Document:

EX-10.49

 Exhibit 10.49 

 

			
	 Confidential Materials omitted and filed separately with the

Securities and Exchange Commission. Double asterisks denote omissions.
	  	EXECUTION COPY

 LICENSE AND COLLABORATION AGREEMENT 

by and between 
 ALNYLAM PHARMACEUTICALS, INC. 
 and 

GENZYME CORPORATION 

 TABLE OF CONTENTS 

 

									
			
	 1.
	 	 DEFINITIONS
	  	 	1	  
			
	 2.
	 	 DEVELOPMENT COLLABORATION
	  	 	16	  
				
		 	 2.1
	 	 Overview.
	  	 	16	  
				
		 	 2.2
	 	 Development Plans.
	  	 	17	  
				
		 	 2.3
	 	 Responsibilities for Development Activities and Costs.
	  	 	18	  
				
		 	 2.4
	 	 Diligence.
	  	 	19	  
				
		 	 2.5
	 	 Records; Reports; Information Sharing.
	  	 	19	  
				
		 	 2.6
	 	 Third Parties.
	  	 	22	  
			
	 3.
	 	 REGULATORY MATTERS.
	  	 	22	  
				
		 	 3.1
	 	 Regulatory Filings and Interactions.
	  	 	22	  
				
		 	 3.2
	 	 Costs of Regulatory Affairs.
	  	 	23	  
				
		 	 3.3
	 	 Right of Reference.
	  	 	23	  
				
		 	 3.4
	 	 Pharmacovigilance.
	  	 	24	  
			
	 4.
	 	 COMMERCIALIZATION OF THE LICENSED PRODUCTS
	  	 	24	  
				
		 	 4.1
	 	 Responsibility, Cost and Diligence.
	  	 	24	  
				
		 	 4.2
	 	 Genzyme Commercialization Plan.
	  	 	24	  
				
		 	 4.3
	 	 Alnylam Commercialization Plan.
	  	 	25	  
				
		 	 4.4
	 	 Advertising and Promotional Materials.
	  	 	25	  
				
		 	 4.5
	 	 Reporting Obligations.
	  	 	26	  
				
		 	 4.6
	 	 Sales and Distribution.
	  	 	26	  
				
		 	 4.7
	 	 Recalls, Market Withdrawals or Corrective Actions.
	  	 	26	  
				
		 	 4.8
	 	 Ex-Territory Sales; Export Monitoring.
	  	 	26	  
			
	 5.
	 	 COLLABORATION MANAGEMENT
	  	 	27	  
				
		 	 5.1
	 	 Joint Steering Committee.
	  	 	27	  
				
		 	 5.2
	 	 Appointment of Subcommittees, Project Teams and Collaboration Managers.
	  	 	27	  
				
		 	 5.3
	 	 Meetings.
	  	 	27	  
				
		 	 5.4
	 	 Minutes.
	  	 	28	  
				
		 	 5.5
	 	 Decision-Making.
	  	 	29	  
				
		 	 5.6
	 	 Term of JSC.
	  	 	30	  
				
		 	 5.7
	 	 Alnylam Third Party Partner.
	  	 	30	  
			
	 6.
	 	 MANUFACTURE AND SUPPLY OF THE LICENSED PRODUCT
	  	 	32	  
				
		 	 6.1
	 	 Supply Agreements.
	  	 	32	  

  
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		 	 6.2
	 	 Transfer of Manufacturing Know-How.
	  	 	32	  
			
	 7.
	 	 LICENSES
	  	 	32	  
				
		 	 7.1
	 	 License Grants to Genzyme.
	  	 	32	  
				
		 	 7.2
	 	 License Grants to Alnylam.
	  	 	34	  
				
		 	 7.3
	 	 Joint Collaboration IP.
	  	 	35	  
				
		 	 7.4
	 	 In-Licenses.
	  	 	35	  
				
		 	 7.5
	 	 Improvement Products Option.
	  	 	39	  
				
		 	 7.6
	 	 Alnylam Territory Right of First Negotiation.
	  	 	42	  
				
		 	 7.7
	 	 Bankruptcy.
	  	 	43	  
				
		 	 7.8
	 	 [**]
	  			
				
		 	 7.9
	 	 No Other Rights.
	  	 	44	  
			
	 8.
	 	 CERTAIN FINANCIAL TERMS
	  	 	44	  
				
		 	 8.1
	 	 Upfront Fee.
	  	 	44	  
				
		 	 8.2
	 	 Development Milestone Fees.
	  	 	44	  
				
		 	 8.3
	 	 Royalties.
	  	 	46	  
				
		 	 8.4
	 	 Audits.
	  	 	50	  
				
		 	 8.5
	 	 Payment Exchange Rate.
	  	 	50	  
				
		 	 8.6
	 	 Late Payments.
	  	 	51	  
				
		 	 8.7
	 	 Blocked Payments.
	  	 	51	  
				
		 	 8.8
	 	 Taxes.
	  	 	51	  
			
	 9.
	 	 CONFIDENTIALITY AND PUBLICATION
	  	 	52	  
				
		 	 9.1
	 	 Nondisclosure Obligation.
	  	 	52	  
				
		 	 9.2
	 	 Publication and Publicity.
	  	 	53	  
			
	 10.
	 	 REPRESENTATIONS, WARRANTIES AND COVENANTS; INDEMNIFICATION
	  	 	55	  
				
		 	 10.1
	 	 Mutual Representations and Warranties.
	  	 	55	  
				
		 	 10.2
	 	 Representations and Warranties of Alnylam.
	  	 	55	  
				
		 	 10.3
	 	 Representations and Warranties of Genzyme.
	  	 	57	  
				
		 	 10.4
	 	 Warranty Disclaimer.
	  	 	57	  
				
		 	 10.5
	 	 Certain Covenants.
	  	 	58	  
			
	 11.
	 	 INDEMNIFICATION; LIMITATION OF LIABILITY; INSURANCE
	  	 	58	  
				
		 	 11.1
	 	 General Indemnification by Genzyme.
	  	 	58	  
				
		 	 11.2
	 	 General Indemnification by Alnylam.
	  	 	59	  
				
		 	 11.3
	 	 Product Liability.
	  	 	59	  
				
		 	 11.4
	 	 Ongoing Litigation.
	  	 	59	  
				
		 	 11.5
	 	 [**]
	  	 	60	  

  
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		 	 11.6
	 	 Indemnification Procedure.
	  	 	60	  
				
		 	 11.7
	 	 Limitation of Liability.
	  	 	60	  
				
		 	 11.8
	 	 Insurance.
	  	 	61	  
			
	 12.
	 	 INTELLECTUAL PROPERTY OWNERSHIP, PROTECTION AND RELATED MATTERS
	  	 	61	  
				
		 	 12.1
	 	 Inventorship.
	  	 	61	  
				
		 	 12.2
	 	 Ownership.
	  	 	61	  
				
		 	 12.3
	 	 Prosecution and Maintenance of Patent Rights.
	  	 	61	  
				
		 	 12.4
	 	 Third Party Infringement.
	  	 	63	  
				
		 	 12.5
	 	 Patent Term Extensions.
	  	 	65	  
				
		 	 12.6
	 	 Common Interest.
	  	 	66	  
				
		 	 12.7
	 	 Trademarks.
	  	 	66	  
				
		 	 12.8
	 	 Cooperative Research and Technology (CREATE) Act Acknowledgment.
	  	 	67	  
			
	 13.
	 	 TERM AND TERMINATION
	  	 	67	  
				
		 	 13.1
	 	 Term.
	  	 	67	  
				
		 	 13.2
	 	 Termination Rights.
	  	 	67	  
				
		 	 13.3
	 	 Effect of Termination.
	  	 	69	  
				
		 	 13.4
	 	 Fundamental Breach of Alnylam’s Development Obligations.
	  	 	71	  
				
		 	 13.5
	 	 Effect of Expiration or Termination; Survival.
	  	 	71	  
			
	 14.
	 	 MISCELLANEOUS
	  	 	71	  
				
		 	 14.1
	 	 Assignment.
	  	 	71	  
				
		 	 14.2
	 	 Governing Law.
	  	 	72	  
				
		 	 14.3
	 	 Jurisdiction.
	  	 	72	  
				
		 	 14.4
	 	 Venue.
	  	 	72	  
				
		 	 14.5
	 	 Entire Agreement; Amendments.
	  	 	72	  
				
		 	 14.6
	 	 Severability.
	  	 	73	  
				
		 	 14.7
	 	 Headings.
	  	 	73	  
				
		 	 14.8
	 	 Waiver of Rule of Construction.
	  	 	73	  
				
		 	 14.9
	 	 Interpretation.
	  	 	73	  
				
		 	 14.10
	 	 No Implied Waivers; Rights Cumulative.
	  	 	73	  
				
		 	 14.11
	 	 Notices.
	  	 	74	  
				
		 	 14.12
	 	 Compliance with Export Regulations.
	  	 	75	  
				
		 	 14.13
	 	 Force Majeure.
	  	 	75	  
				
		 	 14.14
	 	 Independent Contractors.
	  	 	75	  

  
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		 	 14.15
	 	 Counterparts.
	  	 	75	  
				
		 	 14.16
	 	 Performance by Affiliates.
	  	 	75	  
				
		 	 14.17
	 	 Binding Effect; No Third Party Beneficiaries.
	  	 	76	  

  
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 SCHEDULES 

 

			
		
	Schedule 1.4	 	Additional Alnylam In-Licenses
		
	Schedule 1.7	 	ALN-TTR02
		
	Schedule 1.8	 	ALN-TTRsc
		
	Schedule 1.9	 	Alnylam Core Technology Patents
		
	Schedule 1.16	 	Alnylam Product-Specific Patents
		
	Schedule 1.47	 	Existing Alnylam In-Licenses
		
	Schedule 1.52	 	First Phase II Success Objectives
		
	Schedule 2.2.1	 	Global Development Strategy
		
	Schedule 2.2.2	 	Alnylam Territory Development Plan
		
	Schedule 2.2.3	 	Genzyme Territory Development Plan
		
	Schedule 6.1	 	Supply Agreement Principles
		
	Schedule 7.4.3.2	 	Baseball Arbitration Procedure Regarding JPAC/LP Milestone Allocation
		
	Schedule 9.2.2(a)	 	Joint Press Release
		
	Schedule 10.2	 	Disclosure Schedule

  
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 LICENSE AND COLLABORATION AGREEMENT 

THIS LICENSE AND COLLABORATION AGREEMENT (this “Agreement”), effective as of October 18, 2012 (the
“Effective Date”), by and between Alnylam Pharmaceuticals, Inc., a corporation organized and existing under the laws of the State of Delaware (“Alnylam”) and, Genzyme Corporation, a corporation organized and
existing under the laws of the Commonwealth of Massachusetts (“Genzyme”). 
 RECITALS: 

WHEREAS, Alnylam owns or controls certain fundamental intellectual property relating to RNA interference, and is developing
proprietary therapeutic products in the Field (as defined below) targeting the human TTR gene known as ALN-TTR02 and ALN-TTRsc (each, as defined below); 
 WHEREAS, Genzyme desires to develop and commercialize such therapeutic RNA interference products in the Genzyme Territory (as defined below); 

WHEREAS, Alnylam desires to continue to develop and to commercialize such therapeutic RNA interference products in the Alnylam
Territory (as defined below); and 
 WHEREAS, Alnylam and Genzyme believe that a license and collaboration for such
purpose on the terms and conditions of this Agreement would be desirable. 
 NOW, THEREFORE, in consideration of the
foregoing premises and the mutual covenants herein contained, the Parties hereby agree as follows: 
 1. DEFINITIONS

 Unless specifically set forth to the contrary herein, the following terms, whether used in the singular or plural, shall
have the respective meanings set forth below: 
 1.1 “Acquired Business” has the meaning
set forth in Section 14.16.2. 
 1.2 “Acquirer” has the meaning set forth in
Section 14.16.2. 
 1.3 “Action” has the meaning set forth in Section 14.3.

 1.4 “Additional Alnylam In-Licenses” means the agreements set forth on Schedule
1.4. 
 1.5 “Affiliate” means, with respect to a Person, any other Person which
controls, is controlled by, or is under common control with the applicable Person. For purposes of this definition, “control” shall mean: (a) in the case of corporate entities, direct or indirect ownership of at least fifty percent
(50%) of the stock or shares (or such lesser percentage which is the maximum allowed to be owned by a foreign corporation in a particular jurisdiction) entitled to vote for the election of directors, or otherwise having the power to control or
direct the affairs of such Person; and (b) in the case of non-corporate entities, direct or indirect ownership of at least fifty percent (50%) of the equity interest or the power to direct the management and policies of such non-corporate
entities. 

  
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 1.6 “AF11 Lipid Nanoparticle Formulation” means a
lipid-based nanoparticle consisting of the following lipid species: [**]. 
 1.7
“ALN-TTR02” means an siRNA Product Controlled by Alnylam, comprising the siRNA (#AD[**]) formulated in an AF11 Lipid Nanoparticle Formulation, as further described on Schedule 1.7. 

1.8 “ALN-TTRsc” means an siRNA Product Controlled by Alnylam, comprising the siRNA (#AD[**])
conjugated to a Ga1NAc Conjugate, as further described on Schedule 1.8. 
 1.9 “Alnylam
Core Technology Patents” means Patent Rights Controlled by Alnylam during the Term that are reasonably necessary or useful to Develop, Commercialize, and/or Manufacture Licensed Products, other than Alnylam Product-Specific Patents or
Alnylam’s interest in Patent Rights included in Joint Collaboration IP. Alnylam Core Technology Patents include Patent Rights Controlled by Alnylam that claim [**], or (ii) subject matter applicable to siRNA or siRNA delivery in general.
The Alnylam Core Technology Patents existing as of the Effective Date are identified on Schedule 1.9. 

1.10 “Alnylam Developed siRNA Product” means an siRNA product with respect to which
(a) Alnylam Controls Patent Rights Covering such siRNA product; provided that, once a product first satisfies the criterion set forth in this clause (a) such criterion shall be deemed satisfied at all times thereafter as to
such product; and (b) Alnylam or an Affiliate of Alnylam plays(ed) a material role in the Development. 

1.11 “Alnylam Development Candidate” means an siRNA Product for which Alnylam or its Affiliates
have initiated IND-Enabling Toxicology Studies and as to which Alnylam and its Related Parties have not abandoned development and commercialization. 
 1.12 “Alnylam Indemnitees” has the meaning set forth in Section 11.1. 
 1.13 “Alnylam In-Licenses” means (a) the Existing Alnylam In-Licenses, and (b) any agreement between Alnylam and a Third Party entered into after the Effective Date
pursuant to which Alnylam acquires Control of Know-How or Patent Rights that are necessary or useful to Develop, Manufacture or Commercialize Licensed Products in the Field in the Genzyme Territory, but in the case of any such agreement described in
clause (b), solely to the extent that such agreement is designated as an Alnylam In-License pursuant to Section 7.4.2.2. 
 1.14 “Alnylam Know-How” means Know-How Controlled by Alnylam during the Term that is reasonably necessary or useful for Genzyme to Develop, Manufacture and/or Commercialize
Licensed Products in the Field in the Genzyme Territory, other than Alnylam’s interest in Know-How included in Joint Collaboration IP. 

  
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 1.15 “Alnylam Patents” means Alnylam Core Technology
Patents and Alnylam Product-Specific Patents. 
 1.16 “Alnylam Product-Specific Patents”
means Patent Rights Controlled by Alnylam during the Term that claim (a) an siRNA targeting the human TTR gene contained in a Licensed Product, (b) during the Exclusivity Period, an siRNA targeting the human TTR gene not contained in a
Licensed Product and not contained in an Alnylam Development Candidate, (c) the composition of matter of (i) a Licensed Product or (ii) an siRNA targeting the human TTR gene together with a formulation or compound that mediates
delivery of an siRNA Product, which combination is contained in a Licensed Product, (d) methods of using a Licensed Product as a human therapeutic or prophylactic, methods of using a Licensed Product to modulate human TTR, or methods of using a
Licensed Product to inhibit expression of human TTR, or (e) methods and materials specific to the synthesis or analysis of a Licensed Product; provided however, patents that include claims that are directed to subject matter
applicable to siRNA or siRNA delivery in general will not be considered Alnylam Product Specific Patents but will be considered Alnylam Core Technology Patents. Notwithstanding the foregoing, for the purposes of clause (b) above, Alnylam
Product-Specific Patents shall not include any Patent Right that claims any siRNA targeting the human TTR gene that (A) is contained in an Alnylam Development Candidate and (B) is not contained in a Licensed Product. The Alnylam
Product-Specific Patents existing as of the Effective Date are identified on Schedule 1.16. Notwithstanding the foregoing, Alnylam Product-Specific Patents shall exclude Alnylam’s interest in Patent Rights included in Joint Collaboration IP.

 1.17 “Alnylam Technology” means, collectively, Alnylam Know-How, Alnylam Patents and
Alnylam’s interest in Joint Collaboration IP. 
 1.18 “Alnylam Territory” means all
countries and territories of the world other than the Genzyme Territory. 
 1.19 “Alnylam
Territory Commercialization Plan” has the meaning set forth in Section 4.3. 
 1.20
“Alnylam Territory Development Plan” has the meaning set forth in Section 2.2.2. 

1.21 “Alnylam Trademark” has the meaning set forth in Section 12.7(b). 

1.22 “ANDA” means an Abbreviated New Drug Application (or any successor application or procedure)
as defined in regulations promulgated by the FDA under the FDCA, which ANDA is filed with or intended to be filed with the FDA (and, as applicable, any other analogous application filed with a Regulatory Authority in any country other than the U.S.
in the Genzyme Territory) for regulatory approval for marketing and selling a Licensed Product in the Genzyme Territory 
 1.23 “ATTR” means the human disease TTR-mediated amyloidosis. 

  
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 1.24 “Backup Compound” means as to either of
ALN-TTR02 or ALN-TTRsc, as applicable, a replacement product that (a) Alnylam brings forward as a substitute for ALN-TTR02 or ALN-TTRsc, as applicable, pursuant to Section 2.5.3.3; and (b) (i) in the case of such a replacement
product for ALN-TTR02, is [**], (ii) in the case of such a replacement product for ALN-TTRsc, is [**], (iii) in the event that Alnylam discontinues the Development of ALN-TTR02 because an [**], then, notwithstanding clause (b)(i) above, is
any siRNA Product in the Field that Alnylam advances into Clinical Studies (as evidenced by filing of an IND) within [**] years after the Effective Date or (iv) in the event that both ALN-TTR02 and ALN-TTRsc are discontinued prior to receipt of
Regulatory Approval thereof, then, notwithstanding clauses (b)(i) and (b)(ii) above, is any siRNA Product in the Field that Alnylam advances into Clinical Studies (as evidenced by filing of an IND) within [**] years after the Effective Date.

 1.25 “Bankrupt Party” has the meaning set forth in Section 7.7. 

1.26 “Calendar Quarter” means the respective periods of three (3) consecutive calendar months
ending on March 31, June 30, September 30 and December 31 of each Calendar Year; provided that (a) the first Calendar Quarter of the Term shall begin on the Effective Date and end on the first to
occur of March 31, June 30, September 30 or December 31 thereafter and the last Calendar Quarter of the Term shall end on the last day of the Term and (b) the first Calendar Quarter of a Royalty Term for a Licensed
Product in a country shall begin on the First Commercial Sale of a Licensed Product in such country and end on the first to occur of March 31, June 30, September 30 or December 31 thereafter and the last Calendar
Quarter of a Royalty Term shall end on the last day of such Royalty Term. 
 1.27 “Calendar
Year” means each successive period of twelve (12) months commencing on January 1 and ending on December 31; provided that (a) the first Calendar Year of the Term shall begin on the Effective Date and end on
the first December 31 thereafter and the last Calendar Year of the Term shall end on the last day of the Term and (b) the first Calendar Year of a Royalty Term for a Licensed Product in a country shall begin on the First Commercial Sale of
a Licensed Product in such country and end on the first December 31 thereafter and the last Calendar Year of the Term shall end on the last day of such Royalty Term. 

1.28 [**] 
 1.29 “Clinical Study” means a Phase I Study, Phase II Study, Phase III Study, or Post-Marketing Commitment Study, as applicable; but excluding any Post-Approval Studies.

 1.30 “Collaboration” means the collaboration of the Parties in the Development,
Manufacture and Commercialization of Licensed Products under this Agreement. 
 1.31
“Collaboration Manager” has the meaning set forth in Section 5.2. 

  
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 1.32 “Commercialization” or
“Commercialize” means any and all activities directed to marketing, promoting, distributing, importing, exporting, offering to sell and/or selling a product, including the conduct of Post-Approval Studies, and activities directed to
obtaining pricing and reimbursement approvals, as applicable. 
 1.33 “Commercially Reasonable
Efforts” means (a) with respect to each Party’s obligations under this Agreement that relate to a Licensed Product (including Development, Manufacture or Commercialization obligations), those efforts reasonably used by an entity
in the biotechnology/pharmaceutical industry of similar resources and expertise as such Party, for such similar entity’s own products (including internally developed, acquired and in-licensed products) of similar market potential at a similar
stage in development or product life, taking into account all relevant factors, including (i) issues of safety, tolerability and efficacy, (ii) product profile, (iii) difficulty in and costs of developing or manufacturing the Licensed
Product, (iv) competitiveness of the Licensed Product and competitive products (but not taking into account Exempted Complementary TTR Products Controlled by the Party to which the efforts obligation applies) in the marketplace, (v) the
extent of market exclusivity, (vi) the patent or other proprietary position of the Licensed Product, (vii) the regulatory structure involved, and (viii) the potential profitability of the Licensed Product, (but not taking into
account the profitability relative to or the potential profitability of other products Controlled by the Party to which the efforts obligations applies); and (b) with respect to such Party’s other obligations under this Agreement, the
carrying out of such obligations in a diligent, expeditious and sustained manner using efforts and resources, including reasonably necessary personnel and financial resources, that biopharmaceutical companies of comparable size and resources
typically devote to similar tasks under similar circumstances. 
 1.34 “Competitive
Infringement” has the meaning set forth in Section 12.4.1. 
 1.35 “Confidential
Information” means any and all confidential or proprietary information and data, including Alnylam Technology, Genzyme Technology, and Joint Collaboration IP and all other scientific, pre-clinical, clinical, regulatory, manufacturing,
marketing, financial and commercial information or data, whether communicated in writing or orally or by any other method, which is provided by one Party to the other Party in connection with this Agreement. Alnylam Technology is the Confidential
Information of Alnylam. Genzyme Technology is the Confidential Information of Genzyme. Joint Collaboration IP and the terms of this Agreement are the Confidential Information of both Parties, subject to Section 9.2.2. 

1.36 “Control”, “Controls” or “Controlled by” means, with
respect to any Know-How, Patent Rights or other intellectual property right, the possession of (whether by ownership or license, other than pursuant to this Agreement), and the ability of a Person or its Affiliates to assign, transfer, or grant
access to, or to grant a license or sublicense of, such item or right as provided for herein without violating the terms of any agreement or other arrangement with any Third Party existing at the time such Person would be required hereunder to
assign, transfer or grant another Person such access or license or sublicense, provided that, with respect to rights to any Third Party Know-How, Patent Rights or other 

  
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intellectual property right that are licensed to, or otherwise obtained by, (i) a Party pursuant to an agreement entered into by such Party after the Effective Date or (ii) Alnylam
pursuant to any Additional Alnylam In-License, such Third Party Know-How, Patent Rights or other intellectual property right shall be deemed not to be under the Control of such Party or Alnylam, respectively, unless and until the agreement pursuant
to which such rights are obtained becomes an In-License pursuant to Section 7.4.2. 
 1.37
“Cover,” “Covering” or “Covers” means, as to a product and Patent Rights, that, in the absence of a license granted under, or ownership of, such Patent Rights, the manufacture, use, offer for
sale, sale, or importation of such product would infringe such Patent Rights or, as to a pending claim included in such Patent Rights, the manufacture, use, offer for sale, sale, or importation of such product would infringe such Patent Rights if
such pending claim were to issue in an issued patent. 
 1.38 “CPI” shall mean the
Consumer Price Index – Urban Wage Earners and Clerical Workers, U.S. City Average, All Items, 1982-84 = 100, published by the United States Department of Labor, Bureau of Labor Statistics (or its successor equivalent index) in the United
States. 
 1.39 “Development,” “Developing” or
“Develop” means the research and development activities related to the generation, characterization, optimization, construction, expression, use and production of Licensed Products, any other non-clinical, pre-clinical or clinical
research and development activities related to the testing and qualification of Licensed Products, including toxicology studies, statistical analysis and report writing, pre-clinical testing, formulation development, Clinical Studies, regulatory
affairs, product approval and registration activities, and all other activities necessary to seek, obtain and maintain Regulatory Approval, but excluding Post-Approval Studies. 

1.40 “Development Plan” means (a) with respect to Alnylam, the Alnylam Territory Development
Plan and (b) with respect to Genzyme, the Genzyme Territory Development Plan. 
 1.41
“[**]. 
 1.42 “Effective Date” has the meaning set forth in the
preamble. 
 1.43 “EMA” means the European Medicines Agency and any successor
governmental authority having substantially the same function. 
 1.44 “EU” means the
European Union, as its membership may be altered from time to time, and any successor thereto. 
 1.45
“Exclusivity Period” means, on a country-by-country basis within the Genzyme Territory, from the Effective Date until the First Commercial Sale of a Licensed Product in a country, and thereafter until the end of the last Royalty
Term in such country to terminate or expire. 

  
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 1.46 “Exempted Complementary TTR Product” means a
product for administration to ATTR patients that the JSC determines would not, if Commercialized in a country of the Genzyme Territory, reasonably be expected to adversely affect the Development or Commercialization of any Licensed Product in such
country. 
 1.47 “Existing Alnylam In-Licenses” means (a) the Third Party agreements
set forth on Schedule 1.47 and (b) any Additional Alnylam In-License included within the definition of Existing Alnylam In-Licenses pursuant to Section 7.4.2.3. 

1.48 “FDA” means the United States Food and Drug Administration and any successor governmental
authority having substantially the same function. 
 1.49 “FDCA” means the United States
Federal Food, Drug, and Cosmetic Act of 1938, as amended from time to time, and the regulations and guidelines promulgated thereunder. 
 1.50 “Field” means the treatment and/or prevention of all human diseases, including treatment and/or prevention of ATTR, including familial amyloid polyneuropathy (FAP), familial
amyloid cardiomyopathy (FAC) and senile systemic amyloidosis (SSA) in humans. 
 1.51 “First
Commercial Sale” means, with respect to a country, the first sale for end use or consumption of the Licensed Product in such country after all Regulatory Approvals legally required for such sale have been granted by the Regulatory Authority
of such country. 
 1.52 “First Phase II Success” means the completion of a Phase II
Clinical Trial the results of which satisfy the criteria set forth in Schedule 1.52. 
 1.53
“FTE” means [**] hours of work devoted to or in support of the Development or Manufacture of a Licensed Product, that is carried out by one or more qualified scientific or technical employees of a Party or its Affiliates.

 1.54 “FTE Cost” means, for any period, the FTE Rate multiplied by the number of FTEs
in such period. 
 1.55 “FTE Rate” means [**] U.S. Dollars ($[**]) per FTE, increased
annually beginning on January 1, 2014 and thereafter on January 1 of each succeeding year by the percentage increase in the CPI as of December 31 of the then most recently ended calendar year over the level of the CPI on
December 31, 2012. 
 1.56 “Fundamental Breach” means a substantial abandonment of
Alnylam’s Development obligations hereunder as a whole resulting from either (a) Alnylam’s willful failure to exercise Commercially Reasonable Efforts to perform such Development obligations, or (b) Alnylam’s lack of the
financial resources necessary to perform such Development obligations. For the avoidance of doubt, a discontinuation of Development of ALN-TTR02 and/or ALN-TTRsc that is consistent with the exercise of Commercially

  
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Reasonable Efforts shall not constitute a Fundamental Breach, and Alnylam’s failure to Develop a Backup Compound or Improvement Product, or Alnylam’s failure to conduct any
Post-Approval Study, shall not constitute a Fundamental Breach. For clarity, the Parties agree that a breach of Alnylam’s diligence obligations under Section 2.4.2 need not rise to the level of a Fundamental Breach to be considered a
material breach of the Agreement. 
 1.57 “Future Alnylam In-License” has the meaning set
forth in Section 7.4.3.1. 
 1.58 “GAAP” means generally accepted accounting
principles as practiced in the United States or, to the extent applicable, IFRS (International Financial Reporting Standards), in each case, consistently applied. 

1.59 [**]. 
 1.60 “Generic Competition” means, with respect to a Licensed Product in any country in the Genzyme Territory in a given Calendar Quarter, that, during such Calendar Quarter,
(a) [**] Generic Products are commercially available in such country, and (b) aggregate Net Sales of such Licensed Product in such country in such Calendar Quarter equal less than [**] percent ([**]%) of the average aggregate Net Sales of
the Licensed Product over the four (4) consecutive Calendar Quarters immediately prior to the Calendar Quarter in which [**] Generic Products first became commercially available in such country. 

1.61 “Generic Product” for a given country means a pharmaceutical product that (a) is sold by
a Person that is not a Related Party of Genzyme under a marketing authorization granted by a Regulatory Authority to a Third Party, (b) contains the same active ingredient(s) as are contained in a Licensed Product, where the term “active
ingredient” means the siRNA Product(s) responsible for the pharmacological or physiological action of the Licensed Product, and (c) is approved by the Regulatory Authority pursuant to an approval process that relies in part on pivotal
safety and/or efficacy data in such Regulatory Authority’s previous grant of marketing authorization to a Licensed Product. 
 1.62 “Genzyme Collaboration IP” means (a) any Know-How, first identified, discovered or developed solely by employees of Genzyme or its Affiliates or other persons not
employed by Alnylam acting on behalf of Genzyme, in the conduct of the Collaboration and (b) any Patent Rights that claim or cover such Know-How and are Controlled by Genzyme at any time during the Term. Genzyme Collaboration IP excludes
Genzyme’s interest in Joint Collaboration IP, in each case, (a) and (b) other than Genzyme Manufacturing IP. 
 1.63 “Genzyme Disclosed Manufacturing Know-How” means Know-How (a) Controlled by Genzyme at any time during the Term that is useful in the Manufacture of a Licensed Product,
and (b) that Genzyme, in its sole discretion, discloses in writing to Alnylam in the course of the Collaboration. 

  
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 1.64 “Genzyme Indemnitees” has the meaning set forth
in Section 11.2. 
 1.65 “Genzyme In-Licenses” means (a) any agreement between
Genzyme and a Third Party entered into after the Effective Date pursuant to which Genzyme Controls Know-How or Patent Rights, other than Genzyme Manufacturing IP, used to Develop, Manufacture or Commercialize Licensed Products in the Field and
(b) that is designated as a Genzyme In-License pursuant to Section 7.4.2.2. 
 1.66
“Genzyme Know-How” means Know-How Controlled by Genzyme during the Term that is reasonably necessary or useful for Alnylam to Develop, Commercialize and/or Manufacture Licensed Products in the Field in the Alnylam Territory
(other than Genzyme’s rights in Joint Collaboration IP, Genzyme Collaboration IP and Genzyme Manufacturing IP). 
 1.67 “Genzyme Manufacturing IP” means (a) any Know-How related to the Manufacture of Licensed Products (or oligonucleotides generally) Controlled by Genzyme at any time during
the Term, and (b) any Patent Rights that claim or cover such or Know-How and are Controlled by Genzyme at any time during the Term. 
 1.68 “Genzyme Patent Rights” means those Patent Rights Controlled by Genzyme during the Term that are reasonably necessary or useful to Develop, Commercialize and/or Manufacture
Licensed Products in the Field in the Alnylam Territory. Genzyme Patent Rights excludes Patent Rights included in Genzyme Collaboration IP, Genzyme’s interest in Joint Collaboration IP and Genzyme Manufacturing IP. 

1.69 “Genzyme Technology” means, collectively, Genzyme Know-How and Genzyme Patent Rights, Genzyme
Collaboration IP and Genzyme’s interest in Joint Collaboration IP, but excluding Genzyme Manufacturing IP. 

1.70 “Genzyme Territory” means the countries of Australia, Bangladesh, Cambodia, China, East
Timor, Hong Kong, India, Indonesia, Japan, Laos, Malaysia, Micronesia, Mongolia, Myanmar, Nepal, New Zealand, North Korea, Philippines, Singapore, South Korea, Taiwan, Thailand, and Vietnam. 

1.71 “Genzyme Territory Commercialization Plan” has the meaning set forth in Section 4.2.

 1.72 “Genzyme Territory Development Plan” has the meaning set forth in
Section 2.2.3. 
 1.73 “Genzyme Trademark” has the meaning set forth in
Section 12.7(b). 
 1.74 “Global Branding Strategy” has the meaning set forth in
Section 4.4.1. 
 1.75 “Global Development Strategy” has the meaning set forth in
Section 2.2.1. 

  
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 1.76 “Governmental Authority” means any applicable
government authority, court, tribunal, arbitrator, agency, department, legislative body, commission or other instrumentality of (a) any government of any country or territory, (b) any nation, state, province, county, city or other
political subdivision thereof or (c) any supranational body. 
 1.77 “Improvement
Manufacturing Patent Right” means a Patent Right owned exclusively by Genzyme or its Affiliates that claims an invention related to the Manufacture of a Licensed Product that was made (a) by Genzyme or its Affiliates after the
Effective Date in connection with Manufacturing Licensed Products and (b) using Alnylam Know-How that, at the time such Alnylam Know-How was disclosed to Genzyme or its Affiliates, constituted Alnylam’s Confidential Information under
Section 9.1. 
 1.78 “Improvement Product” means any siRNA Product Controlled by
Alnylam, other than (a) ALN-TTR02, (b) ALN-TTRsc or (c) a Back-Up Compound that becomes a Licensed Product pursuant to Section 2.5.3.3. 
 1.79 “Improvement Product Development Budget” has the meaning set forth in Section 7.5. 

1.80 “Improvement Product Development Costs” has the meaning set forth in Section 7.5.3.1.

 1.81 “Improvement Product Development Plan” has the meaning set forth in
Section 7.5. 
 1.82 “Incremental Amounts” has the meaning set forth in
Section 11.4.2. 
 1.83 “IND” means an Investigational New Drug application,
Clinical Trial Application or similar application or submission for approval to conduct human clinical investigations filed with or submitted to a Regulatory Authority in conformance with the requirements of such Regulatory Authority. 

1.84 “IND-Enabling Toxicology Studies” means the pharmacokinetic and toxicology studies required
to meet the requirements for filing an IND. 
 1.85 “Indemnitee” has the meaning set
forth in Section 11.6. 
 1.86 “In-Licenses” means, collectively, the Alnylam
In-Licenses and the Genzyme In-Licenses. 
 1.87 “Joint Collaboration IP” means,
collectively, (a) any Know-How first identified, discovered or developed jointly by employee(s), agent(s) or consultant(s) acting on behalf of Alnylam or its Affiliates, on the one hand, and employee(s), agent(s) or consultant(s) acting on
behalf of Genzyme or its Affiliates, on the other hand, in the conduct of the Collaboration that is Controlled by Alnylam and Genzyme, and (b) any Patent Rights that Cover such Know-How and is Controlled by Alnylam and Genzyme. 

  
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 1.88 “Joint Development Budget” has the meaning set
forth in Section 2.3.3. 
 1.89 “Joint Clinical Study” has the meaning set forth in
Section 2.3.3. 
 1.90 “Joint Development Costs” has the meaning set forth in
Section 2.3.3. 
 1.91 “Joint Development Plan” has the meaning set forth in
Section 2.3.3. 
 1.92 “Joint Steering Committee” or “JSC” means the joint
steering committee as more fully described in Section 5.1. 
 1.93 “JPAC/LP
Milestone” has the meaning set forth in Section 7.4.3.2(b). 
 1.94
“JPAC/LP-Specific Milestone” has the meaning set forth in Section 7.4.3.2(b). 

1.95 “Know-How” means, all chemical or biological materials and other tangible materials,
inventions, improvements, practices, discoveries, developments, data, information, technology, methods, protocols, formulas, knowledge, know-how, trade secrets, processes, assays, skills, experience, techniques and results of experimentation and
testing, including pharmacological, toxicological and pre-clinical and clinical data and analytical and quality control data; provided, however, excluding in any event any Patent Right and Trademarks. 

1.96 “Laws” means all applicable laws, statutes, rules, regulations, orders, judgments,
injunctions, ordinances or other pronouncements having the binding effect of law of any Governmental Authority. 

1.97 “Licensed Product” means any of the following siRNA Products: (a) ALN-TTR02,
(b) ALN-TTRsc, (c) a Backup Compound that becomes a Licensed Product pursuant to Section 2.5.3.3 or other siRNA Product that becomes a Licensed Product pursuant to Section 2.5.3.4, or (d) an Improvement Product that becomes
a Licensed Product pursuant to Section 7.5. 
 1.98 “Licensing Party” has the
meaning set forth in Section 7.4.2.2. 
 1.99 “Lipid Nanoparticle Formulation” means
a lipid-based nanoparticle comprising more than one lipid species designed to enable delivery of siRNAs to mammalian cells. 
 1.100 [**]. 
 1.101 “Losses” has the
meaning set forth in Section 11.1. 
 1.102 “Manufacturing” or
“Manufacture” means, as applicable, all activities associated with the production, manufacture, process of formulating, processing, filling, finishing, packaging, labeling, shipping, importing, and storage of Licensed Products

  
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(including Bulk Drug Product, Bulk Drug Substance, and Finished Product, each as defined in the Supply Agreements), including process development, process validation, stability testing,
manufacturing scale-up, pre-clinical, clinical and commercial manufacture and analytical development, product characterization, quality assurance and quality control development, testing and release. 

1.103 “Manufacturing Claim” means a claim within a Patent Right directed solely to Manufacturing a
Licensed Product. 
 1.104 “MC3” has the meaning set forth in Section 1.6.

 1.105 “MHLW” has the meaning set forth in Section 1.129. 

