UNITED STATES

SECURITIES AND EXCHANGE COMMISSION

WASHINGTON , DC 20549

 

FORM 10-Q

 

(Mark One)

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

For the quarterly period ended September 30, 2016

or

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       No  

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

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

 

 

 

 

 

 

 

 

Large accelerated filer

 

  

Accelerated filer

 

 

 

 

 

Non-accelerated filer

 

  (Do not check if a smaller reporting company)

  

Smaller reporting company

 

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

As of October 31, 2016 there were 41,718,515 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 September 30, 2016 and December 31, 2015

  

3

Condensed Consolidated Statements of Operations and Comprehensive Loss for the three and nine months ended September 30, 2016 and 2015

  

4

Condensed Consolidated Statements of Cash Flows for nine months ended September 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

  

21

Item 3. Quantitative and Qualitative Disclosures About Market Risk

  

27

Item 4. Controls and Procedures

  

28

 

 

 

PART II—OTHER INFORMATION

  

29

 

 

 

Item 1. Legal Proceedings

  

29

Item 1A. Risk Factors

  

29

Item 2. Unregistered Sales of Equity Securities and Use of Proceeds

  

34

Item 3. Defaults Upon Senior Securities

  

35

Item 4. Mine Safety Disclosures

  

35

Item 5. Other Information

  

35

Item 6. Exhibits

  

35

 

 

 

SIGNATURES

  

36

 

 

 

EXHIBIT INDEX

  

37

 

 

 

 

2


 

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)

 

 

September 30,

 

 

December 31,

 

 

2016

 

 

2015

 

 

(Unaudited)

 

 

 

 

 

Assets

 

 

 

 

 

 

 

Current assets:

 

 

 

 

 

 

 

Cash and cash equivalents

$

231,271

 

 

$

221,348

 

Marketable securities

 

 

 

 

37,732

 

Receivable from collaborative partner

 

1,785

 

 

 

449

 

Prepaid expenses and other current assets

 

2,840

 

 

 

1,463

 

Total current assets

 

235,896

 

 

 

260,992

 

Property and equipment, net

 

4,335

 

 

 

3,187

 

Intangible assets

 

16,200

 

 

 

 

Deposit and other long-term assets

 

140

 

 

 

140

 

Total assets

$

256,571

 

 

$

264,319

 

Liabilities and stockholders’ equity

 

 

 

 

 

 

 

Current liabilities:

 

 

 

 

 

 

 

Accounts payable

$

3,067

 

 

$

605

 

Restructuring liabilities

 

25

 

 

 

1,013

 

Accrued expenses and other current liabilities

 

5,777

 

 

 

4,007

 

Deferred rent, current portion

 

89

 

 

 

66

 

Deferred revenue, current portion

 

1,691

 

 

 

883

 

Total current liabilities

 

10,649

 

 

 

6,574

 

Long-term liabilities:

 

 

 

 

 

 

 

Deferred rent, net of current portion

 

378

 

 

 

447

 

Deferred revenue, net of current portion

 

6,834

 

 

 

4,706

 

Deferred tax liability

 

2,025

 

 

 

 

Other noncurrent liabilities

 

455

 

 

 

 

Total liabilities

 

20,341

 

 

 

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 September 30,

   2016 and December 31, 2015; 41,718,515 and 25,858,722 shares issued and

   outstanding at September 30, 2016 and December 31, 2015, respectively

 

4

 

 

 

3

 

Additional paid-in capital

 

411,766

 

 

 

336,768

 

Accumulated other comprehensive loss

 

(19

)

 

 

(11

)

Accumulated deficit

 

(175,521

)

 

 

(84,168

)

Total stockholders’ equity

 

236,230

 

 

 

252,592

 

Total liabilities and stockholders’ equity

$

256,571

 

 

$

264,319

 

 

See accompanying notes to condensed consolidated financial statements

 

 

 

3


 

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 September 30,

 

 

Nine Months Ended September 30,

 

 

2016

 

 

2015

 

 

2016

 

 

2015

 

 

(Unaudited)

 

 

(Unaudited)

 

Collaboration revenue

$

395

 

 

$

953

 

 

$

967

 

 

$

1,359

 

Operating expenses:

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Research and development

 

8,362

 

 

 

7,523

 

 

 

23,772

 

 

 

18,270

 

General and administrative

 

6,146

 

 

 

7,631

 

 

 

19,578

 

 

 

16,733

 

Goodwill impairment charge

 

394

 

 

 

 

 

 

49,514

 

 

 

 

Total operating expenses

 

14,902

 

 

 

15,154

 

 

 

92,864

 

 

 

35,003

 

Operating loss

 

(14,507

)

 

 

(14,201

)

 

 

(91,897

)

 

 

(33,644

)

Other income

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Other income, net

 

206

 

 

 

117

 

 

 

544

 

 

 

285

 

Total other income, net

 

206

 

 

 

117

 

 

 

544

 

 

 

285

 

Net loss

$

(14,301

)

 

$

(14,084

)

 

$

(91,353

)

 

$

(33,359

)

Other comprehensive loss:

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Net unrealized (loss) gain on marketable securities

 

(6

)

 

 

2

 

 

 

 

 

 

12

 

Foreign currency translation adjustment

 

(23

)

 

 

(17

)

 

 

(13

)

 

 

(25

)

Comprehensive loss

$

(14,330

)

 

$

(14,099

)

 

$

(91,366

)

 

$

(33,372

)

Net loss per share attributable to common stockholders-basic

   and diluted

$

(0.35

)

 

$

(0.55

)

 

$

(2.66

)

 

$

(1.31

)

Weighted-average common shares outstanding-basic and

   diluted

 

41,416

 

 

 

25,685

 

 

 

34,382

 

 

 

25,378

 

 

See accompanying notes to condensed consolidated financial statements

 

 

 

4


 

Adverum Biotechnologies, Inc.

(Formerly Avalanche Biotechnologies, Inc.)

Condensed Consolidated Statements of Cash Flows

(Unaudited)

(In thousands)

 

 

Nine Months Ended September 30,

 

 

2016

 

 

2015

 

 

(Unaudited)

 

Cash flows from operating activities:

 

 

 

 

 

 

 

Net loss

$

(91,353

)

 

$

(33,359

)

Adjustments to reconcile net loss to net cash used in operating activities:

 

 

 

 

 

 

 

Depreciation and amortization

 

1,116

 

 

 

506

 

Stock-based compensation expense

 

9,852

 

 

 

7,084

 

Non-cash research and development expense

 

24

 

 

 

 

Goodwill impairment charge

 

49,514

 

 

 

 

Amortization of premium on marketable securities

 

 

 

 

570

 

Changes in operating assets and liabilities:

 

 

 

 

 

 

 

Receivable from collaborative partner

 

(532

)

 

 

 

Prepaid expenses and other current assets

 

(1,317

)

 

 

(542

)

Deposit and other long-term assets

 

 

 

 

(1

)

Accounts payable

 

817

 

 

 

283

 

Accrued expenses and other current liabilities

 

(46

)

 

 

388

 

Restructuring liabilities

 

(988

)

 

 

 

Deferred revenue

 

2,936

 

 

 

(1,359

)

Deferred rent

 

(47

)

 

 

218

 

Net cash used in operating activities

 

(30,024

)

 

 

(26,212

)

Cash flows from investing activities:

 

 

 

 

 

 

 

Purchases of marketable securities

 

 

 

 

(88,427

)

Maturities of marketable securities

 

37,738

 

 

 

19,600

 

Purchases of property and equipment

 

(1,488

)

 

 

(2,804

)

Cash acquired in business acquisition

 

3,449

 

 

 

 

Net cash provided by (used in) investing activities

 

39,699

 

 

 

(71,631

)

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

 

633

 

 

 

181

 

Taxes paid related to net share settlement of restricted stock units

 

(493

)

 

 

 

Proceeds from employee stock purchase plan

 

113

 

 

 

 

Proceeds from financing arrangement

 

100

 

 

 

 

Net cash provided by financing activities

 

353

 

 

 

139,135

 

Effect of foreign currency exchange rate on cash and cash equivalents

 

(105

)

 

 

(20

)

Net increase in cash and cash equivalents

 

9,923

 

 

 

41,272

 

Cash and cash equivalents at beginning of period

 

221,348

 

 

 

159,404

 

Cash and cash equivalents at end of period

$

231,271

 

 

$

200,676

 

 

 

 

 

 

 

 

 

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, accrued expenses and other current liabilities

$

771

 

 

$

182

 

 

See accompanying notes to condensed consolidated financial statements.

 

 

 

5


 

Adverum Biotechnologies, Inc.

(Formerly Avalanche Biotechnologies, Inc.)

September 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 agreements, 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 $175.5 million as of September 30, 2016. The Company expects to incur losses and have negative net cash flows from operating activities as it 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 Company completed the 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 nine months ended September 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.

 

 

 

6


 

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 the significant valuation accounting policies below as a result of the Annapurna acquisition in May 2016, and Editas revenue recognition policy related to the new license and collaboration agreement entered in August 2016.

 

Valuation of Long‑Lived Assets and Purchased Intangible Assets

The Company evaluates the carrying value of amortizable long‑lived assets, whenever events, or changes in business circumstances or the 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. If management’s assumptions about future operating results were to change as a result of events or circumstances, the Company may be required to record an impairment loss on these assets. No impairment indicators were noted for the Company’s amortizable 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 based on respective patent terms. 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 its 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 indicators were noted and no impairment charge was recorded at September 30, 2016.

 

Revenue Recognition

Collaboration and License Revenue - Editas Collaboration, Option and License agreement

In August 2016, the Company entered into a collaboration, option and license agreement with Editas. Refer to Note 6 for details of the agreement.  Under the terms of the agreement, the Company received initial payments of $1.0 million that included $0.5 million for research services.  As the agreement provides for multiple deliverables, the Company accounts for this agreement as a multiple elements revenue arrangement.  At the inception of the agreement, identified deliverables include research services, manufacturing of viral vectors for research, participation in joint research committee and exclusivity during the option period. These deliverables did not appear to have a standalone value and were combined into one unit of accounting. Options for each indication to license the Company’s AAV vector are considered substantive options and do not include significant incremental discounts. Therefore, they are not considered as deliverables under the Agreement.

The Company allocated the $1.0 million received to a single unit of accounting identified in the arrangement.  The Company expects to recognize $1.0 million ratably over the associated period of performance, which is the maximum research period of three years.  As there is no discernible pattern of performance and/or objectively measurable performance measures do not exist, the Company will recognize revenue on a straight-line basis. During the three months ended September 30, 2016, the Company recognized $56,000 as collaboration revenue.

 

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

 

7


 

retrospective approach or report the cumulative effect as of the date of adopti on. 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 effectiv e date of December 15, 2016 . The FASB issued supplemental adoption guidance and clarification to ASU 2014-09 in March 2016, April 2016 and May 2016 within ASU 2016-08 Revenue From Contracts With Customers: Principal vs. Agent Considerations , ASU 2016-10 Re venue From Contracts with Customers: Identifying Performance Obligations and Licensing , and ASU 2016-12 Revenue from Contracts with Customers: Narrow-Scope Improvements and Practical Expedients , respectively. The Company is evaluating the application of th is ASU and method of adoption, but has not yet determined the potential effect 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) classification 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 novel gene therapy products for people living with severe rare diseases. The primary reasons for the acquisition were to expand 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’s 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 stockholder was 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 the 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

 

8


 

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 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 the accelerated vesting of options and shares in its condensed consolidated statement of operations during the second quarter 2016.

Total purchase price consideration was estimated 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 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 assets 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 zero and $2.5 million of acquisition costs for the three-months and nine-months ended September 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. During the third quarter of 2016, as management continued its review of the valuation model, the Company recorded an adjustment to reduce the fair value of the acquired IPR&D asset by $450,000, to adjust the related deferred tax liability by $56,000, and to adjust recorded goodwill by $394,000. The adjusted 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

 

 

16,200

 

Goodwill

 

 

49,514

 

Accounts payable

 

 

(1,118

)

Accrued liabilities

 

 

(1,848

)

Other noncurrent liabilities

 

 

(377

)

Deferred tax liabilities

 

 

(2,025

)

Total purchase price allocation

 

$

64,845

 

 

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

 

IPR&D - Alpha-1 antitrypsin deficiency

 

$

11,700

 

IPR&D - Hereditary angioedema

 

 

4,500

 

Total acquired intangible assets

 

$

16,200

 

 

9


 

 

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 $49.5 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 September 30, 2016 was $1.2 million for the three months and $2.4 million for the nine months ended September 30, 2016. Annapurna did not generate any revenues prior or post acquisition.

The following table presents the unaudited pro forma results for the nine months ended September 30, 2016 and 2015. The pro forma financial information combines the results of operations of Adverum 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 achieved in the current or any future periods.

 

 

 

Nine Months Ended

September 30,

 

 

 

2016

 

 

2015

 

Pro forma information

 

 

 

 

 

 

 

 

Collaboration revenue

 

$

967

 

 

$

1,359

 

Net loss

 

$

(95,167

)

 

$

(38,475

)

Basic and diluted loss per share

 

$

(2.31

)

 

$

(0.97

)

Weighted-average common shares outstanding - basic and

   diluted

 

 

41,118

 

 

 

39,465

 

 

Pro-forma adjustments included the following:

 

 

Actual acquisition-related transaction costs of $2.5 million for nine months ended September 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 the accelerated vesting associated with the acquisition of $0.9 million was excluded from the 2016 pro forma results and was recorded in the nine months ended September 30, 2015.

 

Stock-based compensation expense related to options granted to executives upon the acquisition closing of $0.2 million and $0.3 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 nine months ended September 30, 2015 and $1.0 million for the nine months ended September 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 nine months ended September 30, 2015.

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

 

 

 

10


 

 

b)

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 of 2016, 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 liabilities 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 the 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 balance 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 fair 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 six month period ended June 30, 2016. During the third quarter of 2016, the Company recorded changes in acquired intangible assets, deferred tax liability, and goodwill as discussed above. This resulted in the additional goodwill impairment charge of $0.4 million recorded in the three months ended September 30, 2016. Total goodwill impairment charge was $49.5 million for the nine months ended September 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 September 30, 2016.

 

The Company did not impair recorded IPR&D intangible assets, as there were no impairment indicators as of September 30, 2016.

 

 

4. Cash Equivalents and Marketable Securities

The Company did not hold any marketable securities as of September 30, 2016, all investments of $225.7 million 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

 

 

 

11


 

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 investments 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 their 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 nine months ended September 30, 2016 and the year ended December 31, 2015. As of September 30, 2016, the Company has no Level 3 assets and one Level 3 liability.  As of 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)

 

September 30, 2016

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Assets:

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Money market funds - cash equivalent

 

$

225,735

 

 

$

225,735

 

 

$

 

 

$

 

Total cash equivalents

 

$

225,735

 

 

$

225,735

 

 

$

 

 

$

 

Other noncurrent liability:

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Financing arrangement

 

$

74

 

 

$

 

 

$

 

 

$

74

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

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

 

 

$

 

 

In August 2016, the Company entered into a financing arrangement with an independent third party for a total amount of $0.3 million. Under the terms of the financing arrangement, the Company may be required to repay up to $1.4 million, depending on the

 

12


 

achievement of certain development and commercialization milestones.  The Company elected the fair value option to account for this financing arrangement.  The fair value of the financing arrangement was determined based on the expected value approach and is classified as Level 3 within the fair value hierarchy.  The key unobservable inputs in the valuation model include timing of milestones, probability of achievemen t of development and commercial milestones and a discount factor.

The following table presents quantitative information about the inputs and valuation methodologies used for the fair value measurements classified in Level 3 at the fair value hierarchy at September 30, 2016:

 

 

 

Fair Value  at

 

 

 

 

Significant

 

 

 

 

 

 

September 30, 2016

 

 

Valuation

 

Unobservable

 

Weighted Average

 

 

 

(in thousands)

 

 

Methodology

 

Input

 

(range,   if applicable)

 

Financing arrangement

 

$

74

 

 

Expected value approach

 

Milestone dates

 

2017 to 2023

 

 

 

 

 

 

 

 

 

Discount rate

 

 

5.50

%

 

 

 

 

 

 

 

 

Percent probability of milestone achievements

 

18.2% to 80.0%

 

 

Non-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 Regeneron’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.

 

 

13


 

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 September 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. Under Adverum these programs will be ADVM-043, ADVM-053 and our program targeting severe allergy, respectively.

 

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 Investigational New Drug (“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 $1.1 million as of September 30, 2016 and recorded research and development expenses of $0.8 million for the three months ended September 30, 2016 and $1.3 million (post Annapurna’s acquisition) for the period from May 11, 2016 through September 30, 2016, related to Cornell agreements. No milestone payments were probable to achieve and none were recorded as of September 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, served as a consultant to Annapurna since inception and continues to provide 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.

 

 

14


 

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 $75,000 as of September 30, 2016 and recorded expenses of $49,000 (post Annapurna’s acquisition) for the period May 11, 2016 through September 30, 2016, related to REGENXBIO agreements. No milestone payments were probable to achieve and none were recorded as of September 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  €2.0 million in the aggregate and royalties on sales in the low single-digits, subject to adjustments. The Company accrued $140,000 relating to Inserm as of September 30, 2016 and recorded research and development expenses of $140,000 for the three months ended September 30, 2016 and for the period from May 11, 2016 through September 30, 2016, related to this agreement. No milestone payments were probable to achieve and none were recorded as of September 30, 2016.

 

Editas Medicine, Inc.

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 (AAV) 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 received a $1.0 million non-refundable upfront payment, with $0.5 million of such payment to be credited against Editas’ obligation to fund research and development 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 per Indication.  If Editas elects to develop a product using certain of the Company’s proprietary vectors, the Company will be eligible to receive up to a mid-teen million dollar amount in development and commercialization milestone payments for such product, and tiered royalties between the mid-single digits and low teens on net sales of such product, subject to certain adjustments.

Unless early terminated, the agreement will be in effect until the later of the expiration of the option exercise period or the expiration of the royalty term of the last product.   At any time after the option is first exercised, Editas may terminate the Agreement for convenience in its entirety or on an indication-by indication or country-by-country basis, upon prior written notice to the Company.  The Company may also terminate the agreement if Editas challenges the Company’s patents relating to its proprietary vectors and does not withdraw such challenge within a defined period of time.  In addition, either party may terminate the agreement with written notice upon a bankruptcy of the other party or upon an uncured material breach by the other party.

 

 

 

15


 

7. Property and Equipment, Net

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

 

 

 

September 30, 2016

 

 

December   31,   2015

 

Computer equipment and software

 

$

274

 

 

$

234

 

Laboratory equipment

 

 

4,052

 

 

 

3,041

 

Furniture and fixtures

 

 

552

 

 

 

552

 

Leasehold improvements

 

 

1,518

 

 

 

351

 

Construction in progress

 

 

46

 

 

 

 

Total property and equipment

 

 

6,442

 

 

 

4,178

 

Less accumulated depreciation and amortization

 

 

(2,107

)

 

 

(991

)

Property and equipment, net

 

$

4,335

 

 

$

3,187

 

 

Depreciation and amortization expense related to property and equipment for the three months ended September 30, 2016 and 2015 was $453,000 and $241,000, respectively.  Depreciation and amortization expense related to property and equipment for the nine months ended September 30, 2016 and 2015 was $1.1 million and $506,000, respectively.

 

 

8. Accrued Expenses and Other Current Liabilities

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

 

 

September 30, 2016

 

 

December   31, 2015

 

Employees’ compensation expenses

 

$

2,364

 

 

$

2,047

 

Accrued professional services

 

 

941

 

 

 

1,177

 

Accrued preclinical costs

 

 

1,992

 

 

 

642

 

Accrued clinical and process development costs

 

 

430

 

 

 

101

 

Other

 

 

50

 

 

 

40

 

Total accrued expenses and other current liabilities

 

$

5,777

 

 

$

4,007

 

 

 

9. Other non-current 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 was recorded as a discount at the issuance date. The discount is amortized as an interest expense over the life of the advances. As of September 30, 2016 the carrying value, which approximates the fair value, of the conditional advance was $381,000 and is recorded in other noncurrent liabilities and the Company recorded $11,000 interest expense from the acquisition closing date to September 30, 2016.

 

In July 2016, the Company entered into a sponsored research agreement with The Alpha-1 Project, Inc. (TAP) in which TAP will fund the Company’s A1AT research activities of up to $300,000. The Company may repay up to 4.5 times the received amount if and when certain product approval and sales milestones are achieved. During the third quarter, the Company received $100,000 and issued the common stock warrant for 10,000 shares exercisable anytime during five years from the issuance date at an exercise price of $4.33 per share. Warrants were valued at $26,000 at the issuance date and recorded as equity. Financing arrangement was recorded at estimated fair value of $74,000 in other noncurrent liabilities as of September 30, 2016. Refer to Note 5 for valuation details of this financing arrangement.

 

 

 

 

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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 September 30, 2016, none of the goals had been achieved under the license agreements and no cash milestones were accrued or payable. Since 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 September 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 liability 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 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. On November 3, 2016, the Court granted the Company’s motion to dismiss the consolidated complaint.  It set a deadline of December 2, 2016 for plaintiffs to file an amended consolidated complaint.

In December 2015, a securities class action lawsuit was filed against the Company, its board of directors, underwriters of its January 13, 2015, follow-on public stock offering, and two of its institutional stockholders, in the Superior Court of the State of California for the County of San Mateo. The complaint alleges that, in connection with the Company’s 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. In August 2016, the Court denied the Company’s motion to stay without prejudice, denied the Company’s demurrer, and dismissed with leave to amend certain claims against the underwriter defendants.

 

The Company believes that the claims in the asserted actions are without merit and intends 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

 

17


 

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 estimat e 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 September 30, 2016, a total of 13,162,656 shares of common stock were authorized for issuance and 3,033,936 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 nine months ended September 30, 2016, 52,002 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 September 30, 2016.

