AMENDED AND RESTATED COLLABORATION AGREEMENT BY AND BETWEEN ALNYLAM PHARMACEUTICALS, INC. AND MEDTRONIC, INC

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Title: AMENDED AND RESTATED COLLABORATION AGREEMENT BY AND BETWEEN ALNYLAM PHARMACEUTICALS, INC. AND MEDTRONIC, INC
Governing Law: Delaware Date: 11/8/2007
Industry: Biotechnology and Drugs Law Firm: Wilmer Cutler Pickering Hale and Dorr LLP Sector: Healthcare

AMENDED AND RESTATED
COLLABORATION AGREEMENT
BY AND BETWEEN
ALNYLAM PHARMACEUTICALS, INC.
AND
MEDTRONIC, INC, Parties: alnylam pharmaceuticals inc , medtronic inc


CONFIDENTIAL		EXECUTION COPY

Exhibit 10.4

Confidential Materials omitted and filed separately with the
Securities and Exchange Commission. Asterisks denote omissions.

AMENDED AND RESTATED

COLLABORATION AGREEMENT

BY AND BETWEEN

ALNYLAM PHARMACEUTICALS, INC.

AND

MEDTRONIC, INC.

Table of Contents


	Page
Article I Definitions		1
Section 1.1 “Affiliate”		1
Section 1.2 “Alnylam Intellectual Property”		2
Section 1.3 “Alnylam Know-How”		2
Section 1.4 “Alnylam Patent Rights”		2
Section 1.5 “Alnylam siRNA”		2
Section 1.6 “Blocking Third Party Intellectual Property”		2
Section 1.7 “[**]”		2
Section 1.8 “Collaboration Program”		3
Section 1.9 “Collaboration Term”		3
Section 1.10 “Commercialization” or “Commercialize”		3
Section 1.11 “Commercializing Party”		3
Section 1.12 “Commercially Reasonable Efforts”		3
Section 1.13 “Confidential Information”		3
Section 1.14 “Control” or “Controlled”		4
Section 1.15 “Cover”, “Covering” or “Covered”		4
Section 1.16 “CPI”		4
Section 1.17 “Develop” or “Development”		4
Section 1.18 “Development Candidate”		4
Section 1.19 “Development Costs”		4
Section 1.20 “Device”		5
Section 1.21 “Device-Related”		5
Section 1.22 “Discover” or “Discovery”		5
Section 1.23 “[**]”		5
Section 1.24 “Effective Date”		5
Section 1.25 “Exclusivity Field”		5
Section 1.26 “Executive Officers”		5
Section 1.27 “FDA”		5
Section 1.28 “Field”		5
Section 1.29 “First Commercial Sale”		5
Section 1.30 “FTE Cost”		5
Section 1.31 “GAAP”		6
Section 1.32 “Gene Target”		6
Section 1.33 “IND”		6
Section 1.34 “Initial PDP Workplan”		6
Section 1.35 “Initial Product Development Program”		6
Section 1.36 “JCC Representative”		6
Section 1.37 “JRDC Representative”		6
Section 1.38 “[**] Agreement”		6
Section 1.39 “Know-How”		6
Section 1.40 “Launch Costs”		6
Section 1.41 “Licensed Product”		7
Section 1.42 “Listed or Approved Third Party Agreement”		7


	Page
Section 1.43 “Major Market”		7
Section 1.44 “Manufacturing Cost”		7
Section 1.45 “Medtronic Device”		7
Section 1.46 “Medtronic Fiscal Quarter”		8
Section 1.47 “Medtronic Fiscal Year”		8
Section 1.48 “Medtronic Intellectual Property”		8
Section 1.49 “Medtronic Know-How”		8
Section 1.50 “Medtronic Patent Rights”		8
Section 1.51 “NDA”		8
Section 1.52 “Net Sales”		8
Section 1.53 “Neurodegenerative Disease”		9
Section 1.54 “Party”		9
Section 1.55 “Patent Rights”		9
Section 1.56 “Person”		9
Section 1.57 “Phase I Study”		9
Section 1.58 “Phase II(a) Study”		9
Section 1.59 “Phase II(b) Study”		10
Section 1.60 “Phase III Study”		10
Section 1.61 “[**] Opt Out”		10
Section 1.62 “[**] Opt Out”		10
Section 1.63 “[**] Opt Out”		10
Section 1.64 “[**] Opt Out”		10
Section 1.65 “Preliminary Success Criteria”		10
Section 1.66 “Primary Sequence or Chemical Modification Know-How”		10
Section 1.67 “Product”		10
Section 1.68 “Product Development Program”		10
Section 1.69 “Product Development Term”		11
Section 1.70 “Program Intellectual Property”		11
Section 1.71 “Program Know-How”		11
Section 1.72 “Program Patent Rights”		11
Section 1.73 “Regulatory Approval”		11
Section 1.74 “Regulatory Authority”		11
Section 1.75 “ROW Territory”		11
Section 1.76 “Royalty Term”		11
Section 1.77 “Section 2.5(d)(iii) [**] Agreement”		12
Section 1.78 “siRNA”		12
Section 1.79 “Target Indication”		12
Section 1.80 “Territory”		12
Section 1.81 “Third Party”		12
Section 1.82 “US Territory”		12
Section 1.83 “Valid Claim”		12
Section 1.84 “Workplan”		12
Section 1.85 Additional Definitions		12

Article II Collaboration Program; Commercialization		14
Section 2.1 General		14
Section 2.2 Governance; Decision-Making		14


	Page
Section 2.3 Conduct of the Collaboration Program		17
Section 2.4 Right to Opt Out		20
Section 2.5 Exclusivity, Diligence and RoFN Obligations		22
Section 2.6 Supply of Alnylam siRNAs		24
Section 2.7 SAB Observer Right		25

Article III Grant of Rights		25
Section 3.1 Alnylam Grants		25
Section 3.2 Medtronic Grants		27
Section 3.3 Retained Rights		29

Article IV Financial Provisions		29
Section 4.1 Development Cost and Launch Cost Sharing		29
Section 4.2 Milestone Payments for Product Development Programs		30
Section 4.3 Royalty Payments		31
Section 4.4 Duration of Royalty Payments		33
Section 4.5 Royalties Payable Only Once		33
Section 4.6 Credits Against Future Royalties		33

Section 4.7 Quarterly Reconciliation of Development Costs and Net Sales; Royalty Reports and Accounting		34
Section 4.8 Currency Exchange		35
Section 4.9 Tax Withholding		35
Section 4.10 Late Payments		35

Article V Intellectual Property Ownership, Protection and Related Matters		36
Section 5.1 Ownership of Inventions		36
Section 5.2 Prosecution and Maintenance of Patent Rights		37
Section 5.3 Third Party Infringement		38
Section 5.4 Claimed Infringement; Claimed Invalidity		40
Section 5.5 Patent Term Extensions		41
Section 5.6 Patent Marking		41
Section 5.7 Maintain Licenses in Force		41

Article VI Confidentiality		41
Section 6.1 Confidential Information		42
Section 6.2 Disclosures to Employees, Consultants and Advisors		42
Section 6.3 Term		42
Section 6.4 Publicity		42
Section 6.5 Publications		43

Article VII Representations and Warranties		43
Section 7.1 Representations of Authority		44
Section 7.2 Consents		44
Section 7.3 No Conflict		44
Section 7.4 Enforceability		44
Section 7.5 Employee Obligations		44
Section 7.6 Intellectual Property		44

iii


	Page
Section 7.7 No Warranties		45

Article VIII Term and Termination		45
Section 8.1 Term		45
Section 8.2 Termination For Material Breach		45
Section 8.3 Termination Upon No-Go Decision		46
Section 8.4 Effect of Termination		46
Section 8.5 Survival		49

Article IX Miscellaneous Provisions		50
Section 9.1 Indemnification		50
Section 9.2 Governing Law and Waiver of Jury Trial		51
Section 9.3 Assignment		52
Section 9.4 Entire Agreement; Amendments		52
Section 9.5 Notices		52
Section 9.6 Force Majeure		53
Section 9.7 Independent Contractors		53
Section 9.8 No Strict Construction		54
Section 9.9 Headings		54
Section 9.10 No Implied Waivers; Rights Cumulative		54
Section 9.11 Severability		54
Section 9.12 Execution in Counterparts; Facsimile Signatures		54
Section 9.13 No Consequential or Punitive Damages		54
Section 9.14 Interpretation		54


Schedules
Schedule 1.4		Alnylam Patent Rights
Schedule 1.42		Listed or Approved Third Party Agreements
Schedule 3.1(d)		Existing Third Party Contractual Obligations of Alnylam
Schedule 3.2(d)		Existing Third Party Contractual Obligations of Medtronic
Schedule 4.3(h)		Payments Under Listed or Approved Third Party Agreements

Exhibits
Exhibit A		siRNA Supply Agreement Principal Terms
Exhibit B		Press Release
Exhibit C		Permitted Disclosures
Exhibit D		Device Supply Agreement Principal Terms

AMENDED AND RESTATED COLLABORATION AGREEMENT

This Amended and Restated Collaboration Agreement (this “ Agreement ”) is entered into as of the 27th day of July, 2007 (the “ Restatement Date ”), by and between Alnylam Pharmaceuticals, Inc., a corporation organized and existing under the laws of the State of Delaware and having its principal office at 300 Third Street, Cambridge, Massachusetts 02142 (“ Alnylam ”), and Medtronic, Inc., a corporation organized and existing under the laws of the State of Minnesota and having its principal office at 710 Medtronic Parkway, Minneapolis, Minnesota 55432 (“ Medtronic ”).

INTRODUCTION

1. Alnylam is engaged in the business of discovering and developing siRNA-based therapeutics.

2. Medtronic is engaged in the business of developing and marketing medical devices.

3. On the Effective Date, Alnylam and Medtronic entered into a Collaboration Agreement (as amended prior to the Restatement Date, the “ Original Collaboration Agreement ”), pursuant to which Alnylam and Medtronic agreed to collaborate on the discovery, development, manufacture and commercialization of siRNA-based therapeutics for the treatment of certain diseases using implanted infusion devices for the direct delivery of siRNAs to the human nervous system.

4. Alnylam and Medtronic now desire to amend and restate the Original Collaboration Agreement to reflect their joint determination to commence and carry out the Initial Product Development Program and to otherwise modify the terms of their collaboration on the discovery, development, manufacture and commercialization of siRNA-based therapeutics as set forth herein.

NOW, THEREFORE, in consideration of the respective representations, warranties, covenants and agreements contained herein, and for other valuable consideration, the receipt and adequacy of which are hereby acknowledged, Alnylam and Medtronic hereby amend and restate the Original Collaboration Agreement in its entirety as follows:

Article I

Definitions

When used in this Agreement, each of the following terms shall have the meanings set forth in this Article I:

Section 1.1 “ Affiliate ”. Affiliate of a specified Person shall mean any Person that controls, is controlled by, or is under common control with such Person. For purposes of this Section 1.1 and Section 9.3, “control” shall mean (a) in the case of corporate entities, direct or indirect ownership of at least fifty percent (50%) of the stock or shares having the right to vote for the election of directors, and (b) in the case of non-corporate entities, direct or indirect

ownership of at least fifty percent (50%) of the equity interest with the power to direct the management and policies of such non-corporate entities.

Section 1.2 “ Alnylam Intellectual Property ”. Alnylam Intellectual Property shall mean Alnylam Know-How and Alnylam Patent Rights, collectively.

