Cornell	Events achieved by LICENSEE related to the timing of the issuance of each Sublicense by LICENSEE
[***]	Prior to filing an IND
[***]	After filing an IND but before completion of the first human studies
[***]	After completion of first human studies but prior to submitting a BLA for approval in a Major Market

provided, however that, for clarity, in the event that a Sublicense fee or Sublicense royalty would apply to a Licensed Product under this Agreement as well as under any other license agreement entered into between LICENSEE and Cornell or any of its Affiliates, then only one Sublicense fee or Sublicense royalty rate shall apply for such Licensed Product and the Sublicense fees or Sublicense royalties shall not be stacked or otherwise considered cumulative or additive upon any such Licensed Product, and only the highest Sublicense fee or Sublicense royalty rate applicable under any such agreement between the Parties shall apply to Net Sales of such Licensed Product by any Sublicensee.


Year of Commercial Sale	Minimum Annual Royalty
First	[***]
Second	[***]
Third and each year thereafter	[***]

3.2 Patent Costs. LICENSEE shall reimburse Cornell all Patent Costs within thirty (30) days following the date an itemized invoice is sent from Cornell to LICENSEE.

3.3 Due Diligence.

(a) LICENSEE shall, either directly or through its Affiliate(s) or Sublicensee(s):

(i) use commercially reasonable diligent efforts to proceed with the development, and commercialization of at least one Licensed Product in the Field and in at least one Major Market Region;

(ii) raise [***] within [***] of the Effective Date and a further [***] within [***] of the Effective Date.

(iii ) raise a total of [***] within [***] of the Effective Date. For clarity, any portion or all of such amount shall be counted toward the [***] total required regardless of whether any of such amounts are obtained from existing investors in LICENSEE as of the Effective Date or from new investors, or whether such amount represents the cash funds existing and available to any successor to LICENSEE in the event of a merger, acquisition, consolidation or other business combination.

(iv) file an Investigational New Drug Application for a first Licensed Product within [***] of the Effective Date

(v) commence human testing of a Licensed Product within [***] of the Effective Date.

(vii) submit a Biologics License Application for a Licensed Product to the United States FDA within [***] of the Effective Date;

(viii) submit the equivalent of a Biologics License Application to the equivalent of the FDA in a Major Market other than the US for a Licensed Product within [***] of the Effective Date;

(ix) market Licensed Products in each country within the Territory within nine (9) months of receiving regulatory approval to market such Licensed Products in said country;

(x) reasonably fill the market demand for Licensed Products following commencement of marketing at any time during the term of this Agreement; and

(xi) obtain and maintain all necessary governmental approvals and permits for the manufacture, use and sale of Licensed Products.

ARTICLE 4. REPORTS, RECORDS AND PAYMENTS

4.1 Reports.

(i) the gross sales and Net Sales (as defined in Paragraph 1.11) during the most recently completed calendar quarter and the royalties, in US dollars, payable with respect thereto;

(ii) the number of each type of Licensed Product sold;

(iii) Sublicense fees and royalties received during the most recently completed calendar half in US dollars, payable with respect thereto;

(iv) the method used to calculate the royalties;

(v) the exchange rates used;

(vi) relevant business and corporate development efforts relating to the r ights granted in this Agreement .

If no sales of Licensed Products have been made and no Sublicense revenue has been received by LICENSEE during any reporting period, LICENSEE shall so report.

4.2 Records & Audits.

4.3 Payments .

(b) Royalty Payments.

(i) Royalties shall accrue when Licensed Products are invoiced, or if not invoiced, when delivered to a third party or Affiliate.

ARTICLE 5. INTELLECTUAL PROPERTY MATTERS

5.1 Patent Prosecution and Maintenance .

(a) Provided that LICENSEE has reimbursed Cornell for Patent Costs pursuant to Paragraph 3.2, Cornell shall diligently prosecute and maintain the United States and, if available, foreign patents, and applications in Patent Rights using counsel of its choice. Cornell shall provide LICENSEE with copies of all relevant documentation relating to such prosecution and to all material correspondence with the relevant patent offices throughout the world, and LICENSEE shall keep this documentation confidential. The counsel shall take instructions only from Cornell, and all patents and patent applications in Patent Rights shall be assigned solely to Cornell; provided, however, that LICENSEE shall have the right to provide timely and meaningful input and comments to Cornell and its selected counsel on the content of any proposed patent application filings and for all material correspondence with the relevant patent offices throughout the world for prosecution of the Patent Rights. In the event that Cornell declines to file any patent applications

within the Patent Rights, Cornell shall notify LICENSEE in writing at least forty-five days prior to the relevant filing deadlines, and LICENSEE shall have the right, but not the obligation, to step-in and diligently prosecute and maintain the United States and, if available, foreign patents, and applications for such Patent Rights using counsel of its choice.

5.2 Patent Infringement.

(b) LICENSEE may request Cornell to take legal action against such third party for the infringement of Patent Rights in the Field and within the Territory. Such request shall be made in writing and shall include reasonable evidence of such infringement and damages to LICENSEE. If the infringing activity has not abated ninety (90) days following LICENSEE’s request, Cornell shall elect to or not to commence suit on its own account. Cornell shall give notice of its election in writing to LICENSEE by the end of the one-hundredth (100th) day after receiving notice of such request from LICENSEE. LICENSEE may thereafter bring suit for patent infringement at its own expense, if and only if Cornell elects not to commence suit and the infringement occurred in a jurisdiction where LICENSEE has an exclusive license under this Agreement for the infringing activity. If LICENSEE elects to bring suit, Cornell and/or CRF may join that suit at its own expense.

(d) Not withstanding 5.2 (c), any agreement made by LICENSEE for purposes of settling litigation or other dispute shall comply with the requirements of Section 2.2 (Sublicenses) of this Agreement.

5.3 Patent Marking. LICENSEE shall mark all Licensed Products made, used or sold under the terms of this Agreement, or their containers, in accordance with the applicable patent marking laws.

5.4 Ownership of Technology

(a) Cornell retains ownership of Technology.

(b) LICENSEE shall make no use of Technology outside the scope of this Agreement and the licenses granted hereunder. Any such use shall be a material breach of this Agreement.

ARTICLE 6. GOVERNMENTAL MATTERS

ARTICLE 7. TERMINATION OF THE AGREEMENT

7.1 Termination by Cornell.

7.2 Termination by LICENSEE.

7.3 Survival on Termination. The following Paragraphs and Articles shall survive the termination of this Agreement:

(a) Article 4 (REPORTS, RECORDS AND PAYMENTS);

(b) Paragraph 7.4 (Disposition of Licensed Products on Hand);

(d) Article 9 (USE OF NAMES AND TRADEMARKS);

(e) Paragraph 10.2 hereof (Secrecy); and

(f) Paragraph 10.5 (Failure to Perform).

7.4 Disposition of Licensed Products on Hand. Upon termination of this Agreement, LICENSEE may dispose of all previously made or partially made Licensed Product within a

period of one hundred and twenty (120) days of the effective date of such termination provided that the sale of such Licensed Product by LICENSEE, its Sublicensees, or Affiliates shall be subject to the terms of this Agreement, including but not limited to the rendering of reports and payment of royaltie s required under this Agreement. At the end of such period, LICENSEE shall no longer have rights to use Technology.

ARTICLE 8. LIMITED WARRANTY AND INDEMNIFICATION

8.1 Limited Warranty.

(a) Cornell warrants that , without conducting any investigation or any inquiry, it has the lawful right to grant this license, and that, as of the Effective Date, its Center for Technology Licensing, has not received written notice from any third party of any pending or threatened legal action or suit asserting that the use of the Patent Rights or the Technology as contemplated hereunder for the development and commercialization of any Licensed Product would infringe or misappropriate the patent rights or intellectual property rights of any third party.

(b) T he license granted herein is provided “AS IS” and without WARRANTY OF MERCHANTABILITY or WARRANTY OF FITNESS FOR A PARTICULAR PURPOSE or any other warranty, express or implied. Other than as expressly stated in paragraph (a) above, Cornell makes no representation or warranty that the Licensed Product, Licensed Method or the use of Patent Rights or Technology will not infringe any other patent or other proprietary rights.

(d) Nothing in this Agreement shall be construed as:

(i) a warranty or representation by Cornell as to the validity or scope of any Patent Rights;

(iii) an obligation to bring or prosecute actions or suits against third parties for patent infringement except as provided in Paragraph 5.2 hereof;

(iv) conferring by implication, estoppel or otherwise any license or rights under any patents of Cornell Research Foundation, Inc. or Cornell other than Patent Rights as defined in this Agreement; or

(v) an obligation to furnish any know-how not provided in Patent Rights or Technology; or

(vi) an obligation to update Technology.

8.2 Indemnification.

(a) LICENSEE shall indemnify, hold harmless and defend Cornell, its officers, employees, and agents; the sponsors of the research that led to the Invention; and the Inventors of the patents and patent applications in Patent Rights and their employers (the “Cornell Indemnitees”) against any and all claims, suits, losses, damage, costs, fees, and expenses (“Claims”) resulting from or arising out of exercise of this license by LICENSEE or any of its Affiliates or any Sublicense by any Sublicensee. This indemnification shall include, but not be limited to, any product liability Claims, but shall expressly exclude any Claims to the extent attributable to (i) the willful misconduct or gross negligence of any of the Cornell Indemnitees, or (ii) the breach by Cornell or any of the Cornell Indemnitees of any provision of this Agreement or of any representation, warranty or covenant made by Cornell hereunder.

(ii) the coverage and limits referred to above shall not in any way limit the liability of LICENSEE.

ARTICLE 9. USE OF NAMES AND TRADEMARKS

9.2 Cornell may disclose to the Inventors the terms and conditions of this Agreement upon their request. If such disclosure is made, Cornell shall request the Inventors not disclose such terms and conditions to others , and all such Inventors shall be required to maintain such information as Confidential Information, subject to the obligations of confidentiality and non-use set forth in Section 10.2.

9.4 LICENSEE may acknowledge or make press releases regarding the existence of this Agreement and the extent of the grant in Article 2 but LICENSEE shall not disclose the financial terms of this Agreement , except where LICENSEE is required by law or by the order of a court of competent jurisdiction to do so, or as is reasonably necessary to be disclosed to any of LICENSEEs existing or bona fide potential investors, acquirers, or collaborators. To the extent LICENSEE makes any forward-looking statement in its press releases mentioning Cornell, LICENSEE shall receive prior consent of Cornell which shall not be unreasonably withheld.

ARTICLE 10. MISCELLANEOUS PROVISIONS

10.1 Correspondence. Any notice, invoice or payment required to be given to either party under this Agreement shall be deemed to have been properly given and effective:

(a) on the date of delivery if delivered in person;

(b) on the date of successful transmission if sent by facsimile,

If sent to LICENSEE :

Reports and Notices Contact:

Annapurna Therapeutics

3711 Market Street, Suite 800

Philadelphia, PA 19104

Attention: Amber Salzman

Tel: [***]

email: amber@annapurnatx.com

Accounts Payable Contact:

Annapurna Therapeutics

3711 Market Street, Suite 800

Philadelphia, PA 19104

Attention: Amber Salzman

Tel: [***]

email: amber@annapurnatx.com

Intellectual Property Contact:

Annapurna Therapeutics

3711 Market Street, Suite 800

Philadelphia, PA 19104

Attention: Amber Salzman

Tel: [***]

email: amber@annapurnatx.com

If sent to Cornell:

For all correspondence except payments -

Center for Technology Licensing at Cornell University

Attention: Executive Director

395 Pine Tree Road, Suite 310

Ithaca, NY 14850

FAX: 607-254-5454

TEL: 607-254-5236

EMAIL: ctl-contracts@cornell.edu

For all payments -

If sent by mail :

Center for Technology Licensing at Cornell University

PO Box 6899

Ithaca, NY 14851-6899

If remitted by electronic payments via ACH or Fed Wire :


Receiving bank name:	[***]
Bank account no.:	[***]
Bank routing (ABA) no.: SWIFT code:	[*] [*]
Bank account name:	[***]
Bank ACH format code:	[***]
Bank address:	[***]
Additional information:	[*] [*]

10.2 Secrecy.

(b) Licensee shall:

(i) use the Confidential Information for the sole purpose of performing under the terms of this Agreement;

(ii) safeguard Confidential Information against disclosure to others with the same degree of care as it exercises with its own data of a similar nature;

(A)

LICENSEE can demonstrate by written records was previously known to it;

(B)

is now, or becomes in the future, public knowledge other than through acts or omissions of LICENSEE;

(C)

is lawfully obtained by LICENSEE from sources independent of Cornell; or

(D)

is required to be disclosed by law or a court of competent jurisdiction; and

(c) The secrecy obligations of LICENSEE with respect to Confidential Information shall continue for a period ending five (5) years from the termination date of this Agreement.

10.8 Headings. The headings of the several sections are inserted for convenience of reference only and are not intended to be a part of or to affect the meaning or interpretation of this Agreement.

10.10 Amendments. No amendment or modification of this Agreement shall be valid or binding on the parties unless made in writing and signed on behalf of each party.

IN WITNESS WHEREOF , both Cornell and LICENSEE have executed this Agreement, in duplicate originals, by their respective and duly authorized officers on the day and year written.

ANNAPURNA THERAPEUTICS LIMITED			CORNELL UNIVERSITY

By:			By:
(Signature of an authorized officer)			(Signature of an authorized officer)
Name: Amber Salzman, PhD			Name: Brian J. Kelly, PhD
Title: CEO			Title: Director, Technology Licensing
Date:			Date:

Appendix A : Original Material

[***]

Appendix B : Convertible Note

Annapurna Therapeutics Limited

CONVERTIBLE PROMISSORY NOTE

[***]

December 15, 2015

(a) The date that is twelve (12) months from the date of this Note; or

(b) when Annapurna Therapeutics SAS, a French société par actions simplifiée (RCS Paris No. 799 863 873) (the “Parent”) receives a bona fide equity investment offers from one or more third parties that cumulatively with all other equity investments received by the Parent after the date hereof, equals no less than [***] in one or more arm-length transactions. An arm-length transaction shall mean the sale of stock by company to one or more shareholders who, prior to the sale of the Parent’s stock, do not control or are not controlled by, the Parent.

For the purpose of sub-paragraph (a) above, the principal balance and all accrued interest shall be paid in cash within thirty (30) days of the Maturity Date.

For the purpose of sub-paragraph (b) above, the principal balance and all accrued interest shall be paid, at the sole discretion of the Holder, either in cash, in the Parent’s stock, or in any

(iv) Any material change in the Business Plan provided to CTL for the purpose of negotiating the Agreement and attached the Agreement as Appendix E, to the extent not approved by CTL.

iii) Prepayment (cash). The Company may, at its option, at any time, prepay, in whole or part, the principal and interest due under this Note.

iv) Conversion. In the event the Holder wishes to convert this Note into fully paid and shares of Stock of the Parent (the "Stock") the following articles shall apply:

any portion of this Note into Stock, the Holder shall surrender this Note, duly endorsed, at the principal office of the Company and shall give written notice (Exhibit A) by mail, postage prepaid, to the Company at its principal corporate office, of the election to convert the same pursuant to this Section 5, and shall state therein the portion of the Note to be paid in cash and the portion of the Note to be converted into Stock with the name or names in which the certificate or certificates for shares of the Stock are to be issued. Such conversion shall be deemed to have been made immediately prior to the close of business on the date of such surrender of this Note, and the person or persons entitled to receive the shares of Stock issuable upon such conversion shall be treated for all purposes as the record holder or holders of such shares of Stock as of such date.

(i v ) Fractional Shares; Effect of Conversion . No fractional shares of the Stock shall be issued upon conversion of this Note. In lieu of the Parent issuing any fractional shares to the Holder upon the conversion of this Note, the Company shall pay to the Holder the amount of outstanding principal that is not so converted. Upon conversion and/or payout in cash of the entire principal balance of this Note, the Company shall be forever released from all its obligations and liabilities under this Note, except that the Company shall be obligated to pay the Holder, within ten (10) days after the date of such conversion, any interest accrued and unpaid or unconverted to and including the date of such conversion, and no more.

6. Notices of Record Date, etc. In the event of:

(a) The date on which any such record is to be taken for the purpose of such dividend, distribution or right, and the amount and character of such dividend, distribution or right; and

8. Assignment . The rights and obligations of the Company are binding and personal and may only be assigned or transferred with the written consent by the Holder, which consent shall not be unreasonably withheld. The rights and obligations of the Holder of this Note shall be binding and the benefit be inured, at the discretion of the Holder and in whole or in part, to its successors, assigns, heirs, administrators and transferees.

9. Waiver and Amendment. Any provision of this Note may be amended, waived or modified only upon the written consent of the Company and the Holder of this Note.

14. Governing law. This Agreement shall be governed by and construed in accordance with the laws of the State of New York, excluding that body of law relating to conflict of laws.

IN WITNESS WHEREOF, the Company has caused this Note be issued this fifteenth day of December , 2015.


Annapurna Therapeutics Limited

By:

Its:

Name of Holder:		Cornell University
Address:		c/o Center for Technology Licensing at Cornell University
		395 Pine Tree Road, Suite 310
		Ithaca, New York 14850

Exhibit A

NOTICE OF CONVERSION

(To Be Signed Only Upon Conversion of Note)

TO: Annapurna Therapeutics Limited

Dated: _____________________

(Signature must conform in all respects to name of holder as specified on the face of the Note)

(Address)

Appendix C : Development Report

Company Name

CTL Agreement No

Your Reference No

Reporting Period ( mm / dd / yyyy )

From ______ / ______ / ______ Through _____ / ______ / _____

Expected Date of first sale of

Licensed Product(s)

( mm / dd / yyyy ) ______ / ______ / ______

Please Check One

Your Company Has: o less than 500 employees worldwide o 500 or more employees worldwide

For the reporting period prescribed in the agreement, please provide detailed answers to the questions listed below. Please attach a separate report to this sheet if necessary.

1. Listing of milestones / performance requirements accomplished during the reporting period

Done

Completed

Date

In Progress

Anticipated

Date

Not Done

Anticipated

Date

2. List of Products being developed under this agreement
Product Name	Brief Description	Status
Product Name	Brief Description	Status
Product Name	Brief Description	Status
Product Name	Brief Description	Status
Product Name	Brief Description	Status

3. Total expenditure spent in the reporting period (under this agreement)

4.Sublicense Activity (if applicable)
List of Sublicenses granted during reporting period			List of sublicenses terminated during reporting period





Total Number of active sublicenses during reporting period

Information reported below will only be used in an aggregated manner. Information related to individual licensee will not be released.

5. Jobs and Payroll Information
Number of Full Time Employee equivalents currently employed by company (do not count consultants or contractors hired as independent agents)
Total current company payroll for preceding 12 months

6. Financial Information
Amount of equity investment received :
a)For preceding 12 months
b)Cumulative total
Amount of investment received using other financial instrument to date excluding equity investment above (e.g. loan, warrant, convertible note etc.)
a) For preceding 12 months
b) Cumulative total
Amount of grants and awards received to date. (e.g. Federal grants, Small business, Foundation grants, Competition awards) Please list source, amount and years if applicable.
a) For preceding 12 months




b) Cumulative total




Estimated market value (private) or market capitalization (public) of company

Report Prepared & Approved By

Name ( Please Print )

Title

Signature

Date ( mm / dd / yyyy )

_______ / _______ / ___________

Please submit completed report either via mail or email at address below:

Center for Technology Licensing

At Cornell University

395 Pine Tree Rd., Suite 310

Ithaca, NY 14850

ctl-contracts@cornell.edu

Appendix D : Commercialization Report

Company Name

CTL Agreement No

Your Reference No

Reporting Period ( mm / dd / yyyy )

From _______ / _______ / _____________ Through _______ / _______ / ______________

Date of first sale of

Licensed Product(s)

( mm / dd / yyyy ) ________ / ________ / _____________

Please list all trade names for product(s) incorporating licensed rights whether or not you had sales during this reporting period.
Product Name		Licensed Invention or Patent Rights (No.) used if known or Docket No	Country	Number of Units Sold	Gross Sales	Net Sales ( A )		Royalty Rate ¹ ( B )	Total Royalties ( A * B )









	1 Please refer to the license agreement for: · applicable royalty rate, please provide as decimal; · how Net Sales should be calculated; · applicable share of sublicense fees; · application of minimum royalty rate · If sales were in a currency other than United States Dollars, please specify exchange rate used 2 Subtract minimum royalty already paid from royalty subtotal for Total Royalty Owed						Royalty Subtotal
							Minimum Royalty already paid*
							Total Royalty Owed ²
							Total Sublicense Fees* (if applicable)
							Total Payment

Sublicense Activity (if applicable)
List of sublicenses granted during the reporting period			List of sublicenses terminated or expired during the reporting period





Total Number of active sublicenses during reporting period

List of Products being developed under this agreement
Product Name	Brief Description	Status
Product Name	Brief Description	Status
Product Name	Brief Description	Status
Product Name	Brief Description	Status
Product Name	Brief Description	Status

List of Licensed Product(s) Not Manufactured in the US
Product Name
Product Name
Product Name
Product Name

Jobs and Payroll Information
Number of Full Time Employee equivalents currently employed by company (do not count consultants or contractors hired as independent agents)
Total current company payroll for preceding 12 months

Financial Information
Amount of equity investment received :
c) For preceding 12 months
d) Cumulative total
Amount of investment received using other financial instrument to date excluding equity investment above (e.g. loan, warrant, convertible note etc.)
a) For preceding 12 months
c) Cumulative total
Amount of grants and awards received to date. (e.g. Federal Agency, Small business, NSF grants) Please list source, amount and years if applicable.
a) For preceding 12 months



b) Cumulative total



Estimated market value of company (best guess)

Report Prepared & Approved By

Name ( Please Print )

Title

Signature

Date ( mm / dd / yyyy )

_________ / _________ / ______________

Appendix E: Business Plan

[***]

THE REMAINDER OF THIS PAGE AND THE FOLLOWING 41 PAGES HAVE BEEN OMITTED AND FILED SEPARATELY WITH THE U.S. SECURITIES AND EXCHANGE COMMISSION PURSUANT TO A REQUEST FOR CONFIDENTIAL TREATMENT.

Exhibit 10.7

CONFIDENTIAL

License Agreement

This LICENSE AGREEMENT (“ Agreement ”) is entered into as of October 20, 2015 (“ Effective Date ”) by and between REGENXBIO Inc., a corporation organized under the laws of the State of Delaware, with offices at 9712 Medical Center Drive, Suite 100, Rockville, MD 20850, USA (“ Licensor ”), and Annapurna Therapeutics Limited organized under the laws of Ireland, with offices at 14 Taney Hall, Eglinton Terrace, Dundrum Dublin D14 C7F7, Ireland (“ Licensee ”). Licensor and Licensee are hereinafter referred to individually as a “ Party ” and collectively as the “ Parties .”

WHEREAS, Licensor has rights under the Licensed Patents (as defined herein) pertaining to certain recombinant adeno-associated virus vectors; and

WHEREAS, Licensee desires to obtain from Licensor certain licenses under the Licensed Patents under the terms set forth herein;

NOW, THEREFORE, in consideration of the promises and covenants contained in this Agreement, and intending to be legally bound, the Parties hereby agree as follows:

ARTICLE 1: DEFINITIONS

1.1 “ AAVrh10 ” means (a) the recombinant adeno-associated virus serotype rh10 vector with the specified sequence set forth in GenBank [***]; and (b) any recombinant adeno-associated virus derivatives of such serotype rh10 vector that are covered by the claims of the Licensed Patents.

1.2 “ AATD Field ” means the treatment of alpha-1 anti-trypsin deficiency (“ AATD ”) in human beings by in vivo gene therapy using AAVrh10 delivering a gene encoding human alpha-1 antitrypsin.

1.3 “ AAVrh10 Product ” means any product that incorporates, uses, is based upon or is derived from AAVrh10.

1.4 “ Affiliate ” means any legal entity directly or indirectly, during the Term, controlling, controlled by, or under common control with another entity. For purposes of this Agreement, “control” means the direct or indirect ownership of more than 50% of the outstanding voting securities of a legal entity, or the right to receive more than 50% of the profits or earnings of a legal entity, or the right to control the policy decisions of a legal entity. An entity may be or become an Affiliate of an entity and may cease to be an Affiliate of an entity, in each case, during the Term.

1.5 “ Allergy Field ” means the treatment of allergy in human beings by in vivo gene therapy using AAVrh10 delivering a gene encoding an anti-IgE antibody.

CONFIDENTIAL

1.6 “ Calendar Quarter ” means each three-month period or any portion thereof, beginning on January 1, April 1, July 1, and October 1.

1.7 “ Change of Control ” means (i) any transaction or series of related transactions following which the holders of Licensee’s capital stock or membership or equity interests immediately

prior to such transaction or series of related transactions collectively are the owners of less than 50% of the outstanding equity interests of Licensee entitled to (a) vote with respect to the election of directors (or positions having a similar function) or (b) receive the proceeds upon any sale, liquidation or dissolution of Licensee; (ii) a sale, transfer, or other disposition, in a single transaction or series of related transactions, of all or a material portion of Licensee’s interest in the Licensed Product; (iii) a sale, transfer, or other disposition, in a single transaction or series of related transactions, of all or a material portion of Licensee’s right title, or interest in its assets taken as a whole; (iv) an initial public offering of the stock of Licensee; or (v) the merger of Licensee with a Third Party by operation of law or otherwise.

1.8 “ Commercial Field ” means (a) AATD Field; and (b) if and when an Indication Option is exercised for the Option Field by Licensee pursuant to Section 2.2, the treatment of human beings in the Option Field.

1.9 “ Confidential Information ” means and includes all technical information, inventions, developments, discoveries, software, know-how, methods, techniques, formulae, animate and inanimate materials, data, processes, finances, business operations or affairs, and other proprietary ideas, whether or not patentable or copyrightable, of either Party that are (a) marked or otherwise identified as confidential or proprietary at the time of disclosure in writing; or (b) if disclosed orally, visually, or in another non-written form, identified as confidential at the time of disclosure and summarized in reasonable detail in writing as to its general content within 30 days after original disclosure. The Parties acknowledge that (i) the terms and conditions of this Agreement and (ii) the records and reports referred to in Section 3.9 will be deemed the Confidential Information of both Parties, regardless of whether such information is marked or identified as confidential. Notwithstanding the foregoing, Confidential Information will not include the following, in each case, to the extent evidenced by competent written proof of the Receiving Party:

1.9.1 information that was already known to the Receiving Party, other than under an obligation of confidentiality, at the time of disclosure by the Disclosing Party;

1.9.2 information that was generally available to the public or otherwise part of the public domain at the time of its disclosure to the Receiving Party;

1.9.3 information that became generally available to the public or otherwise part of the public domain after its disclosure, other than through any act or omission of the Receiving Party in breach of this Agreement;

1.9.4 information that is independently discovered or developed by the Receiving Party without the use of Confidential Information of the Disclosing Party; or

CONFIDENTIAL

1.9.5 information that was disclosed to the Receiving Party, other than under an obligation of confidentiality, by a Third Party who had no obligation to the Disclosing Party not to disclose such information to others.

1.10 “ Development Progress Report ” has the meaning set forth in Section 4.2.

1.11 “ Disclosing Party ” has the meaning set forth in Section 5.1.

1.12 “ Domain Antibody ” [***]

1.13 “ FDA ” means the United States Food and Drug Administration, or a successor agency in the United States with responsibilities comparable to those of the United States Food and Drug Administration.

1.14 “ Financing Term ” has the meaning set forth in Section 4.1.2.

1.15 “ GSK Agreement ” means that certain License Agreement entered into between Licensor and SmithKline Beecham Corporation, effective on March 6, 2009, as amended by that certain Amendment to License Agreement dated April 15, 2009, and as amended from time to time.

1.16 “ Indication Option ” has the meaning set forth in Section 2.2.

1.17 “ Licensed Patents ” means (a) all United States patents and patent applications listed in Exhibit A , including patents arising from such patent applications; and (b) any re-examination certificates thereof, and (c) the foreign counterparts of the patents and patent applications in subsection (a) and (b) and extensions, continuations, divisionals, and re-issue applications; provided that “Licensed Patents” will not include any claim of a patent or patent application covering any Manufacturing Technology.

1.18 “ Licensed Product ” means (a) any AAVrh10 Product that is made, made for, used, sold, offered for sale, or imported by Licensee, its Affiliates, and any of its or their Sublicensees, the manufacture, use, sale, offer for sale, or import of which product, in the absence of the license granted pursuant to this Agreement, would infringe or is covered by at least one Valid Claim of the Licensed Patents in the country of manufacture, use, sale, offer for sale, or import, including products manufactured by a process that would infringe or is covered by at least one Valid Claim of the Licensed Patents in the country of manufacture, use, sale, offer for sale, or import or (b) any service sold by Licensee, its Affiliates, and any of its or their Sublicensees with respect to the administration of any AAVrh10 Product to patients that in the absence of the license granted pursuant to this Agreement, would infringe or is covered by at least one Valid Claim of the Licensed Patents in the country of sale.

1.19 “ Licensee Inventions ” means any new or improved composition of matter, process, method, formula, information, product, invention (whether or not patentable or otherwise protectable), discovery, idea, material, or other know-how that, during the term of this Agreement, is first discovered, produced, conceived, or reduced to practice by or on behalf of Licensee or any of its Sublicensees in connection with the exercise of any rights granted under this Agreement that relate to or are applicable to the inventions claimed in the Licensed Patents.

CONFIDENTIAL

1.20 “ Manufacturing Technology ” means any and all patents, patent applications, know-how, and all intellectual property rights associated therewith that are owned or controlled.by Licensor, and including all tangible embodiments thereof, that claim, cover or relate to the manufacture of adeno-associated viruses, adeno-associated virus vectors, research or commercial reagents related thereto, Licensed Products, or other products, including manufacturing processes, technical information relating to the methods of manufacture, protocols, standard operating procedures, batch records, assays, formulations, quality control data, specifications, scale up methods, any and all improvements, modifications, and changes thereto, and any and all activities associated with such manufacture. Any and all chemistry, manufacturing, and controls (CMC), drug master files (DMFs), or similar materials provided to regulatory authorities and the information contained therein are deemed Manufacturing Technology.

1.21 “ Marketing Authorization ” means all approvals, licenses, registrations or authorizations of any federal, state or local regulatory agency, department, bureau or other governmental entity, necessary for the manufacturing, use, storage, import, transport, marketing and sale of Licensed Products in a country or regulatory jurisdiction.

1.22 “ NDA ” means a New Drug Application filed with the FDA as described in 21 C.F.R. § 314, a Biological License Application (“BLA”) pursuant to 21 C.F.R. § 601.2, or any equivalent or any corresponding application for regulatory approval in any country or regulatory jurisdiction other than the United States.