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

 

 

 

 

 

 

 

 

 

 

Weighted-

 

 

 

 

 

 

Number

 

 

Weighted-

 

 

Average Remaining

 

 

Aggregate

 

 

of Options

 

 

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

 

5,010

 

 

$

1.27

 

 

 

 

 

 

 

 

 

Options exercised

 

(1,474

)

 

$

0.45

 

 

 

 

 

 

 

 

 

Options cancelled

 

(1,349

)

 

$

12.02

 

 

 

 

 

 

 

 

 

Balance at September 30, 2016

 

7,681

 

 

$

4.90

 

 

 

8.3

 

 

$

17,866

 

Vested and expected to vest as of September 30, 2016

 

7,557

 

 

$

4.85

 

 

 

8.3

 

 

$

17,838

 

Exercisable as of September 30, 2016

 

3,806

 

 

$

3.89

 

 

 

7.4

 

 

$

12,136

 

 

(a)

The aggregate intrinsic value is calculated as the difference between the option exercise price and the closing price of common stock of $4.11 per share as of September 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 nine months ended September 30, 2016 and 2015 were $1.27 and $23.92, respectively. The total intrinsic value of options exercised during the nine months ended September 30, 2016 and 2015 were $7.1 million and $11.2 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

 

 

Nine Months Ended

 

 

September 30,

 

 

September 30,

 

 

2016

 

 

2015

 

 

2016

 

 

2015

 

Research and development

$

1,608

 

 

$

2,044

 

 

$

5,748

 

 

$

1,883

 

General and administrative

 

1,334

 

 

 

3,708

 

 

 

4,104

 

 

 

5,201

 

Total share-based compensation

$

2,942

 

 

$

5,752

 

 

$

9,852

 

 

$

7,084

 

 

Stock-based compensation expense included additional charges of 0.5 million and $1.5 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 for four Company’s executive officers for the three and nine-months ended September 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. RSUs granted to employees generally vest over a two-to-four year period.

 

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

 

 

 

 

 

 

 

Weighted-Average

 

 

 

Number of

 

 

Grant-Date

 

 

 

Units

(in thousands)

 

 

Fair Value

(in dollars)

 

Outstanding at December 31, 2015

 

 

632

 

 

$

13.07

 

Granted

 

 

1,159

 

 

$

4.59

 

Vested and released

 

 

(375

)

 

$

12.45

 

Forfeited

 

 

(493

)

 

$

7.11

 

Outstanding at September 30, 2016

 

 

923

 

 

$

5.81

 

 

The total fair value of RSUs that vested for the nine months ended September 30, 2016 and 2015 was $4.0 million and $0.1 million, respectively. As of September 30, 2016, there was $3.9 million of unrecognized compensation cost related to unvested RSUs that the Company expects to recognize over a weighted-average period of 3.2 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

 

 

Nine Months Ended

 

 

September 30,

 

 

September 30,

 

 

2016

 

 

2015

 

 

2016

 

 

2015

 

Option grants:

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Expected volatility

 

81

%

 

 

75

%

 

 

81

%

 

 

77

%

Expected term (in years)

 

6.0

 

 

 

6.1

 

 

 

5.9

 

 

 

6.1

 

Expected dividend yield

 

 

 

 

 

 

 

 

 

 

 

Risk-free interest rate

 

1.4

%

 

 

1.8

%

 

 

1.3

%

 

 

1.7

%

 

As of September 30, 2016, there was $12.6 million of unrecognized stock-based compensation expense related to employees’ awards that the Company expects to recognize over a weighted-average period of 3.1 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

 

 

Nine Months Ended

 

 

September 30,

 

 

September 30,

 

 

2016

 

 

2015

 

 

2016

 

 

2015

 

Option grants:

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Expected volatility

 

84

%

 

 

71

%

 

 

83

%

 

 

74

%

Expected term (in years)

 

8.0

 

 

 

2.5

 

 

 

7.5

 

 

 

4.1

 

Expected dividend yield

 

 

 

 

 

 

 

 

 

 

 

Risk-free interest rate

 

1.6

%

 

 

0.7

%

 

 

1.6

%

 

 

1.0

%

 

As of September 30, 2016, there was $2.1 million of unrecognized stock-based compensation expense related to non-employees’ awards that the Company expects to recognize over a weighted-average period of 2.7 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 September 30, 2016 and 2015, the Company contributed $0.1

 

19


 

million and $0 to the 401(k) Plan, respectively. For the nine months ended September 30, 2016 and 2015, the Company co ntributed $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 issued warrants for common stock, stock options and RSUs to purchase approximately 8.7 million and 5.8 million shares of our common stock that were outstanding as of September 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 October 2016, the Company announced the appointment of Amber Salzman, Ph.D., formerly the Company’s President and Chief Operating Officer, as Chief Executive Officer. Dr. Salzman joined Adverum as President and Chief Operating Officer in 2016 after the acquisition of Annapurna Therapeutics. Concurrently, Paul Cleveland, the Company’s former Chief Executive Officer, was appointed to Executive Chairman of the Board. Mr. Cleveland will remain the Company’s Principal Executive Officer. 

 

 

 

20


 

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 living with rare diseases or diseases of the eye, 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 after a single administration of therapy.  We have also acquired certain other gene therapy product candidates through our acquisition on May 11, 2016, of Annapurna Therapeutics SAS, a privately-held French gene therapy company (Annapurna).  Our core capabilities include clinical development expertise, vector optimization, process development, manufacturing technology expertise, and assay development.

We are focused on advancing our three lead gene therapy programs to address unmet needs in wet AMD and rare diseases alpha 1 antitrypsin (A1AT) deficiency and hereditary angioedema (HAE).  For wet AMD, we are moving forward with the preclinical development of new anti-VEGF gene therapy candidates, ADVM-022 and ADVM-032.  These intravitreally administered therapies, which utilize a proprietary vector, have the potential to minimize the treatment burden of frequent injections and maximize visual outcomes in patients living with this disease.  At two recent scientific meetings, we presented preclinical proof-of-concept data of these vectors’ anti-angiogenic effect in a laser-induced choroidal neovascularization (CNV) model, the industry standard.  These data are comparable to the anti-VEGF standard of care when evaluated in a model for the treatment of age-related macular degeneration. Based on these data, we plan to initiate toxicology studies for ADVM-022 and ADVM-032 in the first half of 2017.

Before focusing on these two new therapies for wet AMD, we were developing AVA-101 in a Phase 2a clinical trial in 32 patients with wet AMD.  In June 2015, we announced top-line results indicating 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 (via surgical sub-retinal delivery) in the Phase 2a study.  As a result, we decided not to move forward with the Phase 2b clinical trial for AVA-101 with the current dose and invasive administration procedure and instead decided to move forward with the preclinical development of ADVM-022 and ADVM-032.

For our pipeline of gene therapies for rare diseases, we are advancing ADVM-043 (formerly known as ANN-001) for the treatment of alpha 1 antitrypsin deficiency (A1AT).  ADVM-043 is designed as a single administration treatment and may induce stable, long-term A1AT expression at therapeutic levels, as seen in a preclinical proof-of-concept study.  ADVM-043 has an open IND with the FDA, and we plan to meet with the agency in the first quarter of 2017 to review our development plan.  We plan to initiate patient enrollment in a Phase 1/2 trial in the fourth quarter of 2017.  Concurrently, we are upgrading ADVM-043’s manufacturing process to a baculovirus-based process and plan to transfer our third-party contract manufacturing for this product to a large-scale cGMP contract manufacturer with baculovirus-based manufacturing capabilities.

We are also advancing ADVM-053 (formerly known as ANN-002) to treat hereditary angioedema (HAE).  We plan to initiate toxicology studies for ADVM-053 in the first half of 2017. Our research programs include gene therapies targeting cardiomyopathy associated with Friedreich’s ataxia and severe allergy.  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.

On May 11, 2016, we completed the 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.”

 

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Financial Overview

Summary

We have not generated positive cash flow or net income from operations since our inception and, at September 30, 2016, we had an accumulated deficit of $175.5 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 is a revenue agreement as discussed in Note 6, Significant Agreements , 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 September 30, 2016, we had $231.3 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.  

In August 2016, the Company entered into a collaboration, option and license agreement with Editas. Refer to Note 6 for details of the agreement.  Under the terms of the agreement, the Company received initial payments of $1.0 million that included $0.5 million for research services.  As the agreement provides for multiple deliverables, the Company accounts for this agreement as a multiple elements revenue arrangement.  At the inception of the agreement, identified deliverables include research services, manufacturing of viral vectors for research, participation in joint research committee and exclusivity during the option period. These deliverables did not appear to have a standalone value and were combined into one unit of accounting. Options for each indication to license the Company’s AAV vector are considered substantive options and do not include significant incremental discounts. Therefore, they are not considered as deliverables under the Agreement.

 

22


 

The Company allocated the $1.0 million received to a single unit of accounting identified in the arrangement.  The Company expects to recognize $ 1.0 million ratably over the associated period of performance, which is the maximum research period of three years.  As there is no discernible pattern of performance and/or objectively measurable performance measures do not exist, the Company will recognize revenue on a straight-line basis .  During the three months ended September 30, 2016, the Company recognized $56,000 as collaboration revenue.   The Company recognized $395,000 and $953,000 as revenue during the three months ended September 30, 2016 and 2015, respectively, and $967,000 and $1,359,000 as revenue during the nine months ended September 30, 2016 and 2015, respectively.  The Company recorded $8.5 million of deferred revenue, including $1.7 million as current deferred revenue, and $1.8 million as a receivable from collaborative partner as of September 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 $187,000 and $252,000 for the three and nine months ended September 30, 2016, respectively, and $17,000 and $113,000 for the three and nine months ended September 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.

 

23


 

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 $0.4 million and $49.5 million for the three and nine months ended September 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, 2016.

Refer to Note 2, Summary of Significant Accounting Policies of the accompanying unaudited condensed consolidated financial statements included in this Form 10-Q for our significant valuation accounting policy as a result of the Annapurna acquisition in May 2016, and our revenue recognition policy related to the new collaboration, option and license agreement with Editas in August 2016.

Results of Operations

Comparison of the Three and Nine Months Ended September 30, 2016 and 2015 (in thousands)

 

 

 

Three Months Ended

September 30,

 

 

 

 

 

 

Nine Months Ended

September 30,

 

 

 

 

 

 

 

2016

 

 

2015

 

 

Change

 

 

2016

 

 

2015

 

 

Change

 

Collaboration revenue

 

$

395

 

 

$

953

 

 

$

(558

)

 

$

967

 

 

$

1,359

 

 

$

(392

)

Operating expenses:

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Research and development

 

 

8,362

 

 

 

7,523

 

 

 

839

 

 

 

23,772

 

 

 

18,270

 

 

 

5,502

 

General and administrative

 

 

6,146

 

 

 

7,631

 

 

 

(1,485

)

 

 

19,578

 

 

 

16,733

 

 

 

2,845

 

Goodwill impairment charge

 

 

394

 

 

 

 

 

 

394

 

 

 

49,514

 

 

 

 

 

 

49,514

 

Total operating expenses

 

 

14,902

 

 

 

15,154

 

 

 

(252

)

 

 

92,864

 

 

 

35,003

 

 

 

57,861

 

Operating loss

 

 

(14,507

)

 

 

(14,201

)

 

 

(306

)

 

 

(91,897

)

 

 

(33,644

)

 

 

(58,253

)

Other income, net

 

 

206

 

 

 

117

 

 

 

89

 

 

 

544

 

 

 

285

 

 

 

259

 

Total other income, net

 

 

206

 

 

 

117

 

 

 

89

 

 

 

544

 

 

 

285

 

 

 

259

 

Net loss

 

$

(14,301

)

 

$

(14,084

)

 

$

(217

)

 

$

(91,353

)

 

$

(33,359

)

 

$

(57,994

)

 

Revenue

Collaboration revenue decreased to $0.4 million for the three months ended September 30, 2016, from $1.0 million for the three months ended September 30, 2015, primarily due to the recognition of $0.8 million of revenue related to the delivery of the data package to Regeneron in the third quarter of 2015 off-set by $0.2 million related to license and research services that are deferred and recognized over maximum research terms under Regeneron and Editas agreements.

Collaboration revenue decreased to $1.0 million for the nine months ended September 30, 2016, from $1.4 million for the nine months ended September 30, 2015, primarily due to the recognition of $0.8 million of revenue related to the delivery of the data package to Regeneron in the third quarter of 2015 off-set by $0.4 million related to license and research services that are deferred and recognized over maximum research terms under Regeneron and Editas agreements.

Research and Development Expense

Research and development expense increased to $8.4 million for the three months ended September 30, 2016, from $7.5 million for the three months ended September 30, 2015, primarily due to $1.1 million increase in material production and preclinical expense as

 

24


 

well as $0.2 million increase for outside services expense r elating to toxicology, off-set by a $0.5 million decrease in stock-based compensation expense.

Research and development expense increased to $23.8 million for the nine months ended September 30, 2016, from $18.3 million for the nine months ended September 30, 2015, primarily due to a $3.8 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 and $1.4 million related to the accelerated vesting of executive stock options, $1.2 million increase for outside services expense related to toxicology studies expenses, $0.9 million increase in lab, material production and preclinical expenses, $0.7 million increase in facility and deprecation charges relating to build out of the laboratory space, partially offset by $0.6 million decrease in consulting and recruiting 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 that research and development expenses will 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 decreased to $6.1 million for the three months ended September 30, 2016, from $7.6 million for the three months ended September 30, 2015. The decrease in general and administrative expense was primarily due to $2.4 million decrease in stock-based compensation expense as a result of additional stock options modification expense recorded in the third quarter of 2015 and no such expense recorded in the comparable period of 2016, off-set by $0.6 million increase in severance-related expenses, and a $0.3 million increase in professional service fees.

General and administrative expense increased to $19.6 million for the nine months ended September 30, 2016, from $16.7 million for the nine months ended September 30, 2015. The increase in general and administrative expense was primarily due to increases of $2.4 million in consulting and professional service expenses relating to the Annapurna acquisition, $1.1 million in compensation and benefits, and $0.5 million in facilities allocation relating to new office space, off-set by $1.1 million decrease in stock-based compensation due to lower stock price.

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.

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 preliminary $0.4 million and $49.5 million goodwill impairment charge in our condensed consolidated statements of operations and comprehensive loss for the three and nine months ended September 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 September 30, 2016, we had an accumulated deficit of $175.5 million, primarily as a result of research and development and general and administration expenses and the goodwill impairment charge. As of September 30, 2016, we had $231.3 million in cash and cash equivalents and no marketable securities. We believe that our existing cash and cash equivalents as of September 30, 2016, will be sufficient to fund our operations for at least the next 36 months.

 

25


 

We expect to incur substantial expenditures in the foreseeable future for the development and potential commercialization of our product candidates and ongoing i nternal 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 pr ocess 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 U.S. 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 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 and retain current 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

 

 

 

Nine Months Ended

 

 

 

September 30,

 

 

 

2016

 

 

2015

 

 

 

(in thousands)

 

Net cash used in operating activities

 

$

(30,024

)

 

$

(26,212

)

Net cash provided by (used in) investing activities

 

 

39,699

 

 

 

(71,631

)

Net cash provided by financing activities

 

 

353

 

 

 

139,135

 

Effect of foreign currency exchange rate

 

 

(105

)

 

 

(20

)

Net increase in cash and cash equivalents

 

$

9,923

 

 

$

41,272

 

 

Cash Used in Operating Activities

During the nine months ended September 30, 2016, net cash used in operating activities was $30.0 million, primarily as a result of the net loss of $91.4 million offset by the following non-cash charges: $49.5 million goodwill impairment charge, $9.9 million stock-based compensation expense, $1.1 million depreciation and amortization expense and $0.8 million for net increase in operating assets and liabilities.

 

 

26


 

During the nine months ended September 30, 2015, net cash used in operating activities was $26.2 million, primarily as a result of the net loss of $33.4 million offset by $7.1 million for non-cash charge related to stock-based compensation, $0.5 mi llion for depreciation and amortization, $0.6 million for amortization of premium on marketable securities and $1.0 million for net decrease in operating assets and liabilities.

 

Ca sh Provided by (Used in) Investing Activities

Net cash provided by investing activities for the nine months ended September 30, 2016, was $39.7 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 $1.5 million purchases of property and equipment.

 

Net cash used in investing activities for the nine months ended September 30, 2015, was $71.6 million and primarily relates to the purchases marketable securities of $88.4 million and the purchases of property and equipment of $2.8 million, offset by cash received from maturities of marketable securities of $19.6 million. The purchases of property and equipment consisted primarily of acquisition of laboratory equipment to support our research and development activities.

 

Cash Provided by Financing Activities

The net cash provided by financing activities during the nine months ended September 30, 2016, of $0.4 million relates to $0.7 million from proceeds relating to the exercise of options for common shares and ESPP purchase, off-set by $0.5 million in taxes paid relating to net share settlement of restricted stock units and $0.1 million relating to funds received from financing arrangement.

 

The net cash provided by financing activities during the nine months ended September 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 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.

 

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 the advances. As of September 30, 2016 the carrying value of the conditional advance was $381,000.

 

In July 2016, the Company entered into a sponsored research agreement with The Alpha-1 Project, Inc. (TAP) in which TAP will fund the Company’s A1AT research activities of up to $300,000. The Company may repay up to 4.5 times the received amount for which the Company may make contingent milestone payments up to $1.4 million in the future. The Company accounted for the TAP agreement as a debt financial instrument at fair value of $74,000.  During the third quarter, the Company received $100,000 and the estimated fair value of $74,000 was recorded as other noncurrent liabilities as of September 30, 2016.

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 months ended September 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.

 

 

 

27


 

Item 4.

Controls and Procedures

Evaluation of disclosure controls and procedures . Management, including our Principal 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 September 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 Principal Executive Officer and Chief Financial Officer concluded that as of September 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 Principal 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 September 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 Principal 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 Principal Executive Officer and Chief Financial Officer have concluded that, as of September 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.

 

 

 

28


 

PART II – OTHE R INFORMATION

Item 1.

Legal Proceedings

In July 2015, three 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. On November 3, 2016, the Court granted the Company’s motion to dismiss the consolidated complaint.  It set a deadline of December 2, 2016 for plaintiffs to file an amended consolidated complaint.

In December 2015, a 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. In August 2016, the Court denied the Company’s motion to stay without prejudice, denied the Company’s demurrer, and dismissed with leave to amend certain claims against the underwriter defendants.

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 our Quarterly Reports on Form 10-Q for the periods ending March 31, 2016 and June 30, 2016, and 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, and our Quarterly Reports on Form 10-Q for the periods ending March 31, 2016, and June 30, 2016, other than as set forth below. The below risk factors originally appeared in our Annual Report on Form 10-K or our Quarterly Reports on Form 10-Q for the periods ending March 31, 2016 and June 30, 2016, and have been updated.

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 September 30, 2016, on a pro forma basis, the combined company had an accumulated deficit of $175.5 million. Our losses have resulted primarily from costs incurred in our clinical trials, research and development programs and from our general and administrative expenses.  

 

29


 

In the future, we intend to continue to conduct research and development, clinical testing, regulatory compliance a ctivities 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 product 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.

Risks Related to the Discovery and Development of Our Product Candidates

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.

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, ADVM-022 and ADVM-032, focused on intravitreal delivery and utilizing a proprietary vector.  

We expect to initiate clinical studies for ADVM-043 (formerly ANN-001), in the fourth quarter of 2017. 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 our 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 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, ADMV-043, in the fourth quarter of 2017, 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;

 

30


 

 

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 may not be able to generate sufficient revenue to continue our business.

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 rare disease product candidate, ADVM-043, in the fourth quarter of 2017 and accordingly we expect this to be our next product candidate to enter clinical development. Identifying and qualifying subjects to participate in clinical studies of ADVM-043 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. ADVM-043 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. ADVM-053 (formerly 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. ADVM-063 (formerly 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

 

31


 

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-li nked 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 ca use 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 i n 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 trials 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.

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. Our 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, the 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.

 

32


 

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 supplie rs 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.

In addition, we recently decided to upgrade the ADVM-043 manufacturing process by implementing our proprietary baculovirus-based production system and transferring the third-party contract manufacturing for ADVM-043 to a large-scale contract manufacturer.  If we have difficulties or experience delays in transferring manufacturing to such third-party contract manufacturer, the planned initiation of our Phase 1/2 clinical trial for ADVM-043 in the fourth quarter of 2017 could be delayed.

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 was appointed Executive Chairman of the Board in October 2016 after joining as our President and Chief Executive Officer in December 2015. Amber Salzman, Ph.D. was appointed as our Chief Executive Officer in October 2016 after joining as our President and Chief Operating Officer, following the completion of the transaction with Annapurna in May 2016. 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 transition Mr. Cleveland and Dr. Salzman into their new roles, otherwise integrate newly hired executive officers, including Dr. Salzman and Ms. Patterson, into our management team and develop an effective working relationship among senior management. Our failure to transition and 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 employees. 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 executive team, including Executive Chairman of the Board Paul B. Cleveland, Chief Executive Officer 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

 

33


 

Francisco Bay Area in particular is characterized by a high cost of living. As such, we could have difficulty attracting experienced p ersonnel 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

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.

 

 

Item 2.

Unregistered Sales of Equity Securities and Use of Proceeds

Unregistered Sales of Equity Securities

None.

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

 

34


 

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 approx imately $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 have reallocated 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

None.

 

 

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.

 

 

 

35


 

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: November 08, 2016

 

ADVERUM BIOTECHNOLOGIES, INC.

 

 

 

 

 

By:

 

 /s/ Paul B. Cleveland

 

 

 

 

Paul B. Cleveland

 

 

 

 

Executive Chairman of the Board and Principal Executive Officer

 

 

 

36


 

EXHIBIT INDEX

 

EXHIBIT

NUMBER

 

DESCRIPTION

 

 

 

10.1‡

 

Collaboration, Option and License Agreement with Editas Medicine, Inc., dated August 8, 2016.

 

 

 

31.1

 

Certification of Principal 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 Principal 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 September 30, 2016, formatted in eXtensible Business Reporting Language (XBRL) includes: (i) Condensed Consolidated Balance Sheets at September 30, 2016 (unaudited) and December 31, 2015, (ii) Condensed Consolidated Statements of Operations and Comprehensive Loss (unaudited) for the three and nine months ended September 30, 2016 and 2015, (iii) Condensed Consolidated Statements of Cash Flows (unaudited) for the nine months ended September 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.

 

 

 

37

 

[***] = Certain confidential information contained in this document, marked by brackets, is filed with the Securities and Exchange Commission pursuant to Rule 24b-2 of the Securities Exchange Act of 1934, as amended.

Exhibit 10.1

COLLABORATION, OPTION AND LICENSE AGREEMENT

This Collaboration, Option and License Agreement (the “ Agreement ”) is entered into as of August 8, 2016 (“ Effective Date ”), by and between Adverum Biotechnologies, Inc. , a Delaware corporation having an address at 1035 O’Brien Drive, Menlo Park, CA 94025 (“ Adverum ”), and Editas Medicine, Inc. , a Delaware corporation having an address at 300 Third Street, Cambridge, MA 02142 (“ Editas ”).  Adverum and Editas may be referred to herein individually as a “ Party ” and collectively as the “ Parties .”

RECITALS

Whereas , Adverum is a gene therapy company and Editas is a genome editing company;

Whereas , the Parties are each committed to discovering and developing novel medicines and therapeutics for human diseases, including ophthalmic indications;

Whereas , Adverum controls certain intellectual property related to viral vector technology for gene therapy applications;

Whereas , the Parties wish to collaborate on certain studies using Adverum’s proprietary vector in connection with Editas’ genome editing technology; and

Whereas , Editas wishes to obtain, and Adverum wishes to grant to Editas, an exclusive option to obtain exclusive rights to use Adverum’s proprietary vector in several ophthalmic indications.