Section 1.3 “ Alnylam Know-How ”. Alnylam Know-How shall mean any Know-How, other than Know-How related to [**] and other than Program Know-How, that is (a) developed or acquired by Alnylam prior to or during the Collaboration Term, (b) used to Discover, Develop, manufacture or Commercialize Alnylam siRNAs, Medtronic Devices and/or Licensed Products, and (c) Controlled by Alnylam and (i) used by Alnylam in the Collaboration Program and/or (ii) identified during a Product Development Program as Know-How that will be used in the Commercialization of Licensed Products to be Developed in such Product Development Program.

Section 1.4 “ Alnylam Patent Rights ”. Alnylam Patent Rights shall mean any Patent Rights Controlled by Alnylam and Covering Alnylam Know-How, including those Patent Rights set forth on Schedule 1.4 , but excluding Alnylam’s interest in Program Patent Rights. The Parties acknowledge that Schedule 1.4 attached as of the Restatement Date is identical to Schedule 1.5 of the Original Collaboration Agreement and has not been modified since the Effective Date. Alnylam will provide Medtronic with an update to Schedule 1.4 within thirty (30) days after the Restatement Date.

Section 1.5 “ Alnylam siRNA ”. Alnylam siRNA shall mean any siRNA (a) the Discovery, Development, manufacture, Commercialization or other use of which uses Alnylam Know-How or Program Know-How or is Covered by Alnylam Patent Rights or Program Patent Rights and (b) that is made available or approved by Alnylam’s JRDC Representatives for Development in the Collaboration Program. Subject to Alnylam’s further development obligations pursuant to the siRNA Supply Agreement, if Alnylam opts out of a Product Development Program pursuant to Section 2.4(a), the Alnylam siRNAs with respect to the Licensed Product being developed in such Product Development Program shall be the Alnylam siRNAs made available by Alnylam’s JRDC Representatives for use in the Development of a Licensed Product in such Development Program prior to such opt-out.

Section 1.6 “ Blocking Third Party Intellectual Property ”. Blocking Third Party Intellectual Property shall mean, on a Licensed Product-by-Licensed Product and country-by-country basis, Valid Claims that (a) were not Controlled by Medtronic or by Alnylam as of the Restatement Date, (b) are not acquired or licensed by Medtronic or Alnylam, or any of their Affiliates, from a Third Party after the Restatement Date pursuant to a Section 2.5(d)(iii) [**] Agreement, and (c) Cover the manufacture or use of an siRNA or a Device contained in or used in such Licensed Product in such country. For the avoidance of doubt, Valid Claims Controlled by Alnylam or Medtronic under a [**] shall not constitute Blocking Third Party Intellectual Property.

Section 1.7 “[**] shall mean achievement of [**] criteria, determined pursuant to Section 2.3(a), for a Product Development Program as constituting reasonable evidence of [**].

Section 1.8 “ Collaboration Program ”. Collaboration Program shall mean the research and development program performed by the Parties pursuant to the Original Collaboration Agreement and to be performed by the Parties pursuant to this Agreement, to Develop Licensed Products.

Section 1.9 “ Collaboration Term ”. Collaboration Term shall mean the period commencing on the Effective Date and ending on the earliest of (a) the expiration or termination of all Product Development Terms, (b) the date (if any) on which the Collaboration Term is terminated by mutual written agreement of the Parties and (c) the date of termination of this Agreement in accordance with the provisions hereof.

Section 1.10 “ Commercialization” or “Commercialize ”. Commercialization or Commercialize shall mean any activities directed to marketing, promoting, distributing, importing, offering to sell, and/or selling a product, whether before or after Regulatory Approval for such product has been obtained.

Section 1.11 “ Commercializing Party ”. Commercializing Party shall mean, with respect to each Licensed Product and each country in the Territory, Medtronic, unless and until Alnylam becomes the Commercializing Party for such Licensed Product in such country due to (a) the exercise by Medtronic of its opt-out right pursuant to Section 2.4(b) or (b) Alnylam’s termination of Medtronic’s license rights relating to such Licensed Product in such country pursuant to Section 8.2.

Section 1.12 “ Commercially Reasonable Efforts ”. Commercially Reasonable Efforts shall mean the efforts, expertise and resources normally used by a Party to Discover, Develop, manufacture and Commercialize a product or compound owned by it or to which it has rights, which is of similar market potential at a similar stage in its development or product life, taking into account issues of safety and efficacy, product profile, difficulty in developing the product or compound, competitiveness of the marketplace for the product, the proprietary position of the compound or product, the regulatory structure involved, the availability and level of reimbursement for such treatment by Third Party payors or health insurance plans, the potential total profitability of the applicable product(s) marketed or to be marketed and other relevant factors affecting the cost, risk and timing of Development and the total potential reward to be obtained if a product is Commercialized. The Parties agree that Commercially Reasonable Efforts shall not require a Party to expend efforts, expertise and resources that such Party would not normally expend to Discover, Develop, manufacture and Commercialize a product or compound owned by it or to which it has rights, taking into account the foregoing factors.

Section 1.13 “ Confidential Information ”. Confidential Information of a Party shall mean all Know-How or other information that is of a confidential and proprietary nature to such Party. Confidential Information includes Know-How or other information (whether or not patentable) regarding a Party’s technology, products, business information or objectives and reports and audits under Section 4.7, and all biological materials of a Party. Notwithstanding the foregoing, Confidential Information shall not include Know-How or other information that:

(a) was known or used by the receiving Party or its Affiliates prior to its date of disclosure to the receiving Party as demonstrated by contemporaneous written records; or

(b) either before or after the date of the disclosure to the receiving Party is lawfully disclosed to the receiving Party or its Affiliates by sources other than the disclosing Party rightfully in possession of such Know-How or other information and not bound by confidentiality obligations to the disclosing Party; or

(c) either before or after the date of the disclosure to the receiving Party or its Affiliates is or becomes published or otherwise is or becomes part of the public domain through no breach hereof on the part of the receiving Party or its Affiliates; or

(d) is independently developed by or for the receiving Party or its Affiliates without reference to or reliance upon the Confidential Information of the disclosing Party as demonstrated by contemporaneous written records.

Section 1.14 “ Control” or “Controlled ”. Control or Controlled, with respect to any (a) Know-How or other information or materials or (b) intellectual property right, shall mean the possession (whether by license or ownership) by a Party of the ability to grant to the other Party access and/or a license as provided herein without violating the terms of any agreement with any Third Party existing as of the Effective Date or thereafter during the term of the Original Collaboration Agreement or this Agreement.

Section 1.15 “ Cover ”, “ Covering ” or “ Covered ”. Cover, Covering or Covered, with respect to a product or technology, shall mean that, but for a license granted to a Person under a Valid Claim included in the Patent Rights under which such license is granted, the Discovery, Development, manufacture, Commercialization and/or other use of such product or practice of such technology by such Person would infringe such Valid Claim.

Section 1.16 “ CPI ”. CPI shall mean the Consumer Price Index – Urban Wage Earners and Clerical Workers, U.S. City Average, All Items, 1982-84 = 100, published by the United States Department of Labor, Bureau of Labor Statistics (or its successor equivalent index) in the United States.

Section 1.17 “ Develop” or “Development ”. Develop or Development shall mean preclinical and clinical siRNA and/or Device development activities, including test method development and stability testing, Device design, siRNA-Device compatibility testing, toxicology, animal efficacy studies, formulation, quality assurance/quality control development, statistical analysis, clinical studies, regulatory affairs, product approval and registration.

Section 1.18 “ Development Candidate ”. Development Candidate shall mean an Alnylam siRNA that is designated as a Development Candidate by mutual agreement of the Parties.

Section 1.19 “ Development Costs ”. Development Costs shall mean FTE Costs incurred and costs and expenses paid to Third Parties (or payable to Third Parties and accrued in accordance with GAAP) by either Party after the Restatement Date, in the performance of Development responsibilities assigned to such Party under a Workplan in accordance with a budget under such Workplan that has been approved by the JRDC.

Section 1.20 “ Device ”. Device shall mean any implanted infusion device for delivery of siRNAs to the human nervous system.

Section 1.21 “ Device-Related ”. Device-Related, with respect to Know-How or Patent Rights, shall mean relating specifically to the design or physical features of a Device, any [**] a Device (excluding [**]), any hardware component of a Device, any software that controls a Device and/or any associated medical devices or accessories, such as [**], and any use or implantation of any of the foregoing, but not relating specifically to an siRNA ([**]) to be delivered by such Device.

Section 1.22 “ Discover” or “Discovery ”. Discover or Discovery shall mean any activities conducted to discover and characterize siRNAs as potential therapeutics in the Field and to support the designation of the same as Development Candidates in connection with any Product Development Program.

Section 1.23 “[**] shall mean an [**] produced [**].

Section 1.24 “ Effective Date ”. Effective Date shall mean February 8, 2005.

Section 1.25 “ Exclusivity Field ”. Exclusivity Field, with respect to a [**], shall mean the treatment of Target Indications for which a Licensed Product is to be Commercialized, using Devices for the direct delivery of siRNAs to the human nervous system [**]. Notwithstanding the foregoing, (a) the Exclusivity Field shall not include [**] and (b) the term ‘direct delivery to the human nervous system’ does not encompass [**].

Section 1.26 “ Executive Officers ”. Executive Officers shall mean Medtronic’s Senior Vice President of Medicine and Technology, Medtronic’s Vice President Corporate Technologies and New Ventures, or the President of Medtronic’s Neurological division (or an officer or employee of Medtronic then serving in a substantially equivalent capacity) and Alnylam’s Chief Operating Officer (or the officer or employee of Alnylam then serving in a substantially equivalent capacity).

Section 1.27 “ FDA ”. FDA shall mean the United States Food and Drug Administration.

Section 1.28 “ Field ”. Field shall mean the treatment of Neurodegenerative Diseases using Devices for the direct delivery of siRNAs to the human nervous system [**], it being understood that “direct delivery to the human nervous system” does not encompass [**]. For the avoidance of doubt, the Parties agree that treatment of a Neurodegenerative Disease does not include [**]. Notwithstanding the foregoing, the Field shall not include [**].

Section 1.29 “ First Commercial Sale ”. First Commercial Sale, with respect to a Licensed Product, shall mean the first commercial sale of such Licensed Product by the Commercializing Party, its Affiliates, distributors and/or agents. Sales for test marketing or clinical trial purposes shall not constitute a First Commercial Sale.

Section 1.30 “ FTE Cost ”. FTE Cost shall mean the product obtained by multiplying (a) the number of full-time-equivalent person-years (each consisting of a total of [**] hours) of

scientific, technical or managerial work by each Party’s personnel on or directly related to any Product Development Program by (b) $[**], increased or decreased annually by the percentage increase or decrease in the CPI as of December 31 of the then most recently ended calendar year over the level of the CPI on December 31, 2006 ( i.e. , the first such increase or decrease would occur on January 1, 2008).

Section 1.31 “ GAAP ”. GAAP shall mean then current United States generally accepted accounting principles, consistently applied.

Section 1.32 “ Gene Target ”. Gene Target shall mean [**].

Section 1.33 “ IND ”. IND shall mean an application submitted to a Regulatory Authority to initiate human clinical trials, including (a) an Investigational New Drug application or any successor application or procedure filed with the FDA, (b) except where otherwise specifically provided in this Agreement, any foreign equivalent of a U.S. Investigational New Drug application, and (c) all supplements and amendments that may be filed with respect to the foregoing.

Section 1.34 “ Initial PDP Workplan ”. Initial PDP Workplan shall mean the Workplan for the Initial Product Development Program agreed by the Parties as of the Restatement Date, as amended by the JRDC from time to time.

Section 1.35 “ Initial Product Development Program ”. Initial Product Development Program shall mean the Discovery and Development activities to be performed by the Parties hereunder with respect to Licensed Product(s) for the treatment of Huntington’s disease.