1.23 “ Net Sales ” means the gross receipts from sales or other disposition of a Licensed Product (including fees for services within the definition of “Licensed Product”) by Licensee and/or its Affiliates and/or any Sublicensees to Third Parties less the following deductions that are directly attributable to a sale, specifically and separately identified on an invoice or other documentation and actually borne by Licensee, its Affiliates, or any Sublicensees: [***]. In the event consideration other than cash is paid to Licensee, its Affiliates, or any Sublicensees, for purposes of determining Net Sales, the Parties shall use the cash consideration that Licensee, its Affiliates, or any Sublicensees would realize from an unrelated buyer in an arm’s length sale of an identical item sold in the same quantity and at the time and place of the transaction, as determined jointly by Licensor and Licensee based on transactions of a similar type and standard industry practice, if any.

1.24 “ Option Field ” means the Allergy Field subject to Licensee’s exercise of the Indication Option pursuant to Section 2.2.

1.25 “ Option Term ” means the period beginning on the Effective Date and ending on the first anniversary of the Effective Date.

1.26 “ Penn Agreement ” means that certain License Agreement entered into between Licensor and The Trustees of the University of Pennsylvania, effective on February 24, 2009, as amended by that letter agreement dated March 6, 2009 and by that certain Second Amendment to License Agreement effective on September 9, 2014, and as amended from time to time.

1.27 “ Phase 3 Clinical Trial ” means a pivotal clinical trial in humans performed to gain evidence with statistical significance of the efficacy of a product in a target population, and to

CONFIDENTIAL

obtain expanded evidence of safety for such product that is needed to evaluate the overall benefit-risk relationship of such product, to form the basis for approval of an NDA and to provide an adequate basis for physician labeling, as described in 21 C.F.R. § 312.21(c) or the corresponding regulation in jurisdictions other than the United States.

1.28 “ Prosecute ” means preparation, filing, and prosecuting patent applications and maintaining patents, including any reexaminations, reissues, oppositions, inter partes review, and interferences.

1.29 “ Qualified Financing ” means any combination of (i) the sale of any equity securities (or securities convertible into or exercisable for equity securities) and (ii) unrestricted grants or gifts.

1.30 “ Receiving Party ” has the meaning set forth in Section 5.1.

1.31 “ REGENX Licensors ” means SmithKline Beecham Corporation (or any successor thereto under the GSK Agreement) and The Trustees of the University of Pennsylvania (or any successor thereto under the Penn Agreement).

1.32 “ Retained Rights ” has the meaning set forth in Section 2.3.

1.33 “ Sublicensee ” means (i) any Third Party or Affiliate to whom Licensee grants a sublicense of some or all of the rights granted to Licensee under this Agreement as permitted by this Agreement; and (ii) any other Third Party or Affiliate to whom a sublicensee described in clause (i) has granted a further sublicense as permitted by this Agreement.

1.34 “ Third Party ” means any person or entity other than a Party to this Agreement or Affiliates of a Party to this Agreement.

1.35 “ Valid Claim ” means a claim of an issued and unexpired patent (including any patent claim the term of which is extended by any extension, supplementary protection certificate, patent term restoration, or the like) included within the Licensed Patents or a claim of a pending patent application included within the Licensed Patents, which has not lapsed, been abandoned, been held revoked, or been deemed unenforceable or invalid by a non-appealable decision or an appealable decision from which no appeal was taken within the time allowed for such appeal of a court or other governmental agency of competent jurisdiction.

ARTICLE 2: LICENSE GRANTS

2.1 Exclusive License Grant . Subject to the terms and conditions of this Agreement, including the Retained Rights, Licensor hereby grants to Licensee an exclusive, sublicensable (as provided in Section 2.5 only), non-transferable (except as provided in Section 10.2), royalty-bearing, worldwide license under the Licensed Patents to make, have made, use, import, sell, and offer for sale Licensed Products in the AATD Field, including, for the avoidance of doubt, the right to conduct research and development.

CONFIDENTIAL

2.2 License Option .

2.2.1 Option . Subject to the terms and conditions of this Agreement during the Option Term, Licensor hereby grants to Licensee an exclusive option, exercisable at Licensee’s sole discretion, to obtain an exclusive, sublicensable (as provided in Section 2.5), non-transferable (except as provided in Section 10.2), royalty-bearing, worldwide license in the Option Field (an “ Indication Option ”) in accordance with the following provisions:

2.2.2 Method of Exercise . To exercise the Indication Option, Licensee must provide written notice to Licensor of its desire to include the Option Field in the Commercial Field under this Agreement and pay the fee specified in Section 3.4 prior to the end of the Option Term.

2.2.3 License Grant Upon Exercise . If Licensee exercises the Indication Option for the Option Field by providing such written notice, effective upon Licensor’s receipt of the fee described in Section 3.4 (the “ Grant Date ” for the Option Field ), subject to the terms and conditions of this Agreement, including the Retained Rights, Licensor shall be deemed to have granted to Licensee an exclusive, sublicensable (as provided in Section 2.5 only), nontransferable (except as provided in Section 10.2), royalty-bearing, worldwide license under the Licensed Patents to make, have made, use, import, sell, and offer for sale Licensed Products in the Option Field, including, for the avoidance of doubt, the right to conduct research and development.

2.2.4 Exercised Indication Option . For the avoidance of doubt, the foregoing license granted pursuant to Section 2.2.3 will be deemed granted on the Grant Date with respect to the Option Field. The Indication Option will terminate with respect to the Option Field at the end of the Option Term if Licensee fails to exercise the Indication Option during the Option Term, and Licensee will have no further rights under this Agreement with respect to the Option Field; provided that the termination of the Indication Option will not affect Licensee’s rights under this Agreement with respect to the license granted under Section 2.1.

2.3 Retained Rights .

2.3.1 Except for the rights and licenses specified in Section 2.1 and, if applicable, Section 2.2.3, no license or other rights are granted to Licensee under any intellectual property of Licensor, whether by implication, estoppel, or otherwise and whether such intellectual property is subordinate, dominant, or otherwise useful for the practice of the Licensed Patents. Notwithstanding anything to the contrary in this Agreement, Licensor may use and permit others to use the Licensed Patents for any research, development, commercial, or other purposes inside or outside of the Commercial Field (other than to the extent of the exclusive license under Section 2.1 and if applicable, Section 2.2.3). Without limiting the foregoing, and notwithstanding anything in this Agreement to the contrary, Licensee acknowledges and agrees to the following rights retained by Licensor and the REGENX Licensors (individually and collectively, the “ Retained Rights ”), whether inside or outside the Commercial Field:

2.3.1.1 The rights and licenses granted in Section 2.1 and, if applicable, Section 2.2.3 shall not include any right (and Licensor and the REGENX Licensors retain the exclusive (even as to Licensee), fully sublicensable right) under the Licensed Patents to

CONFIDENTIAL

make, have made, use, sell, offer to sell, and import Domain Antibodies that are expressed by an adeno-associated vector, including AAVrh10.

2.3.1.2 Licensor and the REGENX Licensors retain the following rights with respect to the Licensed Patents:

(a)

A non-exclusive, sublicensable right under the Licensed Patents to make, have made, use, sell, offer to sell, and import products that deliver RNA interference and antisense drugs using an adeno-associated vector, including AAVrh10; and

(b)

A non-exclusive right for the REGENX Licensors (which right is sublicensable by such licensors) to use the Licensed Patents for educational, research, development and other non-commercial purposes and to use the Licensed Patents for such licensors’ discovery research efforts with non-profit organizations and non-profit collaborators.

2.3.1.3 The rights and licenses granted in Section 2.1 and, if applicable, Section 2.2.3 shall not include any right (and Licensor retains the exclusive (even as to Licensee), fully sublicensable right) under the Licensed Patents:

(a)

(b)

to use the Licensed Patents to provide services to any Third Parties; provided that Licensee’s license under Section 2.1 and, if applicable, Section 2.2.3 does include the right to provide services in connection with the administration of Licensed Products to patients.

2.3.1.4 Licensor retains the fully sublicensable right under the Licensed Patents to grant non-exclusive research and development licenses to Affiliates and Third Parties; provided that such development rights granted by Licensor shall not include the right to conduct clinical trials in humans in the Commercial Field using AAVrh10 or any rights to sell products using AAVrh10 in the Commercial Field.

2.3.1.5 The Trustees of the University of Pennsylvania may use and permit other non-profit organizations or other non-commercial entities to use the Licensed Patents for educational and research purposes, solely to the extent required under the terms and conditions of the Penn Agreement.

CONFIDENTIAL

2.4 Government Rights . Licensee acknowledges that the United States government retains certain rights in intellectual property funded in whole or part under any contract, grant, or similar agreement with a federal agency. The license grants hereunder are expressly subject to all applicable United States government rights, including any applicable requirement that products that result from such intellectual property and are sold in the United States must be substantially manufactured in the United States.

2.5 Sublicensing .

2.5.1 The license granted pursuant to Section 2.1 and, if applicable, Section 2.2.3 is sublicensable by Licensee to any Affiliates or Third Parties; provided that any such sublicense must comply with the provisions of this Section 2.5 (including Section 2.5.2).

2.5.2 The right to sublicense granted to Licensee under this Agreement is subject to the following conditions:

(a)

Licensee may only grant sublicenses pursuant to a written sublicense agreement with the Sublicensee; [***]. Licensor must receive written notice as soon as practicable following execution of any such sublicenses.

(b)

In each sublicense agreement, the Sublicensee must be required to comply with the terms and conditions of this Agreement to the same extent as Licensee has agreed and must acknowledge that Licensor is an express third party beneficiary of such terms and conditions under such sublicense agreement.

(c)

The official language of any sublicense agreement shall be English.

(d)

Within [***] after entering into a sublicense, Licensor must receive an unredacted copy of the sublicense written in the English language for Licensor’s records and to share with the REGENX Licensors.

(e)

Licensee’s execution of a sublicense agreement will not relieve Licensee of any of its obligations under this Agreement. Licensee is and shall remain [***] to Licensor for all of Licensee’s duties and obligations contained in this Agreement and for any act or omission of an Affiliate or Sublicensee that would be a breach of this Agreement if performed or omitted by Licensee, and Licensee will be deemed to be in breach of this Agreement as a result of such act or omission.

2.6 Non-Exclusive License Under Licensee Inventions . Licensee hereby grants to Licensor a non-exclusive, worldwide, royalty-free, transferable, sublicensable, irrevocable, perpetual license under Licensee Inventions and any intellectual property rights with respect thereto to practice the Licensee Inventions in connection with AAVrh10, including, for avoidance of doubt, the right to conduct research and develop and commercialize products and services.

CONFIDENTIAL

2.7 Improvements .

2.7.1 Licensee hereby grants to Licensor a non-exclusive, worldwide, royalty-free, transferable, sublicensable, irrevocable, perpetual license:

(a)

to use any Licensed Back Improvements (and any intellectual property rights with respect thereto) for purposes consummate in scope to the Retained Rights, and

(b)

to practice the Licensed Back Improvements (and any intellectual property rights with respect thereto) for any and all purposes, including the right to research, develop, make, have made, use, offer for sale, and sell products and services; provided that, during the term of this Agreement, Licensor shall have no right, under the license in this Section 2.7.1(b), to practice the Licensed Back Improvements with respect to AAVrh10 in the Commercial Field.

2.7.2 For purposes of this Agreement, “ Licensed Back Improvements ” means any patentable modifications or improvements developed by Licensee, any of its Affiliates, or any Sublicensees to any vector that is the subject of a claim within the Licensed Patents, which modification or improvement is developed by Licensee or any of its Affiliates during the term of this Agreement or by any Sublicensee during the term of any sublicense agreement with such Sublicensee.

2.7.3 Licensee agrees to provide prompt notice to Licensor upon the filing of any patent application covering any Licensee Inventions and/or any Licensed Back Improvement, together with a reasonably detailed description of or access to such Licensee Inventions and/or Licensed Back Improvement to permit the practice of any such invention and/or improvement.

2.8 Covenants Regarding In-Licenses . During the term of this Agreement, without the prior written consent of Licensee, which consent shall not be unreasonably withheld, Licensor agrees not to exercise its right to terminate and will not amend either the GSK Agreement or Penn Agreement if such termination or amendment would materially, adversely affect Licensee’s rights under this Agreement with respect to the Licensed Patents.

2.9 Section 365(n) of the Bankruptcy Code . All rights and licenses granted to Licensee or Licensor under or pursuant to this Agreement are and will otherwise be deemed to be, for purposes of Section 365(n) of the United States Bankruptcy Code (Title 11, U.S. Code), as amended (the “ Bankruptcy Code ”) or any comparable law outside the United States, licenses of rights to “intellectual property” as defined in Section 101(35A) of the Bankruptcy Code. The Parties will retain and may fully exercise all of their respective rights and elections under the Bankruptcy Code and any comparable law outside the United States.

CONFIDENTIAL

ARTICLE 3: CONSIDERATION

3.1 Upfront Fee . In partial consideration of the rights and licenses granted to Licensee under this Agreement, Licensee shall pay Licensor an initial fee of [***], which shall be payable as follows: (a) [***] upon the Effective Date; and (b) [***]within six (6) months of the Effective Date; provided that any unpaid portion of the initial fee shall be immediately payable upon termination of this Agreement.

3.2 Additional One Time Fee . In partial consideration of the rights and licenses granted to Licensee under this Agreement, Licensee shall pay Licensor [***], which shall be payable on or before the first of the following to occur: (a) Licenseee obtaining [***] in a Qualified Financing or series of Qualified Financings, or (b) the first anniversary of the Effective Date; provided that any unpaid portion of the additional payment shall be immediately payable upon termination of this Agreement.

3.3 Indication Option Fee . In partial consideration of the Indication Option granted to Licensee under Section 2.2, Licensee shall pay Licensor [***] upon the Effective Date.

3.4 Exercise of Indication Option Fee . For the Option Field for which Licensee exercises the Indication Option pursuant to Section 2.2, Licensee shall, on the date the Indication Option is exercised, pay Licensor a fee of $900,000 U.S. Dollars.

3.5 Annual Maintenance Fee . In partial consideration of the rights and licenses granted to Licensee under this Agreement, Licensee shall pay Licensor the following on-going annual maintenance fees [***] each anniversary of the Effective Date:

(a)

For the AATD Field, [***]; and

(b)

For the Option Field for which Licensee exercises the Indication Option pursuant to Section 2.2, Licensee shall pay Licensor [***].

CONFIDENTIAL

3.6 Milestone Fees .

3.6.1 AATD Field .

3.6.1.1 Development Milestones . In partial consideration of the rights and licenses granted to Licensee under this Agreement, Licensee shall pay Licensor the following milestone payments one time only for only the first Licensed Product in the AATD Field to achieve each of the following milestone events:

Development Milestone	Milestone Payment
1. First treatment of the 4 ^th human subject in a clinical trial	[***]
2. First treatment in Phase 3 Clinical Trial (i.e., first patient, first dose)	[***]
3. NDA submission in any country	[***]
4. Marketing Authorization in the United States	[***]
5. Marketing Authorization in the European Union	[***]
6. Marketing Authorization in any country or territory other than the United States and the European Union	[***]
Total (per Licensed Product in the AATD Field)	[***]

3.6.1.2 For clarity, the milestone payments set forth in Section 3.6.1.1 are payable [***] with respect to only the [***] Licensed Product in the AATD Field to reach each of the foregoing milestone events, [***]. In the event that any development milestone event is met with respect to a specific Licensed Product prior to the satisfaction of any prior milestone event with respect to the applicable Licensed Product, then Licensee shall also pay the amount due for occurrence of all prior milestone events not previously paid with respect to the applicable Licensed Product upon meeting the applicable development milestone (e.g., if an NDA is submitted prior to dosing of a first patient in a Phase 3 Clinical Trial, Licensee shall pay Licensor [***] upon NDA submission).

CONFIDENTIAL

3.6.2 Option Field .

3.6.2.1 Development Milestones . In partial consideration of the rights and licenses granted to Licensee under this Agreement, Licensee shall pay Licensor the following milestone payments one time only for the first Licensed Product in the Option Field licensed by Licensee in accordance with Section 2.2 which achieves each of the following milestone events:

Development Milestone	Milestone Payment
1. First treatment of a human subject in a clinical trial ( i.e. , first patient, first dose)	[***]
2. First treatment in Phase 3 Clinical Trial (i.e., first patient, first dose)	[***]
3. NDA submission in any country	[***]
4. Marketing Authorization in the United States	[***]
5. Marketing Authorization in the European Union	[***]
6. Marketing Authorization in any country or territory other than the United States and the European Union	[***]
Total (per Licensed Product within the Option Field)	[***]

3.6.2.2 For clarity, the milestone payments set forth in Section 3.6.2.1 are payable only [***] with respect to the [***] Licensed Product in the Option Field licensed by Licensee in accordance with Section 2.2 that achieves the milestone event, [***]. In the event that any development milestone event is met with respect to a specific Licensed Product prior to the satisfaction of any prior milestone event with respect to the applicable Licensed Product, then Licensee shall also pay the amount due for occurrence of all prior milestone events not previously paid with respect to the applicable Licensed Product upon meeting the applicable development milestone ( e.g. , if an NDA is submitted prior to dosing of a first patient in a Phase 3 Clinical Trial, Licensee shall pay Licensor [***] upon NDA submission).

3.7 Royalties .

3.7.1 In consideration of the rights and licenses granted to Licensee under this Agreement, Licensee shall pay to Licensor the following royalties based upon the annual Net Sales worldwide of all Licensed Products, on a field-by field basis, in a given calendar year, subject to the reductions in royalty rates set forth in Sections 3.7.2 and 3.7.3:


Cumulative Annual Net Sales of all Licensed Products Worldwide	Royalty Percentage
Portion of Net Sales less than [***]	[***]
Portion of Net Sales between (and including) [*] through (and including) [*]	[***]
Portion of Net Sales greater than [***]	[***]

CONFIDENTIAL

3.7.2 Adjustment of Royalties For Licenses . On a Licensed Product-by-Licensed Product, country-by-country basis, upon the date on which the manufacture, use, sale, offer for sale or import of a Licensed Product does not infringe or is not covered by a Valid Claim existing in such country, no royalty shall be applicable to Net Sales of such Licensed Product under this Section 3.7 in such country.

3.7.3 Third Party Royalties Stacking Provision . If Licensee must obtain a license from a Third Party to avoid infringement of such Third Party’s rights in order to manufacture, use, or commercialize a given Licensed Product and if the royalties required to be paid to such Third Party for such license, together with those royalties payable to Licensor, in the aggregate, exceed [***] of Net Sales for any Licensed Product, then the royalty owed to Licensor for that Licensed Product will be reduced by an amount calculated as follows:

STACKING ROYALTY CALCULATIONS
R = (C * (A / (A+B)))

Where

R = reduction of Licensor royalty,

A = unreduced Licensor royalty,

B = sum of all Third Party royalties,

C = increment of projected total royalty above [***].

Example Calculation:


Assume:		i) all Third Party royalties = [***]
		ii) unreduced Licensor royalty = [***]
		iii) projected total royalty = [***]
		R = ([*] - [])([*] / ([] + [**]))
		R = ([**] [***])
		R = [***]
		Licensor Stacked Royalty = [*] - [] = [**]

Notwithstanding the foregoing, Licensee will pay to Licensor no less than [***] of the royalties that Licensee would otherwise pay to Licensor with respect to Net Sales if there were no royalties due to Third Parties.

3.7.4 Royalty Payment Period . Licensee’s obligation hereunder for payment of a royalty under this Section 3.7 on the Net Sales of Licensed Products in a given country will end on a Licensed Product-by-Licensed Product and country-by-country basis at such time when the Licensed Product ceases to infringe or be covered by a Valid Claim within the Licensed Patents in that country.

CONFIDENTIAL

3.8 Sublicense Fees .

3.8.1 In further consideration of the rights and licenses granted to Licensee under this Agreement, Licensee shall pay Licensor a percentage of any sublicense fees [***] received by Licensee or its Affiliates for the Licensed Products from any Third Party Sublicensee or from any Third Party granted any option to obtain a sublicense. The applicable percentage due to Licensor for each sublicense (or option) in the Commercial Field shall be as follows:


Event	Sublicense Fee Rate
If Licensee or its Affiliates grant a Third Party a sublicense or an option to obtain a sublicense on or before [*] if the sublicense or option relates to the AATD Field, or (ii) [*] if the sublicense or option relates to the Option Field	[***]

If Licensee or its Affiliates grant a Third Party a sublicense or an option to obtain a sublicense after the [*] if the sublicense or option relates to the AATD Field, or (ii) [*] if the sublicense or option relates to the Option Field	[***]

3.8.2 With respect to the obligations under this Section 3.8, Licensee shall not be required to submit any amounts received from a Third Party for the following:

(a)

Reimbursement or payment, in either case, of Licensee’s actual costs for research, development, patent and/or manufacturing activities performed by Licensee or its Affiliates corresponding directly to the research, development and/or manufacturing of Licensed Products pursuant to a specific agreement;

(b)

Consideration received for the purchase of an equity interest in Licensee or its Affiliates at fair market value or in the form of loans at commercially reasonable rates of interest; and

(c)

Any and all amounts paid to Licensee or its Affiliates by a Third Party Sublicensee as royalties on sales of Licensed Product sold by such Sublicensee under a sublicense agreement.

3.8.3 If Licensee or its Affiliate receives sublicense fees from Third Party Sublicensees or from any Third Party granted any option to obtain a sublicense under this Agreement in the form of non-cash consideration, then Licensee shall, at Licensor’s option, pay Licensor payments as required by this Section 3.8 in the form of the non-cash consideration received by Licensee or its Affiliates or (b) a cash payment determined based on the fair market value of such non-cash consideration. If Licensee or its Affiliate enters into any sublicense that is not an arm’s length transaction, fees due under this Section 3.8 will be calculated based on the fair market value of

CONFIDENTIAL

such transaction, at the time of the transaction, assuming an arm’s length transaction made in the ordinary course of business, as determined jointly and in good faith by Licensor and Licensee based on transactions of a similar type and standard industry practice, if any.

3.8.4 To the extent Licensee or its Affiliates receives payment from a Third Party relating to one or more of the milestone events set forth in the tables in Section 3.6, then the amount of the payment made to Licensor under such Section 3.6 with respect to such milestone event shall not be deemed sublicense fees under this Section 3.8; instead, the amounts due under this Section 3.8 shall be calculated by applying the applicable sublicense fee rate set forth in Section 3.8.1 above to the sublicense fees received by Licensee or its Affiliates from such Third Party after deducting the amount of the payment under Section 3.6.

3.9 Reports and Records .

3.9.1 Licensee must deliver to Licensor within [***] after the end of each Calendar Quarter after the first commercial sale of a Licensed Product a report setting forth the calculation of the royalties due to Licensor for such Calendar Quarter, including:

(a)

Number of Licensed Products included within Net Sales, listed by country;

(b)

Gross consideration for Net Sales of Licensed Product, including all amounts invoiced, billed, or received;

(c)

Qualifying costs to be excluded from the gross consideration, as described in Section 1.23, listed by category of cost;

(d)

Net Sales of Licensed Products listed by country;

(e)

A detailed accounting of any royalty reductions applied pursuant to Sections 3.7.2 and 3.7.3;

(f)

Royalties owed to Licensor, listed by category; and

(g)

The computations for any applicable currency conversions.

3.9.2 Licensee shall pay the royalties due under Section 3.7 within [***] following the last day of the Calendar Quarter in which the royalties accrue. Licensee shall send the royalty payments along with the report described in Section 3.9.1.

3.9.3 Within [***] after the occurrence of a milestone event described in Section 3.6, Licensee must deliver to Licensor a report describing the milestone event that occurred, together with a payment of the applicable amount due to Licensor pursuant to Section 3.6.

3.9.4 Within [***] after the receipt of any fees from any Third Party as described in Section 3.8, Licensee must deliver to Licensor a report describing the fees received, together with a payment of the applicable amount due to Licensor pursuant to Section 3.8.

CONFIDENTIAL

3.9.5 All financial reports under this Section 3.9 will be certified by the chief financial officer of Licensee.

3.9.6 Licensee shall maintain and require its Affiliates and all Sublicensees to maintain, complete and accurate books and records which enable the royalties, fees, and payments payable under this Agreement to be verified. The records must be maintained for [***] after the submission of each report under Article 3. Upon reasonable prior written notice to Licensee, Licensee and its Affiliates and all Sublicensees will provide Licensor and/or the REGENX Licensors (and their respective accountants) with access to all of the relevant books, records, and related background information required to conduct a review or audit of the royalties, fees, and payments payable to Licensor under this Agreement to be verified. Access will be made available: (a) during normal business hours; (b) in a manner reasonably designed to facilitate the auditing party’s review or audit without unreasonable disruption to Licensee’s business; and (c) no more than once each calendar year during the term of this Agreement and for a period of five (5) years thereafter. Licensee will promptly pay to Licensor the amount of any underpayment determined by the review or audit, plus accrued interest. If the review or audit determines that Licensee has underpaid any payment by [***] or more, then Licensee will also promptly pay the costs and expenses of Licensor and the REGENX Licensors and their respective accountants in connection with the review or audit.

3.10 Currency, Interest .

3.10.1 All dollar amounts referred to in this Agreement are expressed in United States dollars. All payments to Licensor under this Agreement must be made in United States dollars.

3.10.2 If Licensee receives payment in a currency other than United States dollars for which a royalty or fee or other payment is owed under this Agreement, then (a) the payment will be converted into United States dollars at the conversion rate for the foreign currency as published in the eastern edition of the Wall Street Journal, N.Y. edition, as of the last business day of the Calendar Quarter in which the payment was received by Licensee; and (b) the conversion computation will be documented by Licensee in the applicable report delivered to Licensor under Section 3.9.

3.10.3 All amounts that are not paid by Licensee when due will accrue interest from the date due until paid at a rate equal to one point five percent (1.5%) per month (or the maximum allowed by law, if less).

3.11 Taxes and Withholding .

3.11.1 All payments hereunder will be made free and clear of, and without deduction or deferment in respect of, and Licensee shall pay and be responsible for, and shall hold Licensor harmless from and against, any taxes, duties, levies, fees, or charges, including sales, use, transfer, excise, import, and value added taxes (including any interest, penalties, or additional amounts imposed with respect thereto) but excluding withholding taxes to the extent provided in Section 3.11.2. At the request of Licensee, Licensor will give Licensee such reasonable assistance, which will include the provision of documentation as may be required by the

CONFIDENTIAL

relevant tax authority, to enable Licensee to pay and report and, as applicable, claim exemption from or reduction of, such tax, duty, levy, fee, or charge.

3.11.2 If any payment made by Licensee hereunder becomes subject to withholding taxes with respect to Licensor’s gross or net income under the laws of any jurisdiction, Licensee will deduct and withhold the amount of such taxes for the account of Licensor to the extent required by law and will pay the amounts of such taxes to the proper governmental authority in a timely manner and promptly transmit to Licensor appropriate proof of payment of such withholding taxes. At the request of Licensor, Licensee will give Licensor such reasonable assistance, which will include the provision of appropriate certificates of such deductions made together with other supporting documentation as may be required by the relevant tax authority, to enable Licensor to claim exemption from or reduction of, or otherwise obtain repayment of, such withholding taxes, and will upon request provide such additional documentation from time to time as is reasonably required to confirm the payment of withholding tax.

ARTICLE 4: DILIGENCE

4.1 Diligence Obligations .

4.1.1 Licensed Product Diligence Obligations . Licensee will use commercially reasonable efforts to develop, commercialize, market, promote, and sell Licensed Products in the AATD Field. Furthermore, if Licensee exercises the Indication Option granted to Licensee under Section 2.2, Licensee will use commercially reasonable efforts to develop, commercialize, market, promote, and sell Licensed Products in the Option Field for which Licensee exercised an Indication Option. Commercially reasonable efforts means efforts equivalent to those utilized by [***]. Without limiting the foregoing, if Licensee exercises an Indication Option granted to Licensee under Section 2.2, Licensee shall have an Investigational New Drug application accepted by the FDA, or an application equivalent to an Investigational New Drug application accepted by the European Medicines Agency (or any successor entity thereto), for a Licensed Product in the Option Field for which Licensee has exercised an Indication Option by no later than [***]after the Grant Date for the Option Field; provided, however, that, if Licensee expects not to achieve this milestone on or before the specified deadline, Licensee may pay Licensor an extension fee of [***] on or before such deadline and the deadline shall then be extended by an additional [***]. Licensee will only be entitled to [***] of this milestone and Licensee will provide Licensor written notice within [***] of achieving this milestone.

4.1.2 Financing Diligence Obligations . Licensee shall raise an aggregate of at least [***] in a Qualified Financing or a series of Qualified Financings by no later than [***] after the Effective Date (the “ Financing Term ”).

4.2 Reporting . Within [***] after the Effective Date and within [***] of each December 1 thereafter, Licensee shall provide Licensor with written progress reports, setting forth in such detail as Licensor may reasonably request, the progress of the development, evaluation, testing, and commercialization of each Licensed Product. Licensee will also notify Licensor within [***] of the first commercial sale by Licensee, its Affiliates, or any Sublicensees of each Licensed Product. Such a report (“ Development Progress Report ”), setting forth (i) the current stage of development of Licensed Products, and (ii) until such time as Licensee has raised at least

CONFIDENTIAL

$10,000,000 U.S. Dollars in a Qualified Financing or a series of Qualified Financings, progress reports with respect to any completed or contemplated Qualified Financing. Development Progress Reports shall also include:

4.2.1 Date of Development Progress Report and time covered by such report;

4.2.2 Major activities and accomplishments completed by Licensee, its Affiliates, and any Sublicensees relating directly to the Licensed Product since the last Development Progress Report;

4.2.3 Significant research and development projects relating directly to the Licensed Product currently being performed by Licensee, its Affiliates, and any Sublicensees and good faith, but non-binding, projected dates of completion;

4.2.4 A development plan covering the next two (2) years at least, which will include future development activities to be undertaken by Licensee, its Affiliates, or any Sublicensees during the next reporting period relating directly to the Licensed Product, Licensee’s strategy to bring the Licensed Product to commercialization, and good faith, but non-binding, projected timeline for completing the necessary tasks to accomplish the goals of the strategy;

4.2.5 Projected total development remaining before product launch of each Licensed Product; and

4.2.6 Summary of significant development efforts using the Licensed Patents being performed by Third Parties, including the nature of the relationship between Licensee and such Third Parties.

4.3 Development Plans . Following receipt by Licensor of each development plan, Licensor will promptly notify Licensee of any comments or requested revisions, and the Parties will thereupon negotiate any appropriate revisions in good faith.

4.4 Confidential Information . The Parties agree that Development Progress Reports shall be deemed Licensee’s Confidential Information; provided that Licensor may share a copy of such reports with the REGENX Licensors under confidentiality.

4.5 Improvements . Simultaneously with the Development Progress Report, Licensee shall deliver a detailed description of any Licensee Inventions and any Licensed Back Improvements, if not previously provided pursuant to Section 2.7.3, which shall be Licensee’s Confidential Information.