Now, Therefore , in consideration of the mutual covenants and agreements herein contained, the Parties agree as follows.

1.

Definitions

1.1

[***]” means [***].

1.2

Additional Adverum Viral Vector ” means any of the proprietary viral capsids Controlled by Adverum or any of its Affiliates during the Term containing a nucleic acid sequence containing and capable of expressing a transgene of interest, other than the vector known as “[***]” or the vector known as “[***].”

1.3

Additional Indication ” means each of (i) [***], (ii) [***], (iii) [***], and (iv) [***].  

1.


 

1.4

Additional Indication Option Exercise Period ” has the meaning set forth in Section   3.3 .

1.5

Adverum Expression Elements ” means any Expression Element that is: (a) proprietary to Adverum as of the Effective Date; or (b) generated by or on behalf Adverum during the Term independent of this Agreement, in each case that is used by Adverum under the Research Plan or provided by Adverum to Editas for use under the Research Plan.

1.6

Adverum Indemnitees ” has the meaning set forth in Section 10.2.

1.7

Adverum Know-How ” means, subject to Section 14.5, Know-How Controlled by Adverum or any of its Affiliates as of the Effective Date or during the Term that is necessary or reasonably useful to practice the Vector Technology.

1.8

Adverum Patents ” means, subject to Section 14.5, Patents Controlled by Adverum or any of its Affiliates as of the Effective Date or during the Term (including Adverum’s interest in Joint Patents) that Cover the Vector Technology. The Adverum Patents include the [***] Patents.  The Adverum Patents as of the Effective Date are listed in Exhibit A .

1.9

Adverum Research Personnel ” means all employees, staff and agents of Adverum participating in the conduct of the Research Plan.

1.10

Adverum Technology ” means Adverum Patents and Adverum Know-How.

1.11

Adverum Viral Vector means each of: (a) Adverum’s proprietary viral capsid containing a nucleic acid sequence containing and capable of expressing a transgene of interest, known as “[***]”; (b) Adverum’s proprietary viral capsid containing a nucleic acid sequence containing and capable of expressing a transgene of interest, known as “[***]”; and (c) any Additional Adverum Viral Vector(s) that are added to this Agreement by mutual written agreement of the Parties.

1.12

Affiliate ” means, with respect to a particular Party or other entity, a person, corporation, partnership, or other entity that controls, is controlled by or is under common control with such Party or other entity.  For the purposes of this definition, the word “control” (including, with correlative meaning, the terms “controlled by” or “under common control with”) means the actual power, either directly or indirectly through one or more intermediaries, to direct or cause the direction of the management and policies of such entity, whether by the ownership of fifty percent (50%) or more of the voting stock of such entity, or by contract or otherwise.

1.13

Applicable Laws ” means all laws, statutes, rules, regulations, ordinances and other pronouncements having the effect of law of any federal, national, multinational, state, provincial, county, city or other political subdivision, domestic or foreign.

1.14

Calendar Quarter ” means each respective period of three (3) consecutive months ending on March 31, June 30, September 30, and December 31.

2.

 

[***] = Certain confidential information contained in this document, marked by brackets, is filed with the Securities and Exchange Commission pursuant to Rule 24b-2 of the Securities Exchange Act of 1934, as amended.


 

1.15

Calendar Year ” means each respective period of twelve (12) consec utive months ending on December  31.

1.16

Claims has the meaning set forth in Section 10.1.

1.17

CMO ” means contract manufacturing organization.

1.18

Collaboration Invention ” means an Invention that is conceived or reduced to practice by or on behalf of a Party or any of its Affiliates or any of its sublicensees, individually or jointly, in the course of conducting the activities under the Research Plan.

1.19

Collaboration Therapeutic Molecule ” means (a) (i) one or more nucleic acids [***] (e.g., one or more [***] and/or a [***]), and/or (ii) a nucleic acid [***] that is [***] (e.g., a [***]), and (b) each of (a)(i) and (ii) which can be or is integrated within a Therapeutic Expression Cassette or the Viral Vector, provided that for purposes of this Agreement, references to Collaboration Therapeutic Molecules are intended only to include the molecule or portion of a molecule that fulfills subsection (a) and not Expression Elements.

1.20

Commercialization ” means the conduct of all activities undertaken before and after Regulatory Approval relating to the promotion, marketing, sale, and distribution (including importing, exporting, transporting, customs clearance, warehousing, invoicing, handling, and delivering Products to customers) of Products in the Field in the Territory, including: (i) sales force efforts, detailing, advertising, medical education, planning, marketing, sales force training, and sales and distribution; and (ii) post-approval clinical trials.  “ Commercialize ” and “ Commercializing ” have correlative meanings.

1.21

Commercially Reasonable Efforts ” means those efforts that are consistent with the efforts and resources normally used by a biotechnology company of similar size in the exercise of its reasonable business discretion relating to the research and development of a potential product as part of an active and ongoing program, or the commercialization of a product, in each case owned by it or to which it has exclusive rights, with similar product characteristics as a Product and of similar market potential at a similar stage in its development or product life as the Product, taking into account all relevant factors, including patent coverage, safety and efficacy, product profile, competitiveness of the marketplace, proprietary position and profitability (including pricing and reimbursement), and milestones that may be triggered in connection with the Commercialization of a Product.

1.22

Confidential Information ” of a Party means all Know-How, Materials, and other proprietary scientific, marketing, financial, business or commercial information that is disclosed by or on behalf of such Party or any of its Affiliates or otherwise made available to the other Party or any of its Affiliates, whether made available orally, in writing, or in electronic form.  The existence and terms of this Agreement are the Confidential Information of both Parties.  All information disclosed by a Party under the Confidentiality Agreement is deemed the Confidential Information of such Party pursuant to this Agreement.

3.

 

[***] = Certain confidential information contained in this document, marked by brackets, is filed with the Securities and Exchange Commission pursuant to Rule 24b-2 of the Securities Exchange Act of 1934, as amended.


 

1.23

Confidentiality Agreement ” means that certain Confidential Disclosure Agreement between the Parties dated as of [***] .

1.24

Cover ” means, with respect to a Valid Claim in a country and a Product, that such claim would be infringed, absent a license, by the manufacture, use, offer for sale, sale or importation of such Product in such country.

1.25

Development ” means to develop (including preclinical, clinical, nonclinical, and chemistry manufacturing controls (“ CMC ”) development), analyze, test, and conduct preclinical, clinical, and all other regulatory trials for a Product or a Prototype Product, as well as all related regulatory activities and any and all activities pertaining to new indications, pharmacokinetic studies, and all related activities including work on new formulations, new methods of treatment, and CMC activities including new manufacturing methods.  “ Developing ” and “ Develop ” have correlative meanings.

1.26

Editas Expression Elements ” means any Expression Element that is: (a) proprietary to Editas as of the Effective Date; or (b) generated by or on behalf of Editas during the Term independent of this Agreement, in each case that is used by Editas under the Research Plan or provided by Editas to Adverum for use under the Research Plan.

1.27

Editas Indemnitees ” has the meaning set forth in Section 10.1.

1.28

EU ” means the European Union member states as then constituted.

1.29

Executive Officers ” has the meaning set forth in Section 13.2.

1.30

Expression Elements ” means the portion of a Collaboration Therapeutic Molecule or Therapeutic Expression Cassette that constitutes sequences that is necessary for the Collaboration Therapeutic Molecule to be integrated into or expressed using the Viral Vector, either as part of the viral payload (e.g., promoters, untranslated regions and poly A sequences, ITR sequences, or the like).

1.31

Expression Element Invention ” means any Collaboration Invention that pertains to  the Expression Element Technology.

1.32

Expression Element Technology ” means any technology pertaining to the Expression Element.

1.33

FDA ” means the United States Food and Drug Administration or any successor entity thereto.

1.34

Field ” means, with respect to a particular Product, the prevention or treatment of the Indication [***] to which such Product is directed, provided that, after the Option Period expires for any particular Indication, the Field shall only include the prevention or treatment of such Indication if Editas has exercised its Option with respect to such Indication.

4.

 

[***] = Certain confidential information contained in this document, marked by brackets, is filed with the Securities and Exchange Commission pursuant to Rule 24b-2 of the Securities Exchange Act of 1934, as amended.


 

1.35

FTE means the equivalent of a full-time individual’s work for a twelve (12) month period (consisting of a total of [***] hours per year of dedicated effort).  Any person who devotes more or less than [***] hours per year on the applicable activities shall be treated as an FTE on a pro-rata basis, based upon the actual number of hours worked by such person on such activities, divided by [***] .  For avoidance of doubt, the hours spent by temporary workers and contractors on applicable activities may be treated as FTE on a pro-rata basis, but the hours allocated to the work of general corporate or administrative personnel shall not be incorporated into FTE.

1.36

FTE Rate ” means an initial rate of [***] per FTE per year.

1.37

First Commercial Sale means, with respect to a Product in a country in the Territory, the first commercial sale of the Product in such country by Editas or its Affiliate or sublicensee to a Third Party that is not a sublicensee of Editas or its Affiliates following receipt of Regulatory Approval for sale of such Product in such country.

1.38

Generic Product ” means, with respect to a Product in a particular regulatory jurisdiction, any pharmaceutical product that (a) (i) contains the same active pharmaceutical ingredients as such Product for the same route of administration as such Product and is approved by the Regulatory Authority in such country; or (ii) is approved by the Regulatory Authority in such country as a substitutable generic for such Product; and (b) is sold in such jurisdiction by a Third Party that is not a sublicensee and did not purchase such product in a chain of distribution that included any of Editas or its Affiliates or sublicensees.

1.39

Indemnified Party ” has the meaning set forth in Section 10.3.

1.40

Indemnifying Party ” has the meaning set forth in Section 10.3.

1.41

Indication ” means any or all of the Initial Indication and the Additional Indications, as the context dictates.

1.42

Initial Indication ” means [***].

1.43

Initial Option Exercise Period ” has the meaning set forth in Section 3.2.

1.44

Invention ” means an invention that is conceived or made by a Party or its Affiliates, employees, sublicensees, independent contractors, agents, or consultants, alone or jointly with the other Party, in the course of performing the Research Plan or other activities related to the Development, manufacture, or Commercialization of the Products under this Agreement.

1.45

Joint Invention ” has the meaning set forth in Section 8.1(c).

1.46

Joint Patent ” has the meaning set forth in Section 8.1(c).

1.47

Joint Research Committee or “ JRC ” has the meaning set forth in Section 2.1.

5.

 

[***] = Certain confidential information contained in this document, marked by brackets, is filed with the Securities and Exchange Commission pursuant to Rule 24b-2 of the Securities Exchange Act of 1934, as amended.


 

1.48

Know-How ” means Inventions , discoveries, know-how, trade secrets, information, techniques, data, formulas, procedures, and results, including without limitation physical, chemical, biological, toxicological, pharmacological, safety, and pre-clinical and clinical data, dosage regimens, control assays, and product specifications, but excluding Patents.

1.49

License ” has the meaning set forth in Section 3.4.

1.50

License Effective Date ” means the Option Exercise Date with respect to a particular Indication.

1.51

MAA ” means a marketing authorization application or equivalent application, and all amendments and supplements thereto, filed with the applicable Regulatory Authority in any country or jurisdiction.

1.52

Major Market Countries ” means [***].

1.53

Materials ” means any tangible chemical or biological research materials that are provided or otherwise made available by one Party to the other Party under the terms of this Agreement. The term Materials shall also include any unmodified derivatives or progeny of such Material.

1.54

NDA means a New Drug Application, as defined in the Federal Food, Drug, and Cosmetic Act, as amended, and applicable regulations promulgated thereunder by the FDA.

1.55

Net Sales ” means the gross invoice price of Product (or Royalty Non-Adverum Product, as applicable) sold or otherwise disposed of by Editas or its Affiliates or sublicensee to independent Third Parties, reduced by the following amounts (calculated in accordance with generally accepted accounting principles in accordance with International Financial Reporting Standards as consistently applied by Editas or its Affiliate or sublicensee, as applicable): (a) the amounts actually allowed or taken as volume, trade, quantity, or early payment discounts; (b) credits actually given for returned Product (including withdrawals, recalls, rejections, and returns); (c) all rebates, chargebacks, retroactive price reductions, patient discount programs, and other sales allowances that are actually granted to any payor, including managed health organizations, including rebates, reductions, and allowances mandated by government; (d) taxes (other than income or withholding taxes) directly attributable to the sale of such Product (or Royalty Non-Adverum Product, as applicable), including duties, tariffs, mandated contribution or other governmental charges levied on the sale of such Products, including VAT, excise taxes, sales taxes, and that portion of the annual feel on prescription drug manufacturers imposed by the Patient Protection and Affordable Care Act, Pub. L. No. 111-148 (as amended), that Editas or its Affiliates or sublicensees, as applicable, allocate to the sales of such Product in accordance with Editas or its Affiliate’s or sublicensee’s standard policies and procedures consistently applied across its products, as applicable, in each case, to the extent non-creditable or refundable, (e) bad debt expense and amounts actually written off by reason of uncollectible debt; and (f) transportation costs, including

6.

 

[***] = Certain confidential information contained in this document, marked by brackets, is filed with the Securities and Exchange Commission pursuant to Rule 24b-2 of the Securities Exchange Act of 1934, as amended.


 

insurance and shipping, freight, and handling charges. Any consideration received in exchange for the transfer of Product for use in clinical trials, sampling, promotional, and/or compassionate or charitable uses, or in connection with patient assistance programs, in each case at or below cost, shall not be included in Net Sales.

If Editas or its Affiliates or sublicensees receive non-cash consideration for Product (or Royalty Non-Adverum Product, as applicable) sold or otherwise transferred to an independent Third Party, Net Sales for such sale or transfer will be determined as above based on the average of the gross invoice prices charged to other independent Third Parties in respect of cash sales during the applicable Calendar Quarter.

Sales between Editas and its Affiliates and sublicensees shall be disregarded for purposes of calculating Net Sales except if such purchaser is an end user.

1.56

Non-Adverum Product ” means a genome editing product consisting of the Other Viral Vector containing a Therapeutic Expression Cassette to deliver one (1) or more Collaboration Therapeutic Molecule(s) [***] directed to the Initial Indication, provided, that (A) a Non-Adverum Product for purposes of this Agreement, including without limitation, any payments that may due pursuant to Sections 6.3(b) and 6.5(b),  may only exists if the Parties have agreed to an Other Viral Vector Agreement and (B) such Non-Adverum Product is solely with respect to [***] with respect to the Initial Indication.  

1.57

Option ” has the meaning set forth in Section 3.1.

1.58

Option Exercise Date means the date (if any) on which Editas exercises the Option with respect to an Indication in accordance with Section 3.2.  For clarity, if Editas exercises the Option with respect to each Indication on separate dates, each such date shall be deemed an “Option Exercise Date” for the applicable Indication.

1.59

Option Period ” means the period of time commencing on the Effective Date and ending on the earlier of (a) the last to occur Option Exercise Date; and (b) the date on which the Option expires in its entirety pursuant to Section 3.2.

1.60

Other Viral Vector ” means the [***] viral vector known as [***].

1.61

Out-of-Pocket Cost ” means direct project related expenses paid or payable to Third Parties and specifically identifiable and incurred in accordance with the Research Plan; such expenses shall have been recorded as income statement items in accordance with Adverum’s accounting standards and for the avoidance of doubt, will not include any travel expenses, pre-paid amounts or capital expenditures, or financing costs without Editas’ prior consent.

1.62

Patents means (a) patents, re-examinations, reissues, renewals, extensions and term restorations, and foreign counterparts thereof, and (b) pending applications for patents, including, without limitation, provisional applications, continuations, continuations-in-part, divisional and substitute applications, inventors’ certificates, and extensions.

7.

 

[***] = Certain confidential information contained in this document, marked by brackets, is filed with the Securities and Exchange Commission pursuant to Rule 24b-2 of the Securities Exchange Act of 1934, as amended.


 

1.63

Product ” means a genome editing product consisting of a n Adverum Viral Vector (s uch designation to be made on an Indication by Indication basis) containing a Therapeutic Expression Cassette to deliver one (1) or more Collaboration Therapeutic Molecule(s) [***] for use in the Field.  For clarity, [ *** ] shall be treated as a single Product , including, for purposes of the payments contemplated by Sections 6.3, 6.4 and 6.5 of this Agreement , but Products [ *** ] will be deemed to be a different Product, unless [ *** ] .

1.64

Product Data means testing results, data and trial protocols specific to a Product (whether or not such Product includes a Viral Vector) generated or developed in the course of work performed under this Agreement.  Product Data are a subset of Research Data.

1.65

Prototype Product ” means an Editas genome editing product that includes a Viral Vector that is being tested by Editas during the Option Period for the applicable Indication, subject to Editas’ exclusivity obligation under Section 3.11.  Any Prototype Product shall be deemed a Product after Editas exercises the Option with respect to the Indication applicable to such Product.

1.66

“[***]” means the [***].

1.67

Regulatory Approval ” means any and all approvals, licenses, registrations, permits, notifications, and authorizations (or waivers) of any applicable Regulatory Authority that are necessary for the manufacture, use, storage, import, transport, promotion, marketing, distribution, offer for sale, sale, or other commercialization of a Product in a given country or regulatory jurisdiction.

1.68

Regulatory Authority” means any applicable Governmental Authority responsible for granting Regulatory Approvals for Products, including the FDA, the EMA, and any corresponding national or regional regulatory authorities.

1.69

Regulatory Exclusivity ” means any exclusive marketing rights or data exclusivity rights conferred by any Regulatory Authority with respect to a pharmaceutical product other than Adverum Patents, including orphan drug exclusivity, new chemical entity exclusivity, data exclusivity, or pediatric exclusivity.

1.70

Regulatory Filings means any regulatory application, submission, notification, communication (including meeting minutes), correspondence, registration, briefing documents, and other filings made to, received from, or otherwise conducted with a Regulatory Authority in order to Develop, manufacture, or Commercialize a Product in a particular country or jurisdiction, including any IND, MAA, or Regulatory Approval .

1.71

Research Budget ” has the meaning set forth in Section 2.2(a).

1.72

Research Costs ” means expenses incurred by Adverum in carrying out the work under the Research Plan, calculated as the sum of (i) all Out-of-Pocket Costs incurred by Adverum with respect to the activities outlined in the Research Plan, including the

8.

 

[***] = Certain confidential information contained in this document, marked by brackets, is filed with the Securities and Exchange Commission pursuant to Rule 24b-2 of the Securities Exchange Act of 1934, as amended.


 

cost of acquiring clinical supplies; and (ii) the cost of Adverum employees in carrying out the activities outlined in the Research Plan calculated at the FTE Rate [ *** ] .

1.73

Research Data ” means all data, results, records, reports, information and any other Know-How which are generated in the course of the performance of activities under the Research Plan.

1.74

Research Period ” shall mean the period commencing on the Effective Date and ending on the earlier of (i) completion of all research contemplated by the Research Plan (as may be amended from time to time by mutual agreement of the Parties) and (ii) [***].

1.75

Research Plan ” has the meaning set forth in Section 2.2(a).

1.76

Research Records ” has the meaning set forth in Section 2.3(a).

1.77

Royalty Term ” has the meaning set forth in Section 6.5(c).

1.78

Sole Inventions ” has the meaning set forth in Section 8.1(c).

1.79

Sublicensee Revenue ” means all consideration received by Editas or its Affiliates from a current or prospective sublicensee in consideration for the grant to or by, or the exercise by, such sublicensee or its Affiliate or licensee of an option, license, or other right to Develop or Commercialize any Product (and, for purposes of clarity, the term Product shall not include any Non-Adverum Product), which may include upfront payments, option fees, license fees, annual maintenance fees, minimum annual payments, and milestone payments, but specifically excludes payments received by Editas or its Affiliates (a) that constitute royalties and other payments based upon the magnitude of sales of Products, (b) as consideration for the issuance to such sublicensee of equity or debt securities of Editas or its Affiliates to the extent above the fair market value, (c) for providing Development or Commercialization services to such sublicensee after the effective date of the agreement between Editas and such sublicensee on normal commercial terms; or (d) as reimbursements or funding for research and development costs and reasonable patent prosecution, maintenance, or defense expenses actually incurred by Editas or its Affiliates.

1.80

Term ” has the meaning set forth in Section 12.1.

1.81

Territory ” means worldwide.

1.82

Therapeutic Expression Cassette ” means: (a) one or more nucleic acid sequences containing and capable of expressing a transgene encoding a Collaboration Therapeutic Molecule, and (b) which can be or is integrated within the Viral Vector, provided that for purposes of this Agreement, references to Therapeutic Expression Cassette are intended only to include the sequence or portion of a sequence that fulfills subsection (a) and not Expression Elements.

9.

 

[***] = Certain confidential information contained in this document, marked by brackets, is filed with the Securities and Exchange Commission pursuant to Rule 24b-2 of the Securities Exchange Act of 1934, as amended.


 

1.83

Therapeutic Invention ” means any Collaboration Invention that pertains to: (a) the composition of a Collaboration Therapeutic Molecule or Therapeutic Expression Cassette ; (b) the method of using a Collaboration Therapeutic Molecule or Therapeutic Expression Cassette ; or (c) the method and process of manufacturing the Collaboration Therapeutic Molecule or Therapeutic Expression Cassette , other than any Vector Manufacturing Technology , other than any Vector Invention or Expression Element Invention .

1.84

Third Party” means any Person other than a Party or an Affiliate of a Party.

1.85

“[***]” means that certain [***] Agreement by and between Adverum and the [***] dated as of [***].

1.86

“[***] Agreements ” means those Upstream Agreements between the [***] and Adverum.  The [***] Agreements as of the Effective Date are listed in Exhibit B .

1.87

“[***] Patents ” means those Patents listed in Exhibit A .

1.88

United States or “ US ” means the United States of America, its territories and possessions.

1.89

Upstream Agreements ” means those agreements which concern the Adverum Technology that is Controlled by Adverum pursuant to an agreement with a Third Party, provided that, if any agreement is entered into after the Effective Date under which Adverum obtains any intellectual property from a Third Party, such agreement shall only be included as an Upstream Agreement, and such intellectual property included as Adverum Technology, to the extent Editas consents to such inclusion and agrees to be bound by the terms and conditions of such Third Party agreement and make payments thereunder that are triggered by Editas’ activities under this Agreement, further provided that Editas shall not be required to consent to such inclusion, in which event such Third Party intellectual property shall be excluded from the definition of Adverum Technology.  The Upstream Agreements as of the Effective Date are listed in Exhibit B .

1.90

Vector Invention ” means any Collaboration Invention that pertains to the Vector Technology other than any Expression Element Invention.