1.106 “MicroRNA” or “miRNA” means a structurally defined functional RNA molecule
usually between 19 and 25 nucleotides in length, which is derived from an endogenous, genetically-encoded non-coding RNA which is predicted to be processed into a hairpin RNA structure that is a substrate for the double-stranded RNA-specific
ribonuclease Drosha and subsequently is predicted to serve as a substrate for the enzyme Dicer, a member of the RNase III enzyme family. 
 1.107 “MicroRNA Mimic” means a single-stranded or double-stranded oligonucleotide with the same or substantially similar-base composition and sequence (including chemically
modified bases) as a particular natural, miRNA and which is designed to mimic the activity of such miRNA. For clarity, miRNA Mimic excludes a double-stranded oligonucleotide which functions or is designed to function as an siRNA. 

1.108 “NDA” means a New Drug Application, Biologics License Application, Marketing Authorization
Application or similar application or submission filed with a Regulatory Authority in a country or group of countries to obtain marketing approval for a biological, pharmaceutical or other therapeutic or prophylactic product in that country or in
that group of countries. 
 1.109 “Net Sales” means the aggregate gross invoiced sales
prices from sales of all units of Licensed Products sold by Genzyme and its Related Parties to independent Third Parties (other than a Sublicensee) after deducting, if not previously deducted, from the amount invoiced or received: 

(b) trade, quantity and cash discounts, credits or allowances actually given; 

(c) returns, rejections, recalls, rebates, chargebacks and other credits or allowances actually given; 

(d) retroactive price reductions or billing corrections; 
 (e) value added, sales and use, excise and other similar taxes and surcharges, customary transportation and insurance, custom duties, and other governmental charges; and 

  
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 (f) amounts previously included in Net Sales of such Licensed Products that are adjusted or
written-off by Genzyme or its Related Parties as bad debt or otherwise uncollectible in accordance with the standard practices of Genzyme or its Related Parties for writing off uncollectible amounts consistently applied; provided 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. 
 Such amounts shall be determined from the books and records of Genzyme or its Related Parties, maintained in accordance with GAAP. 
 In the case of any sale or other disposal for value, such as barter or counter-trade, of Licensed Product, or part thereof, other than in an arm’s length transaction exclusively for cash, Net Sales
shall be calculated as above on the value of the non-cash consideration received or the fair market price (if higher) of the Licensed Product in the country of sale or disposal, as determined in accordance with GAAP. 

Notwithstanding the foregoing, the following will not be included in Net Sales: (1) sales between or among Genzyme and its Related Parties shall be
excluded from the computation of Net Sales, (but Net Sales shall include sales to the first Third Party (other than a Sublicensee) by Genzyme or its Related Parties); and (2) Licensed Product used as samples to promote additional Net Sales, in
amounts consistent with normal business practices of Genzyme. 
 1.110 “Non-Bankrupt
Party” has the meaning set forth in Section 7.7. 
 1.111 “Ongoing
Litigation” means (a) any litigation ongoing as of the Effective Date that was brought against Alnylam regarding or relating to any Alnylam Technology or (b) all related or similar actions arising from substantially the same
underlying facts as any litigation described in clause (a), whether brought prior to, on or after the Effective Date. 
 1.112 “Option” has the meaning set forth in Section 7.5. 
 1.113 “Option Exercise Package” has the meaning set forth in Section 7.5. 
 1.114 “Option Exercise Period” has the meaning set forth in Section 7.5. 
 1.115 “Out-of-Pocket Costs” means, with respect to certain activities hereunder, direct expenses paid or payable by either Party or its Affiliates to Third Parties and specifically
identifiable and incurred to conduct such activities for a Licensed Product, including payments to contract personnel. 
 1.116 “Party” means Genzyme and/or Alnylam. 

1.117 “Patent Rights” means (a) all issued patents (extensions, restorations by existing or
future extension or registration mechanism, including patent term adjustments, patent term extension, supplemental protection certificates or the equivalent thereof, substitutions, confirmations, re-registrations, re-examinations, and patents of
addition), (b) patent applications (including all provisional applications, substitutions, requests for continuation, continuations, continuations-in-part, divisionals and renewals), (c) inventor’s certificates, and (d) and all
equivalents of the foregoing in any country of the world. 

  
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 1.118 “Person” shall mean any natural person,
corporation, unincorporated organization, partnership, association, sole proprietorship joint stock company, joint venture, limited liability company, trust or government, or any agency or political subdivision of any government, or any other
similar entity. 
 1.119 “Phase I Study” means a study in humans which provides for the
introduction into humans of a product, conducted in healthy volunteers or patients, to obtain initial information on product safety, tolerability, pharmacological activity or pharmacokinetics, as more fully defined in 21 C.F.R. § 312.21(a) (or
the equivalent thereof outside the United States). 
 1.120 “Phase II Study” means a
study in humans of the safety, dose ranging or efficacy of a product, as further defined in 21 C.F.R. § 312.21(b) (or the equivalent thereof outside the United States). 

1.121 “Phase III Study” means a study in humans of the efficacy and safety of a product, which is
prospectively designed to demonstrate statistically whether such product is effective and safe for use in a particular indication in a manner sufficient (alone or together with one or more other such studies) to file an application for Regulatory
Approval for the product. For the avoidance of doubt, the Parties acknowledge that, because of the nature of ATTR, a Phase III Study for a Licensed Product may not include all of the elements that a Phase III Study for other kinds of drug products
may include (e.g., a Phase III Study for a Licensed Product may be a single study and there may be no prospective plan to run a second pivotal clinical trial independent of such Phase III Study). 

1.122 “PMDA” has the meaning set forth in Section 1.129. 

1.123 “Positive Reimbursement Decision” means The National Health Insurance Bureau issues a
pricing recommendation to MHLW in Japan. 
 1.124 “Post-Approval Study” means a human
clinical study of a Licensed Product initiated after receipt of Regulatory Approval for such Licensed Product in a country or territory, other than a Post-Marketing Commitment Study. 

1.125 “Post-Marketing Commitment Study” means a non-human or human clinical study of a Licensed
Product initiated after receipt of Regulatory Approval for such Licensed Product in a country or territory that is required by the Regulatory Authority in such country or territory to maintain the Regulatory Approval for such Licensed Product in
such country or territory. 
 1.126 “Product Trademark(s)” means the Trademarks for use
in connection with the distribution, marketing, promotion and sale of the Licensed Products. Product Trademarks specifically excludes the corporate names and logos of the Parties and their Affiliates. Product Trademark includes both the Alnylam
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 1.127 “Promotional Materials” has the meaning set
forth in Section 4.4.2. 
 1.128 “Regulatory Approval” means any and all approvals,
licenses, registrations or authorizations of any Regulatory Authority that are necessary for the marketing and sale of a product in a country or group of countries. 

1.129 “Regulatory Authority” means any applicable government regulatory authority involved in
granting approvals for the Development, Manufacturing, Commercialization, reimbursement and/or pricing of Licensed Products, including the FDA, the EMA, the Japanese Ministry of Health, Labour and Welfare (“MHLW”) and the
Pharmaceuticals and Medical Devices Agency in Japan (“PMDA”). 
 1.130
“Regulatory Exclusivity” means, with respect to a Licensed Product in a country, any exclusive marketing right, data exclusivity right, orphan drug designation or other country-wide exclusive right conferred by any Governmental
Authority with respect to such Licensed Product in such country, other than a Patent Right. 
 1.131
“Related Party” means a Party’s Affiliates, permitted Sublicensees and, with respect to Alnylam, licensees in the Alnylam Territory. 
 1.132 “Royalty Term” has the meaning set forth in Section 8.3.2. 
 1.133 “SDEA” has the meaning set forth in Section 3.4. 
 1.134 “siRNA” means a small interfering ribonucleic acid. 
 1.135 “siRNA Product” means an oligonucleotide composition of native or chemically modified RNA, designed to modulate the human TTR gene through activation of the RNA interference
pathway which is not a MicroRNA, MicroRNA antagonist or MicroRNA Mimic. 
 1.136 “SPC”
has the meaning set forth in Section 12.5. 
 1.137 “Sublicensee” means a Third Party to
whom a Party grants a sublicense under any Alnylam Technology or Genzyme Technology, as the case may be, to Develop, Manufacture or Commercialize Licensed Product in the Field pursuant to Section 7.1.3 or Section 7.2.4. 

1.138 “Supply Agreements” means the Clinical Supply Agreement and the Commercial Supply Agreement.

 1.139 “Term” has the meaning set forth in Section 13.1. 

  
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 1.140 “Territory” means (a) with respect to
Alnylam, the Alnylam Territory and (b) with respect to Genzyme, the Genzyme Territory. 
 1.141
“Third Party” means an entity other than a Party and its Affiliates. 
 1.142
“Third Party Collaboration Agreement” has the meaning set forth in Section 5.7. 

1.143 “Third Party License Payment” means royalties, upfront fees, milestones or other amounts
payable under an In-License. 
 1.144 “Third Party Partner” has the meaning set forth in
Section 5.7. 
 1.145 “Trademark” means any trademark, trade name, service mark,
service name, brand, domain name, trade dress, logo, slogan or other indicia of origin or ownership, including the goodwill and activities associated with each of the foregoing. 

1.146 “TTR” means the human TTR gene and its protein product, transthyretin. As of the Effective
Date, the NCBI RefSeq code for the TTR gene is NM_000371.3 and the NCBI RefSeq code for the TTR protein product is NP_000362.1. 
 1.147 “United States” means the United States of America and its territories, possessions and commonwealths. 

1.148 “Valid Claim” means a claim of: (a) an issued and unexpired patent, which claim has not
been withdrawn, cancelled, abandoned, disclaimed, revoked or held unenforceable or invalid by an unappealable decision of a court or other governmental agency of competent jurisdiction, or has not been appealed within the time allowed for appeal, or
by an appealed decision of a court or other governmental agency of competent jurisdiction where the appeal has been pending for more than [**] years (unless and until such decision is subsequently overturned on appeal) and which has not been
abandoned, disclaimed, denied or admitted to be invalid or unenforceable through reissue, re-examination or disclaimer or otherwise, or (b) a patent application that has been pending less than [**] years from the date of filing of the earliest
patent application from which such patent application claims priority, which claim has not been cancelled, withdrawn or abandoned or finally rejected by an administrative agency action from which no appeal can be taken. 

2. DEVELOPMENT COLLABORATION 
 2.1 Overview. Prior to the Effective Date, Alnylam has been engaged in the Development of the Licensed Products. Under this Agreement, the Parties will collaborate in the further Development
of Licensed Products, with Alnylam retaining primary responsibility for the Development of Licensed Products in the Alnylam Territory and Genzyme assuming primary responsibility for the Development of Licensed Products in the Genzyme Territory.

  
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 2.2 Development Plans. 

2.2.1 Global Development Strategy. The global Development strategy for the Licensed Products (“Global
Development Strategy”) is attached hereto as Schedule 2.2.1. Alnylam may amend the Global Development Strategy from time to time by providing notice and a copy of such changes to the JSC. [**] will have final decision-making
authority over all such amendments; provided, however, that [**] may not amend the Global Development Strategy in a manner that would [**] the Development of Licensed Products in the [**] Territory if [**] would [**] Development in the
[**] Territory [**] Development in the [**] Territory. [**] will present any proposed amendments to the Global Development Strategy to the JSC reasonably in advance of implementing such amendments, and [**] shall have the right to review and comment
thereon, and [**] shall consider in good faith [**] timely comments. 
 2.2.2 Alnylam Territory Development
Plan. The Development activities and Post-Approval Studies to be undertaken with respect to each Licensed Product by or on behalf of Alnylam will be set forth in a written work plan and time table (each, a “Alnylam Territory
Development Plan”), a draft framework of which is attached hereto as Schedule 2.2.2, and Alnylam will provide to Genzyme the first complete Alnylam Territory Development Plan for ALN-TTR02 and the then-current draft Development Plan
for ALN-TTRsc by [**]. Each Alnylam Territory Development Plan will set forth a rolling written work plan and time table with respect to the Development of and Post-Approval Studies for a Licensed Product from the Effective Date until the later of
(a) [**] years from date of such plan, and (b) receipt of Regulatory Approval for such Licensed Product. Each Alnylam Territory Development Plan shall subsequently be updated by Alnylam from time to time not later than [**] of each
Calendar Year until such time as no further Development or Post-Approval Studies are occurring or expected to occur with respect to the applicable Licensed Product. Alnylam will have final decision-making authority over the Alnylam Territory
Development Plans; provided, however, that the Alnylam Territory Development Plans shall at all times be materially consistent with the Global Development Strategy and shall not be amended in a manner that would have a material adverse
effect on the Development of Licensed Products in the Genzyme Territory if such material adverse effect would have a disproportionately significant impact on Development in the Genzyme Territory as compared to any such impact on Development in the
Alnylam Territory. Alnylam will present the Alnylam Territory Development Plans and any proposed amendments thereto to the JSC reasonably in advance of implementing such plans or amendments, and Genzyme shall have the right to review and comment
thereon, and Alnylam shall consider in good faith Genzyme’s timely comments. 
 2.2.3 Genzyme Territory Development
Plan. The Development activities and Post-Approval Studies to be undertaken with respect to each Licensed Product by or on behalf of Genzyme will be set forth in a written work plan and time table (each, a “Genzyme Territory
Development Plan”), which will be prepared by Genzyme by [**] and following review and approval, subject to Section 5.5.3(a), by the JSC, will then be attached hereto as Schedule 2.2.3. Each Genzyme Territory Development Plan
will set forth a rolling written work plan and time table with respect to the Development of and Post-Approval Studies for a Licensed Product from the Effective Date until the later of (a) [**] years from the date of such plan, and
(b) receipt of Regulatory Approval for such Licensed Product. The Genzyme Territory Development Plans shall subsequently be updated by Genzyme from time to time not later than [**] of each Calendar Year until such time as no further Development
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or expected to occur with respect to the applicable Licensed Product in the Genzyme Territory. Genzyme will have final decision-making authority over the Genzyme Territory Development Plans;
provided, however, that the Genzyme Territory Development Plans shall at all times be materially consistent with the Global Development Strategy and shall not be amended in a manner that would have a material adverse effect on the
Development of Licensed Products in the Alnylam Territory; provided, however, that Genzyme may, in accordance with Section 5.5, amend the Genzyme Territory Development Plan in a manner that materially adversely affects the
Development of Licensed Products in the Alnylam Territory if the Development activities contemplated by such amendment are reasonably required to obtain Regulatory Approval of a Licensed Product in the Genzyme Territory and there is no reasonable
alternative to such activity that would similarly enable Genzyme or its Related Parties to obtain such Regulatory Approval in the Genzyme Territory with a lesser adverse effect on the Development of Licensed Products in the Alnylam Territory.
Genzyme will present the Genzyme Territory Development Plans and any proposed amendments thereto to the JSC reasonably in advance of implementing such plans or amendments, and Alnylam shall have the right to review and comment thereon and Genzyme
shall consider in good faith Alnylam’s timely comments. 
 2.3 Responsibilities for Development Activities and
Costs. 
 2.3.1 Alnylam Development. Alnylam shall be primarily responsible for the global
Development of Licensed Products and all Development activities the primary purpose of which is to obtain or maintain Regulatory Approval of Licensed Products in the Alnylam Territory. Except as otherwise provided in a Joint Development Plan with
respect to Joint Development Costs agreed to pursuant to Section 2.3.3, Alnylam shall be responsible for one hundred percent (100%) of all Development costs with respect to Development activities that are conducted by Alnylam for the Licensed
Products in the Alnylam Territory pursuant to the Alnylam Territory Development Plan. Alnylam will promptly provide Genzyme with written notice of any decision by Alnylam to commence the first [**] of a Licensed Product by Alnylam or any of its
Related Parties, but in any event, Alnylam will provide such notice no later than [**] days prior to commencement thereof. Except as otherwise agreed by the Parties pursuant to Section 2.3.3 with respect to joint Development activities or
pursuant to Section 7.5 with respect to the Development of an Improvement Product, Alnylam will conduct all Development of the Licensed Products for the Alnylam Territory solely in accordance with the Alnylam Territory Development Plan, as such
Alnylam Territory Development Plan may be amended in accordance with this Agreement. 
 2.3.2 Genzyme
Development. Genzyme shall be responsible for the Development of Licensed Products under the Genzyme Territory Development Plan. Except as otherwise provided in a Joint Development Plan with respect to Joint Development Costs agreed
to pursuant to Section 2.3.3, Genzyme shall be responsible for one hundred percent (100%) of all Development costs with respect to Development activities that are conducted by Genzyme pursuant to the Genzyme Territory Development Plan.
Except as otherwise agreed by the Parties pursuant to Section 2.3.3 with respect to joint Development activities or pursuant to Section 7.5 with respect to the Development of an Improvement Product, Genzyme will conduct all Development of
the Licensed Products for the Genzyme Territory solely in accordance with the applicable Genzyme Territory Development Plan, as such Genzyme Territory Development Plan may be amended in accordance with this Agreement. 

  
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 2.3.3 Joint Development. In the event that the Parties mutually agree
to conduct a Clinical Study of a Licensed Product specifically designed for the purpose of facilitating Regulatory Approval of a Licensed Product in either (a) both the Alnylam Territory and the Genzyme Territory or (b) solely the Genzyme
Territory (a “Joint Clinical Study”), the Parties will (i) agree in writing to a written work plan and time table for conducting such Joint Clinical Study (the “Joint Development Plan”) and a mechanism for
adopting amendments thereto, (ii) agree in writing to governance and management mechanisms for such Joint Clinical Study, including coordination of such Clinical Study through the JSC and (iii) negotiate in good faith a budget therefor
(the “Joint Development Budget”), a mechanism for adopting amendments thereto, and an equitable allocation of costs (“Joint Development Costs”) between the Parties. 

2.4 Diligence. 
 2.4.1 Genzyme Diligence. Genzyme will use Commercially Reasonable Efforts to (a) Develop at least [**] and obtain Regulatory Approval therefor in each of (i) Japan and
(ii) any other country(ies) within the Genzyme Territory where Genzyme determines that it is commercially reasonable to seek Regulatory Approval (taking into account all relevant factors as provided in the definition of “Commercially
Reasonable Efforts”), (b) perform the Development activities under the Genzyme Territory Development Plan and (c) if applicable as to Joint Clinical Studies, the activities allocated to Genzyme under the Joint Development Plan. For
clarity, it may be consistent with Genzyme’s Commercially Reasonable Effort’s obligation to abandon Development of a Licensed Product in favor of another Licensed Product. 

2.4.2 Alnylam Diligence. Alnylam will use Commercially Reasonable Efforts to (a) Develop at least [**] and
obtain Regulatory Approval therefor by the FDA in the U.S. or by the EMA in the European Union, (b) perform the Development activities under the Alnylam Territory Development Plan and (c) if applicable as to Joint Clinical Studies, the
activities allocated to Alnylam under the Joint Development Plan. For clarity, Alnylam’s election not to bring forward a Backup Compound or Improvement Product for Development as a Licensed Product shall not constitute a breach of
Alnylam’s obligations under this Section 2.4.2. 
 2.5 Records; Reports; Information Sharing.

 2.5.1 Development Activities. Each Party will periodically provide to the JSC, but in no event less
than [**], or more frequently as reasonably requested by the other Party, an update regarding Development activities conducted by or on behalf of such Party, as well as any Post-Approval Studies conducted by the other Party. The Parties will
periodically report to the JSC, but in no event less than [**], regarding their respective activities conducted under the Joint Development Plan. 
 2.5.2 Improvement Products. Alnylam will periodically provide to the JSC updates regarding the status of potential Improvement Products, if any, for discussion pursuant to
Section 5.4.1(a). 

  
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 2.5.3 Backup Compounds. 

2.5.3.1. Alnylam will periodically provide to the JSC updates regarding the status of potential Backup Products, if
any, for discussion pursuant to Section 5.4.1(a). 
 2.5.3.2. In the event that Alnylam determines,
following discussion pursuant to Section 5.4.1(a) and subject to its diligence obligations under Section 2.4.2, to discontinue Development of ALN-TTR02 or ALN-TTRsc prior to receipt of Regulatory Approval therefor in the Alnylam Territory,
Alnylam will provide written notice thereof to Genzyme within [**] days following such determination. 

2.5.3.3. In the event that Alnylam, at its election following discussion pursuant to Section 5.4.1(a), intends
to bring forward a Backup Compound as a substitute Licensed Product for a product that has been discontinued under Section 2.5.3.2, Alnylam will provide Genzyme with written notice thereof, together with a statement detailing the results and
data of any pre-clinical or Clinical Studies for such proposed Backup Compound. Genzyme will have [**] days following the receipt of such notice and statement to review the proposed Backup Compound and to decide whether to include such Backup
Compound as a Licensed Product under this Agreement. In the event that Genzyme notifies Alnylam within such [**] day period that it desires to include such proposed Backup Compound as a Licensed Product under this Agreement, such proposed Backup
Compound will thereafter become a Licensed Product for all purposes of this Agreement. Notwithstanding the foregoing, if Alnylam brings forward a Backup Compound as a substitute Licensed Product for a product that has been discontinued under
Section 2.5.3.2, without providing Genzyme with the written notice and information required by this Section 2.5.3.3, such Backup Compound shall automatically become a Licensed Product for all purposes of this Agreement until such time as
Genzyme notifies Alnylam in writing that it does not wish such Backup Compound to be a Licensed Product, in which case such Backup Compound shall cease to be a Licensed Product for all purposes of this Agreement from the date of such notice. If a
Backup Compound becomes a Licensed Product pursuant to this Section 2.5.3, the Licensed Product for which Development has been discontinued that is being replaced by such Backup Compound shall cease to be a Licensed Product for the purposes of
this Agreement. 
 2.5.3.4. In the event that Genzyme determines, subject to its obligations under
Section 2.4.1, to discontinue Development of ALN-TTR02 prior to receipt of Regulatory Approval for ALN-TTR02 in the Genzyme Territory, but Alnylam has not discontinued Development of ALN-TTR02 in the Alnylam Territory prior to receipt of
Regulatory Approval for ALN-TTR02 in the Alnylam Territory, Genzyme may provide Alnylam with written notice of its desire to abandon Development of ALN-TTR02 in the Genzyme Territory and to pursue an alternative siRNA Product that is an siRNA
targeting the human TTR gene formulated in an AF11 Lipid Nanoparticle Formulation. After Alnylam’s receipt of such notice, Alnylam will provide Genzyme with any information in Alnylam’s possession that Genzyme may reasonably request
regarding 

  
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such siRNA Products. After its evaluation of such information, Genzyme may, by providing written notice to Alnylam, cause any one of such siRNA Products to become a Licensed Product for all
purposes of this Agreement from the date of such notice, and may Develop such siRNA Product for the Genzyme Territory; provided, however, that if Genzyme causes such an siRNA Product to become a Licensed Product, Alnylam shall have no
obligation to Develop such siRNA Product in the Alnylam Territory pursuant to this Agreement. If such an siRNA Product becomes a Licensed Product pursuant to this Section 2.5.3.4, then (a) the licenses granted by Alnylam to Genzyme with
respect to ALN-TTR02 under this Agreement shall terminate; (b) without limiting Genzyme’s obligations under Sections 2.4.1 and 4.1.1 as to the Development and Commercialization of Licensed Products generally, Genzyme’s obligations to
Develop and Commercialize ALN-TTR02 shall terminate, including all obligations under Section 2, Section 3, and Section 4 with respect to ALN-TTR02; (c) the development milestone payment under Section 8.2(iv) shall not be
payable by Genzyme with respect to Alnylam’s or its Related Parties’ development of ALN-TTR02 if such development milestone payment has not become payable prior to Genzyme’s discontinuation of development of ALN-TTR02; (d) the
JSC shall have no further responsibilities with respect to decision making or governance relating to the Development or Commercialization of ALN-TTR02, but Alnylam shall continue to provide informational updates to Genzyme regarding ALN-TTR02 to the
extent such information is reasonably useful or necessary to Genzyme with regard to the Development or Commercialization of Licensed Products in the Genzyme Territory; (e) Alnylam’s continued Development of ALN-TTR02 shall continue to
count toward the satisfaction of Alnylam’s obligations under Section 2.4.2; and (f) Alnylam’s obligations set forth in Section 5.7.1 shall cease to apply with respect to Alnylam’s licensing of ALN-TTR02. 

2.5.4 Scientific Records. Each Party will maintain scientific records, in sufficient detail and in good scientific
manner appropriate for patent and regulatory purposes, which will fully and properly reflect all work done and results achieved in the performance of the Development activities and Post-Approval Studies with respect to Licensed Products by such
Party. 
 2.5.5 Information Exchange and Development Assistance. During the Term, upon the reasonable
request of the other Party, each Party shall provide to the other Party, without additional compensation (except as provided in Section 6.2) and in a commercially reasonable format, Know-How Controlled by such Party and/or its Related Parties
that is licensed to the other Party under this Agreement (i.e. Know-How included in Genzyme Technology for Genzyme and Know-How included in Alnylam Technology for Alnylam) to the extent that it is reasonably necessary or useful for Developing a
Licensed Product in the requesting Party’s Territory or for obtaining or maintaining Regulatory Approval for a Licensed Product in the requesting Party’s Territory, including copies of (a) all scientific information and data related
to the Licensed Products (including all data made, collected or otherwise generated in the conduct of any pre-clinical studies, Clinical Studies, Post-Approval Studies or early access/named patient programs for the Licensed Products, as well as CMC
information), and (b) protocols and investigator brochures, in each case, that are reasonably necessary for the other Party (or its Related Parties) to perform its obligations or exploit its rights under this Agreement with respect

  
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to Licensed Products. Notwithstanding the foregoing, Genzyme shall have no obligation to transfer or disclose to Alnylam any Know-How included in the Genzyme Manufacturing IP; provided
however, that if Genzyme elects, in its sole discretion, to transfer or disclose any such Know-How to Alnylam in writing, it shall be “Genzyme Disclosed Manufacturing Know-How” under this Agreement and licensed to Alnylam in
accordance with Section 7.2.3. 
 2.5.6 Personnel. Each Party may request, through the JSC or the
other Party’s Collaboration Manager, if the JSC appoints Collaboration Managers, that the other Party reasonably make available for consultation regarding the Development of Licensed Products certain of its employees engaged in Development
activities and Post-Approval Studies with respect to Licensed Products. The JSC or the Collaboration Managers will reasonably coordinate, upon reasonable notice during normal business hours and at their respective places of employment, consultation
between the Parties on the progress of Licensed Product Development and Post-Approval Studies. 
 2.5.7
Confidentiality. All information exchanged by the Parties under this Section 2.5 will be deemed to be Confidential Information of the disclosing Party and maintained in accordance with Section 9. 

2.6 Third Parties. The Parties shall be entitled to utilize the services of Third Party contract research and contract
manufacturing organizations to perform their respective Development and Manufacturing activities under this Agreement; provided that (a) each Party shall require that such Third Party operates in a manner consistent with the terms
of this Agreement and (b) each Party shall remain at all times fully liable for its respective responsibilities. Each Party shall require that any such Third Party agreement include confidentiality and non-use provisions that are no less
stringent than those set forth in Section 9 of this Agreement and shall use Commercially Reasonable Efforts to obtain ownership of, and/or a fully sublicenseable license under and to, any Know-How and Patent Rights that are developed by such
Third Party in the performance of such agreement and are reasonably necessary or useful to Develop, Manufacture and/or Commercialize Licensed Products in the Field. 
 3. REGULATORY MATTERS. 
 3.1 Regulatory Filings and Interactions.

 3.1.1 Responsibilities. Except as otherwise provided in the Joint Development Plan, (a) each Party
will own the INDs, the NDAs and related regulatory documents submitted to the applicable Regulatory Authorities in its Territory with respect to Licensed Products and (b) each Party will, as to Licensed Products in its Territory
(i) oversee, monitor and coordinate all regulatory actions, communications and filings with, and submissions to, each Regulatory Authority, (ii) be responsible for interfacing, corresponding and meeting with each Regulatory Authority
and(iii) be responsible for maintaining all regulatory filings. 
 3.1.2 Communications. Each Party will, as to
Licensed Products in its Territory, notify the JSC in writing, including a brief description in English of the principal issues raised, of all material communications from Regulatory Authorities within [**] days, provide the JSC with a summary
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possible but in any event within [**] days, and provide a full translation of such material communications in English as soon as reasonably possible thereafter. Each Party will provide the
complete copies of the original correspondence in their native language to the other Party upon request. 
 3.1.3
Meetings. Each Party shall provide the other Party with reasonable advance notice of all substantive meetings with the Government Authorities in its Territory pertaining to any Licensed Products, or with as much advance notice as
practicable under the circumstances. Each Party shall use Commercially Reasonable Efforts, to the extent reasonably practicable, to permit the other Party to have, at the other Party’s expense, one (1) mutually acceptable representative of
the other Party to attend, solely as a non-participating observer, material, substantive meetings with the Governmental Authorities within such Party’s Territory pertaining to any Licensed Product; provided, however, that neither
Party shall be obligated to change the schedule of such a meeting in order to accommodate the schedule of the other Party’s representative. 
 3.1.4 Submissions. In addition, each Party shall provide the other Party with written notice of (a) all filings and submissions for Regulatory Approval (including orphan drug
applications and designations) regarding any Licensed Product in such Party’s Territory in a timely manner; (b) all Regulatory Approvals obtained or denied; and (c) the filing of any IND for any Licensed Product within [**] days after
such event; provided, however, that in all circumstances, each Party shall inform the other Party of such event prior to public disclosure of such event by such Party. 

3.2 Costs of Regulatory Affairs. Unless otherwise agreed to pursuant to Section 2.3.3, each Party shall be
responsible for all costs incurred by such Party connection with applying for Regulatory Approval with respect to Licensed Products in its Territory, and related regulatory affairs activities. 

3.3 Right of Reference. Each Party hereby grants to the other Party, and at the request of the other Party will grant to
the other Party’s Related Parties, a “Right of Reference,” as that term is defined in 21 C.F.R. § 314.3(b) (or any successor rule or analogous Law recognized outside of the United States), to, and a right to copy, access, and
otherwise use, all information and data (including all CMC information as well as data made, collected or otherwise generated in the conduct of any Clinical Studies or Post-Approval Studies or early access/named patient programs for the Licensed
Products) included in any regulatory filing, Regulatory Approval, drug master file or other regulatory documentation (including orphan drug applications and designations) owned or controlled by such Party or its Related Parties that relates to
(a) any Licensed Product or (b) with respect to such information and materials provided to Genzyme, to the extent necessary or useful to obtain Regulatory Approval of a Licensed Product in the Genzyme Territory, the siRNA Product
Controlled by Alnylam and known as ALN-TTR01, and such Party shall provide a signed statement to this effect, if requested by the other Party, in accordance with 21 C.F.R. § 314.50(g)(3) (or any successor or analogous Law outside of the United
States). 

  
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 3.4 Pharmacovigilance. At least [**] months prior to Genzyme obtaining the
authorization to conduct any Genzyme sponsored study, the Parties will negotiate a Safety Data Exchange Agreement (“SDEA”) to be agreed upon in writing, that will define the pharmacovigilance responsibilities of the Parties and
include safety data exchange procedures governing the coordination of collection, investigation, reporting, and exchange of information concerning any adverse experiences, and any product quality and product complaints associated with adverse
experiences, related to Licensed Products, sufficient to enable each Party (and their respective Related Parties, if any) to comply with its legal and regulatory obligations. 
 4. COMMERCIALIZATION OF THE LICENSED PRODUCTS 
 4.1 Responsibility,
Cost and Diligence. 
 4.1.1 Genzyme. Genzyme shall be solely responsible, at its expense, for all
Commercialization activities relating to Licensed Products in the Field in the Genzyme Territory. Genzyme shall use Commercially Reasonable Efforts to Commercialize Licensed Products in each country within the Genzyme Territory where Genzyme has
obtained Regulatory Approval for a Licensed Product. For clarity, it may be consistent with Genzyme’s Commercially Reasonable Effort’s obligation to abandon Commercialization of a Licensed Product in favor of another Licensed Product.

 4.1.2 Alnylam. Alnylam shall be solely responsible, at its expense, for all Commercialization activities
relating to Licensed Products in the Field in the Alnylam Territory. 
 4.1.3 Joint Commercialization. In
the event that the Parties mutually agree to conduct any joint Commercialization activities regarding a Licensed Product, the Parties will (a) agree in writing to a written work plan and time table for conducting such activities, (b) agree
in writing to management and governance mechanisms for such joint activities, including coordination of such activities through the JSC and (c) negotiate in good faith a budget therefor and an equitable allocation of costs between the Parties.

 4.2 Genzyme Commercialization Plan. No less than [**] months in advance of [**] in the Genzyme Territory with
respect to a Licensed Product, and on [**] basis thereafter, Genzyme shall prepare and deliver to the JSC for review a reasonable written plan that summarizes the Commercialization activities to be undertaken with respect to Licensed Products in the
Genzyme Territory in the [**] and, to the extent commercially reasonable, Genzyme’s plans to obtain further Regulatory Approvals and Commercialize Licensed Products in countries in the Genzyme Territory in which Genzyme is not then
Commercializing Licensed Products, and the dates by which such activities are targeted to be accomplished (the “Genzyme Territory Commercialization Plan”). The Genzyme Territory Commercialization Plan shall subsequently be updated
and modified by Genzyme, from time to time at its discretion and no less frequently than [**], based upon, among other things, Genzyme’s Commercialization activities with respect to Licensed Products in the Genzyme Territory, a copy of which
updated plan Genzyme will provide to the JSC. Notwithstanding the foregoing, in the event of any disagreement between the Parties regarding the Genzyme Territory Commercialization Plan pursuant to Section 5.5, the Genzyme representatives on the
JSC shall have final decision-making authority over the preparation and updating of the Genzyme Territory Commercialization Plan; provided that, such decisions do not materially adversely affect the Commercialization of a Licensed
Product in the Alnylam Territory. 

  
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 4.3 Alnylam Commercialization Plan. Reasonably in advance of the
expected [**] in the Alnylam Territory with respect to a Licensed Product, and on [**] basis promptly as it becomes available, Alnylam will deliver to Genzyme its written plan, generated by Alnylam for its internal purposes, that summarizes the
Commercialization activities to be undertaken with respect to Licensed Products in the Alnylam Territory in the [**] (the “Alnylam Territory Commercialization Plan”). 

4.4 Advertising and Promotional Materials.  
 4.4.1 Global Branding. Alnylam shall have the right, from time to time during the Term, to develop (and thereafter modify and update) a global branding strategy (including global
positioning, messages, logo, colors and other visual branding elements) for Licensed Products for use in the Field throughout the world (the “Global Branding Strategy”), which the JSC shall, in accordance with Sections 5.4.2(b) and
5.5, review and approve, and which the Parties shall, following such review and approval, implement. Alnylam will submit the Global Branding Strategy to the JSC at least [**] (or more frequently if reasonably requested by Genzyme). Alnylam shall
consider in good faith any timely comments Genzyme may have with respect to the Global Branding Strategy, but shall have final decision-making authority with respect to such Global Branding Strategy. 

4.4.2 Alnylam. Alnylam will be responsible for the creation, preparation, production, reproduction and filing with
the applicable Regulatory Authorities, of relevant written sales, promotion and advertising materials relating to Licensed Products (“Promotional Materials”) for use in the Alnylam Territory. All such Promotional Material will be
(a) compliant with applicable Law, and (b) if applicable, consistent in all material respects with the Global Branding Strategy. Alnylam will submit representative samples of its Promotional Materials developed by it for use in the Alnylam
Territory to the JSC, at least [**] (or more frequently if reasonably requested by Genzyme). Alnylam shall consider in good faith any timely comments Genzyme may have with respect to such Promotional Materials, but shall have final decision-making
authority with respect to such Promotional Materials. 
 4.4.3 Genzyme. Genzyme will be responsible for the
creation, preparation, production, reproduction and filing with the applicable Regulatory Authorities, of relevant Promotional Materials for use in the Genzyme Territory. All such Promotional Materials will be (a) compliant with applicable Law,
(b) consistent in all material respects with the Genzyme Territory Commercialization Plan, and (c) if applicable, consistent in all material respects with the Global Branding Strategy. Genzyme will submit representative samples of its
Promotional Materials developed by it for use in the Genzyme Territory to the JSC at least [**] thereafter (or more frequently if reasonably requested by Alnylam). Genzyme shall consider in good faith any timely comments Alnylam may have with
respect to such Promotional Materials, but shall have final decision-making authority with respect to such Promotional Materials. 

  
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 4.5 Reporting Obligations. Genzyme shall report to the JSC in writing, by no
later than each [**] following the first Regulatory Approval of a Licensed Product in the Field in the Genzyme Territory (for the period ending December 31 of the prior Calendar Year), summarizing in reasonable detail Genzyme’s
Commercialization activities for Licensed Products performed to date (or updating such report for activities performed since the last such report was given hereunder, as applicable). In addition, Genzyme shall provide Alnylam with written notice of
the First Commercial Sale of each Licensed Product in the Genzyme Territory within [**] days after such event; provided, however, that in all circumstances, Genzyme shall inform Alnylam of such event prior to public disclosure of such
event by Genzyme. Each Party shall provide such other information to the JSC as the other Party may reasonably request and shall keep the JSC reasonably informed of such Party’s Commercialization activities with respect to Licensed Products.
 
 4.6 Sales and Distribution. Each Party and its Related Parties shall be responsible for booking sales and
shall warehouse and distribute Licensed Products in its Territory. If a Party receives any orders for any Licensed Product in the other Party’s Territory, it shall refer such orders to the other Party. Moreover, each Party and its Related
Parties shall be solely responsible for handling all returns of Licensed Product sold in its Territory, as well as all aspects of Licensed Product order processing, invoicing and collection, distribution, inventory and receivables of Licensed
Products sold in its Territory. 
 4.7 Recalls, Market Withdrawals or Corrective Actions. In the event that any
Regulatory Authority issues or requests a recall or takes a similar action in connection with the Licensed Product in a Territory, or in the event either Party determines that an event, incident or circumstance has occurred that may result in the
need for a recall or market withdrawal in its own Territory, the Party notified of such recall or similar action, or the Party that desires such recall or similar action, shall within [**] advise the other Party thereof by telephone, facsimile or
e-mail. Each Party, in consultation with the other Party, shall decide whether to conduct a recall in its own Territory and the manner in which any such recall shall be conducted (except in the case of a government mandated recall, when such Party
may act without such advance notice but shall notify the other Party as soon as possible). Each Party shall bear the expense of any such recall in its own Territory. Each Party will make available all of its pertinent records that may be reasonably
requested by the other Party in order to effect a recall in the other Party’s Territory. 
 4.8 Ex-Territory Sales;
Export Monitoring. 
 4.8.1 Ex-Territory Sales. Subject to applicable Law, neither Party shall engage in
any advertising or promotional activities relating to any Licensed Product directed primarily to customers or other buyers or users of such Licensed Product located outside its Territory or accept orders for Licensed Products from or sell Licensed
Products into such other Party’s Territory for its own account, and if a Party receives any order for Licensed Products in the other Party’s Territory, it shall refer such orders to the other Party. 