ARTICLE 5: CONFIDENTIALITY

5.1 Treatment of Confidential Information . Each Party, as a receiving party (a “ Receiving Party ”), agrees that it will (a) treat Confidential Information received by or on behalf of the other Party under this Agreement (the “ Disclosing Party ”) as strictly confidential; (b) not disclose such Confidential Information to Third Parties without the prior written consent of the Disclosing Party, except as may be permitted in this Agreement; provided that any disclosure permitted hereunder shall be under confidentiality agreements with provisions at least as stringent as those

CONFIDENTIAL

contained in this Agreement; and (c) not use such Confidential Information for purposes other than those authorized expressly in this Agreement. The Receiving Party agrees to ensure that its employees who have access to Confidential Information are obligated in writing to abide by confidentiality obligations at least as stringent as those contained under this Agreement.

5.2 Public Announcements .

5.2.1 The Parties agree they will release a joint press release in the form attached hereto as Exhibit B . Except as provided in Section 5.2.2, any other press releases by either Party with respect to the other Party or any other public disclosures concerning the existence of or terms of this Agreement shall be subject to review and approval by the other Party. Once the joint press release or any other written statement is approved for disclosure by both Parties, either Party may make subsequent public disclosure of the contents of such statement without the further approval of the other Party.

5.2.2 Notwithstanding Section 5.2.1, Licensor has the right to publish (through press releases, scientific journals, or otherwise) and refer to any clinical, regulatory, or research results related to Licensee’s Licensed Product that have been publicly disclosed by Licensee, including referring to Licensee by name as a licensee of Licensor, which publication or referral by Licensor shall not require the prior consent of Licensee, but Licensor will provide Licensee with a copy of any such publications or referrals two business days prior to release.

5.3 Authorized Disclosure . Notwithstanding the provisions of Section 5.1 or 5.2, either Party may disclose the other’s Confidential Information or make such a disclosure of the existence of and/or terms of this Agreement to any [***]; provided that, in each case, such recipient of Confidential Information is obligated to keep such information confidential on terms no less stringent than those set forth in this Agreement. Furthermore, Licensee agrees that Licensor may share a copy of this Agreement, reports and notices provided by Licensee to Licensor pursuant to the terms of this Agreement, and copies of sublicense agreements provided to Licensor hereunder, with the REGENX Licensors to the extent required by the GSK Agreement and Penn Agreement, under confidentiality. In the event that the Receiving Party receives service of legal process that purports to compel disclosure of the Disclosing Party’s Confidential Information or becomes obligated by law, rule, regulation or rules of a securities exchange to disclose the Confidential Information of the Disclosing Party or the existence of or terms of this Agreement to any governmental authority, then, to the extent legally permitted, the Receiving Party shall promptly notify the Disclosing Party, so that the Disclosing Party may seek an appropriate protective order or other remedy with respect to narrowing the scope of such requirement and/or waive compliance by the Receiving Party with the provisions of this Agreement. The Receiving Party will, at the Disclosing Party’s request and expense, provide the Disclosing Party with reasonable assistance in obtaining such protective order or other remedy. If, in the absence of such protective order or other remedy, the Receiving Party is nonetheless required by law, rule, regulation or rules of a securities exchange to disclose the existence of or terms of this Agreement or other Confidential Information of the Disclosing Party, the Receiving Party may disclose such Confidential Information without liability hereunder; provided that the Receiving Party shall furnish only such portion of the Confidential Information that is legally required to be disclosed and only to the extent required by law.

CONFIDENTIAL

5.4 Term of Confidentiality . The obligations of this Article 5 shall continue for a period of [***] following the expiration or termination of this Agreement.

ARTICLE 6: TERM AND TERMINATION

6.1 Term of Agreement . This Agreement will commence on the Effective Date and continue in effect on a country-by-country, Licensed Product-by-Licensed Product basis until the expiration, lapse, abandonment, or invalidation of the last Valid Claim of the Licensed Patents to expire, lapse, become abandoned, or become unenforceable for the applicable Licensed Product, unless sooner terminated as provided in this Agreement.

6.2 Termination for Failure to Exercise Option . This Agreement will terminate automatically with respect to the Option Field for which Licensee has not exercised an Indication Option at the end of the Option Term.

6.3 Licensee’s Right to Terminate . Licensee may, upon six (6) months prior written notice to Licensor, terminate this Agreement for any reason, with or without cause. In exercising such termination right, Licensee may terminate the Agreement in its entirety or, if desired, Licensee may specify in the written notice that this Agreement is terminating only with respect to one or more of the fields within the Commercial Field.

6.4 Termination for Breach .

6.4.1 Licensor may terminate this Agreement, if Licensee is late in paying to Licensor royalties, fees, or any other monies due under this Agreement, and Licensee does not pay Licensor in full within fifteen (15) days upon written demand from Licensor, which termination shall be effective immediately upon the expiration of such fifteen (15)-day cure period.

6.4.2 Either Party may terminate this Agreement, if the other Party materially breaches this Agreement and does not cure such material breach within thirty (30) days after written notice of the breach, which termination shall be effective immediately upon the expiration of such thirty (30)-day cure period.

6.5 Termination for Insolvency .

6.5.1 Licensor may terminate this Agreement, effective immediately upon written notice to Licensee, if Licensee, any of its Affiliates, or any Sublicensees experiences any Trigger Event.

CONFIDENTIAL

commencement by Licensee, any Affiliate, or any Sublicensee, as applicable, of any proceeding under any law related to bankruptcy, insolvency, liquidation, or the reorganization, readjustment, or release of debtors; (c) the entering of any order for relief relating to any of the proceedings described in Section 6.5.2(a) or (b) above; (d) the calling by Licensee, any Affiliate, or any Sublicensee, as applicable, of a meeting of its creditors with a view to arranging a composition or adjustment of its debts; or (e) the act or failure to act by Licensee, any Affiliate, or any Sublicensee, as applicable, indicating its consent to, approval of, or acquiescence in any of the proceedings described in Section 6.5.2(b) through (d) above.

6.6 Patent Challenge .

6.6.1 Licensor may terminate this Agreement, effective immediately upon written notice to Licensee, upon the commencement by Licensee, any of its Affiliates or any Sublicensees of a Patent Challenge.

6.6.2 For purposes of this Section 6.6, “ Patent Challenge ” means any action against Licensor, The Trustees of the University of Pennsylvania, or the REGENX Licensors, including an action for declaratory judgment, to declare or render invalid or unenforceable the Licensed Patents, or any claim thereof.

6.7 Effects of Termination . The effect of termination pursuant to Section 6.2, by Licensee pursuant to Section 6.3, by either Party, as applicable, under Section 6.4, or by Licensor pursuant to Section 6.5 or 6.6 shall be as follows; provided that for any termination with respect to a particular field in the Commercial Field, then the following provisions shall apply only with respect to such field:

6.7.1 The licenses granted by Licensor hereunder shall terminate, and Licensee, its Affiliates, and (unless the sublicense agreement is assigned pursuant to Section 6.7.2) all Sublicensees shall cease to make, have made, use, import, sell, and offer for sale all Licensed Products and shall cease to otherwise practice the Licensed Patents; provided that Licensee, its Affiliates, and Sublicensees shall have the right to continue to sell their existing inventories of Licensed Products for a period not to exceed [***] after the effective date of such termination;

6.7.2 At Licensor’s request, Licensee shall assign to Licensor any or all sublicenses granted to Third Parties to the extent of the rights licensed to Licensee hereunder and sublicensed to the Sublicensee unless the Sublicensee notifies Licensor in writing that the Sublicensee does not wish such sublicense to be so assigned (in which case such sublicense shall terminate); provided that (i) prior to such assignment, Licensee shall advise Licensor whether such Sublicensee is then in full compliance with all terms and conditions of its sublicense and continues to perform thereunder, and, if such Sublicensee is not in full compliance or is not continuing to perform, Licensor may elect not to have such sublicense assigned; and (ii) following such assignment, Licensor shall not be liable to such Sublicensee with respect to any obligations of Licensee to the Sublicensee that are not consistent with, or not required by, Licensor’s obligations to Licensee under this Agreement; and all sublicenses not requested to be assigned to Licensor shall terminate;

CONFIDENTIAL

6.7.3 If termination is by Licensee pursuant to Section 6.3 or by Licensor pursuant to Section 6.4, 6.5 or 6.6, Licensee shall grant, and hereby grants to Licensor a non-exclusive, perpetual, irrevocable, worldwide, royalty-free, transferable, sublicensable license under any patentable modifications or improvements (and any intellectual property rights with respect thereto) developed by Licensee or any Affiliates (during the term of and pursuant to this Agreement) or by any Sublicensees (during the term of and pursuant to any sublicense agreement with such Sublicensee) to any vector that is the subject of a claim within any of the Licensed Patents, for use by Licensor for the research, development, and commercialization of products in any therapeutic indication;

6.7.4 Licensee shall pay all monies then-owed to Licensor under this Agreement;

6.7.5 Each. Receiving Party shall, at the Disclosing Party’s request, return all Confidential information of the Disclosing Party. Notwithstanding the foregoing, one copy may be kept by either Party for a record of that Party’s obligations; and

6.7.6 If termination is only with respect to a particular field within the Commercial Field, but not all fields within the Commercial Field, then the provisions of this Section 6.7 shall only apply with respect to the terminated field(s), and this Agreement shall continue with respect to the non-terminated field(s) within the Commercial Field.

6.8 Survival . Licensee’s obligation to pay all monies due and owed to Licensor under this Agreement which have matured as of the effective date of termination or expiration shall survive the termination or expiration of this Agreement. In addition, the provisions of Section 2.3, (Retained Rights), Section 2.4 (Government Rights), Section 2.6 (Non-Exclusive License Under Licensee Inventions), Section 2.7 (Improvements), Article 3 (Consideration) (with respect to any final reports or to the extent any amounts are due but unpaid), Section 3.9 (Reports and Records), Section 4.4 (Confidential Information), Article 5 (Confidentiality), Article 6 (Term and Termination), Section 8.3 (Disclaimer of Warranties, Damages), Section 8.4 (Indemnification), Section 8.5 (Insurance), Article 9 (Use of Name), and Article 10 (Additional Provisions) shall survive such termination or expiration of this Agreement in accordance with their respective terms.

ARTICLE 7: PATENT MAINTENANCE; PATENT INFRINGEMENT

7.1 Prosecution of Licensed Patents . As between Licensor and Licensee, but subject to any obligations of Licensor to the REGENX Licensors, the Parties agree as follows:.

7.1.1 Licensor shall have the sole right, but not the obligation, to Prosecute patent applications and issued patents within Licensed Patents, in Licensor’s sole discretion.

7.1.2 Nothing in this Agreement obligates Licensor to continue to Prosecute any patent applications or issued patents, and Licensee acknowledges that Licensor shall have no obligation to undertake any inter-party proceedings, such as oppositions or interferences, or to undertake any re-examination or re-issue proceedings, in either case, with respect to the Licensed Patents.

CONFIDENTIAL

7.2 Infringement Actions Against Third Parties .

7.2.1 Licensee is responsible for notifying the Licensor promptly of any infringement of Licensed Patents (other than Retained Rights) that may come to Licensee’s attention, including any “patent certification” filed in the United States under 21 U.S.C. § 355(b)(2) or 21 U.S.C. § 355(j)(2) or similar provisions in other jurisdictions alleging the invalidity, unenforceability or non-infringement of any Licensed Patents, and any notification received pursuant to subsection (k) of 42 U.S.C. § 262 for any Licensed Product that becomes a “reference product.”

7.2.2 As between Licensor and Licensee, but subject to any obligations of Licensor to the REGENX Licensors, Licensor shall have the sole right, but not the obligation, to prosecute any such infringement at its [***] recovered in connection therewith. In any action to enforce any of the Licensed Patents, Licensee, at the request and expense of Licensor, shall cooperate to the fullest extent reasonably possible, including in the event that, if Licensor is unable to initiate or prosecute such action solely in its own name, Licensee shall join such action voluntarily and shall execute all documents necessary to initiate litigation to prosecute, maintain, and settle such action. Nothing in this Agreement obligates Licensor to bring or prosecute lawsuits against Third Parties for infringement of any Licensed Patents.

7.2.3 Licensee shall have no right to undertake prosecution of any such infringement.

7.3 Defense of Infringement Claims . In the event Licensee or Licensor becomes aware that Licensee’s or any of its Affiliates’ or any Sublicensees’ practice of the Licensed Patents is the subject of a claim for patent infringement by a Third Party, that Party shall promptly notify the other, and the Parties shall consider the claim and the most appropriate action to take. Licensee shall cause each of its Affiliates and each Sublicensee to notify Licensee promptly in the event such entity becomes aware that its practice of the Licensed Patents is the subject of a claim of patent infringement by another. To the extent Licensor takes any action, Licensor (or the REGENX Licensors) shall have the right to require Licensee’s reasonable cooperation in any such suit, upon written notice to Licensee; and Licensee shall have the obligation to participate upon Licensor’s request, in which event, Licensor shall bear the cost of Licensee’s participation. Without Licensor’s prior written permission, Licensee must not settle or compromise any such suit in a manner that imposes any material obligations or restrictions on Licensor or the REGENX Licensors or grants any rights to the Licensed Patents other than rights that Licensee has the right to grant under this Agreement.

ARTICLE 8: REPRESENTATIONS AND WARRANTIES; INDEMNIFICATION

8.1 Representations and Warranties by Licensor . Licensor represents and warrants to Licensee as of the Effective Date:

8.1.1 Licensor has the right, power, and authority to enter into this Agreement and to grant to Licensee the licenses specified in this Agreement;

8.1.2 This Agreement when executed shall become the legal, valid, and binding obligation of it, enforceable against it, in accordance with its terms.

CONFIDENTIAL

8.1.3 There are no actions, suits, proceedings, or arbitrations pending, or to Licensor’s knowledge, threatened against Licensor relating to the Licensed Patents that would be inconsistent with the rights granted to Licensee under this Agreement;

8.1.4 To Licensor’s knowledge, (a) the Licensed Patents are solely owned by the Trustees of the University of Pennsylvania, and (b) no Third Party (other than REGENX Licensors) has any right, interest, or claim in or to such Licensed Patents with respect to the AATD Field or the Option Field that are inconsistent with those granted to Licensee with respect to the AATD Field or the Option Field;

8.1.5 To Licensor’s knowledge, no Third Party is infringing any of the Licensed Patents in a manner that is inconsistent with the scope of rights granted to Licensee with respect to the AATD Field or the Option Field; and

8.1.6 Licensor has not received any written notice from any Third Party patentee alleging infringement of such Third Party’s patents by the practice of the Licensed Patents with respect to the AATD Field or the Option Field.

8.2 Representations and Warranties by Licensee . Licensee represents and warrants to Licensor as of the Effective Date that:

8.2.1 Licensee has the right, power, and authority to enter into this Agreement and to grant the licenses granted by it hereunder;

8.2.2 This Agreement when executed shall become the legal, valid, and binding obligation of it, enforceable against it, in accordance with its terms;

8.2.3 Licensee has the ability and the resources, including financial resources, necessary to carry out its obligations under this Agreement.

8.2.4 There are no actions, suits, proceedings, or arbitrations pending or, to Licensee’s knowledge, threatened against Licensee that would impact activities under this Agreement; and

8.2.5 Licensee is not, in any material respect, in violation or default of any provision of its certificate of incorporation or its bylaws.

8.3 Disclaimer of Warranties, Damages . EXCEPT AS SET FORTH IN SECTION 8.1, THE LICENSED PATENTS, LICENSED PRODUCTS, AND ALL RIGHTS LICENSED UNDER THIS AGREEMENT ARE PROVIDED ON AN “AS IS” BASIS, AND LICENSOR MAKES NO REPRESENTATIONS OR WARRANTIES, EXPRESS OR IMPLIED, WITH RESPECT THERETO. BY WAY OF EXAMPLE BUT NOT OF LIMITATION, EXCEPT AS EXPRESSLY SET FORTH IN SECTION 8.1, LICENSOR MAKES NO REPRESENTATIONS OR WARRANTIES, AND HEREBY DISCLAIMS ALL EXPRESS AND IMPLIED REPRESENTATIONS AND WARRANTIES, (i) OF COMMERCIAL UTILITY, ACCURACY, COMPLETENESS, PERFORMANCE, MERCHANTABILITY, FITNESS FOR A PARTICULAR PURPOSE, VALIDITY OR ENFORCEABILITY OF THE LICENSED PATENTS, AND PROFITABILITY; OR (ii) THAT THE USE OF THE LICENSED PATENTS OR LICENSED PRODUCTS WILL NOT INFRINGE ANY PATENT, COPYRIGHT,

CONFIDENTIAL

TRADEMARK, OR OTHER PROPRIETARY RIGHTS OF THIRD PARTIES. EXCEPT AS SET FORTH HEREIN, NONE OF LICENSOR OR EITHER OF THE REGENX LICENSORS SHALL BE LIABLE TO LICENSEE, LICENSEE’S SUCCESSORS OR ASSIGNS, ANY SUBLICENSEES, OR ANY THIRD PARTY WITH RESPECT TO: (a) ANY CLAIM ARISING FROM USE OF THE LICENSED PATENTS, LICENSED PRODUCTS, AND ANY OR ALL RIGHTS LICENSED UNDER THIS AGREEMENT OR FROM THE DEVELOPMENT, TESTING, MANUFACTURE, USE, OR SALE OF LICENSED PRODUCTS; OR (b) ANY CLAIM FOR LOSS OF PROFITS, LOSS OR INTERRUPTION OF BUSINESS, OR FOR INDIRECT, SPECIAL, INCIDENTAL, PUNITIVE, OR CONSEQUENTIAL DAMAGES OF ANY KIND, INCLUDING ANY ARISING FROM OR RELATING TO ANY BREACH OF THIS AGREEMENT OR THE EXERCISE OF RIGHTS HEREUNDER, REGARDLESS OF ANY NOTICE OF SUCH DAMAGES. NOTHING IN THIS SECTION 8.3 IS INTENDED TO LIMIT OR RESTRICT THE INDEMNIFICATION RIGHTS OR OBLIGATIONS OF EITHER PARTY UNDER SECTION 8.4 OR TO LIMIT A PARTY’S LIABILITY FOR BREACHES OF ITS OBLIGATION REGARDING CONFIDENTIALITY UNDER ARTICLE 5.

8.4 Indemnification .

8.4.1 By Licensee . Licensee shall defend, indemnify, and hold harmless Licensor, the REGENX Licensors, and their respective shareholders, members, officers, trustees, faculty, students, contractors, agents, and employees (individually, a “ Licensor Indemnified Party ” and, collectively, the “ Licensor Indemnified Parties ”) from and against any and all Third Party liability, loss, damage, action, claim, fee, cost, or expense (including attorneys’ fees) (individually, a “ Third Party Liability ” and, collectively, the “ Third Party Liabilities ”) suffered or incurred by the Licensor Indemnified Parties from claims of such Third Parties to the extent that such claims result from or arise out of: [***]; provided, however, that Licensee shall not be liable for claims to the extent based on (1) any breach by Licensor of the representations, warranties, or obligations of Licensor under this Agreement or (2) the gross negligence or intentional misconduct of any of the Licensor Indemnified Parties. Without limiting the foregoing, but subject to clauses (1) and (2) above, Licensee must defend, indemnify, and hold harmless the Licensor Indemnified Parties from and against any Third Party Liabilities resulting from:

(a)

any [***] or other claim of any kind related to the [***] by a Third Party of a Licensed Product that was [***] by Licensee, its Affiliates, any Sublicensees, their respective assignees, or vendors;

(b)

any claim by a Third Party that the [***]; and

(c)

[***] conducted by or on behalf of Licensee, its Affiliates, any Sublicensees, their respective assignees, or vendors relating to the Licensed Patents or Licensed Products, including any claim by or on behalf of a [***].

8.4.2 By Licensor . Licensor shall defend, indemnify, and hold harmless Licensee, its shareholders, members, officers, contractors, agents, and employees (individually, a “ Licensee

CONFIDENTIAL

Indemnified Party ” and, collectively, the “ Licensee Indemnified Parties ” ) from and against any and all Third Party Liabilities suffered or incurred by the Licensee Indemnified Parties from claims of such Third Parties to the extent that such claims result from or arise out of: [***]; provided, however, that Licensor shall not be liable for claims to the extent based on (1) any breach by Licensee of the representations, warranties, or obligations of Licensee under this Agreement or (2) the gross negligence or intentional misconduct of any of the Licensee Indemnified Parties.

8.4.3 Indemnification Procedure . Each Party, as an indemnifying party (an “ Indemnifying Party ”), shall not be permitted to settle or compromise any claim or action giving rise to Third Party Liabilities in a manner that imposes any restrictions or obligations on any indemnified party (an “ Indemnified Party ”) without the Indemnified Party’s prior written consent or, if Licensee is the Indemnifying Party, that imposes any restrictions or obligations on Licensor’s direct or indirect licensors or grants any rights to the Licensed Patents or Licensed Products other than those Licensee has the right to grant under this Agreement without Licensor’s prior written consent. The Indemnifying Party shall be permitted to control any litigation or potential litigation involving the defense of any claim subject to indemnification pursuant to this Section 8.4, including the selection of counsel, with the reasonable approval of the Indemnified Party. Upon the Indemnifying Party’s reasonable request, the Indemnified Parties will reasonably cooperate with the Indemnifying Party in the defense and settlement of any such claim, at the Indemnifying Party’s cost and expense. If an Indemnifying Party fails or declines to assume the defense of any such claim or action within [***] after notice thereof, the Indemnified Party may assume the defense of such claim or action at the cost and risk of the Indemnifying Party, and any Third Party Liabilities related thereto shall be conclusively deemed a Third Party Liability of the Indemnifying Party. The indemnification rights of an Indemnified Party contained in this Agreement are in addition to all other rights that such Indemnified Party may have at law or in equity or otherwise. The Indemnifying Party will pay directly all Third Party Liabilities incurred for defense or negotiation of any claim hereunder or will reimburse the Indemnified Party for all documented Third Party Liabilities incident to the defense or negotiation of any such claim within [***] after the Indemnifying Party’s receipt of invoices for such fees, expenses, and charges.

8.5 Insurance . Licensee will procure and maintain insurance policies for the following coverages with respect to product liability, personal injury, bodily injury, and property damage arising out of Licensee’s (and its Affiliates’ and any Sublicensees’) performance under this Agreement: (a) during the term of this Agreement, comprehensive general liability, including broad form and contractual liability, in a minimum amount of [***] combined single limit per occurrence (or claim) and in the aggregate annually; (b) prior to the commencement of clinical trials involving Licensed Products and thereafter for a period of not less than [***] (or such longer period as Licensee is required by applicable law to continue to monitor the participants in the clinical trial), clinical trials coverage in amounts that are reasonable and customary in the U.S. pharmaceutical industry, subject always to a minimum limit of $3,000,000 combined single limit per occurrence (or claim) and in the aggregate annually; and (c) from prior to the first commercial sale of a Licensed Product until [***] after the last sale of a Licensed Product, product liability coverage, in amounts that are reasonable and customary in the U.S. pharmaceutical industry, subject always to a minimum limit of [***] combined single limit per occurrence (or claim) and in the aggregate annually. Licensor may review periodically the

CONFIDENTIAL

adequacy of the minimum amounts of insurance for each coverage required by this Section 8.5, and Licensor reserves the right to require Licensee to adjust the limits accordingly. The required minimum amounts of insurance do not constitute a limitation on Licensee’s liability or indemnification obligations to the Licensor Indemnified Parties under this Agreement. The policies of insurance required by this Section 8.5 will be issued by an insurance carrier with an A.M. best rating of [***] or better and will name Licensor as an additional insured with respect to Licensee’s performance (and its Affiliates’ and any Sublicensees’) under this Agreement. Licensee will provide Licensor with insurance certificates evidencing the required coverage within [***] after the Effective Date and the commencement of each policy period and any renewal periods. Each certificate will provide that the insurance carrier will notify Licensor in writing at least [***] prior to the cancellation or material change in coverage. Licensee will cause all Sublicensees to comply with the terms of this Section 8.5 to the same extent as Licensee.

ARTICLE 9: USE OF NAME

Licensee, its Affiliates, any Sublicensees, and all of its and their employees and agents must not use Licensor’s, the University of Pennsylvania’s, or SmithKline Beecham Corporation’s name, seal, logo, trademark, or service mark (or any adaptation thereof) or the name, seal, logo, trademark, or service mark (or any adaptation thereof) of any of such entities’ representative, school, organization, employee, or student in any way without the prior written consent of Licensor or such entity, as applicable, unless required to do so pursuant to applicable law, rule, regulation or rules of a securities exchange; provided, however that Licensee may acknowledge the existence and general nature of this Agreement, subject to Section 5.2.1.

ARTICLE 10: ADDITIONAL PROVISIONS

10.1 Relationship . Nothing in this Agreement shall be deemed to establish a relationship of principal and agent between Licensee and Licensor, nor any of their agents or employees for any purpose whatsoever, nor shall this Agreement be construed as creating any other form of legal association or arrangement which would impose liability upon one Party for the act or failure to act of the other Party.

10.2 Assignment . The rights and obligations of Licensee and Licensor hereunder shall inure to the benefit of, and shall be binding upon, their respective permitted successors and assigns. Licensee may not assign or otherwise transfer (by operation of law or otherwise) this Agreement or any of its rights or obligations under this Agreement without the prior written consent of Licensor which consent is in the absolute discretion of Licensor; provided, however, Licensee shall be permitted to assign or otherwise transfer (by operation of law or otherwise ) this Agreement without Licensor’s consent, (a) to any Affiliate; or (b) in connection with a Change of Control; provided that, as part of any permitted assignment or transfer, Licensee: (i) requires any assignee, transferee, or successor to agree in writing to be legally bound by this Agreement to the same extent as Licensee and provides Licensor with a copy of such undertaking; (ii) provides Licensor with written notice of the assignment or transfer to Licensor within five (5) days of the consummation of the transaction resulting in the assignment or transfer; (iii) in the event of a Change of Control of Licensee, provides Licensor with redacted copies of the transaction documents resulting in a Change of Control of Licensee within five (5) days of the

CONFIDENTIAL

consummation of the transaction; and (iv) in the event of an assignment or transfer to an Affiliate, remains responsible for the performance of this Agreement by such Affiliate. Notwithstanding anything to the contrary in this Agreement, for clarity, in case of a Licensee Change of Control, in no event shall any intellectual property rights owned or controlled by the acquirer or its Affiliates immediately prior to such Licensee Change of Control be included in any of the licenses granted to Licensor under this Agreement. Licensor may assign this Agreement and its rights and obligations without the consent of Licensee. No assignment shall relieve the assigning Party of responsibility for the performance of any accrued obligations which it has prior to such assignment. Any attempted assignment by Licensee in violation of this Section 10.2 shall be null and void and of no legal effect.

10.3 Waiver . A waiver by either Party of a breach of any provision of this Agreement will not constitute a waiver of any subsequent breach of that provision or a waiver of any breach of any other provision of this Agreement.

10.4 Notices . Notices, payments, statements, reports, and other communications under this Agreement shall be in writing and shall be deemed to have been received as of the date received if sent by public courier (e.g., Federal Express), by Express Mail, receipt requested, by facsimile or electronic mail (with a copy of such facsimile or electronic mail also sent by one of the other methods of delivery) and addressed as follows:

If for Licensor:

REGENXBIO Inc.

9712 Medical Center Drive, Suite 100

Rockville, MD 20850

USA

Attn: Chief Executive Officer

Telephone: 240-552-8181

Facsimile: 240-652-9692

If for Licensee:

Annapurna Therapeutics

3711 Market Street Suite 800

Philadelphia PA 19104

Attn: Amber Salzman, PhD, CEO

[***]

with a copy to:

REGENXBIO Inc.

9712 Medical Center Drive, Suite 100

Rockville, MD 20850

USA

Attn: General Counsel

Telephone: 240-552-8181

Facsimile: 240-652-9692

Either Party may change its official address upon written notice to the other Party in accordance with this Section 10.4.

General communications required under this Agreement (including notices under Sections 2.2, 2.5.2, 2.7.3, 3.9, 4.1, 4.2, 4.3, 7.1, 7.2, 8.5, and 10.2 and notices of changes of address under this Section 10.4) may be sent by any of the means outlined in the first sentence of this Section 10.4 or a copy of the notice letter may be sent by electronic mail (without the requirement of a copy being sent by

CONFIDENTIAL

another means; provided that the receiving Party has confirmed receipt of such electronic mail); however, communications related to requests for disclosures of Confidential Information, breaches or termination of this Agreement, indemnification, and dispute resolution (including notices under Sections 5.2, 6.3, 6.4, 6.5, 6.6, 8.4, and 10.6) must be sent by one of the means outlined in the first sentence of this Section 10.4.

10.5 Applicable Law . This Agreement shall be construed and governed in accordance with the laws of the State of New York, without giving effect to conflict of law provisions that may require the application of the laws of another jurisdiction. Subject to Section 10.6, the Parties hereby submit to the exclusive jurisdiction of and venue in the courts located in the State of New York with respect to any and all disputes concerning the subject of this Agreement.

10.6 Dispute Resolution .

10.6.1 Arbitration . In the event of any controversy or claim arising out of or relating to this Agreement, the Parties shall first attempt to resolve such controversy or claim through good faith negotiations for a period of not less than thirty (30) days following notification of such controversy or claim to the other Party. If such controversy or claim cannot be resolved by means of such negotiations during such period, then such controversy or claim shall be resolved by binding arbitration administered by the American Arbitration Association (“ AAA ”) in accordance with the Commercial Arbitration Rules of the AAA in effect on the date of commencement of the arbitration, subject to the provisions of this Section 10.6. The arbitration shall be conducted as follows:

10.6.1.1 The arbitration shall be conducted by three arbitrators, each of whom by training, education, or experience has knowledge of the research, development, and commercialization of biological therapeutic products in the United States. The arbitration shall be conducted in English and held in New York, New York.

10.6.1.2 In its demand for arbitration, the Party initiating the arbitration shall provide a statement setting forth the nature of the dispute, the names and addresses of all other parties, an estimate of the amount involved (if any), the remedy sought, otherwise specifying the issue to be resolved, and appointing one neutral arbitrator. In an answering statement to be filed by the responding Party within [***] after confirmation of the notice of filing of the demand is sent by the AAA, the responding Party shall appoint one neutral arbitrator. Within [***] from the date on which the responding Party appoints its neutral arbitrator, the first two arbitrators shall appoint a chairperson.

10.6.1.3 If a Party fails to make the appointment of an arbitrator as provided in Section 10.6.1.2, the AAA shall make the appointment. If the appointed arbitrators fail to appoint a chairperson within the time specified in Section 10.6.1.2 and there is no agreed extension of time, the AAA shall appoint the chairperson.