Section 1.36 “ JCC Representative ”. JCC Representative shall mean a Party’s representative designated by such Party to serve on the JCC pursuant to Section 2.2(b).

Section 1.37 “ JRDC Representative ”. JRDC Representative shall mean a Party’s representative designated by such Party to serve on the JRDC pursuant to Section 2.2(a).

Section 1.38 “[**] Agreement ”. [**] Agreement shall mean that certain [**] Research Agreement, signed in [**], by and between Medtronic and [**].

Section 1.39 “ Know-How ”. Know-How shall mean any tangible or intangible know-how, expertise, discoveries, inventions, information, data or materials, including ideas, concepts, formulas, methods, procedures, designs, technologies, compositions, plans, applications, technical data, samples, chemical compounds and biological materials and all derivatives, modifications and improvements thereof.

Section 1.40 “ Launch Costs ”. Launch Costs shall mean, with respect to a Licensed Product in the US Territory, the incremental portion of FTE Costs and costs and expenses paid to Third Parties (or payable to Third Parties and accrued in accordance with GAAP) in connection with pre-launch [**] market development, and the pre-launch [**] promotion, marketing, selling and product support, of such Licensed Product (excluding cost of goods sold) in the US Territory, in accordance with the budget for such Launch Costs that has been approved by the JCC, that represents the amount of such FTE Costs and costs and expenses paid to Third Parties

that is in excess of levels of similar Commercialization expenses that are incurred in periods [**] following First Commercial Sale. Launch Costs shall include the incremental portion described above for the following expenses related to (or the portion thereof reasonably allocable to) the promotion, marketing, selling and product support of such Licensed Product in the US Territory: (i) Third Party marketing expenses (training materials etc.) as well as internal cost for preparation of materials; (ii) medical education events; (iii) convention expenses; (iv) sales calls, (v) market research costs, (vi) sales rep training, (vii) physician training and education, (viii) referral or local marketing events, and (ix) senior product manager.

Section 1.41 “ Licensed Product ”. Licensed Product shall mean a Product within the Field that includes, as an active pharmaceutical ingredient, an Alnylam siRNA for delivery via a Medtronic Device, together with such Medtronic Device, associated delivery hardware, and disposables, in each case whether or not uniquely developed for exclusive delivery of Alnylam siRNA(s).

Section 1.42 “ Listed or Approved Third Party Agreement ”. Listed or Approved Third Party Agreement shall mean any agreement listed on Schedule 1.42 or approved by the JRDC following the Effective Date pursuant to which Alnylam and/or Medtronic acquire or license from a Third Party Valid Claims that Cover an Alnylam siRNA or a Medtronic Device contained or used, alone or in combination, in a Licensed Product. In addition, any agreement between Alnylam and [**] under which Patent Rights are sublicensed to Medtronic pursuant to Section 3.1(e) shall be deemed to be a Listed or Approved Third Party Agreement.

Section 1.43 “ Major Market ”. Major Market shall mean any of the United States, France, Germany, Italy, Spain, the United Kingdom or Japan.

Section 1.44 “ Manufacturing Cost ”. Manufacturing Cost, with respect to the manufacture and/or supply of Alnylam siRNAs or Medtronic Devices for incorporation into Licensed Products, shall mean (a) if either Party or an Affiliate of either Party manufactures such Alnylam siRNAs or Medtronic Devices, such Party’s and/or its Affiliates’ aggregate manufacturing costs, which aggregate costs shall consist of (i) internal and out-of-pocket costs of raw materials, labor and other variable costs directly incurred in the manufacture of such Alnylam siRNAs or Medtronic Devices and (ii) reasonable and appropriate allocations (excluding [**]) pursuant to GAAP of Alnylam siRNA or Medtronic Device manufacturing overhead costs, as applicable, or (b) [**] to a Third Party, such Party’s aggregate internal and out-of-pocket costs of procuring such [**] from the Third Party, testing such [**] and putting such [**].

Section 1.45 “ Medtronic Device ”. Medtronic Device shall mean, with respect to a particular Product Development Program, any Device that is made available or approved by Medtronic’s JRDC Representatives for use in the Development of a Licensed Product in such Product Development Program. Subject to Medtronic’s further development obligations pursuant to the Device Supply Agreement, if Medtronic opts out of a Product Development Program pursuant to Section 2.4(b), the Medtronic Device with respect to the Licensed Product being developed in such Product Development Program shall be the Medtronic Device made available by Medtronic’s JRDC Representatives for use in the Development of a Licensed Product in such Development Program prior to such opt-out.

Section 1.46 “ Medtronic Fiscal Quarter ”. Medtronic Fiscal Quarter shall mean Medtronic’s fiscal quarters used for financial reporting purposes which, as of the Effective Date are the 13-week periods ending on the last Friday in July, October, January and April.

Section 1.47 “ Medtronic Fiscal Year ”. Medtronic Fiscal Year shall mean Medtronic’s fiscal year used for financial reporting purposes, which, as of the Effective Date, is a period consisting of four consecutive Medtronic Fiscal Quarters, and ending on the last Friday in April of the applicable year.

Section 1.48 “ Medtronic Intellectual Property ”. Medtronic Intellectual Property shall mean Medtronic Know-How and Medtronic Patent Rights, collectively.

Section 1.49 “ Medtronic Know-How ”. Medtronic Know-How shall mean any Know-How, other than Know-How related to [**] and other than Program Know-How, that is (a) developed or acquired by Medtronic prior to or during the Collaboration Term, (b) used to Discover, Develop, manufacture or Commercialize Alnylam siRNAs, Medtronic Devices and/or Licensed Products, and (c) Controlled by Medtronic and (i) used by Medtronic in the Collaboration Program and/or (ii) identified during a Product Development Program as Know-How that will be used in the Commercialization of Licensed Products to be Developed in such Product Development Program.

Section 1.50 “ Medtronic Patent Rights ”. Medtronic Patent Rights shall mean any Patent Rights Controlled by Medtronic and Covering Medtronic Know-How, excluding Medtronic’s interest in Program Patent Rights.

Section 1.51 “ NDA ”. NDA shall mean an application submitted to a Regulatory Authority for marketing approval of a product, including (a) a New Drug Application, Product License Application or Biologics License Application filed with FDA or any successor applications or procedures, (b) a foreign equivalent of a U.S. New Drug Application, Product License Application or Biologics License Application or any successor applications or procedures, and (c) all supplements and amendments that may be filed with respect to the foregoing.

Section 1.52 “ Net Sales ”. Net Sales, with respect to a particular Licensed Product in a particular period, shall mean the gross amount invoiced by the Commercializing Party, its Affiliates and/or its sublicensees on sales or other dispositions (excluding sales or dispositions for use in clinical trials or other scientific testing, in either case for which Commercializing Party receives no revenue) of the Licensed Product to unrelated Third Parties during such period, less the following deductions:

(a) Trade, cash and quantity discounts actually allowed and taken directly with respect to such sales or other dispositions;

(b) Tariffs, duties, excises, sales taxes or other taxes imposed upon and paid directly with respect to the delivery, sale or use of the Licensed Product and included and separately stated in the applicable invoice (excluding national, state or local taxes based on income);

(c) Amounts repaid or credited by reason of rejections, defects, recalls or returns or because of reasonable and customary chargebacks, refunds, rebates or retroactive price reductions;

(d) Amounts previously included in Net Sales of Licensed Products that are written-off by the Commercializing Party as uncollectible in accordance with the Commercializing Party standard practices for writing off uncollectible amounts consistently applied; provided that if any such written-off amounts are subsequently collected, such collected amounts shall be included in Net Sales in the period in which they are subsequently collected; and

(e) Freight, insurance and other transportation charges incurred in shipping a Licensed Product to Third Parties, included and separately stated in the applicable invoice.

Such amounts shall, subject to the provisions of Sections 4.7 and 4.8, be determined from the books and records of the Commercializing Party, its Affiliates and/or its sublicensees, maintained in accordance with GAAP, consistently applied.

Section 1.53 “ Neurodegenerative Disease ”. Neurodegenerative Disease shall mean a disease of the brain and/or spinal cord in humans that is characterized by the chronic and progressive death of neurons which leads to the loss of normal neural function. Such diseases include, but are not limited to, Parkinson’s disease, Huntington’s disease, Alzheimer’s disease, and amyotrophic lateral sclerosis. For the avoidance of doubt, Neurodegenerative Disease shall not include [**].

Section 1.54 “ Party ”. Party shall mean Alnylam or Medtronic; “Parties” shall mean Alnylam and Medtronic. As used in this Agreement, references to “Third Parties” do not include a Party or its Affiliates.

Section 1.55 “ Patent Rights ”. Patent Rights shall mean United States and foreign patents, patent applications and/or provisional patent applications, utility models and utility model applications, design patents or registered industrial designs and design applications or applications for registration of industrial designs, and all substitutions, divisionals, continuations, continuation-in-part applications, continued prosecution applications, reissues, reexaminations and extensions thereof.

Section 1.56 “ Person ”. Person shall mean any corporation, limited or general partnership, limited liability company, joint venture, trust, unincorporated association, governmental body, authority, bureau or agency, any other entity or body, or an individual.

Section 1.57 “ Phase I Study ”. Phase I Study shall mean a study of an siRNA or Product in human volunteers or patients the purpose of which is preliminary determination of safety and tolerability of a dosing regime and for which there are no primary endpoints (as recognized by FDA or other Regulatory Authorities) in the protocol relating to efficacy.

Section 1.58 “ Phase II(a) Study ”. Phase II(a) Study shall mean a preliminary efficacy and safety study of an siRNA or Product in the target patient population designed to demonstrate Clinical Proof of Concept.

Section 1.59 “ Phase II(b) Study ”. Phase II(b) Study shall mean a study of an siRNA or Product to evaluate further any preliminary efficacy observed for, and the safety of, the siRNA or Product in the target patient population and/or to provide data that may be useful in the design of subsequent studies of the siRNA or Product such as Phase III Studies or Pivotal Studies.

Section 1.60 “ Phase III Study ”. Phase III Study shall mean a controlled study to confirm with statistical significance the efficacy and safety of an siRNA or Product performed to obtain marketing and/or manufacturing approval for the product in any country.

Section 1.61 “[**] Opt Out ”. [**] Opt Out shall mean, with respect to a Product Development Program, that a Party exercised its option to opt out of such Product Development Program pursuant to Section 2.4 any time after a [**] for the Initial Product Development Program or after the Restatement Date for any Additional Product Development Program but prior to the [**] with respect to any Alnylam siRNA included in such Product Development Program.

Section 1.62 “[**] Opt Out ”. [**] Opt Out shall mean, with respect to a Product Development Program, that a Party exercised its option to opt out of such Product Development Program pursuant to Section 2.4 any time after the [**] but prior to the achievement of [**] with respect to any Alnylam siRNA included in such Product Development Program.

Section 1.63 “[**] Opt Out ”. [**] Opt Out shall mean, with respect to a Product Development Program, that a Party exercised its option to opt out of such Product Development Program pursuant to Section 2.4 any time after the achievement of [**] but prior to the end of the Product Development Term.

Section 1.64 “[**] Opt Out ”. [**] Opt Out shall mean, with respect to a Product Development Program, that a Party exercised its option to opt out of such Product Development Program pursuant to Section 2.4 at any time after the [**] but prior to the [**] with respect to any Alnylam siRNA included in such Product Development Program.

Section 1.65 “ Preliminary Success Criteria ”. Preliminary Success Criteria shall mean the suppression, distribution and therapeutic criteria with respect to an Alnylam siRNA under the Initial Product Development Program as shall be agreed by the Parties or as shall be [**] pursuant to Section 2.3(a).