4.8.2 Export Monitoring. Each Party and its Related Parties will use Commercially Reasonable Efforts to monitor and prevent
exports of Licensed Products from its own Territory for Commercialization in the other Party’s Territory using methods commonly used in the industry for such purpose, and shall promptly inform the other Party of any such exports of

  
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Licensed Products from its Territory, and the actions taken to prevent such exports. Each Party agrees to take reasonable actions requested in writing by the other Party that are consistent with
Law to prevent exports of Licensed Products from its Territory for Commercialization in the other Party’s Territory. 

5. COLLABORATION MANAGEMENT 
 5.1 Joint Steering Committee. The Parties hereby establish a joint steering committee (the “JSC”) to facilitate the Collaboration as follows: 

5.1.1 Composition of the Joint Steering Committee. The Collaboration shall be conducted under the oversight of the JSC,
which shall comprise [**] representatives of each Party. Each Party shall appoint its respective representatives to the JSC from time to time, and may substitute one or more of its representatives, in its sole discretion, effective upon notice to
the other Party of such change. Each Party shall have at least one JSC representative who is a senior employee [**], and all JSC representatives shall have appropriate expertise and ongoing familiarity with the Collaboration. Additional
representatives or consultants may from time to time, by mutual consent of the Parties, be invited to attend JSC meetings, subject to such representatives and consultants undertaking confidentiality obligations, whether in a written agreement or by
operation of law, no less stringent than the requirements of Section 9.1. 
 5.1.2 JSC Chairperson. The JSC
chairperson shall rotate every [**] months between a JSC representative of Alnylam and a JSC representative of Genzyme. The initial JSC chairperson shall be a representative of [**]. The JSC chairperson’s responsibilities shall include
(a) scheduling meetings at least [**], but more frequently if the JSC determines it necessary; (b) setting agendas for meetings with solicited input from other members; (c) coordinating the delivery of draft minutes to the JSC for
review and final approval; and (d) conducting meetings, including ensuring that objectives for each meeting are set and achieved. 
 5.2 Appointment of Subcommittees, Project Teams and Collaboration Managers. The JSC shall be empowered to create such subcommittees of itself and project teams as it may deem appropriate or
necessary, such as for specific oversight of Development, Manufacturing, Commercialization or intellectual property issues. Each such subcommittee and project team shall report to the JSC, which shall have authority to approve or reject
recommendations or actions proposed thereby subject to the terms of this Agreement. The JSC may direct each Party to designate a Collaboration manager (the “Collaboration Manager”) to serve as a primary point of contact for the
other Party under the Collaboration. Each Party may change its Collaboration Manager at any time in its sole discretion with written notice to the other Party. 
 5.3 Meetings. The JSC shall meet in accordance with a schedule established by mutual written agreement of the Parties, but no less frequently than [**] during the Term, with the location for
such meetings alternating between Alnylam and Genzyme facilities (or such other locations as are mutually agreed by the Parties). Alternatively, the JSC may meet by means of teleconference, videoconference or other similar communications equipment,
but at least [**] meetings per [**] shall be conducted in person. All proceedings for the JSC shall take place in English. Each Party shall bear its own expenses relating to attendance at such meetings by its representatives. 

  
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 5.4 Minutes. A secretary shall be appointed for each meeting of the JSC
and shall prepare minutes of the meeting, which shall provide a description in reasonable detail of the discussions held at the meeting and a list of any actions, decisions or determinations approved by the JSC. 

5.4.1 JSC Development Responsibilities. The JSC shall have the following responsibilities with respect to the Development
of Licensed Products pursuant to the Collaboration: 
 (a) reviewing and discussing updates to be provided by Alnylam pursuant
to Section 2.5.1 and Section 7.5 regarding the Development status of potential Backup Compounds and Improvement Products; 
 (b) reviewing and approving, subject to Section 5.5.3(a), the initial Genzyme Territory Development Plan and reviewing and discussing updates provided by each Party regarding the Development of
Licensed Products in such Party’s Territory, including updates to the Global Development Strategy, the Genzyme Territory Development Plan or Alnylam Territory Development Plan, as applicable, provided by the applicable Party in accordance with
Section 2.2, and providing each Party with feedback regarding the same; 
 (c) monitoring and coordinating Development
activities in the Genzyme Territory and the Alnylam Territory for Licensed Products, and regulatory and pharmacovigilance requirements and matters; 
 (d) monitoring, planning and coordinating any Joint Clinical Studies in accordance with any Joint Development Plan, Joint Development Budget, and written agreement between the Parties with respect to the
governance and management of such Joint Clinical Studies; 
 (e) overseeing the manufacturing and supply relationship between
the Parties with respect to the Manufacture of Licensed Products for Development activities (subject to the terms of the Clinical Supply Agreement); and 
 (f) performing such other activities as the Parties agree in writing shall be the responsibility of the JSC. 
 5.4.2 JSC Commercialization Responsibilities. The JSC shall have the following responsibilities with respect to the Commercialization of Licensed Products pursuant to the Collaboration, to
the extent permissible under applicable Laws: 
 (a) reviewing and discussing updates to be provided by each Party regarding the
Commercialization of Licensed Products in such Party’s Territory; 
 (b) reviewing and approving, subject to
Section 5.5.3(b), any Global Branding Strategy developed by Alnylam; 

  
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 (c) reviewing and discussing the Genzyme Territory Commercialization Plan and updates
thereto provided by Genzyme pursuant to Section 4.2; 
 (d) reviewing and discussing Promotional Material of both Parties
in accordance with Sections 4.4.2 and 4.4.3; 
 (e) providing a forum for the Parties to discuss the Commercialization of
Licensed Products in the Field worldwide, including coordination regarding Licensed Product positioning and messaging, key opinion leader relationship management, medical affairs, and marketing and selling materials; 

(f) providing a forum for the Parties to discuss collaborating on commercial activities that can be leveraged for both Parties’
respective Territories and how the Parties would share the costs of such mutually agreed joint Commercialization activities; 

(g) overseeing the manufacturing and supply relationship between the Parties with respect to the Manufacture of Licensed Products for
Commercialization activities (subject to the terms of the Commercial Supply Agreement); and 
 (h) performing such other
activities as the Parties agree in writing shall be the responsibility of the JSC. 
 5.5 Decision-Making.

 5.5.1 With respect to decisions of the JSC, the representatives of each Party shall have collectively one vote on
behalf of such Party. For each meeting of the JSC, at least [**] representatives of each Party shall constitute a quorum. Action on any matter may be taken at a meeting, by teleconference, videoconference or by written agreement. The JSC shall
attempt to resolve any and all disputes before it for decision by consensus. 
 5.5.2 If the JSC is unable to reach a
consensus with respect to a dispute for a period in excess of [**] days, then the dispute shall be submitted to the Chief Executive Officers, or his or her designee (any such designee to be a senior member of the designating Chief Executive
Officer’s management team), of Alnylam and Genzyme for resolution. 
 5.5.3 If such dispute cannot be resolved for a
period in excess of [**] days following escalation, then: 
 (a) subject to Section 5.5.4, the Chief Executive Officer of
Genzyme or his or her designee shall have the deciding vote on any matter involving the Development or Commercialization of Licensed Products in the Field in the Genzyme Territory, including the Genzyme Territory Development Plan and the Genzyme
Territory Commercialization Plan; and 
 (b) subject to Section 5.5.4, the Chief Executive Officer of Alnylam or his or her
designee shall have the deciding vote on any matter involving the Development or Commercialization of Licensed Products in the Field in the Alnylam Territory, including the Alnylam Territory Development Plan and the Alnylam Territory
Commercialization Plan, and on any matter involving the content of the Global Branding Strategy. 

  
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 5.5.4 Neither Party shall have the deciding vote on, and the JSC shall not have
decision-making authority regarding, any of the following matters: 
  

	 	(i)	the allocation of milestone payments to Third Parties under Future Alnylam In-Licenses pursuant to Section 7.4.3.2; 

 

	 	(ii)	the imposition of any requirements on the other Party to undertake obligations beyond those for which it is responsible, or forgo any rights, under this Agreement or
the Supply Agreements; 

  

	 	(iii)	any matters that would cause a material increase in costs that the other Party is required to expend, as determined in the reasonable discretion of such other Party;

  

	 	(iv)	the imposition of any requirements that the other Party take or decline to take any action that would result in a violation of any Law or any agreement with any Third
Party or the infringement of intellectual property rights of Third Parties; 

  

	 	(v)	any matters that would excuse such Party from any of its obligations specifically enumerated under this Agreement or the Supply Agreements; or 

 

	 	(vi)	modifying the terms of this Agreement or any Supply Agreement or taking any action to expand or narrow the responsibilities of the JSC. 

5.6 Term of JSC. After the [**] anniversary of the Effective Date Alnylam shall have the right to terminate its
participation in the JSC. Following any such termination, the Parties will discuss in good faith and agree upon reasonable processes regarding decision making and information sharing in order to provide each Party with substantially the same rights
and information as such Party enjoyed during the period during which the JSC was constituted.  
 5.7 Alnylam Third
Party Partner. If, at any time during the Term, Alnylam enters into an agreement (a “Third Party Collaboration Agreement”) with one or more Third Party(ies) (the “Third Party Partner”) to Develop
and/or Commercialize a Licensed Product in the Field in the Alnylam Territory, Alnylam shall ensure that such agreement is consistent with the terms and conditions of this Agreement. 

5.7.1 Required Terms. Without limitation, Alnylam shall negotiate terms in the Third Party Collaboration Agreement
(a) regarding intellectual property necessary to permit Alnylam to license or sublicense to Genzyme any Patent Rights and Know-How developed in the course of activities pursuant to the Third Party Collaboration Agreement that are necessary for
Genzyme to Develop, Manufacture and Commercialize Licensed Products in accordance with this Agreement, if any, (b) providing Genzyme with a right of reference as set forth in Section 3.3 (Right of Reference), (c) requiring such Third
Party Partner to maintain records substantially as set forth in Section 2.5.4 (Scientific Records), (d) enabling Alnylam to provide Genzyme with 

  
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copies of data and reports, including Clinical Study reports, in a commercially reasonable format, made, collected or otherwise generated by or on behalf of the Third Party Partner in the conduct
of any pre-clinical studies, Clinical Studies or early access/named patient programs for the Licensed Products (excluding, for clarity, information generated in Post-Approval Studies and CMC information), and protocols and investigator brochures
related to the Licensed Product, in each case that are reasonably necessary for Genzyme (or its Related Parties) to Develop and obtain Regulatory Approval for the Licensed Products in the Genzyme Territory, (e) enabling Alnylam to provide
Genzyme with information with respect to matters in the Third Party Partner’s territory as are required to be provided to Genzyme under Sections 2.5.1 (Development Activities), 3.1.2 (Communications), to the extent requiring a brief description
in English of principal issues raised in material communications from Regulatory Authorities and otherwise to the extent reasonably necessary to assist Genzyme with obtaining Regulatory Approvals of Licensed Products, and 3.1.4 (Submissions),
(f) regarding pharmacovigilance that are consistent with Section 3.4 and the SDEA, and (g) regarding recalls that are consistent with Section 4.6. 
 5.7.2 Terms Subject to Commercially Reasonable Efforts. In addition, Alnylam shall use Commercially Reasonable Efforts to negotiate terms in the Third Party Collaboration Agreement
(a) related to intellectual property that would give Genzyme substantially similar rights with respect to intellectual property developed in the course of activities under the Third Party Collaboration Agreement as Genzyme would have received
with respect to intellectual property developed in the course of the Collaboration, and (b) enabling Alnylam to provide Genzyme with reciprocal information, rights and benefits with respect to the Development of Licensed Products and the
conduct of Post Approval Studies for the Third Party Partner’s territory as are provided to Alnylam by Genzyme in this Agreement. 
 5.7.3 Global Coordination Committee. Alnylam shall use reasonable efforts to include in any Third Party Collaboration Agreement relating to rights licensed to a Third Party Partner in
the United States and/or major markets in Europe, the discretionary participation by such Third Party Partner with Genzyme and Alnylam in a global coordination committee, which shall include representatives of Alnylam, Genzyme and the Third Party
Partner and which shall be responsible for facilitating discussions between the parties with respect to the global Development, Manufacture, and Commercialization of Licensed Products. 

5.7.4 Notice. Alnylam shall promptly provide Genzyme with a copy of any fully executed Third Party Collaboration
Agreement, which may be redacted to remove terms and conditions which are not necessary to monitor compliance with this Section 5.7 and such Third Party Collaboration Agreement will be Alnylam Confidential Information for the purposes of
Section 9 (Confidentiality and Publication). 
 5.7.5 Sublicenses. In addition, if the Third Party
Collaboration Agreement grants the Third Party Partner a sublicense under the Genzyme Technology, Alnylam shall ensure that such Third Party Collaboration agreement complies with Section 7.2.4 (Sublicensing Terms). 

5.7.6 Breach; Responsibility. If Alnylam becomes aware of a material breach of the terms of any Third Party
Collaboration Agreement by a Third Party Partner compliance with which is necessary for Alnylam’s compliance with the terms of this Agreement, Alnylam shall 

  
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promptly notify Genzyme of the particulars of the same and use Commercially Reasonable Efforts to cause the Third Party Partner to comply with all the terms of the Third Party Collaboration
Agreement necessary for Alnylam’s compliance with the terms of this Agreement. Notwithstanding any Third Party Collaboration Agreement, Alnylam shall remain primarily liable to Genzyme for the performance of all of Alnylam’s obligations
under, and Alnylam’s compliance with all terms and conditions of, this Agreement with respect to the entire Alnylam Territory. 
 6. MANUFACTURE AND SUPPLY OF THE LICENSED PRODUCT 
 6.1 Supply
Agreements. Within [**] months after the Effective Date, the Parties will negotiate in good faith and enter into a supply agreement for clinical supply of Licensed Product (the “Clinical Supply Agreement”), which will be
consistent with the terms set forth on Schedule 6.1. In addition, at the request of Genzyme reasonably in advance of the first commercial launch of a Licensed Product in the Genzyme Territory, the Parties will negotiate in good faith and
enter into a supply agreement for commercial supply of Licensed Product (the “Commercial Supply Agreement”), which will also be consistent with the terms set forth on Schedule 6.1. 

6.2 Transfer of Manufacturing Know-How. At Genzyme’s request at any time during the Term, Alnylam shall
transfer to Genzyme, a Genzyme Related Party, or a Third Party manufacturer, all Alnylam Know-How necessary or useful to enable the Manufacture of the Licensed Products and not previously transferred to Genzyme, a Genzyme Related Party, or such
Third Party manufacturer, in bulk and/or finished form (as requested by Genzyme), by providing copies or samples of relevant documentation, materials and other embodiments of such Know-How and by making available its qualified technical personnel on
a reasonable basis to consult with Genzyme, its Related Party, or such Third Party manufacturer with respect to such Know-How. If requested by Genzyme, such Know-How transfer shall be conducted pursuant to a mutually-agreed technology transfer plan
developed by the parties for the purpose of ensuring the complete and timely transfer of such Know-How that is consistent with Genzyme’s then current internal Technology Transfer Corporate Standard (or equivalent policy) that have been provided
to Alnylam. Such Know-How transfer shall be conducted at Alnylam’s sole expense for the first [**] hours of Alnylam employees’ time, and thereafter at Genzyme’s expense at the cost of Alnylam employees’ time at the FTE Rate.
Genzyme will reimburse Alnylam for its Out-of-Pocket Costs incurred in the course of such transfer, provided that such Out-of-Pocket Costs are approved in advance by Genzyme and itemized in Alnylam’s invoice. Genzyme shall pay
Alnylam such FTE Rate and reimburse Alnylam for such Out-of-Pocket Costs within [**] days after receipt of an invoice therefor. 

7. LICENSES 
 7.1 License Grants to Genzyme. 
 7.1.1 Development and
Commercialization License in the Genzyme Territory. Subject to the terms and conditions of this Agreement, Alnylam hereby grants Genzyme a non-transferable (except as provided in Section 14.1), sublicensable (subject to
Section 7.1.3) 

  
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exclusive (even as to Alnylam) license under Alnylam Technology to Develop and Commercialize Licensed Products in the Field in the Genzyme Territory. Such license shall be royalty-bearing for the
Royalty Term applicable to each Licensed Product in each country in the Genzyme Territory, and, after the Royalty Term applicable to such Licensed Product in such country, shall convert to a fully-paid license to Develop and Commercialize such
Licensed Product in the Field in such country. 
 7.1.2 Manufacturing License. Subject to the terms and conditions
of this Agreement, Alnylam hereby grants Genzyme a non-transferable (except as provided in Section 14.1), sublicensable (subject to Section 7.1.3), worldwide, exclusive license under Alnylam Technology to Manufacture Licensed Products
inside or outside of the Genzyme Territory solely for Development and Commercialization in the Genzyme Territory and, to the extent permitted pursuant to Section 2.3.3, for Development in the Alnylam Territory. Notwithstanding the foregoing,
Alnylam retains the exclusive right under the Alnylam Technology, with the right to grant licenses through multiple tiers without restriction, to Manufacture Licensed Products anywhere in the world (i) for Development and Commercialization in
the Alnylam Territory and, to the extent permitted pursuant to Section 2.3.3 for Development in the Genzyme Territory, and (ii) to supply Genzyme pursuant to the Supply Agreements to be agreed by the Parties pursuant to Section 6.1.

 7.1.3 Sublicensing Terms. 
 (a) Genzyme shall have the right to sublicense any of its rights under Section 7.1.1 and 7.1.2 to any of its Affiliates or to any Third Party (which sublicensed rights may be further sublicensable
through multiple tiers) without the prior consent of Alnylam, subject to the requirements of this Section 7.1.3. Notwithstanding the foregoing, Genzyme shall not have the right to sublicense to a Third Party either (i) its primary
Development or Commercialization rights in Japan; or (ii) all or substantially all of its rights under this Agreement. 

(b) Each sublicense granted by Genzyme pursuant to this Section 7.1.3 shall be subject and subordinate to the terms and conditions
of this Agreement and shall contain terms and conditions consistent with those in this Agreement. Genzyme shall promptly provide Alnylam with a copy of the fully executed sublicense agreement covering any sublicense granted hereunder (which copy may
be redacted to remove terms and conditions which are not necessary to monitor compliance with this Section 7.1.3), and each such sublicense agreement shall contain the following provisions: (i) a requirement that the Sublicensee comply
with the confidentiality and non-use provisions of Section 9 with respect to Alnylam’s Confidential Information, (ii) if such sublicense agreement contains a sublicense of Licensed Product Commercialization rights, such sublicense
agreement shall also contain the following provisions: (x) a requirement that the Sublicensee submit applicable sales or other reports to Genzyme to the extent necessary or relevant to the reports required to be made or records required to be
maintained under this Agreement; and (y) the audit requirement set forth in Section 8.4; and (iii) a requirement that the Sublicensee comply with the applicable provisions under any Alnylam In-License. 

  
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 (c) If Genzyme becomes aware of a material breach of the terms of any sublicense by any
Genzyme Sublicensee, compliance with which is necessary for Genzyme’s compliance with the terms of this Agreement, Genzyme shall promptly notify Alnylam of the particulars of the same and use Commercially Reasonable Efforts to cause the
Sublicensee to comply with all the terms of the sublicense necessary for Genzyme’s compliance with the terms of this Agreement. In the event that (i) the Sublicensee has failed to cure a material breach within [**] days after notice of
such breach and (ii) such material breach also constitutes a breach of this Agreement, Genzyme shall terminate the sublicense at the request of Alnylam. Notwithstanding any sublicense, Genzyme shall remain primarily liable to Alnylam for the
performance of all of Genzyme’s obligations under, and Genzyme’s compliance with all terms and conditions of, this Agreement. 
 7.2 License Grants to Alnylam. 
 7.2.1 Development and
Commercialization License in the Alnylam Territory. Genzyme hereby grants Alnylam a non-transferable (except as provided in Section 14.1), sublicensable (subject to Section 7.2.4), exclusive, royalty-free license, under
(a) Genzyme Collaboration IP, Genzyme’s interest in Joint Collaboration IP and (b) any Genzyme Technology that is produced, generated, conceived and reduced to practice as a result of, or used by Genzyme or its Related Parties in, the
Development or Commercialization activities of Genzyme and its Related Parties under this Agreement, in each case of (a) and (b), to Develop and Commercialize Licensed Products in the Field in the Alnylam Territory. 

7.2.2 License to Improvement Manufacturing Patent Rights. Subject to the terms and conditions of this Agreement, Genzyme
hereby grants Alnylam a non-transferable (except as provided in Section 14.1), sublicensable (subject to Section 7.2.4), worldwide, non-exclusive license under the Improvement Manufacturing Patent Rights, to Manufacture (a) Alnylam
Developed siRNA Products targeting any human gene; and (b) Licensed Products for Development and Commercialization in the Alnylam Territory and, to the extent permitted pursuant to Section 2.3.3, for Development in the Field in the Genzyme
Territory. 
 7.2.3 License to Genzyme Disclosed Manufacturing Know-How. Subject to the terms and conditions of
this Agreement, Genzyme hereby grants Alnylam a non-transferable (except as provided in Section 14.1), sublicensable (subject to Section 7.2.4), worldwide, non-exclusive license under the Genzyme Disclosed Manufacturing Know-How, to
Manufacture Licensed Products for Development and Commercialization in the Alnylam Territory and, to the extent permitted pursuant to Section 2.3.3, for Development in the Field in the Genzyme Territory. 

7.2.4 Sublicensing Terms. 
 (a) Alnylam shall have the right to sublicense any of its rights under Section 7.2.1, 7.2.2 and 7.2.3 (which sublicensed rights may be further sublicensable through multiple tiers) to any of its
Affiliates or to any Third Party without the prior consent of Genzyme, and subject to the requirements of this Section 7.2.4; provided that Alnylam’s right to sublicense the rights granted to it under Section 7.2.2(a) to Third Parties
shall be limited to licensees of Alnylam that 

  
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have been granted the right to develop and/or commercialize Alnylam Developed siRNA Products and have been granted the right to use Alnylam manufacturing technology to manufacture Alnylam
Developed siRNA Products. 
 (b) Each sublicense granted by Alnylam pursuant to this Section 7.2.4 shall be subject and
subordinate to the terms and conditions of this Agreement and shall contain terms and conditions consistent with those in this Agreement. Alnylam shall promptly provide Genzyme with a copy of the fully executed sublicense agreement covering any
sublicense granted hereunder (which copy may be redacted to remove terms and conditions which are not necessary to monitor compliance with this Section 7.2.4), and each such sublicense agreement shall contain the following provisions:
(i) a requirement that the Sublicensee comply with the confidentiality and non-use provisions of Section 9 with respect to Genzyme’s Confidential Information and (ii) a requirement that the Sublicensee comply with the applicable
provisions under any Genzyme In-License. 
 (c) If Alnylam becomes aware of a material breach of any sublicense by any Alnylam
Sublicensee, compliance with which is necessary for Alnylam’s compliance with the terms of this Agreement, Alnylam shall promptly notify Genzyme of the particulars of the same and use Commercially Reasonable Efforts to cause the Sublicensee to
comply with all the terms of the sublicense necessary for Alnylam’s compliance with the terms of this Agreement. In the event that (i) the Sublicensee has failed to cure a material breach within [**] days after notice of such breach and
(ii) such material breach also constitutes a breach of this Agreement, Alnylam shall terminate the sublicense at the request of Genzyme. Notwithstanding any sublicense, Alnylam shall remain primarily liable to Genzyme for the performance of all
of Alnylam’s obligations under, and Alnylam’s compliance with all terms and conditions of, this Agreement. 
 7.3
Joint Collaboration IP. Subject to the rights and licenses granted to, and the obligations (including royalty obligations) of, each Party under this Agreement, either Party is entitled to practice Joint Collaboration IP for all purposes
on a worldwide basis and license without consent of and without a duty of accounting to the other Party. Each Party will grant and hereby does grant all permissions, consents and waivers with respect to, and all licenses under, the Joint
Collaboration IP, throughout the world, necessary to provide the other Party with such rights of use and exploitation of the Joint Collaboration IP, and will execute documents as necessary to accomplish the foregoing. 

7.4 In-Licenses. 
 7.4.1 Compliance with In-Licenses. All licenses and other rights granted to Genzyme under this Section 7 are subject to the rights and obligations of Alnylam under the Alnylam
In-Licenses. All licenses and other rights granted to Alnylam under this Section 7 are subject to the rights and obligations of Genzyme under the Genzyme In-Licenses. Each Party shall comply with all applicable terms and conditions of the
In-Licenses, and shall perform and take such actions as may be required to allow the Party that is party to such In-License to comply with its obligations thereunder, including obligations relating to sublicensing, patent matters, confidentiality,
reporting, audit rights, indemnification and diligence. Without limiting the foregoing, each Party shall prepare and deliver to the other Party any additional reports required 

  
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under the applicable In-Licenses and requested by such other Party, in each case sufficiently in advance to enable the Party that is party to such In-License to comply with its obligations under
the applicable In-Licenses. Each Party agrees, upon the other Party’s request, to provide the other Party with copies of any In-Licenses to which it is a party. Confidential Information of the providing Party or its counterparty may be redacted
from such copies, except to the extent that such information is required in order to enable the other Party to comply with its obligations to the providing Party under this Agreement with respect to such In-License or in order to enable the
providing Party to ascertain compliance with the provisions of this Agreement. 
 7.4.2 New In-Licenses; Additional
Alnylam In-Licenses. 
 7.4.2.1. Alnylam Negotiation of Future Alnylam In-Licenses. In the
event that Alnylam determines to enter into an agreement with a Third Party after the Effective Date pursuant to which Alnylam would acquire a license under Patent Rights that are necessary or useful to Develop, Manufacture or Commercialize Licensed
Products in the Field in the Alnylam Territory, Alnylam shall, if counterparts of such Patent Rights exist in the Genzyme Territory and a license under such Patent Rights is available for the Genzyme Territory, also obtain a comparable license under
such Patent Rights with respect to Licensed Products in the Genzyme Territory. 
 7.4.2.2. Acceptance of
Future In-Licenses. In the event that a Party (the “Licensing Party”) enters into an agreement with a Third Party after the Effective Date that meets the criteria set forth in clause (a) of the definition of
Genzyme In-License (in the case of Genzyme) or that meets the criteria set forth in clause (b) of the definition of Alnylam In-License (in the case of Alnylam), then the Licensing Party will promptly provide the other Party with notice and a
copy of the applicable Third Party agreement. Within [**] days following receipt of such notice, such other Party will decide, in its sole discretion, whether to accept the applicable Third Party agreement as a Genzyme In-License or Alnylam
In-License, as applicable, and provide notice of such other Party’s decision to the Licensing Party. In the event that such other Party declines to accept such agreement as a Genzyme In-License or Alnylam In-License, as applicable, any rights
granted to such Party thereunder will not be deemed to be “Controlled” by the Licensing Party or licensed to such other Party under this Agreement, and will not be subject to the payment provisions under this Agreement relating to
In-Licenses. In the event that such other Party accepts such Third Party agreement as a Genzyme In-License or Alnylam In-License, as applicable, such agreement will thereafter be included within the definition of Genzyme In-License or Alnylam
In-License, respectively, and any rights granted to the Licensing Party thereunder will be deemed to be “Controlled” by the Licensing Party and sublicensed to such other Party under this Agreement. Notwithstanding the foregoing, in the
event that Genzyme enters into a Third Party agreement that meets the criteria set forth in clause (a) of the definition of Genzyme In-License and such Agreement relates solely to the Genzyme Territory, then such agreement shall automatically
be included within the definition of Genzyme In-License. 
 7.4.2.3. Additional Alnylam In-Licenses. In
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or will be infringed by Genzyme’s Commercialization of Licensed Products in the Genzyme Territory or Genzyme’s Manufacture or Development of Licensed Products in accordance with this
Agreement, then such agreement will thereafter be included within the definition of Existing Alnylam In-Licenses, and all rights granted to Alnylam thereunder will be deemed to be “Controlled” by Alnylam and sublicensed to Genzyme under
this Agreement effective as of the later of the date the applicable Patent Right issues or the date that Genzyme’s Commercialization of Licensed Products in the Genzyme Territory or Genzyme’s Manufacture or Development of Licensed Products
in accordance with this Agreement would infringe such Patent Right in the absence of a license thereunder from Alnylam. 

7.4.3 Payments Under In-Licenses. 

7.4.3.1. Existing Alnylam In-Licenses and Alnylam In-Licenses Related to Existing Products. Subject
to Sections 7.4.2 (New In-Licenses-Additional Alnylam In-Licenses), 7.4.4 (Amendments to In-Licenses), 7.5.4 (Improvement Product - Royalty Adjustments) and 8.3.5 (Royalty Floor), Alnylam shall bear one hundred percent (100%) of any Third Party
License Payments under (a) the Existing Alnylam In-Licenses, and (b) Alnylam In-Licenses entered into after the Effective Date (“Future Alnylam In-Licenses”) in which Alnylam obtains licenses under Patent Rights that Cover
ALN-TTR02 or ALN-TTRsc, which Third Party License Payments become payable based on the licensing or sublicensing to, or exercise by, Genzyme or its Related Parties of rights thereunder with respect to Licensed Products. 

7.4.3.2. Future Alnylam In-Licenses Related to New Products. Subject to Section 7.4.4
(Amendments to In-Licenses), 7.5.4 (Improvement Products - Royalty Adjustments) and 8.3.5 (Royalty Floor), with respect to Future Alnylam In-Licenses accepted by Genzyme pursuant to Sections 7.4.2 (New In-Licenses; Additional Alnylam In-Licenses)
that do not include licenses under Patent Rights that Cover ALN-TTR02 or ALN-TTRsc, (x) Alnylam shall bear one hundred percent (100%) of any Third Party License Payments under such Future Alnylam In-Licenses other than milestone payments
and (y) milestone payments under Future Alnylam In-Licenses that do not include licenses under Patent Rights that Cover ALN-TTR02 or ALN-TTRsc shall be allocated between Genzyme and Alnylam as follows: 

(a) Base Rule – Alnylam Pays 100%. Except as allocated to Genzyme in this Section 7.4.3.2 below, Alnylam shall bear one
hundred percent (100%) of such milestone payments. 
 (b) [**]% of JPAC/LP-Specific Milestones. Genzyme shall,
subject to its right to apply credits against royalties as set forth in Section 7.4.3.2(e), pay [**] percent ([**]%) of milestone payments that become payable based on (i) [**] for a Licensed Product in the Genzyme Territory,
(ii) [**] of a Licensed Product in the Genzyme Territory or (iii) [**] of a Licensed Product in the Genzyme Territory (any such milestone ((i) through (iii)) a “JPAC/LP Milestone”), but only if such JPAC/LP Milestone could
only have been triggered by a Licensed Product in the Genzyme Territory (such a JPAC/LP Milestone, a “JPAC/LP-Specific Milestone”). For clarity, a JPAC/LP Milestone is a JPAC/LP-Specific Milestone (and allocated

  
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one hundred percent (100%) to Genzyme) only if the JPAC/LP Milestone could not have been triggered, in whole or in part, (A) by a product other than a Licensed Product (e.g., in
the case of a milestone for [**] in Japan, if such milestone was first achieved by a Licensed Product, but could have been achieved by a product other than a Licensed Product in Japan, or, in the case of a sales milestone, if sales in the Genzyme
Territory of products other than Licensed Products could have contributed to the achievement of such milestone), or (B) by the occurrence of an event outside the Genzyme Territory (e.g., in the case of a milestone for [**] Japan and countries
outside the Genzyme Territory, if [**] Japan, or, in the case of a sales milestone, if worldwide sales could have contributed to the achievement of such milestone). 
 (c) [**] Non-Specific JPAC/LP Milestones. With respect to JPAC/LP Milestones that are not JPAC/LP-Specific Milestones (and therefore are not [**] percent ([**]%) payable by Genzyme under subsection
7.4.3.2(b) above), the [**] of such JPAC/LP Milestone payments between the Parties, and Genzyme shall, subject to crediting against royalties as set forth in Section 7.4.3.2(e), pay the portion of such milestone payments allocated by the JSC to
Genzyme. In the event that [**] or if the Parties cannot agree as to whether a JPAC/LP Milestone payment is or is not a JPAC/LP-Specific Milestone following escalation pursuant to Section 5.5, the Parties shall submit the matter to
“baseball” style arbitration in accordance with the arbitration procedure set forth in Schedule 7.4.3.2. 

(d) Ceiling on Genzyme Share of JPAC/LP Milestones. Notwithstanding clauses (b) and (c) of this Section 7.4.3.2,
if the amount of any JPAC/LP Milestone payment payable under a Future Alnylam In-License exceeds the amount payable for the achievement of a comparable milestone in either the United States or the EU under such Future Alnylam In-License, then the
amount of such JPAC/LP Milestone payment that is allocable to [**] pursuant to this Section 7.4.3.2(b) and 7.4.3.2(c) shall be deemed to be the lowest amount that would be payable under such Future Alnylam In-License for achievement of the
comparable milestone in either the United States or the EU. 
 (e) Genzyme Credit for JPAC/LP Milestones. Subject to
Sections 7.5.4 (Improvement Products - Royalty Adjustments) and 8.3.5 (Royalty Floor), Genzyme shall be entitled to credit against the royalties due to Alnylam on Net Sales of Licensed Products to which the relevant Alnylam In-License applies the
amount [**] of any JPAC/LP Milestone paid by Genzyme pursuant to this Section 7.4.3.2, and Genzyme shall have the right to carry forward unused portions of such credit amounts for application against royalties payable to Alnylam with respect to
Net Sales of such Licensed Products to future royalty periods until such credit amounts have been fully applied against such royalty obligations. 
 7.4.3.3. Genzyme In-Licenses. Genzyme shall bear one hundred percent (100%) of any Third Party License Payments under the Genzyme In-Licenses that become payable based on the
licensing or sublicensing to or exercise by Genzyme or its Related Parties of rights thereunder with respect to Licensed Products in or for the Genzyme Territory. If Alnylam accepts such Genzyme In-License pursuant to Section 7.4.2.2, then
Alnylam will pay for one hundred percent (100%) of any portion of Third Party License Payments that become payable based on the licensing or sublicensing to or exercise by Alnylam of rights thereunder in the Alnylam Territory. 

  
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 7.4.4 Amendments to In-Licenses. If a Party amends an In-License to
which it is a Party in a manner that increases the royalty payable by the other Party under such In-License without the prior written consent of the other Party, such Party shall be solely responsible for any such additional payments due under such
In-License. 
 7.4.5 Stand-by Licenses. Upon Genzyme’s reasonable request during the Term, Alnylam
shall reasonably cooperate in good faith with Genzyme’s efforts to obtain stand-by license agreements with Alnylam In-License licensors pursuant to which, upon a termination of such Alnylam In-License, Genzyme would receive a direct license
from such licensor of the Patent Rights and Know-How licensed to Alnylam pursuant to such Alnylam In-License that are sublicensed to Genzyme pursuant to this Agreement. Such stand-by agreement will be in a form approved in advance by Alnylam. Any
costs incurred by Alnylam in cooperating with Genzyme’s efforts to obtain any such stand-by license agreement shall be reimbursed by Genzyme. 
 7.4.6 Breach or Termination of In-Licenses. In the event that (a) a Party receives notice of an alleged breach by such Party under an In-License Agreement to which it is a party,
or (b) a Party intends to terminate an In-Licensed Agreement to which it is a party, then such Party will promptly, but in no event less than [**] days thereafter, provide written notice thereof to the other Party. 

7.5 Improvement Products Option.  
 7.5.1 Option Grant. During the Term, Alnylam will provide the JSC with timely updates regarding Alnylam’s development plans and progress developing, or having developed, any
Improvement Product. So long as the Exclusivity Period in Japan continues, Genzyme shall have the option to designate any particular Improvement Product as a Licensed Product under this Agreement (the “Option”) as provided in this
Section 7.5. Following the completion of the [**] of an Improvement Product and prior to the commencement of the [**] of such Improvement Product, Alnylam shall provide Genzyme with a written notice to such effect accompanied by copies of the
development plan for development through Regulatory Approval for such Improvement Product in the Alnylam Territory (the “Improvement Product Development Plan”) and development budget for such Improvement Product for the Alnylam
Territory (the “Improvement Product Development Budget”), a statement detailing all Improvement Product Development Costs incurred by Alnylam with respect to the Development of such Improvement Product from the date of commencement
of [**] for such Improvement Product to the present date, and the [**], including a copy of the [**], for such Improvement Product (such notice and accompanying information, the “Option Exercise Package”). At any time prior to the
completion of the [**] of an Improvement Product but after the [**] for such Improvement Product, Genzyme may request that Alnylam provide reasonable information, of the type to be included in the Option Exercise Package, regarding the Development
of an Improvement Product. Alnylam will use good faith efforts to provide such information, and Alnylam will thereafter permit Genzyme to exercise its Option with respect to such Licensed Product prior to the Option Exercise Period; provided,
however, that, if Genzyme exercises the Option prior to the Option Exercise Period, the cost sharing provisions of Section 7.5.3 shall apply commencing upon Genzyme’s early exercise of the Option, but the budgeting process in

  
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Section 7.5.3 shall not apply during the period commencing with Genzyme’s early exercise of the Option and ending on the [**]. Such request will not relieve Alnylam of its obligation to
provide the Option Exercise Package as set forth above if Genzyme does not exercise the Option early with respect to such Improvement Product. Genzyme may exercise the Option by providing written notice of exercise to Alnylam at any time following
Genzyme’s receipt of the Option Exercise Package until [**] days following Genzyme’s receipt of the Option Exercise Package (the “Option Exercise Period”). During such Option Exercise Period, Alnylam will promptly provide
any patent, regulatory, or other information that Genzyme may reasonably request regarding such Improvement Product to assist Genzyme in deciding whether to exercise the Option for such Improvement Product. 