1.91

Vector Manufacturing Cassette ” means a nucleic acid sequence containing and capable of expressing viral genes that are necessary or useful for the replication, packaging or production of an Adverum Viral Vector in a host cell.

1.92

Vector Manufacturing Technology ” means compositions of matter and methods of use that pertains to (a) Vector Manufacturing Cassettes that are useful for improving the production of Adverum Viral Vector by a host cell, and/or (b) baculoviruses, in each case that is not specific to the expression of the Collaboration Therapeutic Molecule.

10.

 

[***] = Certain confidential information contained in this document, marked by brackets, is filed with the Securities and Exchange Commission pursuant to Rule 24b-2 of the Securities Exchange Act of 1934, as amended.


 

1.93

Vector Technology ” means technology pertaining to: (a) compositions of matter comprising, and methods of and compositions for using, designing, discovering or creating (but specifically not manufacturing), an Adverum Viral Vector, and/or (b) the Vector Manufacturing Technology.

1.94

Viral Vector ” means an Adverum Viral Vector or the Other Viral Vector.

2.

Governance and Research During THE RESEARCH Period

2.1

Joint Research Committee .

 

(a)

Establishment .  The Parties will establish a joint research committee (the “ Joint Research Committee ” or “ JRC ”) , composed of three (3) representatives of each Party, each of whom have experience in pharmaceutical discovery and development.  Within thirty (30) days following the Effective Date, each Party will notify the other Party of the dates of availability for the first meeting of the JRC.  Each Party may replace its representatives on the JRC on written notice to the other Party. The initial members of the JRC are listed in Exhibit C .

 

(b)

Responsibilities . The JRC shall oversee and review the execution of the Research Plan. In particular, the JRC shall be responsible for discussing and reviewing the status, progress, and results of Adverum’s performance of the Research Plan and the Research Budget.

 

(c)

Meetings .  The JRC Committee shall meet at least once per Calendar Quarter during the Research Period. The JRC shall hold its first meeting as soon as reasonably practicable, but in no event later than sixty (60) days following the Effective Date. Meetings will be held at such place or places as are mutually agreed or by teleconference or videoconference. Each Party may from time to time invite a reasonable number of participants who are under obligations of confidentiality consistent with this Agreement, in addition to its representatives, to attend JRC meetings in a non‑voting capacity, with the consent of the other Party (which shall not be unreasonably withheld). At each JRC meeting, each Party will update the other Party on, and the Parties will review and discuss, the performance of the Research Plan, the status of Development activities with respect to the Products for the Indications, and possible amendments to the Research Plan. Each Party shall solely bear all costs it incurs in connection with its participation at any meetings under this Section 2.1(c).

11.

 

[***] = Certain confidential information contained in this document, marked by brackets, is filed with the Securities and Exchange Commission pursuant to Rule 24b-2 of the Securities Exchange Act of 1934, as amended.


 

 

(d)

Decision Making . The JRC will make decisions by unanimous vote , with the representatives of each Party col lectively having one (1) vote. In the event the Parties’ JRC representatives do not agree on any particular matter, then :

 

(i)

the [***] representatives shall have the final decision making authority with respect to (A) [***], (B) any [***] that is [***]; and (C) the [***] and [***]; and

 

(ii)

all other disagreements are to be decided by the mutual agreement of the Parties, including decisions with respect to the [***] or [***].

 

(e)

JRC Authority.   The JRC shall have no authority to amend or interpret this Agreement, nor to expand the obligations of either Party under this Agreement.

2.2

The Research Plan .

 

(a)

Content .  All studies of the Prototype Product during the Research Period shall be conducted pursuant to a written research plan (as amended in accordance with this Agreement, the “ Research Plan ” and the activities contemplated thereby, the “ Research ”).  The Research Plan shall set forth the timeline and details of all the activities to be conducted by each Party or its Affiliates and, in the case of activities to be carried out by Adverum, the anticipated budget for all Research Costs (the “ Research Budget ”).  The initial version of the Research Plan, which has been agreed to by the Parties, is attached hereto as Exhibit D .

 

(b)

Research Plan Responsibilities .  Each Party shall be responsible for conducting the activities assigned to it in the Research Plan and shall conduct such activities in accordance with the Research Plan and, in the case of Adverum, the Research Budget.

 

(c)

Research Costs .  Editas shall be responsible for (i) all costs Editas incurs in performing its obligations under the Research Plan, and (ii) all Research Costs reasonably incurred by Adverum in performing its obligations under the Research Plan, subject to a maximum payment obligation of [***] of the Research Budget each Calendar Quarter or such greater amount as Editas may approve in writing, provided, that such approval must be obtained in advance of Adverum incurring expenses in excess of such amounts.  Adverum shall submit an invoice to Editas on a Calendar Quarter basis within [***] calendar days following the end of such Calendar Quarter for reimbursement of Research Costs, which invoice will set forth in detail the costs to be reimbursed, and Editas shall pay each such invoice within [***] days of receipt of such invoice to the extent (i) such invoice is not subject to a good faith dispute and (ii) is not, when taken together with any prior invoices, in excess of [***] of the Research Costs in the aggregate or [***] of the Research Costs allocated to the applicable Calendar Quarter.  In the event that Adverum anticipates that Research Costs will exceed the Research Budget by more than [***], Adverum shall promptly notify the JRC so that it may review any such

12.

 

[***] = Certain confidential information contained in this document, marked by brackets, is filed with the Securities and Exchange Commission pursuant to Rule 24b-2 of the Securities Exchange Act of 1934, as amended.


 

 

anticipated increase and propose an amend ment to the Research Budget , provided, that any change to the Research Budget shall require Editas’ written approval.

 

(d)

Revisions to Research Plan . The Parties agree and acknowledge that the initial version of the Research Plan is subject to change and that Editas may request that other studies or tasks be performed by Adverum with respect to Prototype Products, which Adverum shall agree to conduct, provided, that [***] (such requests, “ Additional Requests ”). Adverum shall propose to Editas within [***] business days (or [***] days in the event it is not practicable for Adverum to provide such proposal within [***] business days) (i) a reasonable increase of the Research Budget attributable to the Additional Request, including, without limitation, the number of necessary FTEs (and, for purposes of clarity, the costs of FTEs shall be the FTE rate [***]), and (ii) a reasonable timeframe for completing the Additional Request.  The scope of the Additional Request, as well as the related Research Budget and timeline, shall be subject to the mutual agreement of both Parties. In the event an Additional Request is mutually agreed to pursuant to the prior sentence, then the Research Plan and Research Budget shall be updated by the Parties to reflect such changes. If Editas [***], then Editas shall provide Adverum an Additional Request with respect to the research and development activities involving such [***], and Adverum shall provide [***], which Editas shall have the right to review and comment on.  Following the Parties’ agreement of [***] (the “ Other Viral Vector Agreement ”), the Research Plan and Research Budget shall be updated by the Parties to reflect such Other Viral Vector Agreement, and Adverum shall perform the research and development in accordance with such updated Research Plan.

 

(e)

Conflict .  If the terms of the Research Plan contradict, or create inconsistencies or ambiguities with, the terms of this Agreement, then the terms of this Agreement shall govern.

 

(f)

Conduct . Each Party shall, and cause any of its Affiliates to, conduct the activities assigned to such Party pursuant to the Research Plan: (i) in a professional manner; (ii) in accordance with good scientific practices and Applicable Law; and (iii) on a timely basis. Each Party shall ensure that all personnel employed or engaged by such Party in connection with the conduct of such activities are bound by written agreements to assign to such Party all of their right, title and interest in and to any Collaboration Invention. Other than routine service vendors, contract research organizations and clinical research organizations, neither Party shall use any Third Party to perform its obligations under the Research Plan unless approved in writing by the other Party, and as of the Effective Date, Editas approves Adverum’s use of [***] to perform its obligations under the Research Plan, provided, in all cases that each Party shall be liable for the actions and omissions of such Third Parties engaged by it. During the Research Period, Adverum shall devote substantially the number of FTEs to the conduct the Research as is specified in the Research Plan.  

13.

 

[***] = Certain confidential information contained in this document, marked by brackets, is filed with the Securities and Exchange Commission pursuant to Rule 24b-2 of the Securities Exchange Act of 1934, as amended.


 

 

(g)

Scope of Adverum Technology.   The central focus of the Research to be carried out by Adverum under this Agreement involves the testing and optimization of the Viral Vector for a potential Prototype Product, including, without limitation, any Other Viral Vector in accordance with the terms of Section 2 .2( d ) or Section 3.11 .  The Parties recognize that Adverum also possesses other technology , including [ *** ] that may be useful to individual Prototype Products.  Prior to incorporating any such Adverum technology into Prototype Products beyond Vector Technology, the Parties shall discuss the terms of any expanded license and, if mutually agreed, amend this Agreement accordingly.

 

(h)

Technology Transfer.   In order to facilitate the Research, each Party shall, as set forth in the Research Plan, provide to the other Party certain Materials and Know-How Controlled by the supplying Party for use by the other Party in furtherance of the Research. All Materials transferred pursuant to the Research Program shall be used (i) only for the specific purpose provided for in the Research Plan and (ii) solely under the control of the receiving Party. The Materials may not be used or delivered to or for the benefit of any Third Party without the prior written consent of the supplying Party, and shall not be used in research or testing involving human subjects, except within the scope of the commercial license under this Agreement. All Materials shall be returned to the supplying Party or destroyed (at the election of the supplying Party) promptly after completion of the use permitted under this Agreement. In order to properly assess whether it wants to exercise its option with respect to an Additional Indication, Editas shall have the right to reasonably request Materials and Know-How from Adverum that are necessary or reasonably useful for Editas to make such assessment, which Adverum shall supply to Editas within a reasonable timeframe, and which Editas can use solely to evaluate whether or not to exercise its Option with respect to an Additional Indication.

2.3

Research Data .

 

(a)

Records .  Each Party shall maintain, and shall ensure that personnel employed or engaged by such Party in connection with the activities under the Research Plan maintain complete, current, and accurate records of all activities conducted under the Research Plan (“ Research Records ”) and all Research Data.  Such records shall fully and properly reflect all work done and results achieved in good scientific manner appropriate for regulatory and patent purposes.  Each Party shall maintain such records in a professional manner in compliance with, and for as long as required by, all Applicable Laws.  Neither Party shall not destroy any such records without first providing the other Party a reasonable opportunity to take possession of such records.

 

(b)

Ownership.   All Research Records and Research Data shall be: (i) if [***] or [***] or [***] or [***], in each case, solely owned by Editas and deemed Editas’ Confidential Information; (ii) if [***] and [***] and/or [***], solely owned by Adverum and deemed Adverum’s Confidential Information; and (iii) if [***]

14.

 

[***] = Certain confidential information contained in this document, marked by brackets, is filed with the Securities and Exchange Commission pursuant to Rule 24b-2 of the Securities Exchange Act of 1934, as amended.


 

 

and/or [ *** ] , jointly owned by the Parties and deemed Confidential Information of both Parties .  Each Party hereby assigns its rights, title and interest in and to any such Research Records and Research Data to effectuate the intent of this S ection 2.3(b) .

 

(c)

Delivery .  Each Party shall provide the other Party updates to the Research Data (or sooner if contemplated by the Research Plan) (i) at each regularly schedule JRC meeting and (ii) upon reasonable request from the other Party. In addition, each Party shall provide the other Party with copies of all Research Data, to the extent not previously delivered, within thirty (30) days of completion of the Research. Following the expiration or termination of the Research Period, each Party shall deliver a final report to the JRC, which shall include a summary of all the Research Records and Research Data, including any raw data for the work conducted under the Research Plan.

2.4

Material Impediment .  In the event the Parties mutually agree, in good faith, that there has been a material impediment in using the Adverum Viral Vector for any Indication, then Editas shall have the right to terminate this Agreement with respect to such Indication pursuant to Section 12.3, provided that: (a) if such termination occurs prior to Editas’ exercise of its Option with respect to such termination, the non-exercise of such Option by Editas in such Indication shall not prejudice Editas’ option exercise with respect to any other Indication as set forth in Section 3.3; (b) Section 4.6 and the provisions pertaining to Non-Adverum Product(s), if applicable, shall survive such termination even if such termination occurs with respect to the Initial Indication.

3.

Option and LicenseS

3.1

Option Grant. Subject to the terms and conditions of this Agreement, Adverum hereby grants to Editas an exclusive option to obtain the License (“ Option ”) exercisable as set forth in Sections 3.2 and 3.3.

3.2

Option for Initial Indication .    Editas may elect, in its sole discretion, to exercise the Option with respect to the Initial Indication by providing written notice to Adverum at any time within twelve (12) months following the Effective Date (the “ Initial Option Exercise Period ”).  If Editas exercises such Option (the “ Option Exercise ”), it shall designate the Adverum Viral Vector that Editas selects for use with the Product directed to the Initial Indication and Editas shall (1) pay an exercise fee pursuant to Section 6.2 and (2) receive the license set forth in Section 3.4(a).  For clarity, Editas may, in its sole discretion, elect to use the Other Viral Vector solely with respect to [***] with respect to the Initial Indication solely in accordance with Section 4.6.

3.3

Option For Additional Indications.   Whether or not Editas exercises the Option with respect to the Initial Indication within the Initial Option Exercise Period, Editas shall have the right to elect, in its sole discretion, to exercise the Option with respect to one or more (and up to all) of the Additional Indications by providing written notice to Adverum, provided that Editas shall exercise all such Options within the three years

15.

 

[***] = Certain confidential information contained in this document, marked by brackets, is filed with the Securities and Exchange Commission pursuant to Rule 24b-2 of the Securities Exchange Act of 1934, as amended.


 

following the Effective Date (the “ Additional Indication Option Exercise Period ”), provided , that Editas has either made the Initial Option Exercise or has made an option exercise pursuant to this S e ction 3.3 during the two (2) year period following the Effective Date .  With each exercise of the Option with respect to each Additional Indication, Editas shall ( a ) pay the option exercise fee under Section 6.2 , ( b ) receive the license set forth in Section 3.4(a) with respect to such Additional Indication and (c ) designate the Adverum Viral Vector that will be used with the Product directed to such Additional Indication (which must be an Adverum Viral Vector and not the Other Viral Vector) .  I f there are any Additional Indications as to which Editas does not exercise the Option wi thin the Additional Indication Option Exercise Period, then: (i) the Option with respect to such Additional Indication(s) shall no longer be exercisable and the License granted under Section 3.4 shall be of no force or effect with respect to such Additional Indication(s); (ii) Adverum will be free to initiate, solicit, discuss, negotiate or enter into any agreement or arrangement with any Third Party regarding licensing or other disposition of any rights to the Adverum Technology with respect to such Additional Indication(s), without further obligation to Editas and (iii) Section 3.11 shall lapse with respect to such Additional Indication(s) .

3.4

License Grant to Editas .  As used herein, the term “ License ” shall refer to the license granted by Adverum to Editas under either Section 3.4(a) or 3.4(b), as the case may be.

 

(a)

If Editas designates an Adverum Viral Vector for use with a Product pursuant to Section 3.2 or Section 3.3, then Adverum shall grant and hereby grants to Editas, effective as of the License Effective Date, an exclusive (even as to Adverum), worldwide, royalty-bearing, license, with the right to sublicense as set forth in Section 3.8, under the Adverum Technology to Develop, make, have made, use, import, export, offer for sale, sell, and otherwise Commercialize such Product in the Field applicable to such Product (which, in the case of a License granted with respect to an Additional Indication, shall include any disease causing mutation related to such Additional Indication) in the Territory, but with respect only to Products that incorporate an Adverum Viral Vector.  This License (and the Parties’ rights and obligations thereunder) shall automatically become effective on the License Effective Date without the need for further action by the Parties.

 

(b)

If the Parties reach the Other Viral Vector Agreement, Adverum shall grant and hereby grants to Editas, effective as of the License Effective Date, an exclusive (even as to Adverum), worldwide, royalty-bearing, license, with the right to sublicense as set forth in Section 3.8, under the Adverum Technology (excluding, however, Vector Manufacturing Technology and any rights under the [***] Agreements) to Develop, use, import, export, offer for sale, sell, and otherwise Commercialize a Non-Adverum Product in the Initial Indication in the Field and in the Territory.  The License (and the Parties’ rights and obligations thereunder) shall automatically become effective on the License Effective Date without the need for further action by the Parties.

16.

 

[***] = Certain confidential information contained in this document, marked by brackets, is filed with the Securities and Exchange Commission pursuant to Rule 24b-2 of the Securities Exchange Act of 1934, as amended.


 

3.5

License Grant to Adverum .  Editas hereby grants to Adverum , effective as of the Effective Date, a non-exclusive, royalty-free license under the relevant Patents and Know-How Controlled by Editas (the “ Editas IP ”) solely to perform its obligations under the Research Plan and for no other purpose .

3.6

No Non-Permitted Use .  Editas hereby covenants that it will not, nor will it cause or permit any Affiliate or sublicensee to, knowingly use or practice, directly or indirectly, any Adverum Patents and/or Adverum Know-How transferred to Editas for any purposes other than those expressly permitted by this Agreement.  Adverum hereby covenants that it will not, nor will it cause or permit any Affiliate or sublicensee to, knowingly use or practice, directly or indirectly, any Editas IP transferred to Adverum for any purposes other than those expressly permitted by Section 3.5 of this Agreement.  Without limiting the foregoing, the Parties hereby covenant that they will not, nor will they cause or permit any Affiliate or sublicensee to: (a) derivatize or reverse engineer the other Party’s Materials (specifically, in the case of Editas, modify, derivatize or reverse engineer any Adverum Viral Vector), and/or (b) knowingly use or practice, directly or indirectly, any of the other Party’s intellectual property transferred pursuant to the terms of this Agreement for any purpose other than the research, Development, or Commercialization of the Products pursuant to this Agreement (specifically, in the case of Editas, research, Develop and/or Commercialize any Product outside an Indication for which Editas has exercised its Option therefor, except for a Non-Adverum Product in accordance with this Agreement).  

3.7

No Other Licenses .   Neither Party grants to the other Party any rights or licenses in or to any intellectual property, whether by implication or otherwise, other than the license rights that are expressly granted under this Agreement.

3.8

Sublicensing .

 

(a)

Restrictions .  Editas shall have the right to sublicense any of the license rights granted to it under Section 3.4 to any of its Affiliates or any Third Party, provided that: (i) each sublicense is generally consistent with the terms and conditions of this Agreement, (ii) each sublicense under Section 3.4(a) sets forth the date upon which Adverum’s license with respect to the [***] Patents expires, and (iii) Editas remains responsible for the performance of its obligations under this Agreement.

 

(b)

Copies .  Editas shall notify Adverum within thirty (30) days after execution of a sublicense entered into hereunder and provide a copy of the fully executed sublicense agreement to Adverum at the same time, which sublicense agreement shall be deemed the Confidential Information of Editas.  If Adverum is required by any Upstream Agreement to provide Adverum’s upstream licensor a copy of such sublicense agreement, Editas shall provide to Adverum a copy of such sublicense agreement which may be redacted to the extent permitted under such Upstream Agreement, as set forth in Section 3.9, and Adverum shall use and/or disclose such copy solely and only to the extent necessary to fulfill its obligations to such upstream licensor.

17.

 

[***] = Certain confidential information contained in this document, marked by brackets, is filed with the Securities and Exchange Commission pursuant to Rule 24b-2 of the Securities Exchange Act of 1934, as amended.


 

3.9

Upstream Agreements .

 

(a)

All licenses granted by Adverum under this Article 3, to the extent licensed or sublicensed to Adverum under an Upstream Agreement and licensed to Editas under this Article 3, are subject to the relevant terms and conditions of the Upstream Agreements.  Any exclusive licenses that are granted under this Article 3 that constitute sublicenses under the Upstream Agreements are exclusive only to the extent of the nature of the license granted to Adverum under the Upstream Agreements.  Editas acknowledges that it has received copies of the Upstream Agreements prior to the Effective Date.

 

(b)

Any sublicense granted to any Third Party under any of the [***] Agreements must include the following: (i) a statement setting forth the date upon which Adverum’s exclusive rights, privileges, and licenses to the Patents expire under the [***] Agreements, (ii) provisions passing through to sublicensees all of the rights of the [***] under the [***] Agreements and requiring the performance of all applicable obligations due under the [***] Agreements, other than those that are the direct obligations of Adverum, (iii) an indemnity from such sublicensee in favor of the [***] upon the same terms as set forth in such [***] Agreement.

 

(c)

Any sublicense granted to any Third Party under any of the [***] Agreements may provide such sublicensee the right to further sublicense only to the extent such sublicensee deems such sublicenses commercially reasonable, useful, or necessary for the development and/or commercialization of the Licensed Product(s) or Licensed Method(s) (solely for purposes of this Section 3.9(c), both as defined under Sections [***] of the [***] Agreements) in accordance with the [***] Agreements, provided that (i) such further sublicenses are subject to a written agreement, consistent with the terms and conditions of the [***] Agreements and (ii) each sublicensee shall, within thirty (30) days after issuing any further sublicense, furnish to Adverum, subject to any confidentiality provisions with third parties but in any event sufficient for Adverum to fulfill its obligations under the [***] Agreements, all material terms of any such sublicenses pertaining to the [***] interests, including the sublicensee name and address and the indemnification of the [***] as provided in the [***] Agreements.

 

(d)

Editas shall, within thirty (30) days following the grant of any sublicense under a [***] Agreement, provide to Adverum for delivery to the [***], subject to any confidentiality provisions with third parties but in any event sufficient for Adverum to fulfill its obligations under the [***] Agreements, all material terms of such sublicense pertaining to the [***] interests, including the sublicensee name and address, and confirmation of the foregoing indemnification. Additionally, Editas shall provide to Adverum so that Adverum can provide the [***] with a copy of each sublicense agreement, which may be redacted to protect sensitive information, but must contain sufficient information to assure the [***] that the sublicense is consistent with the [***] Agreement, and under no circumstances shall any financial terms necessary to calculate payments due to the

18.

 

[***] = Certain confidential information contained in this document, marked by brackets, is filed with the Securities and Exchange Commission pursuant to Rule 24b-2 of the Securities Exchange Act of 1934, as amended.


 

 

[***] be redacted. Editas consents to Adverum ’s provision of this Agreement to the [***] pursuant to Section [ *** ] of the [***] Agreements , subject to any confidentiality provisions with third parties but in any event sufficient for Adverum to fulfill its obligations under the [***] Agreements .

 

(e)

Pursuant to Sections [***] of the [***] Agreement [***], the Inventions (solely for purposes of this Section 3.9(e) and Section 3.9(g), as defined in the [***] Agreement [***]), were funded in part by the U.S. government.  Products covered by patent applications or patents claiming the Inventions and sold in the United States shall, to the extent required by applicable Law (including PL 96-517, as amended by PL 98-620), be substantially manufactured in the United States.