Section 1.66 “ Primary Sequence or Chemical Modification Know-How ”. Primary Sequence or Chemical Modifications Know-How shall mean information about the primary sequence of any siRNA or chemical modifications incorporated into any siRNA.

Section 1.67 “ Product ”. Product shall mean a human therapeutic product that includes siRNA(s) as active pharmaceutical ingredient(s) delivered or approved for delivery via a Device, together with any Device, associated delivery hardware, and disposables whether or not uniquely developed for exclusive delivery of such siRNA(s).

Section 1.68 “ Product Development Program ”. Product Development Program shall mean the Initial Product Development Program and/or any Additional Product Development Program(s).

Section 1.69 “ Product Development Term ”. Product Development Term, with respect to each Product Development Program, shall mean the period commencing on (a) with respect to the Initial Product Development Program, the Restatement Date, and (b) with respect to any Additional Product Development Program, the date on which the Parties mutually agree to commence such Additional Product Development Program in accordance with Section 2.3(e), and, subject to [**], ending on the earliest date on which a First Commercial Sale of Licensed Product(s) for the treatment of each of the Target Indication(s) designated for such Product Development Program has occurred.

Section 1.70 “ Program Intellectual Property ”. Program Intellectual Property shall mean Program Know-How and Program Patent Rights, collectively.

Section 1.71 “ Program Know-How ”. Program Know-How shall mean any Know-How or interest therein, other than Know-How related to [**], that is developed or acquired, either solely by a Party and/or its Affiliate(s) or jointly by both Parties and/or their Affiliate(s), in the conduct of the Collaboration Program. For the avoidance of doubt, any Know-How, including any Know-How that is Covered by Patent Rights Controlled by Medtronic, that is sublicensed by Medtronic to Alnylam (or, in the case of Know-How assigned to Medtronic under the [**] Agreement, that is licensed by Medtronic to Alnylam) under the letter agreement dated [**] between the Parties concerning the [**] Agreement shall be deemed Program Know-How hereunder.

Section 1.72 “ Program Patent Rights ”. Program Patent Rights shall mean any Patent Rights or interest therein Controlled by either Party or Controlled jointly by the Parties that Cover Program Know-How.

Section 1.73 “ Regulatory Approval ”. Regulatory Approval shall mean the approval of the applicable Regulatory Authority necessary for the marketing and sale of a Licensed Product for a particular indication in a country, excluding separate pricing and/or reimbursement approvals that may be required.

Section 1.74 “ Regulatory Authority ”. Regulatory Authority shall mean a federal, national, multinational, state, provincial or local regulatory agency, department, bureau or other governmental entity with authority over the testing, manufacture, use, storage, import, promotion, marketing or sale of a Product in a country or territory.

Section 1.75 “ ROW Territory ”. ROW Territory shall mean all countries in the world other than the US Territory.

Section 1.76 “ Royalty Term ”. Royalty Term, with respect to each Licensed Product in each country of the Territory, shall mean the period of time commencing with the First Commercial Sale of such Licensed Product in such country and ending on the later of (a) the latest date on which the use, offer for sale, sale or importation of such Licensed Product in such country or the manufacture of such Licensed Product in the country of manufacture is Covered by a Valid Claim of Alnylam Patent Rights, Medtronic Patent Rights or Program Patent Rights, or (b) a specified number of years after First Commercial Sale of such Licensed Product in such

country, which number shall be fifteen (15) years with respect to any Licensed Product resulting from the Initial Product Development Program.

Section 1.77 “ Section 2.5(d)(iii) [**] Agreement ”. Section 2.5(d)(iii) [**] Agreement shall mean an agreement entered into by a [**] with a Third Party, as described in Section 2.5(d)(iii), that was not approved by the JRDC.

Section 1.78 “ siRNA ”. siRNA shall mean a composition designed to act primarily through an RNAi mechanism which consists of either (a) two separate oligomers of native or chemically modified RNA that are hybridized to one another along a substantial portion of their lengths, or (b) a single oligomer of native or chemically modified RNA that is hybridized to itself by self-complementary base-pairing along a substantial portion of its length to form a hairpin.

Section 1.79 “ Target Indication ”. Target Indication shall mean, with respect to an Alnylam siRNA Developed in the Initial Product Development Program, Huntington’s disease, and, with respect to an Alnylam siRNA Developed in any Additional Product Development Program, each human disease or condition that is designated by the Parties as a Target Indication with respect to such Alnylam siRNA in accordance with Section 2.3(e).

Section 1.80 “ Territory ”. Territory shall mean, subject to Section 8.2(b), the US Territory and/or the ROW Territory.

Section 1.81 “ Third Party ”. Third Party shall mean any Person other than Alnylam or Medtronic and their respective Affiliates.

Section 1.82 “ US Territory ”. US Territory shall mean the United States of America, including its territories, possessions and Puerto Rico.

Section 1.83 “ Valid Claim ”. Valid Claim shall mean (a) a claim of any issued, unexpired patent that has not been revoked or held unenforceable or invalid by a decision of a court or governmental agency of competent jurisdiction from which no appeal can be taken, or with respect to which an appeal is not taken within the time allowed for appeal, and that has not been disclaimed or admitted to be invalid or unenforceable through reissue, disclaimer or otherwise, or (b) a claim of any published patent application filed by a Party in good faith that has not been cancelled, withdrawn or abandoned, nor been pending for more than [**] years from the filing date of the earliest patent application from which such patent application claims priority.

Section 1.84 “ Workplan ”. Workplan shall mean the Initial PDP Workplan or any other work plan describing the activities to be undertaken during the applicable Product Development Program, as adopted, updated or amended pursuant to Section 2.3.

Section 1.85 Additional Definitions . Each of the following definitions is set forth in the section of this Agreement indicated below:


Definition	Section
“Additional Product Development Program”		2.3(e)
“Agreement”		Preamble
“Alnylam”		Preamble
“Alnylam Discontinuation Notice”		2.4(a)
“Alnylam Indemnified Parties”		9.1(a)
“[**] Agreement”		Schedule 1.42
“[**] Licensors”		3.2(e)
“Breaching Party”		8.2(a) or 8.2(c)
“[**]”		2.5(d)
“[**]”		9.3
“[**]”		3.1(e)
“Device Inventions”		5.1(b)
“Device Supply Agreement”		8.4(a)(vii)
“Electing Party”		5.2(c)
“Enjoined Period”		4.6
“Exclusive Negotiation Period”		2.5(c)(ii)
“GI”		Schedule 1.42
“GI Agreements”		Schedule 1.42
“Go Decision”		2.3(c)(i)
“Indemnified Party”		9.1(d)
“Indemnifying Party”		9.1(d)
“Initial Commitment”		4.1(a)
“Invalidity Claim”		5.4(c)
“Isis Agreement”		Schedule 1.42
“JCC”		2.1
“Jointly Developed Inventions”		5.1(c)
“JRDC”		2.2(a)
“[**]”		2.3(d)
“Losses”		9.1(a)
“[**]”		2.5(a)
“Medtronic”		Preamble
“Medtronic Discontinuation Notice”		2.4(b)
“Medtronic Indemnified Parties”		9.1(b)
“[**] Agreement”		Schedule 1.42
“[**] Agreement”		Schedule 1.42
“No-Go Decision”		2.3(c)(i)
“Non-Breaching Party”		8.2(a) or 8.2(c)
“Non-Electing Party”		5.2(c)
“Non-Performing Party”		2.3(f)
“Original Collaboration Agreement”		Introduction
“Performing Party”		2.3(f)
“[**]”		Schedule 1.42
“Program Data”		5.1(e)
“Quarterly Reports”		4.6(a)
“[**]”		2.5(d)
“Reimbursable Launch Costs”		4.3(f)


Definition	Section
“Restatement Date”		Preamble
“Right of Access”		5.1(e)
“RoFN Notice”		2.5(c)(i)
“RoFN Offer”		2.5(c)(iii)
“RoFN Opportunity”		2.5(c)
“RoFN Response Notice”		2.5(c)(i)
“RoFN Response Period”		2.5(c)(i)
“RoFN Term”		2.5(c)
“SEC”		6.1
“Severed Clause”		9.11
“siRNA Supply Agreement”		2.6(b)
“Sole Inventions”		5.1(c)
“Stanford Agreement”		Schedule 1.42
“Third Party Infringement Claim”		5.4(a)
“[**]”		2.5(a)

Article II

Collaboration Program; Commercialization

Section 2.1 General . Prior to the Restatement Date, the Parties conducted the Technology Development Program (as defined in the Original Collaboration Agreement). Pursuant to the terms of this Agreement, the Parties have agreed to terminate the Technology Development Program and to transition their collaboration on the Discovery, Development, manufacture and Commercialization of Licensed Products to the Initial Product Development Program commencing on the Restatement Date. The objective of the Collaboration Program shall continue to be the Discovery and Development of Licensed Products. Both Parties will continue to be engaged in the conduct of the Collaboration Program, and shall be responsible for various Collaboration Program activities as set forth in this Agreement. In connection with this amendment and restatement of the Original Collaboration Agreement, the Parties have also agreed to establish a Joint Commercialization Committee (the “ JCC ”) to oversee the Commercialization of Licensed Products

Section 2.2 Governance; Decision-Making .

(a) JRDC . The Joint Research and Development Committee (the “ JRDC ”) shall be comprised of four (4) JRDC Representatives designated by Alnylam and four (4) JRDC Representatives designated by Medtronic, one of which JRDC Representatives from each Party shall be designated as the co-chair of the JRDC and each of which JRDC Representatives shall be of the seniority and experience appropriate for service on the JRDC in light of the functions, responsibilities and authority of the JRDC. The JRDC shall continue to oversee the worldwide research and development activities of the Parties under the Collaboration Program, including regulatory matters, as set forth below. Each Party shall make its designation of its post-Restatement Date JRDC Representatives not later than thirty (30) days after the Restatement Date. Subject to Sections 2.2(c) and 2.4 below, the JRDC shall meet at least quarterly until the

end of the Collaboration Term, to (i) review the efforts of the Parties in the conduct of the Collaboration Program and monitor the progress of the Product Development Program(s) on a regular basis, (ii) review and, subject to Sections 2.2(e) and 2.3(a), approve proposed updates and amendments to the Workplan for each Product Development Program, and (iii) otherwise oversee and direct the Collaboration Program activities undertaken pursuant to this Agreement. The JRDC shall be dissolved and its activities and authority terminated upon the earliest of (A) the end of the Collaboration Term, (B) Alnylam’s election to discontinue participation in the JRDC pursuant to Section 2.2(c), and (C) the exercise by either Party of its right to opt out of all Product Development Programs pursuant to Section 2.4.

(b) JCC . Upon filing of an NDA in the United States for a Licensed Product hereunder, the Parties shall establish the JCC, comprised of three (3) JCC Representatives designated by Alnylam and three (3) JCC Representatives designated by Medtronic, each of which JCC Representatives shall be of the seniority and experience appropriate for service on the JCC in light of the functions, responsibilities and authority of the JCC. The JCC shall be responsible for overseeing Commercialization activities of the Parties with respect to Licensed Product in the United States. Subject to Sections 2.2(c) and 2.4 below, the JCC shall meet at least quarterly until the end of the last-to-expire Royalty Term for a Licensed Product in the United States.

(c) Alnylam Right to Discontinue Participation . At any time after filing of an NDA in the United States for a Licensed Product hereunder, Alnylam shall have the right to discontinue its participation in the JRDC and/or the JCC, and such discontinuation by Alnylam shall not constitute a breach of any of Alnylam’s obligations hereunder. For the avoidance of doubt, Alnylam may exercise its right to discontinue its participation in the JRDC and/or the JCC pursuant to this Section 2.2(c) without opting out of any Product Development Program pursuant to Section 2.4(a).