7.5.2 Option Not Exercised. If Genzyme does not exercise the Option as to an Improvement Product during the Option
Exercise Period applicable to such Improvement Product, Genzyme’s Option with respect to such Improvement Product shall expire, Genzyme’s rights under this Section 7.5 shall lapse and Alnylam shall thereafter be free to develop and/or
commercialize, alone or with one or more Third Parties, such Improvement Product without further obligation to Genzyme with respect to such Improvement Product; provided that, the restrictions set forth in Section 10.5.1 as to
such Improvement Products, if applicable, shall continue to apply in accordance with their terms.  
 7.5.3
Option Exercised. If Genzyme exercises the Option as to an Improvement Product during the Option Exercise Period applicable to such Improvement Product, such Improvement Product shall become a Licensed Product hereunder and the
following shall apply: 
 7.5.3.1. Genzyme shall, within [**] days after Alnylam’s invoice therefor,
pay Alnylam [**] percent ([**]%) of Alnylam’s worldwide Development costs and expenses (including Alnylam’s Out-of-Pocket Costs and FTE Costs) incurred by Alnylam with respect to such Improvement Product (“Improvement Product
Development Costs”) from the date of commencement of [**] for such Improvement Product to the present date of Genzyme’s exercise of the Option. 
 7.5.3.2. Additionally, following Genzyme’s exercise of the Option, the Development of such Improvement Product for the Alnylam Territory shall be included in the Alnylam Territory Development
Plan and the Development of such Improvement Product for the Genzyme Territory shall be included in the Genzyme Territory Development Plan. Genzyme shall pay [**] percent ([**]%) and Alnylam shall pay [**] percent ([**]%) of the Improvement Product
Development Costs incurred by the Parties with respect to Development of the Improvement Product pursuant to the Alnylam Territory Development Plan (which costs shall be reflected in the Improvement Product Development Budget). 

7.5.3.3. Genzyme shall pay [**] percent ([**]%) of the Improvement Product Development Costs incurred by the
Parties with respect to such Improvement Product for the Genzyme Territory pursuant to the Genzyme Territory Development Plan. 

  
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 7.5.3.4. Alnylam will provide Genzyme with updates to the Improvement
Product Development Budget for such Improvement Product (a) prior to the commencement of [**] that Alnylam plans to conduct concurrently for such Improvement Product following the [**] conducted concurrently following Genzyme’s exercise of
the Option for such Improvement Product and (b) otherwise with each update to the Alnylam Territory Development Plan that Alnylam provides in accordance with Section 2.2.2. The Improvement Product Development Budget provided to Genzyme
prior to its exercise of the Option shall be binding on the Parties with respect to the Improvement Product Development Costs budgeted for the [**] to be conducted concurrently for such Improvement Product following such Option exercise, and each
updated Improvement Product Development Budget provided by Alnylam to Genzyme in accordance with clause (a) above for each subsequent [**] to be conducted concurrently for such Improvement Product shall be binding on the Parties with respect to
such [**] for such Improvement Product; provided, however that to the extent that a Party (or its Related Parties) incurs Improvement Product Development Costs for any such [**] for which such Party is responsible under the
Improvement Product Development Plan that exceed the amounts set forth in the Improvement Product Development Budget for such activities by [**] percent ([**]%) or less, then such overage amount shall automatically be included in the Improvement
Product Development Budget and the Parties shall share such costs as set forth in this Section 7.5.3. Following Genzyme’s receipt of each updated Improvement Product Development Budget as provided in clause (a) above, Genzyme shall
have the right, exercisable within [**] days after receipt of such Improvement Product Development Budget, to opt-out of the Development of such Improvement Product (other than with respect to then-ongoing [**], for which Genzyme will remain
obligated to continue to participate in funding) by providing Alnylam written notice thereof, in which case such Improvement Product shall no longer be a Licensed Product for the purposes of this Agreement. 

7.5.4 Improvement Products - Royalty Adjustments. Notwithstanding Section 7.4.3.2 (Future Alnylam In-Licenses
Related to New Products), Section 8.3.1 (Royalties Payable on Licensed Products), Section 8.3.3 (No Alnylam Patents or Regulatory Exclusivity), and Section 8.3.4 (Royalty Adjustments for Generic Products) (which Sections 8.3.3 and
8.3.4 will apply in part as expressly provided for below), in no event will the royalties payable by Genzyme to Alnylam on Net Sales of Improvement Products in the Genzyme Territory for any Calendar Quarter during the applicable Royalty Term for
such Improvement Product be less than the sum of (a) the amount necessary to fully cover Alnylam’s obligations to pay sales milestones and royalties due under Alnylam In-Licenses with respect to sales of such Improvement Product in the
Genzyme Territory during such Calendar Quarter in accordance with Section 7.4.3 and (b) [**] percent ([**]%) of Net Sales of such Improvement Product, subject to adjustment of the component set forth in this clause (b) as provided in
Sections 8.3.3 and 8.3.4. Furthermore, in no event will the royalties payable by Genzyme to Alnylam on Net Sales of an Improvement Product in any country in the Genzyme Territory for any Calendar Quarter after the applicable Royalty Term for such
Improvement Product, after all reductions to such royalties are applied, be less than the royalty floor established in clause (b) of Section 8.3.5. For the avoidance of doubt, Genzyme will not be entitled to apply any credit pursuant to
Section 7.4.3.2(e) against the royalty payment payable by Genzyme to Alnylam on Net Sales of an Improvement Product in 

  
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the Genzyme Territory for any Calendar Quarter to the extent such credit would reduce the amount of such royalty payment to an amount less than the applicable minimum payment established by the
two immediately preceding sentences. Notwithstanding the foregoing, no portion of any sales milestone payment under any Future Alnylam In-License paid by Genzyme pursuant to Section 7.4.3.2 shall be taken into account for the purpose of
calculating the royalty floor under this Section 7.5.4 (i.e., no double-counting). The following two examples are provided for illustrative purposes only: 
 (x) Example #1. In the event that (i) Net Sales of an Improvement Product by made Genzyme or its Related Parties in the Genzyme Territory are less than [**] dollars ($[**]) in the first
Calendar Quarter of a Calendar Year and therefore the royalty percentage due under Section 8.3.1 with respect to such Improvement Product would be [**] percent ([**]%), (ii) Alnylam is responsible for paying aggregate royalties equal to
[**] percent ([**]%) of Net Sales of such Improvement Product in the Genzyme Territory under Alnylam In-License Agreements, (iii) Genzyme is not entitled to credit any amounts against such royalties pursuant to Section 7.4.3.2(e) (Genzyme
Credit for JPAC/LP Milestones), and (iv) no reductions are applicable pursuant to Section 8.3.3 (No Alnylam Patents or Regulatory Exclusivity) or 8.3.4 (Royalty Adjustment for Generic Products), then the royalty due under this Agreement on
such Net Sales, as adjusted based on this Section 7.5.4, would be [**] percent ([**]%) plus [**] percent ([**]%), or [**] percent ([**]%) of such Net Sales. 
 (y) Example #2. In the event that (i) Net Sales of an Improvement Product by made Genzyme or its Related Parties in the Genzyme Territory are less than [**] dollars ($[**]) in the first
Calendar Quarter of a Calendar Year and therefore the royalty percentage due under Section 8.3.1 with respect to such Improvement Product would be [**] percent ([**]%), (ii) Alnylam is responsible for paying aggregate royalties equal to
[**] percent ([**]%) of Net Sales of such Improvement Product in the Genzyme Territory under Alnylam In-License Agreements, (iii) Genzyme is not entitled to credit any amounts against such royalties pursuant to Section 7.4.3.2(e) (Genzyme
Credit for JPAC/LP Milestones), and (iv) a reduction is applicable pursuant to Section 8.3.4 (Royalty Adjustment for Generic Products), then the royalty due under this Agreement on such Net Sales, as adjusted based on this
Section 7.5.4 would be [**]% plus [**]% (i.e., [**]%), or [**]% of such Net Sales. 
 7.5.5 Improvement
Products. All other provisions of this Agreement applicable to Licensed Products, including without limitation the royalty provisions in Section 8.3, shall apply to such Improvement Product. 

7.6 Alnylam Territory Right of First Negotiation. If, at any time during the Term, Alnylam desires to grant any Third Party
rights to Develop and/or Commercialize one or more Licensed Product(s) in the Field in any portion of the Alnylam Territory, Alnylam shall notify Genzyme in writing of its intent. Genzyme shall have [**] days from receipt of such written notice to
notify Alnylam in writing as to whether Genzyme desires to negotiate for such rights in such territory, and if Genzyme so notifies Alnylam that it does desire to negotiate for such rights in such territory, Genzyme shall have the exclusive right for
[**] days from the date of such notification to Alnylam to negotiate with Alnylam and to make one or more written non-binding offers to Alnylam concerning the acquisition of such rights in such territory by Genzyme.

  
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Genzyme shall have the exclusive right for [**] days (or such longer period as may be mutually agreed by the Parties) after such [**] day period, to finalize and enter into a definitive agreement
with Alnylam for such rights in such territory; provided that, if either Genzyme does not provide such written notice within such [**] day period or Genzyme does provide such written non-binding offer within such subsequent [**] day
period, or Genzyme provides such notice of interest and such written offer but for any reason Genzyme and Alnylam do not enter into a definitive agreement within the [**] day negotiation period, Alnylam shall be free to enter into an agreement with
a Third Party(ies) relating to such rights in such territory, without further obligation to Genzyme. Alnylam shall not, during the exclusive [**] and [**] day negotiating periods described above, enter into discussions, exchange information, or
otherwise negotiate with any Third Party with respect to an agreement with respect to the Development and/or Commercialization of a Licensed Product in the Field in the Alnylam Territory. Notwithstanding the foregoing, during the period of [**]
months after the termination of any such negotiation that does not result in a definitive agreement between Alnylam and Genzyme, Alnylam shall not enter into a transaction with respect to such rights in such territory with any Third Party on terms
that in the aggregate are materially more favorable to the Third Party than the last terms offered in writing by Genzyme to Alnylam unless Alnylam first re-offers such transaction to Genzyme on such more favorable terms and Genzyme does not accept
such offer and enter into such transaction with Alnylam within [**] days after such re-offer. For clarity, prior to the exclusive negotiating periods described above, Alnylam shall be free to engage in discussions and exchange information with Third
Parties with respect to such Licensed Product rights, but shall not enter into any binding agreement with any Third Party with respect to such rights. 
 7.7 Bankruptcy. All rights and licenses granted under or pursuant to this Agreement by a Party to the other, including those set forth in Sections 7.1, 7.2, and 3.3, are and shall otherwise
be deemed to be, for purposes of Section 365(n) of the U.S. Bankruptcy Code, licenses of right to “intellectual property” as defined under Section 101 of the U.S. Bankruptcy Code. The Parties agree that the Parties and their
respective Sublicensees, as sublicensees of such rights under this Agreement, shall retain and may fully exercise all of their rights and elections under the U.S. Bankruptcy Code and any foreign counterpart thereto. The Parties further agree that
that upon commencement of a bankruptcy proceeding by or against a Party (the “Bankrupt Party”) under the Bankruptcy Code, the other Party (the “Non-Bankrupt Party”) will be entitled to a complete duplicate of, or
complete access to (as the Non-Bankrupt Party deems appropriate), all such intellectual property and all embodiments of such intellectual property. Such intellectual property and all embodiments of such intellectual property will be promptly
delivered to the Non-Bankrupt Party (a) upon any such commencement of a bankruptcy proceeding and upon written request by the Non-Bankrupt Party, unless the Bankrupt Party elects to continue to perform all of its obligations under this
Agreement, or (b) if not delivered under (a) above, upon the rejection of this Agreement by or on behalf of the Bankrupt Party and upon written request by the Non-Bankrupt Party. Without limiting the foregoing, Alnylam hereby grants to
Genzyme a right of access to and to obtain possession of (a) copies of research data, (b) laboratory samples, (c) samples of Licensed Product, (d) formulas, (e) laboratory notes and notebooks, (f) data and results
related to clinical trials, (g) regulatory filings and approvals, (h) rights of reference in respect of regulatory filings and approvals, (i) pre-clinical research data and results, (j) marketing, advertising and promotional
materials, all of which (in clauses (a) through (j)) constitute “embodiments” of intellectual property pursuant to Section 365(n) of the Bankruptcy 

  
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Code and (k) all other embodiments of such intellectual property, and in respect of each of the foregoing clauses (a) through (k), solely for the purpose of the exercise of
Genzyme’s rights and licenses under this Agreement, whether any of the foregoing are in Alnylam’s possession or control or in the possession and control of Third Parties. The Bankrupt Party (in any capacity, including debtor-in-possession)
and its successors and assigns (including any trustee) agrees not to interfere with the exercise by Non-Bankrupt Party or its Related Parties of its rights and licenses to such intellectual property and such embodiments of intellectual property in
accordance with this Agreement, and agrees to assist the Non-Bankrupt Party and its Related Parties in obtaining such intellectual property and such embodiments of intellectual property in the possession or control of Third Parties as reasonably
necessary or desirable for the Non-Bankrupt Party to exercise such rights and licenses in accordance with this Agreement. The foregoing provisions are without prejudice to any rights the Non-Bankrupt Party may have arising under the Bankruptcy Code
or other Laws. 
 7.8 [**].
 7.9 No Other Rights. Except as otherwise expressly provided in this Agreement, under no circumstances shall a Party, as a result of this Agreement, obtain any ownership interest or other
right in any Know-How, Patent Rights or other intellectual property rights of the other Party, including items owned, controlled or developed by the other Party, or provided by the other Party to the receiving Party at any time pursuant to this
Agreement. 
 8. CERTAIN FINANCIAL TERMS 
 8.1 Upfront Fee. In consideration for the rights, licenses and options granted by Alnylam to Genzyme under this Agreement, within [**] days after the Effective Date, Genzyme shall pay
Alnylam a non-creditable initial payment of Twenty-Two Million Five Hundred Thousand U.S. Dollars ($22,500,000). 
 8.2
Development Milestone Fees. Genzyme shall make the non-creditable milestone payments to Alnylam set forth below, each payable once, no later than [**] days after either the earliest date on which the corresponding milestone event has
first been achieved with respect to a Licensed Product, with respect to milestone events achieved by Genzyme or its Related Parties, or the date on which Genzyme receives notice from Alnylam of completion of the milestone event, with respect to
milestone events achieved by Alnylam or its Related Parties. 
  

					
	 Milestone Event
	  	Milestone Payment	 
		
	 (i) First Phase II Success by Alnylam or any of its Related Parties
	  	$	7,000,000	  
		
	 [**]
	  	 	[**	] 
		
	 [**]
	  	 	[**	] 
		
	 [**]
	  	 	[**	] 
		
	 [**]
	  	 	[**	] 
		
	 [**]
	  	 	[**	] 

  
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 (a) If following the completion of a Phase II Study the Parties either (I) do not agree
whether First Phase II Success has been achieved or (II) agree that the First Phase II Success has not been achieved, then, in each case of either (I) or (II): 
  

	 	(i)	Genzyme shall have the right to terminate this Agreement by providing forty-five (45) days prior written notice to Alnylam. Genzyme shall have no obligation to pay
to Alnylam the milestone payment for the milestone event described in Section 8.2(i) if Genzyme so terminates prior to the later of (1) Alnylam’s or any of its Related Parties’ commencement of the first [**] with respect to a
Licensed Product, or (2) forty-five (45) days following the date on which Alnylam delivers written notice pursuant to Section 2.3.1 to Genzyme of its intent to commence such a [**] with respect to a Licensed Product.

  

	 	(ii)	If Genzyme does not terminate this Agreement in accordance with Section 8.2(a)(i) above prior to the later of (1) [**] with respect to the Licensed Product
conducted by Alnylam or any of its Related Parties, or (2) forty-five (45) days following the date on which Alnylam delivers written notice pursuant to Section 2.3.1 to Genzyme of its intent to commence such a [**] with respect to a
Licensed Product, then the milestone payment for milestone event described in Section 8.2(i) shall be paid by Genzyme to Alnylam as follows: (x) [**] U.S. Dollars ($[**]) shall be paid together with the milestone payment described in
Section 8.2(ii) and (y) [**] U.S. Dollars ($[**]) shall be paid upon the earliest of (A) the first filing by Alnylam or any of its Related Parties of [**] in (I) the United States, (II) in the EU (with the EMA), or (III) in any
one of the following countries: France, Germany, Portugal, Sweden and the United Kingdom, or (B) the first filing by Genzyme or any of its Related Parties of [**] in a country in the Genzyme Territory or the [**] for the Licensed Product in
Japan. For clarity, payment under (x) and (y) above is in addition to payments due under 8.2(ii) and 8.2(iii). 

 (b) If Alnylam or any of its Related Parties [**], but (i) Genzyme or any of its Related Parties [**] as contemplated by the Genzyme Territory Development Plan, and, (ii) Alnylam or any of its
Related Parties [**], then the milestone payment for the milestone event described in Section 8.2(iv) shall be paid by Genzyme to Alnylam within [**] days following the events described in both clause (i) and (ii) of this paragraph
being satisfied. 

  
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 (c) Each milestone payment by Genzyme to Alnylam hereunder shall be payable only once,
regardless of the number of times achieved with respect to a Licensed Product. 
 (d) Genzyme shall provide Alnylam with written
notice of the achievement by Genzyme or any of its Related Parties of any milestone event set forth in Section 8.2(iii), (v) and (vi) and Alnylam shall provide Genzyme with written notice of the achievement by Alnylam or any of its
Related Parties of any milestone event set forth in Section 8.2(i), (ii) and (iv), in each case within [**] days after such event; provided, however, that the notifying Party shall inform the other Party of such event prior
to any public disclosure of such event by the notifying Party. 
 8.3 Royalties. 

8.3.1 Royalties Payable on Licensed Products. Subject to the terms and conditions of this Agreement, Genzyme shall pay to
Alnylam royalties on aggregate Net Sales by Genzyme and its Related Parties of all Licensed Products in the Genzyme Territory, as follows: 
  

					
	 Aggregate Calendar Year Net Sales in the Genzyme Territory
	  	Royalty
(as a percentage 
of Net Sales)	 
		
	 [**]
	  	 	[**	] 
		
	 [**]
	  	 	[**	] 
		
	 [**]
	  	 	[**	] 
		
	 Greater than $[**]
	  	 	[**	] 

 By way of example only, if Genzyme receives [**] U.S. Dollars ($[**]) in Net Sales in the Genzyme
Territory during a given Calendar Year, then the royalties payable by Genzyme under Section 8.3.1 during such Calendar Year would be calculated as follows: 
 [**] 
 Royalties on aggregate Net Sales shall be paid at the rate
applicable to the portion of such aggregate Net Sales within each of the Net Sales levels above during such Calendar Year.
 If (i) more than one Licensed Product is sold in the Genzyme Territory during any Calendar Quarter, (ii) all portions of aggregate Net Sales during such Calendar Quarter fall within
the same Net Sales level during such Calendar Quarter, (iii) such Licensed Products are subject to different royalty rates pursuant to Section 8.3.3 or 8.3.4, and (iv) the aggregate Net Sales of such Licensed
Products during the Calendar Year fall within different Net Sales levels, then the Net Sales of each Licensed Product shall be deemed to be distributed proportionally on a percentage basis relative to the Net Sales of each
Licensed Product in the Calendar Year, according to such differing royalty rates. For example, if: 
  

	 	•	 	 [**] U.S. Dollars ($[**]) of aggregate Net Sales occur for two Licensed Products during the first Calendar Quarter of a Calendar Year during which
aggregate Net Sales total [**] U.S. Dollars ($[**]), and 

  
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	 	•	 	 [**] percent ([**]%) of aggregate Net Sales during such Calendar Year are attributed to the first Licensed Product and [**] percent ([**]%) to the
second Licensed Product, and 

  

	 	•	 	 the first Licensed Product is subject to a full royalty and the second is subject to a [**] percent ([**]%) royalty pursuant to Section 8.3.4,

 then royalties during such Calendar Quarter will be calculated as follows: 

[**] 
 If
(i) more than one Licensed Product is sold in the Genzyme Territory during any Calendar Quarter, (ii) portions of aggregate Net Sales during such Calendar Quarter fall within more than one of the above Net Sales levels,
(iii) such Licensed Products are subject to different royalty rates pursuant to Section 8.3.3 or 8.3.4, and (iv) the aggregate Net Sales of such Licensed Products during the Calendar Year fall within different Net Sales levels,
then the Net Sales of each Licensed Product shall be deemed to be distributed proportionally on a percentage basis relative to the Net Sales of each Licensed Product in the Calendar Year, according to such differing royalty rates and between the
applicable Net Sales levels. For example, if: 
  

	 	•	 	 [**] U.S. Dollars ($[**]) of aggregate Net Sales occur for two Licensed Products during the fourth Calendar Quarter of a Calendar Year during which
aggregate Net Sales total [**] U.S. Dollars ($[**]), 

  

	 	•	 	 [**] percent ([**]%) of aggregate Net Sales during such Calendar Year are attributed to the first Licensed Product and [**] percent ([**]%) to the
second Licensed Product, 

  

	 	•	 	 [**] U.S. Dollars ($[**]) of aggregate Net Sales during such Calendar Quarter fall into the $[**] Net Sales level and [**] U.S. Dollars ($[**]) fall
into the $[**] Net Sales level, and 

  

	 	•	 	 and the first Licensed Product is subject to a full royalty and the second is subject to a [**] percent ([**]%) royalty pursuant to Section 8.3.4,

 then royalties during such Calendar Quarter will be calculated as follows: 

[**] 
 8.3.2
Royalty Term. Subject to Section 8.3.5, the period during which the royalties set forth in Section 8.3.1 shall be payable, on a Licensed Product-by-Licensed Product and country-by-country basis, shall commence with the First
Commercial Sale of the Licensed 

  
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Product in such country and continue until the latest of (a) the expiration of the last Valid Claim of the Alnylam Patents or any Patent Right included in the Joint Collaboration IP Covering
the Manufacture, use, offer for sale, sale or importation of the Licensed Product in the country of sale, (b) the expiration of Regulatory Exclusivity for such Licensed Product in such country, or (c) subject to Section 8.3.3, the
twenty-fifth (25th) anniversary of the First Commercial Sale of the Licensed Product in such country (each such period, a “Royalty Term”). For purposes of the foregoing clause (a), following the twelfth (12) anniversary of
the First Commercial Sale of a Licensed Product in a country, Manufacturing Claims shall no longer constitute Valid Claims with respect to such Licensed Product in such country. Notwithstanding the foregoing, at any time during the Royalty Term for
a Licensed Product in a country following the latest of (a) the expiration of the last Valid Claim of the Alnylam Patents or any Patent Right included in the Joint Collaboration IP Covering the Manufacture, use, offer for sale, sale or
importation of such Licensed Product in such country, (b) the expiration of Regulatory Exclusivity for such Licensed Product in such country, or (c) the twelfth (12th) anniversary of the First Commercial Sale of such Licensed Product
in such country, Genzyme may terminate the Royalty Term with respect to such Licensed Product in such country (and its obligation to pay royalties under this Section 8.3 with respect to such Licensed Product in such country) by providing
written notice to Alnylam, which termination will be effective commencing in the next full Calendar Quarter commencing at least thirty (30) days following the date of such notice. 

8.3.3 No Alnylam Patents or Regulatory Exclusivity. The royalties to be paid by Genzyme to Alnylam pursuant to
Section 8.3.1 shall be reduced to [**] percent ([**]%) of the amounts otherwise payable pursuant to Section 8.3.1 with respect to Net Sales in a country of the Genzyme Territory of Licensed Products as to which both (i) the
Manufacture, use, offer for sale, sale or importation of which is not Covered by any Valid Claim in any Alnylam Patent or in any Patent Right included in the Joint Collaboration IP in such country and (ii) there is no applicable Regulatory
Exclusivity in such country. 
 8.3.4 Royalty Adjustments for Generic Products. If, during a given Calendar
Quarter when a Licensed Product is being Commercialized by or on behalf of Genzyme in a particular country in the Genzyme Territory, there is Generic Competition in such country with respect to a Licensed Product, then, subject to
Section 8.3.5, the royalties payable pursuant to Section 8.3.1 on the Net Sales of such Licensed Product in such country shall thereafter be reduced to [**] percent ([**]%) of the amounts otherwise payable pursuant to Section 8.3.1
with respect to such Licensed Product in such country for such Calendar Quarter for so long as such Generic Competition remains. 
 8.3.5 Royalty Floor. Notwithstanding Section 7.4.3 or the foregoing provisions of this Section 8.3 (a) in no event during the applicable Royalty Term for a Licensed Product in
a country of the Genzyme Territory shall the royalties payable to Alnylam hereunder for such Licensed Product in such country for any Calendar Quarter be reduced pursuant to Sections 8.3.3 and 8.3.4 to less than [**] percent ([**]%) of the royalties
payable pursuant to Section 8.3.1 as to such Licensed Product in such country for such Calendar Quarter and (b) in no event shall the royalties payable to Alnylam hereunder for a Licensed Product in a country of the Genzyme Territory for
any Calendar Quarter, whether or not reduced pursuant to Section 8.3.3 or 8.3.4, and whether or not during or after the applicable Royalty Term for such Licensed Product in 

  
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such country, be less than the amount necessary to fully cover Alnylam’s obligations to pay royalties and sales milestones due under Alnylam In-Licenses with respect to sales of such
Licensed Product in such country during such Calendar Quarter in accordance with Section 7.4.3. If the royalties payable to Alnylam hereunder for a Licensed Product in a country of the Genzyme Territory for any Calendar Quarter would otherwise
not be sufficient to fully cover Alnylam’s obligations to pay royalties and sales milestones due under Alnylam In-Licenses with respect to sales of such Licensed Product in such country during such Calendar Quarter in accordance with
Section 7.4.3, Genzyme shall pay Alnylam such additional royalty amounts with respect to sales of such Licensed Product in such country for such Calendar Quarter as are necessary to fully cover Alnylam’s obligations to pay such royalties
and sales milestones and Genzyme shall not be entitled to credit any amount pursuant to Section 7.4.3 against royalties payable to Alnylam on sales of such Licensed Product in such country during such Calendar Quarter. If the royalties payable
to Alnylam hereunder for a Licensed Product in a country of the Genzyme Territory for any Calendar Quarter exceed the amount necessary to fully cover Alnylam’s obligations to pay royalties and sales milestones with respect to sales of such
Licensed Product in such country during such Calendar Quarter in accordance with Section 7.4.3, Genzyme shall be entitled to credit amounts pursuant to Section 7.4.3 with respect to sales of such Licensed Product in such country during
such Calendar Quarter against the portion of such royalties payable to Alnylam that exceeds Alnylam’s obligations to pay royalties and sales milestones due under Alnylam In-Licenses with respect to sales of such Licensed Product in such country
during such Calendar Quarter. Notwithstanding the foregoing, no portion of any sales milestone that is a JPAC/LP Milestone payment under any Future Alnylam In-License paid by Genzyme pursuant to Section 7.4.3.2 shall be taken into account for
the purpose of calculating the royalty floor under this Section 8.3.5 (i.e., no double-counting). 
 8.3.6 Validation
Information. At Genzyme’s request, Alnylam will provide Genzyme with such information as Genzyme may reasonably request to validate the amount of the royalty floor described in Section 8.3.5. 

8.3.7 Reports; Payment of Royalty. During the Term, following the First Commercial Sale of the Licensed Product in the
Genzyme Territory, Genzyme shall furnish to Alnylam a written report within [**] days after the end of each Calendar Quarter showing, on a Licensed Product-by-Licensed Product and country-by-country basis, the Net Sales of each Licensed Product in
each country of the Genzyme Territory, royalties payable under Genzyme In-Licenses with respect to such Net Sales and the royalties payable under this Agreement. Quarterly reports shall be due no later than the [**] day following the end of
each Calendar Quarter. Royalties shown to have accrued by each royalty report shall be due and payable on the date such royalty report is due. In addition Genzyme shall prepare and deliver to Alnylam (a) any additional reports as required under
the Alnylam In-Licenses and requested by Alnylam; and (b) an annual report no later than [**] of each Calendar Year listing gross sales and Net Sales of Licensed Products in each Calendar Quarter in the prior Calendar Year (A) in Japan and
(B) in all other countries in the Genzyme Territory in the aggregate. Upon Alnylam’s reasonable request no more than [**], Genzyme shall prepare a report detailing the deductions from gross sales (itemized by deduction category) included
in the calculation of Net Sales for each Licensed Product in Japan and the Genzyme Territory as a whole. Genzyme and its Related Parties involved in Commercializing Licensed Products shall keep complete and accurate records in sufficient detail to
enable the royalties and other payments payable hereunder and by Alnylam to Third Parties under the Alnylam In-Licenses to be determined. 

  
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 8.4 Audits.  

8.4.1 Upon the written request of a Party and not more than [**], the other Party and its Related Parties shall permit an
independent certified public accounting firm of internationally-recognized standing selected by the requesting Party and reasonably acceptable to the other Party, at the requesting Party’s expense except as set forth below, to have access
during normal business hours to such of the records of the other Party as may be reasonably necessary to verify the accuracy of the royalty, Improvement Product Development Cost, and other amounts payable or reports under this Agreement for any year
ending not more than [**] years prior to the date of such request for the sole purpose of verifying the basis and accuracy of payments made under Sections 6, 7.5 and 8. 
 8.4.2 If such accounting firm identifies a discrepancy made during such period, the appropriate Party shall pay the other Party the amount of the discrepancy, together with late-payment interest in
accordance with Section 8.6, within [**] days after the date the requesting Party delivers to the other Party such accounting firm’s written report so concluding, or as otherwise agreed by the Parties in writing. The fees charged by such
accounting firm shall be paid by the requesting Party, unless such discrepancy represents an underpayment by the other Party of at least five percent (5%) of the total amounts due hereunder in the audited period, in which case such fees shall
be paid by the other Party. 
 8.4.3 Each Party shall comply with all applicable audit requirements in the In-Licenses
and shall include in each sublicense granted by it pursuant to this Agreement a provision requiring the Sublicensee to make reports to the Party that is party to such In-License, to keep and maintain records of sales made pursuant to such sublicense
and to grant access to such records by the independent accountant of the Party that is party to such In-License to the same extent required of a Party under this Agreement. 
 8.4.4 Unless an audit for such year has been commenced prior to and is ongoing upon the [**] anniversary of the end of such year, the calculation of royalties, expense reimbursement and other
payments payable with respect to such year shall be binding and conclusive upon both Parties, and each Party and its Related Parties shall be released from any further liability or accountability with respect to such royalties or expense
reimbursement for such year. 
 8.4.5 Each Party shall treat all financial information subject to review under this
Section 8.4 or under any sublicense agreement in accordance with the confidentiality and non-use provisions of this Agreement, and shall cause its accounting firm to enter into a confidentiality agreement with the other Party and/or its Related
Parties obligating it to retain all such information in confidence pursuant to such confidentiality agreement, which terms shall be no less stringent than the provisions of Section 9. 

8.5 Payment Exchange Rate. All payments to be made under this Agreement shall be made in United States dollars and shall be
paid by bank wire transfer in immediately available funds to such bank account in the United States as may be designated in writing by the receiving 

  
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Party from time to time. In the case of Net Sales made or expenses incurred by a Party and its Related Parties in currencies other than United States dollars during a Calendar Quarter, the rate
of exchange to be used in computing the amount of United States dollars due shall be the rate of exchange utilized by such Party in its worldwide accounting system and calculated in accordance with GAAP. 

8.6 Late Payments. Any amount owed by a Party to the other Party under this Agreement that is not paid on or before the
date such payment is due shall bear interest at a rate per annum equal to the lesser of (a) the then current one (1) month London Inter-Bank Offering Rate for US Dollars, as quoted on the British Banker’s Association’s website
currently located at www.bba.org.uk (or such other source as may be mutually agreed by the Parties) plus [**] percentage points per annum or (b) the highest rate permitted by Law, calculated on the number of days such payments are paid after
such payments are due and compounded monthly. 
 8.7 Blocked Payments. If, by reason of Laws in any jurisdiction
in a Party’s Territory, it becomes impossible or illegal for a Party to transfer milestone payments, royalties or other payments under this Agreement to the other Party, the payor shall promptly notify the payee. During any such period
described above, the payor shall deposit such payments in local currency in the relevant jurisdiction to the credit of the payee in a recognized banking institution designated by the payee or, if none is designated by the payee within a period of
[**] days, in a recognized banking institution selected by the payor and identified in a written notice given to the payee. 

8.8 Taxes. If a timely and appropriately completed and executed Internal Revenue Service Form W-9 is provided by the
receiving Party to the paying Party, the Parties acknowledge and agree that no United States tax withholding shall be applied with respect to the payments due under Sections 8.1 and 8.2. Each Party shall use reasonable efforts to minimize tax
withholding on payments made to the other Party. Notwithstanding such efforts, if such Party concludes that tax withholdings under the Laws of any country are required with respect to payments to the other Party, such Party shall first notify the
other Party and provide such Party with [**] days to determine whether there are actions such receiving Party can undertake to avoid such withholding. During this notice period, the paying Party shall refrain from making such payment until the
receiving Party instructs the paying Party that (a) the receiving Party intends to take actions (satisfactory to both Parties) that will obviate the need for such withholding, in which case the paying Party shall make such payment only after it
is instructed to do so by the receiving Party, or (b) the paying Party should make such payment and withhold the required amount and pay it to the appropriate governmental authority. In such case, the withholding Party shall promptly provide
the other Party with copies of receipts or other evidence reasonably required and sufficient to allow the other Party to document such tax withholdings adequately for purposes of claiming foreign tax credits and similar benefits. The Parties will
cooperate reasonably in completing and filing documents required under the provisions of any applicable tax laws or under any other applicable law, in connection with the making of any required tax payment or withholding payment, or in connection
with any claim to a refund of or credit for any such payment. The Parties will cooperate to minimize such taxes in accordance with applicable Laws, including using reasonable efforts to access the benefits of any applicable treaties. Notwithstanding
the foregoing, if, as a result of (i) the assignment of this 

  
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Agreement by Genzyme to an Affiliate or a Third Party outside of the United States or (ii) the exercise by Genzyme of its rights under this Agreement through an Affiliate or Third Party
outside of the United States (or the direct exercise of such rights by an Affiliate of Genzyme outside of the United States), foreign withholding tax in excess of the foreign withholding tax amount that would have been payable in the absence of such
assignment or exercise of rights becomes payable with respect to amounts due to Alnylam hereunder, such amount due to Alnylam will be increased so that the amount actually paid to Alnylam equals the amount that would have been payable to Alnylam in
the absence of such excess withholding (after withholding of the excess withholding tax and any additional withholding tax on such increased amount). However, if a similar assignment or exercise of rights described in (i) or (ii) of the
preceding sentence by Alnylam results in foreign withholding tax in excess of the foreign withholding tax amount that would have been payable in the absence of such assignment or exercise of rights, any amount due to Alnylam will not be increased
for such excess withholding and, subject to the terms of this Agreement, the required amount will be withheld and submitted to the appropriate governmental authority. 
 9. CONFIDENTIALITY AND PUBLICATION 
 9.1 Nondisclosure
Obligation. (a) All Confidential Information disclosed by one Party to the other Party hereunder shall be maintained in confidence by the receiving Party and shall not be disclosed to a Third Party or used for any purpose except as set
forth herein without the prior written consent of the disclosing Party, except to the extent that such Confidential Information: 
  

	 	(i)	is known by the receiving Party at the time of its receipt, and not through a prior disclosure by the disclosing Party, as documented by the receiving Party’s
business records; 

  

	 	(ii)	is known to the public before its receipt from the disclosing Party, or thereafter becomes generally known to the public through no breach of this Agreement by the
receiving Party; 

  

	 	(iii)	is subsequently disclosed to the receiving Party by a Third Party who is not known by the receiving Party to be under an obligation of confidentiality to the disclosing
Party; or 

  

	 	(iv)	is developed by the receiving Party independently of Confidential Information received from the disclosing Party, as documented by the receiving Party’s business
records. 

 (b) Notwithstanding the obligations of confidentiality and non-use set forth above and in
Section 9.1(c) below, a receiving Party may provide Confidential Information disclosed to it, and disclose the existence and terms of this Agreement as may be reasonably required in order to perform its obligations and to exploit its rights
under this Agreement, and specifically to (i) Related Parties, and their employees, directors, agents, consultants, advisors and/or other Third Parties for the performance of its obligations hereunder (or for such entities to determine their
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under an obligation of confidentiality with respect to such information that is no less stringent than the terms of this Section 9.1(b); (ii) governmental or other Regulatory
Authorities in order to obtain patents or perform its obligations or exploit its rights under this Agreement; provided that such Confidential Information shall be disclosed only to the extent reasonably necessary to do so,
(iii) the extent required by Law, including by the rules or regulations of the United States Securities and Exchange Commission or similar regulatory agency in a country other than the United States or of any stock exchange or listing entity,
(iv) any bona fide actual or prospective acquirers, underwriters, investors, lenders or other financing sources and any bona fide actual or prospective collaborators or strategic partners and to consultants and advisors of such Party, in each
case who are under an obligation or confidentiality with respect to such information that is no less stringent than the terms of this Section 9.1(b) and (v) to Third Parties to the extent a Party is required to do so pursuant to the terms
of an Existing Alnylam In-License. If a Party is required by Law to disclose Confidential Information that is subject to the non-disclosure provisions of this Section 9.1(b) or Section 9.1(c), such Party shall promptly inform the other
Party of the disclosure that is being sought in order to provide the other Party an opportunity to challenge or limit the disclosure obligations. Confidential Information that is required to be disclosed by Law shall remain otherwise subject to the
confidentiality and non-use provisions of this Section 9.1(b) and Section 9.1(c). If either Party concludes that a copy of this Agreement must be filed with the United States Securities and Exchange Commission or similar regulatory agency
in a country other than the United States, such Party will provide the other Party with a copy of this Agreement showing any provisions hereof as to which the Party proposes to request confidential treatment, will provide the other Party with an
opportunity to comment on any such proposed redactions and to suggest additional redactions, and will take such Party’s reasonable comments into consideration before filing the Agreement. 