 

(f)

Pursuant to Section [***] of the [***] Agreements, for any Patent Rights licensed to Adverum pursuant to the [***] Agreements, upon termination of one or more of the [***] Agreements for any reason, so long as Editas is in compliance with this Agreement as of the date of such termination of the [***] Agreement(s), the license to the applicable Patent Rights under Section 3.4 shall survive termination of the [***] Agreement(s) and Editas shall be allowed, at its discretion, to become a direct licensee of the [***], provided that (i) each such direct license shall be subject to the same non-financial terms and conditions as those in the terminated [***] Agreement(s) except that the [***] shall not be bound to perform any duties or obligations set forth in this Agreement that extend beyond the duties and obligations of the [***] under the terminated [***] Agreement(s); (ii) Editas (or if there is at such time more than one surviving sublicensee, such sublicensees [***]) shall be required to make [***] payments due pursuant to Section [***] of the terminated [***] Agreement(s) or any [***] due pursuant to Section [***] of the terminated [***] Agreements; and (iii) Editas shall be required to make any other monetary payment(s) that, had the terminated [***] Agreement(s) not been terminated, Adverum would have been required to make under the [***] Agreements as a result of its license to or the activities of Editas.

 

(g)

[***] and [***] expressly reserve the right to [***] (solely for purposes of this Section 3.9(g), as defined in the [***] Agreements or with respect to [***], as defined in [***] Agreement [***]) for [***]; to [***] and [***], or [***] and/or [***] (solely for purposes of this Section 3.9(g), as defined in the [***] Agreements or with respect to [***], as defined in [***] Agreement [***]) to [***] for [***] and [***] for [***].

3.10

Non-Encumbrance . During the Initial Option Exercise Period, Adverum shall not, and shall cause its Affiliates not to, license, dispose of, sell, grant an option or any other right to acquire a right or license to, or otherwise transfer or encumber, directly or indirectly, any right, title or interest in the Adverum Technology or Vector Technology to any extent such Adverum Technology or Vector Technology is subject to the Option contemplated by Section 3.2(a), in a manner that would prevent Editas from obtaining the rights it would have otherwise obtained upon the exercise of the Option hereunder with respect to the Initial Indication. During the Additional Indication Option Exercise Period, Adverum

19.

 

[***] = Certain confidential information contained in this document, marked by brackets, is filed with the Securities and Exchange Commission pursuant to Rule 24b-2 of the Securities Exchange Act of 1934, as amended.


 

shall not, and shall cause its Affiliates not to, license, dispose of, sell, grant an option or any other right to acquire a right or license to, or otherwise transfer or encumber, directly or indirectly, any of its Adverum Technology or Vector Technology to any extent such Adverum Technology or Vector Technology is subject to the Option contemplated by Section 3.3 , in a manner that would prevent Editas from obtaining the rights it would have otherwise obtained upon the exercise of the Option hereunder with respect to such Additional Indication(s).

3.11

Exclusivity.   Other than as contemplated by this Agreement, Editas shall not have the right to conduct any [***] activities, either by itself or through any of its Affiliates or with a Third Party, with respect to [***] (including without limitation [***]) and directed at: (a) the [***] (other than [***]) or any [***], in each case, during the Option Period for such Indication; or (b) [***], (other than [***]) (such exclusivity, the “ Editas Exclusivity ”). Other than as contemplated by this Agreement, Adverum shall not have the right to conduct any [***] activities, either by itself or through any of its Affiliates or a Third Party, with respect to [***] (including without limitation [***] and directed at: (i) [***], in each case, during the Option Period [***]; or (ii) [***] (such exclusivity, the “ Adverum Exclusivity ”). Notwithstanding the foregoing sentence, Adverum and its Affiliates shall not have the right to [***] with respect to [***]. Notwithstanding the foregoing, (A) Editas may terminate this Agreement on an Indication-by-Indication basis by providing written notice to Adverum under Section 12.3, upon which termination the exclusivity obligation under this Section 3.11 with respect to such terminated Indication shall be of no further effect with respect to both Adverum and Editas; and (B) the Editas Exclusivity shall terminate with respect to the Initial Indication if the Agreement is terminated with respect to the Initial Indication for any material impediment in accordance with Section 2.4 of this Agreement. For purposes of clarity though, Editas may always terminate the Agreement on an Indication-by-Indication basis, including the Initial Indication, pursuant to clause (A) of this sentence and Section 12.3, regardless of whether there has been a material impediment pursuant to the terms of Section 2.4 of this Agreement.

4.

Development and Regulatory

4.1

Disclosure of Know-How. Following the License Effective Date, Adverum shall disclose to Editas such Adverum Know-How as Editas reasonably requires to carry out the Research Plan.  Thereafter, on a Calendar Quarter basis during the Term, Adverum, without additional consideration but at the reasonable request of Editas, shall disclose to Editas or its designated Affiliate any additional Adverum Know-How not previously disclosed, to the extent necessary for Editas’ conduct of the Research Plan during the Option Period or Editas’ practice of the license granted under Section 3.4 after its exercise of the Option.  

4.2

Development Costs.   Subject to Section 4.6, Editas shall be solely responsible, at its own cost, for the Development of Products in the Field in the Territory, other than any activities assigned to be performed by Adverum pursuant to the Research Plan.

20.

 

[***] = Certain confidential information contained in this document, marked by brackets, is filed with the Securities and Exchange Commission pursuant to Rule 24b-2 of the Securities Exchange Act of 1934, as amended.


 

4.3

Joint Development Committee .

 

(a)

Establishment .  The Parties will establish a Joint Development Committee (the “JDC”), composed of three (3) representatives of each Party, each of whom have experience in pharmaceutical discovery and development.  Within thirty (30) days following the notice by Editas that it is exercising its Option, each Party will designate its initial members to serve on the JDC and notify the other Party of the dates of availability for the first meeting of the JRC.  Each Party may replace its representatives on the JDC on written notice to the other Party.

 

(b)

Responsibilities .  The purpose of the JDC shall be to be solely advisory, to serve as a forum for Editas to present its activities related to the Development of a Product and to discuss and review the status, progress, and results of Editas’ performance of such Development .

 

(c)

Meetings .  The JDC Committee shall meet at least once every six months during the period commencing with Editas’ exercise of the Option and continuing until the date provided in Section 4.3(e) below.  The JDC shall hold its first meeting as soon as reasonably practicable following Editas’ exercise of the Option.  Meetings will be held at such place or places as are mutually agreed or by teleconference or videoconference.  Each Party may from time to time invite a reasonable number of participants who are under obligations of confidentiality consistent with this Agreement, in addition to its representatives, to attend JDC meetings, with the consent of the other Party (which shall not be unreasonably withheld).  At each JDC meeting, Editas will update, in its sole discretion, Adverum on, and the Parties will review and discuss, the status of Development activities with respect to the Products for the Indications for which Editas has exercised its Option.  Each Party shall solely bear all costs it incurs in connection with its participation at any meetings under this Section 4.3(c).

 

(d)

Decision Making .  The JDC shall have no decision-making authority.  The purpose of the JDC is to concurrently inform, to the extent and at the sole discretion of Editas, Adverum as to the ongoing Development of Products while enabling Adverum to provide informed advice to the extent useful.

 

(e)

Termination .  The JDC shall be disbanded at such time (i) that each Product being Developed by Editas under this Agreement has (A) commenced a Phase III clinical trial (first patient dosing), (B) been discontinued by Editas, (ii) Editas elects to disband the JDC or (iii) Editas has opted to terminate all Licenses for which it has exercised its Option.

4.4

[Intentionally Reserved]

4.5

Development Diligence .  Editas shall use Commercially Reasonable Efforts to Develop and Commercialize Products for use in the Field in the Territory for any Indication for which Editas has exercised its Option or, if the Parties have agreed [***] and, in each

21.

 

[***] = Certain confidential information contained in this document, marked by brackets, is filed with the Securities and Exchange Commission pursuant to Rule 24b-2 of the Securities Exchange Act of 1934, as amended.


 

case, to obtain Regulatory Approval for such Product in at least one of the Major Market Countries.  If Editas fails to commence or ceases to use Commercially Reasonable Efforts to Develop a Product pursuant to the prior sentence , Adverum may terminate the license granted to Editas under Section 3.4 with respect to such Product, in accordance with the procedures set forth in Section 12.5 . Without limitation of the foregoing, with respect to each Additional Indication as to which Editas exercises its Option pursuant to Section 3.3, Editas shall [ *** ] within [ *** ] following [ *** ] and [ *** ] within [ *** ] following the [ *** ] unless [ *** ] .  If Editas fails to achieve such milestones, Adverum may commence a proceeding under Section 12.5 to terminate Editas’ license rights to all Products directed to such Indication, subject to Editas’ rights to cure such breach as set forth in such Section 12.5 (it being recognized that in such event [ *** ] shall [ *** ] ).  Once Editas has [ *** ] , the diligence obligation for such Product shall [ *** ] . Notwithstanding the foregoing, Editas’ application of Commercially Reasonable Efforts [ *** ] in any country or territory in which [ *** ] for such Product .

4.6

Non-Adverum Product .  If the Parties have reached  the Other Viral Vector Agreement, then Adverum shall have the right to elect to co-develop and co-commercialize the Non-Adverum Product.  At the time Editas decides to [***] with respect to such Non-Adverum Product [***], Editas shall notify Adverum in writing and provide Adverum with a reasonable summary development plan and budget for such Non-Adverum Product, and Adverum shall then make such election within [***] after receiving such notice and information (a “ Co-Development and Co-Commercialization Election ”). If Adverum does not exercise such Co-Development and Co-Commercialization Election, such Non-Adverum Product shall be deemed the “ Royalty Non-Adverum Product .”  If Adverum exercises its Co-Development and Co-Commercialization Election with respect to the Non-Adverum Product, the Parties shall negotiate in good faith to prepare and enter into an agreement for Adverum to co-develop and co-commercialize such Non-Adverum Product, provided, that such agreement shall include the following terms: (i) an Adverum participation rate between [***] and [***] (the “ Participation Rate ”), which is at the election of Adverum, (ii) the Parties shall split all costs, including development and commercialization of the Non-Adverum Product, and gross profits related to the sale of the Non-Adverum Product, in each case, based on the Participation Rate, (iii) reasonable decision making authorities for such Non-Adverum Product taking into consideration the Participation Rate, and (iv) [***] between the Parties with respect to such Non-Adverum Product, and, to the extent [***] or [***] with respect to such Non-Adverum Product, [***] under the terms of such definitive agreement.  In the event the Parties do not reach agreement on the terms and conditions for such co-development and co-commercialization arrangements within [***] days, [***].

22.

 

[***] = Certain confidential information contained in this document, marked by brackets, is filed with the Securities and Exchange Commission pursuant to Rule 24b-2 of the Securities Exchange Act of 1934, as amended.


 

4.7

Development Reports .   To the extent the first sentence of Section 4.5 is applicable, Editas will keep Adverum fully informed regarding the progress and results of the Development activities conducted by or on behalf of Editas or its Affiliates or sublicensees . Such information shall constitute the Confidential Information of Editas .  Within sixty (60) days after each June 30 and December 31, Editas shall provide Adverum with a written report that summarizes all Development activities performed by or on behalf of Editas or its Affiliates or sublicensees during such the six month period preceding, as applicable, June 30 and December 31 .  

4.8

Standards of Conduct.   Editas shall perform, and shall ensure that its Affiliates, sublicensees, and Third Party contractors perform, all Development activities in good scientific manner and in compliance with all Applicable Laws.

4.9

Regulatory Filings .  As between the Parties, Editas shall be solely responsible, at its own expense (provided, that if Adverum has made the Co-Development and Co-Commercialization Election, then costs associated with a Non-Adverum Product shall be split between the Parties based on the Participation Rate), for preparing and filing all Regulatory Filings and seeking all Regulatory Approvals in the Territory, including preparing all reports necessary to obtain or maintain any Regulatory Approval.  As between the Parties, Editas shall be the legal and beneficial owner of all Regulatory Approvals in the Territory and shall be responsible for all communications and other dealings with the Regulatory Authorities relating to the Products in the Territory.

4.10

Manufacture and Supply .

 

(a)

Vector Supply Following Research.   During the performance of the Research Plan, the Parties shall consult regarding the most effective means of providing for the manufacture and supply of Viral Vectors for Editas following the Effective Date.  Except as set forth in the foregoing sentence, Editas shall be responsible for the manufacturing and supply of the Products under the Agreement, provided that, with respect to the manufacture and supply of the Adverum Viral Vector, Editas may: (i) engage Adverum to manufacture and supply the Adverum Viral Vector to Editas for Development and Commercialization purposes, either by itself or through Adverum’s contract manufacturer, under a mutually-agreed supply agreement at Adverum’s cost of goods (fully loaded using customary accounting allocations) [***]; or (ii)  engage a Third Party contract manufacturer mutually agreed by the Parties (provided, that Adverum will not unreasonably withhold its consent with respect to Editas choice of such Third Party) to manufacture and supply the Adverum Viral Vector to Editas for Development and Commercialization purposes.

 

(b)

Technology Transfer .  If Editas elects to transfer Product supply to a Third Party manufacturer pursuant to Section 4.10(a)(ii), upon written request from Editas, Adverum shall commence a technology transfer to such manufacturer of all Adverum Know-How related to the relevant Viral Vector as reasonably necessary for such manufacturer to be able to implement the manufacturing process used by

23.

 

[***] = Certain confidential information contained in this document, marked by brackets, is filed with the Securities and Exchange Commission pursuant to Rule 24b-2 of the Securities Exchange Act of 1934, as amended.


 

 

Adverum (or its Affiliate or CMO) to manufacture such Products.   Such transfer to a CMO shall occur under agreements reasonably satisfactory to Adverum to protect its Confidential Information.   Editas shall reimburse all reasonable out-of-pocket costs incurred by Adverum in the course of such technology transfer (including any payments to any contract manufacturer engaged by Adverum) plus compensate Adverum for its professional time at the FTE Rate , provided, that Adverum needs to estimate the related cost to be incurred in connection with such transfer and provide written notice to Editas of the anticipated cost prior to commencing it .   The Parties shall cooperate to complete such technology transfer as soon as reasonably practicable after its commencement.

 

(c)

Drug Master File.   If Editas elects a license under Section 3.4(a) and to the extent requested by Editas, Adverum shall on a timely basis establish a Drug Master File with the FDA and provide Editas rights of cross-reference thereto, at Editas’ expense.

5.

Commercialization

5.1

Commercialization.   Editas will be solely responsible for all aspects of Commercialization of the Product in the Field in the Territory, including planning and implementation, distribution, booking of sales, pricing and reimbursement.   The Commercialization of the Products shall be in Editas’ sole discretion.  

5.2

Commercialization Reports.   Following the First Commercial Sale, Editas shall keep Adverum fully informed regarding the progress and results of the Commercialization activities performed by or on behalf of Editas or its Affiliate or sublicensee.  Within [***] days after the end of each Calendar Quarter following the First Commercial Sale in a country, Editas shall provide Adverum with a written report that summarizes, in reasonable detail, all Commercialization activities performed in such country during such Calendar Quarter, and compares such performance with the goals and timelines set forth in the Commercialization Plan.  Editas shall also promptly provide Adverum with any additional information reasonably requested by Adverum regarding Commercialization.

5.3

Standards of Conduct. Editas shall perform, or shall ensure that its Affiliates, sublicensees and Third Party contractors perform, all Commercialization activities in a good scientific and ethical business manner and in compliance with all Applicable Laws.

24.

 

[***] = Certain confidential information contained in this document, marked by brackets, is filed with the Securities and Exchange Commission pursuant to Rule 24b-2 of the Securities Exchange Act of 1934, as amended.


 

6.

Fees and Payments

6.1

Option Grant Fee.   In consideration of the Option granted to Editas under Section 3.1, Editas shall pay to Adverum a one-time, non-refundable payment of one million dollars ($1,000,000) within [***] business days of the Effective Date; provided that five hundred thousand dollars ($500,000) of such payment shall be creditable against the amounts Editas may owe to Adverum pursuant to Section 2.2(c).

6.2

Option Exercise Fee.   Editas shall make a one-time, non-refundable, non‑creditable payment to Adverum of one million dollars ($1,000,000) for each Indication for which it exercises its Option to take a license under Section 3.4(a) within [***] business days after the applicable Option Exercise Date.

6.3

Development Milestones Payments .

 

(a)

Development Milestones for Products . Editas shall pay to Adverum the milestone payments set forth in the table below upon the first achievement of each milestone event by each Product whether such achievement is by or on behalf of Editas, its Affiliates, or sublicensees (and with respect to the Initial Indication, such payments are due whether or not Editas is also Developing a Royalty Non-Adverum Product and making development milestone payments under Section 6.3(b)) :

 

Milestone Event

Milestone Payment

1.     [***]

[***]

2.   [***]

[***]

3.   [***]

[***]

4.   [***]

[***]

Each milestone payment above shall be payable one time only for each Product to achieve the milestone. Under no circumstances shall Editas be obligated to pay Adverum more than [***] pursuant to this Section 6.3(a) for any one Product, no milestones will be due under this Section 6.3(a) with respect to a Royalty Non-Adverum Product and for purposes of determining the achievement of milestones contemplated by the foregoing, the definition of Product as defined in this Agreement shall be taken into account.

25.

 

[***] = Certain confidential information contained in this document, marked by brackets, is filed with the Securities and Exchange Commission pursuant to Rule 24b-2 of the Securities Exchange Act of 1934, as amended.


 

 

(b)

Development Milestones for Royalty Non-Adverum Product .  Editas shall pay to Adverum the milestone payments set forth in the table below upon the first achievement of each milestone event by the Royalty Non-Adverum Product (whether or not Editas is also Developing a Product directed to the Initial Indication and making development milestone payments under Section 6.3(a)) whether such achievement is by or on behalf of Editas, its Affiliates, or sublicensees:

 

Milestone Event

Milestone Payment

1.   [***]

[***]

2.   [***]

[***]

3.   [***]

[***]

4.   [***]

[***]

5.   [***]

[***]

Each milestone payment above shall be payable one time only for each Royalty Non-Adverum Product to achieve the milestone.  Under no circumstances shall Editas be obligated to pay Adverum more than [***] pursuant to this Section 6.3(b) for any one Royalty Non-Adverum Product. For purposes of clarity, (i) [***] a Royalty Non-Adverum Product [***] and [***] shall be treated as a single Royalty Non-Adverum Product and (ii) the foregoing milestones are only payable once for the Royalty Non-Adverum Product.

 

(c)

Notice and Payment .  Editas shall notify Adverum within ten [***] days after the achievement of any milestone event set forth in this Section 6.3.  Upon receipt of such notice, Adverum shall deliver an invoice to Editas regarding the achievement of such milestone and Editas shall pay to Adverum the applicable milestone payment within [***] days after the delivery of such invoice.

6.4

Commercial Milestone Payments .

 

(a)

Commercial Milestones .  Editas shall pay to Adverum the commercial milestone payments set forth below upon the first achievement by each Product of aggregate Net Sales in the Territory (i.e., cumulative sales from the first sale of such Product) exceeding the values indicated below.

 

Aggregate Net Sales of a Product

in the Territory

Milestone Payment

1.   Exceed [***]

[***]

2.   Exceed [***]

[***]

Each milestone payment above shall be payable one time only for each Product.  Under no circumstances shall Editas be obligated to pay Adverum more than [***] pursuant to this Section 6.4 for any one Product. For purposes of this Section 6.4, [***] any of the commercial milestones contemplated hereby.

26.

 

[***] = Certain confidential information contained in this document, marked by brackets, is filed with the Securities and Exchange Commission pursuant to Rule 24b-2 of the Securities Exchange Act of 1934, as amended.


 

 

(b)

Notice and Payment .  Editas shall notify Adverum within [***] days after the achievement of any milestone event set forth in Section 6.4(a) , whether sold by Editas, its Affiliates, or sublicensees.   Upon receipt of such notice, Adverum shall deliver an invoice to Editas regarding the achievement of such milestone and Editas shall pay to Adverum the applicable milestone payment within [***] days after the delivery of such invoice.

6.5

Royalty Payments .

 

(a)

Royalty Rate for Products .  Editas shall make quarterly royalty payments to Adverum, on a Product-by-Product basis, on the Net Sales of each Product sold in the Territory during the applicable Royalty Term, as calculated by multiplying the applicable royalty rate set forth below by the corresponding amount of Net Sales of such Product in the applicable Calendar Year.  

 

Annual Net Sales of each Product in the Territory

Royalty

Rate

For that portion of annual Net Sales less than or equal

   to [***]

[***]

For that portion of annual Net Sales greater than [***]

   but less than or equal to [***]

[***]

For that portion of annual Net Sales greater than [***]

[***]

 

(b)

Royalty Rate for Royalty Non-Adverum Products .  Editas shall make quarterly royalty payments to Adverum on the Net Sales of the Royalty Non-Adverum Product sold in the Territory during the applicable Royalty Term, as calculated by multiplying the applicable royalty rate set forth below by the corresponding amount of Net Sales of the Royalty Non-Adverum Product in the applicable Calendar Year.  

 

Annual Net Sales of each Royalty Non-Adverum

Product in the Territory

Royalty

Rate

For that portion of annual Net Sales less than or equal

   to [***]

[***]

For that portion of annual Net Sales greater than [***]

   but less than or equal to [***]

[***]

For that portion of annual Net Sales greater than [***]

[***]

 

(c)

Royalty Term . Royalties shall be paid on a Product-by-Product and Royalty Non-Adverum Product-by Royalty Non-Adverum Product basis in the Territory from the First Commercial Sale of such Product or the Royalty Non-Adverum Product, as applicable, in such country until the latest of (i) expiration of the last‑to‑expire Valid Claim of the Adverum Patents Covering such Product or Royalty Non-Adverum Product, as applicable, in such country; (ii) the expiration of any Regulatory Exclusivity for such Product or Royalty Non-Adverum

27.

 

[***] = Certain confidential information contained in this document, marked by brackets, is filed with the Securities and Exchange Commission pursuant to Rule 24b-2 of the Securities Exchange Act of 1934, as amended.


 

 

Product, as applicable, in such country; or (iii)  [***] years after the First Commercial Sale of such Product or Royalty Non-Adverum Product, as applicable, in such country (the “ Royalty Term ”).

 

(d)

Patent Expiration . If the Applicable Laws in a particular country or jurisdiction requires a royalty reduction after the expiration of the relevant patents, and the Royalty Term for a particular Product or Royalty Non-Adverum Product, as applicable, in a country or jurisdiction extends beyond the time period set forth in Section 6.5(c)(i), then the royalty rates provided in Section 6.5 shall be reduced by [***] for such Product or Royalty Non-Adverum Product, as applicable, in such country during the remainder of the Royalty Term that extends beyond the time period set forth in Section 6.5(c)(i).