10.6.1.4 The arbitrators will render their award in writing and, unless all Parties agree otherwise, will include an explanation in reasonable detail of the reasons for their award. Judgment upon the award rendered by the arbitrators may be entered in any

CONFIDENTIAL

court having jurisdiction thereof, including in the courts described in Section 10.5. The arbitrators will have the authority to grant injunctive relief and other specific performance; provided that the arbitrators will have no authority to award damages in contravention of this Agreement, and each Party irrevocably waives any claim to such damages in contravention of this Agreement. The arbitrators will, in rendering their decision, apply the substantive law of the State of New York, without giving effect to conflict of law provisions that may require the application of the laws of another jurisdiction. The decision and award rendered by the arbitrators will be final and non-appealable (except for an alleged act of corruption or fraud on the part of the arbitrator).

10.6.1.5 The Parties shall use their reasonable efforts to conduct all dispute resolution procedures under this Agreement expeditiously, efficiently, and cost-effectively.

10.6.1.6 All expenses and fees of the arbitrators and expenses for hearing facilities and other expenses of the arbitration will be borne equally by the Parties unless the Parties agree otherwise or unless the arbitrators in the award assess such expenses against one of the Parties or allocate such expenses other than equally between the Parties. Each of the Parties will bear its own counsel fees and the expenses of its witnesses except to the extent otherwise provided in this Agreement or by applicable law.

10.6.1.7 Compliance with this Section 10.6 is a condition precedent to seeking relief in any court or tribunal in respect of a dispute, but nothing in this Section 10.6 will prevent a Party from seeking equitable or other interlocutory relief in the courts of appropriate jurisdiction, pending the arbitrators’ determination of the merits of the controversy, if applicable to protect the confidential information, property, or other rights of that Party or to otherwise prevent irreparable harm that may be caused by the other Party’s actual or threatened breach of this Agreement.

10.7 No Discrimination . Licensee and its Affiliates, and Licensee shall use reasonable efforts to require that any Sublicensees, in their respective activities under this Agreement, shall not discriminate against any employee or applicant for employment because of race, color, sex, sexual, or affectional preference, age, religion, national, or ethnic origin, handicap, or because he or she is a disabled veteran or a veteran (including a veteran of the Vietnam Era).

10.8 Compliance with Law . Licensee (and its Affiliates’ and any Sublicensees’) must comply with all prevailing laws, rules, and regulations that apply to its activities or obligations under this Agreement. Without limiting the foregoing, it is understood that this Agreement may be subject to United States laws and regulations controlling the export of technical data, computer software, laboratory prototypes, and other commodities, articles, and information, including the Arms Export Control Act as amended in the Export Administration Act of 1979 and that Licensee’s obligations are contingent upon compliance with applicable United States export laws and regulations. The transfer of certain technical data and commodities may require a license from the cognizant agency of the United States Government and/or written assurances by Licensee that Licensee shall not export data or commodities to certain foreign countries without prior approval of such agency. Licensor neither represents that a license is not required nor that, if required, it will issue.

CONFIDENTIAL

10.9 Entire Agreement . This Agreement, together with all exhibits hereto, embody the entire understanding between the Parties relating to the subject matter hereof and supersede all prior understandings and agreements, whether written or oral, including that certain Mutual Non-Disclosure Agreement dated May 15, 2015 between Licensor and AAVLife SAS. All “Confidential Information” (as defined in such Mutual Non-Disclosure Agreement) disclosed by one Party to the other Party pursuant to such Mutual Non-Disclosure Agreement shall be deemed “Confidential Information” of such disclosing Party under this Agreement (unless and until it falls within one of the exclusions set forth in Section 1.9). This Agreement may not be varied except by a written document signed by duly authorized representatives of both Parties.

10.10 Marking . Licensee, its Affiliates, and any Sublicensees shall mark any Licensed Product (or their containers or labels) made, sold, or otherwise distributed by it or them with any notice of patent rights necessary or desirable under applicable law to enable the Licensed Patents to be enforced to their full extent in any country where Licensed Products are made, used, sold, offered for sale, or imported.

10.11 Severability and Reformation . If any provision of this Agreement is held to be invalid or unenforceable by the arbitrators or a court of competent jurisdiction, then such invalid or unenforceable provision will be automatically revised to be a valid or enforceable provision that comes as close as permitted by law to the Parties’ original intent; provided that, if the Parties cannot agree upon such valid or enforceable provision, the remaining provisions of this Agreement will remain in full force and effect, unless the invalid or unenforceable provisions are of such essential importance to this Agreement that it is to be reasonably assumed that the Parties would not have entered into this Agreement without the invalid or unenforceable provisions.

10.12 Further Assurances . Each Party hereto agrees to execute, acknowledge, and deliver such further instruments, and to do all other reasonable acts, as may be necessary or appropriate in order to carry out the purposes and intent of this Agreement.

10.13 Interpretation; Construction . The captions to the several Articles and Sections of this Agreement are included only for convenience of reference and shall not in any way affect the construction of, or be taken into consideration in interpreting, this Agreement. In this Agreement, unless the context requires otherwise, (a) the word “ including ” shall be deemed to be followed by the phrase “ without limitation ” or like expression; (b) references to the singular shall include the plural and vice versa; (c) references to masculine, feminine, and neuter pronouns and expressions shall be interchangeable; (d) the words “ herein ” or “ hereunder ” relate to this Agreement; (e) “ or ” is disjunctive but not necessarily exclusive; (f) the word “ will ” shall be construed to have the same meaning and effect as the word “ shall ”; (g) all references to “ dollars ” or “ $ ” herein shall mean U.S. Dollars; (h) unless otherwise provided, all reference to Sections, Articles, and exhibits in this Agreement are to Sections, Articles, and exhibits of and in this Agreement; and (i) whenever this Agreement refers to a number of days, such number shall refer to calendar days unless business days are specified. Business days shall mean a day on which banking institutions in Washington, D.C. are open for business. Each Party represents that it has been represented by legal counsel in connection with this Agreement and acknowledges that it has participated in the drafting hereof. In interpreting and applying the terms and provisions of this Agreement, the Parties agree that no presumption will apply against the Party which drafted such terms and provisions.

CONFIDENTIAL

10.14 Cumulative Rights and Remedies . The rights and remedies provided in this Agreement and all other rights and remedies available to either Party at law or in equity are, to the extent permitted by law, cumulative and not exclusive of any other right or remedy now or hereafter available at law or in equity. Neither asserting a right nor employing a remedy shall preclude the concurrent assertion of any other right or employment of any other remedy, nor shall the failure to assert any right or remedy constitute a waiver of that right or remedy.

10.15 Counterparts . This Agreement may be executed in one or more counterparts, each of which will be deemed an original, but all of which together will constitute one and the same instrument.

[REMAINDER OF PAGE INTENTIONALLY LEFT BLANK]

CONFIDENTIAL

IN WITNESS WHEREOF, the Parties, intending to be legally bound, have caused this License Agreement to be executed by their duly authorized representatives.

REGENXBIO INC.		ANNAPURNA THERAPEUTICS LIMITED

By:		By:
Name:	Kenneth Mills	Name:	Amber Salzman, PhD
Title:	President & CEO	Title:	CEO

CONFIDENTIAL

Exhibit A

Licensed Patents (AAVrh10)


Appln #	Title	Inventors	Nos	Docket
[***]	[***]	[***]	[***]	[***]

Docket	Country	Appln No	Filing Date	Patent Number	Issue Date	Pubn Number	Pub Date
[***]	[***]	[***]	[***]	[***]	[***]
[***]	[***]	[***]	[***]
[***]	[***]	[***]	[***]
[***]	[***]	[***]	[***]	[***]	[***]	[***]	[***]
[***]	[***]	[***]	[***]	[***]	[***]
[***]	[***]	[***]	[***]
[***]	[***]	[***]	[***]	[***]	[***]
[***]	[***]	[***]	[***]	[***]	[***]
[***]	[***]	[***]	[***]

Exhibit B

Press Release

In process to be agreed to by both parties

Exhibit 10.8

LICENSE AGREEMENT

This LICENSE AGREEMENT (“ Agreement ”) is entered into as of April 10, 2014 (“ Effective Date ”) by and between ReGenX Biosciences, LLC, a limited liability company organized under the laws of the State of Delaware, with offices at 750 17th Street, NW, Suite 1100, Washington, DC 20006, USA (“ Licensor ”), and AAVLife, a French simplified joint stock company (Société par actions simplifiée) whose registered office is 183/189 avenue de Choisy — 75013 Paris, France (“ Licensee ”). Licensor and Licensee are hereinafter referred to individually as a “ Party ” and collectively as the “ Parties .”

WHEREAS, Licensor has rights under certain Licensed Patents (as defined herein) pertaining to certain recombinant adeno-associated virus vectors; and

WHEREAS, Licensee desires to obtain from Licensor certain licenses under the Licensed Patents under the terms set forth herein;

NOW, THEREFORE, in consideration of the promises and covenants contained in this Agreement, and intending to be legally bound, the Parties hereby agree as follows:

ARTICLE 1: DEFINITIONS

1.1 “ AAV7 ” means (a) the recombinant adeno-associated virus serotype 7 vector with the specified sequence set forth in GenBank [***] and (b) any recombinant adeno-associated virus derivatives of such serotype 7 vector that are covered by the claims of the Licensed Patents set forth on Exhibit A-1 (or other Licensed Patents relating thereto described in Section 1.19(b) or 1.22(b), as applicable).

1.2 “ AAV8 ” means (a) the recombinant adeno-associated virus serotype 8 vector with the specified sequence set forth in GenBank [***] and (b) any recombinant adeno-associated virus derivatives of such serotype 8 vector that are covered by the claims of the Licensed Patents set forth on Exhibit A-2 (or other Licensed Patents relating thereto described in Section 1.19(b) or 1.22(b), as applicable).

1.3 “ AAV9 ” means (a) the recombinant adeno-associated virus serotype 9 vector with the specified sequence set forth in GenBank [***] and (b) any recombinant adeno-associated virus derivatives of such serotype 9 vector that are covered by the claims of the Licensed Patents set forth on Exhibit A-3 (or other Licensed Patents relating thereto described in Section 1.19(b) or 1.22(b), as applicable).

1.4 “ AAVrh10 ” means (a) the recombinant adeno-associated virus serotype rh10 vector with the specified sequence set forth in GenBank [***] and (b) any recombinant adeno-associated virus derivatives of such serotype rh10 vector that are covered by the claims of the Licensed Patents set forth on Exhibit A-4 (or other Licensed Patents relating thereto described in Section 1.19(b) or 1.22(b), as applicable).

1.5 “ AAV Materials ” means AAV Vectors, and any materials that are made or used for the sole purpose of making AAV Vectors, in each case, which, in the absence of the license granted pursuant to Section 2.2, would infringe or is covered by at least one Valid Claim of the applicable Licensed Research Patents in the country of manufacture or use.

1.6 “ AAV Vectors ” means, collectively, AAV7, AAV8, AAV9, and AAVrh10.

1.7 “ Affiliate ” means any legal entity directly or indirectly, during the Term, controlling, controlled by, or under common control with another entity. For purposes of this Agreement, “control” means the direct or indirect ownership of more than 50% of the outstanding voting securities of a legal entity, or the right to receive more than 50% of the profits or earnings of a legal entity, or the right to control the policy decisions of a legal entity. An entity may be or become an Affiliate of an entity and may cease to be an Affiliate of an entity, in each case, during the Term.

1.8 “ Calendar Quarter ” means each three-month period or any portion thereof, beginning on January 1, April 1, July 1, and October 1.

1.9 “ Commercial Field ” means (a) the treatment of Friedreich’s Ataxia (Systemic) in human beings by in vivo gene therapy with AAVrh10; and (b) if and when a Commercial Option is exercised for a Disease Indication by Licensee under Section 2.3, the treatment of such Disease Indication in human beings by in vivo gene therapy with the Specified Vector selected for such Disease Indication.

1.10 “ Commercial Option ” has the meaning set forth in Section 2.3.

1.11 “ Confidential Information ” means and includes all technical information, inventions, developments, discoveries, software, know-how, methods, techniques, formulae, animate and inanimate materials, data, processes, finances, business operations or affairs, and other proprietary ideas, whether or not patentable or copyrightable, of either Party that are (a) marked or otherwise identified as confidential or proprietary at the time of disclosure in writing; or (b) if disclosed orally, visually, or in another non-written form, identified as confidential at the time of disclosure and summarized in reasonable detail in writing as to its general content within 30 days after original disclosure. The Parties acknowledge that (i) the terms and conditions of this Agreement and (ii) the records and reports referred to in Section 3.7 will be deemed the Confidential Information of both Parties, regardless of whether such information is marked or identified as confidential. Notwithstanding the foregoing, Confidential Information will not include the following, in each case, to the extent evidenced by competent written proof of the Receiving Party:

1.11.1 information that was already known to the Receiving Party, other than under an obligation of confidentiality, at the time of disclosure by the Disclosing Party;

1.11.2 information that was generally available to the public or otherwise part of the public domain at the time of its disclosure to the Receiving Party;

1.11.3 information that became generally available to the public or otherwise part of the public domain after its disclosure, other than through any act or omission of the Receiving Party in breach of this Agreement;

1.11.4 information that is independently discovered or developed by the Receiving Party without the use of Confidential Information of the Disclosing Party; or

1.11.5 information that was disclosed to the Receiving Party, other than under an obligation of confidentiality, by a Third Party who had no obligation to the Disclosing Party not to disclose such information to others.

1.12 “ Disclosing Party ” has the meaning set forth in Section 5.1.

1.13 “ Disease Indication(s) ” means Friedreich’s Ataxia (CNS) and Friedreich’s Ataxia (Systemic).

1.14 “ Domain Antibody ” [***]

1.15 “ FDA ” means the United States Food and Drug Administration, or a successor agency in the United States with responsibilities comparable to those of the United States Food and Drug Administration.

1.16 “ Friedreich’s Ataxia (CNS) ” means Friedreich’s Ataxia that is treated by administration of the applicable AAV Vector directly to the central nervous system (brain and spinal cord).

1.17 “ Friedreich’s Ataxia (Systemic) ” means Friedreich’s Ataxia that is treated by administration of the applicable AAV Vector by any route except administration directly to the central nervous system (brain and spinal cord).

1.18 “ GSK Agreement ” means that certain License Agreement entered into between Licensor and SmithKline Beecham Corporation, effective on March 6, 2009, as amended by that certain Amendment to License Agreement dated April 15, 2009, and as amended from time to time.

1.19 “ Licensed Commercial Patents ” means, on a Specified Vector-by-Specified Vector basis, to the extent they cover such Specified Vector, (a) all United States patents and patent applications listed in Exhibit A-1 (if the Specified Vector is AAV7), Exhibit A-2 (if the Specified Vector is AAV8), Exhibit A-3 (if the Specified Vector is AAV9), or Exhibit A-4 (if the Specified Vector is AAVrh10), including patents arising from such patent applications; and (b) any re-examination certificates thereof, and their foreign counterparts and extensions, continuations, divisionals, and re-issue applications; provided that “Licensed Commercial Patents” will not include any claim of a patent or patent application covering any Manufacturing Technology.

1.20 “ Licensed Patents ” means the Licensed Commercial Patents or Licensed Research Patents, as applicable.

1.21 “ Licensed Product ” means (a) any product using the applicable Specified Vector that is made, made for, used, sold, offered for sale, or imported by Licensee, its Affiliates, and any of its or their Sublicensees, the manufacture, use, sale, offer for sale, or import of which product, in the absence of the license granted pursuant to this Agreement, would infringe or is covered by at least one Valid Claim of the Licensed Commercial Patents in the country of manufacture, use, sale, offer for sale, or import, including products manufactured by a process that would infringe or is covered by at least one Valid Claim of the Licensed Commercial Patents in the country of manufacture, use, sale, offer for sale, or import; or (b) any service sold by Licensee, its Affiliates, and any of its or their Sublicensees with respect to the administration of any product

using the applicable Specified Vector to patients that, in the absence of the license granted pursuant to this Agreement, would infringe or is covered by at least one Valid Claim of the Licensed Commercial Patents in the country of sale.

1.22 “ Licensed Research Patents ” means (a) all United States patents and patent applications listed in Exhibit A-1 (in the case of AAV7), Exhibit A-2 (in the case of AAV8), Exhibit A-3 (in the case of AAV9), and Exhibit A-4 (in the case of AAVrh10), in each case, including patents arising from such patent applications; and (b) any re-examination certificates thereof, and their foreign counterparts and extensions, continuations, divisionals, and re-issue applications; provided that “Licensed Research Patents” will not include any claim of a patent or patent application covering any Manufacturing Technology.

1.23 “ Manufacturing Technology ” means any and all patents, patent applications, know-how, and all intellectual property rights associated therewith that are owned or controlled by Licensor, and including all tangible embodiments thereof, that are necessary or useful for the manufacture of adeno-associated viruses, adeno-associated virus vectors, research or commercial reagents related thereto, Licensed Products, or other products, including manufacturing processes, technical information relating to the methods of manufacture, protocols, standard operating procedures, batch records, assays, formulations, quality control data, specifications, scale up, any and all improvements, modifications, and changes thereto, and any and all activities associated with such manufacture. Any and all chemistry, manufacturing, and controls (CMC), drug master files (DMFs), or similar materials provided to regulatory authorities and the information contained therein are deemed Manufacturing Technology.

1.24 “ NDA ” means a New Drug Application filed with the FDA as described in 21 C.F.R. § 314, a Biological License Application (BLA) pursuant to 21 C.F.R. § 601.2, or any equivalent or any corresponding application for regulatory approval in any country or regulatory jurisdiction other than the United States.

1.25 “ Net Sales ” means the gross receipts from sales or other disposition of a Licensed Product (including fees for services within the definition of “Licensed Product”) by Licensee and/or its Affiliates and/or any Sublicensees to Third Parties less the following deductions that are directly attributable to a sale, specifically and separately identified on an invoice or other documentation and actually borne by Licensee, its Affiliates, or any Sublicensees: [***]. In the event consideration other than cash is paid to Licensee, its Affiliates, or any Sublicensees, for purposes of determining Net Sales, the Parties shall use the cash consideration that Licensee, its Affiliates, or any Sublicensees would realize from an unrelated buyer in an arm’s length sale of an identical item sold in the same quantity and at the time and place of the transaction, as determined jointly by Licensor and Licensee based on transactions of a similar type and standard industry practice, if any.

1.27 “ Phase 3 Clinical Trial ” means a pivotal clinical trial in humans performed to gain evidence with statistical significance of the efficacy of a product in a target population, and to

1.29 “ Receiving Party ” has the meaning set forth in Section 5.1.

1.30 “ ReGenX Licensors ” means SmithKline Beecham Corporation (or any successor thereto under the GSK Agreement) and The Trustees of the University of Pennsylvania (or any successor thereto under the Penn Agreement).

1.31 “ Research Field ” means Licensee’s internal research and pre-clinical development for the treatment of either Disease Indication in humans by in vivo gene therapy using AAV Materials (excluding AAVrh10 for Friedreich’s Ataxia (Systemic)). “Research Field” specifically excludes (without limitation) (a) all human clinical trial use, diagnostic use, therapeutic use, and prophylactic use, and (b) any commercial uses.

1.32 “ Research Term ” means the following:

(a)

with respect to Friedreich’s Ataxia (Systemic), a period beginning with the Effective Date and ending on the earlier of (i) the Grant Date, if any, for such Disease Indication and (ii) the first anniversary of the Effective Date; and

(b)

with respect to Friedreich’s Ataxia (CNS), a period beginning with the Effective Date and ending on the earlier of (i) the Grant Date, if any, for such Disease Indication and (ii) the second anniversary of the Effective Date.

1.33 “ Retained Rights ” has the meaning set forth in Section 2.4.

1.34 “ Specified Vector ” means the following:

(a)

with respect to Friedreich’s Ataxia (Systemic), (i) AAVrh10 and (ii) if a Commercial Option is exercised with respect to Friedreich’s Ataxia (Systemic), the AAV Vector that is selected by Licensee pursuant to Section 2.3, and

(b)

with respect to Friedreich’s Ataxia (CNS), if a Commercial Option is exercised with respect to Friedreich’s Ataxia (CNS), the AAV Vector that is selected by Licensee pursuant to Section 2.3.

The Specified Vectors and applicable Disease Indication will be set forth on Exhibit B (to be amended as of the applicable Grant Date as provided in Section 2.3).

1.35 “ Sublicensee ” means (i) any Third Party or Affiliate to whom Licensee grants a sublicense of some or all of the rights granted to Licensee under this Agreement as permitted by this Agreement; and (ii) any other Third Party or Affiliate to whom a sublicensee described in clause (i) has granted a further sublicense as permitted by this Agreement.

1.36 “ Third Party ” means any person or entity other than a Party to this Agreement or Affiliates of a Party to this Agreement.

1.37 “ Valid Claim ” means a claim of an issued and unexpired patent (including any patent claim the term of which is extended by any extension, supplementary protection certificate, patent term restoration, or the like) included within the Licensed Patents or a claim of a pending patent application included within the Licensed Patents, which has not lapsed, been abandoned, been held revoked, or been deemed unenforceable or invalid by a non-appealable decision or an appealable decision from which no appeal was taken within the time allowed for such appeal of a court or other governmental agency of competent jurisdiction.

ARTICLE 2: LICENSE GRANTS

2.1 Exclusive License Grant . Subject to the terms and conditions of this Agreement, including the Retained Rights, Licensor hereby grants to Licensee an exclusive, sublicensable (as provided in Section 2.6 only), non-transferable (except as provided in Section 10.2), royalty-bearing, worldwide license under the Licensed Commercial Patents to make, have made, use, import, sell, and offer for sale Licensed Products using AAVrh10 solely in the Commercial Field of Friedreich’s Ataxia (Systemic), including, for the avoidance of doubt, the right to conduct research and development.

2.2 Research License Grant . Subject to the terms and conditions of this Agreement, including the Retained Rights, during the Research Term, Licensor hereby grants to Licensee a non-exclusive, sublicensable (as provided in Section 2.6 only), non-transferable (except as provided in Section 10.2), worldwide license under the Licensed Research Patents to make, have made, and use AAV Materials in the Research Field (including, for the avoidance of doubt, the right to conduct research and pre-clinical development) solely for purposes of selecting Specified Vector(s) for use in the Commercial Field upon exercise of a Commercial Option. For the avoidance of doubt, the foregoing license in this Section 2.2 does not include the right to sell, offer for sale, or import any AAV Materials.

2.3 Commercial License Option . Subject to the terms and conditions of this Agreement, Licensor hereby grants to Licensee the option, exercisable at Licensee’s sole discretion, to obtain a non-exclusive worldwide license with respect to each of the Disease Indications and a single Specified Vector for such Disease Indication (each such right with respect to a particular Disease Indication, a “ Commercial Option ”) in accordance with the following provisions:

2.3.1 Method of Exercise . To exercise the Commercial Option for a particular Disease Indication, Licensee must provide written notice to Licensor prior to the end of the applicable Research Term, which written notice must specify the Disease Indication and Specified Vector (as further described in Section 2.3.2) with respect to which Licensee desires to exercise its

Commercial Option. For Friedreich’s Ataxia (CNS), such written notice must be accompanied by a wire transfer of the commercial option fee set forth in Section 3.2.

2.3.2 Specified Vector . For purposes of selecting a Specified Vector for use with a Disease Indication, the Specified Vector must be [***]. Upon Licensor’s receipt of the notice and, if applicable, fee described in Section 2.3.1, Exhibit B will be amended to set forth the Specified Vector for each Disease Indication with respect to which a Commercial Option is exercised.

2.3.3 License Grant Upon Exercise . If Licensee exercises the Commercial Option for a particular Disease Indication, effective upon Licensor’s receipt of the notice and, if applicable, fee described in Section 2.3.1 (the “ Grant Date ” for such Disease Indication with respect to the applicable Specified Vector), subject to the terms and conditions of this Agreement, including the Retained Rights, Licensor shall be deemed to have granted to Licensee a non-exclusive, sublicensable (as provided in Section 2.6 only), non-transferable (except as provided in Section 10.2), royalty-bearing, worldwide license under the applicable Licensed Commercial Patents to make, have made, use, import, sell, and offer for sale Licensed Products using the Specified Vector solely in the Commercial Field of such Disease Indication, including, for the avoidance of doubt, the right to conduct research and development.

2.3.4 Disease Indications . For the avoidance of doubt, the foregoing license granted pursuant to Section 2.3.3 will be deemed granted on the Grant Date on a Disease Indication-by-Disease Indication basis, solely with respect to the Commercial Field associated with the Disease Indication for which the Commercial Option was exercised under this Section 2.3 and solely with respect to Licensed Products using the Specified Vector selected for the particular Disease Indication. The Parties acknowledge that there may be different Grant Dates for each Disease Indication, depending on when and if Licensee exercises the Commercial Option for a particular Disease Indication. As set forth above, Licensee, at its sole discretion, may exercise the Commercial Option with respect to either or both of the two Disease Indications. If Licensee exercises the Commercial Option with respect to only one of the Disease Indications but not both, the Commercial Option will terminate with respect to the unexercised Disease Indication at the end of the applicable Research Term (together with the license granted under Section 2.2), and Licensee will have no further rights under this Agreement with respect to Friedreich’s Ataxia (CNS) if it is the unexercised Disease Indication or with respect to Friedreich’s Ataxia (Systemic) with respect to any Specified Vector (other than AAVrh10) if it is the unexercised Disease Indication; provided that the termination of a Commercial Option with respect to Friedreich’s Ataxia (Systemic) will not affect Licensee’s rights under this Agreement with respect to the license granted under Section 2.1.

2.4 Retained Rights . Except for the rights and licenses specified in Sections 2.1, 2.2, and, if applicable, 2.3.3, no license or other rights are granted to Licensee under any intellectual property of Licensor, whether by implication, estoppel, or otherwise and whether such intellectual property is subordinate, dominant, or otherwise useful for the practice of the Licensed Patents. Notwithstanding anything to the contrary in this Agreement, Licensor may use and permit others to use the Licensed Patents for any research, development, commercial, or other purposes inside or outside of the Commercial Field (other than to the extent of the exclusive license under Section 2.1) or the Research Field. Without limiting the foregoing, and

notwithstanding anything in this Agreement to the contrary, Licensee acknowledges and agrees to the following rights retained by Licensor and the ReGenX Licensors (individually and collectively, the “ Retained Rights ” ), whether inside or outside the Commercial Field or Research Field:

2.4.1 The rights and licenses granted in Sections 2.1, 2.2, and, if applicable, 2.3.3 shall not include any right (and Licensor and the ReGenX Licensors retain the exclusive (even as to Licensee), fully sublicensable right) under the Licensed Patents to make, have made, use, sell, offer to sell, and import Domain Antibodies that are expressed by an adeno-associated vector, including any Specified Vector.

2.4.2 Licensor and the ReGenX Licensors retain the following rights with respect to the Licensed Patents:

(a)

(b)

A non-exclusive right for the ReGenX Licensors (which right is sublicensable by such licensors) to use the Licensed Patents for noncommercial research purposes and to use the Licensed Patents for such licensors’ discovery research efforts with non-profit organizations and collaborators.

2.4.3 The rights and licenses granted in Sections 2.1, 2.2 and, if applicable, 2.3.3 shall not include any right (and Licensor retains the exclusive (even as to Licensee), fully sublicensable right) under the Licensed Patents:

(a)

to conduct commercial reagent and services businesses, which includes the right to make, have made, use, sell, offer to sell, and import research reagents, including any viral vector construct; provided that, for clarity, the foregoing retained right does not give Licensor (i) the right to conduct clinical trials in humans in the Commercial Field for Friedreich’s Ataxia (Systemic) using AAVrh10 or (ii) the exclusive right to conduct clinical trials in humans in any other Commercial Field with respect to which a Commercial Option has been exercised, though Licensor retains the nonexclusive right to do so; or

(b)

to use the Licensed Patents to provide services to any Third Parties; provided that Licensee’s license under Sections 2.1 and, if applicable, 2.3.3 does include the right to provide the service of the administration of Licensed Products to patients.

2.4.4 Licensor retains the fully sublicensable right under the Licensed Patents to grant non-exclusive research and development licenses to Affiliates and Third Parties; provided that such development rights granted by Licensor shall not include the right to conduct clinical trials in humans in the Commercial Field for Friedreich’s Ataxia (Systemic) using AAVrh10 or any rights to sell products using AAVrh10 in the Commercial Field for Friedreich’s Ataxia (Systemic).

2.4.5 The Trustees of the University of Pennsylvania may use and permit other nonprofit organizations or other non-commercial entities to use the Licensed Patents for educational and research purposes.

2.5 Government Rights . Licensee acknowledges that the United States government retains certain rights in intellectual property funded in whole or part under any contract, grant, or similar agreement with a federal agency. The license grants hereunder are expressly subject to all applicable United States government rights, including any applicable requirement that products that result from such intellectual property and are sold in the United States must be substantially manufactured in the United States.

2.6 Sublicensing .

2.6.1 The research license granted pursuant to Section 2.2 is not sublicensable by Licensee, except to its Affiliates; provided that any such sublicense to an Affiliate must comply with the provisions of this Section 2.6 (including Section 2.6.2). The license granted pursuant to Sections 2.1 and, if applicable, 2.3.3 is sublicensable by Licensee to any Affiliates or Third Parties; provided that any such sublicense must comply with the provisions of this Section 2.6 (including Section 2.6.2).

2.6.2 The right to sublicense granted to Licensee under this Agreement is subject to the following conditions:

(a)

(b)

(c)

The official language of any sublicense agreement shall be English.

(d)

(e)

Licensee’s execution of a sublicense agreement will not relieve Licensee of any of its obligations under this Agreement. Licensee is and shall

remain [***] to Licensor for all of Licensee’s duties and obligations contained in this Agreement and for any act or omission of an Affiliate or Sublicensee that would be a breach of this Agreement if performed or omitted by Licensee, and Licensee will be deemed to be in breach of this Agreement as a result of such act or omission.

2.7 Improvements .

2.7.1 Licensee hereby grants to Licensor a non-exclusive, worldwide, royalty-free, transferable, sublicensable, irrevocable, perpetual license:

(a)

to use any Licensed Back Improvements (and any intellectual property rights with respect thereto) consummate in scope to the Retained Rights, and

(b)

2.7.2 For purposes of this Agreement, “ Licensed Back Improvements ” means any patentable modifications or improvements developed by Licensee, any of its Affiliates, or any Sublicensees to any vector that is the subject of a claim within the Licensed Patents, which modification or improvement is developed by Licensee or any of its Affiliate during the term of this Agreement or by any Sublicensee during the term of any sublicense agreement with such Sublicensee.

2.7.3 Licensee agrees to provide prompt notice to Licensor upon the filing of any patent application covering any Licensed Back Improvement, together with a reasonably detailed description of or access to such Licensed Back Improvement to permit the practice of any such invention or improvement.