(c) Alnylam recognizes the value of the license granted in this Agreement depends, in part, on Alnylam protecting the secrecy of the
Alnylam Know-How. Therefore, without limiting Alnylam’s right to license the Alnylam Know-How in any way it chooses, Alnylam shall use Commercially Reasonable Efforts to protect the confidentiality of the Alnylam Know-How as determined by
Alnylam in its reasonable business judgment. 
 9.2 Publication and Publicity. 

9.2.1 Publication. Genzyme and Alnylam each acknowledge the other Party’s interest in publishing certain key results
of the Collaboration. Each Party also recognizes the mutual interest in obtaining valid patent protection and in protecting trade secret information. Consequently, except for disclosures permitted pursuant to Section 9.1 and 9.2.2(a), either
Party wishing to make a publication or public presentation that contains the Confidential Information of the other Party shall deliver to the other Party a copy of the proposed written publication or presentation at least [**] days prior to
submission for publication or presentation. The reviewing Party shall have the right (a) to propose modifications to the publication or presentation for patent reasons, trade secret reasons or business reasons, and the publishing Party will
remove all Confidential Information of the other Party if requested by the reviewing Party, and (b) to request a reasonable delay in publication or presentation in order to protect patentable information. If the reviewing Party requests a
delay, the publishing Party shall delay submission or presentation for a period of [**] days (or such shorter period as may be mutually agreed by the 

  
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Parties) to enable the non-publishing Party to file patent applications protecting such Party’s rights in such information in accordance with Section 12. With respect to any proposed
publications or disclosures by investigators or academic or non-profit collaborators, such materials shall be subject to review under this Section 9.1(c) to the extent that Genzyme or Alnylam, as the case may be, has the right and ability
(after using Commercially Reasonable Efforts to obtain such right and ability) to do so. 
 9.2.2 Publicity.
Except as set forth in Section 9.1 above and Section 9.2.2(a) and 9.2.2(b) below, the terms of this Agreement may not be disclosed by either Party, and no Party shall use the name, trademark, trade name or logo of the other Party or
its employees in any publicity, news release or disclosure relating to this Agreement, its subject matter, or the activities of the Parties hereunder without the prior express written permission of the other Party, except as may be required by Law
or expressly permitted by the terms hereof. 
 (a) Following the execution of this Agreement, the Parties shall issue a joint
press release in the form set forth in Schedule 9.2.2(a). After such initial press release, except as provided in Section 9.2.2(b), neither Party shall issue a press release or public announcement relating to this Agreement without
the prior written approval of the other Party, which approval shall not be unreasonably withheld, conditioned or delayed, except that a Party may (i) once a press release or other public statement is approved in writing by both Parties, make
subsequent public disclosure of the information contained in such press release or other written statement without the further approval of the other Party, and (ii) issue a press release or public announcement as required, in the reasonable
judgment of such Party, by Law, including by the rules or regulations of the United States Securities and Exchange Commission or similar regulatory agency in a country other than the United States or of any stock exchange or listing entity.

 (b) Notwithstanding anything in this Section 9.2.2 to the contrary, either Party may issue a press release or make a
public disclosure relating to such Party’s Development, Manufacturing or Commercialization activities with respect to Licensed Products in such Party’s Territory, provided that such press release or public disclosure does not
disclose Confidential Information of the other Party. Furthermore, either Party may issue a press release or make a public disclosure relating to the other Party’s Development, Manufacturing or Commercialization activities with respect to the
Licensed Products in the other Party’s Territory, provided that (i) such press release or public disclosure does not disclose Confidential Information of the other Party and (ii) such press release or public disclosure
merely repeats subject matter previously disclosed by the other Party in a manner that is substantially consistent with such prior disclosure. Prior to making any such disclosure, however, the Party making the disclosure shall provide the
other Party with a draft of such proposed disclosure a reasonable time prior to disclosure to allow the other Party to review and comment prior to making any such disclosure, for the other Party’s review and comment, and the disclosing Party
shall consider in good faith any timely comments provided by the other Party. 

  
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 10. REPRESENTATIONS, WARRANTIES AND COVENANTS; INDEMNIFICATION 

10.1 Mutual Representations and Warranties. Each Party represents and warrants to the other Party that as of the Effective
Date: 
 10.1.1 It is duly organized and validly existing under the laws of its jurisdiction of incorporation or
formation, and has full corporate or other power and authority to enter into this Agreement, and to carry out the provisions hereof. 
 10.1.2 It is duly authorized to execute and deliver this Agreement, and to perform its obligations hereunder, and the person or persons executing this Agreement on its behalf has been duly
authorized to do so by all requisite corporate action. 
 10.1.3 This Agreement is legally binding upon it and
enforceable in accordance with its terms. The execution, delivery and performance of this Agreement by it does not conflict with any agreement, instrument or understanding, oral or written, to which it is a party and by which it may be bound, or
with its charter or by-laws. 
 10.1.4 It has not granted, and will not grant, during the Term, any right to any Third
Party that would conflict with the rights granted to the other Party hereunder. 
 10.1.5 Neither Party nor any of its
Affiliates has been debarred or is subject to debarment and neither Party nor any of its Affiliates will use in any capacity, in connection with the Collaboration or the performance of its obligations under this Agreement, any person or entity that
has been debarred pursuant to Section 306 of the United States Federal Food, Drug, and Cosmetic Act, as amended, or that is the subject of a conviction described in such section. Each Party agrees to inform the other Party in writing
immediately if it or any person or entity that is performing activities in the Collaboration or under this Agreement, is debarred or is subject to debarment or is the subject of a conviction described in Section 306, or if any action, suit,
claim, investigation or legal or administrative proceeding is pending or, to the best of the notifying Party’s knowledge, is threatened, relating to the debarment or conviction of the notifying Party or any person or entity used in any capacity
by such Party or any of its Affiliates in connection with the Collaboration or the performance of its other obligations under this Agreement. 
 10.2 Representations and Warranties of Alnylam. Except as provided in Schedule 10.2, Alnylam represents and warrants to Genzyme that as of the Effective Date: 

10.2.1 Alnylam is the sole and exclusive owner of, or otherwise Controls pursuant to an Alnylam In-License (or will Control
pursuant to an Additional Alnylam In-License at such time that such Additional Alnylam In-License is included as an Alnylam In-License pursuant to Section 7.4.2), the Alnylam Technology, and all of the Alnylam Technology licensed to Genzyme
hereunder in the Genzyme Territory that is solely and exclusively owned by Alnylam is free and clear of liens, charges or encumbrances other than licenses granted to Third Parties that are not inconsistent with the rights and licenses granted to
Genzyme under this Agreement. 

  
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 10.2.2 Alnylam has sufficient legal and/or beneficial title and ownership of, or
sufficient license rights under, the Alnylam Technology to grant the licenses to such Alnylam Technology granted to Genzyme pursuant to this Agreement. 
 10.2.3 (a) Schedule 1.9 and Schedule 1.16 collectively set forth a complete and accurate list of the Alnylam Patents owned, either solely or jointly, by Alnylam, and to Alnylam’s
knowledge, Schedule 1.9 and Schedule 1.16 collectively set forth a complete and accurate list of the Alnylam Patents licensed, either exclusively or nonexclusively, to Alnylam, (b) to Alnylam’s knowledge, each issued Alnylam
Patent remains in full force and effect and (c) Alnylam or its Affiliates have timely paid all filing and renewal fees payable with respect to such Alnylam Patents for which Alnylam controls prosecution and maintenance. Schedule 1.9 and
Schedule 1.16 indicate whether each Alnylam Patent is owned exclusively by Alnylam, is owned jointly by Alnylam and one or more Third Parties, or is licensed to Alnylam. For each Alnylam Patent Right that is owned, but not owned
exclusively, by Alnylam, or that is licensed to Alnylam, Schedule 1.9 and Schedule 1.16 identify the Third Party owner(s) and, if applicable, the Alnylam In-License pursuant to which Alnylam Controls such Alnylam Patent. For each
Alnylam Product-Specific Patent that is licensed, but not exclusively licensed, to Alnylam, Schedule 1.16 indicates the non-exclusive nature of the license. For each Alnylam Core Technology Patent family (other than Patent Rights licensed
from Isis Pharmaceuticals, Inc.) that is licensed, but not exclusively licensed, to Alnylam, Schedule 1.9 indicates the non-exclusive nature of the license. Alnylam is the sole and exclusive owner of all Patent Rights identified in
Schedule 1.9 and Schedule 1.16 as being owned exclusively by Alnylam and Controls all other Patent Rights identified on such schedules. 
 10.2.4 To Alnylam’s knowledge, the Alnylam Product-Specific Patents, are, or, upon issuance, will be, valid and enforceable patents and no Third Party has challenged or threatened to challenge
the scope, validity or enforceability of any Alnylam Product-Specific Patent (including, by way of example, through opposition or the institution or written threat of institution of interference, nullity or similar invalidity proceedings before the
United States Patent and Trademark Office or any analogous foreign Governmental Authority). 
 10.2.5 Alnylam has
complied with all applicable Laws, including any duties of candor to applicable patent offices, in connection with the filing, prosecution and maintenance of the Alnylam Patent Rights. 

10.2.6 Alnylam owns or Controls all Know-How that is or has been used by Alnylam in the Development and Manufacture of the
Licensed Products, and has sufficient legal or beneficial title and ownership of, or sufficient license rights under such Know-How to transfer Know-How to Genzyme as provided in Section 6.2. 

10.2.7 Schedule 1.47 sets forth a complete and accurate list of the Existing Alnylam In-Licenses. Alnylam Controls all
Know-How and Patent Rights licensed to Alnylam under the Existing Alnylam In-Licenses that is necessary or useful for Genzyme to Develop, Manufacture and/or Commercialize Licensed Products in the Field in the Genzyme Territory. Without limiting the
generality of the foregoing, Alnylam has obtained all necessary consents and fulfilled all necessary conditions, if any, to sublicense to Genzyme under this Agreement such Know-How 

  
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and Patent Rights licensed to Alnylam under Existing Alnylam In-Licenses. At such time that an Additional Alnylam In-License is included as an Alnylam In-License pursuant to Section 7.4.2,
Alnylam will Control all Know-How, if any, and Patent Rights licensed to Alnylam under such Additional Alnylam In-License that is necessary or useful for Genzyme to Develop, Manufacture and/or Commercialize Licensed Products in the Field in the
Genzyme Territory. 
 10.2.8 To Alnylam’s knowledge, neither Alnylam nor its Affiliates are in breach or default
under any Existing Alnylam In-License or Additional Alnylam In-License, and neither Alnylam nor its Affiliates have received any written notice of breach or default with respect to any Existing Alnylam In-License or Additional Alnylam In-License.

 10.2.9 Alnylam has obtained from all inventors of Alnylam Technology owned by Alnylam valid and enforceable agreements
assigning to Alnylam each such inventor’s entire right, title and interest in and to all such Alnylam Technology. 

10.2.10 No Alnylam Technology existing as of the Effective Date is subject to any funding agreement with any government or
Governmental Authority. 
 10.2.11 To Alnylam’s knowledge, the use, Development, Manufacture or Commercialization by
Alnylam or Genzyme (or their respective Related Parties) of any Licensed Product as formulated and manufactured as of the Effective Date, or as intended to be formulated and manufactured as of the Effective Date (a) does not and will not
infringe any issued patent of any Third Party or (b) will not infringe the claims of any published Third Party patent application when and if such claims were to issue in their current form. 

10.2.12 There is no (a) claim, demand, suit, proceeding, arbitration, inquiry, investigation or other legal action of any
nature, civil, criminal, regulatory or otherwise, pending or, to Alnylam’s knowledge, threatened against Alnylam or any of its Affiliates or (b) judgment or settlement against or owed by Alnylam or any of its Affiliates, in each case in
connection with the Alnylam Technology or any Licensed Product. 
 10.3 Representations and Warranties of Genzyme.
Genzyme represents and warrants to Alnylam as of the Effective Date that is not a party to any agreement with a Third Party under which it Controls Know-How or Patent Rights that are sublicensed to Alnylam under this Agreement. 

10.4 Warranty Disclaimer. EXCEPT AS OTHERWISE EXPRESSLY PROVIDED IN THIS AGREEMENT, NEITHER PARTY MAKES ANY REPRESENTATION
OR EXTENDS ANY WARRANTY OF ANY KIND, EITHER EXPRESS OR IMPLIED, TO THE OTHER PARTY WITH RESPECT TO ANY TECHNOLOGY, LICENSED PRODUCT, GOODS, SERVICES, RIGHTS OR OTHER SUBJECT MATTER OF THIS AGREEMENT AND HEREBY DISCLAIMS ALL IMPLIED WARRANTIES OF
MERCHANTABILITY, FITNESS FOR A PARTICULAR PURPOSE AND NON-INFRINGEMENT WITH RESPECT TO ANY AND ALL OF THE FOREGOING. EACH PARTY HEREBY DISCLAIMS ANY REPRESENTATION OR WARRANTY THAT THE DEVELOPMENT, MANUFACTURE OR COMMERCIALIZATION OF THE LICENSED
PRODUCT PURSUANT TO THIS AGREEMENT WILL BE SUCCESSFUL OR THAT ANY PARTICULAR SALES LEVEL WITH RESPECT TO THE LICENSED PRODUCT WILL BE ACHIEVED. 

  
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 10.5 Certain Covenants. 

10.5.1 Exclusivity. 
 (a) During the Exclusivity Period in a country in the Genzyme Territory, Genzyme will not, alone or with an Affiliate or Third Party, Develop or Commercialize in such country any product, including any
Improvement Product, for the treatment of ATTR, other than a Licensed Product or an Exempted Complementary TTR Product, without the prior written agreement of Alnylam. 
 (b) During the Exclusivity Period in a country in the Genzyme Territory, Alnylam will not, alone or with an Affiliate or Third Party, Develop or Commercialize in such country any product, including any
Improvement Product, for the treatment of ATTR, other than a Licensed Product or an Exempted Complementary TTR Product, without the prior written agreement of Genzyme.  
 (c) Alnylam shall not grant any license or other right under the Alnylam Technology that is inconsistent with the exclusivity granted to Genzyme with respect thereto under Section 7.1.1 and 7.1.2.
Without limiting the generality of the foregoing, during the Exclusivity Period in a country in the Genzyme Territory, Alnylam shall also not, alone or with an Affiliate or Third Party, Develop (except as permitted herein for or on behalf of
Genzyme) or Commercialize any Licensed Product in such country without the prior written agreement of Genzyme. 
 10.5.2
Compliance. Each Party and its Related Parties shall conduct the Collaboration and the Development, Manufacture and Commercialization of the Licensed Product in accordance with all Laws, including current governmental regulations
concerning good laboratory practices, good clinical practices and good manufacturing practices. 
 10.5.3 Conflicting
Transactions. During the Term, Alnylam shall not (a) transfer or assign any of its rights, title or interests in the Alnylam Technology other than as part of a transaction pursuant to which this Agreement is also assigned and
assumed in accordance with Section 14.1, or (b) enter into any agreement granting a license or other right under the Alnylam Technology that is inconsistent with the terms of this Agreement. 

11. INDEMNIFICATION; LIMITATION OF LIABILITY; INSURANCE 
 11.1 General Indemnification by Genzyme. Genzyme shall indemnify, hold harmless, and defend Alnylam, its Related Parties, and their respective directors, officers, employees and agents
(“Alnylam Indemnitees”) from and against any and all Third Party claims, suits, losses, liabilities, damages, costs, fees and expenses (including reasonable attorneys’ fees and litigation expenses) (collectively,
“Losses”) arising out of or resulting from, directly or indirectly, (a) any breach of, or inaccuracy in, any representation or warranty made by Genzyme in this Agreement, or any breach or violation of any covenant or agreement
of Genzyme in or in the performance of this Agreement, or (b) the negligence or willful misconduct by or of Genzyme and its Related Parties, and their respective directors, officers, employees and

  
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agents in the performance of Genzyme’s obligations under this Agreement. Genzyme shall have no obligation to indemnify the Alnylam Indemnitees to the extent that the Losses arise out of or
result from, directly or indirectly, any breach of, or inaccuracy in, any representation or warranty made by Alnylam in this Agreement, or any breach or violation of any covenant or agreement of Alnylam in or in the performance of this Agreement, or
the negligence or willful misconduct by or of any of the Alnylam Indemnitiees, or matters for which Alnylam is obligated to indemnify Genzyme under Section 11.2 or 11.3 or 11.4. 

11.2 General Indemnification by Alnylam. Alnylam shall indemnify, hold harmless, and defend Genzyme, its Related Parties
and their respective directors, officers, employees and agents (“Genzyme Indemnitees”) from and against any and all Losses arising out of or resulting from, directly or indirectly, (a) any breach of, or inaccuracy in, any
representation or warranty made by Alnylam in this Agreement, or any breach or violation of any covenant or agreement of Alnylam in or in the performance of this Agreement, or (b) the negligence or willful misconduct by or of Alnylam and its
Related Parties, and their respective directors, officers, employees and agents in the performance of Alnylam’s obligations under this Agreement. Alnylam shall have no obligation to indemnify the Genzyme Indemnitees to the extent that the
Losses arise out of or result from, directly or indirectly, any breach of, or inaccuracy in, any representation or warranty made by Genzyme in this Agreement, or any breach or violation of any covenant or agreement of Genzyme in or in the
performance of this Agreement, or the negligence or willful misconduct by or of any of the Genzyme Indemnitees, or matters for which Genzyme is obligated to indemnify Alnylam under Section 11.1 or 11.3. 

11.3 Product Liability. Any Losses arising out of Third Party product liability claims arising from the Development or
Commercialization of Licensed Products shall be (a) borne by Genzyme, to the extent such Losses were incurred with respect to the Development or Commercialization of the Licensed Product in or for the Genzyme Territory by or on behalf of
Genzyme and its Related Parties, and (b) be borne by Alnylam, to the extent such Losses were incurred with respect to Development or Commercialization of the Licensed Product in or for the Alnylam Territory by or on behalf of Alnylam and its
Related Parties. The Party bearing such Losses in accordance with the immediately preceding sentence shall indemnify, hold harmless and defend the other Party and its Related Parties and their respective directors, officers, employees and agents
from and against such Losses. 
 11.4 Ongoing Litigation. Without limiting Alnylam’s obligations in
Section 11.2 or 11.3: 
 11.4.1 Alnylam shall indemnify, hold harmless and defend the Genzyme Indemnitees from and
against any and all Losses and, subject to Section 11.6, any other amounts paid by Genzyme (such as through settlement) arising out of or resulting from any claim asserted (whether in the Ongoing Litigation or otherwise, but solely to the
extent substantially related to the subject matter of the Ongoing Litigation) by the plaintiffs in the Ongoing Litigation. 

11.4.2 In the event that Alnylam agrees (whether as part of any settlement or otherwise), or is required as part of any judgment
or order, to pay to one or more plaintiffs in the Ongoing Litigation amounts that result in the aggregate amount of Third Party License Payments 

  
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under an Existing Alnylam In-License exceeding, in duration or amount, the amount that Alnylam would be required to pay under such Existing Alnylam In-License based on Alnylam’s assertions
in the Ongoing Litigation (any such excess, “Incremental Amounts”), Alnylam shall be fully responsible for such Incremental Amounts. Without limitation, Genzyme shall not be responsible for any Incremental Amounts pursuant to
Section 7.4.3 and Incremental Amounts shall not be taken into account when calculating the royalty floor pursuant to Section 8.3.5. 
 11.5 [**]. 
 11.5.1 [**]. 

11.5.2 [**]. 
 11.6 Indemnification Procedure. In the event of any such claim against any Genzyme Indemnitee or Alnylam Indemnitee (individually, an “Indemnitee”), the indemnified Party
shall promptly notify the other Party in writing of the claim and the indemnifying Party shall manage and control, at its sole expense, the defense of the claim and its settlement. The Indemnitee shall cooperate with the indemnifying Party and may,
at its option and expense, be represented in any such action or proceeding. The indemnifying Party shall not be liable for any settlements, litigation costs or expenses incurred by any Indemnitee without the indemnifying Party’s written
authorization. Notwithstanding the foregoing, if the indemnifying Party believes that any of the exceptions to its obligation of indemnification of the Indemnitees set forth in Sections 11.1, 11.2, 11.3 or 11.4 may apply, the indemnifying Party
shall promptly notify the Indemnitees, which shall then have the right to be represented in any such action or proceeding by separate counsel at their expense; provided that the indemnifying Party shall be responsible for payment of
such expenses if the Indemnitees are ultimately determined to be entitled to indemnification from the indemnifying Party for the matters to which the indemnifying Party notified the Indemnitees that such exception(s) may apply. 

11.7 Limitation of Liability. NEITHER PARTY HERETO WILL BE LIABLE FOR SPECIAL, INCIDENTAL, CONSEQUENTIAL OR PUNITIVE
DAMAGES ARISING OUT OF THIS AGREEMENT OR THE EXERCISE OF ITS RIGHTS HEREUNDER, INCLUDING LOST PROFITS ARISING FROM OR RELATING TO ANY BREACH OF THIS AGREEMENT, REGARDLESS OF ANY NOTICE OF SUCH DAMAGES, EXCEPT AS A RESULT OF A PARTY’S WILLFUL
MISCONDUCT OR A BREACH OF SECTION 7.6 (ALNYLAM TERRITORY RIGHT OF FIRST NEGOTIATION), SECTION 9 (CONFIDENTIALITY AND PUBLICATION), OR SECTION 10.5.1 (EXCLUSIVITY). NOTHING IN THIS SECTION 11.7 IS INTENDED TO LIMIT OR RESTRICT THE
INDEMNIFICATION RIGHTS OR OBLIGATIONS OF EITHER PARTY. NOTWITHSTANDING THE FOREGOING, ALNYLAM SHALL NOT BE LIABLE FOR ANY SPECIAL, INCIDENTAL, CONSEQUENTIAL OR PUNITIVE DAMAGES ARISING OUT OF ANY BREACH OF SECTION 7.6 (ALNYLAM TERRITORY RIGHT OF
FIRST NEGOTIATION) UNLESS GENZYME BRINGS AN ACTION SEEKING SUCH DAMAGES WITHIN SIX (6) MONTHS AFTER THE EARLIER OF THE DATE ON WHICH THE TRANSACTION BETWEEN ALNYLAM AND A THIRD PARTY ENTERED INTO IN BREACH OF SECTION 7.6 FIRST BECOMES PUBLICLY
KNOWN OR THE DATE ON WHICH ALNYLAM NOTIFIES GENZYME OF SUCH TRANSACTION. 

  
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 11.8 Insurance. Each Party shall maintain insurance during the Term and for a
period of at least [**] years after the last commercial sale of any Licensed Product under this Agreement, with a reputable, solvent insurer in an amount appropriate for its business and products of the type that are the subject of this Agreement,
and for its obligations under this Agreement. Specifically, each Party shall maintain product liability insurance and clinical trial liability insurance with limits of at least [**] U.S. Dollars ($[**]) per occurrence and in annual aggregate. Upon
request, each Party shall provide the other Party with evidence of the existence and maintenance of such insurance coverage. 

12. INTELLECTUAL PROPERTY OWNERSHIP, PROTECTION AND RELATED MATTERS 

12.1 Inventorship. Inventorship for inventions and discoveries first made during the course of the performance of
activities pursuant to this Agreement shall be determined in accordance with United States patent Laws for determining inventorship. 
 12.2 Ownership. Alnylam shall own the entire right, title and interest in and to all inventions and discoveries (and Patent Rights claiming patentable inventions therein) first made or
discovered solely by employees or consultants of Alnylam or acquired solely by Alnylam in the course of conducting the Collaboration. Genzyme shall own the entire right, title and interest in and to all inventions and discoveries (and Patent Rights
claiming patentable inventions therein) first made or discovered solely by employees or consultants of Genzyme or acquired solely by Genzyme in the course of conducting the Collaboration. The Parties shall jointly own any inventions and discoveries
(and Patent Rights claiming patentable inventions therein) first made or discovered jointly in the course of conducting the Collaboration. 
 12.3 Prosecution and Maintenance of Patent Rights. 
 12.3.1
Genzyme Technology. 
 (a) Subject to Section 12.3.1(b) Genzyme has the sole responsibility to, at
Genzyme’s discretion, file, prosecute, and maintain (including the defense of any interference or opposition proceedings), all Patent Rights comprising Genzyme Technology (other than Joint Collaboration IP), in Genzyme’s name. 

(b) In the event that Genzyme elects not to seek or continue to seek or maintain patent protection on any Genzyme Collaboration IP in the
Alnylam Territory, subject to the terms and conditions of any applicable Genzyme In-License, Alnylam shall have the right (but not the obligation), at its expense, to seek, prosecute and maintain in any country patent protection on such Genzyme
Collaboration IP in the name of Genzyme. Genzyme shall use Commercially Reasonable Efforts to make available to Alnylam its authorized attorneys, agents or representatives, such of its employees as are reasonably necessary to assist Alnylam in
obtaining and maintaining the patent protection described under this Section 12.3.1(b). Genzyme shall sign or use Commercially Reasonable Efforts to have signed all legal documents necessary to file and prosecute such patent applications or to
obtain or maintain such patents. 

  
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 12.3.2 Alnylam Technology. 

(a) Subject to Section 12.3.2(c), Alnylam has the sole responsibility to, at Alnylam’s discretion, file, conduct prosecution,
and maintain (including the defense of any interference or opposition proceedings), all Patent Rights comprising Alnylam Technology (other than Joint Collaboration IP), in Alnylam’s name. Alnylam agrees to use Commercially Reasonable Efforts to
prosecute and maintain the Alnylam Patents in the Genzyme Territory. 
 (b) Notwithstanding the foregoing
Section 12.3.2(a), Alnylam shall consult with Genzyme on the preparation, filing, prosecution, and maintenance of all Alnylam Product-Specific Patents in the Genzyme Territory and the Alnylam Territory. Alnylam shall furnish Genzyme with copies
of proposed filings and documents received from or filed with the relevant patent offices with respect to Alnylam Product-Specific Patents and such other documents directly related to the prosecution and maintenance of Alnylam Product-Specific
Patents reasonably necessary for Genzyme to exercise its rights under this Section 12.3.112.3.1(b), and as applicable in sufficient time prior to filing such document or making any payment due thereunder to allow for review and comment by
Genzyme and shall consider in good faith timely comments from Genzyme thereon. Furthermore, Alnylam shall provide Genzyme with copies of documents received from or filed with the relevant national patent offices with respect to the filing,
prosecution, and maintenance of Alnylam Core Technology Patents in the Genzyme Territory within a reasonable time after the filing of such documents. 
 (c) In the event that Alnylam elects not to seek or continue to seek or maintain patent protection on any Alnylam Product-Specific Patent in the Genzyme Territory or the Alnylam Territory, subject to the
terms and conditions of any applicable Alnylam In-License, Genzyme shall have the right (but not the obligation), at its expense, to seek, prosecute and maintain in any country patent protection on such Alnylam Product-Specific Patent in the Genzyme
Territory. If Genzyme exercises such right, Alnylam shall thereafter and hereby does assign all right, title and interest in and to such Patent Rights to Genzyme. Alnylam shall use Commercially Reasonable Efforts to make available to Genzyme
its authorized attorneys, agents or representatives, such of its employees as are reasonably necessary to assist Genzyme in obtaining and maintaining the patent protection described under this Section 12.3.2(b). Alnylam shall sign or use
Commercially Reasonable Efforts to have signed all legal documents necessary to file and prosecute such patent applications or to obtain or maintain such patents. 
 (d) Alnylam shall, as provided in Section 12.3.2(b), consult with Genzyme prior to its filing of any patent application which would, if patented, be included in the definition of Alnylam
Product-Specific Patents. Furthermore, (a) promptly after filing, any provisional or non-provisional patent application that is included in Alnylam Product Specific Patents and (b) promptly after publication, any non-provisional patent
application that is included in the Alnylam Core Technology Patents that Cover a Licensed Product or an siRNA Product that Alnylam has identified to Genzyme as a potential Improvement Product, Alnylam shall promptly provide a copy of such patent
application to Genzyme. All information provided by the Alnylam under this Section 12.3.3 will be deemed to be Confidential Information of Alnylam and maintained in accordance with Section 9. 

  
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 12.3.3 Joint Collaboration IP. 

(a) Alnylam shall have the first right to, at Alnylam’s discretion, file, prosecute and maintain (including the defense of any
interference or opposition proceedings), all Patent Rights comprising Joint Collaboration IP, in the names of both Alnylam and Genzyme. Alnylam shall provide Genzyme an opportunity to review and comment on material documents related to such filing,
prosecution and maintenance in accordance with Section 12.3.4, which comments Alnylam will consider in good faith. Each Party shall sign, or use Commercially Reasonable Efforts to have signed, all legal documents necessary to file and prosecute
patent applications or to obtain or maintain patents in respect of such Joint Collaboration IP, at its own cost. 
 (b)
Notwithstanding the foregoing Section 12.3.3(a), Alnylam shall consult with Genzyme on the preparation, filing, prosecution, and maintenance of all Patent Rights included within the Joint Collaboration IP to be filed or pending in the Genzyme
Territory. Alnylam shall furnish Genzyme with copies of documents relevant to such preparation, filing, prosecution, and maintenance in sufficient time prior to filing such document or making any payment due thereunder to allow for review and
comment by Genzyme and shall consider in good faith timely comments from Genzyme thereon. 
 (c) In the event that Alnylam
elects not to file or continue to prosecute or maintain patent protection on any Joint Collaboration IP, Genzyme shall have the right (but not the obligation) to file, prosecute and maintain Patent Rights comprising Joint Collaboration IP in the
names of both Alnylam and Genzyme. If Genzyme exercises such right, Alnylam shall use Commercially Reasonable Efforts to make available to Genzyme its authorized attorneys, agents or representatives, such of its employees as are reasonably necessary
to assist Genzyme in obtaining and maintaining the patent protection described under this Section 12.3.3(c). Alnylam shall sign or use Commercially Reasonable Efforts to have signed all legal documents necessary to file and prosecute such
patent applications or to obtain or maintain such patents. 
 (d) The Parties shall share equally the out-of-pocket patent
filing, prosecution and maintenance expenses incurred with respect to Patent Rights comprising Joint Collaboration IP. 

12.3.4 Cooperation. Each Party hereby agrees: (a) to make its employees, agents and consultants reasonably available
to the other Party (or to the other Party’s authorized attorneys, agents or representatives), to the extent reasonably necessary to enable such Party to undertake patent prosecution; (b) to provide the other Party with copies of all
material correspondence pertaining to prosecution with the patent offices; (c) to cooperate, if necessary and appropriate, with the other Party in gaining patent term extensions wherever applicable to Patent Rights licensed under this
Agreement; and (d) to endeavor in good faith to coordinate its efforts with the other Party to minimize or avoid interference with the prosecution and maintenance of the other Party’s patent applications. 

12.4 Third Party Infringement. 
 12.4.1 Notices. Each Party shall promptly report in writing to the other Party any (a) known or suspected infringement of any Alnylam Technology, Genzyme Technology or Joint
Collaboration IP or (b) unauthorized use or misappropriation of any Confidential Information or 

  
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Know-How of a Party by a Third Party of which it becomes aware, in each case to the extent such infringing, unauthorized or misappropriating activities involve, as to a Licensed Product, a
competing product in the Field (“Competitive Infringement”), and shall provide the other Party with all available evidence of such infringement, unauthorized use or misappropriation. 

12.4.2 Rights to Enforce. 
 (a) Genzyme Technology. Subject to the provisions of any In-License, Genzyme shall have the sole and exclusive right to initiate an infringement or other appropriate suit anywhere in the
world against any Third Party as to any infringement, or suspected infringement of, any Patent Rights, or of any use or suspected use without proper authorization of any Know-How, comprising Genzyme Patent Rights, Genzyme Know-How, or Genzyme
Collaboration IP. Genzyme will consider in good faith any request from Alnylam to initiate an infringement or other appropriate suit against any Third Party with respect to Competitive Infringement in the Alnylam Territory of Genzyme Patent Rights,
Genzyme Know-How or Genzyme Collaboration IP licensed to Alnylam under Section 7, however Genzyme shall not be required to initiate any such suit or permit Alnylam to initiate any such suit. 

(b) Alnylam Technology. Subject to the provisions of any In-License, Genzyme shall have the first right to initiate an
infringement or other appropriate suit anywhere in the world against any Third Party with respect to any Competitive Infringement in the Genzyme Territory of any Alnylam Product-Specific Patent or Joint Collaboration IP, or, with Alnylam’s
prior written consent, Alnylam Core Technology Patent or Alnylam Know-How. Alnylam will consider in good faith any request from Genzyme to initiate an infringement or other appropriate suit against any Third Party with respect to a Competitive
Infringement in the Genzyme Territory of any Alnylam Core Technology Patent; provided, however, that Alnylam shall not be required to initiate any such suit or permit Genzyme to initiate any such suit. 

(c) Step-In Right.  
  

	 	(i)	If within [**] days (or such shorter period of time as required by applicable Law to avoid loss of material enforcement rights) after Genzyme’s receipt of a notice
of a Competitive Infringement with respect to any Alnylam Product-Specific Patent or Joint Collaboration IP, Genzyme does not take any action as described in Section 12.4.2(b) and permitted hereunder against such Competitive Infringement in the
Genzyme Territory, Alnylam may in its sole discretion, bring and control any legal action in connection therewith at its sole expense. 

  

	 	(ii)	 If (A) there are no Alnylam Product-Specific Patents or Patent Rights included in Joint Collaboration IP that can be asserted against a
Competitive Infringement in the Genzyme Territory, (B) there are Alnylam Core Technology Patent(s) that can reasonably be asserted, but Alnylam refuses to either permit Genzyme to assert or itself assert at least one of such Alnylam Core
Technology Patent(s) that can reasonably be asserted against a Competitive Infringement in the Genzyme Territory and (C) Genzyme and Alnylam are unable to stop the 

  
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Competitive Infringement through enforcement of any other Patent Rights or Know-How Controlled by either Party, then the royalties to be paid by Genzyme to Alnylam pursuant to Section 8.3
with respect to the applicable Licensed Product shall be reduced throughout the Genzyme Territory as specified in Section 8.3.3 (regardless of whether any Alnylam Patent or Patent Right included in the Joint Collaboration IP Covers the Licensed
Product) during the period after the conditions in the foregoing clauses (A), (B) and (C) exist when such Competitive Infringement continues. 

 12.4.3 Procedures; Expenses and Recoveries. The Party having the right to initiate any infringement suit under Section 12.4.2 above shall have the sole and exclusive right to select
counsel for any such suit and shall pay all expenses of the suit, including attorneys’ fees and court costs and reimbursement of the other Party’s reasonable Out-of-Pocket expense in rendering assistance requested by the initiating Party.
If required under applicable Law in order for the initiating Party to initiate and/or maintain such suit, or if either Party is unable to initiate or prosecute such suit solely in its own name or it is otherwise advisable to obtain an effective
legal remedy, in each case, the other Party shall join as a party to the suit and will execute and cause its Affiliates to execute all documents necessary for the initiating Party to initiate litigation to prosecute and maintain such action. In
addition, at the initiating Party’s request, the other Party shall provide reasonable assistance to the initiating Party in connection with an infringement suit at no charge to the initiating Party except for reimbursement by the initiating
Party of reasonable Out-of-Pocket expenses incurred in rendering such assistance. The non-initiating Party shall have the right to participate and be represented in any such suit by its own counsel at its own expense. If the Parties obtain from a
Third Party, in connection with such suit, any damages, license fees, royalties or other compensation (including any amount received in settlement of such litigation), such amounts shall be allocated in all cases as follows: 

 

	 	(i)	first, to reimburse each Party for all expenses of the suit incurred by the Parties, including attorneys’ fees and disbursements, court costs and other litigation
expenses; 

  

	 	(ii)	second, [**] percent ([**]%) of the balance to be paid to the Party initiating the suit; and 

 

	 	(iii)	third, the remainder to the other Party. 

 Notwithstanding the foregoing, in the event that Alnylam elects to itself assert an Alnylam Core Technology Patent against a Competitive Infringement in the Genzyme Territory, the Parties shall each be
entitled to [**] percent ([**]%) of the balance of any recovery therefrom after reimbursement of expenses as described in clause (i) above. 
 12.5 Patent Term Extensions. Subject to the provisions of any Alnylam In-License, Alnylam shall use Commercially Reasonable Efforts to obtain all available supplementary protection
certificates (“SPC”) and other extensions of Alnylam Product-Specific Patents in the Genzyme Territory. If more than one Alnylam Product-Specific Patent is eligible for extension or patent term restoration in the Genzyme Territory,
Genzyme will determine, in its sole discretion, a strategy that will be designed to maximize patent protection and commercial value for the Licensed Product, and the Parties, subject to the provisions of any In-License, will seek

  
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patent term extensions, restorations and SPCs for Alnylam Product-Specific Patents in the Genzyme Territory in accordance with that strategy. If Genzyme determines not to so file for any SPC for
any Alnylam Product-Specific Patent in the Genzyme Territory, it will give notice of such determination to Alnylam at least [**] days prior to the date on which such a filing must be made or the right to do so is lost, and Alnylam will have the
right to make such filing. Where required under national law, Alnylam will make the filings for such extensions, restorations and SPCs for Alnylam Product-Specific Patents in the Genzyme Territory as directed by Genzyme. Each Party will execute such
authorizations and other documents and take such other actions as may be reasonably requested by the other Party to obtain any such extensions, restorations and SPCs for Alnylam Product-Specific Patents in the Genzyme Territory. 

12.6 Common Interest. All information exchanged between the Parties representatives regarding the preparation,
filing, prosecution, maintenance, or enforcement of the Patents Rights under this Section 12 will be deemed Confidential Information. In addition, the Parties acknowledge and agree that, with regard to such preparation, filing, prosecution,
maintenance, and enforcement of the Patents Rights under this Section 12, the interests of the Parties as collaborators and licensor and licensee are to obtain the strongest patent protection possible, and as such, are aligned and are legal in
nature. The Parties agree and acknowledge that they have not waived, and nothing in this Agreement constitutes a waiver of, any legal privilege concerning the Patents Rights under this Section 12, including privilege under the common interest
doctrine and similar or related doctrines. 
 12.7 Trademarks. 