(d) Meetings; Representatives . The location of such meetings of the JRDC and JCC shall alternate between Minneapolis, MN and Cambridge, MA, unless otherwise agreed by the JRDC or JCC, as the case may be. The JRDC and JCC may also meet by means of a telephone or video conference call, and may take action by vote at a meeting or telephone or video conference call, or pursuant to a written vote; provided that the JRDC and the JCC shall hold at least one meeting per year in person in Minneapolis and one meeting per year in person in Cambridge. Each Party may change any one or more of its JRDC Representatives or JCC Representatives, as the case may be, at any time upon written notice to the other Party. Each Party shall use Commercially Reasonable Efforts to cause its JRDC Representatives and JCC Representatives to attend the meetings of the JRDC and JCC, respectively. If any of a Party’s JRDC Representatives or JCC Representatives, as the case may be, is unable to attend a meeting, such Party may designate an alternate to attend such meeting in place of the absent JRDC Representative or JCC Representative. In addition, each Party may, at its discretion, invite non-voting employees, and, with the consent of the other Party, consultants or scientific advisors (provided they are engaged as such under obligations of confidentiality) to attend the meetings of the JRDC or JCC.

(e) Decision-Making Authority . All decisions of the JRDC and JCC, as the case may be, shall be made by majority vote, with each Party’s JRDC

Representatives or JCC Representatives collectively having one vote, and the goal of all decision making shall be to achieve consensus. Upon fifteen (15) days prior written notice, either Party may convene a special meeting of the JRDC or JCC, as the case may be, for the purpose of resolving any failure to reach agreement on a matter within the scope of the authority and responsibility of the JRDC or JCC, as the case may be. If the JRDC or JCC, as the case may be, is unable to reach agreement on any matter so referred to it for resolution by one or more of the Parties within thirty (30) days after the matter is so referred to it, such matter shall be referred to the Executive Officers for resolution. If the matter is not resolved by the Executive Officers within thirty (30) days after referral to the Executive Officers, then:

(i) if such matter relates primarily to Collaboration Program activities with respect to any Alnylam siRNA, Alnylam shall have the right to decide the matter; provided that Alnylam has not discontinued its participation in the JRDC pursuant to Section 2.2(c) or opted out of the Product Development Program pursuant to Section 2.4; provided further that , if Alnylam has discontinued its participation in the JRDC pursuant to Section 2.2(c) or opted out of the Product Development Program pursuant to Section 2.4, Medtronic shall have the right to decide the matter;

(ii) notwithstanding clause (i) above, if such matter relates primarily to the Development of Medtronic Devices for use in Licensed Products, Medtronic shall have the right to decide the matter; provided that Medtronic has not opted out of the Product Development Program pursuant to Section 2.4; provided further that , if Medtronic has opted out of the Product Development Program pursuant to Section 2.4, Alnylam shall have the right to decide the matter;

(iii) if such matter relates primarily to Commercialization matters, the Commercializing Party shall have the right to decide the matter; provided that the budget for Launch Costs for any Licensed Product shall be subject to the approval of both Parties, such approval not to be unreasonably withheld, delayed or conditioned; and

(iv) if such matter is not described in paragraphs (i), (ii) or (iii) above, then neither Party shall have the unilateral right to decide the matter.

Notwithstanding anything in this Section 2.2(e), neither Party shall have a unilateral right to resolve any dispute involving the breach or alleged breach of this Agreement, to amend or modify this Agreement or the Parties’ respective rights and obligations hereunder or, except as expressly provided in this Section 2.2(e), any Workplan or the Parties’ respective rights and obligations thereunder.

Furthermore, notwithstanding anything in this Section 2.2(e), neither Party shall have a unilateral right to amend or modify any Workplan if such amendment or modification would require the use of additional Know-How or a license under additional Patent Rights that is Controlled by the other Party and subject to financial obligations to any Third Party (other than financial obligations under a Section 2.5(d)(iii) [**] Agreement) unless in connection with such amendment or modification the applicable Third Party agreement (other than a Section 2.5(d)(iii) [**] Agreement) is approved by the JRDC as a Listed or Approved Third Party Agreement.

Section 2.3 Conduct of the Collaboration Program .

(a) Workplans . The Parties shall undertake each Product Development Program in accordance with a Workplan for such Product Development Program. The Initial PDP Workplan has been agreed by the Parties as of the Restatement Date, except that (i) the Preliminary Success Criteria shall be agreed by the Parties within ninety (90) days after the Restatement Date or, if the Parties are unable to agree within such 90-day period, each Party shall notify the other Party, in writing, of [**] Preliminary Success Criteria, and (ii) the [**] criteria for the Initial Product Development Program, including the design and protocols for conducting studies suitable to demonstrate [**], shall be agreed to by the Parties within [**]; provided that if the Parties are unable to agree upon the [**] criteria within such [**] period, then either Party may refer the matter for resolution pursuant to the procedures set forth in the second and third sentences of Section 2.2(e). The first dosing of a participant in the first such Phase II(a) Study or Phase II(b) Study shall not be undertaken by or on behalf of either Party until after the [**] criteria have been determined and documented for such Product Development Program. Notwithstanding anything to the contrary in a Workplan, Medtronic shall not have any liability for any failure to develop any improvement to or next generation of a Medtronic Device. The Workplan, the license royalty rates and the minimum duration of the Royalty Term for each Additional Product Development Program shall be agreed by the Parties in connection with the Parties’ agreement to initiate such Additional Product Development Program. Each Workplan shall address, in reasonable detail, the roles and responsibilities of each Party with respect to the Discovery and Development of Licensed Product(s) covered by such Product Development Program, including each Party’s roles and responsibilities with respect to (x) clinical study activities, such as filing INDs with Regulatory Authorities, the selection of centers, negotiation and execution of clinical agreements, training, monitoring, data collection, notice of adverse events and other regulatory requirements, and (y) other activities as necessary to effect the Discovery and Development of Licensed Products under such Collaboration Program. Such Workplan shall further (A) set forth the Target Indication(s) for the corresponding Product Development Program, (B) include budgets for the Parties’ Discovery and Development activities pursuant to such Product Development Program, and (C) except as provided above with respect to the Initial Workplan, set forth the clinical results which, if achieved, would demonstrate [**] for such Product Development Program and the design and protocols for conducting studies suitable to demonstrate whether such results are achieved. The Parties acknowledge that in the course of the Collaboration Program, the Parties (but not the JRDC) may modify the designation of the Development Candidate and Target Indication(s), the clinical results which, if achieved, would demonstrate [**], and the design and protocols for conducting studies designed to produce such clinical results, by amending the relevant Workplan to reflect such modification(s). Subject to the foregoing, each Workplan shall be updated annually by the JRDC. Each Party, through its JRDC Representatives may, at any time or from time to time, also submit proposed additions, updates or amendments to the Workplan to the JRDC for its review and approval. Any such additions, updates or amendments shall not become effective until approved in writing by the JRDC. The JRDC shall review and consider any such proposed Workplans, additions, updates or amendments on an expeditious basis, and all such Workplans, additions, updates and amendments approved as set forth above shall thereafter govern the Parties’ Discovery and Development activities pursuant to the applicable Product Development Program.

(b) General Responsibilities of Each Party . Subject to Section 2.4,

(i) Medtronic shall be responsible for all Collaboration Program activities relating to the Development, manufacture and Commercialization of Licensed Product(s) solely for sale in the ROW Territory.

(ii) Each Party shall use Commercially Reasonable Efforts to (A) undertake the responsibilities assigned to such Party in any applicable Workplan, (B) perform its obligations hereunder in a scientifically sound and workmanlike manner; (C) as appropriate, make available to the other Party those resources set forth in any applicable Workplan; and (D) carry out all work done in the course of the Collaboration Program in material compliance with all applicable federal, state or local laws, regulations and guidelines governing the conduct of such work. Either Party may perform its Collaboration Program responsibilities hereunder through its Affiliates or through the use of Third Party contractors such as contract research organizations, contract employees, consultants and the like who merely conduct activities on behalf of such Party, are subject to such Party’s supervision and control, and will not have any rights (other than non-exclusive research rights) in any intellectual property created in conjunction with such activities; provided that such Party shall remain primarily liable for its obligations under this Agreement.

(i) The initial phase of the Initial Product Development Program shall consist of certain activities designated in the Initial PDP Workplan directed toward the achievement of the mutually agreed Preliminary Success Criteria or, if the Parties are unable to agree upon the Preliminary Success Criteria, the achievement of [**]. Such initial phase activities consist primarily of [**] studies, and the Parties’ funding obligations with respect to such activities are set forth in Section 4.1(a). Upon completion of such initial phase activities, the Parties will continue the Initial Product Development Program if (A) both Parties agree that the mutually agreed Preliminary Success Criteria or, if the Parties are unable to agree upon the Preliminary Success Criteria, [**] Preliminary Success Criteria have been achieved, (B) both Parties otherwise agree to continue, or (C) the Parties are unable to agree as to whether the mutually agreed Preliminary Success Criteria or, if the Parties are unable to agree upon the Preliminary Success Criteria, [**] Preliminary Success Criteria have been achieved, and a [**] determines that the mutually agreed Preliminary Success Criteria or, if the Parties are unable to agree upon the Preliminary Success Criteria, [**] Preliminary Success Criteria have been achieved pursuant to Section 2.3(d)(i) (a “ Go Decision ”). Alternatively, subject to Section 2.3(c)(iii), the Initial Product Development Program will not continue beyond the Initial Commitment if either (x) the mutually agreed Preliminary Success Criteria or, if the Parties are unable to agree upon the Preliminary Success Criteria, [**] Preliminary Success Criteria have not been achieved or (y) the Parties are unable to agree as to whether the Preliminary Success Criteria have been achieved and a [**] determines that the mutually agreed Preliminary Success Criteria or, if the Parties are unable to agree upon the Preliminary Success Criteria, [**] Preliminary Success Criteria have not been achieved pursuant to Section 2.3(d)(i) (a “ No-Go Decision ”).

(ii) If a Go Decision results from the initial phase of the Initial Product Development Program, the Parties shall proceed to the next phase of Development under the Initial PDP Workplan.

(iii) If a No-Go Decision results from the initial phase of the Initial Product Development Program, the Parties shall not proceed to the next phase of Development under the Initial PDP Workplan and, unless otherwise agreed by the Parties, either Party may terminate this Agreement in accordance with Section 8.3.

(d) Certain Matters Subject to Third Party Determination .

(i) The Parties shall submit to a panel of three [**] the following matters: (A) if the Parties are unable to agree, whether the [**], (B) whether the [**] or (C) if the Parties are unable to agree, whether [**] in any Product Development Program. One member of any such [**] shall be nominated by Alnylam, one member shall be nominated by Medtronic and the third shall be selected by the two members nominated by the Parties. If the Parties pursue more than one Product Development Program, the Parties may elect to [**] for different Product Development Programs in order to [**] of the respective Product Development Programs. The determination of such [**] as to such dispute shall be binding on both Parties. Each Party shall be responsible for [**] member nominated by it and the Parties shall share equally in [**]. The Parties may also elect by mutual agreement to use a [**] for guidance on other issues that may arise in the course of the Collaboration Program.

(ii) If the Parties have not entered into an siRNA Supply Agreement within the timeframe set forth in Section 2.6(b) or a Device Supply Agreement within the timeframe set forth in Section 8.4(a)(vii), the Parties shall [**] (in the case of the siRNA Supply Agreement) or [**] (in the case of the Device Supply Agreement) for the purpose of promptly finalizing negotiations of the applicable agreement. Each Party shall [**]. Such [**] shall [**] the provisions set forth in Exhibit A or Exhibit D , as applicable and, to the extent not addressed in Exhibit A or Exhibit D , as applicable, [**]. The Parties shall enter into the form of agreement [**] within one (1) week of [**].