ARTICLE 3: CONSIDERATION

3.1 Initial Fee . In consideration of the rights and licenses granted to Licensee under this Agreement, Licensee shall pay Licensor an initial fee of $600,000, of which [***] will be paid upon the Effective Date and [***] will be paid upon the earlier of (a) December 31, 2014 and (b) the closing of a transaction (or series of transactions) involving the issuance or sale of equity securities of Licensee pursuant to which Licensee receives proceeds of not less than US [***]; provided that such [***] portion of the initial fee will be immediately payable upon any termination of this Agreement prior to the earlier of those events.

3.2 Commercial Option Fee . If Licensee exercises the Commercial Option granted to Licensee under Section 2.3 with respect to Friedreich’s Ataxia (CNS), Licensee shall pay Licensor a fee of $300,000. For clarity, no such fee will be required with respect to exercising the Commercial Option with respect to Friedreich’s Ataxia (Systemic).

3.3 Annual Maintenance Fee . In consideration of the rights and licenses granted to Licensee under this Agreement, Licensee shall pay Licensor on-going annual maintenance fees no later than [***] after each anniversary of the Effective Date. The annual maintenance fees will be as follows:

(a)

[***] for Friedreich’s Ataxia (Systemic) and

(b)

if the Commercial Option with respect to Friedreich’s Ataxia (CNS) is exercised, then, following such exercise, [***] for Friedreich’s Ataxia (CNS).

3.4 Milestone Fees . In consideration of the rights and licenses granted to Licensee under this Agreement, Licensee shall pay Licensor the following milestone payments on a per-Disease Indication basis for the first Licensed Product to achieve such milestone event:

3.4.1 Friedreich’s Ataxia (Systemic) Milestones .

	Friedreich’s Ataxia (Systemic) Milestone		Milestone Payment

	Friedreich’s Ataxia (Systemic) Milestone		Milestone Payment
1.	First treatment of human subject in a clinical trial (i.e., first patient, first dose)		[***]
2.	First treatment in Phase 3 Clinical Trial (i.e., first patient, first dose)		[***]
3.	NDA submission in the United States
4.	NDA submission in the European Union or the rest of the world (excluding the United States)		[***]
5.	NDA approval in the United States		[***]
6.	NDA approval in the European Union or the rest of the world (excluding the United States)		[***]
		Total (per such Disease Indication):	$8,850,000

3.4.2 Friedreich’s Ataxia (CNS) .

	Friedreich’s Ataxia (CNS) Milestone		Milestone Payment

1.	First treatment of human subject in a clinical trial (i.e., first patient, first dose)		[***]
2.	First treatment in Phase 3 Clinical Trial (i.e., first patient, first dose)		[***]
3.	NDA submission in the United States		[***]
4.	NDA submission in the European Union or the rest of the world (excluding the United States)		[***]
5.	NDA approval in the United States		[***]
6.	NDA approval in the European Union or the rest of the world (excluding the United States)		[***]
		Total (per such Disease Indication):	$5,000,000

3.4.3 For clarity, the milestone payments set forth in Section 3.4.1 are payable [***] with respect to Friedreich’s Ataxia (Systemic), and the milestone payments set forth in Section 3.4.2 are payable [***] with respect to Friedreich’s Ataxia (CNS), in each case, with respect to the [***] Licensed Product for such Disease Indication that achieves the milestone event, [***]. To the extent that either of the two development milestones in Section 3.4.1 or 3.4.2 (i.e., first treatment of human subject in a clinical trial or first treatment in Phase 3 Clinical Trial in the applicable Disease Indication) has not been paid at the time of achievement of either NDA submission milestone within the same Disease Indication, then, upon the achievement of either of such NDA submission milestones, the preceding unpaid development milestone payments within such Disease Indication shall be made in addition to the payment corresponding to the NDA submission milestone that has been achieved.

3.5 Royalties .

3.5.1 In consideration of the rights and licenses granted to Licensee under this Agreement, Licensee shall pay to Licensor the following royalties based upon the annual Net Sales worldwide of all Licensed Products in a given calendar year, subject to the reductions in royalty rates set forth in Section 3.5.2:

Cumulative Annual Net Sales of all Licensed Products Worldwide		Royalty Percentage
Portion of Net Sales less than $300,000,000		[***]
Portion of Net Sales between (and including)		[***]
$600,000,0000
Portion of Net Sales greater than $600,000,000		[***]

3.5.2 Third Party Royalties Stacking Provision . If Licensee must obtain a license from a Third Party to avoid infringement of such Third Party’s rights in order to manufacture, use, or commercialize a given Licensed Product and if the royalties required to be paid to such Third Party for such license, together with those royalties payable to Licensor, in the aggregate, exceed [***] of Net Sales for any Licensed Product, then the royalty owed to Licensor for that Licensed Product will be reduced by an amount calculated as follows:

STACKING ROYALTY CALCULATIONS

R = (C * (A / (A+B)))

Where

R = reduction of Licensor royalty,

A = unreduced Licensor royalty,

B = sum of all Third Party royalties,

C = increment of projected total royalty above [***].

Example Calculation:


Assume:		i) all Third Party royalties = [***]
		ii) unreduced Licensor royalty = [***]
		iii) projected total royalty = [***]

		R = ([*] - []) ([*] /([] + [**]))
		R = ([**] [***])
		R = [***]
		Licensor Stacked Royalty = [*] - [] = [**]

Notwithstanding the foregoing, Licensee will pay to Licensor no less than [***] of the royalties that Licensee would otherwise pay to Licensor with respect to Net Sales of Licensee if there were no royalties due to Third Parties.

3.5.3 Royalty Payment Period . Licensee’s obligation hereunder for payment of a royalty under this Section 3.5 on the Net Sales of Licensed Products in a given country will end on a Licensed Product-by-Licensed Product and country-by-country basis when the Licensed Product ceases to infringe or be covered by a Valid Claim within the Licensed Commercial Patents in that country. For clarity, only one royalty, determined in accordance with this Section 3.5, is payable on the Net Sales of any unit of a Licensed Product.

3.6 Sublicense Fees .

3.6.1 In further consideration of the rights and licenses granted to Licensee under this Agreement, Licensee will pay Licensor a percentage of any sublicense fees [***] received by Licensee or its Affiliates for the Licensed Commercial Patents from any Third Party Sublicensee or from any Third Party granted any option to obtain a sublicense. The applicable percentage due to Licensor for each sublicense (or option) in the Commercial Field of Friedreich’s Ataxia (CNS) shall be [***]. The applicable percentage due to Licensor for each sublicense (or option) in the Commercial Field of Friedreich’s Ataxia (Systemic) shall be as follows:

Friedreich’s Ataxia (Systemic)		Sublicense Fee Rate
If sublicensed (or optioned) on or before [***]		[***]

If sublicensed (or optioned) on or before [***]		[***]

If sublicensed (or optioned) on or before [***]		[***]

If sublicensed (or optioned) after [***]		[***]

For the avoidance of doubt, with respect to an option to obtain a sublicense in the Commercial Field of Friedreich’s Ataxia (Systemic), if a sublicense is later granted as a result of the exercise of such option, the sublicense fees applicable to such sublicense will be determined by reference to [***].

3.6.2 With respect to the obligations under this Section 3.6, Licensee shall not be required to submit any amounts received from a Third Party for the following:

(a)

Reimbursement or payment, in either case, of Licensee’s actual costs for research, development, and/or manufacturing activities performed by Licensee or its Affiliates corresponding directly to the research, development and/or manufacturing of Licensed Products pursuant to a specific agreement;

(b)

Consideration received for the purchase of an equity interest in Licensee or its Affiliates at fair market value or in the form of loans at commercially reasonable rates of interest; and

(c)

Any and all amounts paid to Licensee or its Affiliates by a Third Party Sublicensee as royalties on sales of Licensed Product sold by such Sublicensee under a sublicense agreement.

3.6.3 If Licensee or its Affiliate receives sublicense fees from Third Party Sublicensees or from any Third Party granted any option to obtain a sublicense under this Agreement in the form of non-cash consideration, then, at Licensor’s option, Licensee shall pay Licensor payments as required by this Section 3.6 (a) in the form of the non-cash consideration received by Licensee or its Affiliates or (b) a cash payment determined based on the fair market value of such non-cash consideration. If Licensee or its Affiliate enters into any sublicense that is not an arm’s

length transaction, fees due under this Section 3.6 will be calculated based on the fair market value of such transaction, at the time of the transaction, assuming an arm’s length transaction made in the ordinary course of business, as determined jointly and in good faith by Licensor and Licensee based on transactions of a similar type and standard industry practice, if any.

3.6.4 To the extent Licensee or its Affiliates receives payment from a Third Party relating to one or more of the milestone events set forth in the tables in Section 3.4, then the amount of the payment made to Licensor under such Section 3.4 with respect to such milestone event shall not be deemed sublicense fees under this Section 3.6; instead, the amounts due under this Section 3.6 shall be calculated by applying the applicable sublicense fee rate set forth in Section 3.6.1 above to the sublicense fees received by Licensee or its Affiliates from such Third Party after deducting the amount of the payment under Section 3.4.

3.7 Reports and Records .

3.7.1 Licensee must deliver to Licensor within [***] after the end of each Calendar Quarter after the first commercial sale of a Licensed Product a report setting forth the calculation of the royalties due to Licensor for such Calendar Quarter, including:

(a)

Number of Licensed Products included within Net Sales, listed by country;

(b)

Gross consideration for Net Sales of Licensed Product, including all amounts invoiced, billed, or received;

(c)

Qualifying costs to be excluded from the gross consideration, as described in Section 1.25, listed by category of cost;

(d)

Net Sales of Licensed Products listed by country;

(e)

A detailed accounting of any royalty reductions applied pursuant to Section 3.5.2;

(f)

Royalties owed to Licensor, listed by category; and

(g)

The computations for any applicable currency conversions.

3.7.2 Licensee shall pay the royalties due under Section 3.5 within [***] following the last day of the Calendar Quarter in which the royalties accrue. Licensee shall send the royalty payments along with the report described in Section 3.7.1.

3.7.3 Within [***] after the occurrence of a milestone event described in Section 3.4, Licensee must deliver to Licensor a report describing the milestone event that occurred, together with a payment of the applicable amount due to Licensor pursuant to Section 3.4.

3.7.4 Within [***] after the receipt of any fees from any Third Party as described in Section 3.6, Licensee must deliver to Licensor a report describing the fees received, together with a payment of the applicable amount due to Licensor pursuant to Section 3.6.

3.7.5 All financial reports under this Section 3.7 will be certified by the chief financial officer of Licensee.

3.7.6 Licensee shall maintain and require its Affiliates and all Sublicensees to maintain, complete and accurate books and records which enable the royalties, fees, and payments payable under this Agreement to be verified. The records must be maintained for [***] after the submission of each report under Article 3. Upon reasonable prior written notice to Licensee, Licensee and its Affiliates and all Sublicensees will provide Licensor and/or the ReGenX Licensors (and their respective accountants) with access to all of the relevant books, records, and related background information required to conduct a review or audit of the royalties, fees, and payments payable to Licensor under this Agreement to be verified. Access will be made available: (a) during normal business hours; (b) in a manner reasonably designed to facilitate the auditing party’s review or audit without unreasonable disruption to Licensee’s business; and (c) no more than once each calendar year during the term of this Agreement and for a period of five years thereafter. Licensee will promptly pay to Licensor the amount of any underpayment determined by the review or audit, plus accrued interest. If the review or audit determines that Licensee has underpaid any payment by [***] or more, then Licensee will also promptly pay the costs and expenses of Licensor and the ReGenX Licensors and their respective accountants in connection with the review or audit.

3.8 Currency, Interest .

3.8.1 All dollar amounts referred to in this Agreement are expressed in United States dollars. All payments to Licensor under this Agreement must be made in United States dollars.

3.8.2 If Licensee receives payment in a currency other than United States dollars for which a royalty or fee or other payment is owed under this Agreement, then (a) the payment will be converted into United States dollars at the conversion rate for the foreign currency as published in the eastern edition of the Wall Street Journal, N.Y. edition, as of the last business day of the Calendar Quarter in which the payment was received by Licensee; and (b) the conversion computation will be documented by Licensee in the applicable report delivered to Licensor under Section 3.7.

3.8.3 All amounts that are not paid by Licensee when due will accrue interest from the date due until paid at a rate equal to 1.5% per month (or the maximum allowed by law, if less).

3.9 Taxes and Withholding .

3.9.1 All payments hereunder will be made free and clear of, and without deduction or deferment in respect of, and Licensee shall pay and be responsible for, and shall hold Licensor harmless from and against, any taxes, duties, levies, fees, or charges, including sales, use, transfer, excise, import, and value added taxes (including any interest, penalties, or additional amounts imposed with respect thereto) but excluding withholding taxes to the extent provided in Section 3.9.2. At the request of Licensee, Licensor will give Licensee such reasonable assistance, which will include the provision of documentation as may be required by the relevant tax authority, to enable Licensee to pay and report and, as applicable, claim exemption from or reduction of, such tax, duty, levy, fee, or charge.

3.9.2 If any payment made by Licensee hereunder becomes subject to withholding taxes with respect to Licensor’s gross or net income under the laws of any jurisdiction, Licensee will deduct and withhold the amount of such taxes for the account of Licensor to the extent required by law and will pay the amounts of such taxes to the proper governmental authority in a timely manner and promptly transmit to Licensor appropriate proof of payment of such withholding taxes. At the request of Licensor, Licensee will give Licensor such reasonable assistance, which will include the provision of appropriate certificates of such deductions made together with other supporting documentation as may be required by the relevant tax authority, to enable Licensor to claim exemption from or reduction of, or otherwise obtain repayment of, such withholding taxes, and will upon request provide such additional documentation from time to time as is reasonably required to confirm the payment of withholding tax.

ARTICLE 4: DILIGENCE

4.1 Diligence Obligations . Licensee will use commercially reasonable efforts to develop, commercialize, market, promote, and sell Licensed Products for Friedreich’s Ataxia (Systemic) in the Commercial Field. Furthermore, if Licensee exercises the Commercial Option granted to Licensee under Section 2.3 with respect to Friedreich’s Ataxia (CNS), Licensee will use commercially reasonable efforts to develop, commercialize, market, promote, and sell Licensed Products for Friedreich’s Ataxia (CNS) in the Commercial Field. Commercially reasonable efforts means efforts equivalent to those utilized by [***]. Without limiting the foregoing, Licensee will meet the following:

(a)

acceptance by the FDA of an Investigational New Drug application, or acceptance by the European Medicines Agency (or any successor entity thereto) of an equivalent application, for a Licensed Product using AAVrh10 for Friedreich’s Ataxia (Systemic) by no later than [***] after the Effective Date; and

(b)

if Licensee exercises the Commercial Option granted to Licensee under Section 2.3 with respect to Friedreich’s Ataxia (Systemic), acceptance by the FDA of an Investigational New Drug application, or acceptance by the European Medicines Agency (or any successor entity thereto) of an equivalent application, for a Licensed Product using the Specified Vector selected in the exercise of such Commercial Option for Friedreich’s Ataxia (Systemic) by no later than [***] after the Grant Date;

provided, however, that, if Licensee expects not to achieve one of the milestones set forth in clause (a) or (b) on or before the specified deadline in such clause (a) or (b), Licensee may pay Licensor an extension fee of [***] on or before such deadline and the relevant deadline in clause (a) or (b), as applicable, shall then be extended by an additional [***]. Licensee will only be entitled to [***] for [***] of the milestones in clauses (a) and (b), [***].

of the first commercial sale by Licensee, its Affiliates, or any Sublicensees of each Licensed Product. Such a report ( “ Development Progress Report ” ), setting forth the current stage of development of Licensed Products, shall include:

4.2.1 Date of Development Progress Report and time covered by such report;

4.2.2 Major activities and accomplishments completed by Licensee, its Affiliates, and any Sublicensees relating directly to the Licensed Product since the last Development Progress Report;

4.2.4 A development plan covering the next two years at least, which will include future development activities to be undertaken by Licensee, its Affiliates, or any Sublicensees during the next reporting period relating directly to the Licensed Product, Licensee’s strategy to bring the Licensed Product to commercialization, and projected timeline for completing the necessary tasks to accomplish the goals of the strategy;

4.2.5 Projected total development remaining before product launch of each Licensed Product; and

4.2.6 Summary of significant development efforts using the Licensed Patents being performed by Third Parties, including the nature of the relationship between Licensee and such Third Parties.

4.3 Confidential Information . The Parties agree that Development Progress Reports shall be deemed Licensee’s Confidential Information; provided that Licensor may share a copy of such reports with the ReGenX Licensors.

4.4 Improvements . Simultaneously with the Development Progress Report, Licensee shall deliver a detailed description of any Licensed Back Improvements, if not previously provided pursuant to Section 2.7.3.

ARTICLE 5: CONFIDENTIALITY

5.1 Treatment of Confidential Information . Each Party, as a receiving party (a “ Receiving Party ”), agrees that it will (a) treat Confidential Information of the other Party (the “ Disclosing Party ”) as strictly confidential; (b) not disclose such Confidential Information to Third Parties without the prior written consent of the Disclosing Party, except as may be permitted in this Agreement; provided that any disclosure permitted hereunder be under confidentiality agreements with provisions at least as stringent as those contained in this Agreement; and (c) not use such Confidential Information for purposes other than those authorized expressly in this Agreement. The Receiving Party agrees to ensure that its employees who have access to Confidential Information are obligated in writing to abide by confidentiality obligations at least as stringent as those contained under this Agreement.

5.2 Public Announcements .

5.2.1 The Parties agree they will release a joint press release in the form attached hereto as Exhibit C . Except as provided in Section 5.2.2, any other press releases by either Party with respect to the other Party or any other public disclosures concerning the existence of or terms of this Agreement shall be subject to review and approval by the other Party. Once the joint press release or any other written statement is approved for disclosure by both Parties, either Party may make subsequent public disclosure of the contents of such statement without the further approval of the other Party.

5.2.2 Notwithstanding Section 5.2.1, Licensor has the right to publish (through press releases, scientific journals, or otherwise) and refer to any clinical, regulatory, or research results related to Licensee’s Licensed Product or Specified Vector program that have been publicly disclosed by Licensee, including referring to Licensee by name as a licensee of Licensor, which publication or referral by Licensor shall not require the prior consent of Licensee, but Licensor will provide Licensee with a copy of any such publications or referrals two business days prior to release.

5.3 Authorized Disclosure . Notwithstanding the provisions of Section 5.1 or 5.2, either Party may disclose the other’s Confidential Information or make such a disclosure of the existence of and/or terms of this Agreement to any [***]; provided that, in each case, such recipient of Confidential Information is obligated to keep such information confidential on terms no less stringent than those set forth in this Agreement. Furthermore, Licensee agrees that Licensor may share a copy of this Agreement, reports and notices provided by Licensee to Licensor pursuant to the terms of this Agreement, and copies of sublicense agreements provided to Licensor hereunder, with the ReGenX Licensors to the extent required by the GSK Agreement and Penn Agreement. In the event that the Receiving Party receives service of legal process that purports to compel disclosure of the Disclosing Party’s Confidential Information or becomes obligated by law to disclose the Confidential Information of the Disclosing Party or the existence of or terms of this Agreement to any governmental authority, then, to the extent legally permitted, the Receiving Party shall promptly notify the Disclosing Party, so that the Disclosing Party may seek an appropriate protective order or other remedy with respect to narrowing the scope of such requirement and/or waive compliance by the Receiving Party with the provisions of this Agreement. The Receiving Party will, at the Disclosing Party’s request and expense, provide the Disclosing Party with reasonable assistance in obtaining such protective order or other remedy. If, in the absence of such protective order or other remedy, the Receiving Party is nonetheless required by law to disclose the existence of or terms of this Agreement or other Confidential Information of the Disclosing Party, the Receiving Party may disclose such Confidential Information without liability hereunder; provided that the Receiving Party shall furnish only such portion of the Confidential Information that is legally required to be disclosed and only to the extent required by law.

5.4 Term of Confidentiality . The obligations of this Article 5 shall continue for a period of [***] following the expiration or termination of this Agreement.

ARTICLE 6: TERM AND TERMINATION

6.1 Term of Agreement . This Agreement, unless sooner terminated as provided in this Agreement, expires upon the expiration, lapse, abandonment, or invalidation of the last Valid Claim of the Licensed Commercial Patents to expire, lapse, or become abandoned or unenforceable in all the countries of the world.

6.2 Termination for Failure to Exercise Option . This Agreement will terminate automatically with respect to Friedreich’s Ataxia (CNS) at the end of the Research Term for Friedreich’s Ataxia (CNS) if Licensee does not exercise the Commercial Option for Friedreich’s Ataxia (CNS) in accordance with Section 2.3. This Agreement will terminate automatically with respect to Friedreich’s Ataxia (Systemic) with respect to any Specified Vector (other than AAVrh10) at the end of the Research Term for Friedreich’s Ataxia (Systemic) if Licensee does not exercise the Commercial Option for Friedreich’s Ataxia (Systemic) in accordance with Section 2.3; provided that such termination will not affect Licensee’s rights under this Agreement with respect to the license granted under Section 2.1.

6.3 Licensee’s Right to Terminate . Licensee may, upon six months’ prior written notice to Licensor, terminate this Agreement for any reason, with or without cause; provided that, if such termination notice is sent prior to the first anniversary of the Effective Date, such termination notice shall be accompanied by Licensee’s payment of $500,000 in satisfaction of the remainder of the initial fee under Section 3.1. In exercising such termination right, Licensee may terminate the Agreement in its entirety or, if desired, Licensee may specify in the written notice that this Agreement is terminating only with respect to one or more of the Disease Indications within the Research Field or Commercial Field, as applicable.

6.4 Termination for Breach .

6.4.1 Licensor may terminate this Agreement, if Licensee is late in paying to Licensor royalties, fees, or any other monies due under this Agreement, and Licensee does not pay Licensor in full within 15 days upon written demand from Licensor, which termination shall be effective immediately upon the expiration of such 15-day cure period.

6.4.2 Either Party may terminate this Agreement, if the other Party materially breaches this Agreement and does not cure such material breach within 30 days after written notice of the breach, which termination shall be effective immediately upon the expiration of such 30-day cure period.

6.4.3 If the allegedly breaching Party disputes in good faith the allegation of breach or non-cure prior to the expiration of the applicable cure period, this Agreement shall not be terminated until such dispute is resolved in favor of the non-breaching Party in accordance with Section 10.6, and the breaching Party has not cured such material breach within an additional 30 days, or such payment breach within an additional 15 days, after such resolution; provided that Licensor shall be entitled to terminate this Agreement at the end of the original 15-day or 30-day, as applicable, cure period, without waiting for resolution of the dispute in accordance with Section 10.6 if the breach by Licensee of this Agreement would cause Licensor to be in breach of the GSK Agreement or the Penn Agreement.

6.5 Termination for Insolvency .

6.5.1 Licensor may terminate this Agreement, effective immediately upon written notice to Licensee, if Licensee, any of its Affiliates, or any Sublicensees experiences any Trigger Event.

6.5.2 For purposes of this Section 6.5, “ Trigger Event ” means any of the following: (a) if Licensee, any Affiliate, or any Sublicensee, as applicable, (i) becomes insolvent, becomes bankrupt, or generally fails to pay its debts as such debts become due, (ii) is adjudicated insolvent or bankrupt, (iii) admits in writing its inability to pay its debts, (iv) suffers the appointment of a custodian, receiver, or trustee for it or its property and, if appointed without its consent, is not discharged within 30 days, (v) makes an assignment for the benefit of creditors, or (vi) suffers proceedings being instituted against it under any law related to bankruptcy, insolvency, liquidation, or the reorganization, readjustment, or release of debtors and, if contested by it, not dismissed or stayed within ten days; (b) the institution or commencement by Licensee, any Affiliate, or any Sublicensee, as applicable, of any proceeding under any law related to bankruptcy, insolvency, liquidation, or the reorganization, readjustment, or release of debtors; (c) the entering of any order for relief relating to any of the proceedings described in Section 6.5.2(a) or (b) above; (d) the calling by Licensee, any Affiliate, or any Sublicensee, as applicable, of a meeting of its creditors with a view to arranging a composition or adjustment of its debts; or (e) the act or failure to act by Licensee, any Affiliate, or any Sublicensee, as applicable, indicating its consent to, approval of, or acquiescence in any of the proceedings described in Section 6.5.2(b) through (d) above.

6.6 Patent Challenge .

6.6.1 Licensor may terminate this Agreement, effective immediately upon written notice to Licensee, upon the commencement by Licensee, any of its Affiliates, or any Sublicensee of a Patent Challenge.

6.6.2 For purposes of this Section 6.6, “ Patent Challenge ” means any action against Licensor, The Trustees of the University of Pennsylvania, or the ReGenX Licensors, including an action for declaratory judgment, to declare or render invalid or unenforceable the Licensed Patents, or any claim thereof.

6.7.1 The licenses granted by Licensor hereunder shall terminate, and Licensee, its Affiliates, and (unless the sublicense agreement is assigned pursuant to Section 6.7.2) all Sublicensees shall cease to make, have made, use, import, sell, and offer for sale all AAV Materials or Licensed Products and shall cease to otherwise practice the Licensed Patents; provided that Licensee, its Affiliates, and Sublicensees shall have the right to continue to sell their existing inventories of Licensed Products for a period not to exceed [***] after the effective date of such termination;

6.7.2 At Licensor’s request, Licensee shall assign to Licensor any or all sublicenses granted to Third Parties to the extent of the rights licensed to Licensee hereunder and sublicensed

to the Sublicensee; provided that (i) prior to such assignment, Licensee shall advise Licensor whether such Sublicensee is then in full compliance with all terms and conditions of its sublicense and continues to perform thereunder, and, if such Sublicensee is not in full compliance or is not continuing to perform, Licensor may elect not to have such sublicense assigned; and (ii) following such assignment, Licensor shall not be liable to such Sublicensee with respect to any obligations of Licensee to the Sublicensee that are not consistent with, or not required by, Licensor’s obligations to Licensee under this Agreement; and all sublicenses not requested to be assigned to Licensor shall terminate;

6.7.3 If termination is by Licensee pursuant to Section 6.3 or by Licensor pursuant to Section 6.4, 6.5, or 6.6, Licensee shall grant, and hereby grants to Licensor a non-exclusive, perpetual, irrevocable, worldwide, royalty-free, transferable, sublicensable license under any patentable modifications or improvements (and any intellectual property rights with respect thereto) developed by Licensee or any Affiliates (during the term of this Agreement) or by any Sublicensees (during the term of any sublicense agreement with such Sublicensee) to any vector that is the subject of a claim within any of the Licensed Patents, for use by Licensor for the research, development, and commercialization of products in any therapeutic indication;

6.7.4 Licensee shall pay all monies then-owed to Licensor under this Agreement;

6.7.5 Each Receiving Party shall, at the Disclosing Party’s request, return all Confidential Information of the Disclosing Party. Notwithstanding the foregoing, one copy may be kept by either Party for a record of that Party’s obligations; and

6.7.6 If termination is only with respect to a particular Disease Indication within the Research Field or the Commercial Field, but not all Disease Indications, then the provisions of this Section 6.7 shall only apply with respect to the terminated Disease Indications, and this Agreement shall continue with respect to the non-terminated Disease Indications.

6.8 Survival . Licensee’s obligation to pay all monies due and owed to Licensor under this Agreement which have matured as of the effective date of termination or expiration shall survive the termination or expiration of this Agreement. [In addition, the provisions of Section 2.4, (Retained Rights), Section 2.5 (Government Rights), Section 2.7 (Improvements), Article 3 (Consideration) (with respect to any final reports or to the extent any amounts are due but unpaid), Section 3.7 (Reports and Records), Section 4.3 (Confidential Information), Article 5 (Confidentiality), Article 6 (Term and Termination), Section 8.3 (Disclaimer of Warranties, Damages), Section 8.4 (Indemnification), Section 8.5 (Insurance), Article 9 (Use of Name), and Article 10 (Additional Provisions) shall survive such termination or expiration of this Agreement in accordance with their respective terms.] [Subject to final review]

ARTICLE 7: PATENT MAINTENANCE; PATENT INFRINGEMENT

7.1 Prosecution of Licensed Patents . As between Licensor and Licensee, but subject to any obligations of Licensor to the ReGenX Licensors, the Parties agree as follows:

7.1.1 Licensor shall have the sole right, but not the obligation, to Prosecute patent applications and issued patents within Licensed Patents, in Licensor’s sole discretion.

7.2 Infringement Actions Against Third Parties .

7.2.1 Licensee is responsible for notifying Licensor promptly of any infringement of Licensed Patents (other than Retained Rights) that may come to Licensee’s attention.

7.2.2 As between Licensor and Licensee, but subject to any obligations of Licensor to the ReGenX Licensors, Licensor shall have the sole right, but not the obligation, to prosecute any such infringement at its [***] recovered in connection therewith. In any action to enforce any of the Licensed Patents, Licensee, at the request and expense of Licensor, shall cooperate to the fullest extent reasonably possible, including in the event that, if Licensor is unable to initiate or prosecute such action solely in its own name, Licensee shall join such action voluntarily and shall execute all documents necessary to initiate litigation to prosecute, maintain, and settle such action. Nothing in this Agreement obligates Licensor to bring or prosecute lawsuits against Third Parties for infringement of any Licensed Patents.

7.2.3 Licensee shall have no right to undertake prosecution of any such infringement.

7.3 Defense of Infringement Claims . In the event Licensee or Licensor becomes aware that Licensee’s or any of its Affiliates’ or any Sublicensees’ practice of the Licensed Patents is the subject of a claim for patent infringement by a Third Party, that Party shall promptly notify the other, and the Parties shall consider the claim and the most appropriate action to take. Licensee shall cause each of its Affiliates and each Sublicensee to notify Licensee promptly in the event such entity becomes aware that its practice of the Licensed Patents is the subject of a claim of patent infringement by another. To the extent Licensor takes any action, Licensor (or the ReGenX Licensors) shall have the right to require Licensee’s reasonable cooperation in any such suit, upon written notice to Licensee; and Licensee shall have the obligation to participate upon Licensor’s request, in which event, Licensor shall bear the cost of Licensee’s participation. Without Licensor’s prior written permission, Licensee must not settle or compromise any such suit in a manner that imposes any material obligations or restrictions on Licensor or the ReGenX Licensors or grants any rights to the Licensed Patents other than rights that Licensee has the right to grant under this Agreement.

ARTICLE 8: REPRESENTATIONS AND WARRANTIES; INDEMNIFICATION

8.1 Representations and Warranties by Licensor . Licensor represents and warrants to Licensee as of the Effective Date:

8.1.1 Licensor has the right, power, and authority to enter into this Agreement and to grant to Licensee the licenses specified in this Agreement;

8.1.2 This Agreement when executed shall become the legal, valid, and binding obligation of it, enforceable against it, in accordance with its terms;

8.1.3 There are no actions, suits, proceedings, or arbitrations pending or, to Licensor’s knowledge, threatened against Licensor relating to the Licensed Research Patents that would be inconsistent with the rights granted to Licensee under this Agreement;

8.1.4 To Licensor’s knowledge, (a) the Licensed Research Patents are solely owned by the Trustees of the University of Pennsylvania, and (b) no Third Party (other than the ReGenX Licensors) has any right, interest, or claim in or to such Licensed Research Patents with respect to the Disease Indications that are inconsistent with those granted to Licensee with respect to the Disease Indications;

8.1.5 To Licensor’s knowledge, no Third Party is infringing any of the Licensed Research Patents in a manner that is inconsistent with the scope of rights granted to Licensee with respect to the Disease Indications; and

8.1.6 Licensor has not received any written notice from any Third Party patentee alleging infringement of such Third Party’s patents by the practice of the Licensed Research Patents with respect to the Disease Indications.