(a) Each Party has the right to use any trademark it owns or controls for Licensed Products in its Territory at its sole discretion, and
each Party and its Affiliates shall retain all right, title and interest in and to its and their respective corporate names and logos. 
 (b) Genzyme will develop and propose, and the JSC shall review and comment on, one or more Product Trademark(s) for use by Genzyme and its Related Parties throughout the Genzyme Territory. Such Product
Trademark(s) considered by the JSC may include, in Genzyme’s sole discretion, the Product Trademark(s) developed and/or used by Alnylam with respect to the Commercialization of Licensed Products in the Alnylam Territory (the “Alnylam
Trademarks”), but may not include other trademarks owned or controlled by Alnylam. Any Product Trademark(s) (other than the Alnylam Trademarks) that are used by Genzyme to promote and sell Licensed Products in the Genzyme Territory are
hereinafter referred to as the “Genzyme Trademarks.” Alnylam (or its Related Parties, as appropriate) shall own all rights to Alnylam Trademarks, and all goodwill associated therewith, throughout the Alnylam Territory and the
Genzyme Territory. Genzyme (or its Related Parties, as appropriate) shall own all rights to Genzyme Trademarks and all goodwill associated therewith, throughout the Genzyme Territory. Alnylam shall also own rights to any Internet domain names
incorporating the applicable Alnylam Trademarks or any variation or part of such Alnylam Trademarks used as its URL address or any part of such address; and Genzyme shall also own rights to any Internet domain names incorporating the applicable
Genzyme Trademarks or any variation or part of such Genzyme Trademarks used as its URL address or any part of such address. 

  
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 (c) If Genzyme determines to use Alnylam Trademarks to promote and sell any Licensed Product
in the Genzyme Territory, then Alnylam and Genzyme shall enter into a separate trademark license agreement containing commercially reasonable and customary terms pursuant to which Alnylam will grant Genzyme an exclusive, royalty-free license to use
the applicable Alnylam Trademark(s) to Commercialize Licensed Products in the Genzyme Territory. 
 (d) In the event either
Party becomes aware of any infringement of any Product Trademark by a Third Party, such Party shall promptly notify the other Party and the Parties shall consult with each other and jointly determine the best way to prevent such infringement,
including by the institution of legal proceedings against such Third Party. 
 (e) For the avoidance of doubt, neither Party
shall have any right to use the other Party’s or the other Party’s Affiliates’ corporate names or logos in connection with Commercialization of Licensed Products. 

12.8 Cooperative Research and Technology (CREATE) Act Acknowledgment. It is the intention of the Parties that this
Agreement is a “joint research agreement” as that phrase is defined in Section 35 U.S.C. 103(c). 
 13. TERM
AND TERMINATION 
 13.1 Term. This Agreement shall be effective as of the Effective Date and, unless
terminated earlier pursuant to Section 13.2, this Agreement shall continue in effect on a Licensed Product-by-Licensed Product and country-by-country basis until expiration of the last Royalty Term to expire under this Agreement
(“Term”). Upon expiration of the Term, all licenses of the Parties under Section 7 then in effect shall become fully paid-up, perpetual, exclusive licenses. 

13.2 Termination Rights. 
 13.2.1 Termination for Convenience. Genzyme shall have the right to terminate this Agreement in its entirety at any time after the Effective Date on six (6) months prior written notice
to Alnylam. 
 13.2.2 Termination for Cause. This Agreement may be terminated at any time during the Term upon
written notice by either Party if the other Party is in material breach of its obligations hereunder and has not cured such breach within [**] days in the case of a payment breach, or within [**] days in the case of all other breaches, after notice
requesting cure of the breach; provided, however, that if any breach other than a payment breach is not reasonably curable within [**] days and if a Party is making a bona fide effort to cure such breach, such termination shall be
delayed for a time period to be agreed by both Parties, not to exceed an additional [**] days, in order to permit such Party a reasonable period of time to cure such breach; provided, further, that in the event that the breach relates
to a dispute between the Parties regarding Genzyme’s obligations to use Commercially Reasonable Efforts in Developing or Commercializing the Licensed Products and Genzyme disputes whether it has breached such obligation or whether such breach
gives Alnylam the right to terminate this agreement and initiates a legal action against Alnylam to resolve such dispute within the foregoing [**] day cure 

  
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period, then this Agreement shall not terminate during the pendency of such legal action; provided that if Genzyme is found in an unappealable decision by a court of competent jurisdiction
or an appealable decision of a court of competent jurisdiction that has not been appealed in the time allowed for an appeal in such legal action to have materially breached this Agreement or if Genzyme admits in such legal action or settlement
thereof that it has materially breached this Agreement then this Agreement shall terminate immediately following the Parties’ receipt of such decision or immediately following such admission, as applicable. 

13.2.3 No First Phase II Success. Genzyme may also terminate this Agreement in accordance with Section 8.2(a)(i).

 13.2.4 Challenges of Patent Rights. If during the Term Genzyme or any of its Affiliates
(a) commences or participates in any action or proceeding (including any patent opposition or re-examination proceeding), or otherwise asserts any claim, challenging or denying the validity or enforceability of any Alnylam Patent or any claim
thereof or (b) actively assists any other person or entity in bringing or prosecuting any action or proceeding (including any patent opposition or re-examination proceeding) challenging or denying the validity or enforceability of any of such
Patent Rights or any claim thereof (each of (a) and (b), a “Patent Challenge”), then, to the extent permitted by the applicable Laws, Alnylam shall have the right, exercisable within [**] days following receipt of notice
regarding such Patent Challenge, in its sole discretion, to give notice to Genzyme that Alnylam may terminate this Agreement ninety (90) days following such notice (or such longer period as Alnylam may designate in such notice), and, unless
Genzyme or such Affiliate withdraws or causes to be withdrawn all such challenge(s) (or in the case of ex-parte proceedings, multi-party proceedings, or other Patent Challenges that Genzyme or Genzyme’s Affiliates do not have the power
to unilaterally withdraw or cause to be withdrawn, Genzyme and Genzyme’s Affiliates cease actively assisting any other party to such Patent Challenge and, to the extent Genzyme or a Genzyme Affiliate is a party to such Patent Challenge, it
withdraws from such Patent Challenge) within such ninety (90)-day period, Alnylam will have the right to terminate this Agreement by providing written notice thereof to Genzyme. The foregoing sentence shall not apply (i) with respect to any
Alnylam Patent that Alnylam first asserts against Genzyme or any of its Affiliates where the Patent Challenge is made in defense of such assertion, (ii) with respect to any Patent Challenge commenced by a Third Party that after the Effective
Date acquires or is acquired by Genzyme or its Affiliates or its or their business or assets, whether by stock purchase, merger, asset purchase or otherwise, but only with respect to Patent Challenges commenced prior to the closing of such
acquisition. 
 13.2.5 Abandonment of Development. At any time on or after the tenth
(10th) anniversary of the Effective Date, either
Party may terminate this Agreement in its entirety if (a) no Licensed Product has received Regulatory Approval anywhere in the Genzyme Territory, (b) no Licensed Product is being Developed in the Genzyme Territory, (c) no Genzyme
Territory Development Plan is in effect for any Licensed Product, provided that, if Genzyme provides Alnylam with a good faith Genzyme Territory Development Plan pursuant to Section 2.2.3 during the termination notice period set forth below in
this Section 13.2.5, then the condition set forth in this clause (c) shall be deemed not satisfied at such time and the applicable termination notice shall be deemed not to have effect, and (d) the absence of Development in the
Genzyme Territory or a good faith Genzyme Development Plan is not the result of a breach by the Party 

  
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seeking to terminate this Agreement of its obligations under Section 2.4. In order to terminate this Agreement pursuant to this Section 13.2.5, the terminating Party must provide at
least six (6) months’ prior written notice to the other Party referencing this Section 13.2.5 and specifying a termination date on or after the tenth (10th) anniversary of the Effective Date; provided that. for a termination by Alnylam, such notice must also include an
update regarding the current status of Alnylam’s development activities with respect to Licensed Products, Backup Compounds and Improvement Products. 
 13.3 Effect of Termination. 
 13.3.1 Termination by Genzyme
for Alnylam Breach. Without limiting any other legal or equitable remedies that either Party may have, if this Agreement is terminated by Genzyme pursuant to Section 13.2.2, then: 

(a) all license grants in this Agreement from either Party to the other shall immediately terminate; and 

(b) Genzyme shall as promptly as practicable transfer to Alnylam or Alnylam’s designee (i) possession and ownership of all
Regulatory Approvals and pricing and reimbursement approvals relating to the Development, Manufacture or Commercialization of the Licensed Product, and (ii) copies of all non-clinical and clinical data and material regulatory correspondence
relating to the Licensed Products. 
 13.3.2 Termination by Alnylam for Genzyme Breach or by Genzyme for
Convenience. Without limiting any other legal or equitable remedies that either Party may have, if this Agreement is terminated by Genzyme pursuant to Section 13.2.1 or 13.2.3 or by Alnylam under Section 13.2.2 or 13.2.4,
then: 
 (a) the license grants to Alnylam in Section 7.2 shall survive and shall be expanded to include the Genzyme
Territory, 
 (b) Genzyme shall as promptly as practicable transfer to Alnylam or Alnylam’s designee (i) possession
and ownership of all governmental or regulatory correspondence, conversation logs, filings and approvals (including all Regulatory Approvals and pricing and reimbursement approvals) relating to the Development, Manufacture or Commercialization of
the Licensed Product and all Genzyme Trademarks, (ii) copies of all data, reports, records and materials, and other sales and marketing related information in Genzyme’s possession or Control to the extent that such data, reports, records,
materials or other information relate to the Development, Manufacture or Commercialization of the Licensed Product, including all non-clinical and clinical data relating to the Licensed Product, and customer lists and customer contact information
and all adverse event data in Genzyme’s possession or Control; provided that Genzyme shall use Commercially Reasonable Efforts to obtain for Alnylam the right to access all such data, reports, records, materials, and other sales
and marketing related information, and (iii) all records and materials in Genzyme’s possession or Control containing Confidential Information of Alnylam. Genzyme shall further appoint Alnylam as Genzyme’s and/or Genzyme’s Related
Parties’ agent for all Licensed Product-related matters involving Regulatory Authorities in the Genzyme Territory until all Regulatory Approvals and other regulatory filings have been transferred to Alnylam or its designee, 

  
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 (c) if the effective date of termination is after First Commercial Sale, then Genzyme shall
appoint Alnylam as its exclusive distributor of the Licensed Product in the Genzyme Territory and grant Alnylam the right to appoint sub-distributors, until such time as all Regulatory Approvals in the Genzyme Territory have been transferred to
Alnylam or its designee, 
 (d) if Genzyme or its Related Parties are Manufacturing Finished Product, at Alnylam’s option,
supply the Finished Product to Alnylam in the Genzyme Territory on terms no less favorable than those on which Genzyme supplied the Finished Product prior to such termination to its most favored distributor in the Genzyme Territory, until the
earlier of (i) such time as all Regulatory Approvals in the Genzyme Territory have been transferred to Alnylam or its designee, Alnylam has obtained all necessary manufacturing approvals and Alnylam has procured or developed its own source of
Finished Product supply or (ii) [**] months following the effective date of such termination, 
 (e) if Alnylam so
requests, and to the extent permitted under Genzyme’s obligations to Third Parties at the time of termination, Genzyme shall transfer to Alnylam any Third Party agreements relating solely and exclusively to the Development, Manufacture or
Commercialization of the Licensed Product to which Genzyme is a party, subject to any required consents of such Third Party, which Genzyme shall use Commercially Reasonable Efforts to obtain promptly, 

(f) Genzyme shall promptly transfer and assign to Alnylam all of Genzyme’s and its Affiliates’ rights, title and interests in
and to the Genzyme Trademark(s) (but not any Genzyme house marks or any trademark containing the word “Genzyme” owned by Genzyme and used for the Licensed Products in the Field in the Genzyme Territory) owned by Genzyme and used for the
Licensed Products in the Field in the Genzyme Territory 
 (g) Genzyme shall transfer to Alnylam any inventory of Licensed
Products Controlled by Genzyme or its Affiliates as of the termination date at the actual price paid by Genzyme for such supply, 
 (h) Genzyme shall provide any other assistance reasonably requested by Alnylam for the purpose of allowing Alnylam or its designee to proceed expeditiously with the Development, Manufacture and
Commercialization of Licensed Products in the Genzyme Territory, and 
 (i) Genzyme shall execute all documents and take all
such further actions as may be reasonably requested by Alnylam in order to give effect to the foregoing clauses. 
 13.3.3
Termination for Abandonment of Development. If this Agreement is terminated by either Party pursuant to Section 13.2.5, then the license granted to Alnylam under Section 7.2.2 shall survive and all other licenses granted in this
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 13.4 Fundamental Breach of Alnylam’s Development Obligations.
Without limiting Genzyme’s rights under Section 13.2.2 with respect to other material breaches, in the event that Alnylam commits a Fundamental Breach of its Development obligations under Section 2.4.2 and Genzyme does not terminate
this Agreement for cause pursuant to Section 13.2.2, then Genzyme may elect to receive the following remedies for such Fundamental Breach: 
 13.4.1 Genzyme’s obligation to pay development milestone fees under Section 8.2 shall automatically terminate; 
 13.4.2 Genzyme will receive a credit, which Genzyme may offset against royalties due to Alnylam pursuant to Section 8.3, in an amount equal to [**] percent ([**]%) of all costs
(i) incurred by Genzyme to Develop the Licensed Products for the Genzyme Territory that are in excess of the costs budgeted by Genzyme in connection with the Genzyme Territory Development Plan in effect at the time of Alnylam’s Fundamental
Breach of Section 2.4.2 and (ii) are incurred by Genzyme as a direct consequence of Alnylam’s Fundamental Breach of Section 2.4.2; 
 13.4.3 Genzyme may, in its discretion, terminate any or all of the following provisions of this Agreement (or any subsection thereof): Section 2.3.3, Section 3.1.3, Section 4.1.3,
Section 4.2, Section 4.3, Section 4.4, Section 4.5, and Section 5; and 
 13.4.4 Without
limiting Genzyme’s remedies under this Agreement or otherwise with respect to breaches of Alnylam’s Development obligations under Section 2.4.2(a) other than Fundamental Breaches, if Genzyme elects to receive the remedies set forth in
this Section 13.4, such remedies shall be Genzyme’s sole and exclusive remedies with respect to such Fundamental Breach and Genzyme shall have no right to seek any further remedies or damages against Alnylam and its Affiliates with respect
to such Fundamental Breach by Alnylam of Section 2.4.2(a). 
 13.5 Effect of Expiration or Termination; Survival.
Expiration or termination of this Agreement shall not relieve the Parties of any obligation accruing prior to such expiration or termination. Any expiration or termination of this Agreement shall be without prejudice to the rights of either
Party against the other accrued or accruing under this Agreement prior to expiration or termination, including the obligation to pay royalties for the Licensed Product sold prior to such expiration or termination. The provisions of Sections 1, 9, 11
and 14 and Sections 10.4, 12.1, 12.2, 13.3, and 13.5 shall survive any expiration or termination of this Agreement. Sections 8.3.5 shall survive any expiration of this Agreement or any termination with respect to royalties accruing prior to such
termination. Section 8.3.7 (Reports; Payment of Royalty) and Section 8.4 (Audits) will survive for so long as any royalties are due under this Agreement plus three (3) years. Except as otherwise set forth in this Section 13, upon
termination or expiration of this Agreement all rights and obligations of the Parties under this Agreement cease. 
 14.
MISCELLANEOUS 
 14.1 Assignment. Except as provided in this Section 14.1, this Agreement may not be
assigned or otherwise transferred, nor may any right or obligation hereunder be assigned or transferred, by either Party without the written consent of the other Party. However, either Party

  
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may, without the other Party’s written consent, assign this Agreement and its rights and obligations hereunder in whole or in part to an Affiliate or to a party that acquires, by or
otherwise in connection with, merger, sale of assets or otherwise, all or substantially all of the business of the assigning Party to which the subject matter of this Agreement relates. The assigning Party shall remain responsible for
the performance by its assignee of this Agreement or any obligations hereunder so assigned. An assignment to an Affiliate shall terminate, and all rights so assigned shall revert to the assigning Party, if and when such Affiliate ceases to be an
Affiliate of the assigning Party. Any purported assignment in violation of this Section 14.1 shall be void. 
 14.2
Governing Law. This Agreement shall be construed and the respective rights of the Parties determined in accordance with the substantive Laws of the Commonwealth of Massachusetts, notwithstanding any provisions of Massachusetts Law or any
other Law governing conflicts of laws to the contrary, and the patent Laws of the relevant jurisdiction without reference to any rules of conflict of laws. 
 14.3 Jurisdiction. Each Party by its execution hereof, (a) hereby irrevocably submits to the jurisdiction of the United States District Court and state courts located in Boston,
Massachusetts for the purpose of any dispute arising between the Parties in connection with this Agreement (each, an “Action”) and (b) hereby waives to the extent not prohibited by applicable Law, and agrees not to assert, by
way of motion, as a defense or otherwise, in any such Action, any claim that it is not subject personally to the jurisdiction of the above-named court, that its property is exempt or immune from attachment or execution, that any such Action brought
in the above-named court should be dismissed on grounds of forum non conveniens, should be transferred or removed to any court other than the above-named court, or should be stayed by reason of the pendency of some other proceeding in any other
court other than the above-named court, or that this Agreement or the subject matter hereof may not be enforced in or by such court and (c) hereby agrees not to commence any such Action other than before the above-named court. Notwithstanding
the previous sentence a Party may commence any Action in a court other than the above-named court solely for the purpose of enforcing an order or judgment issued by the above-named court. 

14.4 Venue. Each Party agrees that for any Action between the Parties arising in whole or in part under or in
connection with this Agreement, such Party bring Actions only in the state and federal courts of the United States of America located in Boston, Massachusetts and any appellate court having jurisdiction over appeals from such courts. Each Party
further waives any claim and will not assert that venue should properly lie in any other location within the selected jurisdiction. 
 14.5 Entire Agreement; Amendments. This Agreement contains the entire understanding of the Parties with respect to the subject matter hereof, and supersedes all previous arrangements with
respect to the subject matter hereof, whether written or oral. This Agreement (including the Schedules hereto) may be amended, or any term hereof modified, only by a written instrument duly-executed by authorized representatives of both Parties
hereto. 

  
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 14.6 Severability. If any provision hereof should be held invalid, illegal or
unenforceable in any respect in any jurisdiction, the Parties hereto shall substitute, by mutual consent, valid provisions for such invalid, illegal or unenforceable provisions, which valid provisions in their economic effect are sufficiently
similar to the invalid, illegal or unenforceable provisions that it can be reasonably assumed that the Parties would have entered into this Agreement with such valid provisions. In case such valid provisions cannot be agreed upon, the invalid,
illegal or unenforceable of one or several provisions of this Agreement shall not affect the validity of this Agreement as a whole, unless the invalid, illegal or unenforceable provisions are of such essential importance to this Agreement that it is
to be reasonably assumed that the Parties would not have entered into this Agreement without the invalid, illegal or unenforceable provisions. 
 14.7 Headings. The captions to the Sections hereof are not a part of this Agreement, but are merely for convenience to assist in locating and reading the several Sections hereof. 

14.8 Waiver of Rule of Construction. Each Party has had the opportunity to consult with counsel in connection with the
review, drafting and negotiation of this Agreement. Accordingly, the rule of construction that any ambiguity in this Agreement shall be construed against the drafting Party shall not apply. 

14.9 Interpretation. Except where the context expressly requires otherwise, (a) the use of any gender herein shall be
deemed to encompass references to either or both genders, and the use of the singular shall be deemed to include the plural (and vice versa), (b) the words “include”, “includes” and “including” shall be deemed to
be followed by the phrase “without limitation” and shall not be interpreted to limit the provision to which it relates, (c) the word “will” shall be construed to have the same meaning and effect as the word
“shall”, (d) any definition of or reference to any agreement, instrument or other document herein shall be construed as referring to such agreement, instrument or other document as from time to time amended, supplemented or otherwise
modified (subject to any restrictions on such amendments, supplements or modifications set forth herein), (e) any reference herein to any Person shall be construed to include the Person’s successors and assigns, (f) the words
“herein”, “hereof” and “hereunder”, and words of similar import, shall be construed to refer to this Agreement in its entirety and not to any particular provision hereof, (g) all references herein to Sections,
Exhibits or Schedules shall be construed to refer to Sections, Exhibits or Schedules of this Agreement, and references to this Agreement include all Exhibits and Schedules hereto, (h) the word “notice” means notice in writing (whether
or not specifically stated) and shall include notices, consents, approvals and other written communications contemplated under this Agreement, (i) provisions that require that a Party, the Parties or any committee hereunder “agree,”
“consent” or “approve” or the like shall require that such agreement, consent or approval be specific and in writing, whether by written agreement, letter, approved minutes or otherwise (but excluding e-mail and instant
messaging), (j) references to any specific law, rule or regulation, or article, section or other division thereof, shall be deemed to include the then-current amendments thereto or any replacement or successor law, rule or regulation thereof,
and (k) the term “or” shall be interpreted in the inclusive sense commonly associated with the term “and/or.” 
 14.10 No Implied Waivers; Rights Cumulative. No failure on the part of Alnylam or Genzyme to exercise, and no delay in exercising, any right, power, remedy or privilege under

  
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this Agreement, or provided by statute or at Law or in equity or otherwise, shall impair, prejudice or constitute a waiver of any such right, power, remedy or privilege or be construed as a
waiver of any breach of this Agreement or as an acquiescence therein, nor shall any single or partial exercise of any such right, power, remedy or privilege preclude any other or further exercise thereof or the exercise of any other right, power,
remedy or privilege. 
 14.11 Notices. All notices which are required or permitted hereunder shall be in
writing and sufficient if delivered personally, sent by facsimile (and promptly confirmed by personal delivery, registered or certified mail or overnight courier), sent by nationally-recognized overnight courier or sent by registered or certified
mail, postage prepaid, return receipt requested, addressed as follows: 
  

			
	If to Alnylam, to:	  	 Alnylam Pharmaceuticals, Inc.

300 Third Street
 Cambridge, MA 02142

Attention: Vice President - Legal
 Facsimile No.:
(617) 551-8101

		
	With a copy to:	  	 WilmerHale LLP
 60 State
Street
 Boston, MA 02109
 Attention:
Steven D. Barrett, Esq.
 Facsimile No.: (617) 526-5000

		
	If to Genzyme, to:	  	 Genzyme Corporation
 500
Kendall Street
 Cambridge, Massachusetts 02142
 Attention: President of Rare Disease
 Facsimile No.: (617) 374-2424

		
	With a copy to:	  	 Genzyme Corporation
 500
Kendall Street
 Cambridge, Massachusetts 02142
 Attention: General Counsel
 Facsimile: (617) 252-7553

		
	And to:	  	 Ropes & Gray LLP

Prudential Tower
 800 Boylston Street

Boston, MA 02199-3600
 Attention: David M.
McIntosh, Esq.
 Facsimile No.: (617) 235-0507

 or to such other address as the Party to whom notice is to be given may have furnished to the other Party in writing in
accordance herewith. Any such notice shall be deemed to have been 

  
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given: (a) when delivered if personally delivered or sent by facsimile on a business day (or if delivered or sent on a non-business day, then on the next business day); (b) on receipt
if sent by overnight courier; and/or (c) on receipt if sent by mail. 
 14.12 Compliance with Export Regulations.
Neither Party shall export any technology licensed to it by the other Party under this Agreement except in compliance with U.S. export Laws and regulations. 
 14.13 Force Majeure. Neither Party shall be held liable to the other Party nor be deemed to have defaulted under or breached this Agreement for failure or delay in performing
any obligation under this Agreement to the extent that such failure or delay is caused by or results from causes beyond the reasonable control of the affected Party, potentially including embargoes, war, acts of war (whether war be declared or not),
insurrections, riots, civil commotions, strikes, lockouts or other labor disturbances, fire, floods, or other acts of God. The affected Party shall notify the other Party of such force majeure circumstances as soon as reasonably practical, and shall
promptly undertake all reasonable efforts necessary to cure such force majeure circumstances. 
 14.14 Independent
Contractors. It is expressly agreed that Alnylam and Genzyme shall be independent contractors and that the relationship between Alnylam and Genzyme shall not constitute a partnership, joint venture or agency. Alnylam shall not have the
authority to make any statements, representations or commitments of any kind, or to take any action, which shall be binding on Genzyme, without the prior written consent of Genzyme, and Genzyme shall not have the authority to make any statements,
representations or commitments of any kind, or to take any action, which shall be binding on Alnylam without the prior written consent of Alnylam. 
 14.15 Counterparts. The Agreement may be executed in two or more counterparts, including by facsimile or PDF signature pages, each of which shall be deemed an original, but all of which
together shall constitute one and the same instrument. 
 14.16 Performance by Affiliates. 

14.16.1 Each Party acknowledges and accepts that the other Party may exercise its rights and perform its obligations under this
Agreement either directly or through one or more of its Affiliates. A Party’s Affiliates will have the benefit of all rights (including all licenses) of such Party under this Agreement. Accordingly, in this Agreement “Genzyme” will be
interpreted to mean “Genzyme and/or its Affiliates” and “Alnylam” will be interpreted to mean “Alnylam and/or its Affiliates” where necessary to give each Party’s Affiliates the benefit of the rights provided to
such Party in this Agreement; provided, however, that in any event each Party will remain responsible for the acts and omissions, including financial liabilities, of its Affiliates. 

14.16.2 Notwithstanding Section 14.16.1 or anything to the contrary in this Agreement, in the event of (a) an
acquisition of a Party or its business or assets by a Third Party (an “Acquirer”) or (b) an acquisition by a Party of the business or assets of a Third Party that includes any program(s) of the acquired Third Party that, but
for this Section 14.16.2, would violate Section 10.5.1, which program(s) represent less than [**] percent ([**]%) of the value of 

  
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the acquired business or assets (an “Acquired Business”), in each case of (a) and (b) whether by merger, asset purchase or otherwise, then (i) as to any such
Acquirer, the non-acquired Party shall not obtain rights, licenses, options or access to any Patent Rights, Know-How or products that are held by the Acquirer or any Affiliate of the Acquirer that becomes an Affiliate of the acquired Party as a
result of such acquisition and that were not generated through any use or access to the Know-How or Patent Rights of the acquired Party and are not used by the acquired Party in connection with a Licensed Product; and (ii) as to any such
Acquirer or Acquired Business, the Acquirer or Acquired Business and any Affiliate of the Acquirer or Acquired Business that becomes an Affiliate of the acquired or acquiring Party as a result of such acquisition shall not be subject to the
restrictions in Section 10.5.1 as to programs for products of that such Acquirer, Acquired Business or Affiliate of such Acquirer or Acquired Business in existence prior to the closing date of such acquisition, or for the subsequent development
and commercialization of such products following the closing date of such acquisition. 
 14.17 Binding Effect; No Third
Party Beneficiaries. As of the Effective Date, this Agreement shall be binding upon and inure to the benefit of the Parties and their respective permitted successors and permitted assigns. Except as expressly set forth in this Agreement, no
person or entity other than the Parties and their respective Affiliates and permitted assignees hereunder shall be deemed an intended beneficiary hereunder or have any right to enforce any obligation of this Agreement. 

[THE REMAINDER OF THIS PAGE HAS BEEN LEFT INTENTIONALLY BLANK] 

  
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 IN WITNESS WHEREOF, the Parties have executed this Agreement as of the Effective Date.

  

									
	GENZYME CORPORATION	 		 	ALNYLAM PHARMACEUTICALS, INC.
					
	BY:	 	 /s/ David Meeker
	 		 	BY:	 	 /s/ John M. Maraganore

					
	NAME:	 	David Meeker, M.D.	 		 	NAME:	 	John M. Maraganore, Ph.D
					
	TITLE:	 	President and Chief Executive Officer	 		 	TITLE:	 	Chief Executive Officer

  
 Confidential

 Signature page to License and Collaboration Agreement 

by and between Alnylam Pharmaceuticals, Inc. and Genzyme Corporation, 

dated as of October 18, 2012 

 SCHEDULE 1.4 

ADDITIONAL ALNYLAM IN-LICENSES 
  

	•	 	 The License Agreement between Cancer Research Technology Ltd. and Alnylam, dated July 18, 2003. 

 

	•	 	 The agreement between the Board of Trustees of the Leland Stanford Junior University and Alnylam, dated September 17, 2003.

  
 Confidential

 SCHEDULE 1.7 

ALN-TTR02 
 ALN-TTR02 is
an investigational ribonucleic acid interference (RNAi) therapeutic agent that is comprised of active pharmaceutical ingredient ALN-[**] (see sequence & diagram below), a synthetic small interfering RNA (siRNA) that is targeted to the TTR
messenger RNA (mRNA) formulated in the AF-011 lipid nanoparticle (see description below). 
 [**] 

AF-011 lipid nanoparticle Description: 
 AF-011 is a multi-component particle comprised of: 
 MC3/DSPC/Cholesterol/PEG-DMG
(descriptions & diagrams below) in the following ratio: 
 50%/10%/38.5%/1.5% 
 MC3 
 (6Z,9Z,28Z,31Z)-heptatriaconta-6,9,28,31-tetraen-19-yl 4-(dimethylamino)butanoate

  
 

 
 CAS Name: (10Z,13Z)-1-(9Z,12Z)-9,12-octadecadien-1-yl-10,13-nonadecadien-1-yl-4
(dimethylamino)-butanoic acid ester 
 CAS Registry Number: 1224606-06-7 
 DSPC 
 1,2-Distearoyl-sn-glycero-3-phosphatidylcholine 

 
 

 
 CAS Name: 1,2-Dioctadecanoyl-sn-glycero-3-phosphocholine 

  
 Confidential

 CAS Registry Number: 816-94-4 
 Cholesterol 
  
 

 
 CAS Name: (3b)-Cholest-5-en-3-ol 

CAS Registry Number: 57-88-5 
 PEG-DMG
(mPEG2000-DMG; mPEG-DOMG) 
 (R)-2,3-bis(tetradecyloxy)propyl 1-(methoxy poly(ethylene glycol)2000)propylcarbamate 

 
 

 
 a-[3-[[[(2R)-2,3-Bis(tetradecyloxy)propoxy]carbonyl]amino]propyl]-w-(2-methoxyethoxy)- poly(oxy-1,2-ethanediyl) polymer 
 CAS Formula: (C2 H4 O)n
C38
H77 N O6 
 CAS Registry Number: 1301751-57-4 

  
 Confidential

 SCHEDULE 1.8 

ALN-TTRsc 
 ALN-TTRsc is an investigational ribonucleic acid interference (RNAi) therapeutic agent that is comprised of active pharmaceutical ingredient ALN-[**] (see sequence & diagram below), a synthetic
small interfering RNA (siRNA) that is targeted to the TTR messenger RNA (mRNA) and covalently linked on the 3’ end of the sense strand to a triantennary N-acetylgalactosamine (GalNAc3) ligand (see diagram below). 
 [**] 
 [**] 

  
 Confidential

 SCHEDULE 1.9 

ALNYLAM CORE TECHNOLOGY PATENTS 
 See attached. 

  
 Confidential

 1.9 Lipid-formulation 

 

																					
	[**]	  	 	  	 	  	 	  	 	  	 	  	 	  	 	  	 	  	 	  	 
	Our Ref. No.	  	Country	  	 Case
 Type
	  	Status	  	Application
No.	  	 Filing
 Date
	  	 Publication
 No.
	  	 Patent
 No.
	  	Title	  	 Alnylam
 Rights
	  	In
License
		  		  		  		  		  		  		  		  		  		  	
		  		  		  		  		  		  		  		  		  		  	
		  		  		  		  		  		  		  		  		  		  	
		  		  		  		  		  		  		  		  		  		  	

 Confidential materials omitted and filed separately with the Securities and Exchange Commission. A total of 18 pages were
omitted. [**] 

  
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 1.9 Lipid-formulation 

 

																					
	[**]	  	 	  	 	  	 	  	 	  	 	  	 	  	 	  	 	  	 	  	 
	Our Ref. No.	  	Country	  	 Case
 Type
	  	Status	  	Application
No.	  	Filing
Date	  	 Publication
 No.
	  	Patent
No.	  	Title	  	Alnylam
Rights	  	 In
 License

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	Our Ref. No.	  	Country	  	Case
Type	  	Status	  	Application
No.	  	Filing
Date	  	Publication
No.	  	Patent
No.	  	Title	  	Alnylam
Rights	  	In
License
	 [**]
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 1.9 Lipid-formulation 

 

																					
	CaseNumber	  	Country	  	Case
Type	  	Status	  	Application
No.	  	Filing
Date	  	Publication
No.	  	Patent
No.	  	Title	  	Alnylam
Rights	  	In
License
	[**]	  	 	  	 	  	 	  	 	  	 	  	 	  	 	  	 	  	 	  	 
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	CaseNumber	  	Country	  	Case
Type	  	Status	  	Application
No.	  	Filing
Date	  	Publication
No.	  	Patent
No.	  	Title	  	Alnylam
Rights	  	In
License
	[**]	  	 	  	 	  	 	  	 	  	 	  	 	  	 	  	 	  	 	  	 
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 Confidential

 1.9 Linker-Conjugate 

 

																					
	[**]	  	 	  	 	  	 	  	 	  	 	  	 	  	 	  	 	  	 	  	 
	Our Ref. No.	  	Country	  	Case
Type	  	Status	  	Application
No.	  	Filing
Date	  	Publication
No.	  	Patent
No.	  	Title	  	Alnylam
Rights	  	In
License
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	[**]	  	 	  	 	  	 	  	 	  	 	  	 	  	 	  	 	  	 	  	 
	Our Ref. No.	  	Country	  	Case
Type	  	Status	  	Application
No.	  	Filing
Date	  	Publication
No.	  	Patent
No.	  	Title	  	Alnylam
Rights	  	In
License
	 [**]
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 Confidential

 1.9 Manufacturing 

 

																					
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	Our Ref. No.	  	Country	  	Case
Type	  	Status	  	Application
No.	  	Filing
Date	  	Publication
No.	  	Patent
No.	  	Title	  	Alnylam
Rights	  	In
License
	 [**]
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 Confidential

 1.9 PBL 
  

																					
	[**]	  	 	  	 	  	 	  	 	  	 	  	 	  	 	  	 	  	 	  	 
	Our Ref. No.	  	Country	  	Case
Type	  	Status	  	Application
No.	  	Filing
Date	  	Publication
No.	  	Patent
No.	  	Title	  	Alnylam
Rights	  	In
License
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 Confidential

 1.9 PBL 
  

											
	 DocketNumber
	  	 Country
	  	 Application/Patent
 Number
	  	 Application
 Date
	  	 Title
	  	 Issue Date

		  		  		  		  		  	
		  		  		  		  		  	
		  		  		  		  		  	
		  		  		  		  		  	

 Confidential Materials omitted and filed separately with the Securities and Exchange Commission. A total of 29 pages were
omitted. [**] 

  
 Confidential

 SCHEDULE 1.16 

ALNYLAM PRODUCT-SPECIFIC PATENTS 
 See attached. 

  
 Confidential

																					
	[**]	  	 	  	 	  	 	  	 	  	 	  	 	  	 	  	 	  	 	  	 
	Our Ref. No.	  	Country	  	Case
Type	  	Status	  	Application
No.	  	Filing
Date	  	Publication
No.	  	Patent
No.	  	Title	  	Alnylam
Rights	  	In
License
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	[**]	  	 	  	 	  	 	  	 	  	 	  	 	  	 	  	 	  	 	  	 
	Our Ref. No.	  	Country	  	Case
Type	  	Status	  	Application
No.	  	Filing
Date	  	Publication
No.	  	Patent
No.	  	Title	  	Alnylam
Rights	  	In
License
	 [**]
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	[**]	  	 	  	 	  	 	  	 	  	 	  	 	  	 	  	 	  	 	  	 
	Our Ref. No.	  	Country	  	Case
Type	  	Status	  	Application
No.	  	Filing
Date	  	Publication
No.	  	Patent
No.	  	Title	  	Alnylam
Rights	  	In
License
	 [**]
	  	[**]	  	[**]	  	[**]	  		  		  		  		  	[**]	  	[**]	  	[**]
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 Confidential

																					
	[**]	  	 	  	 	  	 	  	 	  	 	  	 	  	 	  	 	  	 	  	 
	Our Ref. No.	  	Country	  	Case
Type	  	Status	  	Application
No.	  	Filing
Date	  	Publication
No.	  	Patent
No.	  	Title	  	Alnylam
Rights	  	In
License
	 [**]
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	[**]	  	 	  	 	  	 	  	 	  	 	  	 	  	 	  	 	  	 	  	 
	Our Ref. No.	  	Country	  	Case
Type	  	Status	  	Application
No.	  	Filing
Date	  	Publication
No.	  	Patent
No.	  	Title	  	Alnylam
Rights	  	In
License
	 [**]
	  	[**]	  	[**]	  	[**]	  	[**]	  	[**]	  	[**]	  	[**]	  	[**]	  	[**]	  	
	 [**]
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	[**]	  	 	  	 	  	 	  	 	  	 	  	 	  	 	  	 	  	 	  	 
	Our Ref. No.	  	Country	  	Case
Type	  	Status	  	Application
No.	  	Filing
Date	  	Publication
No.	  	Patent
No.	  	Title	  	Alnylam
Rights	  	In
License
	 [**]
	  	[**]	  	[**]	  	[**]	  	[**]	  	[**]	  	[**]	  	[**]	  	[**]	  	[**]	  	

  
 Confidential

 SCHEDULE 1.47 

EXISTING ALNYLAM IN-LICENSES 
 A. As of the Effective Date, Existing Alnylam In-Licenses includes the following Third Party agreements: 
  

	1.	Amended and Restated Strategic Collaboration and License Agreement between Isis Pharmaceuticals, Inc. and Alnylam Pharmaceuticals, Inc., dated April 28, 2009, as
amended by letter agreement dated August     , 2012. 