 

(e)

Third Party Licenses .  If it is necessary for Editas, its Affiliates, or sublicensees to obtain a license from a Third Party under such Third Party’s Patents, Know-How or any other intellectual property right to manufacture, use or sell a Product or Royalty Non-Adverum Product, as applicable, in the Field in the Territory or Editas has already obtained a license to such rights, then Editas shall have the right to credit [***] of the payments made to such Third Party pursuant to such license against any royalty payments owed to Adverum hereunder with respect to such Product or Royalty Non-Adverum Product, as applicable, subject to Section 6.5(g).

 

(f)

Generic Products .  If one or more Generic Products to a Product or Royalty Non-Adverum Product, as applicable, is sold in any country in the Territory during the Royalty Term for such Product or Royalty Non-Adverum Product, as applicable, in such country, and such Generic Products in the aggregate have a unit market share in that country of greater than or equal to [***] during that Calendar Year, the royalty rates provided in Section 6.5(a) for such Product or Royalty Non-Adverum Product, as applicable, shall be reduced in such country by [***] for such Calendar Quarter.

 

(g)

Royalty Floor .  In no event will the royalty reduction in Sections 6.5(d), (e) and (f) (by itself or in any combination) reduce the average royalty rate payable for any Product or Royalty Non-Adverum Product in any Calendar Year to an amount less than [***] or [***] , respectively.

6.6

Sublicensee Revenue.   Editas shall make annual payments to Adverum on any Sublicensee Revenue received by Editas during the applicable Calendar Year, as calculated by multiplying the sublicense fee of [***] by the corresponding amount of Sublicensee Revenue received during the applicable Calendar Year, provided, however, that if the transaction giving rise to the Sublicensee Revenue included the grant of any other intellectual property rights to the sublicensee in addition to rights to Products, Editas may reasonably apportion the proceeds it receives that would otherwise constitute Sublicensee Revenue as between the Products and other products included in such license grant, based on the relative value of the Products and such other products.  In addition, Editas may

28.

 

[***] = Certain confidential information contained in this document, marked by brackets, is filed with the Securities and Exchange Commission pursuant to Rule 24b-2 of the Securities Exchange Act of 1934, as amended.


 

credit against payments due under this Section 6.6 , milestone payments previously made by Editas under Section 6.3 , to the extent the milestone payments under Section 6.3 were made in respect of the achievement of a milestone by the same sublicensee, and the same intellectual property rights , that were the subject of the transaction which generated the Sublicensee Revenue giving rise to the payment under this Section 6.6 .

6.7

Upstream Payments .  Adverum will be solely responsible for all payments due to Third Parties after the Effective Date pursuant to Upstream Agreements, including, for the avoidance of doubt, the [***] Agreements.

7.

Payment; Records; Audits

7.1

Payment; Reports .

 

(a)

Royalties .  Following the First Commercial Sale, Editas will calculate and report royalty payments due by Editas to Adverum under Section 6.5 each Calendar Quarter.  Editas shall pay all royalty payments due under Section 6.5 within [***] days after the end of each Calendar Quarter and shall include with each payment a report setting forth, on a country-by-country and Product-by-Product basis, (i) the number of Products manufactured and the number of Products sold in such Calendar Quarter, (ii) the amount of gross sales of the Products in such Calendar Quarter, (iii) the amount of Net Sales of the Product in such Calendar Quarter, (iv) a calculation of the royalty payment due on such sales, including the application of any reduction made in accordance with Section 6.5(d), 6.5(e), and/or 6.5(f), and (v) the exchange rate for such country.

 

(b)

Sublicense Revenue.   Editas will calculate and report Sublicensee Revenue payments due by Editas to Adverum under Section 6.6 each Calendar Year, provided, that no such report shall be required to be delivered by Editas if there was no Sublicense Revenue for the applicable Calendar Year.  Editas shall pay all payments due under Section 6.6 within [***] days after the end of each Calendar Year and shall include with each payment a report setting forth the amount and description of all Sublicensee Revenue received by Editas and its Affiliates during such Calendar Quarter, and a calculation of the payment due to Adverum on such Sublicensee Revenue pursuant to Section 6.6.

7.2

Exchange Rate; Manner and Place of Payment .  All references to dollars and “$” herein shall refer to U.S. dollars.  All payments hereunder shall be payable in U.S. dollars.  When conversion of payments from any currency other than U.S. dollars is required, such conversion shall be at an exchange rate equal to the weighted average of the rates of exchange for the currency of the country from which such payments are payable as published by The Wall Street Journal , Western U.S. Edition, during the Calendar Quarter in which the applicable sales were made.  All payments owed under this Agreement shall be made by wire transfer in immediately available funds to a bank and an account designated in writing by Adverum.

29.

 

[***] = Certain confidential information contained in this document, marked by brackets, is filed with the Securities and Exchange Commission pursuant to Rule 24b-2 of the Securities Exchange Act of 1934, as amended.


 

7.3

Taxes .

 

(a)

Taxes on Income .  Each Party shall be solely responsible for the payment of all taxes imposed on its share of income arising directly or indirectly from the activities of the Parties under this Agreement.

 

(b)

Tax Cooperation .  The Parties agree to cooperate with one another and use reasonable efforts to avoid or reduce tax withholding or similar obligations in respect of royalties, milestone payments, and other payments made by Editas to Adverum under this Agreement.  To the extent Editas is required to deduct and withhold taxes on any payment to Adverum, Editas shall deduct those taxes from such payment, pay the amounts of such taxes to the proper Governmental Authority in a timely manner, and promptly transmit to Adverum an official tax certificate or other evidence of such withholding sufficient to enable Adverum to claim such payment of taxes.  Adverum shall provide Editas any tax forms that may be reasonably necessary in order for Editas not to withhold tax or to withhold tax at a reduced rate under an applicable bilateral income tax treaty.  Each Party shall provide the other with reasonable assistance to enable the recovery, as permitted by Applicable Laws, of withholding taxes, value added taxes, or similar obligations resulting from payments made under this Agreement, such recovery to be for the benefit of the Party bearing such withholding tax or value added tax.

7.4

Records; Audit .  Editas shall keep, and shall require its Affiliates and sublicensees to keep, complete and accurate records pertaining to the sale or other disposition of Products in sufficient detail to permit Adverum to confirm the accuracy of commercial milestone and royalty payments due hereunder.  Adverum shall keep complete and accurate records pertaining to the Research Costs in sufficient detail to permit Editas to confirm the accuracy of the incurrence of Research Costs by Adverum. In each case, such records shall be kept for [***] years following the end of the Calendar Quarter to which they pertain.  Adverum shall have the right to have an independent, certified public accountant reasonably acceptable to Editas audit such records to confirm Net Sales, royalties, commercial milestone payments, and Sublicense Revenue payments for a period covering not more than [***] years following the Calendar Quarter to which they pertain.  Such audits may be conducted during normal business hours upon reasonable prior written notice to Editas, and not more than [***] per Calendar Year.  Any such auditor shall not disclose Editas’ Confidential Information to Adverum, except to the extent such disclosure is necessary to verify the accuracy of the financial reports furnished by Editas or the amount of payments by Editas under this Agreement, and shall enter into a customary confidentiality agreement with Editas.  Any amounts shown to be owed but unpaid shall be paid within [***] days after the accountant’s report.  Any overpayment by Editas revealed by an audit shall be credited against future payments owed by Editas to Adverum (and if no further payments are due, shall be refunded by Adverum to Editas within [***] days after the accountant’s report).  Editas shall have the right to audit Adverum’s records regarding the incurrence of Research Costs by Adverum and, in the event of an overpayment by Editas to Adverum for such Research Costs, Adverum shall

30.

 

[***] = Certain confidential information contained in this document, marked by brackets, is filed with the Securities and Exchange Commission pursuant to Rule 24b-2 of the Securities Exchange Act of 1934, as amended.


 

refund such overpayment to Editas within [***] calendar days following the date on which Editas discovers such overpayment. The cost of any audit initiated by a Party pursuant to this Agreement shall be borne by the Party initiating such audit , provided that, if such audit discloses an underpayment by the audited Party of more than [***] for the audited period or [***] , whichever is greater, the audited Party shall bear the reasonable cost of such audit.

7.5

Late Payments.   In the event that any undisputed payment due under this Agreement is not paid when due in accordance with the applicable provisions of this Agreement, the payment shall accrue interest from the date due at the annual interest rate of [***]; provided, however, that in no event shall such rate exceed the maximum legal annual interest rate.  The payment of such interest shall not limit the Party entitled to receive payment from exercising any other rights it may have as a consequence of the lateness of any payment.

8.

Intellectual Property

8.1

Ownership .

 

(a)

Vector Inventions and Adverum Expression Elements .  Adverum shall solely own all Vector Inventions and all Expression Element Inventions that constitute improvements to Adverum Expression Elements (collectively, “ Vector Related Inventions ”).  Editas shall assign and hereby assigns to Adverum all of its right, title and interest in and to all Vector Related Inventions.  

 

(b)

Therapeutic Inventions and Editas Expression Elements .   Editas shall own all Therapeutic Inventions and all Expression Element Inventions that constitute improvements to Editas Expression Elements (collectively, “ Therapeutic Related Inventions ”).  Adverum shall assign and hereby assigns all of its right, title and interest in and to Therapeutic Related Inventions.

 

(c)

Other Inventions .  Ownership of all Inventions other than those contemplated by Sections 8.1(a) and (b) shall be based on inventorship, as determined in accordance with the rules of inventorship under United States patent laws.  Each Party shall solely own any Inventions made solely by its or its Affiliates’ employees, agents, or independent contractors (“ Sole Inventions ”).  The Parties shall jointly own any Inventions that are made jointly by employees, agents, or independent contractors of one Party or its Affiliates together with employees, agents, or independent contractors of the other Party or its Affiliates (“ Joint Inventions ”).  All Patents claiming Joint Inventions shall be referred to herein as “ Joint Patents. ”  Except to the extent either Party is restricted by the licenses granted to the other Party under this Agreement, each Party shall be entitled to practice, license, assign, and otherwise exploit the Joint Inventions and Joint Patents without the duty of accounting or seeking consent from the other Party.

31.

 

[***] = Certain confidential information contained in this document, marked by brackets, is filed with the Securities and Exchange Commission pursuant to Rule 24b-2 of the Securities Exchange Act of 1934, as amended.


 

8.2

Patent Prosecution .

 

(a)

Adverum Patents .

 

(i)

Subject to Section 8.2(a)(ii), as between the Parties, Adverum shall have the first right, but not the obligation, to control the preparation, filing, prosecution, and maintenance (including any interferences, derivation proceedings, reissue proceedings, reexaminations, patent term extensions, applications for supplementary protection certificates, oppositions, invalidation proceedings and defense of validity or enforceability challenges) of the Adverum Patents (other than Joint Patents) worldwide, at its sole cost and expense and using counsel of its own choice.  Adverum shall keep Editas informed of material progress with regard to the preparation, filing, prosecution, and maintenance of Adverum Patents, sufficiently in advance for Editas to be able to review any material documents, including content, timing, and jurisdiction of the filing of such Adverum Patents, and Adverum shall consult with, and consider in good faith the requests and suggestions of, Editas with respect to strategies for filing, prosecuting, and defending, if any, Adverum Patents in the Territory.

 

(ii)

If, during the Term, Adverum desires to abandon or cease prosecution or maintenance of any Adverum Patent in any country in the Territory, Adverum shall provide reasonable prior written notice to Editas of such intention to abandon (which notice shall, to the extent practical, be given no later than sixty (60) days prior to the next deadline for any action that must be taken with respect to any such Adverum Patent in the relevant patent office).  In such case for an Adverum Patent which is not a [***] Patent, Editas shall have the right, but not the obligation, to assume responsibility for the prosecution and maintenance of such Adverum Patent in the name of Adverum and at the expense of Editas.  In such case for a [***] Patent, upon Editas’ written election provided no later than thirty (30) days after such notice from Adverum, Adverum shall notify the [***] to continue prosecution and maintenance of such [***] Patent at Editas’ direction and reasonable expense and subject to the [***] Agreement.

 

(b)

Joint Patents .  [***] shall have the first right, but not the obligation, to control the preparation, filing, prosecution, and maintenance (including any interferences, derivation proceedings, reissue proceedings, reexaminations, patent term extensions, applications for supplementary protection certificates, oppositions, invalidation proceedings and defense of validity or enforceability challenges) of all Joint Patents, except for those that are [***], worldwide, at its own cost and by counsel of its own choice, but which is reasonably acceptable to [***]. [***] shall have the first right, but not the obligation, to control the preparation, filing, prosecution, and maintenance (including any interferences, reissue proceedings,

32.

 

[***] = Certain confidential information contained in this document, marked by brackets, is filed with the Securities and Exchange Commission pursuant to Rule 24b-2 of the Securities Exchange Act of 1934, as amended.


 

 

reexaminations, patent term extensions, applications for supplementary protection certificates, oppositions, invalidation proceedings and defense of validity or enforceability challenges) of all Joint Patents worldwide that [***] , at its own cost and by counsel of its own choice, but which is reasonably acceptable to [***] .  Each Party shall keep the other Party informed of the status of each such Joint Patent for which it is controlling prosecution , and shall reasonably consider the other Party’s suggestions or recommendations concerning the preparation, filing, prosecution, and maintenance thereof.  If, during the Term, the Party having the first right under this Section 8.2(b) intends not to file or continue prosecuting or maintaining a Joint Patent, such Party shall notify the other Party of such intention at least thirty (30) days prior to any applicable deadline, and the other Party shall have the right, but not the obligation, to assume responsibility for the prosecution and maintenance of such Joint Patent, in the joint name of the Parties and at the expense of the Party assuming control.

 

(c)

Cooperation .  The Parties agree to reasonably cooperate in the preparation, filing, prosecution, and maintenance of all Patents under this Section 8.2, including obtaining and executing necessary powers of attorney and assignments by the named inventors, providing relevant technical reports to the filing Party concerning the invention disclosed in such Patent, obtaining execution of such other documents which shall be needed in the filing and prosecution of such Patent, and, as requested, updating each other regarding the status of such Patent, and shall cooperate with the other Party so far as reasonably necessary with respect to furnishing all information and data in its possession reasonably necessary to obtain or maintain such Patents.  For clarity, neither Party shall have the right to file, prosecute or maintain any Patents claiming or disclosing Collaboration Inventions made by it but are assigned to the other Party under Section 8.1.

8.3

Infringement by Third Parties .

 

(a)

Notice .  Each Party shall notify the other within fifteen (15) business days of becoming aware of any alleged or threatened infringement by a Third Party of any of the Adverum Patents (including Joint Patents) in the Territory, including any declaratory judgment, opposition, or similar action alleging the invalidity, unenforceability, or non-infringement of any of the Adverum Patents or other Joint Patents.

 

(b)

Enforcement Right .  If Editas believes that a Third Party is infringing an Adverum Patent through the Commercialization of a product that competes directly with a Product (“ Field Infringement ”), Editas shall confer with Adverum regarding the possible assertion of such Adverum Patent against such Third Party.  [***] shall then have the right, but not the obligation, to bring and control any action or proceeding with respect to infringement of such Adverum Patent(s) (including Joint Patents) in the Field and in the Territory, at its own expense and by counsel of its own choice, but which is reasonably acceptable to

33.

 

[***] = Certain confidential information contained in this document, marked by brackets, is filed with the Securities and Exchange Commission pursuant to Rule 24b-2 of the Securities Exchange Act of 1934, as amended.


 

 

[***] .   [***] shall have the right, at their own expense, to be represented in any such action by counsel of their own choice, and [***] and their counsel will reasonably cooperate with [***] and its counsel in strategizing, preparing, and litigating any such action or proceeding.  I f [***] fails to bring an action or proceeding with respect to infringement of any Adverum Patent in the Field and within the Territory within (A)  [***] days following a notice of alleged infringement by Adverum to Editas or (B)  [***] days before the time limit, if any, set forth in the appropriate laws and regulations for the filing of such actions, whichever comes first, and after considering, in good faith, [***] reasons for not bringing an action, [***] shall have the right, but not the obligation, to bring and control any such action at its own expense and by counsel of its own choice, and [***] shall have the right, at its own expense, to be represented in any such action by counsel of its own choice.    Adverum shall retain the sole right, exclusive of Editas, to (A) commence and control any enforcement action for Adverum Patents involving Third Party infringement outside of the Field and (B) control the defense of any Third Party challenges to the validity or enforceability of the Adverum Patents not arising from an assertion of Field Infringement.

 

(c)

Recovery .   Except as otherwise agreed by the Parties as part of a cost-sharing arrangement, any recovery or damages realized as a result of such action or proceeding with respect to Adverum Patents or Joint Patents shall be used first to reimburse the Parties’ reasonable and documented out-of-pocket legal expenses relating to the action or proceeding, and any remaining compensatory damages relating to Products and/or Joint Patents (including lost sales or lost profits with respect to Products) and punitive damages shall be retained by the Party that brought and controlled such action or proceeding, and in the case that Editas brought and controlled such action or proceeding, such remaining compensatory and punitive damages for the Territory shall be deemed to be Net Sales subject to royalty payments to Adverum in accordance with the royalty provisions of Section 6.5 .

 

(d)

Cooperation.   In the event that a Party brings an action in accordance with this Section 8.3, the other Party shall cooperate fully, including, if required to bring such action, the furnishing of a power of attorney or being named as a party to such action.

8.4

Infringement of Third Party Rights.   If any Product used or sold by Editas, its Affiliates, or sublicensees becomes the subject of a Third Party’s claim or assertion of infringement of any intellectual property rights in a jurisdiction within the Territory, Editas shall promptly notify Adverum and the Parties shall promptly meet to consider the claim or assertion and the appropriate course of action and may, if appropriate, agree on and enter into a “common interest agreement” wherein the Parties agree to their shared, mutual interest in the outcome of such potential dispute.  Absent any agreement to the contrary, and subject to claims for indemnification under Article 10, each Party will defend itself from any such Third Party claim at its own cost and

34.

 

[***] = Certain confidential information contained in this document, marked by brackets, is filed with the Securities and Exchange Commission pursuant to Rule 24b-2 of the Securities Exchange Act of 1934, as amended.


 

expense, provided, however, that the provisions of Section 8.3 shall govern the right of the Parties to assert a counterclaim of infringement of any Adverum Patent or Joint Patent.

8.5

Consent for Settlement.   Neither Party shall unilaterally enter into any settlement or compromise of any action or proceeding under this Article 8 that would in any manner alter, diminish, or be in derogation of the other Party’s rights under this Agreement without the prior written consent of such other Party, which shall not be unreasonably withheld.

8.6

Patent Marking. Editas shall, and shall require its Affiliates and sublicensees to, mark Products sold hereunder (in a reasonable manner consistent with industry custom and practice) with appropriate patent numbers or indicia to the extent permitted by Applicable Law, in those countries in which such markings or such notices impact recoveries of damages or equitable remedies available with respect to infringements of patents.

9.

Representations, Warranties, and Covenants

9.1

Representations, Warranties and Covenants by Each Party.   Each Party represents, warrants, and/or covenants (as applicable) to the other the following:

 

(a)

Corporate Existence .  As of the Effective Date, it is a company or corporation duly organized, validly existing, and in good standing under the Applicable Laws of the jurisdiction in which it is incorporated.

 

(b)

Corporate Power, Authority and Binding Agreement .  As of the Effective Date, (i) it has the corporate power and authority and the legal right to enter into this Agreement and perform its obligations hereunder; (ii) it has taken all necessary corporate action on its part required to authorize the execution and delivery of this Agreement and the performance of its obligations hereunder; and (iii) this Agreement has been duly executed and delivered on behalf of such Party, and constitutes a legal, valid, and binding obligation of such Party that is enforceable against it in accordance with its terms.

 

(c)

Employees, Consultants and Contractors.   Each Party has obtained written agreements from each of its employees, consultants, and contractors who perform any activity under this Agreement, which agreements will obligate such persons to obligations of confidentiality and non-use and to assign Inventions in a manner consistent with the provisions of this Agreement.

 

(d)

Debarment.   Each Party is not debarred or disqualified under the U.S. Federal Food, Drug and Cosmetic Act, as may be amended, or comparable laws in any country or jurisdiction other than the U.S., and it does not, and will not during the Term, employ or use the services of any person who is debarred or disqualified, in connection with activities relating to any Product.  In the event that either Party becomes aware of the debarment or disqualification or

35.

 

[***] = Certain confidential information contained in this document, marked by brackets, is filed with the Securities and Exchange Commission pursuant to Rule 24b-2 of the Securities Exchange Act of 1934, as amended.


 

 

threatened debarment or disqualification of any person providing services to such Party, including the Party itself or its Affiliates or sublicensees, that directly or indirectly relate to activities contemplated by this Agreement, such Party shall immediately notify the other Party in writing and such Party shall cease employing, contracting with, or retaining any such person to perform any such services.

9.2

Representations, Warranties and Covenants by Adverum.   Adverum represents, warrants and/or covenants (as applicable) to Editas as of the Effective Date and as of the date of any Option exercise (other than set forth in any schedule of exceptions provided by Adverum to Editas following Adverum’s receipt of the notification of any Option exercise, provided, that such schedule of exceptions can only modify the following: 9.2(c), 9.2(d), 9.2(e), 9.2(f) and 9.2(g), and to the extent Adverum delivers such schedule of exceptions, Editas can rescind its Option and Adverum shall refund any amounts paid by Editas in connection with such Option exercise) that:

 

(a)

Adverum has the full and legal rights and authority to grant Editas the Option and the License;

 

(b)

Adverum has not granted, and will not grant, to any Third Party any rights to the Adverum Technology that would otherwise interfere or be inconsistent with Editas’ rights hereunder;

 

(c)

Adverum has not received any notice from any Third Party asserting or alleging that the manufacture, use, sale, offer for sale, supply, or importation by Adverum (or its Affiliates) of products employing the Adverum Technology infringes any claim of an issued Patent of any Third Party, or if and when issued, any claim within any published Patent existing as of the Effective Date of any Third Party, in the Territory in the Field;

 

(d)

There are no judgments or settlements against or owed by Adverum or any of its Affiliates with respect to the Adverum Technology, and there is no action, claim, demand, suit, proceeding, arbitration, citation, summons, subpoena or investigation of any nature, civil, criminal, regulatory or otherwise, in law or in equity, pending or, to the knowledge of Adverum, threatened against Adverum or any of its Affiliates, in each case in connection with the Adverum Technology or relating to the transactions contemplated by this Agreement;

 

(e)

All Upstream Agreements as of the Effective Date are listed on Exhibit B .

 

(f)

Adverum is not, and to Adverum’s knowledge, the other parties thereto are not, in material breach, violation or default under any of the agreements listed on Exhibit B and there does not exist, to the knowledge of Adverum, any event that, with the giving of notice or the lapse of time or both, would constitute such a breach, violation or default. Each of the agreements listed on Exhibit B (i) constitutes a valid and binding obligation of Adverum, and (ii) to Adverum’s

36.