(e) Additional Product Development Programs . At any time during the Collaboration Term, either pursuant to Section 2.5(c) or otherwise, the Parties may mutually agree (i) to discuss and, if the Parties agree, initiate additional program(s) (each, an “ Additional Product Development Program ”) to Discover and Develop additional Alnylam siRNA(s), Development Candidate(s) and Licensed Product(s) in the Field, (ii) to adopt additional Workplan(s) for any such Additional Product Development Program(s), and (iii) on the Target Indication(s) for Alnylam siRNA(s) or Development Candidate(s) within each such Additional Product Development Program. In connection with each JRDC meeting, each Party shall provide to the other Party any material data and information Controlled by such Party (A) relating to any proposed Additional Product Development Program or (B) during the RoFN Term, obtained by such Party from any [**] in the Field pursuant to Section 2.5(d) for which the providing Party is the [**], other than such data and information relating to RoFN Opportunities for which Alnylam has the right to enter into definitive agreements with Third Parties pursuant to Section 2.5(c)(iv). For the avoidance of doubt, additional Development relating to delivery of the same siRNA to the same location to treat a different indication shall not constitute a Product

Development Program separate from an existing Product Development Program in which such siRNA is Developed for delivery to such location; provided that any such additional Development shall be subject to approval of any associated modifications to the applicable Workplan, as set forth in Sections 2.2(a) and 2.2(e).

(f) Non-Exclusive Remedy for Failure to Perform Workplan Responsibilities . If either Party (the “ Performing Party ”) reasonably determines that the other Party (the “ Non-Performing Party ”) has materially failed to fulfill such Non-Performing Party’s responsibilities under the Workplan for a Product Development Program, then, without limiting any remedies that may be available under this Agreement to the Performing Party for such material failure by the Non-Performing Party, the Performing Party may elect the following non-exclusive remedy for such material failure: (i) the Performing Party may provide the Non-Performing Party with written notice of the Non-Performing Party’s material failure, which notice shall set forth with reasonable specificity the steps that the Performing Party believes the Non-Performing Party must take to cure such material failure; (ii) during the sixty (60) day period following the foregoing written notice from the Performing Party, the Non-Performing Party shall have the right to cure its material failure, if any, and to respond in writing to the Performing Party regarding the steps taken by the Non-Performing Party to effect such cure and/or disputing the Performing Party’s assertions of material failure; (iii) if after such sixty (60) day period, the Performing Party reasonably determines that the Non-Performing Party has still materially failed to perform the Non-Performing Party’s responsibilities under the Workplan, as previously set forth in the Performing Party’s notice to the Non-Performing Party, the Performing Party may elect, either itself or through a Third Party, to (x) perform the specific Workplan activities that the Non-Performing Party materially failed to perform, (y) modify the applicable Workplan budget to include and allocate the costs of such performance by or on behalf of the Performing Party ( i.e. , require the Non-Performing Party to share in such costs in accordance with Section 4.1(a) or Section 4.1(b), as applicable) and (z) exclude the Non-Performing Party’s costs relating to its material failure to perform from the applicable Workplan budget ( i.e. , not permit the Non-Performing Party to include such costs in the costs that the Performing Party is required to share in accordance with Section 4.1(a) or Section 4.1(b), as applicable). Any dispute under this Section 2.3(f) as to whether a material failure has occurred or whether any such failure has been cured shall be subject to resolution in the same manner as that to which any other alleged breach of this Agreement is subject; provided that the Performing Party may elect to pursue the remedy set forth in clause (x) above before any such dispute has been resolved, in which case the costs of such performance by or on behalf of the Performing Party shall be borne by the Parties as finally determined through dispute resolution ( i.e. , the Performing Party may go “at risk” to perform such activities and, if such dispute is resolved in the Performing Party’s favor, the costs of such performance shall be shared by the Non-Performing Party as set forth in clause (y) above).

Section 2.4 Right to Opt Out .

(a) Discontinuation of Participation in Product Development Program by Alnylam . Notwithstanding anything to the contrary in this Agreement, Alnylam may at any time during any Product Development Term, or, in the case of the Initial Development Program, only at any time after a Go Decision and prior to the end of the Product Development Term for the Initial Product Development Program, in its sole discretion, by ninety (90) days’ prior written notice to Medtronic (an “ Alnylam Discontinuation Notice ”), discontinue its participation in any

Product Development Program, and no such discontinuation shall constitute a breach of Alnylam’s obligations hereunder. If Alnylam discontinues its participation in a Product Development Program, then (i) the Parties shall perform a final reconciliation of applicable Development Costs for the US Territory pursuant to Section 4.7(a) through the effective date of such discontinued participation, and thereafter, Alnylam shall have no further obligation to share in the Development Costs for such Product Development Program pursuant to Section 4.1(b); (ii) the JRDC and JCC shall cease to have oversight over such Product Development Program and the Licensed Products Developed thereunder; (iii) subject to Alnylam’s obligations pursuant to the siRNA Supply Agreement, Alnylam shall have no further Workplan responsibilities in connection with such Product Development Program; (iv) Medtronic may elect to continue Developing Licensed Product(s) Developed in such Product Development Program unilaterally; (v) if Medtronic elects to continue Developing Licensed Product(s) Developed in such Product Development Program unilaterally, Alnylam shall, if requested by Medtronic, enter into an arrangement under which Alnylam will, directly or through a Third Party, supply Alnylam siRNAs to Medtronic for use in Licensed Products Developed under such Product Development Program as set forth in Section 8.4(c)(vi); (vi) Alnylam’s license rights set forth in Section 3.2(b) with respect to the Commercialization of Licensed Products Developed in such Product Development Program shall terminate and (vii) from and after such discontinuation by Alnylam, the royalties payable by Medtronic to Alnylam on Net Sales of Licensed Products Developed in such Product Development Program shall be reduced as set forth in Section 4.3(b).

(b) Discontinuation of Participation in Product Development Program by Medtronic . Notwithstanding anything to the contrary in this Agreement, Medtronic may at any time during any Product Development Term, or, in the case of the Initial Development Program, only at any time after a Go Decision and prior to the end of the Product Development Term for the Initial Product Development Program, in its sole discretion, by ninety (90) days’ prior written notice to Alnylam (a “ Medtronic Discontinuation Notice ”), discontinue its participation in any Product Development Program, and no such discontinuation shall constitute a breach of Medtronic’s obligations hereunder. If Medtronic discontinues its participation in a Product Development Program, then (i) the Parties shall perform a final reconciliation of applicable Development Costs for the US Territory pursuant to Section 4.6(a) through the effective date of such discontinued participation, and thereafter, Medtronic shall have no further obligation to share in the Development Costs for such Product Development Program pursuant to Section 4.1(b); (ii) the JRDC and JCC shall cease to have oversight over such Product Development Program and the Licensed Products Developed thereunder; (iii) subject to Medtronic’s obligations pursuant to the Device Supply Agreement, Medtronic shall have no further Workplan or Commercialization responsibilities in connection with such Product Development Program; (iv) Alnylam may elect to continue Developing Licensed Product(s) Developed in such Product Development Program unilaterally; (v) if Alnylam elects to continue Developing Licensed Product(s) Developed in such Product Development Program unilaterally, Medtronic shall, if requested by Alnylam, enter into a Device Supply Agreement as set forth in Section 8.4(a)(vii); (vi) Medtronic’s license rights set forth in Section 3.1(b) with respect to the Commercialization of Licensed Products Developed in such Product Development Program shall terminate and, if Alnylam elects to continue Developing the applicable Licensed Product(s), Alnylam shall thereafter be the Commercializing Party for such Licensed Products in both the US Territory and the ROW Territory; and (vii) from and after such discontinuation by Medtronic, Alnylam shall

pay royalties to Medtronic on Net Sales of Licensed Products Developed in such Product Development Program as set forth in Section 4.3(b).

(c) If a Party elects to discontinue its participation in a Product Development Program pursuant to Section 2.4(a) or Section 2.4(b), and thereafter the other Party determines not to continue unilaterally Developing any Licensed Product Developed in such Product Development Program, then the Parties shall discuss whether and on what terms they may desire to jointly seek a licensee for such Licensed Product. In such circumstances, if the Parties elect not to jointly seek a licensee for such Licensed Product, then such Product Development Program shall terminate and the consequences set forth in Section 8.4(d) shall apply with respect to such Product Development Program.

Section 2.5 Exclusivity, Diligence and RoFN Obligations .

(a) Exclusivity in Exclusivity Field . During the Product Development Term for any Product Development Program, neither Party shall, directly or indirectly, by itself or jointly with or through any of its Affiliates or any Third Parties (but excluding minority investments in Third Parties where such Party’s engagement is limited to holding such minority investments and typical rights associated therewith), engage in the [**] for such Product Development Program, other than pursuant to this Agreement. In addition, commencing with [**] and continuing for the [**], neither Party shall, directly or indirectly, by itself or jointly with or through any of its Affiliates or any Third Parties (but excluding minority investments in Third Parties where such Party’s engagement is limited to holding such minority investments), engage in the [**] in such Licensed Product, other than pursuant to this Agreement. Notwithstanding the foregoing, (i) Alnylam shall be [**] and (ii) Alnylam shall [**].

(b) Diligence Obligations . With respect to each Product Development Program, the Commercializing Party shall use its Commercially Reasonable Efforts to obtain Regulatory Approvals for and Commercialize at least one Licensed Product in each Major Market for each Target Indication. The non-Commercializing Party acknowledges that a failure by the Commercializing Party to obtain a Regulatory Approval for or to Commercialize a Licensed Product in a Major Market for a Target Indication may be consistent with the exercise of Commercially Reasonable Efforts under appropriate circumstances. The non-Commercializing Party’s sole and exclusive remedy and the Commercializing Party’s sole and exclusive liability for any failure to use its Commercially Reasonable Efforts to obtain Regulatory Approvals for and/or to Commercialize at least one Licensed Product in one or more particular Major Markets, as well as for any failure to use Commercially Reasonable Efforts to continue to Commercialize a Licensed Product in any Major Market, shall be the termination of the Commercializing Party’s license rights for such Major Market pursuant to Section 8.2(b) or, if such failure relates to all Major Markets and to all Target Indications, the termination of this Agreement pursuant to Section 8.2(c). For the avoidance of doubt, the Commercializing Party’s obligation hereunder will not survive the expiration or termination of this Agreement.

(c) RoFN . During the period commencing on the Restatement Date and ending on the earlier of (i) [**], (ii) [**], or (iii) [**] (the “ RoFN Term ”), in the event that (A) Alnylam desires to [**] and (B) Alnylam desires to [**] (other than [**]) for (x) the collaborative [**] of

such Product and/or (y) a [**] of such Product (such [**], and such [**], each, a “ RoFN Opportunity ”):

(i) Alnylam shall give to Medtronic notice of [**] to do so (the “ RoFN Notice ”) prior to [**]; provided , however , that this Section 2.5(c) shall not prevent Alnylam from [**]. Not later than [**] days after the date of the RoFN Notice (the “ RoFN Response Period ”), Medtronic shall, by written notice to Alnylam (the “ RoFN Response Notice ”), advise Alnylam whether Medtronic has a bona fide interest in discussing a collaboration with Alnylam with respect to such RoFN Opportunity.