  

	2.	Co-Exclusive License Agreement between Max Planck Innovation GmbH (formerly Garching Innovation GmbH) and Alnylam Pharmaceuticals, Inc., dated December 20, 2002,
as amended by Amendment dated July 2, 2003, the Requirements Amendment effective June 15, 2005, the Waiver Amendment effective August 9, 2007 and the Amendment to the Alnylam Co-Exclusive License Agreement dated as of March 14,
2011, by and between Alnylam Pharmaceuticals, Inc., on the one hand, and Whitehead Institute for Biomedical Research, Massachusetts Institute of Technology and Max-Planck-Innovation GmbH, on the other hand; and Co-Exclusive License Agreement between
Max Planck Innovation GmbH (formerly Garching Innovation GmbH) and Alnylam Europe AG (formerly Ribopharma AG), dated June 30, 2003. 

  

	3.	Amended and Restated Cross-License Agreement between Alnylam Pharmaceuticals, Inc. and Protiva Biotherapeutics Inc., effective May 30, 2008, as amended by
Amendment No. 1 effective October 25, 2010. 

  

	4.	Amended and Restated License and Collaboration Agreement between Tekmira Pharmaceuticals Corporation and Alnylam Pharmaceuticals, Inc., effective May 30, 2008.

  

	5.	Sponsored Research Agreement among Alnylam Pharmaceuticals, Inc., The University of British Columbia, and AlCana Technologies, Inc., dated July 27, 2009, as
amended by Amendment No. 1 dated July 27, 2011, and as supplemented by the Supplemental Agreement among Alnylam Pharmaceuticals, Inc., Tekmira Pharmaceuticals Corporation, Protiva Biotherapeutics Inc., The University of British Columbia,
and AlCana Technologies, Inc., effective July 27, 2009. 

  
 Confidential

 SCHEDULE 1.52 

FIRST PHASE II SUCCESS OBJECTIVES 
 [**] 

  
 Confidential

 SCHEDULE 2.2.1 

GLOBAL DEVELOPMENT STRATEGY 
 See attached. 

 Confidential Materials omitted and filed separately with the Securities and Exchange Commission. A total of
2 pages were omitted. [**] 
  

					
		 	Confidential	 	

 SCHEDULE 2.2.2 

ALNYLAM TERRITORY DEVELOPMENT PLAN 
 See attached. 

 Confidential Materials omitted and filed separately with the Securities and Exchange
Commission. A total of 5 pages were omitted. [**] 
  

					
		 	Confidential	 	

 SCHEDULE 2.2.3 

GENZYME TERRITORY DEVELOPMENT PLAN 
 (To be attached when developed pursuant to Section 2.2.3.) 

 SCHEDULE 6.1 

SUPPLY AGREEMENT TERMS 
  

	1.	Overview. Both the Clinical Supply Agreement and the Commercial Supply Agreement will provide for the manufacture and supply of Bulk Drug
Substance, Bulk Drug Product, and/or Finished Product forms of Licensed Products (each a “Product” and collectively “Products”) on commercially reasonable terms customary to Third Party contract manufacturing
organization supply agreements for pharmaceuticals that are consistent with the principles set forth below. Genzyme may elect, on the terms to be set forth in one or more Clinical Supply Agreements and one or more Commercial Supply Agreements to be
negotiated by the Parties, which shall be consistent with the principles set forth in the Agreement and in this Schedule 6.1, for Alnylam to supply, either itself or through an Affiliate or Third Party manufacturer (including, in cases where
a Third Party manufacturer is being used, facilitating arrangements where Genzyme may order directly from the Third Party manufacturer in lieu of ordering through Alnylam, if appropriate), any Product that Alnylam is manufacturing or having
manufactured for the Alnylam Territory. Genzyme may also elect for Alnylam to provide technology transfer on the terms set forth in Section 6.2 of the Agreement. 

 

	 	a.	“Bulk Drug Substance” means an siRNA Product in bulk form manufactured for use as an active pharmaceutical ingredient in a Licensed Product. For the
avoidance of doubt, (a) as to ALN-TTR02, Bulk Drug Substance is siRNA duplex AD [**], which may be separately manufactured and therefore may be separately supplied to Genzyme by Alnylam under a Supply Agreement, and (b) as to ALN-TTRsc,
Bulk Drug Substance is siRNA duplex AD [**] conjugated to a GalNAc Conjugate. 

  

	 	b.	“Bulk Drug Product” means a formulated Bulk Drug Substance, in bulk form prior to filling and finishing. For the avoidance of doubt, (a) as to
ALN-TTR02, Bulk Drug Product is siRNA duplex AD [**] formulated in an AF11 Lipid Nanoparticle Formulation, and (b) as to ALN-TTRsc, Bulk Drug Product is siRNA Duplex AD [**] conjugated to a Ga1NAc Conjugate, in water for injection.

  

	 	c.	“Finished Product” means a Licensed Product in Bulk Drug Product form, filled into unit packages including final labeling and packaging.

  

	2.	 Assumptions. This Schedule 6.1 is based on the assumption that Alnylam will be performing or managing the manufacture and
supply of Product for use and sale throughout the Alnylam Territory. If Alnylam is not sourcing a Product for the Alnylam Territory, Alnylam shall not be obligated 2to establish a supply chain solely for Genzyme’s benefit, but in such case
Alnylam will cooperate with Genzyme’s efforts to establish its own supply chain as set forth in Section 6.2 of the Agreement. The Parties also assume that Alnylam’s Cost of Goods for Bulk Drug Product will not be greater than

	 	
$[**] per gram from [**] and not greater than $[**] per gram from [**] and thereafter. If these assumptions are not correct, the Parties will re-evaluate the applicable terms set forth herein.
Notwithstanding the foregoing, Alnylam makes no guarantee as to Alnylam’s Cost of Goods and, unless otherwise agreed by the Parties in an applicable Clinical Supply Agreement or Commercial Supply Agreement, the Supply Price shall be determined
as described below. For the avoidance of doubt, the intent of the Parties is that any Clinical Supply Agreement or Commercial Supply Agreement that the Parties enter into in which Alnylam may be obligated to supply Genzyme will be structured so that
Alnylam does not bear any liability to Genzyme for a Third Party manufacturer’s failure to meet its obligations beyond the actual amounts (net of Alnylam’s enforcement costs), if any, recovered by Alnylam from such Third Party for such
failure. 

  

	3.	Supply of Licensed Product. 

  

	 	a.	Supply Obligation. At Genzyme’s election, Alnylam will supply Bulk Drug Substance, Bulk Drug Product, and/or Finished Product to Genzyme in
accordance with the Supply Agreement(s) to be negotiated by the Parties consistent with the principles set forth in this Schedule 6.1. 

  

	 	b.	Supply Price. 

  

	 	i.	Genzyme shall pay to Alnylam a per unit “Supply Price” with respect to supply of Product, which Supply Price will be equivalent to the following:

  

	 	1.	Product that Alnylam Does Not Manufacture Itself. Any Product manufactured by Alnylam’s Third Party manufacturers and supplied by Alnylam to Genzyme will be
supplied at a price equal to the Product’s Cost of Goods plus [**]%. 

  

	 	2.	Product that Alnylam Does Manufacture Itself. Any Product manufactured by Alnylam or its Affiliates and supplied to Genzyme will be supplied at a price equal to
the Product’s Cost of Goods plus [**]%. 

 Agreement Mechanics. The Supply Agreement will contain a
mechanism by which the Parties determine and agree upon a per unit Supply Price for each Product for the upcoming Calendar Year (“Estimated Supply Price”). At the end of each Calendar Year, the Parties will compare the Estimated
Supply Prices with the Supply Prices as determined by Alnylam’s actual Cost of Goods for the Products during such Calendar Year (the “Actual Supply Price”). Genzyme or Alnylam, as applicable, will thereafter make a payment to
the other in order to reconcile the Estimated Supply Price paid with the Actual Supply Price during that Calendar Year. The Supply Agreement will also contain appropriate audit provisions, including to verify the amounts and calculations described
in this Section. 
  

	 	ii.	 “Cost of Goods” means, with respect to the supply of Product, the reasonable internal and external costs Alnylam and its Affiliates
incurred 

	 	
in Manufacturing or having Manufactured such Product, including: (a) to the extent that such Product is Manufactured by Alnylam or its Affiliates, the fully allocated cost of Manufacture of
such Product, consisting of direct material and direct labor costs, plus Manufacturing overhead attributable to such Product (including facilities start-up costs, all directly incurred Manufacturing variances and a reasonable allocation of related
Manufacturing administrative and facilities costs and depreciation for such Product, but excluding corporate administrative overhead and/or costs associated with excess capacity), all calculated strictly in accordance with GAAP, and (b) to the
extent that such Product is Manufactured by a Third Party manufacturer, the actual fees paid by Alnylam and its Affiliates to the Third Party for the Manufacture, supply and packaging of such Product. 

 

	 	c.	Genzyme Territory Process Development Costs. If Genzyme requests any change to the specifications or Manufacturing process for the supply of
Product for the Genzyme Territory, Alnylam will use Commercially Reasonable Efforts to make such changes, and if the changes are not also required for the Alnylam Territory, Genzyme will bear one hundred percent (100%) of such costs.

  

	 	d.	Forecasts. On a Calendar Quarterly basis Genzyme will provide rolling [**] Calendar Quarter forecasts for its orders of supply of Product. The
first [**] Calendar Quarters of any forecast will constitute a firm obligation for Genzyme to issue purchase orders for the forecasted amount of Product. Notwithstanding the foregoing, to the extent that Alnylam is supplying through a Third Party
manufacturer, Genzyme shall be required to comply with the forecasting and ordering provisions of Alnylam’s agreement with the Third Party manufacturer. 

 

	 	e.	Specifications. The Supply Agreements will contain mutually agreed written specifications for the Bulk Drug Substance, Bulk Drug Product and
Finished Product, as applicable. 

  

	4.	Third Party Manufacturing Agreements. The Clinical Supply Agreement(s) and Commercial Supply Agreement(s) shall include provisions
(a) requiring Alnylam to reasonably consult with Genzyme through the JSC regarding proposed supply agreements to be entered into between Alnylam and Third Party Manufacturers to the extent Products to be supplied to Genzyme will be manufactured
under such Third Party supply agreements; and (b) requiring Alnylam to use commercially reasonable efforts to include in applicable supply agreements with Third Party manufacturers rights for Genzyme to enforce such agreements against such
Third Parties as such agreements relate to the supply of Product(s) for the Genzyme Territory, including by identifying Genzyme as a third party beneficiary under such agreements, and if Alnylam is not able to negotiate such third party beneficiary
rights for Genzyme’s benefit, provisions requiring Alnylam to enforce such Third Party supply agreements at Genzyme’s direction and expense as such agreements relate to the supply of the applicable Product(s) for the Genzyme Territory.

	5.	Term and Termination. The Clinical Supply Agreement will continue in effect through the completion of Clinical Studies in the Genzyme Territory.
The Commercial Supply Agreement will have a term of at least three (3) years with yearly renewals at Genzyme’s option term for two (2) additional years, each such renewal option to be exercised by providing Alnylam at least twelve
(12) months written notice prior to the expiration of the then-current term. The Supply Agreements will contain customary termination provisions. Genzyme will have the right to terminate each Supply Agreement for convenience on at least twelve
(12) months advanced written notice. Alnylam will have the right to terminate each Supply Agreement on at least twelve (12) months advanced written notice (or such longer period of time as reasonably necessary to avoid a supply disruption)
if Alnylam determines to cease sourcing the applicable Product for the Alnylam Territory, but in such case Alnylam will cooperate with Genzyme to enable Genzyme to establish its own source for the Product (including, to the extent requested by
Genzyme and within Alnylam’s ability to do so, by transferring Alnylam’s applicable Third Party manufacturing relationships to Genzyme). The Supply Agreements will terminate immediately upon termination of the Agreement. Notwithstanding
the foregoing, to the extent that Alnylam is supplying through a Third Party manufacturer, Genzyme’s termination rights may be subject to limitations on termination set forth in Alnylam’s agreement with the Third Party manufacturer. Unless
otherwise agreed by the Parties, following termination Genzyme shall remain obligated to purchase any orders of Product that have become firm orders prior to termination. 

 

	6.	Compliance, Warranties, Acceptance, Recalls, Indemnification and Limitations of Liability. The Supply Agreements will contain terms and conditions
regarding compliance with Laws (including cGMPs and the Regulatory Approvals for the Licensed Products) and specifications for the Licensed Products, delivery, acceptance, recalls, indemnification and limitations of liability that are customary in
Third Party contract manufacturing agreements. In any event, Alnylam shall not be required to provide warranties or indemnification that are more extensive than Third Party contract manufacturers typically provide and, with respect to Products not
manufactured by Alnylam, Alnylam shall not have obligations to Genzyme under any Supply Agreement for such Product that are greater than the obligations that Alnylam’s supplier of such Product has to Alnylam. 

 

	7.	Shortages, Inventory, Backup Suppliers. The Supply Agreements will provide that in the event Alnylam is unable to supply Product to meet the demand in the
combined Alnylam Territory and Genzyme Territory, then it will allocate Product between the two Territories on a pro rata basis based on forecasts of demand in the two Territories existing at the time of the shortfall. The Supply Agreements may also
contain provisions requiring Alnylam to maintain backup suppliers and appropriate levels of Product inventory as agreed by the Parties; provided that, Alnylam may require that Genzyme purchase safety stock of Product in exchange for
Alnylam’s agreement to maintain such safety stock in inventory. 

  

	 	8.	Miscellaneous. The Supply Agreements will contain other customary terms and provisions for agreements of their type as mutually agreed by the
Parties. 

 SCHEDULE 7.4.3.2 

BASEBALL ARBITRATION PROCEDURE REGARDING JPAC/LP MILESTONE 

ALLOCATION 

Selection of Expert and Submission of Positions. The Parties shall select and agree upon a mutually acceptable independent Third Party
expert who is neutral, disinterested and impartial, and has experience relevant to the valuation of pharmaceutical and biotechnology industry license agreements (the “Expert”). If the Parties are unable to mutually agree upon an
Expert within [**] days following the delivery of the Expert Resolution Notice, then upon request by either Party, the Expert shall be an arbitrator appointed by Judicial and Mediation Services (“JAMS”), which arbitrator need not
have the above-described experience. Once the Expert has been selected, each Party shall within [**] days following selection of the Expert provide the Expert and the other Party with a written report setting forth its position with respect to the
substance of the dispute and may submit a revised or updated report and position to the Expert within [**] days of receiving the other Party’s report. If so requested by the Expert, each Party shall make oral submissions to the Expert based on
such Party’s written report, and each Party shall have the right to be present during any such oral submissions. 
 JAMS
Supervision. In the event the Expert is a JAMS arbitrator selected by JAMS as provided in this Schedule 7.4.3.2 above, the matter shall be conducted as a binding arbitration in accordance with JAMS procedures, as modified by this Schedule
7.4.3.2 (including that the arbitrator shall adopt as his or her decision the position of one Party or the other, as described below). In such event, the arbitrator may retain a Third Party expert with experience relevant to the valuation of
pharmaceutical and biotechnology industry license agreements to assist in rendering such decision, and the expenses of any such expert shall be shared by the Parties as costs of the arbitration as provided in this Schedule 7.4.3.2 below. 

Determination by the Expert. The Expert shall, no later than [**] days after the last submission of the written reports and, if any, oral
submissions, select one of the Party’s positions as his or her final decision, and shall not have the authority to modify either Party’s position or render any substantive decision other than to so select the position of either Genzyme or
Alnylam as set forth in their respective written report (as initially submitted, or as revised in accordance with this Schedule 7.4.3.2 above, as applicable). The Parties agree that the decision of the Expert shall be the sole, exclusive and binding
remedy between them regarding any the allocation of JPAC/LP Milestone payments, and the Expert’s decision shall become the decision of the JSC on the matter. 
 Location; Costs. Unless otherwise mutually agreed upon by the Parties, the in-person portion (if any) of such proceedings shall be conducted in Boston, Massachusetts. The Parties agree that
they shall share equally the costs and fees of the Expert in connection with any proceeding under this Schedule 7.4.3.2, including the cost of the arbitration filing and hearing fees, the cost of any independent expert retained by the arbitrator and
the cost of the arbitrator and administrative fees of JAMS if applicable. Each Party shall bear its own costs and attorneys’ and witnesses’ fees and associated costs and expenses incurred in connection with any proceeding under this
Schedule 7.4.3.2. 

 Timetable for Completion in [**] Days. The Parties shall use, and shall direct the
Expert to use, commercially reasonable efforts to resolve a dispute within [**] days after the selection of the Expert, or if resolution within [**] days is not reasonably achievable, as determined by the Expert, then as soon thereafter as is
reasonably practicable. 

 SCHEDULE 9.2.2(A) 

JOINT PRESS RELEASE 
  

 
  

			
	Contacts:	  	
	 Alnylam Pharmaceuticals, Inc. 
 Cynthia Clayton
 Vice President, Investor Relations and

Corporate Communications

617-551-8207
	  	 Genzyme 
 Lori
Gorski
 Director

Corporate Communications

617-768-9344

		
	 Amanda Sellers (Media)

Spectrum
 202-955-6222 x2597
	  	

 Alnylam and Genzyme Form Alliance to Develop and Commercialize 

RNAi Therapeutics in Asia 
 - Genzyme to Advance ALN-TTR02 and ALN-TTRsc Programs as Breakthrough Therapies for 
 Patients with ATTR in Japan and in the Broader Asian Market - 
 - Alnylam
to Receive $22.5 Million in Upfront Payment in Addition to Milestone Payments 
 and Royalties on Product Sales;

 Alnylam Maintains All Rights in U.S., Europe, and Rest of World - 

Cambridge, Mass., October 22, 2012, 2012 - Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY) and Genzyme, a Sanofi company
(EURONEXT: SAN and NYSE: SNY), announced today that they have formed an exclusive alliance to develop and commercialize RNAi therapeutics targeting transthyretin (TTR) for the treatment of transthyretin-mediated amyloidosis (ATTR) in Japan and other
Asia-Pacific countries. ATTR is a rare, debilitating, hereditary disease that damages the nervous system and heart, resulting in a life expectancy of 5 to 15 years. 
 “Our ALN-TTR program holds promise as a breakthrough therapy for the treatment of ATTR, a debilitating orphan disease. As the lead program in our ‘Alnylam 5x15’ product strategy, we also
view this program as a key part of building Alnylam for the future,” said John Maraganore, Ph.D., Chief Executive Officer of Alnylam. “In this important collaboration, Genzyme will advance our ALN-TTR program with their proven capabilities
in the Japanese and broader Asian market, while we maintain our plans to develop and commercialize this potential breakthrough medicine in the U.S., Europe, and rest of world. In addition, a key part of the value proposition in this alliance for
Alnylam is the potential for significant royalty payments on sales of products.” 

  
 Confidential

 ATTR is an endemic disease in Japan, with a significant number of patients carrying the V30M TTR mutation
which leads to onset of a severe form of ATTR known as familial amyloidotic polyneuropathy (FAP). Together, Alnylam and Genzyme intend to maximize the value of ALN-TTR worldwide by developing the program in FAP and other ATTR indications, such as
familial amyloidotic cardiomyopathy (FAC) and senile systemic amyloidosis (SSA). Alnylam’s ALN-TTR program currently includes ALN-TTR02, which is in a Phase II clinical trial, and ALN-TTRsc, a subcutaneously administered RNAi therapeutic in
late stage pre-clinical development. 
 Under the terms of the agreement, Genzyme will make an upfront cash payment of $22.5 million to Alnylam.
The agreement also includes development milestone payments and tiered royalties expected to yield an effective rate in the mid-teens to mid-twenties on Genzyme’s sales of ALN-TTR products in their territory. In addition, each party will be
responsible for the development and commercialization activities in their respective territories. 
 “We are encouraged by Alnylam’s
progress with their ALN-TTR program and are excited by the potential for this innovative drug candidate to make a difference in the lives of patients with ATTR. The results to date demonstrate impressive clinical activity and support advancement of
this promising therapeutic into pivotal studies and toward the market,” said David Meeker, M.D., President and Chief Executive Officer of Genzyme. “As we work to build our pipeline through both internal research and development, and
through external collaborations, we look forward to working with Alnylam on this important program.” 
 Recently, Alnylam presented
positive clinical results from its ALN-TTR02 Phase I trial demonstrating robust and unprecedented knockdown of serum TTR protein levels of up to 94%; the overall results were highly significant (p<0.00001 by ANOVA). Suppression of TTR, the
disease-causing protein in ATTR, was found to be rapid, dose dependent, durable, and specific after just a single dose. The drug was generally safe and well tolerated in this Phase I study. Alnylam is currently enrolling patients in a Phase II
multi-dose study of ALN-TTR02 in ATTR patients and aims to initiate a Phase III pivotal study of ALN-TTR02 by the end of 2013. 
 About ATTR

 Transthyretin (TTR)-mediated amyloidosis (ATTR) is a hereditary, systemic disease caused by mutations in the TTR gene. TTR protein is
produced primarily in the liver and is normally a carrier for thyroid hormones and retinol binding proteins. Mutations in TTR cause abnormal amyloid proteins to accumulate and damage body organs and tissue, such as the peripheral nerves and heart,
resulting in intractable peripheral sensory neuropathy, autonomic neuropathy, and/or cardiomyopathy. ATTR represents a major unmet medical need with significant morbidity and mortality; FAP affects approximately 10,000 people worldwide and FAC
affects at least 40,000 people worldwide. FAP patients have a mean life expectancy of five to 15 years from symptom onset, and the only treatment options for early stage disease are liver transplantation and tafamidis (approved in Europe). As a
result, there is a significant need for novel therapeutics to treat patients who have inherited mutations in the TTR gene. 

 About RNA Interference (RNAi) 
 RNAi (RNA interference) is a revolution in biology, representing a breakthrough in understanding how genes are turned on and off in cells, and a completely new approach to drug discovery and development.
Its discovery has been heralded as “a major scientific breakthrough that happens once every decade or so,” and represents one of the most promising and rapidly advancing frontiers in biology and drug discovery today which was awarded the
2006 Nobel Prize for Physiology or Medicine. RNAi is a natural process of gene silencing that occurs in organisms ranging from plants to mammals. By harnessing the natural biological process of RNAi occurring in our cells, the creation of a major
new class of medicines, known as RNAi therapeutics, is on the horizon. Small interfering RNA (siRNA), the molecules that mediate RNAi and comprise Alnylam’s RNAi therapeutic platform, target the cause of diseases by potently silencing specific
mRNAs, thereby preventing disease-causing proteins from being made. RNAi therapeutics have the potential to treat disease and help patients in a fundamentally new way. 
 About Alnylam Pharmaceuticals 
 Alnylam is a biopharmaceutical company developing novel
therapeutics based on RNA interference, or RNAi. The company is leading the translation of RNAi as a new class of innovative medicines with a core focus on RNAi therapeutics for the treatment of genetically defined diseases, including ALN-TTR for
the treatment of transthyretin-mediated amyloidosis (ATTR), ALN-AT3 for the treatment of hemophilia, ALN-PCS for the treatment of severe hypercholesterolemia, ALN-HPN for the treatment of refractory anemia, and ALN-TMP for the treatment of
hemoglobinopathies. As part of its “Alnylam 5x15TM” strategy, the company expects to have five RNAi therapeutic products for genetically defined diseases in clinical development, including programs in advanced stages, on its own or with a
partner by the end of 2015. Alnylam has additional partnered programs in clinical or development stages, including ALN-RSV01 for the treatment of respiratory syncytial virus (RSV) infection, ALN-VSP for the treatment of liver cancers, and ALN-HTT
for the treatment of Huntington’s disease. The company’s leadership position on RNAi therapeutics and intellectual property have enabled it to form major alliances with leading companies including Merck, Medtronic, Novartis, Biogen Idec,
Roche, Takeda, Kyowa Hakko Kirin, Cubist, Ascletis, Monsanto and Genzyme. In addition, Alnylam and Isis co-founded Regulus Therapeutics Inc., a company focused on discovery, development, and commercialization of microRNA therapeutics; Regulus has
formed partnerships with GlaxoSmithKline, Sanofi, AstraZeneca and Biogen Idec. Alnylam has also formed Alnylam Biotherapeutics, a division of the company focused on the development of RNAi technologies for applications in biologics manufacturing,
including recombinant proteins and monoclonal antibodies. Alnylam’s VaxiRNATM platform applies RNAi technology to improve the manufacturing processes for vaccines; GlaxoSmithKline is a collaborator in this effort. Alnylam scientists and
collaborators have published their research on RNAi therapeutics in over 100 peer-reviewed papers, including many in the world’s top scientific journals such as Nature, Nature Medicine, Nature Biotechnology, and Cell. Founded in
2002, Alnylam maintains headquarters in Cambridge, Massachusetts. For more information, please visit www.alnylam.com. 
 Alnylam
Forward-Looking Statements 
 Various statements in this release concerning Alnylam’s future expectations, plans and prospects,
including without limitation, statements regarding Alnylam’s views with respect to the 

 
potential for RNAi therapeutics, including the potential for ALN-TTR02 and ALN-TTRsc, its expectations regarding the receipt upfront, and potential development milestone and royalty payments
under the Genzyme agreement, its expectations regarding the market opportunity for ALN-TTR, including in Japan, its expectations with respect to the timing and success of its clinical trials for ALN-TTR02, including the possible initiation of a
Phase III pivotal trial, and the expected timing of an IND filing for ALN-TTRsc, and Alnylam’s expectations regarding its “Alnylam 5x15” product strategy, constitute forward-looking statements for the purposes of the safe harbor
provisions under The Private Securities Litigation Reform Act of 1995. Actual results may differ materially from those indicated by these forward-looking statements as a result of various important factors, including, without limitation,
Genzyme’s ability to successfully advance ALN-TTR02 and/or ALN-TTRsc in Japan and other Asian countries including China, Australia, and India, as well as Alnylam’s ability to develop ALN-TTR02 and/or ALN-TTRsc in the rest of the world,
resulting in the potential payment of development milestones and royalties to Alnylam, Alnylam’s ability to successfully demonstrate the efficacy and safety of its drug candidates, the pre-clinical and clinical results for these product
candidates, which may not support further development of such product candidates, actions of regulatory agencies, which may affect the initiation, timing and progress of clinical trials for such product candidates, obtaining, maintaining and
protecting intellectual property, obtaining regulatory approval for products, competition from others using technology similar to Alnylam’s and others developing products for similar uses, and Alnylam’s ability to establish and maintain
strategic business alliances, including its collaboration with Genzyme, and new business initiatives, as well as those risks more fully discussed in the “Risk Factors” section of its most recent quarterly report on Form 10-Q on file with
the Securities and Exchange Commission. In addition, any forward-looking statements represent Alnylam’s views only as of today and should not be relied upon as representing its views as of any subsequent date. Alnylam does not assume any
obligation to update any forward-looking statements. 
 About Genzyme, a Sanofi Company 

Genzyme has pioneered the development and delivery of transformative therapies for patients affected by rare and debilitating diseases for over 30 years.
We accomplish our goals through world-class research and with the compassion and commitment of our employees. With a focus on rare diseases and multiple sclerosis, we are dedicated to making a positive impact on the lives of the patients and
families we serve. That goal guides and inspires us every day. Genzyme’s portfolio of transformative therapies, which are marketed in countries around the world, represents groundbreaking and life-saving advances in medicine. As a Sanofi
company, Genzyme benefits from the reach and resources of one of the world’s largest pharmaceutical companies, with a shared commitment to improving the lives of patients. Learn more at www.genzyme.com. 

Sanofi Forward Looking Statements 

This press release contains forward-looking statements as defined in the Private Securities Litigation Reform Act of 1995, as amended. Forward-looking
statements are statements that are not historical facts. These statements include projections and estimates and their underlying assumptions, statements regarding plans, objectives, intentions and expectations with respect to future financial
results, events, operations, services, product development and potential, and statements regarding future performance. Forward-looking statements are generally identified by the words “expects”, “anticipates”,
“believes”, “intends”, “estimates”, “plans” and similar 

 
expressions. Although Sanofi’s management believes that the expectations reflected in such forward-looking statements are reasonable, investors are cautioned that forward-looking information
and statements are subject to various risks and uncertainties, many of which are difficult to predict and generally beyond the control of Sanofi, that could cause actual results and developments to differ materially from those expressed in, or
implied or projected by, the forward-looking information and statements. These risks and uncertainties include among other things, the uncertainties inherent in research and development, future clinical data and analysis, including post marketing,
decisions by regulatory authorities, such as the FDA or the EMA, regarding whether and when to approve any drug, device or biological application that may be filed for any such product candidates as well as their decisions regarding labelling and
other matters that could affect the availability or commercial potential of such product candidates, the absence of guarantee that the product candidates if approved will be commercially successful, the future approval and commercial success of
therapeutic alternatives, the Group’s ability to benefit from external growth opportunities, trends in exchange rates and prevailing interest rates, the impact of cost containment policies and subsequent changes thereto, the average number of
shares outstanding as well as those discussed or identified in the public filings with the SEC and the AMF made by Sanofi, including those listed under “Risk Factors” and “Cautionary Statement Regarding Forward-Looking
Statements” in Sanofi’s annual report on Form 20-F for the year ended December 31, 2011. Other than as required by applicable law, Sanofi does not undertake any obligation to update or revise any forward-looking information or
statements. 

 SCHEDULE 10.2 

DISCLOSURE SCHEDULE 

Section 10.2.1: 
 - Reference is
made to certain claims alleged by the plaintiffs in the action entitled: 
 [**] 
 - Reference is made to certain claims alleged by the plaintiff in the action entitled: 
 [**]

 Section 10.2.2: 
 -
Reference is made to certain claims alleged by the plaintiffs in the [**] Litigation. 
 - Reference is made to certain claims alleged by the
plaintiff in the [**] Litigation. 
 Section 10.2.4: 
 - Reference is made to certain claims alleged by the plaintiffs in the [**] Litigation. 

Section 10.2.6: 
 - Reference is
made to certain claims alleged by the plaintiffs in the [**] Litigation. 
 - Reference is made to certain claims alleged by the plaintiff in
the [**] Litigation. 
 Section 10.2.7: 
 - Reference is made to certain claims alleged by the plaintiffs in the [**] Litigation. 
 -
Reference is made to certain claims alleged by the plaintiff in the [**] Litigation. 
 Section 10.2.8: 

- Reference is made to certain claims alleged by the plaintiffs in the [**] Litigation. 
 Section 10.2.11: 
 - Reference is made to certain claims alleged by the plaintiffs in
the [**] Litigation. 

  
 Confidential

 Section 10.2.12(a): 
 - Reference is made to certain claims alleged by the plaintiffs in the [**] Litigation. 
 -
Reference is made to certain claims alleged by the plaintiff in the [**] Litigation. 
 Section 10.2.12(b): 

- Reference is made to the [**]. 

  
 Confidential

 AMENDMENT TO LICENSE AND COLLABORATION AGREEMENT 

THIS AMENDMENT TO LICENSE AND COLLABORATION
AGREEMENT (this “Amendment”) is entered into as of February 19, 2013 (the “Amendment Effective Date”), by and between ALNYLAM PHARMACEUTICALS,
INC., a Delaware corporation (“Alnylam”) and GENZYME CORPORATION, a Massachusetts corporation (“Genzyme”). 

BACKGROUND 
 A. Alnylam and Genzyme are parties to a License and Collaboration Agreement dated as of October 18, 2012 (the “Collaboration Agreement”).  

B. Following the Effective Date, Alnylam resolved certain disputes regarding intellectual property and technology that relate to the
subject matter of the Collaboration Agreement. 
 C. As part of that resolution, Alnylam terminated the Amended and Restated
Cross-License Agreement between Alnylam and Protiva Biotherapeutics Inc., (“Protiva”) effective May 30, 2008, as amended by Amendment No. 1 effective October 25, 2010 (the “Protiva License”) and the
Amended and Restated License and Collaboration Agreement between Tekmira Pharmaceuticals Corporation (“Tekmira”) and Alnylam effective May 30, 2008 (the “Tekmira Collaboration Agreement”), and Alnylam, Protiva
and Tekmira terminated, solely as among and between each other, the Sponsored Research Agreement among Alnylam, The University of British Columbia (“UBC”), and AlCana Technologies, Inc. (“AlCana”), dated
July 27, 2009, as amended by Amendment No. 1 dated July 27, 2011, and as supplemented by the Supplemental Agreement among Alnylam, Tekmira, Protiva, UBC, and AlCana, effective July 27, 2009 (collectively with the Protiva License
and the Tekmira Collaboration Agreement, the “Terminated In-Licenses”). 
 D. In replacement of the Terminated
In-Licenses, Alnylam, Tekmira and Protiva entered into a Cross-License Agreement dated as of November 12, 2012 (the “New Cross License”). 
 E. Alnylam and Genzyme now wish to amend the Collaboration Agreement as set forth in this Amendment. 
 AMENDMENT 
 Alnylam and Genzyme hereby agree, and the
Collaboration Agreement is hereby amended, as of the Amendment Effective Date, as follows: 
 1. Definitions from the Collaboration
Agreement. Initially capitalized terms used but not defined in this Amendment shall have the meanings ascribed to them in the Collaboration Agreement. 

 2. Deletion of Section 1.41 of the Collaboration Agreement. Section 1.41 of the
Collaboration Agreement is hereby amended and restated in its entirety to read as follows: “1.41             Reserved.” 

3. Deletion of Section 11.5 of the Collaboration Agreement. Section 11.5 of the Collaboration Agreement is hereby amended and restated
in its entirety to read as follows: “11.5             Reserved.” 

4. Amendment to Schedule 1.47 (Existing Alnylam In-Licenses). Schedule 1.47 of the Agreement is hereby amended to read in its entirety as set
forth in the Schedule 1.47 attached to this Amendment. 
 5. Amendment to Schedule 1.9 (Alnylam Core Technology Patents). Schedule
1.9 is hereby amended to reflect that the Patent Rights identified on Schedule 1.9 as the “Semple/Wheeler” Patent Rights are licensed to Alnylam pursuant to the Sublicense Agreement dated January 8, 2007 between Alnylam
Pharmaceuticals, Inc. and Tekmira Pharmaceuticals Corporation (as successor in interest to Inex Pharmaceuticals Corporation), rather than pursuant to the Tekmira Amended and Restated Cross-License, as originally indicated.  

6. No Loss of Rights; Incremental Amounts. Alnylam hereby represents and warrants that the termination of the Terminated In-Licenses and the entry
into the New Cross License in replacement thereof has not resulted in any Loss of Rights and Alnylam continues to Control all Know-How and Patent Rights licensed to Alnylam under the Terminated In-Licenses that are necessary or useful for Genzyme to
Develop, Manufacture and/or Commercialize Licensed Products in the Genzyme Territory. In addition, Alnylam hereby represents and warrants that the aggregate amount of Third Party License Payments required to be paid under the New Cross License does
not exceed, in duration or amount, the amount that Alnylam would have been required to pay under the Terminated In-Licenses (had they not been terminated) based on Alnylam’s assertions in the Ongoing Litigation, or, alternatively, Alnylam
agrees that to the extent it does exceed such amount, such excess shall be Incremental Amounts for all purposes of the Collaboration Agreement. Alnylam represents and warrants that it has provided Genzyme with an accurate and complete and unredacted
copy of the New Cross License.  
 7. Future Termination of In-Licenses. Following the Amendment Effective Date, neither Party
will voluntarily amend or terminate an In-License to which it is a party in a manner that terminates any rights sublicensed to the other Party that are necessary or useful for the other Party to Develop, Manufacture and/or Commercialize Licensed
Products under the Collaboration Agreement with respect to the other Party’s Territory, without the prior written consent of the other Party.  
 8. Miscellaneous. As amended hereby, the Collaboration Agreement remains in full force and effect. 
 [SIGNATURE PAGE FOLLOWS] 

  
 2 

 IN WITNESS WHEREOF, the Parties have by duly authorized
persons executed this Amendment as of the Amendment Effective Date. 
  

									
	ALNYLAM PHARMACEUTICALS, INC.:	 		 	GENZYME CORPORATION:
					
	By:	 	/s/ John M. Maraganore	 		 	By:	 	/s/ David Meeker
		 	 Title: Chief Executive Officer
  

Date: February 19, 2013
	 		 		 	 Title: President & Chief Executive Officer
  

Date: February 19, 2013

  
 3 

 SCHEDULE 1.47 

EXISTING ALNYLAM IN-LICENSES 
 Existing Alnylam In-Licenses includes the following Third Party agreements: 
 1. Amended and
Restated Strategic Collaboration and License Agreement between Isis Pharmaceuticals, Inc. and Alnylam Pharmaceuticals, Inc., dated April 28, 2009, as amended by letter agreement dated August 27, 2012. 

2. Co-Exclusive License Agreement between Max Planck Innovation GmbH (formerly Garching Innovation GmbH) and Alnylam Pharmaceuticals, Inc., dated
December 20, 2002, as amended by Amendment dated July 2, 2003, the Requirements Amendment effective June 15, 2005, the Waiver Amendment effective August 9, 2007 and the Amendment to the Alnylam Co-Exclusive License Agreement
dated as of March 14, 2011, by and between Alnylam Pharmaceuticals, Inc., on the one hand, and Whitehead Institute for Biomedical Research, Massachusetts Institute of Technology and Max-Planck-Innovation GmbH, on the other hand; and
Co-Exclusive License Agreement between Max Planck Innovation GmbH (formerly Garching Innovation GmbH) and Alnylam Europe AG (formerly Ribopharma AG), dated June 30, 2003. 
 3. Sponsored Research Agreement among Alnylam Pharmaceuticals, Inc., The University of British Columbia, and AlCana Technologies, Inc., dated July 27, 2009, as amended by Amendment No. 1 dated
July 27, 2011, and as supplemented by the Supplemental Agreement among Alnylam Pharmaceuticals, Inc., Tekmira Pharmaceuticals Corporation, Protiva Biotherapeutics Inc., The University of British Columbia, and AlCana Technologies, Inc.,
effective July 27, 2009. 
 4. Sublicense Agreement dated January 8, 2007 between Alnylam Pharmaceuticals, Inc. and Tekmira
Pharmaceuticals Corporation (as successor in interest to Inex Pharmaceuticals Corporation). 
 5. Cross-License Agreement dated
November 12, 2012 among Alnylam Pharmaceuticals, Inc., Tekmira Pharmaceuticals Corporation, and Protiva Biotherapeutics Inc. 