 

[***] = Certain confidential information contained in this document, marked by brackets, is filed with the Securities and Exchange Commission pursuant to Rule 24b-2 of the Securities Exchange Act of 1934, as amended.


 

 

knowledge, is binding and enforceable against the other parties thereto.  Neither Adverum nor any of its Affiliates has received or given any written notice, of an intention to terminate, not renew or challenge the validity or enforceability of any of the agreements listed on Exhibit B ;

 

(g)

Adverum has provided to Editas, or allowed Editas access to review, a true and complete copy of each Upstream Agreement.  Each Upstream Agreement is, to Adverum’s knowledge, in full force and effect as of the Effective Date. Adverum shall maintain each Upstream Agreement in full force and effect and to perform its obligations thereunder in all material respects, and to keep Editas informed of any material development pertaining thereto that would reasonably be expected to have a material adverse effect on Editas’ rights under this Agreement;

 

(h)

Adverum shall not, without the prior written approval of Editas, (i) amend or waive any provision of an Upstream Agreement that would adversely impact Editas’ rights under this Agreement, (ii) make any election or exercise any right or option to terminate in whole or in part any Upstream Agreement or (iii) make any election or exercise any right or option that would result in the increase in any royalties owed by Adverum under any Upstream Agreement; and

 

(i)

Adverum shall promptly provide to Editas true and correct copies of all reports generated in respect of the Upstream Agreements or received from a counterparty to any Upstream Agreements, in each case that are relevant to activities conducted under or rights and licenses granted under this Agreement, provided that Adverum shall be permitted to redact from such reports any information that Adverum is restricted from disclosing due to confidentiality obligations to Third Parties.

9.3

No Other Warranties.   EXCEPT AS EXPRESSLY SET FORTH IN THIS AGREEMENT, EACH PARTY EXPRESSLY DISCLAIMS ANY AND ALL WARRANTIES OF ANY KIND, EXPRESS OR IMPLIED, INCLUDING THE WARRANTIES OF DESIGN, MERCHANTABILITY, FITNESS FOR A PARTICULAR PURPOSE, NONINFRINGEMENT OF THE INTELLECTUAL PROPERTY RIGHTS OF THIRD PARTIES, OR ARISING FROM A COURSE OF DEALING, USAGE OR TRADE PRACTICES.  MATERIALS ARE PROVIDED “AS IS” AND WITHOUT ANY REPRESENTATION O WARRANTY. Without limiting the foregoing, neither Party represents or warrants the success of any study or test conducted by it pursuant to this Agreement or the safety or usefulness for any purpose of the technology it provides hereunder.

10.

Indemnification

10.1

Indemnification by Adverum .  Adverum shall defend, indemnify, and hold Editas and its Affiliates and their respective officers, directors, employees, and agents (the “ Editas Indemnitees ”) harmless from and against any and all damages or other amounts payable to a Third Party claimant, as well as any reasonable attorneys’ fees and costs of litigation incurred by such Editas Indemnitees, resulting from any claims, suits, proceedings or

37.

 

[***] = Certain confidential information contained in this document, marked by brackets, is filed with the Securities and Exchange Commission pursuant to Rule 24b-2 of the Securities Exchange Act of 1934, as amended.


 

causes of action brought by such Third Party (collectively, “ Claims ”) against such Editas Indemnitee to the extent arising from or based on (a) the conduct of the activities under the Research Plan by or on behalf of Adverum or its Affiliates except when such activities are included in the Research Plan determined through Editas’ final decision making authority , (b) the material breach of any of Adverum ’s obligations, representations, or warranties under this Agreement, or ( c ) the willful misconduct or grossly negligent acts of Adverum , its Affiliates, or the officers, directors, employees, or agents of Adverum or its Affiliates.  The foregoing indemnity obligation shall not apply to the extent that (i) the Editas Indemnitees fail to comply with the indemnification procedures set forth in Section 10.3 and Adverum ’s defense of the relevant Claims is prejudiced by such failure, or (ii) any Claim arises from or is based on any activity set forth in Section 10. 2 for which Editas is obligated to indemnify the Adverum Indemnitees under Section 10.2 .

10.2

Indemnification by Editas .  Editas shall defend, indemnify, and hold Adverum and its Affiliates and their respective officers, directors, employees, and agents (the “ Adverum Indemnitees ”) harmless from and against damages or other amounts payable to a Third Party claimant, as well as any reasonable attorneys’ fees and costs of litigation incurred by such Adverum Indemnitees, resulting from any Claims against such Adverum Indemnitee to the extent arising from or based on (a) the conduct of the activities under the Research Plan by or on behalf of Adverum or its Affiliates except when such activities are included in the Research Plan determined through Adverum’s final decision making authority, (b) the Development or Commercialization of the Products, Prototype Products or Non-Adverum Products by or on behalf of Editas or its Affiliates or sublicensees, (c) the material breach of any of Editas’ obligations, representations, or warranties under this Agreement, or (d) the willful misconduct or grossly negligent acts of Editas, its Affiliates, or the officers, directors, employees, or agents of Editas or its Affiliates.  The foregoing indemnity obligation shall not apply to the extent that (i) the Adverum Indemnitees fail to comply with the indemnification procedures set forth in Section 10.3 and Editas’ defense of the relevant Claims is prejudiced by such failure, or (ii) any Claim arises from or is based on any activity set forth in Section 10.1 for which Adverum is obligated to indemnify the Editas Indemnitees under Section 10.1.

10.3

Indemnification Procedures .  The Party claiming indemnity under this Article 10 (the “ Indemnified Party ”) shall give written notice to the Party from whom indemnity is being sought (the “ Indemnifying Party ”) promptly after learning of such Claim.  The Indemnified Party shall provide the Indemnifying Party with reasonable assistance, at the Indemnifying Party’s expense, in connection with the defense of the Claim for which indemnity is being sought.  The Indemnified Party may participate in and monitor such defense with counsel of its own choosing at its sole expense; provided, however, the Indemnifying Party shall have the right to assume and conduct the defense of the Claim with counsel of its choice.  The Indemnifying Party shall not settle any Claim without the prior written consent of the Indemnified Party, not to be unreasonably withheld, unless the settlement involves only the payment of money.  So long as the Indemnifying Party is actively defending the Claim in good faith, the Indemnified Party shall not settle or

38.

 

[***] = Certain confidential information contained in this document, marked by brackets, is filed with the Securities and Exchange Commission pursuant to Rule 24b-2 of the Securities Exchange Act of 1934, as amended.


 

compromise any such Claim without the prior written consent of the Indemnifying Party.  If the Indemnifying Party does not assume and conduct the defense of the Claim as provided above, (a) the Indemnified Party may assume and conduct the defense of the Claim with counsel of its choice, which shall include, without limitation, the right to defend against, consent to the entry of any judgment, or enter into any settlement with respect to such Claim in any manner the Indemnified Party may deem reasonably appropriate (and the Indemnified Party need not consult with, or obtain any consent from, the Indemnifying Party in connection therewith), and (b) the Indemnifying Party shall remain responsible to indemnify the Indemnified Party as provided in this Article 10 .

10.4

Insurance.   Each Party, at its own expense, shall maintain appropriate insurance (or self-insure) in an amount consistent with sound business practice and reasonable in light of its obligations under this Agreement during the Term.  Each Party shall provide a certificate of insurance (or evidence of self-insurance) evidencing such coverage to the other Party upon request.

10.5

Limitation of Liability .  NEITHER PARTY SHALL BE LIABLE TO THE OTHER FOR ANY SPECIAL, CONSEQUENTIAL, INCIDENTAL, PUNITIVE, OR INDIRECT DAMAGES ARISING FROM OR RELATING TO ANY BREACH OF THIS AGREEMENT, REGARDLESS OF ANY NOTICE OF THE POSSIBILITY OF SUCH DAMAGES.  NOTWITHSTANDING THE FOREGOING, NOTHING IN THIS SECTION 10.5 IS INTENDED TO OR SHALL LIMIT OR RESTRICT THE INDEMNIFICATION RIGHTS OR OBLIGATIONS OF ANY PARTY UNDER SECTION 10.1 OR 10.2 OR DAMAGES AVAILABLE FOR BREACH OF ARTICLES 8 or 11.

11.

Confidentiality

11.1

Confidential Information.   Except to the extent expressly authorized by this Agreement or otherwise agreed in writing by the Parties, the Parties agree that, during the Term and for [***] years thereafter, but in any event for at least [***] years after the Option Effective Date, the receiving Party shall keep confidential and shall not publish or otherwise disclose and shall not use for any purpose other than as expressly provided for in this Agreement any Confidential Information of the other Party under this Agreement, and both Parties shall keep confidential and, except as expressly set forth in this Article 11, shall not publish or otherwise disclose the terms of this Agreement.  Each Party may disclose and/or use the other Party’s Confidential Information only to the extent required to accomplish the purposes of this Agreement, including exercising its rights or performing its obligations.  Each Party will use at least the same standard of care as it uses to protect proprietary or confidential information of its own (but no less than reasonable care) to ensure that its employees, agents, consultants, contractors, and other representatives do not disclose or make any unauthorized use of the Confidential Information of the other Party.  Each Party will promptly notify the other upon discovery of any unauthorized use or disclosure of the Confidential Information of the other Party.

39.

 

[***] = Certain confidential information contained in this document, marked by brackets, is filed with the Securities and Exchange Commission pursuant to Rule 24b-2 of the Securities Exchange Act of 1934, as amended.


 

11.2

Exceptions.   The obligations of confidentiality and restriction s on use under Section   11.1 will not apply to any information that the receiving Party can prove by competent written evidence: (a)  is now, or hereafter becomes, through no act or failure to act on the part of the receiving Party, generally known or available to the public; (b)  is known by the receiving Party at the time of receiving such information, other than by previous disclosure of the disclosing Party, or its Affiliates, employees, agents, consultants, or contractors; (c) is hereafter furnished to the receiving Party without restriction by a Third Party who has no obligation of confidentiality or limitations on use with respect thereto, as a matter of right; or (d)  is independently discovered or developed by the receiving Party without the use of Confidential Information belonging to the disclosing Party .

11.3

Authorized Disclosure.   Each Party may disclose Confidential Information belonging to the other Party as expressly permitted by this Agreement or if and to the extent such disclosure is reasonably necessary in the following instances:

 

(a)

filing, prosecuting, or maintaining Joint Patents or patents related to Vector Related Inventions or Therapeutic Related Inventions as permitted by this Agreement, provided, that each Party shall submit such request in writing to the other Party prior to making such filing and such other Party shall have the right to remove any of its Confidential Information from such filing and verify that such filing does not disclose or claim Collaboration Inventions owned by such other Party (and such other Party shall not unreasonably withhold its consent to the filing of such patent);

 

(b)

Regulatory Filings for Products consistent with its rights and obligations under this Agreement, provided, that each Party shall submit such request in writing to the other Party prior to making such filing and such other Party shall have the right to remove any of its Confidential Information from such filing and verify that such filing does not disclose or claim Collaboration Inventions owned by such other Party (and such other Party shall not unreasonably withhold its consent to the filing of such patent);

 

(c)

prosecuting or defending litigation as permitted by this Agreement;

 

(d)

complying with applicable court orders or governmental regulations, including regulations applicable to the public sale of securities;

 

(e)

disclosure to its and its Affiliates’ employees, consultants, contractors, and agents, and to sublicensees (in the case of Editas), in each case on a need-to-know basis in connection with the Development, manufacture, and Commercialization of Products in accordance with the terms of this Agreement, in each case under written obligations of confidentiality and non-use at least as stringent as those herein; and

40.

 

[***] = Certain confidential information contained in this document, marked by brackets, is filed with the Securities and Exchange Commission pursuant to Rule 24b-2 of the Securities Exchange Act of 1934, as amended.


 

 

(f)

disclosure to potential and actual investors, acquirors and other financial partners solely for the purpose of evaluating or carrying out an actual or potential investment or acquisition in each case under written obligations of confidentiality and non-use at least as stringent as those herein.

In the event that a Party is required to make a disclosure of the other Party’s Confidential Information pursuant to Section 11.3(c) or (d), it will, except where impracticable, give reasonable advance notice to the other Party of such disclosure and use reasonable efforts to secure confidential treatment of such Confidential Information at least as diligent as such Party would use to protect its own confidential information, but in no event less than reasonable efforts.  Any information disclosed pursuant to Section 11.3(c) or (d) shall remain Confidential Information and subject to the restrictions set forth in this Agreement, including the foregoing provisions of this Article 11.  Notwithstanding the foregoing, the Parties shall take all reasonable action to avoid disclosure of Confidential Information hereunder.

11.4

Publications. Neither Party shall disclose any Research Results or Research Data owned by the other Party, whether by oral presentation, manuscript, or abstract, without the other Party’s consent except as required by law.  In the event any such disclosure is required by law, then the Party seeking such disclosure shall first review it with the other Party and shall consider in good faith and reasonably incorporate such other Party’s comments.  

11.5

Publicity.   Each Party shall have the right to issue a press release substantially in the form attached hereto as Exhibit E , on or after the Effective Date.  If following such press release, either Party desires or is required to issue a press release relating to this Agreement or activities hereunder, such Party shall consult with the other Party reasonably and in good faith with respect to the text and timing of such press release prior to the issuance thereof, to the extent practicable, and obtain such other Party’s consent to such press release; provided that either Party may issue press releases or make such disclosures to the SEC or other applicable agency as it determines, based on advice of counsel, are reasonably necessary to comply with laws or regulations or for appropriate market disclosure.  Each Party shall provide the other Party with advance notice of legally required disclosures to the extent practicable.  The Parties will consult with each other on the provisions of this Agreement to be redacted in any filings made by a Party with the SEC or as otherwise required by Applicable Laws; provided that each Party shall have the right to make any such filing as it reasonably determines necessary under Applicable Laws.  In addition, either Party shall be free to disclose, without the other Party’s prior written consent, the existence of this Agreement, the identity of the other Party, and those terms of the Agreement which have already been publicly disclosed in accordance herewith.

41.

 

[***] = Certain confidential information contained in this document, marked by brackets, is filed with the Securities and Exchange Commission pursuant to Rule 24b-2 of the Securities Exchange Act of 1934, as amended.


 

12.

Term and Termination

12.1

Term.   This Agreement shall commence on the Effective Date and, unless terminated earlier as provided in this Article 12, shall continue until the later of (i) the expiration of the Additional Indication Option Exercise Period, or (ii) the expiration of the Royalty Term if an Option is exercised (the “ Term ”).

12.2

Termination by Mutual Agreement .  The Parties may terminate this Agreement at any time upon mutual written agreement.

12.3

Termination for Convenience .  Editas shall have the right to terminate this Agreement without cause in its entirety or on an Indication-by-Indication or country-by-country basis at any time after the License Effective Date on [***] prior written notice.

12.4

Termination for Challenge of Adverum Patents .  Adverum may terminate this Agreement in its entirety upon [***] written notice to Editas if Editas, its Affiliates, or a Third Party on behalf of Editas challenges the validity, scope, or enforceability of any Adverum Patent, [***].  Editas shall include provisions in all agreements under which a sublicensee obtains a sublicense under any Adverum Patent providing that if the sublicensee challenges the validity or enforceability of any such Adverum Patent under which such sublicensee is sublicensed, Editas may terminate such sublicense, and Editas shall enforce such provision if such sublicensee takes any such action.  Pursuant to Section [***] of the [***] Agreements, the [***] Agreement, and Editas’ sublicense thereunder, terminates immediately if [***] files a claim that in any way asserts that any of the [***] Patent Rights (as defined in the applicable [***] Agreement), is invalid or unenforceable where the filing is by [***], by a Third Party on behalf of [***] (and with the actual knowledge of [***]), or a Third Party at the written urging of [***].

12.5

Termination for Cause .

 

(a)

Material Breach .  Subject to Section 12.5(b) , each Party shall have the right to terminate this Agreement in its entirety upon written notice to the other Party if such other Party materially breaches this Agreement and has not cured such breach within [***] days ([***] days with respect to any payment breach) after notice of such breach from the non-breaching Party; provided, however, that if any breach is not reasonably curable within [***] days and if the breaching Party has provided a cure plan reasonably acceptable to the other Party during such [***] period and is making a bona fide effort to cure such breach by diligently implementing such plan, such cure period will be extended for a time period to be agreed by both Parties (but in no event more than an additional [***] days) in order to permit the breaching Party a reasonable period of time to cure such breach in accordance with such plan.

 

(b)

Disputed Breach .  If the alleged breaching Party disputes in good faith the existence or materiality of a breach specified in a notice provided by the other Party in accordance with Section 12.5(a), and such alleged breaching Party provides the other Party notice of such dispute within the [***] day or [***] day cure period, as

42.

 

[***] = Certain confidential information contained in this document, marked by brackets, is filed with the Securities and Exchange Commission pursuant to Rule 24b-2 of the Securities Exchange Act of 1934, as amended.


 

 

the case may be, then the non-breaching Party shall not have the right to terminate this Agreement under Section 12.5(a) unless and until the arbitrators, in accordance with Article 13 , have determined that the alleged breaching Party has materially breached the Agreement, or the diligence obligation , as the case may be, and such Party fails to cure such breach of the Agreement within [***] days following such arbitrators’ decision.  (If the arbitrators determine that a breach of Section [***] occurred and was not cured, then no further cure period shall apply following the arbitrator decision.)  It is understood and agreed that during the pendency of such dispute, all of the terms and conditions of this Agreement shall remain in effect and the Parties shall continue to perform all of their respective obligations hereunder.

 

(c)

Bankruptcy .  Each Party shall have the right to terminate this Agreement in its entirety upon written notice to the other Party if such other Party makes a general assignment for the benefit of creditors, files an insolvency petition in bankruptcy, petitions for or acquiesces in the appointment of any receiver, trustee or similar officer to liquidate or conserve its business or any substantial part of its assets, commences under the laws of any jurisdiction any proceeding involving its insolvency, bankruptcy, reorganization, adjustment of debt, dissolution, liquidation or any other similar proceeding for the release of financially distressed debtors or becomes a party to any proceeding or action of the type described above and such proceeding is not dismissed within [***] days after the commencement thereof.

12.6

Effects of Termination .

 

(a)

Termination of Licenses and Other Rights .  If this Agreement is terminated in its entirety, the Option granted to Editas in Section 3.1 and/or any License granted to Editas in Section 3.4, as applicable, will automatically terminate and if terminated on an Indication-by-Indication basis, then the Option granted to Editas in Section 3.1 and/or any License granted to Editas in Section 3.4 shall automatically terminate with respect to the given Indication, and, solely in the case of a termination of this Agreement in its entirety, all other rights and obligations of the Parties under this Agreement will terminate (except for those rights that survive pursuant to Section 12.10 ).  

 

(b)

Remaining Inventories .  Editas shall have the right to sell and have sold the remaining Product inventory held by Editas as of the date of termination for up to [***] months following the date of termination, provided that all such sales shall be subject to the applicable payment provisions set forth in Article 6.

12.7

Rights in Bankruptcy .  All licenses and rights to licenses granted under or pursuant to this Agreement are, and shall otherwise be deemed to be, for purposes of Section 365(n) of the United States Bankruptcy Code (the “ Code ”), licenses of rights to “intellectual property” as defined under Section 101(35A) of the Code. Each Party, as a recipient of such rights under this Agreement, shall retain and may fully exercise all of its rights and elections under the Code. Upon commencement of a bankruptcy

43.

 

[***] = Certain confidential information contained in this document, marked by brackets, is filed with the Securities and Exchange Commission pursuant to Rule 24b-2 of the Securities Exchange Act of 1934, as amended.


 

proceeding by or against the other Party under the Code, such party shall be entitled to a complete duplicate of, or complete access to (as such Party deems appropriate), any such intellectual property and all embodiments of such intellectual property. Such intellectual property and all embodiments thereof shall be promptly delivered to such Party (a) upon any such commencement of a bankruptcy proceeding upon written request therefor by such Party, unless Adverum elects to continue to perform all of its obligations under this Agreement or (b) if not delivered under (a) above, upon the rejection of this Agreement by or on behalf of the other Party upon written request therefor by such Party. The foregoing provisions are without prejudice to any rights such Party may have arising under the Code or other applicable Law.

12.8

Confidential Information .  Upon expiration or termination of this Agreement, except to the extent that a Party obtains or retains the right to use the other Party’s Confidential Information, each Party shall promptly return to the other Party, or delete or destroy, all relevant records and materials in such Party’s possession or control containing Confidential Information of the other Party; provided that such Party’s legal counsel may keep one copy of such materials for archival purposes only subject to continuing confidentiality and non-use obligations.

12.9

Damages; Relief.   Subject to Section 10.5, termination of this Agreement shall not preclude either Party from claiming any other damages, compensation or relief that it may be entitled to upon such termination.  

12.10

Survival.   Expiration or termination of this Agreement for any reason shall not relieve the Parties of any obligation or right that has already accrued prior to such expiration or termination.  Except as set forth below or elsewhere in this Agreement, the obligations and rights of the Parties under the following provisions shall survive expiration or termination of this Agreement: Articles 1 (Definitions); 10 (Indemnification); 11 (Confidentiality); 13 (Dispute Resolution); and 14 (General Provisions); and Sections 2.3(c) (Delivery), 7.4 (Records; Audits); 8.1-8.2 (Ownership; Patent Prosecution); 9.3 (No Other Warranties); 12.6 and 12.8 – 12.10 (Effects of Termination, etc.).

13.

Dispute Resolution

13.1

Objective.   The Parties recognize that disputes as to matters arising under or relating to this Agreement or either Party’s rights and obligations hereunder may arise from time to time.  It is the objective of the Parties to establish procedures to facilitate the resolution of such disputes in an expedient manner by mutual cooperation and without resort to litigation.  To accomplish this objective, the Parties agree to follow the procedures set forth in this Article 13 to resolve any such dispute if and when it arises.

13.2

Resolution by Executive Officers.   If an unresolved dispute as to matters arising under or relating to this Agreement or either Party’s rights and obligations hereunder arises, either Party may refer such dispute to the Chief Executive Officer of Adverum and the Chief Executive Officer of Editas (collectively, the “ Executive Officers ”), who shall meet in person or by telephone within [***] days after such referral to attempt in good

44.

 

[***] = Certain confidential information contained in this document, marked by brackets, is filed with the Securities and Exchange Commission pursuant to Rule 24b-2 of the Securities Exchange Act of 1934, as amended.


 

faith to resolve such dispute.  If such matter cannot be resolved by discussion of such officers within such [***] period, or such other time period as the Parties may agree to in writing, such dispute shall be resolved in accordance with Section 13 . 3 .

13.3

Arbitration .