8.2 Representations and Warranties by Licensee . Licensee represents and warrants to Licensor as of the Effective Date that:

8.2.1 Licensee has the right, power, and authority to enter into this Agreement and to grant the licenses granted by it hereunder;

8.2.2 This Agreement when executed shall become the legal, valid, and binding obligation of it, enforceable against it, in accordance with its terms;

8.2.3 Licensee has the ability and the resources, including financial resources, necessary to carry out its obligations under this Agreement; and

8.2.4 There are no actions, suits, proceedings, or arbitrations pending or, to Licensee’s knowledge, threatened against Licensee that would impact activities under this Agreement.

8.3 Disclaimer of Warranties, Damages . EXCEPT AS SET FORTH IN SECTION 8.1, THE LICENSED PATENTS, AAV MATERIALS, LICENSED PRODUCTS, AND ALL RIGHTS LICENSED UNDER THIS AGREEMENT ARE PROVIDED ON AN “AS IS” BASIS, AND LICENSOR MAKES NO REPRESENTATIONS OR WARRANTIES, EXPRESS OR IMPLIED, WITH RESPECT THERETO. BY WAY OF EXAMPLE BUT NOT OF LIMITATION, LICENSOR MAKES NO REPRESENTATIONS OR WARRANTIES, AND HEREBY DISCLAIMS ALL EXPRESS AND IMPLIED REPRESENTATIONS AND WARRANTIES, (i) OF COMMERCIAL UTILITY, ACCURACY, COMPLETENESS, PERFORMANCE, MERCHANTABILITY, FITNESS FOR A PARTICULAR PURPOSE, VALIDITY OR ENFORCEABILITY OF THE LICENSED PATENTS, AND PROFITABILITY; OR (ii) THAT THE USE OF THE LICENSED PATENTS, AAV MATERIALS, OR LICENSED PRODUCTS WILL NOT INFRINGE ANY PATENT, COPYRIGHT, TRADEMARK, OR OTHER PROPRIETARY RIGHTS OF THIRD PARTIES. EXCEPT AS SET FORTH HEREIN, NONE OF LICENSOR OR EITHER OF THE REGENX LICENSORS SHALL BE LIABLE TO LICENSEE, LICENSEE’S SUCCESSORS OR

ASSIGNS, ANY SUBLICENSEES, OR ANY THIRD PARTY WITH RESPECT TO: (a) ANY CLAIM ARISING FROM USE OF THE LICENSED PATENTS, AAV MATERIALS, LICENSED PRODUCTS, AND ANY OR ALL RIGHTS LICENSED UNDER THIS AGREEMENT OR FROM THE DEVELOPMENT, TESTING, MANUFACTURE, USE, OR SALE OF AAV MATERIALS OR LICENSED PRODUCTS; OR (b) ANY CLAIM FOR LOSS OF PROFITS, LOSS OR INTERRUPTION OF BUSINESS, OR FOR INDIRECT, SPECIAL, INCIDENTAL, PUNITIVE, OR CONSEQUENTIAL DAMAGES OF ANY KIND, INCLUDING ANY ARISING FROM OR RELATING TO ANY BREACH OF THIS AGREEMENT OR THE EXERCISE OF RIGHTS HEREUNDER, REGARDLESS OF ANY NOTICE OF SUCH DAMAGES. NOTHING IN THIS SECTION 8.3 IS INTENDED TO LIMIT OR RESTRICT THE INDEMNIFICATION RIGHTS OR OBLIGATIONS OF EITHER PARTY UNDER SECTION 8.4 OR TO LIMIT A PARTY’S LIABILITY FOR BREACHES OF ITS OBLIGATION REGARDING CONFIDENTIALITY UNDER ARTICLE 5.

8.4 Indemnification .

8.4.1 By Licensee . Licensee shall defend, indemnify, and hold harmless Licensor, the ReGenX Licensors, and their respective shareholders, members, officers, trustees, faculty, students, contractors, agents, and employees (individually, a “ Licensor Indemnified Party ” and, collectively, the “ Licensor Indemnified Parties ”) from and against any and all Third Party liability, loss, damage, action, claim, fee, cost, or expense (including attorneys’ fees) (individually, a “ Third Party Liability ” and, collectively, the “ Third Party Liabilities ”) suffered or incurred by the Licensor Indemnified Parties from claims of such Third Parties to the extent that such claims result from or arise out of: [***]; provided, however, that Licensee shall not be liable for claims to the extent based on (1) any breach by Licensor of the representations, warranties, or obligations of Licensor under this Agreement or (2) the gross negligence or intentional misconduct of any of the Licensor Indemnified Parties. Without limiting the foregoing, but subject to clauses (1) and (2) above, Licensee must defend, indemnify, and hold harmless the Licensor Indemnified Parties from and against any Third Party Liabilities resulting from:

(a)

any [***] or other claim of any kind related to the [***] by a Third Party of a Licensed Product that was [***] by Licensee, its Affiliates, any Sublicensees, their respective assignees, or vendors;

(b)

any claim by a Third Party that the [***]; and

(c)

[***] conducted by or on behalf of Licensee, its Affiliates, any Sublicensees, their respective assignees, or vendors relating to the Licensed Patents, AAV Materials, or Licensed Products, including any claim by or on behalf of a [***].

8.4.2 By Licensor . Licensor shall defend, indemnify, and hold harmless Licensee, its shareholders, members, officers, contractors, agents, and employees (individually, a “ Licensee Indemnified Party ” and, collectively, the “ Licensee Indemnified Parties ”) from and against any and all Third Party Liabilities suffered or incurred by the Licensee Indemnified Parties from claims of such Third Parties to the extent that such claims result from or arise out of: [***]; provided, however, that Licensor shall not be liable for claims to the extent based on (1) any

breach by Licensee of the representations, warranties, or obligations of Licensee under this Agreement or (2) the gross negligence or intentional misconduct of any of the Licensee Indemnified Parties.

8.4.3 Indemnification Procedure . Each Party, as an indemnifying party (an “ Indemnifying Party ”), shall not be permitted to settle or compromise any claim or action giving rise to Third Party Liabilities in a manner that imposes any restrictions or obligations on any indemnified party (an “ Indemnified Party ”) without the Indemnified Party’s prior written consent or, if Licensee is the Indemnifying Party, that imposes any restrictions or obligations on Licensor’s direct or indirect licensors or grants any rights to the Licensed Patents or Licensed Products other than those Licensee has the right to grant under this Agreement without Licensor’s prior written consent. The Indemnifying Party shall be permitted to control any litigation or potential litigation involving the defense of any claim subject to indemnification pursuant to this Section 8.4, including the selection of counsel, with the reasonable approval of the Indemnified Party. Upon the Indemnifying Party’s reasonable request, the Indemnified Parties will reasonably cooperate with the Indemnifying Party in the defense and settlement of any such claim, at the Indemnifying Party’s cost and expense. If an Indemnifying Party fails or declines to assume the defense of any such claim or action within [***] after notice thereof, the Indemnified Party may assume the defense of such claim or action at the cost and risk of the Indemnifying Party, and any Third Party Liabilities related thereto shall be conclusively deemed a Third Party Liability of the Indemnifying Party. The indemnification rights of a Indemnified Party contained in this Agreement are in addition to all other rights that such Indemnified Party may have at law or in equity or otherwise. The Indemnifying Party will pay directly all Third Party Liabilities incurred for defense or negotiation of any claim hereunder or will reimburse the Indemnified Party for all documented Third Party Liabilities incident to the defense or negotiation of any such claim within [***] after the Indemnifying Party’s receipt of invoices for such fees, expenses, and charges.

policies of insurance required by this Section 8.5 will be issued by an insurance carrier with an A.M. best rating of [***] or better and will name Licensor as an additional insured with respect to Licensee’s performance (and its Affiliates’ and any Sublicensees’) under this Agreement. Licensee will provide Licensor with insurance certificates evidencing the required coverage within [***] after the Effective Date and the commencement of each policy period and any renewal periods. Each certificate will provide that the insurance carrier will notify Licensor in writing at least [***] prior to the cancellation or material change in coverage. Licensee will cause all Sublicensees to comply with the terms of this Section 8.5 to the same extent as Licensee.

ARTICLE 9: USE OF NAME

Licensee, its Affiliates, any Sublicensees, and all of its and their employees and agents must not use Licensor’s, the University of Pennsylvania’s, or SmithKline Beecham Corporation’s name, seal, logo, trademark, or service mark (or any adaptation thereof) or the name, seal, logo, trademark, or service mark (or any adaptation thereof) of any of such entities’ representative, school, organization, employee, or student in any way without the prior written consent of Licensor or such entity, as applicable; provided, however that Licensee may acknowledge the existence and general nature of this Agreement, subject to Section 5.3.

ARTICLE 10: ADDITIONAL PROVISIONS

10.2 Assignment . The rights and obligations of Licensee and Licensor hereunder shall inure to the benefit of, and shall be binding upon, their respective permitted successors and assigns. Licensee may not assign this Agreement or any of its rights or obligations under this Agreement without the prior written consent of Licensor; provided, however, that Licensee may assign this Agreement, without Licensor’s prior written consent, pursuant to a merger or sale of all or substantially all of the assets of Licensee to which the Agreement relates; provided that, as part of any permitted assignment, (a) Licensee provides Licensor with written notice of such assignment at least five business days prior to the effectiveness of such assignment, and (b) Licensee requires any such assignee to agree in writing to be legally bound by this Agreement to the same extent as Licensee and provides Licensor with a copy of such assignee undertaking. In addition, Licensee will provide Licensor with written notice of any change of control (i.e., the acquisition by a person or group of “control” of Licensee, as defined in Section 1.7) of Licensee at least five business days prior to the effectiveness of such change of control. Licensor may assign this Agreement and its rights and obligations without the consent of Licensee. No assignment shall relieve the assigning Party of responsibility for the performance of any accrued obligations which it has prior to such assignment. Any attempted assignment by Licensee in violation of this Section 10.2 shall be null and void and of no legal effect.

10.4 Notices . Notices, payments, statements, reports, and other communications under this Agreement shall be in writing and shall be deemed to have been received as of the date received if sent by public courier (e.g., Federal Express), by Express Mail, receipt requested, or by facsimile (with a copy of such facsimile also sent by one of the other methods of delivery) and addressed as follows:

If for Licensor:
		Telephone:[ ]
		Facsimile: [ ]
	ReGenX Biosciences, LLC
	750 17th Street, NW
	Suite 1100
	Washington, DC 20006
	USA
	Attn: Chief Executive Officer
	Telephone:202-785-7438
	Facsimile:202-785-7439

If for Licensee:

	AAVLife
	183/189 avenue de Choisy
	75013 Paris
	France
	Attn: [ ]

with a copy to:		with a copy to:

	ReGenX Biosciences, LLC	WilmerHale
	750 17th Street, NW	60 State Street
	Suite 1100	Boston, MA 02109
	Washington, DC 20006	USA
	USA	Attn: Belinda M. Juran, Esq.
	Attn: General Counsel	Telephone: [ ]
	Telephone: 202-785-7438	Facsimile: 617-526-5000
	Facsimile: 202-785-7439

Either Party may change its official address upon written notice to the other Party in accordance with this Section 10.4.

hereby submit to the exclusive jurisdiction of and venue in the courts located in the State of New York with respect to any and all disputes concerning the subject of this Agreement.

10.6 Dispute Resolution . In the event of any controversy or claim arising out of or relating to this Agreement, the Parties shall first attempt to resolve such controversy or claim through good faith negotiations for a period of not less than 30 days following notification of such controversy or claim to the other Party. If such controversy or claim cannot be resolved by means of such negotiations during such period, then such controversy or claim shall be resolved by binding arbitration administered by the American Arbitration Association (“ AAA ”) in accordance with the Commercial Arbitration Rules of the AAA in effect on the date of commencement of the arbitration, subject to the provisions of this Section 10.6. The arbitration shall be conducted as follows:

10.6.1 The arbitration shall be conducted by three arbitrators, each of whom by training, education, or experience has knowledge of the research, development, and commercialization of biological therapeutic products in the United States. The arbitration shall be conducted in English and held in New York, New York.

10.6.2 In its demand for arbitration, the Party initiating the arbitration shall provide a statement setting forth the nature of the dispute, the names and addresses of all other parties, an estimate of the amount involved (if any), the remedy sought, otherwise specifying the issue to be resolved, and appointing one neutral arbitrator. In an answering statement to be filed by the responding Party within [***] after confirmation of the notice of filing of the demand is sent by the AAA, the responding Party shall appoint one neutral arbitrator. Within [***] from the date on which the responding Party appoints its neutral arbitrator, the first two arbitrators shall appoint a chairperson.

10.6.3 If a Party fails to make the appointment of an arbitrator as provided in Section 10.6.2, the AAA shall make the appointment. If the appointed arbitrators fail to appoint a chairperson within the time specified in Section 10.6.2 and there is no agreed extension of time, the AAA shall appoint the chairperson.

10.6.4 The arbitrators will render their award in writing and, unless all Parties agree otherwise, will include an explanation in reasonable detail of the reasons for their award. Judgment upon the award rendered by the arbitrators may be entered in any court having jurisdiction thereof, including in the courts described in Section 10.5. The arbitrators will have the authority to grant injunctive relief and other specific performance; provided that the arbitrators will have no authority to award damages in contravention of this Agreement, and each Party irrevocably waives any claim to such damages in contravention of this Agreement. The arbitrators will, in rendering their decision, apply the substantive law of the State of New York, without giving effect to conflict of law provisions that may require the application of the laws of another jurisdiction. The decision and award rendered by the arbitrators will be final and non-appealable (except for an alleged act of corruption or fraud on the part of the arbitrator).

10.6.5 The Parties shall use their reasonable efforts to conduct all dispute resolution procedures under this Agreement as expeditiously, efficiently, and cost-effectively as possible.

10.6.6 All expenses and fees of the arbitrators and expenses for hearing facilities and other expenses of the arbitration will be borne equally by the Parties unless the Parties agree otherwise or unless the arbitrators in the award assess such expenses against one of the Parties or allocate such expenses other than equally between the Parties. Each of the Parties will bear its own counsel fees and the expenses of its witnesses except to the extent otherwise provided in this Agreement or by applicable law.

10.6.7 Compliance with this Section 10.6 is a condition precedent to seeking relief in any court or tribunal in respect of a dispute, but nothing in this Section 10.6 will prevent a Party from seeking equitable or other interlocutory relief in the courts of appropriate jurisdiction, pending the arbitrators’ determination of the merits of the controversy, if applicable to protect the confidential information, property, or other rights of that Party or to otherwise prevent irreparable harm that may be caused by the other Party’s actual or threatened breach of this Agreement.

10.8 Compliance with Law. Licensee (and its Affiliates’ and any Sublicensees’) must comply with all prevailing laws, rules, and regulations that apply to its activities or obligations under this Agreement. Without limiting the foregoing, it is understood that this Agreement may be subject to United States laws and regulations controlling the export of technical data, computer software, laboratory prototypes, and other commodities, articles, and information, including the Arms Export Control Act as amended in the Export Administration Act of 1979 and that Licensee’s obligations are contingent upon compliance with applicable United States export laws and regulations. The transfer of certain technical data and commodities may require a license from the cognizant agency of the United States Government and/or written assurances by Licensee that Licensee shall not export data or commodities to certain foreign countries without prior approval of such agency. Licensor neither represents that a license is not required nor that, if required, it will issue.

10.9 Entire Agreement . This Agreement embodies the entire understanding between the Parties relating to the subject matter hereof and supersedes all prior understandings and agreements, whether written or oral, including that certain Mutual Non-Disclosure Agreement dated January 9, 2014 between the Parties. All “Confidential Information” (as defined in such Mutual Non-Disclosure Agreement) disclosed by one Party to the other Party pursuant to such Mutual Non-Disclosure Agreement shall be deemed “Confidential Information” of such disclosing Party under this Agreement (unless and until it falls within one of the exclusions set forth in Section 1.11). This Agreement may not be varied except by a written document signed by duly authorized representatives of both Parties.

10.10 Marking . Licensee, its Affiliates, and any Sublicensees shall mark any Licensed Product (or their containers or labels) made, sold, or otherwise distributed by it or them with any notice of patent rights necessary or desirable under applicable law to enable the Licensed Commercial Patents to be enforced to their full extent in any country where Licensed Products are made, used, sold, offered for sale, or imported.

10.13 Interpretation; Construction . The captions to the several Articles and Sections of this Agreement are included only for convenience of reference and shall not in any way affect the construction of, or be taken into consideration in interpreting, this Agreement. In this Agreement, unless the context requires otherwise, (a) the word “including” shall be deemed to be followed by the phrase “without limitation” or like expression; (b) references to the singular shall include the plural and vice versa; (c) references to masculine, feminine, and neuter pronouns and expressions shall be interchangeable; (d) the words “herein” or “hereunder” relate to this Agreement; (e) “or” is disjunctive but not necessarily exclusive; (t) the word “will” shall be construed to have the same meaning and effect as the word “shall”; (g) all references to “dollars” or “$” herein shall mean U.S. Dollars; (h) unless otherwise provided, all reference to Sections, Articles, and exhibits in this Agreement are to Sections, Articles, and exhibits of and in this Agreement; and (i) whenever this Agreement refers to a number of days, such number shall refer to calendar days unless business days are specified. Business days shall mean a day on which banking institutions in Washington, D.C. are open for business. Each Party represents that it has been represented by legal counsel in connection with this Agreement and acknowledges that it has participated in the drafting hereof. In interpreting and applying the terms and provisions of this Agreement, the Parties agree that no presumption will apply against the Party which drafted such terms and provisions.

10.15 Counterparts . This Agreement may be executed in one or more counterparts, each of which will be deemed an original, but all of which together will constitute one and the same instrument.

[REMAINDER OF PAGE INTENTIONALLY LEFT BLANK]

IN WITNESS WHEREOF, the Parties, intending to be legally bound, have caused this License Agreement to be executed by their duly authorized representatives.

REGENX BIOSCIENCES, LLC		AAVLIFE
By:		By:
Name:	Kenneth Mills	Name:	Amber Salzman, PhD
Title:	President & CEO	Title:	President

Exhibit A-1

Licensed Research Patents (AAV7)

Application #	Patent #	Filing Date	Country	Status
	[***]	[***]	[***]	[***]
[***]		[***]	[***]	[***]
[***]		[***]	[***]	[***]
	[***]	[***]	[***]	[***]
[***]		[***]	[***]	[***]
	[***]	[***]	[***]	[***]
	[***]	[***]	[***]	[***]
	[***]	[***]	[***]	[***]
	[***]	[***]	[***]	[***]
[***]	[***]	[***]	[***]	[***]
	[***]	[***]	[***]	[***]
[***]		[***]	[***]	[***]
	[***]	[***]	[***]	[***]
[***]		[***]	[***]	[***]
	[***]	[***]	[***]	[***]
	[***]	[***]	[***]	[***]
	[***]	[***]	[***]	[***]
	[***]	[***]	[***]	[***]
	[***]	[***]	[***]	[***]
[***]		[***]	[***]	[***]
[***]		[***]	[***]	[***]
	[***]	[***]	[***]	[***]
	[***]	[***]	[***]	[***]
[***]		[***]	[***]	[***]
	[***]	[***]	[***]	[***]

Exhibit A-1

Licensed Research Patents (AAV7)

Application #	Patent #	Filing Date	Country	Status
	[***]	[***]	[***]	[***]
[***]		[***]	[***]	[***]
[***]		[***]	[***]	[***]
	[***]	[***]	[***]	[***]
[***]		[***]	[***]	[***]
	[***]	[***]	[***]	[***]
	[***]	[***]	[***]	[***]
	[***]	[***]	[***]	[***]
	[***]	[***]	[***]	[***]
[***]	[***]	[***]	[***]	[***]
	[***]	[***]	[***]	[***]
[***]		[***]	[***]	[***]
	[***]	[***]	[***]	[***]
[***]		[***]	[***]	[***]
	[***]	[***]	[***]	[***]
	[***]	[***]	[***]	[***]
	[***]	[***]	[***]	[***]
	[***]	[***]	[***]	[***]
	[***]	[***]	[***]	[***]
[***]		[***]	[***]	[***]
[***]		[***]	[***]	[***]
	[***]	[***]	[***]	[***]
	[***]	[***]	[***]	[***]
[***]		[***]	[***]	[***]
	[***]	[***]	[***]	[***]

Exhibit A-2

Licensed Research Patents (AAV8)

Application #	Patent #	Filing Date*	Country	Status
[***]		[***]	[***]	[***]
[***]		[***]	[***]	[***]
[***]		[***]	[***]	[***]
[***]	[***]	[***]	[***]	[***]
[***]		[***]	[***]	[***]
[***]		[***]	[***]	[***]
[***]	[***]	[***]	[***]	[***]
[***]	[***]	[***]	[***]	[***]
[***]	[***]	[***]	[***]	[***]
[***]		[***]	[***]	[***]
[***]		[***]	[***]	[***]
[***]		[***]	[***]	[***]
[***]		[***]	[***]	[***]
[***]	[***]	[***]	[***]	[***]
[***]		[***]	[***]	[***]

* International Filing Date, where national stage application or foreign divisional thereof

Exhibit A-3

Licensed Research Patents (AAV9)

Application #	Patent #	Filing Date	Country	Status
[***]	[***]	[***]	[***]	[***]
[***]		[***]	[***]	[***]
[***]	[***]	[***]	[***]	[***]
[***]		[***]	[***]	[***]
[***]	[***]	[***]	[***]	[***]
[***]	[***]	[***]	[***]	[***]
[***]	[***]	[***]	[***]	[***]
[***]		[***]	[***]	[***]
[***]	[***]	[***]	[***]	[***]
[***]	[***]	[***]	[***]	[***]
[***]		[***]	[***]	[***]
[***]	[***]	[***]	[***]	[***]
[***]		[***]	[***]	[***]
[***]	[***]	[***]	[***]	[***]
[***]	[***]	[***]	[***]	[***]
[***]	[***]	[***]	[***]	[***]
[***]		[***]	[***]	[***]

Exhibit A-4

Licensed Research Patents (AAVrh10)

Appln #	Title	Inventors	Nos	Docket
[***]	[***]	[***]	[***]	[***]

Docket	Country	Appln No	Filing Date	Patent Number	Issue Date	Pubn Number	Pub Date
[***]	[***]	[***]	[***]	[***]	[***]
[***]	[***]	[***]	[***]
[***]	[***]	[***]	[***]
[***]	[***]	[***]	[***]			[***]	[***]
[***]	[***]	[***]	[***]
[***]	[***]	[***]	[***]
[***]	[***]	[***]	[***]	[***]	[***]
[***]	[***]	[***]	[***]	[***]	[***]
[***]	[***]	[***]	[***]

Exhibit B

Specified Vectors

Specified Vector		Disease Indication
AAVrh10		Friedreich’s Ataxia (Systemic)

Exhibit C

Press Release

In process to be agreed to by both parties

Exhibit 10.9

CONFIDENTIAL AAVLife

Réf. Inserm Transfert : 12364A10

LICENSE AGREEMENT

THIS LICENSE AGREEMENT (the “ Agreement ”) is made and entered into effective as of July 4, 2014 (the “ Effective Date ”) by and between Inserm Transfert , a limited company organized under the laws of France, whose registered headquarters are located at 7 rue Watt, 75013 PARIS, France, N° SIRET 434 033 619 00025, co de APE 7219Z, RCS Paris B 434 033 619, represented by its Chairman of the Board of Management, Mrs. Pascale AUGE (“ Inserm Transfert ”), acting as delegatee of Institut National de la Santé Et de la Recherche Médicale (“ Inserm ”), French National Institute of Health and Medical Research, a public scientific and technological establishment having its principal offices at 101 rue de Tolbiac, 75654 Paris Cedex 13, France, as part of the activities of lnserm Unit U964 “ INSTITUTE OF GENETICS AND MOLECULAR AND CELLULAR BIOLOGY, ” directed by Brigitte KIEFFER located at Parc d’Innovation - 1 rue Laurent Fries - 67404 Illkirch Cedex France, and of lnserm Unit U986 “ GENOMICS, ENVIRONMENT FACTORS AND BIOTHERAPY OF ENDOCRINE AND NEUROLOGIC DISEASES, ” directed by Pierre BOUGNERES and located at Hôpital de Bicêtre - 80 rue du Général Leclerc - 94276 Le Kremlin Bicêtre Cedex France (the “ Laboratories ”). CNRS, Unistra, Paris XI and Cornell gave power to lnserm Transfert to act in its name and on its behalf for this Agreement. lnserm, CNRS, Unistra, Paris XI and Cornell are collectively referred as “ Licensors ”, on the one hand,

And

AAVLife , a French simplified joint stock company (Société par actions simplifiée) registered with the Paris Trade and Companies Registry number No. B 799 863 873 00011, whose registered office is 183/185 avenue de Choisy — 75013 Paris, France, represented by Amber Salzman, Chairman (“ Licensee ”), on the other hand.

RECITALS

WHEREAS , Licensee is engaged in the research and development of products for rare diseases and conditions, including, without limitation, Friedreich ataxia;

WHEREAS , Licensors possess certain intellectual property rights, know-how and biological materials useful for the research, development and commercialization of products for rare diseases and conditions, including, without limitation, Friedreich ataxia;

WHEREAS , Inserm Transfert is Inserm’s wholly owned technology transfer subsidiary, created by a French decree in June 6, 2000; effective January 1 ^st 2006; lnserm delegated to lnserm Transfert the management of its technology transfer activities; accordingly lnserm Transfert is empowered to negotiate, sign and manage license agreements, including this Agreement;

WHEREAS , Licensee wishes to obtain, and Licensors wish to grant to Licensee, an exclusive, royalty-bearing license under the Patent Rights and a non-exclusive, royalty-bearing

CONFIDENTIAL AAVLife Draft June 4 2014

license under Know-How, to develop, make, have made, use, import, offer for sale and sell or otherwise distribute Products within the Field with the right to sublicense, subject to the terms and conditions of this Agreement (as these capitalized terms are defined hereunder); and

Now THEREFORE , the Parties agree as follows:

ARTICLE 1

DEFINITIONS

1.1 “Affiliate” means any corporation, company, partnership, joint venture or other entity whether organized under French law or foreign law, which, via a share to the capital or any other means, controls, is controlled by or is under common control with a Licensor or Licensee, as the case may be, where the term “control” means direct or indirect beneficial ownership of at least fifty percent (50%) of the voting rights or the right to direct the management and policies of an entity. The rights granted to Affiliates under the terms of this Agreement only apply to entities qualifying as an Affiliate at the time the rights are exercised. If, during the term of this Agreement, an entity were to lose the qualification of Affiliate, the rights acquired by this entity solely in its capacity as an Affiliate would automatically terminate, unless written consent of the other Party is given, but this entity would however remain subject to any obligation under this Agreement to which it was then already subject and that shall by nature remain in force, in particular obligations relating to Confidential Information. Licensee and each Licensor shall remain liable for the ongoing performance of the obligations under this Agreement by its respective Affiliates.

1.2 “Business Day” means any day that is not a Saturday, a Sunday or other day on which banks are required or authorized by law to be closed in France.

1.3 “Commercialization Sublicense” means a sublicense (or an option to obtain a sublicense) granted by Licensee or its Affiliates to a Sublicensee under the Patent Rights and Know-How to research, develop, make, have made, use, import, offer for sale and sell or otherwise distribute Products within the Field in the Territory.

1.4 “Commercially Reasonable Efforts” mean, with respect to Licensee’s efforts to research, develop or commercialize Products, use of those efforts and resources, consistent with the exercise of prudent scientific and business judgment, as are applied by a similarly situated company to other pharmaceutical products of comparable commercial potential, stage of medical/scientific development, probability of technical success, technical and regulatory profile, and patent protection.

1.5 “Confidential Information” means all information (whether in written, oral, electronic, visual, tangible or other form) and materials, including, without limitation, biological and other tangible materials, that are disclosed by one Party (the “owning Party”) to the other Party (the “receiving Party”) prior to the Effective Date in the negotiation of this Agreement or during the term of this Agreement.

1.6 “Development Plan” has the meaning set forth in Section 3.1.

CONFIDENTIAL AAVLife Draft June 4 2014

1.7 “ Euro ” or “ EUR ” or “ € ” means the legal tender of the European Union.

1.8 “FDA” means the U.S. Food and Drug Administration or any successor agency thereto.

1.9 “Field” means all therapeutic, prognostic and diagnostic applications using vector comprising FXN gene.

1.10 “First Commercial Sale” means, with respect to a country in the Territory and a Product, the first sale to a Third Party of such Product in such country by Licensee or its Affiliate or Sublicensee after Regulatory Approval is granted with respect to such Product in such country.

1.11 “Improvements” mean any improvements to the patent applications and issued patents referred to in the definition of Patent Rights and inventions claimed or disclosed therein, which cannot be exploited without a license under the Patent Rights.

1.12 “Know-How” means all technical information, know-how, processes, compositions, materials, including, without limitation, biological and other tangible materials, data or other subject matter developed by the Laboratories owned or controlled by Licensors that exists as of the Effective Date and is provided to Licensee through the Laboratories, which is reasonably necessary or useful for the industrial and/or commercial exploitation of the Patent Rights, and which is not subject to any other existing options, licenses or contractual obligations (except vis-à-vis non-profit organizations) as of the Effective Date. The Know-How is further described in Appendix A to this Agreement.

1.13 “ Infringe” or “Infringement” means, (a) with respect to a patent, that, in the absence of a license granted to a person or entity under a claim included in such patent, the practice by such person or entity of an invention claimed in such patent would infringe such claim, or (b) with respect to a patent application, that, in the absence of a license granted to a person or entity under a claim included in such patent application, the practice by such person or entity of an invention claimed in such patent application would infringe such claim if such patent application were to issue as a patent.

1.14 “Licensee’s lndemnitees” has the meaning set forth in Section 9.2.

1.15 “Licensors’ lndemnitees” has the meaning set forth in Section 9.1.

1.16 “Liquidity Event” has the meaning set forth in Section 4.7(a).

1.17 “Losses” has the meaning set forth in Section 9.1.

1.18 “Milestone Event” has the meaning set forth in Section 4.2.

1.19 “Milestone Payments” has the meaning set forth in Section 4.2.