(ii) If either (A) Medtronic fails to timely give a RoFN Response Notice with respect to a RoFN Notice, or (B) the RoFN Response Notice does not state that Medtronic has a bona fide interest in discussing a collaboration with or license from (as applicable) Alnylam with respect to the RoFN Opportunity described in the RoFN Notice, then all of Medtronic’s rights under this Section 2.5(c) with respect to such RoFN Opportunity shall terminate as of the date of the RoFN Response Notice or the expiration of the RoFN Response Period (whichever is earlier), and Alnylam shall thereafter be free to pursue such RoFN Opportunity with no participation by Medtronic for [**] after which if Alnylam has not reached an agreement with respect to such RoFN Opportunity [**]. If the RoFN Response Notice timely given by Medtronic to Alnylam states that Medtronic has a bona fide interest in discussing a collaboration with or license from (as applicable) Alnylam with respect to the RoFN Opportunity described in the RoFN Notice, the Parties shall undertake, on an exclusive basis and for a [**] (unless a shorter period is mutually agreed by the Parties) (the “ Exclusive Negotiation Period ”), good faith discussions and negotiations of definitive agreements setting forth all applicable terms and conditions of the collaboration or license between them with respect to the RoFN Opportunity.

(iii) Prior to the end of the Exclusive Negotiation Period, Medtronic shall furnish to Alnylam a written offer (the “ RoFN Offer ”) which shall (A) clearly specify that such written offer, and no other, constitutes the RoFN Offer hereunder with respect to the relevant RoFN Opportunity, and (B) set forth all material terms and conditions on which Medtronic is prepared to [**] with respect to such RoFN Opportunity. If Medtronic fails to timely furnish to Alnylam a RoFN Offer with respect to a RoFN Opportunity, Medtronic’s rights and Alnylam’s obligations under this Section 2.5(c) shall terminate with respect to such RoFN Opportunity for a [**] after which if Alnylam has not reached an agreement with respect to such RoFN Opportunity the provisions of this Section 2.5(c) shall once again apply to such RoFN Opportunity.

(iv) If, as of the end of the Exclusive Negotiation Period, the Parties have not entered into a legally binding definitive agreement with respect to the RoFN Opportunity described in the RoFN Notice, Alnylam shall have the right to undertake detailed discussions and negotiations with respect to such RoFN Opportunity with one or more Third Parties and to enter into definitive agreements for the same on terms more favorable to Alnylam, taken as a whole, than the terms set forth in the RoFN Offer; provided , however , that if no such definitive agreement is entered into prior to [**], then the provisions of this Section 2.5(c) shall once again apply to such RoFN Opportunity. Alnylam shall not be obligated to reveal to Medtronic the identity of any Third Party involved in any such transaction.

(d) Certain [**]. If during the Collaboration Term either Party (the “[**]”) intends to [**], and such proposed [**], and such [**] either (x) would not include [**] or (y) would require the [**] (an “[**]”), then:

(i) The [**] shall provide written notice to the JRDC of such intention to [**] and during the [**] days following such notification provide such reasonable and available information about such proposed [**] to the JRDC as the other Party’s JRDC Representatives may request;

(ii) The JRDC shall consider the advisability of such proposed [**] based on its potential to [**] without unduly burdening [**], and if the JRDC determines that such proposed [**] is advisable, the JRDC shall approve such [**] and the agreement between the [**] and [**]; and

(iii) If the JRDC does not approve such [**], the [**] may, after such [**] day period, following the notification, elect to enter into such [**] at its own expense and the agreement between the [**] and [**].

Notwithstanding the foregoing, if during the [**] days following the [**]’s notice to the JRDC of such intention to engage such [**], the other Party provides written notice to the [**] that (A) the other Party desires to promptly negotiate a Workplan for, and enter into, an Additional Product Development Program that would have [**] would fall and (B) the other Party desires that the [**] not engage the [**] in such proposed [**], then the [**] shall delay entering into such proposed [**] for a period of [**] days in order to provide the Parties with an opportunity to negotiate a Workplan for and initiate such proposed Additional Product Development Program. If the Parties do not initiate such proposed Additional Product Development Program within such [**] day period, then the [**] shall be free to enter into the proposed [**]. If the Parties do initiate such proposed Additional Product Development Program within such [**] day period, the proposed [**] shall be subject to Section 2.5(a) above, if such [**] would [**] for such Additional Product Development Program.

Section 2.6 Supply of Alnylam siRNAs .

(a) Preclinical and Clinical Supply . Subject to Section 2.4, during each Product Development Program Term, unless otherwise agreed by the Parties, Alnylam shall initially have responsibility for procuring and providing Alnylam siRNAs for use by the Parties in the conduct of Workplan activities relating to such Product Development Program, and the Manufacturing Cost of such supply shall constitute a Development Cost that will be shared by the Parties pursuant to Section 4.1.

(b) Commercial Supply . If Medtronic continues as the Commercializing Party with respect to Licensed Products Developed in a Product Development Program, after successful completion of the Phase I Study for such Product Development Program, the Parties shall negotiate and enter into a separate manufacturing and supply agreement that shall include the terms set forth in Exhibit A attached hereto (the “ siRNA Supply Agreement” ) under which Alnylam shall, directly or through a Third Party, provide the commercial supply of Alnylam siRNA(s) for such Licensed Products, at Alnylam’s Manufacturing Cost plus [**] percent

([**]%) (as reflected in a standard cost as described below), in stable bulk material form and meeting mutually agreed manufacturing specifications to be set forth in the siRNA Supply Agreement, to Medtronic or its designee. If the Parties have not entered into an siRNA Supply Agreement within sixty (60) days after commencing negotiations, either Party may submit such impasse for resolution pursuant to Section 2.3(d)(ii). [**].

Section 2.7 SAB Observer Right . During the Collaboration Term, Alnylam shall continue to permit a Medtronic representative reasonably acceptable to Alnylam to attend all meetings of Alnylam’s Scientific Advisory Board as an observer. Alnylam consents to [**] as Medtronic’s initial representative for such purpose.

Article III

Grant of Rights

Section 3.1 Alnylam Grants .

(a) Product Development Program Licenses .

(i) Subject to the terms and conditions of this Agreement (including Section 2.5(a)) and Alnylam’s right to perform its obligations hereunder, Alnylam hereby grants to Medtronic and its Affiliates a non-exclusive, non-royalty-bearing right and license in the Territory during the applicable Product Development Term, without the right to grant sublicenses (except in accordance with Section 3.1(c)), under Alnylam’s rights in Alnylam Intellectual Property, to perform Medtronic’s obligations hereunder and to use Alnylam siRNAs in the course of the Product Development Program(s) to (A) Discover and Develop Licensed Products in the Field and (B) subject to Section 3.1(f), to make or have made Licensed Products in the Field.

(ii) Subject to the terms and conditions of this Agreement (including Section 2.5(a)) and Alnylam’s right to perform its obligations hereunder, Alnylam hereby grants to Medtronic and its Affiliates a non-exclusive, non-royalty-bearing right and license in the Territory during the applicable Product Development Term, with the right to grant sublicenses, under Alnylam’s rights in Program Intellectual Property, to perform Medtronic’s obligations hereunder and to use Alnylam siRNAs in the course of the Product Development Program(s) to (A) Discover and Develop Licensed Products in the Field and (B) subject to Section 3.1(f), to make or have made Licensed Products in the Field.

(iii) For the avoidance of doubt, the foregoing licenses in this Section 3.1(a) to Discover any Licensed Product are subject to Alnylam’s first having made available or approved the siRNA contained in such Licensed Product.

(b) Commercialization Licenses .

(i) Subject to the terms and conditions of this Agreement (including Section 2.5(a)) and Alnylam’s right to perform its obligations hereunder, Alnylam hereby grants to Medtronic and its Affiliates (subject to Section 8.1(a)) a royalty-bearing right and license in the Territory, with the right (subject to Section 3.1(c)) to grant sublicenses, under Alnylam’s

rights in Alnylam Intellectual Property, (A) on an exclusive basis, to Commercialize Licensed Products Developed in the course of the Collaboration Program for which Medtronic is the Commercializing Party and (B) on a non-exclusive basis and subject to Section 3.1(f), to make or have made Licensed Products Developed in the course of the Collaboration Program for which Medtronic is the Commercializing Party.

(ii) Subject to the terms and conditions of this Agreement (including Section 2.5(a)) and Alnylam’s right to perform its obligations hereunder, Alnylam hereby grants to Medtronic and its Affiliates (subject to Section 8.1(a)) a royalty-bearing right and license in the Territory, with the right to grant sublicenses, under Alnylam’s rights in Program Intellectual Property, (A) on an exclusive basis, to Commercialize Licensed Products Developed in the course of the Collaboration Program for which Medtronic is the Commercializing Party and (B) on a non-exclusive basis and subject to Section 3.1(f), to make or have made Licensed Products Developed in the course of the Collaboration Program for which Medtronic is the Commercializing Party.

(c) Medtronic Sublicense Rights . Subject to Section 3.1(d), if Medtronic determines in good faith that, solely for the purpose of facilitating a Product Development Program or the Commercialization of a Licensed Product, it would be advantageous to grant to a Third Party, for such purpose, a sublicense of the rights licensed to Medtronic under Section 3.1(a)(i) or Section 3.1(b)(i), then Medtronic may grant such sublicense; provided that :

(i) Medtronic’s sublicensees shall have no right to grant further sublicenses without Alnylam’s written consent, which consent shall not be unreasonably withheld;

(ii) Medtronic shall be primarily liable for any failure by its sublicensees to comply with, and Medtronic guarantees to Alnylam the compliance by each of its sublicensees with, all relevant restrictions, limitations and obligations in this Agreement; and

(iii) such sublicense is granted pursuant to a written sublicense agreement and Medtronic provides Alnylam with a copy of such sublicense agreement within thirty (30) days after the execution of such sublicense agreement.

(d) Existing Third Party Contractual Obligations . With respect to Alnylam Intellectual Property that is subject to contractual obligations between Alnylam and Third Parties, Medtronic’s rights and licenses under Section 3.1 of this Agreement are subject to the restrictions and other terms described in Schedule 3.1(d) . During the Collaboration Program and the Royalty Term (and, with respect to any continuing obligations under such Third Party contracts, such as record-keeping and audit obligations, thereafter for so long as such obligations continue), Medtronic hereby agrees to comply, and to cause its Affiliates and sublicensees to comply, with such restrictions and other terms.

(e) License Exclusions . Notwithstanding anything to the contrary herein, the licenses to Alnylam Patent Rights hereunder initially shall not include a license to [**] under any agreement between Alnylam and [**] in effect as of the Effective Date; provided that if any such licensed Patent Rights [**], Medtronic shall have the option of expanding its licenses hereunder

to include such issued patents by notifying Alnylam of such election (in which case [**]) and agreeing to [**] under such sublicense during the Royalty Term attributable to such Licensed Product. In addition, if after the Effective Date Alnylam exercises any option under its sponsored research agreement with [**] or its materials exchange agreement with [**] to obtain a license to Patent Rights useful in the Field and controlled by [**], as applicable, and such license includes the right to grant a sublicense to Medtronic, then such Patent Rights licensed from [**], as applicable, shall constitute Alnylam Patent Rights hereunder from and after the date Medtronic requests a sublicense thereto from Alnylam. Medtronic shall [**] by Alnylam to [**] attributable to Medtronic’s sublicense for so long as such sublicense continues. If Medtronic exercises its right under this Section 3.1(e) to obtain sublicense(s) under Patent Rights licensed by Alnylam from [**], Schedule 3.1(d) shall thereupon be amended as necessary to describe applicable restrictions and other terms imposed by such contractual obligations for purposes of Section 3.1(d).

(f) Medtronic Covenant [**]. Medtronic covenants [**] unless and until there has been a [**], and thereafter only (i) as permitted pursuant to Article VIII; (ii) if Alnylam files for bankruptcy protection or has an involuntary bankruptcy action filed against it, which involuntary bankruptcy action is not dismissed within sixty (60) days after being filed, prior to [**] or (iii) pursuant to the terms of an siRNA Supply Agreement, if such agreement is entered into by the Parties.