 

(a)

If the Parties are unable to resolve a disputed using the process described in Section 13.2, then a Party seeking further resolution of the dispute may submit the disputed matter to resolution by final and binding arbitration.  If a Party intends to begin an arbitration to resolve a dispute arising under this Agreement, such Party shall provide written notice to the other Party of such intention and the issues for resolution.  Arbitration will be held in [***], and administered by the [***] pursuant to its [***] Arbitration Rules (the “ Rules ”) then in effect, except as otherwise provided herein and applying the substantive law specified in Section 14.1.  The arbitration shall be conducted by three (3) arbitrators who are knowledgeable in the subject matter at issue in the dispute.  One (1) arbitrator will be selected by Adverum, one (1) arbitrator will be selected by Editas, and the third arbitrator will be selected by mutual agreement of the two (2) arbitrators selected by the Parties.  In addition to the authority conferred by the Rules, discovery will be permitted by either Party in accordance with and subject to all applicable privileges and other immunities under the U.S. Federal Rules of Civil Procedure.  The arbitrators may proceed to an award, notwithstanding the failure of either Party to participate in the proceedings.  The arbitrators shall, within [***] days after the conclusion of the arbitration hearing, issue a written award and statement of decision describing the essential findings and conclusions on which the award is based, including the calculation of any damages awarded.  The arbitrators shall be authorized to award compensatory damages, but shall not be authorized to award non-economic damages or punitive damages, or to reform, modify, or materially change this Agreement or any other agreements contemplated hereunder.  The arbitrators also shall be authorized to grant any temporary, preliminary, or permanent equitable remedy or relief the arbitrators deem just and equitable and within the scope of this Agreement, including, without limitation, an injunction or order for specific performance.  The arbitrators’ award shall be the sole and exclusive remedy of the Parties (except for those remedies set forth in this Agreement).  Judgment on the award rendered by the arbitrators may be enforced in any court having competent jurisdiction thereof, subject only to revocation on grounds of fraud or clear bias on the part of the arbitrators.  Notwithstanding anything contained in this Section 13.3 to the contrary, each Party shall have the right to institute judicial proceedings against the other Party or anyone acting by, through, or under such other Party, in order to enforce the instituting Party’s rights hereunder through specific performance, injunction, or similar equitable relief. Notwithstanding the foregoing, if the Parties have a dispute that is brought under Section [***] of this Agreement, the arbitrators shall have the authority to resolve any issues and require the Parties to [***], provided, that the arbitrators must [***].

45.

 

[***] = Certain confidential information contained in this document, marked by brackets, is filed with the Securities and Exchange Commission pursuant to Rule 24b-2 of the Securities Exchange Act of 1934, as amended.


 

 

(b)

Notwithstanding the foregoing, this Section 13.3 shall not apply to any dispute, controversy or claim that concerns the validity, enforceability or infringement of a patent, trademark or copyright, each of which shall be subject to the jurisdiction of a court in the country in which such right arises.

13.4

Costs; Satisfaction .    Each Party shall bear its own attorneys’ fees, costs, and disbursements arising out of the arbitration pursuant to Section 13.3, and shall pay an equal share of the fees and costs of the arbitrators; provided, however, that the arbitrators shall be authorized (but shall not be obligated) to determine whether a Party is the prevailing Party, and if so, to award to that prevailing Party reimbursement for its reasonable attorneys’ fees, costs, and disbursements, and/or the fees and costs of the arbitrators.  Absent the filing of an application to correct or vacate the arbitration award as permitted by applicable law, each Party shall fully perform and satisfy the arbitration award within [***] days of the service of the award.

14.

General Provisions

14.1

Governing Law.   This Agreement shall be governed by and construed in accordance with the laws of the State of Delaware, US, without reference to any rules of conflict of laws.

14.2

Entire Agreement; Amendment .  This Agreement, including the exhibits, is both a final expression of the Parties’ agreement and a complete and exclusive statement with respect to all of its terms.  This Agreement supersedes all prior and contemporaneous agreements and communications, whether oral, written, or otherwise, concerning any and all matters contained herein, including, without limitation that certain Confidentiality Agreement .   This Agreement may only be modified or supplemented in a writing expressly stated for such purpose and signed by the Parties to this Agreement.

14.3

Relationship Between the Parties.   The Parties’ relationship, as established by this Agreement, is solely that of independent contractors.  This Agreement does not create any partnership, joint venture, or similar business relationship between the Parties.  Neither Party is a legal representative of the other Party, and neither Party can assume or create any obligation, representation, warranty, or guarantee, express or implied, on behalf of the other Party for any purpose whatsoever.

14.4

Non-Waiver.   The failure of a Party to insist upon strict performance of any provision of this Agreement or to exercise any right arising out of this Agreement shall neither impair that provision or right nor constitute a waiver of that provision or right, in whole or in part, in that instance or in any other instance.  Any waiver by a Party of a particular provision or right shall be in writing, shall be as to a particular matter and, if applicable, for a particular period of time and shall be signed by such Party.

14.5

Assignment.   Except as expressly provided hereunder, neither this Agreement nor any rights or obligations hereunder may be assigned or otherwise transferred by either Party without the prior written consent of the other Party (which consent shall not be

46.

 

[***] = Certain confidential information contained in this document, marked by brackets, is filed with the Securities and Exchange Commission pursuant to Rule 24b-2 of the Securities Exchange Act of 1934, as amended.


 

unreasonably withheld, conditioned, or delayed) , provided that either Party may assign or otherwise transfer this Agreement and its rights and obligations hereunder without the other Party’s consent in connection with the transfer or sale of all or substantially all of its business or assets to which this Agreement pertains , provided, further, that in such case: (a ) the exclusivity obligation of such assigning Party shall not apply to any products being developed and/or commercialized by any such successor in interest or assignee or purchaser (such successor in interest or assignee or purchaser, as applicable, an “ Acquiror ”) or its affiliates prior to the applicable transaction or thereafter developed independent of this Agreement and (b ) the exclusivity obligations of the non-assigning Party shall lapse .   The rights and obligations of the Parties under this Agreement shall be binding upon and inure to the benefit of the successors and permitted assigns of the Parties specified above and such assignee shall agree in writing to be bound by the terms and conditions of this Agreement to the same extent of the assignee except as expressly set forth herein , and the name of a Party appearing herein will be deemed to include the name of such Party’s successors and permitted assigns to the extent necessary to carry out the intent of this section.  Any assignment not in accordance with this Section 14.5 shall be null and void.   The intellectual property owned or controlled by any such Acquiror or its affiliates prior to the applicable transaction or thereafter developed independent of this Agreement shall be excluded from the license from the Party undergoing transaction to the other Party, and the Acquiror and its affiliates shall be excluded from “Affiliate” solely for purposes of the applicable components of the intellectual property definitions set forth herein.

14.6

Severability.   If, for any reason, any part of this Agreement is adjudicated invalid, unenforceable, or illegal by a court of competent jurisdiction, such adjudication shall not, to the extent feasible, affect or impair, in whole or in part, the validity, enforceability, or legality of any remaining portions of this Agreement.  All remaining portions shall remain in full force and effect as if the original Agreement had been executed without the invalidated, unenforceable, or illegal part.

14.7

Notices.   Any notice to be given under this Agreement must be in writing and delivered either in person, by (a) air mail (postage prepaid) requiring return receipt, (b) overnight courier, or (c) facsimile confirmed thereafter by any of the foregoing, to the Party to be notified at its address(es) given below, or at any address such Party may designate by prior written notice to the other in accordance with this Section 14.7.  Notice shall be deemed sufficiently given for all purposes upon the earliest of:  (i) the date of actual receipt; (ii) if air mailed, five (5) days after the date of postmark; or (iii) if delivered by overnight courier, the next day the overnight courier regularly makes deliveries

If to Adverum, notices must be addressed to:

Adverum Biotechnologies, Inc.

1035 O’Brien Drive

Menlo Park, CA 94025

Attention:  Associate General Counsel

Attention: Chief Executive Officer

47.

 

[***] = Certain confidential information contained in this document, marked by brackets, is filed with the Securities and Exchange Commission pursuant to Rule 24b-2 of the Securities Exchange Act of 1934, as amended.


 

If to Editas, notices must be addressed to:

Editas Medicine, Inc.

300 Third Street

Cambridge, MA 02142

Attention: Chief Operating Officer

Attention: Senior Legal Officer

14.8

Force Majeure.   Each Party shall be excused from liability for the failure or delay in performance of any obligation under this Agreement (other than failure to make payment when due) by reason of any event beyond such Party’s reasonable control including but not limited to Acts of God, fire, flood, explosion, earthquake, pandemic flu, or other natural forces, war, civil unrest, acts of terrorism, accident, destruction or other casualty, any lack or failure of transportation facilities, any lack or failure of supply of raw materials, or any other event similar to those enumerated above.  Such excuse from liability shall be effective only to the extent and duration of the event(s) causing the failure or delay in performance and provided that the Party has not caused such event(s) to occur.  Notice of a Party’s failure or delay in performance due to force majeure must be given to the other Party within ten (10) days after its occurrence.  All delivery dates under this Agreement that have been affected by force majeure shall be tolled for the duration of such force majeure.  In no event shall any Party be required to prevent or settle any labor disturbance or dispute.

14.9

Performance by Affiliates.   To the extent a Party authorizes an Affiliate to perform some or all of its obligations under this Agreement, such Party shall remain primarily liable for any acts or omissions of its Affiliates.

14.10

Compliance with Law.   Each Party shall perform its obligations under this Agreement in accordance with all Applicable Laws.  No Party shall, or shall be required to, undertake any activity under or in connection with this Agreement which violates, or which it believes, in good faith, may violate, any Applicable Law.

14.11

No Third Party Beneficiary Rights.   The provisions of this Agreement are for the sole benefit of the Parties and their successors and permitted assigns, and they shall not be construed as conferring any rights to any Third Party (including any Third Party beneficiary rights).

14.12

Interpretation.   The headings of clauses contained in this Agreement preceding the text of the sections, subsections, and paragraphs hereof are inserted solely for convenience and ease of reference and shall not constitute any part of this Agreement, or have any effect on its interpretation or construction.  All references in this Agreement to the singular shall include the plural where applicable.  Unless otherwise specified, references in this Agreement to any Article shall include all Sections, subsections, and paragraphs in such Article, references to any Section shall include all subsections and paragraphs in such Section, and references in this Agreement to any subsection shall include all paragraphs in such subsection.  The word “including” and similar words means including

48.

 

[***] = Certain confidential information contained in this document, marked by brackets, is filed with the Securities and Exchange Commission pursuant to Rule 24b-2 of the Securities Exchange Act of 1934, as amended.


 

without limitation.  The word “or” means “and/or” unless the context dictates otherwise because the subject of the conjunction are mutually exclusive.  The words “herein,” “hereof,” and “hereunder” and other words of similar import refer to this Agreement as a whole and not to any particular Section or other subdivision.  All references to days in this Agreement mean calendar days, unless otherwise specified.   All references to dollars and “$” herein shall refer to U.S. dollars.  Ambiguities and uncertainties in this Agreement, if any, shall not be interpreted against either Party, irrespective of which Party may be deemed to have caused the ambiguity or uncertainty to exist.  This Agreement has been prepared in the English language and the English language shall control its interpretation.  In addition, all notices required or permitted to be given hereunder, and all written, electronic, oral, or other communications between the Parties regarding this Agreement shall be in the English language.

14.13

Further Actions. Each Party agrees to execute, acknowledge, and deliver such further instruments, and to do all such other acts, as necessary or appropriate in order to carry out the purposes and intent of this Agreement.

14.14

Counterparts; Electronic or Facsimile Signatures.   This Agreement may be executed in any number of counterparts, each of which shall be an original, but all of which together shall constitute one instrument.  This Agreement may be executed and delivered electronically or by facsimile and upon such delivery such electronic or facsimile signature will be deemed to have the same effect as if the original signature had been delivered to the other Party.

{Signature Page Follows}

 

 

49.

 

[***] = Certain confidential information contained in this document, marked by brackets, is filed with the Securities and Exchange Commission pursuant to Rule 24b-2 of the Securities Exchange Act of 1934, as amended.


 

In Witness Whereof, the Parties hereto have caused this Collaboration, Option and License Agreement to be executed and entered into by their duly authorized representatives as of the Effective Date.

 

Adverum Biotechnologies, Inc.

 

Editas Medicine, Inc.

 

 

 

 

 

By:

 

/s/ Paul B. Cleveland

 

By:

 

/s/ Katrine Bosley

Name:

 

Paul B. Cleveland

 

Name:

 

Katrine Bosley

Title:

 

Chief Executive Officer

 

Title:

 

Chief Executive Officer

 

 

Signature Page


 

L ist of Exhibits

Exhibit A: Adverum Patents as of the Effective Date

Exhibit B: Upstream Agreements as of the Effective Date

Exhibit C: JRC Members

Exhibit D: Research Plan

Exhibit E: Form of Press Release

 

 

[***] = Certain confidential information contained in this document, marked by brackets, is filed with the Securities and Exchange Commission pursuant to Rule 24b-2 of the Securities Exchange Act of 1934, as amended.


Exhibit A

Adverum Patents as of the Effective Date

 

Appl. No.

Title

Country

Patent No.

[***]

[***]

[***]

[***]

[***]

[***]

[***]

[***]

[***]

[***]

[***]

[***]

[***]

[***]

[***]

[***]

[***]

[***]

[***]

[***]

[***]

[***]

[***]

[***]

[***]

[***]

[***]

[***]

[***]

[***]

[***]

[***]

[***]

[***]

[***]

[***]

[***]

[***]

[***]

[***]

[***]

[***]

[***]

[***]

[***]

[***]

[***]

[***]

[***]

[***]

[***]

[***]

[***]

[***]

[***]

[***]

[***]

[***]

[***]

[***]

[***]

[***]

[***]

[***]

[***]

[***]

[***]

[***]

[***]

[***]

[***]

[***]

[***]

[***]

[***]

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[***] = Certain confidential information contained in this document, marked by brackets, is filed with the Securities and Exchange Commission pursuant to Rule 24b-2 of the Securities Exchange Act of 1934, as amended.


Exhibit B

Upstream Agreements as of the Effective Date

 

[***]

 

 

[***] = Certain confidential information contained in this document, marked by brackets, is filed with the Securities and Exchange Commission pursuant to Rule 24b-2 of the Securities Exchange Act of 1934, as amended.


Exhibit C

JRC Members

Adverum JRC Members

[***]

Editas JRC Members

[***]

 

 

[***] = Certain confidential information contained in this document, marked by brackets, is filed with the Securities and Exchange Commission pursuant to Rule 24b-2 of the Securities Exchange Act of 1934, as amended.


Exhibit D

Research Plan

[*** ]

 

 

 

[***] = Certain confidential information contained in this document, marked by brackets, is filed with the Securities and Exchange Commission pursuant to Rule 24b-2 of the Securities Exchange Act of 1934, as amended.


 

Exhibit E

Form of Press Release

ADVERUM BIOTECHNOLOGIES AND EDITAS MEDICINE ANNOUNCE

COLLABORATION TO EXPLORE DELIVERY OF GENOME EDITING MEDICINES

TO THE EYE

-Collaboration Brings Together Vector and Ophthalmology Expertise of Adverum with

Genome Editing Capabilities of Editas-

MENLO PARK, Calif. And CAMBRIDGE, Mass., August XX, 2016 – Adverum Biotechnologies, Inc. (Nasdaq: ADVM) and Editas Medicine, Inc. (Nasdaq: EDIT) today announced a collaboration to explore the delivery of genome editing medicines to treat up to five inherited retinal diseases.  This collaboration brings together Adverum’s next-generation adeno-associated viral (AAV) vectors for use with Editas’ leading genome editing technologies to create a series of novel therapies for debilitating eye diseases that have poor therapeutic options.

"We are pleased to bring together our gene therapy capabilities with Editas’ CRISPR based approach to genome editing,” said Paul Cleveland, chief executive officer of Adverum Biotechnologies. “Our innovative vectors have the potential to deliver Editas’ genome editing components efficiently to the retina. This collaboration expands our opportunities to capitalize on our science, ophthalmology expertise and vector development know-how.”

“As we continue to invest in our genome editing platform, we are delighted to collaborate with Adverum Biotechnologies on next-generation AAV vectors,” said Katrine Bosley, president and chief executive officer of Editas Medicine. “Adverum brings a distinctive technology and experience base, and this collaboration aligns highly with our broader, multi-faceted delivery strategy.”

Under the terms of the agreement, Editas will pay Adverum an upfront fee of $1 million to evaluate Adverum next-generation vectors for use in clinical development.  Editas will support all preclinical activities related to this collaboration, with a portion of the upfront fee to be credited against this funding obligation. In addition, Editas will also pay an additional option exercise fee of $1 million for an exclusive license to Adverum’s next-generation AAV vectors for use in each indication chosen as part of the collaboration. Adverum also is eligible to receive development and commercial milestone payments, as well as royalties on any resulting commercialized Editas products that incorporate Adverum’s next-generation AAV vectors.  

About Adverum Biotechnologies, Inc.

Adverum is a gene therapy company committed to discovering and developing novel medicines that can offer life-changing benefits to patients living with rare diseases or diseases of the eye who currently have limited or burdensome treatment options .  Adverum has a robust pipeline and is leveraging its 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. Our focus on the patient is supported by clinical development expertise and core capabilities in vector optimization, process development, manufacturing, and assay development.  For more information, please visit www.adverumbio.com

 

[***] = Certain confidential information contained in this document, marked by brackets, is filed with the Securities and Exchange Commission pursuant to Rule 24b-2 of the Securities Exchange Act of 1934, as amended.


About Editas Medicine

Editas Medicine is a leading genome editing company dedicated to treating patients with genetically defined diseases by correcting their disease-causing genes.  Editas was founded by world leaders in genome editing, and its mission is to translate the promise of genome editing science into a broad class of transformative genomic medicines to benefit the greatest number of patients.  

Forward-Looking Statements for Adverum Biotechnologies

Statements contained in this press release regarding matters that are not historical facts are “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995. Such statements include, but are not limited to, statements regarding Adverum’s plans, potential opportunities, expectations, projections, goals, objectives, milestones, strategies, product pipeline, the sufficiency of its resources to fund the advancement of any development program or the completion of any clinical trials, and the safety, efficacy, and projected development timeline and commercial potential of products under development, all of which are based on certain assumptions made by us on current conditions, expected future developments and other factors we believe are appropriate in the circumstances. Adverum may not consummate any plans or product development goals in a timely manner, or at all, or otherwise carry out the intentions or meet the expectations or projections disclosed in our forward-looking statements, and you should not place undue reliance on these forward-looking statements. Actual results and the timing of events could differ materially from those anticipated in such forward-looking statements as a result of various risks and uncertainties, which include, without limitation, risks and uncertainties associated with the ability to project future cash utilization and reserves needed for contingent future liabilities and business operations, the availability of sufficient resources for Adverum’s operations and to conduct or continue planned development programs and planned clinical trials and the ability to successfully develop any of its product candidates. Risks and uncertainties facing Adverum are described more fully in Adverum’s periodic reports filed with the SEC. All forward-looking statements contained in this press release speak only as of the date on which they were made. Adverum undertakes no obligation to update such statements to reflect events that occur or circumstances that exist after the date on which they were made.

Forward Looking Statements for Editas Medicine

This press release contains forward-looking statements within the meaning of the “safe harbor” provisions of The Private Securities Litigation Reform Act of 1995.  All statements, other than statements of historical facts, contained in this presentation, including statements regarding Editas’ strategy, future operations, future financial position, future revenue, projected costs, prospects, plans, and objectives of management, are forward-looking statements. The words ‘‘anticipate,’’ ‘‘believe,’’ ‘‘continue,’’ ‘‘could,’’ ‘‘estimate,’’ ‘‘expect,’’ ‘‘intend,’’ ‘‘may,’’ ‘‘plan,’’ ‘‘potential,’’ ‘‘predict,’’ ‘‘project,’’ ‘‘target,’’ ‘‘should,’’ ‘‘would,’’ and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. Editas may not actually achieve the plans, intentions, or expectations disclosed in these forward-looking statements, and you should not place undue reliance on these forward-looking statements. Actual results or events could differ

 

[***] = Certain confidential information contained in this document, marked by brackets, is filed with the Securities and Exchange Commission pursuant to Rule 24b-2 of the Securities Exchange Act of 1934, as amended.


materially from the plans, intentions and expectations disclosed in these forward-looking statements as a result of various factors, including:  uncertainties inherent in the initiation and completion of preclinical studies and clinical trials and clinical development of Editas’ product candidates; availability and timing of results from preclinical studies and clinical trials; whether interim results from a clinical trial will be predictive of the final results of the trial or the results of future trials; expectations for regulatory approvals to conduct trials or to market products; availability of funding sufficient for Editas’ foreseeable and unforeseeable operating expenses and capital expenditure requirements; and other factors discussed in the “Risk Factors” section of Editas’ Quarterly Report on Form 10-Q, which is on file with the Securities and Exchange Commission, and in other filings that the Company may make with the Securities and Exchange Commission in the future. In addition, the forward-looking statements included in this presentation represent Editas’ views as of the date of this presentation.  Editas anticipates that subsequent events and developments will cause its views to change. However, while Editas may elect to update these forward-looking statements at some point in the future, it specifically disclaims any obligation to do so.  These forward-looking statements should not be relied upon as representing the Editas’ views as of any date subsequent to the date of this press release.

###

Investor and Media Contact for Adverum:

Lauren Glaser

(650) 656-9347

lglaser@adverumbio.com

Investor Contact for Editas Medicine:

Jesse Baumgartner

Stern Investor Relations, Inc.

(212) 362-1200

jesse@sternir.com  

Media Contact for Editas Medicine:

Dan Budwick

Pure Communications

(973) 271-6085

dan@purecommunicationsinc.com

 

 

[***] = Certain confidential information contained in this document, marked by brackets, is filed with the Securities and Exchange Commission pursuant to Rule 24b-2 of the Securities Exchange Act of 1934, as amended.

Exhibit 31.1

CERTIFICATION OF THE PRINCIPAL 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:

 

a.

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;

 

b.

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;

 

c.

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

 

d.

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: November 08, 2016

 

 /s/ Paul B. Cleveland

Paul B. Cleveland

Executive Chairman of the Board and 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:

 

a.

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;

 

b.

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;

 

c.

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

 

d.

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: November 08, 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 September 30, 2016, as filed with the Securities and Exchange Commission (the “Report”), Paul B. Cleveland, Executive Chairman of the Board and Principal 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: November 08, 2016

 

 /s/ Paul B. Cleveland

Paul B. Cleveland

Executive Chairman of the Board and Principal Executive Officer

 

 /s/ Leone Patterson

Leone Patterson

Chief Financial Officer

(principal financial and accounting officer)