CONFIDENTIAL AAVLife Draft June 4 2014

1.20 “ Net Sales ” mean the total amount invoiced during each calendar year that this Agreement is in effect (subject to Section 4.5) to independent Third Parties (excluding Sublicensees), including distributors, on sales or other modes of transfer of the Products (in all of their forms), by Licensee and/or its Affiliates in each country of the Territory, less any normal deductions (calculated in accordance with generally accepted accounting principles consistently applied by Licensee and its Affiliates or Sublicensees across its product lines), including:

(i) packing, shipping, handling, storage and insurance expenses, and governmental and other rebates (or equivalents thereof),

(ii) trade, cash and quantity discounts, delayed ship order credits, allowances, chargebacks, retroactive price reductions that are, in each case, granted to managed health care organizations, pharmacy benefit managers (or equivalents thereof), national, state/provincial, local, and other governments, their agencies and purchasers, and reimbursers, or to trade customers,

(iii) credit notes issued or other allowances granted in respect of returned, rejected, recalled, damaged or defective Products,

(iv) bad debts,

(v) discounts pursuant to indigent patient programs of [***] and patient discount programs of [***], which means that for this patient Licensee should paid only the amount actually paid by the patient, not the amount shown on the invoice.

(vi) costs, expenses, charges and any other amounts attributable to any medical care or procedures, other than the amount paid by such Third Party solely for the purchase of such Product, and

(vii) sales, license and excise taxes, value added taxes, use taxes, tariffs, export license fees and any other taxes and duties paid to government entities, including any fees under the United States Affordable Care Act and the equivalent under any other applicable law.

Net Sales shall not include intermediate sales between Licensee and its Affiliates or sales of Products between Affiliates, as the case may be, or royalties or other revenues received from Affiliates or paid by one Affiliate to another, but shall include only amounts invoiced to Third Parties (excluding Sublicensees), less any deductions referred to above. In the case of non-cash consideration received by Licensee and/or its Affiliates for the sale or other modes of transfer of Products, Net Sales shall be the fair market value of such consideration received by Licensee and/or its Affiliates as of the date of receipt as determined in good faith by Licensee, less normal deductions as referred to above. The sale of Products at costs only for humanitarian purposes or for use for clinical trials or provided as samples shall not be included in the calculation of Net Sales.

It is understood that the deductions described under ii) above for a calendar year shall not exceed [***] of the total amount invoiced (excluding taxes) for all Products sold or otherwise transferred in all countries of the Territory.

CONFIDENTIAL AAVLife Draft June 4 2014

If a Product is sold in a kit or in combination with other products that are not Products and that are sold separately, Net Sales shall be calculated by multiplying Net Sales of the kit or combination product by the fraction A/(A+B), where A is the total catalogue price of the Products during the applicable calendar quarter in the country in which the sale was offered if sold separately and B is the total of the catalogue prices of all other products in the kit or combination product during the applicable calendar quarter in a country if sold separately.

If a Product is sold in a kit or in combination with other products that are not Products and one or more of the Product or such other products is not sold separately, Net Sales shall be calculated by multiplying Net Sales of the kit or combination product by a mutually agreed percentage.

1.21 “Party” means Licensors or Licensee individually, and “Parties” mean Licensors and Licensee collectively.

1.22 “Patent Rights” mean all rights under the patents and patent applications as listed in Appendix A , and any foreign patents or patent applications corresponding thereto, and, with respect to any such patents, any patent applications from which such patent claim priority, and any divisions, provisional, substitutions, additions, limitations, continuations, continuations in part, re-examination applications, reissues, renewals, extensions and term restorations, and each patent that issues or reissues from any of these patent applications and any reexamination patents with respect to any such patents (for the avoidance of doubt, Patent Rights does not include any improvements to the patents and patent applications as listed in Appendix A , even if such improvements are invented in whole or in part by lnserm, unless such improvements are included in continuations-in-part to any patent application listed in Appendix A ).

1.23 “Phase I Trial” means a human clinical trial of a Product that would satisfy the requirements of 21 C.F.R. Part 312.21(a) (as amended from time to time) or other comparable regulation imposed by an applicable regulatory authority in any country other than the U.S., for the principal purpose of first introducing such Product into humans to assess the safety of such product. A Phase 1 Trial shall be deemed initiated upon the first dosing of the first patient with such Product, or first introducing such Product into the first patient, in such trial. For clarification, a Phase I/II trial or Phase Ila trial shall be deemed a Phase I Trial, not a Phase II Trial.

1.24 “Phase Ill Trial” means a pivotal human clinical trial of a Product that would satisfy the requirements of 21 C.F.R. Part 312.21(c) (as amended from time to time) or other comparable regulation imposed by an applicable regulatory authority in any country other than the U.S., for the principal purpose of achieving a determination of safety and efficacy that is prospectively designed, statistically powered and conducted to provide an adequate basis for submission of an application for Regulatory Approval for patients with the disease or condition under study. A Phase III Trial shall be deemed initiated upon the first dosing of the first patient with such Product, or first introducing such Product into the first patient, in such trial. For clarification, a Phase II/III trial shall be deemed a Phase III Trial, not a Phase II Trial.

CONFIDENTIAL AAVLife Draft June 4 2014

1.25 “ Product ” means

(i) any product, composition, method or process the manufacture, use or sale of which would constitute, but for the license granted herein, an Infringement of the Patent Rights and/or which include and/or are developed and/or manufactured using the Know-How, whether such product, composition, method or process developed by Licensee alone, with or through others (including its Affiliates and Sublicensees), or jointly by Licensee and Laboratories in the frame of a potential future collaboration agreement between Licensee and Laboratories. Products shall be deemed to include the performance of services in the Field using the Know-How or, which services which would constitute, but for the license granted herein, an Infringement of the Patent Rights, and/or

(ii) any product used in combination with product defined in (a), composition, method or process that cannot be dissociated from product, composition, method or process defined in (b), from a commercial point of view (i.e said non dissociable products (such as delivery devices, buffers...) are not offered for sale separately) or from a regulatory point of view (i.e product defined in (a) and non dissociable products defined in (b) are part of the same and unique regulatory approval and/or are statutorily required to be sold as a single item).

1.26 “Regulatory Approval” means any and all approvals (including price and reimbursement approvals, if required), licenses, registrations, exemptions or authorizations of the FDA in the U.S. or comparable regulatory authority in any jurisdiction outside the U.S. that are necessary to market and sell a Product in the applicable country or jurisdiction.

1.27 “Sublicense Revenue” means the total gross proceeds received by Licensee or any of its Affiliates from any Sublicensee to the extent in consideration of the grant of a Commercialization Sublicense (or an option to obtain a Commercialization Sublicense) under the Patent Rights and/or Know-How, including, without limitation, any license fees, maintenance fees, milestone payments and royalty payments, but excluding reimbursement or funding for research, development, manufacturing or commercialization activities performed by Licensee or its Affiliates on behalf of Sublicensee.

In case Sublicensee grants other kinds of compensation to Licensee in consideration for access to Patent Rights and/or Know-How,(A) such as for example the transfer of securities and/or a participation into the Sublicensee and/or an investment to the capital of Licensee or a loan to Licensee, the amount, up to the fair market value, of such compensation shall be excluded from Sublicense Revenue (but the amount above such fair market value shall be included in Sublicense Revenue), and (B) for other compensation, Inserm Transfert and Licensee shall confer together to define an appropriate and fair compensation for Licensors. Any non-cash Sublicense Revenue received by Licensee shall be valued at its fair market value as of the date of receipt as determined in good faith by Licensee. Sublicense Revenue shall not include proceeds from a sale or acquisition of the business, equity or assets of Licensee. Where a grant of rights under other intellectual property is included in the same transaction as the grant of a sublicense to Patent Rights and/or Know-How, Licensee shall, using a fair methodology, reasonably allocate consideration paid for the intellectual property rights in the transaction as between such other intellectual property and the sublicense to the Patent Rights and/or Know-How.

CONFIDENTIAL AAVLife Draft June 4 2014

1.28 “ Sublicensee ” means any Third Party to whom Licensee has granted a sublicense (or an option to obtain a sublicense) under the Patent Rights and/or Know-How.

1.29 “Territory” means [***] .

1.30 “Third Party” means any person or entity other than Licensee or Licensors or their respective Affiliates.

1.31 “U.S.” means the United States of America and its territories and possessions.

1.32 “Valid Claim” means a claim of an issued and unexpired patent (including any patent claim the term of which is extended by any extension, supplementary protection certificate, patent term restoration, or the like) included within the Patent Rights or a claim of a pending application included within the Patent Rights, which has not lapsed, been abandoned, been held revoked, or been deemed unenforceable or invalid.

ARTICLE 2

LICENSE

2.1 License.

(a) Subject to the terms and conditions of this Agreement, Licensors hereby grant to Licensee (i) an exclusive, royalty-bearing license, with the right to sublicense, under the Patent Rights, and (ii) a non-exclusive, royalty-bearing license, with the right to sublicense, under the Know-How, in each case of clauses (i) and (ii) to research, develop, make, have made, use, import, offer for sale and sell or otherwise distribute Products within the Field in the Territory.

(b) Licensee shall have the right to grant sublicenses of the rights granted under the Patent Rights and/or Know-How to its Affiliates and Sublicensees. Prior to the execution of any Commercialization Sublicense with a Sublicensee, Licensee shall provide Inserm Transfert with written notification of the identity and address of the Sublicensee, as well as the terms of the sublicense (except that Licensee may remove any confidential terms other than the identity of the Sublicensee, the Sublicense Revenue under such sublicense and any other terms necessary for Licensors to confirm compliance with this Agreement). No prior written approval by Inserm Transfert of any sublicense shall be required, provided that, unless the Sublicensee under a Commercialization Sublicensee is an industrial company or other entity doing business in the pharmaceutical field listed on a major regulated stock exchange market in the European Union, in North America or in Japan, Inserm Transfert shall have to object to such sublicense ten (10) Business Days from the date that Licensee notifies Inserm Transfert of the proposed Commercialization Sublicense by written notice to Licensee, if and only if, such proposed Sublicensee (i) has violated French laws or regulations so that the sublicense would conflict with the public order/ethical obligations of Licensors, or (ii) in which case Licensee shall not grant such sublicense unless lnserm Transfert approves such sublicense in writing, and Inserm Transfert shall provide written notice to Licensee within ten (10) Business Days from the date that Licensee notifies Inserm Transfert of the proposed Commercialization Sublicense if such proposed Sublicensee is or has within the past five (5)

CONFIDENTIAL AAVLife Draft June 4 2014

years been in a lawsuit or arbitration proceeding with Licensors, in which case Licensee shall not grant such sublicense unless Inserm Transfert approves such sublicense in writing.

2.2 Licensors’ Research Rights . Licensors reserve the right to use the Patent Rights and the related Know-How for educational, academic, and research purposes only (including the right to grant to any Third Party academic institution the right to use the Patent Rights for their educational, academic and research purposes only), in each case to the exclusion of programs conducted in collaboration with or on behalf of a Third Party that is a for-profit or industrial entity.

2.3 Improvements .

(a) Licensee’s Improvements . Licensee shall remain the sole owner of any Improvements developed by Licensee and/or any of its or its Affiliates’ or Sublicensees’ employees, agents or subcontractors, without any contribution from any of Licensors and/or one or more of Licensors’ employees, agents or subcontractors.

(b) Licensors’ Improvements . Licensors shall remain the sole owner of any Improvements developed by Licensors and/or its Affiliates’, without any contribution from Licensee and/or one or more of Licensee’s employees, agents or subcontractors.

(c) Joint Improvements . Licensors and Licensee shall be the co-owners of any Improvements developed jointly by Licensors and/or one or more of Licensors’ employees, agents or subcontractors, on the one hand, and Licensee and/or one or more of Licensee’s employees, agents or subcontractors. The management and use of any co-owned Improvements shall be defined in a separate agreement regarding such joint development activities. The Licensee will have a right of exclusive option of [***] in order to obtain the grant of an exclusive license to such Improvements in the Territory and in the Field.

(d) Notification of Improvements . Inserm Transfert undertakes, for a period of [***] from the Effective Date, to notify the Licensee in writing of any Improvement which is described in Section 2.3(b) or 2.3(c), generated by Licensors through the Laboratories and brought to the attention of Inserm Transfert, if and only if:

(i) the said Improvements are the property of Inserm or any of its Affiliates or co-owned by Inserm or any of its Affiliates, to the exclusion of development co-ownership with a Third Party;

(ii) Inserm Transfert is mandated for the management of such Improvements; and

(iii) such Improvements are not subject to any Third Party rights.

(iv) Licensee will have a right of exclusive option of [***] from such notice to obtain the grant of an exclusive right to license such Improvements in the Territory and in the Field. Non-patented Improvements that find application outside the scope of Patent Rights will be granted on a non-exclusive basis.

CONFIDENTIAL AAVLife Draft June 4 2014

2.4 No Other Licenses . Neither Party grants to the other Party any rights or licenses in or to any intellectual property, whether by implication, estoppel, or otherwise, other than the license rights and option rights that are expressly granted under this Agreement.

ARTICLE 3

DEVELOPMENT PLAN; REPORTS; DILIGENCE

3.1 Development Plan . Licensee shall provide Inserm Transfert with (i) a development plan which describes the tasks and experiments to be conducted by Licensee or on behalf of Licensee to develop the Product (as may be amended, the “Development Plan”) and (ii) the anticipated date of first introduction of the Product into the commercial market. Licensee agrees to inform Inserm Transfert of the occurrence of any event identified in the Development Plan. Such Development Plan may be amended by Licensee from time to time to reflect the current state of development activities, and Licensee will provide Inserm Transfert a copy of such amended Development Plan.

3.2 Development Reports . Within sixty (60) days after December 31 of each calendar year, Licensee shall provide Inserm Transfert with a written annual progress report on the progress of its Product development and commercialization efforts under the Development Plan. Such progress reports shall include, among others, the following topics: summary of work completed, summary of work in progress, current schedule of anticipated milestones achievements and Regulatory Approvals, manufacturing, sublicensing efforts and market plans for introduction of Product.

3.3 Diligence .

(a) Licensee undertakes to use Commercially Reasonable Efforts to develop Product as soon as practical, consistent with reasonable business practices and in compliance with the Development Plan.

(b) Licensee undertakes to use Commercially Reasonable Efforts to introduce Product into the commercial market as soon as practical, consistent with reasonable business practices and necessary Regulatory Approvals and any other approvals by the regulatory authorities in each country of the Territory.

3.4 Compliance with Laws . Licensee shall comply with all applicable laws and regulations in connection with its activities pursuant to this Agreement.

CONFIDENTIAL AAVLife Draft June 4 2014

ARTICLE 4

PAYMENTS

4.1 License Payments . In consideration of the licenses and rights granted under this Agreement, Licensee shall pay to Licensors the following non-refundable and non-creditable payments:

(a) [***] after the Effective Date;

(b) [***] after the Effective Date; and

4.2 Development Milestones . Licensee shall pay to Inserm Transfert the payments indicated below (the “ Milestone Payments ”) within thirty (30) days after the first achievement by the Licensee and/or its Affiliates or by a subcontractor on behalf of the Licensee and/or its Affiliates of the corresponding event indicated below (each, a “ Milestone Event ”) with respect to a Product, the manufacture, use or sale of which would constitute, but for the license granted herein, an Infringement of the Patent Rights.

Milestone Event		Milestone Payments
Initiation of the first Phase I Trial		[***]
Initiation of the first Phase III Trial		[***]
Obtaining the first Regulatory Approval from FDA or comparable regulatory authority in any jurisdiction outside the U.S.		[***]
Upon First Commercial Sale in the US		[***]
Upon First Commercial Sale in a EMEA country:		[***]

The above Milestone Payments shall be non-refundable and non-creditable against royalty payments hereunder, whether such Milestone Payments are reached by Licensee and/or its Affiliates. Each Milestone Payment is payable only once for the first such Product to achieve the applicable Milestone Event, regardless of the number of Products which achieve such Milestone Event. The Milestone Payments payable to Inserm Transfert, if all the Milestone Events are achieved by Licensee and/or its Affiliates or by a subcontractor on behalf of Licensee and/or its Affiliates, shall not exceed [***].

4.3 Royalties .

(A) Licensee agrees to pay to Inserm Transfert a running royalty of [***] on Net Sales of Products in the Field in a country in the Territory by Licensee and/or its Affiliates if the manufacture, use or sale of such Product in such country would constitute, but for the license granted herein, an Infringement of a Valid Claim in the Patent Rights.

CONFIDENTIAL AAVLife Draft June 4 2014

(B) If a Product is not covered by at least one Valid Claim in the Patent Rights in the country of the Territory where it is sold, the royalty rate mentioned above will be reduced by [***] for the part of Net Sales of such Product made in said country. This royalty rate on Net Sales of Products shall not be less than [***] of Net Sales of Products.

In the case of sales of any Product by Licensee or its Affiliates to a Sublicensee, no royalty will be owed under this Section 4.3, but instead Licensee will pay Inserm Transfert a payment based upon Sublicense Revenue generated as a result of the sale of such Product pursuant to Section 4.6.

4.4 Royalty Credit . In the event that an issued patent owned by a Third Party is required to be licensed in order to utilize the Patent Rights, Licensee or its Affiliate or Sublicensee may, if it has not already done so, negotiate with the owner or Licensee of such patents for a license on such terms as Licensee or its Affiliate or Sublicensee deems appropriate. Should the license with the owner or Licensee of such patents require the payment of royalties on Net Sales or other payments to such owner or Licensee, then the royalties on Net Sales otherwise payable under this Agreement for the applicable calendar year may be reduced by [***] of the royalties on Net Sales or other payments owed to the Third Party for the applicable calendar year, provided that in no event shall the royalties payable under this Agreement be less than [***] of the amount stated in Section 4.3 of this Agreement for the applicable calendar year. Notwithstanding the reduction described in the previous sentence, the royalty rate on Net Sales of Products in the Field by Licensee or its Affiliates or Sublicensees during the royalty period shall not be less than [***] of Net Sales of such Products.

4.5 Royalty Term . Royalties will be payable under Section 4.2 and 4.3 on a Product-by- Product and country-by-country basis in the Territory commencing upon the First Commercial Sale of a Product if the manufacture, use or sale of such Product would constitute, but for the license granted herein, an Infringement of the Patent Rights in a particular country and expiring on the expiration of the last-to-expire of the Valid Claims in the Patent Rights claiming the composition of matter or method of manufacture or use in the Field of such Product in such country. No royalties will be payable with respect to Net Sales of any Product in a country if the manufacture, use or sale of such Product would not constitute, but for the license granted herein, an Infringement of the Patent Rights in such country.

4.6 Sublicense Revenue . Licensee shall pay to Inserm Transfert an amount equal to:

(a) [***] of Sublicense Revenue received by Licensee or its Affiliates from any Sublicensee to whom a Commercialization Sublicense is granted, if the Commercialization Sublicense is granted before the Initiation of the first Phase I Trial;

(b) [***] of Sublicense Revenue received by Licensee or its Affiliates from any Sublicensee to whom a Commercialization Sublicense is granted, if the Commercialization Sublicense is granted after the Initiation of the first Phase I Trial but before the Initiation of the first Phase III Trial;

(c) [***] of Sublicense Revenue received by Licensee or its Affiliates from any Sublicensee to whom a Commercialization Sublicense is granted, if the Commercialization Sublicense is granted after the Initiation of the first Phase III Trial.

CONFIDENTIAL AAVLife Draft June 4 2014

In any event, Inserm Transfert shall receive as a minimum, [***] . Amounts will be payable under this Section 4.6, with respect to any country, until the expiration of the royalty periods pursuant to Section 4.5 with respect to such country.

If a Product is not covered by at least one Valid Claim in the Patent Rights in the country of the Territory where it is sold, the Sublicense Revenue mentioned above will be reduced by [***] for the part of Sublicense Revenue of such Product made in said country.

In the event that an issued patent owned by a Third Party is required to be licensed in order to utilize the Patent Rights, Licensee or its Affiliate or Sublicensee may, if it has not already done so, negotiate with the owner or Licensee of such patents for a license on such terms as Licensee or its Affiliate or Sublicensee deems appropriate. Should the license with the owner or Licensee of such patents require the payment of royalties on Net Sales or other payments to such owner or Licensee, then the Sublicense Revenue otherwise payable under this Agreement for the applicable calendar year may be reduced by [***] of the royalties on Net Sales or other payments owed to the Third Party for the applicable calendar year, provided that in no event shall the Sublicense Revenue payable under this Agreement be less than [***] of the amount stated in Section 4.6 of this Agreement for the applicable calendar year. Notwithstanding the reduction described in the previous sentence, the royalty rate on Net Sales of Products in the Field by Licensee or its Affiliates or Sublicensees during the royalty period shall not be less than [***] of Sublicense Revenue of such Products.

4.7 Liquidity Events .

(a) “Liquidity Event” means (i) the first firm commitment underwritten initial public offering of Licensee’s Common Stock registered under the Securities Act of 1933, as amended, or (ii) a consolidation, merger or corporate reorganization of Licensee with or into any other industrial corporation or other entity or person doing business in the pharmaceutical field, in which consolidation, merger or reorganization the holders of outstanding voting securities of Licensee immediately prior to or at the time of such consolidation, merger or reorganization, receive, in consideration for such consolidation, merger or reorganization, cash, promissory notes or securities then listed upon a national exchange or quotation system, but do not beneficially own, directly or indirectly, at least fifty percent (50%) of the combined outstanding voting power of the acquiring entity (or of Licensee if it is the surviving entity in such transaction), or its direct or indirect parent entity, immediately after such transaction, or (iii) the sale, lease or other disposition of all or substantially all of the assets of Licensee to the benefit of a third industrial company doing business in the pharmaceutical field in consideration for cash, promissory notes or securities then listed upon such a national exchange or quotation system, where the holders of outstanding voting securities of Licensee immediately prior to or at the time of such transaction do not beneficially own, directly or indirectly, at least fifty percent (50%) of the combined outstanding voting power of the acquiring entity, or its direct or indirect parent entity, immediately after such transaction.

(b) Licensee shall notify Inserm Transfert prior to consummation of a Liquidity Event. In the case of any Liquidity Event, (i) this Agreement shall continue in accordance with its terms, provided that, in the case of a Liquidity Event described in Section 4.7(a)(ii) or (iii), unless the transaction described in Section 4.7(a)(ii) or (iii) is with an industrial

CONFIDENTIAL AAVLife Draft June 4 2014

company or other entity doing business in the pharmaceutical field listed on a major regulated stock exchange market in the European Union, in North America or in Japan, Inserm Transfert shall have thirty (30) days from the date that Licensee notifies Inserm Transfert of the transaction to terminate this Agreement by written notice to Licensee if, and only if, such industrial company or other entity in such Liquidity Event (A) has violated French laws or regulations so that continuance of the Agreement would conflict with the public order/ethical obligations of Licensors, or (B) is or has within the past five (5) years been in a lawsuit or arbitration proceeding with Licensors, and (ii) Licensee shall pay to Inserm Transfert within sixty (60) days following the completion of such Liquidity Event, a cash payment equal to:

[***] if the Liquidity Event has net proceeds received by Licensee or its stockholders is between [***] (the “Additional Payment” ), or

[***] if the Liquidity Event has net proceeds received by Licensee or its stockholders in excess of [***] (the “Additional Payment” ), or

No Additional Payment shall be due or payable if the Liquidity Event has net proceeds of [***] or less. The Additional Payment shall only be due once.

(c) Notwithstanding the intuitu personae character of the Agreement, it is understood and agreed that this Agreement (and the licenses and other rights granted herein) shall remain in full force and effect following any such Liquidity Event for the benefit of the Licensee or of the acquirer, the surviving entity, the successor in interest or the assignee under the Liquidity Event, as the case may be, except as otherwise agreed in writing by the Parties.

ARTICLE 5

PAYMENT; REPORTS; AUDITS

5.1 Licensee Payments and Reports.

(a) Licensee shall provide Inserm Transfert with annual written reports within ninety (90) days after the end of each calendar year regarding all sales of the Product in the Territory by Licensee and its Affiliates, the first report being due following the First Commercial Sale of the first Product in the Field in the Territory and the last report being due after the end of all the royalty periods. Each such written report shall indicate:

(i) The aggregate Net Sales;

(ii) The amount of Additional Payment, if any; and ̻

(iii) The detail of the royalties due to Inserm Transfert pursuant to Article 4 during said calendar year.

CONFIDENTIAL AAVLife Draft June 4 2014

Each such written report shall be certified as true and accurate by a duly authorized officer of Licensee.

(b) For so long as Licensee receives any Sublicense Revenue of which a portion is payable to Inserm Transfert, Licensee agrees to make written reports to Licensors within ninety (90) days after the end of each calendar year stating the amount and description of any Sublicense Revenue received by Licensee or its Affiliates during the applicable calendar year, and a calculation of the payment due to Licensors with respect to such Sublicense Revenue pursuant to Section 4.6.

5.2 Accounting. Licensee agrees to keep true, accurate and complete records regarding Net Sales and Sublicense Revenues for a period of three (3) years after the relevant payment is owed pursuant to this Agreement, setting forth the sales and other disposition of Products sold in sufficient detail to enable royalties and compensation payable to Inserm Transfert hereunder to be determined. Upon reasonable prior written notice to Licensee of at least thirty (30) days, Inserm Transfert shall have the right to audit directly, or, by appointing an independent auditor Licensee’s books of account and records within three (3) years following the yearly report pursuant to Section 5.1. Such audit shall not be performed more frequently than once per calendar year nor more frequently than once with respect to records covering any specific period of time, and such audit shall be performed during normal business hours and without unreasonable disruption to Licensee’s business. Such examination is to be made at the expense of Licensors, except in the event that the results of the audit reveal an underpayment of royalties, milestones, or other payments to Licensors under this Agreement of five percent (5%) or more over the period being audited, in which case reasonable audit fees for such examination shall be paid by Licensee.

5.3 Methods of Payments. All payments due to Licensors under this Agreement shall be paid in Euros by wire transfer within thirty (30) days following issuance of a corresponding invoice by Inserm Transfert after acceptance of the annual written report, which shall state the amount of the sums due pursuant to this Agreement. Payments shall be made with reference to the invoice number and shall be paid by bank wire transfer to:

[***]

5.4 Taxes. If any law or regulation of any country of the Territory requires withholding of taxes of any type, levies or other charges with respect to any amounts payable hereunder to Inserm Transfert or any other Licensor, Licensee shall promptly pay such tax, levy or charge for and on behalf of Inserm Transfer or such Licensor to the proper governmental authority, and shall promptly furnish Inserm Transfert with receipt of such payment. Licensee shall have the right to deduct any such tax, levy or charge actually paid from payment due Inserm Transfert or such Licensor or be promptly reimbursed by Inserm Transfert if no further payments are due Inserm Transfert. Licensee agrees to assist, at Inserm Transfert’s request and expense, Inserm Transfert in claiming exemption from such deductions or withholdings under double taxation or similar agreement or treaty from time to time in force and in minimizing the amount required to be so withheld or deducted.

CONFIDENTIAL AAVLife Draft June 4 2014

ARTICLE 6

PATENTS AND KNOW-HOW

6.1 Patent Costs and Prosecution.

(a) Licensee shall be responsible for all patent costs incurred for the prosecution, defense and maintenance of the Patent Rights in the Territory following the Effective Date and during the term of this Agreement. Licensee shall be responsible for all patent costs incurred for the prosecution, defense and maintenance of the Patent Rights in the Territory following the Effective Date during the term of this Agreement. Such patent costs are non-refundable and non-creditable against any royalty payments and milestones payments due hereunder.

(b) Licensee shall have the right to control the prosecution, defense and maintenance of the Patent Rights in the Territory; provided however that Licensee (i) shall notify Inserm Transfert before taking any substantive actions with respect to (A) the scope and content of all patent applications within the Patent Rights and (B) the content or proposed responses to official actions of patent offices regarding the prosecution of the Patent Rights; (ii) shall give Inserm Transfert a reasonable opportunity to comment; and (iii) shall consider in good faith incorporating any comments received from Inserm Transfert. For purposes of this provision, the “prosecution, defense and maintenance” of patents and patent applications shall be deemed to include, without limitation, the preparation and filing, the grant, the examination, the conduct of interferences or oppositions, any invalidity suits and/or requests for re-examinations, any reissues or extensions of patent terms with respect to patent applications and patents within the Patent Rights.

(c) Each Party agrees to cooperate fully in the preparation, filing, prosecution and maintenance of Patent Rights under this Section 6.1. Such cooperation includes, but is not limited to: (i) executing all papers and instruments, or requiring its employees or contractors, to execute such papers and instruments, so as to enable Licensee to apply for and to prosecute Patent Rights in any country as permitted by this Section 6.1; and (ii) promptly informing the other Party of any matters coming to such Party’s attention that may affect the preparation, filing, prosecution or maintenance of any such Patent Rights.

(d) Licensee may grant any Affiliate or Sublicensee the right to control the prosecution, defense and maintenance of the Patent Rights in the Territory in connection with the grant of a sublicense to such Affiliate or Sublicensee, and references in this Section 6.1 shall include any Affiliate or Sublicensee to whom such rights are granted.

(e) Licensee may elect, with at least sixty (60) days’ prior written notice to Inserm Transfert, to discontinue payment and control for the prosecution, defense and maintenance of any patent application and/or patent within the Patent Rights. Any such patent application or patent so elected shall be excluded from the definition of Patent Rights and from the scope of the license granted under this Agreement, and all rights relating thereto shall revert exclusively to Licensors.

CONFIDENTIAL AAVLife Draft June 4 2014

6.2 Patent Enforcement.

(a) If either Party becomes aware of any infringement, threatened infringement, or alleged infringement of Patent Rights, it will promptly notify the other Party thereof including available evidence of infringement. The Parties will cooperate and, subject to Section 6.2(b), use reasonable efforts to stop such alleged infringement without litigation.

(b) Licensee will have the first right (but not the obligation), at its sole expense, to bring an action against any Third Party for infringement of the Patent Rights, including, without limitation, the initiation of a suit, proceeding or other legal action by counsel of its own choice. Licensors shall provide reasonable cooperation in connection with any such suit, proceeding or action, including, without limitation, the furnishing of a power of attorney to Licensee or being named as a party. Licensee shall inform Licensors of any decision not to enforce the Patent Rights. If Licensee does not take action within ninety (90) days of written notice of infringement (or sooner, if failure to take such action would adversely affect Licensors’ ability to bring such an action), Licensors will have the right (but not the obligation), at their sole expense, to take the right of action, including, without limitation, the initiation of a suit, proceeding or other legal action by counsel of its own choice. Licensors may, at their own expense, join in any action to enforce the Patent Rights brought by Licensee, and Licensee may, at its own expense, join in the action to enforce the Patent Rights brought by Licensors.

(c) If one Party brings any suit, proceeding or action under this Section 6.2, the other Party agrees to provide reasonable assistance to such Party, including, without limitation, by providing access to relevant documents and other evidence and making its employees available, subject to reimbursement of any out-of-pocket expenses incurred by the non-enforcing or defending Party in providing such assistance. Neither Party will settle or otherwise compromise any such suit, proceeding or action in a way that adversely affects the other Party’s rights or interests with respect to the Patent Rights without such other Party’s prior written consent.