(g) Medtronic Obligation with Respect to Affiliates . Medtronic shall be primarily liable for any failure by its Affiliates to comply with, and Medtronic guarantees to Alnylam the compliance by each of its Affiliates with, all relevant restrictions, limitations and obligations in this Agreement.

Section 3.2 Medtronic Grants .

(a) Product Development Program Licenses .

(i) Subject to the terms and conditions of this Agreement (including Section 2.5(a)) and Medtronic’s right to perform its obligations hereunder, Medtronic hereby grants to Alnylam and its Affiliates a non-exclusive, non-royalty-bearing right and license in the Territory during the applicable Product Development Term, without the right to grant sublicenses (except in accordance with Section 3.2(c)), under Medtronic’s rights in Medtronic Intellectual Property, to perform Alnylam’s obligations hereunder and to use Medtronic Devices in the course of the Product Development Program(s) to (A) Discover and Develop Licensed Products in the Field and (B) subject to Section 3.2(e), to make or have made Licensed Products in the Field.

(ii) Subject to the terms and conditions of this Agreement (including Section 2.5(a)) and Medtronic’s right to perform its obligations hereunder, Medtronic hereby grants to Alnylam and its Affiliates a non-exclusive, non-royalty-bearing right and license in the Territory during the applicable Product Development Term, with the right to grant sublicenses, under Medtronic’s rights in Program Intellectual Property, to perform Alnylam’s obligations hereunder and to use Medtronic Devices in the course of the Product Development Program(s) to

(A) Discover and Develop Licensed Products in the Field and (B) subject to Section 3.2(e), to make or have made Licensed Products in the Field.

(iii) For the avoidance of doubt, the foregoing licenses in this Section 3.2(a) to Discover any Licensed Product are subject to Medtronic’s first having made available or approved the Medtronic Device for use in such Licensed Product.

(b) Commercialization Licenses .

(i) In the event Alnylam becomes the Commercializing Party for any Licensed Product in any country, and subject to the terms and conditions of this Agreement (including Section 2.5(a)) and Medtronic’s right to perform its obligations hereunder, Medtronic shall, and hereby does, grant to Alnylam and its Affiliates (subject to Section 8.1(a)) a royalty-bearing right and license in the Territory, with the right (subject to Section 3.2(c)) to grant sublicenses, under Medtronic’s rights in Medtronic Intellectual Property, (A) on an exclusive basis, to Commercialize Licensed Products Developed in the course of the Collaboration Program for which Alnylam is the Commercializing Party and (B) on a non-exclusive basis and subject to Section 3.2(e), to make or have made Licensed Products Developed in the course of the Collaboration Program for which Alnylam is the Commercializing Party.

(ii) In the event Alnylam becomes the Commercializing Party for any Licensed Product in any country, and subject to the terms and conditions of this Agreement (including Section 2.5(a)) and Medtronic’s right to perform its obligations hereunder, Medtronic shall, and hereby does, grant to Alnylam and its Affiliates (subject to Section 8.1(a)) a royalty-bearing right and license in the Territory, with the right to grant sublicenses, under Medtronic’s rights in Program Intellectual Property, to (A) on an exclusive basis, Commercialize Licensed Products Developed in the course of the Collaboration Program for which Alnylam is the Commercializing Party and (B) on a non-exclusive basis and subject to Section 3.2(e), make or have made Licensed Products Developed in the course of the Collaboration Program for which Alnylam is the Commercializing Party.

(c) Alnylam Sublicense Rights . Subject to Section 3.2(d), if Alnylam determines in good faith that, solely for the purpose of facilitating a Product Development Program or the Commercialization of a Licensed Product, it would be advantageous to grant to a Third Party, for such purpose, a sublicense of the rights licensed to Alnylam under Section 3.2(a)(i) or Section 3.2(b)(i), then Alnylam may grant such sublicense; provided that :

(i) Alnylam’s sublicensees shall have no right to grant further sublicenses without Medtronic’s written consent, which consent shall not be unreasonably withheld;

(ii) Alnylam shall be primarily liable for any failure by its sublicensees to comply with, and Alnylam guarantees to Medtronic the compliance by each of its sublicensees with, all relevant restrictions, limitations and obligations in this Agreement; and

(iii) such sublicense is granted pursuant to a written sublicense agreement and Alnylam provides Medtronic with a copy of such sublicense agreement within thirty (30) days after the execution of such sublicense agreement.

(d) Existing Third Party Contractual Obligations . With respect to Medtronic Intellectual Property that is subject to contractual obligations between Medtronic and Third Parties, Alnylam’s rights and licenses under Section 3.2 of this Agreement are subject to the restrictions and other terms described in Schedule 3.2(d) . During the Collaboration Program and, if and to the extent Alnylam is the Commercializing Party, during the Royalty Term (and, with respect to any continuing obligations under such Third Party contracts, such as record-keeping and audit obligations, thereafter for so long as such obligations continue), Alnylam hereby agrees to comply, and to cause its Affiliates and sublicensees to comply, with such restrictions and other terms.

(e) License Exclusions . Notwithstanding anything to the contrary herein, the licenses to Medtronic Patent Rights hereunder initially shall not include a license to Patent Rights licensed by Medtronic from [**] (collectively, the “[**] Licensors ”) under any agreement between Medtronic and the [**] Licensors in effect as of the Restatement Date; provided that if any such licensed Patent Rights Cover a Licensed Product and Alnylam requires a sublicense be granted by Medtronic under such licensed Patent Rights in order to exercise its rights with respect to Licensed Products hereunder or under a Device Supply Agreement, Medtronic shall grant such sublicense, either directly to Alnylam and/or to any Third Party contract manufacturer of Devices mutually agreed in connection with a Device Supply Agreement, as requested by Alnylam.

(f) Alnylam Covenant [**]. Alnylam covenants [**] unless and until there has been a [**], and thereafter only (i) as permitted pursuant to Article VIII; (ii) if Medtronic files for bankruptcy protection or has an involuntary bankruptcy action filed against it, which involuntary bankruptcy action is not dismissed within sixty (60) days after being filed, prior to [**] or (iii) pursuant to the terms of a Device Supply Agreement, if such agreement is entered into by the Parties.

Section 3.3 Retained Rights . Subject to Sections 2.5, 3.1 and 3.2 of this Agreement, each Party retains and shall have the right to practice and license its rights in the Program Intellectual Property without obtaining the other Party’s consent and without any duty to account to the other Party.

Article IV

Financial Provisions

Section 4.1 Development Cost and Launch Cost Sharing .

(a) Initial Commitment Amount . The Parties shall each initially commit to contributing fifty percent (50%) of an aggregate funding amount that shall not exceed $[**] without approval by the JRDC, in accordance with the Initial PDP Workplan and the Initial Commitment Budget (as defined in the Initial PDP Workplan), to fund the Initial Commitment Activities (as defined in the Initial PDP Workplan), which Initial Commitment Activities shall consist primarily of certain [**] studies (the “ Initial Commitment ”).

(b) US Development Costs . Medtronic and Alnylam shall each be responsible for fifty percent (50%) of all Development Costs incurred during each Product Development Program to support regulatory filing for Licensed Product(s) in the US Territory or satisfy conditions of receiving Regulatory Approval in the US Territory; provided that if either Party has exercised its right to opt out of such Product Development Program pursuant to Section 2.4, the continuing Party shall be responsible for all Development Costs incurred during such Product Development Program following the effective date of such opt-out.

(c) ROW Development Costs and Device Costs . Medtronic shall be solely responsible for 100% of all Development Costs incurred during each Product Development Program (i) solely to support regulatory filing for Licensed Product(s) in the ROW Territory, or solely to satisfy conditions of receiving Regulatory Approval in the ROW Territory, or (ii) in the Development of Medtronic Devices for use in Licensed Products in the ROW Territory; provided that if Medtronic has exercised its right to opt out of such Product Development Program pursuant to Section 2.4(b) and Alnylam has elected to become the Commercializing Party, Alnylam shall be responsible for all Development Costs incurred during such Product Development Program following the effective date of such opt-out.

(d) Launch Costs . The Commercializing Party shall be solely responsible for Launch Costs, subject to partial reimbursement as set forth in Section 4.3(f).

Section 4.2 Milestone Payments for Product Development Programs . The Commercializing Party shall make the following milestone payments to the other Party upon the first occurrence of the following milestones for the first Licensed Product to reach such milestone in each Product Development Program for which such Party is the Commercializing Party:


		Milestone Payment
Milestones		Upon Occurrence of Milestone
Upon filing of an NDA with a Regulatory Authority in a Major Market other than the United States		$[**]
Upon receipt of Regulatory Approval in a Major Market other than the United States		$[**]

If for any reason a milestone event corresponding to a milestone payment under this Section 4.2 does not occur prior to the occurrence of the next milestone event listed in the table above in this Section 4.2 for such Product Development Program, then such prior non-occurring milestone event shall be deemed to occur concurrently with the occurrence of the next milestone event. Each milestone payment shall be made within thirty (30) days after the achievement of the applicable milestone.

Section 4.3 Royalty Payments .

(a) Royalty . During the Royalty Term applicable to each Licensed Product, and subject to adjustment as set forth in Sections 4.3(b), 4.3(c), 4.3(d), and 4.3(e) and offsetting credits as set forth in Sections 4.3(f), 5.2(a) and 5.4(c), the Commercializing Party shall pay to the other Party royalties on a Licensed Product-by-Licensed Product basis, with the amount of such royalties calculated as a percentage of Net Sales in a Medtronic Fiscal Year for such Licensed Product. Such royalties for the Licensed Product(s) resulting from the Initial Product Development Program are as follows:

(i) With respect to Net Sales of each Licensed Product in the US Territory, as follows:


	Percentage of
Annual Net Sales in US Territory	Incremental Amount
Up to and including $[**]		[**]	%

Above $[] up to and including $[]		[**]	%

Above $[] up to and including $[]		[**]	%

Above $[] up to and including $[]		[**]	%

Above $[**]		[**]	%

(ii) With respect to Net Sales of each Licensed Product in the ROW Territory, as follows:


		Percentage of
Annual Net Sales in ROW Territory		Incremental Amount
Up to and including $[**]		[**]%

Above $[] up to and including $[]		[**]%

Above $[] up to and including $[]		[**]%

Above $[] up to and including $[]		[**]%

Above $[**]		[**]%

For example, if Net Sales for a Licensed Product throughout the ROW Territory totaled $[**] in a Medtronic fiscal year, the total royalties (before applying any adjustments or credits) for such Net Sales would be $[**], calculated as follows: [**].

(b) Opt-Out Adjustment . The royalty payment due to the non-Commercializing Party following any exercise by the non-Commercializing Party of its right pursuant to Section 2.4 to opt out of a Product Development Program shall be reduced to a percentage of the royalty

payment determined pursuant to Section 4.3(a) ( i.e. , treating the Commercializing Party as the royalty-paying Party and the other Party as the royalty-receiving Party) for each Licensed Product included in such Product Development Program, determined as set forth below based on the point during such Product Development Program that the non-Commercializing Party provided notice that it was exercising its right to opt out of such Product Development Program:


Timing of Opt Out Notice	Percentage
[**] Opt Out		[**]	%

[**] Opt Out		[**]	%

[**] Opt Out		[**]	%

[**] Opt Out		[**]	%

(c) Reduction for Lack of Patent Coverage . Subject to Section 4.3(g), the royalty set forth in Sections 4.3(a) and 4.3(b) payable by the Commercializing Party to the other Party with respect to Net Sales of a Licensed Product in the Territory shall be reduced by [**] percent ([**]%) during any por

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