(d) Except as otherwise agreed to by the Parties in writing (by e-mail) as part of a cost-sharing arrangement, any settlements, damages or other monetary awards recovered pursuant to a suit, proceeding or action brought pursuant to Section 6.2 will first be applied to reimburse Licensee and/or Licensors for all litigation costs and expenses with any remainder being retained by the Party that brought such suit, proceeding or action, and, in the case that Licensee brought such suit, proceeding or action, such remainder shall be treated as Sublicense Revenue that are subject to royalty payments under Section 4.6, said Sublicense Revenue being reduced by [***]. Licensee may grant any Affiliate or Sublicensee the right to bring and control any suit, proceeding or action against any Third Party for infringement of the Patent Rights in connection with the grant of a sublicense to such Affiliate or Sublicensee, and references in this Section 6.2 shall include any Affiliate or Sublicensee to whom such rights are granted.

6.3 Defense of Infringement Actions. Licensee or its Affiliate or Sublicensee, as applicable, shall, at its expense, have the sole right, but not the obligation, to defend any suits against Licensee or its Affiliate or Sublicensee alleging infringement of any Third Party intellectual property right due to Licensee’s or its Affiliate’s or Sublicensee’s practice of the Patent Rights or its research, development, manufacture, use, importation, offering for sale, sale

CONFIDENTIAL AAVLife Draft June 4 2014

or other commercialization of Products. Licensee shall promptly notify Licensors in writing of such claims, and Licensors shall, at their own expense, have the right to retain separate independent counsel to assist in defending any such actions to the extent involving Licensors.

6.4 Cooperation. In any suit, action or other proceeding in connection with enforcement and/or defense of the Patent Rights, Licensee and Licensors shall cooperate fully, including without limitation by joining as party plaintiff(s) and executing such documents as any Party may reasonably request. Subject to Section 6.2(c), upon the request of and, at the expense of the requesting Party, Licensee or Licensors shall make available at reasonable times and under appropriate conditions all relevant personnel, records, papers, information, samples, specimens and other similar materials in its possession.

ARTICLE 7

REPRESENTATIONS, WARRANTIES, AND COVENANTS

7.1 Representations and Warranties. Licensors hereby represents and warrants that (a) they have the full right and power to enter into this Agreement and to grant the license and other rights granted to Licensee herein and (b) without limiting the foregoing, no Third Party has a right to obtain a license to the Patent Rights in the Field from Licensors.

7.2 Disclaimer. EXCEPT AS PROVIDED IN SECTION 7.1, EACH PARTY EXPRESSLY DISCLAIMS ANY AND ALL WARRANTIES OF ANY KIND, EXPRESS OR IMPLIED, INCLUDING, WITHOUT LIMITATION, THE WARRANTIES OF MERCHANTABILITY, FITNESS FOR A PARTICULAR PURPOSE, AND NONINFRINGEMENT OF THE INTELLECTUAL PROPERTY RIGHTS OF THIRD PARTIES, ARISING FROM A COURSE OF DEALING, USAGE OR TRADE PRACTICES, IN ALL CASES WITH RESPECT THERETO. FURTHER, LICENSORS HAVE MADE NO INVESTIGATION AND MAKE NO REPRESENTATION OR WARRANTY THAT THE PATENT RIGHTS, BIOLOGICAL MATERIAL AND KNOW-HOW ARE SUITABLE FOR LICENSEE’S PURPOSES, AND LICENSEE MAKES NO REPRESENTATION OR WARRANTY REGARDING THE SUCCESS OF EFFORTS TO DEVELOP AND COMMERCIALIZE PRODUCTS.

Licensee acknowledges that this Agreement subject matter is licensed “as-is” without any warranties express or implied except as expressly set out in Article 7.1. Neither Licensors nor the inventors offer any warranty express or implied as to the grant, validity or scope of the Patent Rights under this Agreement.

7.3 Limitation of Liability. NEITHER PARTY SHALL BE ENTITLED TO RECOVER FROM THE OTHER PARTY ANY SPECIAL, INCIDENTAL, CONSEQUENTIAL OR PUNITIVE DAMAGES IN CONNECTION WITH THIS AGREEMENT, EACH PARTY’S PERFORMANCE OR LACK OF PERFORMANCE HEREUNDER, OR ANY LICENSE GRANTED HEREUNDER, EXCEPT FOR DAMAGES ARISING FROM A BREACH OF ARTICLE 8, PROVIDED THAT THE FOREGOING SHALL NOT LIMIT THE INDEMNIFICATION OBLIGATIONS UNDER ARTICLE 9.

CONFIDENTIAL AAVLife Draft June 4 2014

ARTICLE 8

CONFIDENTIALITY

8.1 Confidentiality. Each Party (i) shall maintain in confidence all Confidential Information of the other Party; (ii) shall not use Confidential Information of the other Party for any purpose except as permitted by this Agreement; and (iii) shall not disclose Confidential Information of the other Party to anyone other than its and its Affiliates’ employees, consultants, agents or subcontractors who are bound by written obligations of nondisclosure and non-use consistent with those set forth in this Article 8 and to whom such disclosure is necessary in connection with such Party’s activities as contemplated in this Agreement, and in the case of Licensee, actual and prospective Sublicensees and Third Party investors, financing sources and acquirers who are bound by written obligations of nondisclosure and non-use consistent with those set forth in this Article 8. Each Party shall use reasonable efforts to ensure that any such persons and entities to whom a Party discloses Confidential Information of the other Party as permitted by this Section 8.1 shall comply with such confidentiality and non-use obligations but in any event shall remain liable to the other Party if such person or entity breaches such obligations. Each Party shall notify the other promptly on discovery of any unauthorized use or disclosure of the other Party’s trade secrets or proprietary information. Exceptions . The obligations set forth in Section 8.1 shall not apply to the extent the receiving Party can prove that the disclosed information was (a) disclosed by the mutual agreement of both Parties, or was disclosed by the owning Party; (ii) in the public domain or publicly known prior to the time of disclosure or entered the public domain or becomes publicly known through no act or fault of the receiving Party; (iii) made available as a matter of lawful right by a Third Party, without obligation of confidentiality, to the receiving Party; or (iv) in the possession of the receiving Party at the time of disclosure by the owning Party or was developed by its, or its Affiliates’ employees, consultants, agents or subcontractors independently from the Confidential Information received from the other Party. Notwithstanding the obligations set forth in Section 8.1, the receiving Party may disclose Confidential Information of the other Party to the extent that such disclosure is required by a compulsory legal or regulatory provision, lawful right or a final court decision or arbitration settlement, or to remain in compliance with applicable laws and regulations, provided that the receiving Party gives the other Party prior notice of such disclosure and an opportunity to seek a protective order or confidential treatment with respect to such disclosure, if it is allowed by law.

8.2 Confidentiality Period. The confidentiality obligations shall remain in effect during the term of the Agreement and shall survive the expiration or the termination of the Agreement for any reason for a period of ten (10) years following the expiration or termination date of the Agreement.

ARTICLE 9

INDEMNIFICATION

9.1 Indemnification by Licensee. Licensee shall indemnify, hold harmless and defend Licensors, their Affiliates, and their directors, officers, employees and agents (the “Licensors’ Indemnitees” ) from and against any and all liabilities, expenses and/or losses

CONFIDENTIAL AAVLife Draft June 4 2014

(including, without limitation, attorneys ’ fees, court costs, witness fees, damages, judgments, fines and amounts paid in settlement) ( “ Losses ” ) incurred by Licensors ’ Indemnitees in connection with any Third Party suits, claims, actions or demands to the extent that they arise out of (a) the practice by or under the authority of Licensee or its Affiliates and Sublicensees of the Patent Rights or Know-How, or (b) the design, manufacture, distribution or use of Products by or under the authority of Licensee or its Affiliates or Sublicensees; provided that any Licensors ’ Indemnitee seeking indemnification hereunder shall (i) promptly notify Licensee of such claim (ii) give Licensee sole control of the defense or settlement of such claim, and (iii) provide Licensee, at Licensee ’ s expense, with reasonable assistance and full information with respect to such claim. Notwithstanding the foregoing, Licensee ’ s indemnification obligation under this Section 9.1 shall not apply to the extent any Losses arise out of (x) the negligence or willful misconduct of any of the Licensors ’ Indemnitees or (y) Licensors ’ breach of this Agreement.

ARTICLE 10

TERM AND TERMINATION

10.1 Term. The term of this Agreement shall begin on the Effective Date and, unless earlier terminated in accordance with the terms of this Article 10, will expire on a Product-by-Product and country-by-country basis until the later of: (i) the expiration of the last to expire of the Valid Claims in the Patent Rights which cover the manufacture, use or sale of such Product in such country or (ii) ten (10) years after the First Commercial Sale of such Product in such country in which such Product is sold. Upon a country-by-country and Product-by-Product basis, Licensee will have a fully paid up, perpetual, irrevocable license with respect to such Product in such country under the Patent Rights and Know-How following expiration of this Agreement with respect to such Product in the applicable country.

10.2 Termination for Breach. Subject to the terms and conditions of this Section 10.2, a Party may, in addition to any other rights and remedies, terminate this Agreement in the event the other Party is in material breach or default in the performance of any of its material obligations under this Agreement. The non-breaching Party shall first provide written notice to the breaching Party, which notice shall identify in detail the alleged breach. The breaching Party shall have a period of ninety (90) days after such written notice is provided to cure such breach. If such breach is not cured within such period, this Agreement shall terminate immediately at the end of such period on written notice from the non-breaching Party.

10.3 Termination by Inserm Transfert.

(a) Licensee Bankruptcy . In the event Licensee becomes the subject of a voluntary or involuntary petition in bankruptcy, Licensee shall immediately notify Licensors in writing. Inserm Transfert shall have the right to terminate this Agreement by giving Licensee written notice, subject to application of Articles L.622-13 and L. 641-10 of the French Commercial Code or other law applicable to the Licensee. Termination of this Agreement pursuant to this provision shall be effective upon Licensee’s receipt of such written notice.

CONFIDENTIAL AAVLife Draft June 4 2014

(b) Failure to Meet Development Milestones . In the event that (i) Licensee has not met at their respective scheduled date any of the development milestones as set forth in the Development Plan, as may be amended, and/or any of its development obligations under Article 3; and (ii) Licensee has not remedied its failure in connection therewith within ninety (90) days from written notice by Inserm Transfert to do so, Inserm Transfert (on behalf of Licensors) may terminate this Agreement with immediate effect and without judicial intervention, or may alternatively decide, at its sole discretion, to convert the license into a non-exclusive license.

(c) Interrupted Development, Marketing or Commercial Use . Inserm Transfert shall have the right to terminate the license granted to Licensee in a given country upon thirty (30) days prior written notice to Licensee, if Licensee (i) before Regulatory Approval of a Product in any country, has ceased directly (or through an Affiliate or Sublicensee) conducting any development of Products in all countries for a period of twelve (12) consecutive months (i.e., no Product is being developed anywhere in the Territory for a period of twelve (12) consecutive months); or (ii) after Regulatory Approval of a Product in a given country, has ceased directly (or through an Affiliate or Sublicensee), marketing such Product in such country for a period of twelve (12) consecutive months; provided, however, that no termination shall occur to the extent that any of the foregoing is due to circumstances outside the reasonable control of Licensee, including any delay or decision by any regulatory authority or resolves such matter prior to the end of such thirty (30) day notice period.

10.4 Termination by Licensee. Licensee may terminate this Agreement, in its entirety, at any time upon sixty (60) days prior written notice to Inserm Transfert.

10.5 Effects of Expiration or Termination.

(a) Upon expiration or termination of this Agreement, all rights and obligations of the Parties shall terminate, except as provided in this Section 10.5 and the provisions of this Agreement referenced in this Section 10.5; provided, however, that expiration or termination of this Agreement shall not affect any rights and obligations which accrued hereunder prior to the effective date of such expiration or termination nor preclude either Party from pursuing all rights and remedies it may have hereunder or at law or in equity with respect to any breach of this Agreement, as applicable.

(b) Each Party shall promptly return to the other Party all relevant records and materials in its possession or control containing or comprising the other Party’s Confidential Information, except Licensee may retain Confidential Information of Licensors to the extent necessary or useful to practice any fully paid irrevocable license in any country or countries as provided in Section 10.1 or its rights under Section 10.5(d).

(c) Upon any early termination of this Agreement, at the election of the applicable Sublicensee upon written notice to Licensors, the sublicense granted hereunder to such Sublicensee that was in effect immediately prior to termination of this Agreement will survive such termination, with Licensors as the Sublicensee’s direct licensor (with any amounts payable to Licensors limited to the amounts expressly set forth under this Agreement with respect to such Sublicensee’s activities, and any other amounts, and any rights and obligations of

CONFIDENTIAL AAVLife Draft June 4 2014

Licensee under the relevant sublicense agreement, other than with respect to the Patent Rights and Know-How, shall remain with Licensee), provided that such Sublicensee is not then in default under its sublicense.

(d) Upon any early termination of this Agreement, Licensee and its Affiliates and Sublicensees (to the extent they do not become direct licensees of Licensors as provided under Section 10.5(c)) shall be entitled to finish any work-in-progress and to sell any completed inventory of Products that remain on hand as of the termination date, subject to payment of any royalties due and payable in accordance with the provisions of this Agreement, provided that no such sales shall be permitted following the date that is six (6) months after the termination date.

(e) The rights and obligations of the Parties under the following provisions of this Agreement shall survive expiration or any termination of this Agreement: Articles 1, 8, 9, 11 and 12 and Sections 5.2 (for the period described therein), 7.2, 7.3 and 10.5 and any fully paid irrevocable license in any country or countries as provided in Section 10.1.

ARTICLE 11

DISPUTE RESOLUTION; GOVERNING LAW

11.1 Disputes. In the event of any dispute between the Parties arising out of or relating to this Agreement, including, without limitation, the breach thereof, the Parties shall refer such dispute to designated officers of each Party with decision-making authority, and such officers shall attempt in good faith to resolve such dispute. Any such dispute arising out of this Agreement which has not been resolved amicably within three (3) months after first written notice by a Party to the other Party of such dispute shall be resolved by the French Courts.

11.2 Choice of Law. The validity, performance, construction and effect of this Agreement shall be governed by the laws of France, without regard to conflicts of law principles that would provide for application of the law of another jurisdiction.

ARTICLE 12

MISCELLANEOUS

12.1 Assignment.

(a) This Agreement is entered into intuitu personae and shall not be assigned or otherwise transferred by a Party except with the express prior written consent of the other Party or as otherwise provided in this Agreement. Any assignment in violation of this Section 12.1 shall be null and void. This Agreement shall be binding on and shall inure to the benefit of the permitted successors and assigns of the Parties hereto.

CONFIDENTIAL AAVLife Draft June 4 2014

(b) Notwithstanding anything to the contrary herein, Licensee may assign or transfer this Agreement (or its rights and obligations hereunder) without the express prior written consent of Licensors:

(i) to any of Licensee’s Affiliates; provided that, unless the Affiliate is an industrial company or other entity doing business in the pharmaceutical field listed on a major regulated stock exchange market in the European Union, in North America or in Japan, (A) Inserm Transfert shall have to object to such assignment or transfer of this Agreement in its entirety ten (10) Business Days from the date that Licensee notifies Inserm Transfert of such proposed assignment or transfer by written notice to Licensee, if and only if, such Affiliate has violated French laws or regulations so that the assignment or transfer would conflict with the public order/ethical obligations of Licensors, in which case Licensee shall not so assign or transfer this Agreement to such Affiliate unless Inserm Transfert approves such assignment or transfer in writing, and (B) Inserm Transfert shall provide written notice to Licensee within ten (10) Business Days from the date that Licensee notifies Inserm Transfert of the proposed assignment or transfer if such Affiliate is or has within the past five (5) years been in a lawsuit or arbitration proceeding with Licensors, but Inserm Transfert shall have no right to object to such assignment or transfer;

(ii) to any entity by way of merger, acquisition or sale of all or substantially all of its assets to which this Agreement relates; provided that if such assignment or transfer is an assignment or transfer of this Agreement in its entirety to an entity that is not an industrial company doing business in the pharmaceutical field in the European Union, North America or Japan, then Inserm Transfert shall have to object to such assignment within ten (10) Business Days from the date that Licensee notifies Inserm Transfert of the proposed assignment by written notice to Licensee, if and only if, such proposed assignee or transferee has violated French laws or regulations so that the assignment or transfer would conflict with the public order/ethical obligations of Licensors, in which case (A) Licensee shall not complete such transaction unless Inserm Transfert approves in writing; (B) if Licensee completes such transaction, Licensee will pay to Inserm Transfert, within sixty (60) days of the completion of such transaction, the Additional Payment (it being agreed that in no event will more than one Additional Payment be made to Inserm Transfert under this Agreement); and (C) the Parties agree that in no event does this proviso apply to a Liquidity Event; or

(iii) in connection with a Liquidity Event, except as expressly provided in Section 4.7.

(c) Notwithstanding the intuitu personae character of the Agreement, it is understood and agreed that this Agreement (and the licenses and other rights granted herein) shall remain in full force and effect following any such assignment for the benefit of the Licensee or of the acquirer, the surviving entity, the successor in interest or the assignee of the relevant assets, as the case may be and if applicable regarding this article 12.1 above.

12.2 Force Majeure. If either Party shall be delayed, interrupted in or prevented from the performance of any obligation hereunder by reason of force majeure, including an act of God, fire, flood, earthquake, war (declared or undeclared), public disaster, act of terrorism, strike or labor differences, or any other cause beyond such Party’s control, such Party shall not be

CONFIDENTIAL AAVLife Draft June 4 2014

liable to the other for such matter; and the time for performance of such obligation shall be extended for a period equal to the duration of the force majeure which occasioned the delay, interruption or prevention. The Party invoking such force majeure rights must notify the other Party in writing within a period of fifteen (15) days of both the first and last day of the force majeure unless the force majeure renders such notification impossible in which case notification will be made as soon as possible. If the delay resulting from the force majeure exceeds three (3) months, both Parties shall consult together to find an appropriate solution.

12.3 Entire Agreement; Amendment. This Agreement constitutes the entire agreement between the Parties with respect to the subject matter herein and, effective on the Effective Date, supersedes all previous agreements between the Parties with respect to the subject matter herein, whether written or oral. This Agreement shall not be amendment, changed or modified orally, but only by an instrument in writing signed by both Parties.

12.4 Severability. If any provision of this Agreement is declared invalid by a court of last resort or by any court or other governmental body pursuant to a decision of which an appeal is not taken within the time provided by law, then and in such event, this Agreement will be deemed to have been terminated only as to the portion thereof that relates to the provision invalidated by that decision and only in the relevant jurisdiction, but this Agreement, in all other respects and all other jurisdictions, will remain in force; provided, however, that if the provision so invalidated is essential to the Agreement as a whole, then the Parties shall negotiate in good faith to amend the terms hereof as nearly as practical to carry out the original intent of the Parties.

12.5 Notices. Any notice or report required or permitted to be given under this Agreement shall be in writing and shall be delivered as follows: (a) by personal delivery, with notice effective when received; (b) by international courier, with notice effective two (2) Business Days following delivery to such overnight courier; (c) by confirmed facsimile, with notice effective at the time of such confirmation; or (d) by certified or registered mail, with notice effective ten (10) Business Days after such mailing.

If to Licensors:

Inserm Transfert

7 rue Watt

75013 PARIS, France

N°SIRET 434 033 619 00025

code APE 731Z

RCS Paris B 434 033 619

If to Licensee :

AAVLife

183/189 avenue de Choisy

75013 Paris

France

Attn: Amber Salzman

CONFIDENTIAL AAVLife Draft June 4 2014

12.6 Government Approval or Registration. If this Agreement or any associated transaction (in particular registration at the Registre National des Brevets and National Patent Office, and any fiscal registration) is required by the law of any nation to be either approved or registered with any governmental agency, Licensee shall assume all legal obligations to do so with reasonable assistance from Licensors at Licensee ’ s request and expense.

12.7 Independent Contractors. The relationship of Licensee and Licensors established by this Agreement is that of independent contractors. Nothing in this Agreement shall be construed to create any other relationship between Licensee and Licensors. Neither Party shall have any right, power or authority to contract or incur any expense, liability or obligation, express or implied, on behalf of the other Party.

12.8 No Use of Name. Except as required by law, neither Licensee nor Licensors shall use the name of the other Party in issuing any press release or other public statements in connection with this Agreement intended for use in the public media without the written approval of such other Party, which approval shall not be unreasonably withheld; provided, however, that Licensee may publicize that it is licensed by Licensors under the Patent Rights.

12.9 No Waiver. Any omission or delay by either Party at any time to enforce any right or remedy reserved to it, or to require performance of any of the terms, covenants or provisions hereof, by the other Party, shall not constitute a waiver of such Party’s rights to the future enforcement of its rights under this Agreement. Any waiver by a Party of a particular breach or default by the other Party shall not operate or be construed as a waiver of any subsequent breach or default by the other Party.

12.10 Headings. The captions used herein are inserted for convenience of reference only and shall not be construed to create obligations, benefits, or limitations.

12.11 Counterparts. This Agreement may be executed in counterparts, all of which taken together shall be regarded as one and the same instrument.

[Signature Page Follows]

CONFIDENTIAL AAVLife Draft June 4 2014

IN WITNESS WHEREOF , the Parties have executed this License Agreement through their duly authorized representatives to be effective as of the Effective Date.

Licensors :	Licensee :

Inserm Transfert	AAVLife

Name: Pascale Augé	Name: Amber Salzman

Title:	Title:

Date:	Date:

CONFIDENTIAL AAVLife Draft June 4 2014

APPENDIX A

KNOW-HOW

Know-how from Hélène PUCCIO, Pierre BOUGNERES and Patrick AUBOURG (Inserm, CNRS, Universities ParisXI and University of Strasbourg) to be transferred to AAVLIVE through the License:

[***]

CONFIDENTIAL AAVLife Draft June 4 2014

APPENDIX B

[***]

Exhibit 10.10

CONFIDENTIAL

AMENDMENT N°1

TO LICENSE AGREEMENT N°12364A10

This Amendment n°1 (the “Amendment 1”) is made by and between

Inserm Transfert , a limited company organized under the laws of France, whose registered headquarters are located at 7 rue Watt, 75013 PARIS, France, N° SIRET 434 033 619 00025, code APE 7219Z, RCS Paris B 434 033 619, represented by its Chairman of the Board of Management, Mrs. Pascale AUGE (“ Inserm Transfert ”), acting as delegatee of Institut National de la Santé Et de la Recherche Medicale (“ Inserm ”), French National Institute of Health and Medical Research, a public scientific and technological establishment having its principal offices at 101 rue de Tolbiac, 75654 Paris Cedex 13, France, as part of the activities of Inserm Unit U964 “INSTITUTE OF GENETICS AND MOLECULAR AND CELLULAR BIOLOGY,” directed by Brigitte KIEFFER located at Parc d’Innovation - 1 rue Laurent Fries - 67404 Illkirch Cedex France, and of Inserm Unit U986 “GENOMICS, ENVIRONMENT FACTORS AND BIOTHERAPY OF ENDOCRINE AND NEUROLOGIC DISEASES,” directed by Pierre BOUGNERES and located at Hopital de Bicêtre - 80 rue du Général Leclerc - 94276 Le Kremlin Bicêtre Cedex France (the “ Laboratories ”). CNRS, Unistra, Paris XI, and Cornell gave power to Inserm Transfert to act in its name and on its behalf for this Amendment 1.

Centre Chirurgical Marie Lannelongue , « association régie par la loi de 1901 », whose registered headquarters are located at 133 avenue de la Résistance — 92350 Le Plessis Robinson, represented by its Vice General Manager, Mr. Oliver Vallet Hereinafter referred to as the “ CCML ”

Inserm, CNRS, Unistra, Paris XI Cornell and CCML are collectively referred as “ Licensors ”, on the one hand,

And

RECITALS

Inserm Transfert and AAVLIFE entered into a license agreement on July 4, 2014 (hereinafter referred to as the “ Agreement ”, ref. IT N°12364A10).

CONFIDENTIAL

Inserm Transfert, CCML and AAVLIFE entered into Collaboration Agreement with option on March 31, 2014 (hereinafter referred to as the “ Collaboration ”, ref. IT N°12364A20). The Parties agree in the Collaboration that in case of Joints Results are Improvements the purpose of the Agreement regarding the patents will be extended through an amendment to the Agreement, if AAVLIFE exercises the option within the period set forth in the Article 11.3.2 of the Collaboration.

The Centre Chirurgical Marie Lannelongue (CCML) is a nonprofit Private Health establishment specializing in surgical and interventional management of diseases related to thoracic organs: heart, lungs, and vascular diseases in adults, children and infants. The CCML has research Laboratory to work, innovate and develop projects aimed at finding therapeutic solutions, new medical devices in the desire to advance medicine deal with rare and complex diseases. As a party of the Collaboration Agreement , CCML has developed a Know How that will enter in the scope of the license .

As a consequence, CCML is included in the definition of the Licensors.

AAVLIFE exercises the option within time period by sending a letter to Inserm Transfert.

In consideration thereof, the Parties now desire to amend the Agreement.

NOW, THEREFORE THE PARTIES HERETO AGREE AS FOLLOWS :

Except as otherwise specified in present Amendment n° 1 (hereinafter referred to as “ Amendment 1 ”), the terms hereby used in capitalized form shall have the meaning assigned to them in the Agreement.

ARTICLE 1 — OBJECT AND SCOPE OF THIS AMENDMENT 2

By this Amendment 1, the Parties hereby agree to:

to introduce CCML as a Licensor

extend the scope of the Agreement

provide an additional financial contribution.

ARTICLE 2 — ADDITIONAL RIGHTS FOR LICENSEE

2.1

Subject to the terms and conditions of the Agreement, Licensors hereby grant to Licensee (i) an exclusive, royalty-bearing license, with the right to sublicense, under the results (hereinafter “ Results ”) as described in the Appendix A , and (ii) a non-exclusive, royalty-bearing license, with the right to sublicense, under the new know-how (hereinafter “ New Know-How ”) as described in Appendix B, in each case of clauses (i) and (ii) to research, develop, make, have made, use, import, offer for sale and sell or otherwise distribute Products within the Field in the Territory.

A-2

CONFIDENTIAL

The Parties agree that New Know-How and Results shall be considered and assimilated respectively than Know-How and Patents Rights through the Agreement.

2.2	The following provisions will be added to the end of the article 1.12 “Know How” of the Agreement :

“Know-How means also New Know-How as described in the Appendix B of the Amendment 1.”

2.3	The following provisions will be added to the end of the article 1.22 “Patent Right” of the Agreement :

“Patent Rights mean also the Results as described in the Appendix A of the Amendment 1.”

ARTICLE 3 – PAYEMENT

In consideration of the licenses and rights granted under this Amendment 1, Licensee shall pay to Licensors a non-refundable and non-creditable lump sum of [***], thirty (30) days after the Effective Date of this Amendment 1.

ARTICLE 4 — EFFECTIVE DATE - TERM

The present Amendment 1 shall become effective at the last date of the signature by all Parties (hereinafter “ Effective Date of this Amendment 1 ”) until the end of the Agreement with respect to its article 10.

ARTICLE 5 — GENERAL TERMS

All provisions of the Agreement not specifically modified or amended by this Amendment 1 shall remain in full force and effect.

Signed in three (3) original counterparts drafted in the English language, one (1) of which is for each of the Parties.

Licensors:		Licensee:

Inserm Transfert		AAVLife

Name: Augustin Godard		Name: Amber Salzman

Title: Executive Vice President		Title: President

Date: 5 Oct. 2015		Date: 24/9/15

		CCML

		Name: Olivier Vallet

		Title: General Manager

A-3

Appendix A

DESCRIPTION OF RESULTS

From the Report of the Collaboration sent by Patrick Aubourg (INSERM) to AAVLife the March 25, 2015

InsermTransfert

RESULTS OTHER THAN KNOW-HOW

v Joint Results

[***]

May 2015 – olivier.bignolais@inserm-transfert.fr. 5

__________________________________________________________________________

Appendix B

DESCRIPTION OF NEW KNOW-HOW

From the Report of the Collaboration sent by Patrick Aubourg (INSERM) to AAVLife the March 25, 2015

InsermTransfert

KNOW-HOW

v Institutions KNOW-HOW

[***]

v Joint KNOW-HOW

[***]

May 2015 – olivier.bignolais@inserm-transfert.fr. 4

Exhibit 31.1

CERTIFICATION OF THE CHIEF EXECUTIVE OFFICER

PURSUANT TO

SECURITIES EXCHANGE ACT RULES 13A-14(A) AND 15D-14(A)

I, Paul B. Cleveland, certify that:

1.	I have reviewed this Quarterly Report on Form 10-Q of Adverum Biotechnologies, Inc. (formerly Avalanche Biotechnologies, Inc.);

2.	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;

3.	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;

4.	The registrant’s other certifying officer(s) 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)) 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;

5.	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):

(a)

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

(b)

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: August 09, 2016

/s/ Paul B. Cleveland

Paul B. Cleveland

Chief Executive Officer

(principal executive officer)

Exhibit 31.2

CERTIFICATION OF THE CHIEF FINANCIAL OFFICER

PURSUANT TO

SECURITIES EXCHANGE ACT RULES 13A-14(A) AND 15D-14(A)

I, Leone Patterson, certify that:

1.	I have reviewed this Quarterly Report on Form 10-Q of Adverum Biotechnologies, Inc. (formerly Avalanche Biotechnologies, Inc);

2.	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;

3.	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;

4.	The registrant’s other certifying officer(s) 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)) for the registrant and have:

5.	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):

(a)

(b)

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: August 09, 2016

/s/ Leone Patterson

Leone Patterson

Chief Financial Officer

(principal financial and accounting officer)

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 of Adverum Biotechnologies, Inc. (formerly Avalanche Biotechnologies, Inc.) (the “Company”) on Form 10-Q for the fiscal quarter ended June 30, 2016, as filed with the Securities and Exchange Commission (the “Report”), Paul B. Cleveland, Chief Executive Officer of the Company, and Leone Patterson, Senior Vice President and Chief Financial Officer of the Company, respectively, do each hereby certify, pursuant to 18 U.S.C. Section 1350, as adopted pursuant to Section 906 of the Sarbanes-Oxley Act of 2002, that:

•

The Report fully complies with the requirements of Section 13(a) or 15(d) of the Securities Exchange Act of 1934; and

•

The information in the Report fairly presents, in all material respects, the financial condition and results of operations of the Company.

Date: August 09, 2016

/s/ Paul B. Cleveland

Paul B. Cleveland

Chief Executive Officer

(principal executive officer)

/s/ Leone Patterson

Leone Patterson

Chief Financial Officer

(principal financial and accounting officer)