  
 4EX-10.50

 EXECUTION COPY 

 

			
	 Confidential Materials omitted and filed separately with the

Securities and Exchange Commission. Double asterisks denote omissions.
	 	Exhibit 10.50

 CROSS-LICENSE AGREEMENT 
 By and Among 
 ALNYLAM PHARMACEUTICALS, INC. 

TEKMIRA PHARMACEUTICALS CORPORATION 
 And 
 PROTIVA BIOTHERAPEUTICS INC. 

Dated: November 12, 2012 

 TABLE OF CONTENTS 

 

							
	 ARTICLE I - DEFINITIONS
	  	 	2	  
		
	 ARTICLE II - LICENSE GRANTS AND RELATED RIGHTS
	  	 	12	  
			
	 2.1
	 	 License Grants to Tekmira
	  	 	12	  
			
	 2.2
	 	 License Grants to Alnylam
	  	 	12	  
			
	 2.3
	 	 Sublicensing
	  	 	13	  
			
	 2.4
	 	 Coordination with Supplemental Agreement
	  	 	14	  
			
	 2.5
	 	 Covenants Not to Sue
	  	 	15	  
			
	 2.6
	 	 Retained Rights
	  	 	15	  
			
	 2.7
	 	 Rights in Bankruptcy
	  	 	15	  
		
	 ARTICLE III - SELECTION OF ADDITIONAL TARGETS
	  	 	16	  
			
	 3.1
	 	 Tekmira Additional Targets
	  	 	16	  
			
	 3.2
	 	 Alnylam Additional Exclusive Targets
	  	 	16	  
			
	 3.3
	 	 Selection Process
	  	 	16	  
		
	 ARTICLE IV - FINANCIAL PROVISIONS
	  	 	17	  
			
	 4.1
	 	 Manufacturing Opt-Out Payment
	  	 	17	  
			
	 4.2
	 	 Restructuring Payment
	  	 	17	  
			
	 4.3
	 	 Milestones with Respect to Tekmira Milestone Products
	  	 	17	  
			
	 4.4
	 	 Milestones with Respect to Biodefense Targets
	  	 	18	  
			
	 4.5
	 	 Milestones with Respect to Alnylam Products
	  	 	19	  
			
	 4.6
	 	 Milestones for Certain Alnylam Existing Exclusive Targets
	  	 	20	  
			
	 4.7
	 	 Royalty Term
	  	 	21	  
			
	 4.8
	 	 Royalties Payable by Tekmira
	  	 	21	  
			
	 4.9
	 	 Royalties on Alnylam Products
	  	 	21	  
			
	 4.10
	 	 Royalty Reduction
	  	 	23	  
			
	 4.11
	 	 Third Party License Payments
	  	 	23	  
			
	 4.12
	 	 Reports
	  	 	23	  
			
	 4.13
	 	 Tax Withholding
	  	 	24	  
			
	 4.14
	 	 Payments
	  	 	24	  
			
	 4.15
	 	 Audits
	  	 	24	  
		
	 ARTICLE V - INTELLECTUAL PROPERTY
	  	 	25	  
			
	 5.1
	 	 Category 1, 2 and 3 Patents
	  	 	25	  

  
 i 

							
	 5.2
	 	 Prosecution and Maintenance of Other Patents
	  	 	25	  
			
	 5.3
	 	 Third Party Infringement of Alnylam’s Patents
	  	 	25	  
			
	 5.4
	 	 Competitive Infringement of Category 1 Patents
	  	 	26	  
			
	 5.5
	 	 Third Party Infringement of Tekmira’s Patents
	  	 	26	  
			
	 5.6
	 	 Patent Certification
	  	 	27	  
		
	 ARTICLE VI - CONFIDENTIAL INFORMATION AND PUBLICITY
	  	 	27	  
			
	 6.1
	 	 Non-Disclosure of Confidential Information
	  	 	27	  
			
	 6.2
	 	 Limitation on Disclosures
	  	 	29	  
			
	 6.3
	 	 Publicity
	  	 	29	  
		
	 ARTICLE VII - INDEMNIFICATION AND INSURANCE
	  	 	30	  
			
	 7.1
	 	 Tekmira Indemnification
	  	 	30	  
			
	 7.2
	 	 Alnylam Indemnification
	  	 	30	  
			
	 7.3
	 	 Tender of Defense; Counsel
	  	 	30	  
			
	 7.4
	 	 Tekmira Insurance
	  	 	31	  
			
	 7.5
	 	 Alnylam Insurance
	  	 	31	  
		
	 ARTICLE VIII - EXPORT
	  	 	32	  
			
	 8.1
	 	 General
	  	 	32	  
			
	 8.2
	 	 Delays
	  	 	32	  
			
	 8.3
	 	 Assistance
	  	 	32	  
		
	 ARTICLE IX - TERM AND TERMINATION
	  	 	32	  
			
	 9.1
	 	 Term; Expiration
	  	 	32	  
			
	 9.2
	 	 Material Breach
	  	 	33	  
			
	 9.3
	 	 Challenges of Alnylam’s Patents
	  	 	33	  
			
	 9.4
	 	 Challenges of Tekmira Patents
	  	 	33	  
			
	 9.5
	 	 Consequences of Termination; Survival
	  	 	34	  
			
	 9.6
	 	 Licenses upon Termination
	  	 	34	  
		
	 ARTICLE X - MISCELLANEOUS
	  	 	35	  
			
	 10.1
	 	 Representations and Warranties
	  	 	35	  
			
	 10.2
	 	 Dispute Resolution; Arbitration Procedures
	  	 	37	  
			
	 10.3
	 	 Force Majeure
	  	 	37	  
			
	 10.4
	 	 Consequential Damages
	  	 	37	  
			
	 10.5
	 	 Assignment
	  	 	37	  

  
 ii 

							
	 10.6
	 	 Notices
	  	 	38	  
			
	 10.7
	 	 Independent Contractors
	  	 	39	  
			
	 10.8
	 	 Governing Law; Jurisdiction
	  	 	39	  
			
	 10.9
	 	 Severability
	  	 	39	  
			
	 10.10
	 	 No Implied Waivers
	  	 	39	  
			
	 10.11
	 	 Headings
	  	 	39	  
			
	 10.12
	 	 Entire Agreement
	  	 	39	  
			
	 10.13
	 	 Waiver of Rule of Construction
	  	 	40	  
			
	 10.14
	 	 No Third Party Beneficiaries
	  	 	40	  
			
	 10.15
	 	 Further Assurances
	  	 	40	  
			
	 10.16
	 	 Performance by Affiliates
	  	 	40	  
			
	 10.17
	 	 Counterparts
	  	 	40	  

  

					
	 EXHIBIT A - IP MANAGEMENT TERMS
	  	 	42	  
		
	 SCHEDULE 1.9 - ALNYLAM EXISTING IN-LICENSES
	  	 	47	  
		
	 SCHEDULE 1.10 - ALNYLAM EXISTING SUBLICENSES
	  	 	48	  
		
	 SCHEDULE 1.15 - CERTAIN ALNYLAM PATENTS
	  	 	49	  
		
	 SCHEDULE 1.19 - CERTAIN BIODEFENSE TARGETS
	  	 	50	  
		
	 SCHEDULE 1.22 - CATEGORY 1 PATENTS
	  	 	51	  
		
	 SCHEDULE 1.23 - CATEGORY 2 PATENTS
	  	 	52	  
		
	 SCHEDULE 1.24 - CATEGORY 3 PATENTS
	  	 	53	  
		
	 SCHEDULE 1.70 - TEKMIRA MANUFACTURING DOCUMENTS
	  	 	54	  

  
 iii

 CROSS-LICENSE AGREEMENT 

This Cross-License Agreement (this “Agreement”) is entered into as of November 12, 2012 (the “Effective Date”),
by and among ALNYLAM PHARMACEUTICALS, INC., a corporation organized under the laws of the State of Delaware having a principal office at 300 Third Street, Cambridge, MA 02142, U.S.A. (“Alnylam”), TEKMIRA PHARMACEUTICALS CORPORATION, a
Canadian corporation having a principal office at 100-8900 Glenlyon Parkway, Burnaby, B.C., Canada V5J 5J8 (“Tekmira”), and, solely with respect to Section 10.12, PROTIVA BIOTHERAPEUTICS INC., a wholly-owned subsidiary of Tekmira and
a British Columbia corporation with a principal place of business at 100-8900 Glenlyon Parkway, Burnaby, B.C., Canada V5J 5J8 (“Protiva”). 
 RECITALS 
 WHEREAS, Tekmira owns or controls certain intellectual
property covering certain nucleic acid delivery technology known as Lipid Nanoparticle or SNALP (“LNP”) technology (the “LNP/SNALP Technology”) that is useful for the delivery of a variety of therapeutic products, including those
that function through RNA interference (“RNAi”) or the modulation of microRNAs (“miRNAs”), and is also engaged in the business of discovering, developing, manufacturing and commercializing human therapeutic products; 

WHEREAS, Alnylam owns or controls certain intellectual property covering fundamental aspects of the structure and uses of
therapeutic products that function through RNAi or the modulation of miRNA and certain intellectual property covering LNP/SNALP Technology; and Alnylam is developing capabilities to develop and commercialize such therapeutic products; 

WHEREAS, Alnylam and Tekmira are parties to several existing agreements relating to RNAi, miRNA and SNALP/LNP Technology,
including an Amended and Restated License and Collaboration Agreement dated May 30, 2008 (the “Alnylam-Tekmira LCA”); an Amended and Restated Cross-License Agreement dated May 30, 2008, between Alnylam and Protiva, now a wholly
owned subsidiary of Tekmira (as amended, the “Alnylam-Protiva CLA” and collectively with the Alnylam-Tekmira LCA, the “Prior Cross-License Agreements”); a Development, Manufacturing and Supply Agreement dated January 2,
2009, as amended, and a Quality Assurance Agreement dated January 29, 2009 (collectively, the “Manufacturing Agreements”); a Supplemental Agreement dated July 27, 2009, among Tekmira, Protiva, Alnylam, AlCana Technologies, Inc.
(“AlCana”) and the University of British Columbia (“UBC”) (the “Supplemental Agreement”) and a related Sponsored Research Agreement dated July 26, 2009, among Alnylam, UBC and AlCana (the “Sponsored Research
Agreement”); and a Sublicense Agreement dated January 8, 2007, between Alnylam and Inex Pharmaceuticals Corporation (to which Tekmira is the successor in interest) (the “UBC Sublicense”); 

WHEREAS, the Parties have entered into a Settlement Agreement concurrently with the execution of this Agreement (the
“Settlement Agreement”) pursuant to which they have agreed to settle certain disputes between them; 

 WHEREAS, in connection with the Settlement Agreement, the Parties have agreed to
replace the Prior Cross-License Agreements with this Agreement, supersede rights and obligations under the Supplemental Agreement as between themselves with the rights and obligations set forth in this Agreement, and terminate the Manufacturing
Agreements; and 
 NOW, THEREFORE, in consideration of the mutual covenants contained herein, and other good and valuable
consideration, the receipt of which is hereby acknowledged, Alnylam and Tekmira enter into this Agreement effective as of the Effective Date: 
 ARTICLE I - DEFINITIONS 
 General. When used in this Agreement, each
of the following terms, whether used in the singular or plural, will have the meanings set forth in this Article I. 
 1.1
Act means the United States Federal Food, Drug, and Cosmetic Act of 1938, 21 U.S.C. §§321 et seq., as such may be amended from time to time, and its implementing regulations. 

1.2 Active Internal Development Program means, with respect to a particular siRNA Product or miRNA Product, that, as of the time
of Target selection under Section 3.3(a), there is an active program of Research, Development or Commercialization with respect to such siRNA Product or miRNA Product at such Party or any of its Affiliates. 

1.3 Affiliate means, with respect to a Person, any corporation, company, partnership, joint venture and/or firm which controls, is
controlled by, or is under common control with such Person. For purposes of the foregoing sentence, “control” means (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, or (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. 
 1.4 Aggregate Annual Net Sales means, for each calendar year starting with
the calendar year in which the First Commercial Sale occurs for a Product, the total Net Sales of such Product during such calendar year. 
 1.5 ALN-TTR means Alnylam’s siRNA Product in an LNP Formulation that is designed to target the human TTR gene product. 
 1.6 ALN-VSP means Alnylam’s siRNA Product in an LNP Formulation that is designed to target the human VEGF and KSP gene products. 

1.7 Alnylam Exclusive Target means any of the Alnylam Existing Exclusive Targets or any of the Alnylam Additional Exclusive
Targets. 
 1.8 Alnylam Existing Exclusive Target means any of the following Targets: VSP (VEGF and KSP used in
combination), TTR and PCSK9. 

  
 2 

 1.9 Alnylam Existing In-License means any of the agreements set forth on
Schedule 1.9, pursuant to which Alnylam has a license from any Third Party under any Alnylam Licensed Technology. 
 1.10
Alnylam Existing Sublicense means any of the agreements set forth on Schedule 1.10, pursuant to which Alnylam has granted a sublicense to any Third Party under any Tekmira Combined Licensed Technology and/or Category 1 Patent. 

1.11 Alnylam Field means the use of siRNA Products or miRNA Products directed to an Alnylam Target for the prevention, treatment
or palliation of human disease, and related Research, Development and Commercialization activities. 
 1.12 Alnylam
Know-How means all Know-How Controlled by Alnylam as of the Effective Date and that, prior to the Effective Date, was (a) disclosed by Alnylam to Tekmira or (b) otherwise learned by Tekmira; provided, that Alnylam
Know-How shall not include Know-How learned by Tekmira solely as a result of the litigation settled pursuant to the Settlement Agreement. 
 1.13 Alnylam Licensed Technology means, collectively, the Alnylam Patents and the Alnylam Know-How. 
 1.14 Alnylam Non-Exclusive Target means any Target that is not an Alnylam Exclusive Target or a Tekmira Exclusive Target. 
 1.15 Alnylam Patent means any Patent Controlled by Alnylam as of the Effective Date that was filed, or claims priority to a Patent that was filed, before April 15, 2010, or any foreign
counterpart of any of the foregoing Patents, and that either: 
 (a) is listed on Schedule 1.15; or 

(b) is related to general siRNA structures or modifications (excluding conjugated siRNAs); or 

(c) has claims relating to a lipid or an LNP Formulation or its manufacture; or 

(d) has claims relating to non-conjugated siRNAs directed to a Tekmira Target. 

Alnylam Patents shall not include any Patent that (i) is a UBC Patent; or (ii) is Controlled by Alnylam pursuant to an
in-license that is not an Alnylam Existing In-License. 
 Notwithstanding the foregoing, the licenses granted to Tekmira under
Section 2.1 with respect to the Patents in Section 1.15(c) above will only include Researching, Developing and Commercializing Tekmira Products in an LNP Formulation. 

1.16 Alnylam Product means an siRNA Product or miRNA Product Researched, Developed or Commercialized by Alnylam, its Affiliates or
Sublicensees that is directed to an Alnylam Target. 

  
 3 

 1.17 Alnylam Sublicensable Product means an Alnylam Product that has been developed
by Alnylam or its Affiliates [**]. Any such Alnylam Product described in clause (a) may also include existing or future back up or improvement oligonucleotide products directed to the same Target as such Product in LNP Formulations or other
lipid-based formulations. 
 1.18 Alnylam Target means any of the Alnylam Exclusive Targets or Alnylam Non-Exclusive
Targets. 
 1.19 Biodefense Target means (a) a Target within the genome of one or more Category A, B and C
pathogens, as defined by the National Institute of Allergy and Infectious Diseases, including without limitation, pathogens set forth on Schedule 1.19, but specifically excluding influenza virus, or (b) an endogenous cellular Target against
which Alnylam Develops and/or Commercializes an Alnylam Product for commercial supply to one or more Funding Authorities. 

1.20 Bona Fide Collaboration means a collaboration between Alnylam and one or more Third Parties involving Research, Development,
Manufacture and/or Commercialization of one or more Alnylam Products and established under a written agreement in which (a) the scope of the licenses granted, and financial or other commitments of value, are of material value to Alnylam, and
(b) Alnylam undertakes and performs substantial, mutual research, development and/or commercialization activity with the Third Party. For purposes of clarity, it is understood and agreed that no collaboration in which all or substantially all
of Alnylam’s contributions or anticipated contributions are or will be in the form of the grant by Alnylam of licenses or sublicenses to one or more intellectual property rights will be considered a Bona Fide Collaboration. 

1.21 Business Day means a day on which banking institutions in Boston, Massachusetts and Vancouver, British Columbia, Canada, are
open for business. 
 1.22 Category 1 Patent means any Patent set forth on Schedule 1.22, any Patent Controlled by
Tekmira after the Effective Date that claims priority to any of the Patents set forth on Schedule 1.22, or any foreign counterpart of any of the foregoing Patents. 
 1.23 Category 2 Patent means any Patent set forth on Schedule 1.23, any Patent Controlled by Alnylam after the Effective Date that claims priority to any of the Patents set forth on Schedule 1.23,
or any foreign counterpart of any of the foregoing Patents. 
 1.24 Category 3 Patent means any Patent set forth on
Schedule 1.24, any Patent Controlled by Alnylam after the Effective Date that claims priority to any of the Patents set forth on Schedule 1.24, or any foreign counterpart of any of the foregoing Patents. 

1.25 Combination Product means a product that incorporates in a combination one or more pharmacologically active ingredients in
addition to the active pharmaceutical ingredient in the Alnylam Product or Tekmira Product, as applicable. 
 1.26
Commercialize or Commercialization means any and all activities directed to Manufacturing (including, without limitation, by means of contract manufacturers), marketing, promoting, distributing, importing, exporting and selling a
Product, in each case for commercial purposes, and activities directed to obtaining pricing and reimbursement approvals, as applicable. 

  
 4 

 1.27 Confidential Information means all proprietary or confidential information and
materials, patentable or otherwise, of a Party disclosed by or on behalf of such Party to the other Party before, on or after the Effective Date, including, without limitation, chemical substances, formulations, techniques, methodology, equipment,
data, reports, Know-How, sources of supply, patent positioning, business plans, and also including without limitation proprietary and confidential information of Third Parties in possession of such Party under an obligation of confidentiality,
whether or not related to making, using or selling Products. 
 1.28 Control, Controls or Controlled by
means, with respect to any Know-How or Patent, the possession of (whether by ownership or license, other than pursuant to this Agreement), or the ability of a Party or any of its Existing Affiliates to grant access to, or a license or sublicense of,
such Know-How or Patent as provided for herein without violating the terms of any agreement or other arrangement with any Third Party existing at the time such Party would be required hereunder to grant the other Party such access or license or
sublicense. 
 1.29 Cover, Covers or Covered by means, with respect to a product and a Patent, that, but
for ownership of or a license or sublicense under such Patent, the making, using, selling, offering for sale or importing of, or other stated action with respect to, such product would infringe such Patent (or, if such Patent is a patent
application, would infringe a patent issued from such patent application). 
 1.30 Develop, Developing or
Development means with respect to a Product, preclinical and clinical drug development activities, including without limitation: test method development and stability testing, toxicology, formulations, manufacturing scale-up, preclinical and
clinical Manufacture, quality assurance/quality control development, statistical analysis and report writing; clinical studies and regulatory affairs; Regulatory Approval and registration. 

1.31 Existing Affiliate means, with respect to a Party, an Affiliate of such Party as of the Effective Date. 

1.32 FDA means the United States Food and Drug Administration or any successor agency thereto. 

1.33 First Commercial Sale means, with respect to each Product, the first commercial sale in a country as part of a nationwide
introduction after receipt by a Product Seller of Regulatory Approval in such country, excluding de minimis named patient and compassionate use sales. 
 1.34 Follow-On Product means a Product directed towards a Target that is the same Target that is targeted by a Successful Tekmira Milestone Product, a Successful Alnylam Product or a Successful
Biodefense Product, as applicable, but that contains a different chemical structure for the siRNA and/or a different cationic lipid component for the LNP Formulation. 

  
 5 

 1.35 Funding Authority means the United States Department of Health and Human
Services or other United States or foreign government or international agencies responsible for requesting, approving and/or funding the development and manufacture of products for biodefense purposes. 

1.36 GAAP means United States generally accepted accounting principles applied on a consistent basis. 

1.37 IND means a United States investigational new drug application or its equivalent or any corresponding foreign application.

 1.38 Institutional Collaborator means any academic or non-profit institution or Person employed by or otherwise
affiliated with such an institution that does not meet the definition of Permitted Contractor. 
 1.39 Know-How means
biological materials and other tangible materials, information, data, inventions, practices, methods, protocols, formulas, formulations, knowledge, know-how, trade secrets, processes, assays, skills, experience, techniques and results of
experimentation and testing, including without limitation pharmacological, toxicological and preclinical and clinical test data and analytical and quality control data, patentable or otherwise. 

1.40 LNP Formulation means an LNP formulation, characterized by its components and its unique ratios among components. 

1.41 Major Market means, individually and collectively, the United States, the European Union, Canada, the United Kingdom, France,
Germany, Italy, Spain, China and Japan. 
 1.42 Manufacturing or Manufacture means, with respect to a Product, all
activities associated with the production, manufacture and processing of such Product, and the filling, finishing, packaging, labeling, shipping, and storage of such Product, including without limitation formulation process scale-up for toxicology
and clinical study use, aseptic fill and finish, stability testing, analytical development, quality assurance and quality control, and the production of the bulk finished dosage form of such Product from the siRNA and miRNA. 

1.43 miRNA Product means a product containing, comprised of or based on native or chemically modified RNA oligomers designed to
either (a) modulate, inhibit or interfere with a particular miRNA transcript; or (b) provide the function and/or mimic the activity of an miRNA. 
 1.44 Necessary Third Party IP means, with respect to any country in the Territory, on a country-by-country basis, any Patent in such country owned or controlled by a Third Party that Covers Alnylam
Products and/or Tekmira Products. 
 1.45 Net Sales means the gross amount invoiced by Alnylam, its Affiliates or
Sublicensees for Alnylam Products, or by Tekmira, its Affiliates or Sublicensees for Tekmira Products (in each case, such invoicing entity, a “Product Seller”), on sales or other dispositions in the Territory of such Products during the
applicable Royalty Term to Third Parties which are not Affiliates or Sublicensees of the Product Seller, less (a) to the extent allowed and taken, sales 

  
 6 

 
returns and allowances, granted or accrued, including trade, quantity and cash discounts and any other adjustments, including those granted on account of price adjustments, billing errors,
rejected goods, damaged or defective goods, recalls, returns, rebates, chargebacks, reimbursements or similar payments granted or given to wholesalers or other distributors, buying groups, health care insurance carriers or other institutions;
(b) adjustments arising from consumer discount programs or similar programs; (c) customs or excise duties, sales tax, consumption tax, value added tax, and other similar taxes (except income taxes) measured by the production, sale, or
delivery of goods; (d) duties relating to sales and any payments in respect of sales to the United States government, any State government or any foreign government, or to any governmental authority, or with respect to any government subsidized
program or managed care organization; and (e) charges for freight and insurance related to the return of Products and not otherwise paid by the customer. 
 In the event that a Product is sold in any country in the form of a Combination Product in any year, Net Sales of such Combination Product will be adjusted by multiplying actual Net Sales of such
Combination Product in such country by the fraction A/(A+B), where A is the average Net Sales price per daily dose during such year of the Product in such country, if sold separately in such country, and B is the average Net Sales price per daily
dose of any product containing the other pharmacologically active ingredients in the Combination Product in such country, if sold separately in such country. If, in a specific country, the product containing the other pharmacologically active
ingredients in the Combination Product are not sold separately in such country, Net Sales will be calculated by multiplying actual Net Sales of such Combination Product by the fraction A/C, where A is the average Net Sales price per daily dose of
the Product in such country and C is the average Net Sales price per daily dose of the Combination Product in such country. If, in a specific country, the Product is not sold separately in such country, Net Sales will be calculated by multiplying
actual Net Sales of such Combination Product by the fraction (C-B)/C, where B is the average Net Sales price per daily dose of the product containing the other pharmacologically active ingredients in the Combination Product in such country and C is
the average Net Sales price per daily dose of the Combination Product in such country. If, in a specific country, both the Product and the product containing the other pharmacologically active ingredients in the Combination Product are not sold
separately in such country, the Net Sales price for the Product and the product containing the other pharmacologically active ingredients in the Combination Product will be negotiated by the Parties in good faith based upon the costs, overhead and
profit as are then incurred for the Product and all similar substances then being made and marketed by the selling Party and having an ascertainable market price. 
 Net Sales shall be determined from books and records maintained in accordance with GAAP, consistently applied throughout the organization and across all products of the entity whose sales of Product are
giving rise to Net Sales. 
 1.46 Party means either Alnylam or Tekmira or, solely with respect to Section 10.12,
Protiva; Parties means Alnylam and Tekmira and, solely with respect to Section 10.12, Protiva. 
 1.47 Patent
means any patent (including any reissue, extension, substitution, confirmation, re-registrations, re-examination, invalidation, supplementary protection certificate or patents of addition) or patent application (including any provisional
application, continuation, continuation-in-part or divisional). 

  
 7 

 1.48 Permitted Contractor means a Third Party that performs activities (e.g.,
as a contractor or consultant) under a bona fide contract services arrangement on behalf of a Party or its Affiliates. 

1.49 Person means any person or entity. 
 1.50 Phase I Clinical Trial means the first study of a Product in humans the primary purpose of which is the determination of safety and which may include the determination of pharmacokinetic
and/or pharmacodynamic profiles in healthy individuals or patients. 
 1.51 Phase II Clinical Trial means (a) a
study of dose exploration, dose response, duration of effect, kinetics or preliminary efficacy and safety study of a Product in the target patient population, (b) a controlled dose-ranging clinical trial to evaluate further the efficacy and
safety of such Product in the target population and to define the optimal dosing regimen or (c) a clinical trial that the sponsoring Party or its Affiliate refers to in a press release as a Phase II Clinical Trial or Study. 

1.52 Phase III Clinical Trial or Pivotal Trial means (a) a controlled study of a Product in patients of the efficacy and
safety of such Product which is prospectively designed to demonstrate statistically whether such Product is effective and safe for use in a particular indication in a manner sufficient to obtain Regulatory Approval to market such Product or
(b) a clinical trial that the sponsoring Party or its Affiliate refers to in a press release as a Phase III Clinical Trial or Study. 
 1.53 Product means a Tekmira Product or an Alnylam Product. 
 1.54
Protiva Patent means any Patent Controlled by Protiva on or after the Effective Date that was filed, or that claims priority to a Patent that was filed before April 15, 2010, but excluding Patent claims that Cover Tekmira Products, which
excluded Patent claims are solely directed to PLK1, APOB, Ebola, WEE1, ALDH2 or CSN5. 
 1.55 Protiva Know-How means all
Know-How Controlled by Protiva as of the Effective Date and that, prior to the Effective Date, was (a) disclosed to Alnylam by Protiva or (b) otherwise learned by Alnylam; provided, that Protiva Know-How shall not include
Know-How learned by Alnylam solely as a result of the litigation settled pursuant to the Settlement Agreement. 
 1.56
Qualifying Patent means an Alnylam Patent or, if there is no Valid Claim of an Alnylam Patent remaining in the applicable sublicensed territory, any Patent Controlled by Alnylam that claims the composition of matter or method of use of a
product. 
 1.57 Regulatory Approval means, with respect to each Product Developed and Commercialized, the receipt of
sufficient authorization from the appropriate regulatory authority on a country-by-country basis to market and sell such Product in a country, including (where necessary in a particular country prior to marketing a Product) all separate pricing
and/or reimbursement approvals that may be required for marketing. 

  
 8 

 1.58 Research or Researching means identifying, evaluating, validating and
optimizing Products prior to pre-IND GLP toxicology studies. 
 1.59 Royalty Quarter means each of the four
(4) calendar quarters that begin January 1, April 1, July 1 and October 1 of each year. 

1.60 siRNA means a double-stranded ribonucleic acid (RNA) composition designed to act primarily through an RNA interference
mechanism that 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. 
 1.61 siRNA Product means a product containing, comprised of or based on siRNAs or other double-stranded moieties effective in gene function modulation and designed to modulate the function of
particular genes or gene products by causing degradation through RNA interference of a Target mRNA to which such siRNAs or other double-stranded moieties are complementary. 
 1.62 Sublicensee means (a) a Third Party to whom Alnylam has granted (or to whom another permitted sublicensee under an Alnylam Existing Sublicense grants) a sublicense pursuant to any of the
Alnylam Existing Sublicenses, or (b) a Third Party to whom a Party (or another permitted sublicensee of such Party under this Agreement) grants a sublicense of all or a portion of the rights licensed to it hereunder as permitted herein.

 1.63 Sublicensable Product means an Alnylam Sublicensable Product or a Tekmira Sublicensable Product. 

1.64 Target means (a) a nucleic acid that encodes or is required for expression of a polypeptide (including without
limitation messenger RNA and miRNA), together with all variants of such polypeptide; (b) the set of nucleic acids that encode a defined non-peptide entity, including a microorganism, virus, bacterium or single cell parasite; provided
that the entire genome of a microorganism, virus, bacterium, or single cell parasite shall be regarded as a single Target; or (c) a naturally occurring interfering RNA or miRNA or precursor thereof. 

1.65 Tekmira Additional Target means a Tekmira Additional Exclusive Target or a Tekmira Additional Non-Exclusive Target.

 1.66 Tekmira Combined Licensed Technology means, collectively, the Protiva Patents, the Protiva Know-How, the Tekmira
Patents and the Tekmira Know-How. 
 1.67 Tekmira Exclusive Target means ALDH2 or any of the Tekmira Additional Exclusive
Targets. 

  
 9 

 1.68 Tekmira Field means the use of siRNA Products directed to a Tekmira Target for
the prevention, treatment or palliation of human disease, and related Research, Development and Commercialization activities. 

1.69 Tekmira Know-How means all Know-How, other than Protiva Know-How, Controlled by Tekmira as of the Effective Date and that,
prior to the Effective Date, was (a) disclosed by Tekmira to Alnylam or (b) otherwise learned by Alnylam; provided, that Tekmira Know-How shall not include Know-How learned by Alnylam solely as a result of the litigation
settled pursuant to the Settlement Agreement. 
 1.70 Tekmira Manufacturing Documents means the documents identified in
Schedule 1.70. 
 1.71 Tekmira Milestone Product means any Tekmira Product Covered by a Valid Claim within the
Alnylam Patents and that is directed to a Tekmira Non-Exclusive Target other than Ebola. 
 1.72 Tekmira Non-Exclusive
Target means any of the following Targets: PLK1, APOB, Ebola, WEE1, CSN5, or any of the Tekmira Additional Non-Exclusive Targets. 
 1.73 Tekmira Patent means any Patent, other than a Protiva Patent, UBC Patent or Category 1 Patent, that is Controlled by Tekmira on or after the Effective Date and that was filed, or that claims
priority to a Patent that was filed, before April 15, 2010. 
 1.74 Tekmira Product means an siRNA Product
Researched, Developed or Commercialized by Tekmira, its Affiliates or Sublicensees that is directed to a Tekmira Target. 
 1.75
Tekmira Royalty-Bearing Patent means any Patent within the Tekmira Combined Licensed Technology, any Category 1 Patent, any Category 2 Patent as to which a Tekmira employee is listed as an inventor, any Category 3 Patent as to which a Tekmira
employee is listed as an inventor, and any UBC Patent. 
 1.76 Tekmira Sublicensable Product means a Product that has
been developed by Tekmira or its Affiliates for which (a) a Target has been identified, and a potential therapeutic intervention described, and (b) one (1) or more oligonucleotide(s) have been screened in in vitro studies and
(c) non-GLP rodent pharmacology data has been generated. 
 1.77 Tekmira Target means a Tekmira Exclusive Target or
a Tekmira Non-Exclusive Target. 
 1.78 Tekmira-UBC License Agreement means that certain license agreement between
Tekmira and UBC, dated effective July 1, 1998, as amended by Amendment Agreement between Tekmira and UBC dated effective July 11, 2006, and Second Amendment Agreement dated effective August 14, 2007. 

1.79 Territory means worldwide. 

  
 10 

 1.80 Third Party means any Person other than Tekmira, Alnylam or any of their
respective Affiliates. 
 1.81 UBC Patent means a Patent sublicensed to Alnylam pursuant to the UBC Sublicense and that
was filed, or that claims priority to a Patent that was filed, before April 15, 2010. 
 1.82 Valid Claim means
(a) any claim in an issued and unexpired patent within the Alnylam Patents or the Tekmira Royalty-Bearing Patents, as applicable, that has not been held unenforceable, unpatentable or invalid by a decision of a court or other governmental
agency of competent jurisdiction, which decision is unappealable or unappealed within the time allowed for appeal, and which has not been admitted by the holder of the patent to be invalid or unenforceable through reissue, re-examination, or
disclaimer or otherwise and (b) a patent application within the Alnylam Patents or the Tekmira Royalty-Bearing Patents, as applicable, a claim of which has been pending less than [**] years and which claim has not been cancelled, withdrawn or
abandoned or finally rejected by an administrative agency action from which no appeal can be taken. 
  

			
	 Additional Defined Terms
	  	 Section Reference

		
	AAA	  	10.2
	Agreement	  	PREAMBLE
	AlCana	  	RECITALS
	Alnylam	  	PREAMBLE
	Alnylam Additional Exclusive Target	  	3.2
	Alnylam Indemnitee	  	7.1
	Alnylam-Protiva CLA	  	RECITALS
	Alnylam-Tekmira LCA	  	RECITALS
	Ascletis	  	4.6
	Code	  	2.7
	Competitive Infringement	  	5.4(a)
	Effective Date	  	PREAMBLE
	IP Management Terms	  	5.1
	Lead Development Candidate	  	1.17
	LNP	  	RECITALS
	LNP Improvements	  	2.2(d)
	LNP/SNALP Technology	  	RECITALS
	Losses	  	7.1
	miRNA	  	RECITALS
	Manufacturing Agreements	  	RECITALS
	Prior Cross-License Agreements	  	RECITALS
	Product Seller	  	1.45
	Protiva	  	PREAMBLE
	RNAi	  	RECITALS
	Royalty Term	  	4.7
	Settlement Agreement	  	RECITALS

  
 11 

			
	 Additional Defined Terms
	  	 Section Reference

		
	Sponsored Research Agreement	  	RECITALS
	Successful Alnylam Product	  	4.5
	Successful Biodefense Product	  	4.4
	Successful Tekmira Milestone Product	  	4.1
	Supplemental Agreement	  	RECITALS
	Tekmira	  	PREAMBLE
	Tekmira Additional Exclusive Target	  	3.1
	Tekmira Additional Non-Exclusive Target	  	3.1
	Tekmira Indemnitee	  	7.2
	UBC	  	RECITALS
	UBC Sublicense	  	RECITALS

 ARTICLE II - LICENSE GRANTS AND RELATED RIGHTS 

2.1 License Grants to Tekmira. 
 (a) Subject to the terms and conditions of this Agreement and the Alnylam Existing In-Licenses, Alnylam hereby grants to Tekmira and its Affiliates an exclusive right and license under the Alnylam
Licensed Technology to Research, Develop and Commercialize Tekmira Products directed to any Tekmira Exclusive Target in the Tekmira Field in the Territory. 
 (b) Subject to the terms and conditions of this Agreement and the Alnylam Existing In-Licenses, Alnylam hereby grants to Tekmira and its Affiliates a non-exclusive right and license under the Alnylam
Licensed Technology to Research, Develop and Commercialize Tekmira Products directed to any Tekmira Non-Exclusive Target in the Tekmira Field in the Territory. 
 (c) The licenses set forth in this Section 2.1 include the right to grant sublicenses as provided in, and subject to, Section 2.3 below. 

2.2 License Grants to Alnylam. 
 (a) Subject to the terms and conditions of this Agreement, Tekmira hereby grants to Alnylam and its Affiliates an exclusive right and license under the Tekmira Combined Licensed Technology and the
Category 1 Patents to Research, Develop and Commercialize Alnylam Products directed to any Alnylam Exclusive Target in the Alnylam Field in the Territory. 
 (b) Subject to the terms and conditions of this Agreement, Tekmira grants to Alnylam and its Affiliates a non-exclusive right and license under the Tekmira Combined Licensed Technology and the Category 1
Patents to Research, Develop and Commercialize Alnylam Products directed to any Alnylam Non-Exclusive Target in the Alnylam Field in the Territory. 
 (c) Subject to the terms and conditions of this Agreement, Tekmira grants to Alnylam and its Affiliates a non-exclusive right and license (without the right to grant sublicenses outside

  
 12 

 
of the Alnylam Field) under the Category 1 Patents for any and all purposes, both in the Alnylam Field and outside of the Alnylam Field, in the Territory. The license granted pursuant to this
Section 2.2(c) shall be fully paid-up and royalty-free outside the Alnylam Field. 
 (d) Subject to the terms and
conditions of this Agreement, Tekmira grants to Alnylam and its Affiliates a non-exclusive, non-sublicensable, fully paid-up, royalty-free right and license under the Tekmira Combined Licensed Technology and the Category 1 Patents to research,
develop, make, have made and use improvements to such technology and inventions claimed or covered by such Patents (“LNP Improvements”) and to research, develop, make, have made, use and commercialize LNP Improvements. As between the
Parties, Alnylam shall own all LNP Improvements made by Alnylam and its Affiliates pursuant to the license granted under this Section 2.2(d); provided, however, that such ownership of LNP Improvements shall not extinguish or alter
any of Alnylam’s obligations to Tekmira for any products that are Alnylam Products. 
 (e) The licenses set forth in
subsections (a), (b) and (c) of this Section 2.2 include the right to grant sublicenses as provided in, and subject to, Section 2.3 below. 
 2.3 Sublicensing. 
 (a) The licenses granted to Tekmira in Section 2.1
include the right for Tekmira to grant sublicenses, but only on a Tekmira Sublicensable Product-by-Tekmira Sublicensable Product basis, to Third Parties to Research, Develop and/or Commercialize Tekmira Products that are Tekmira Sublicensable
Products. Tekmira shall require that the terms of any sublicense under its rights in this Agreement are fully in compliance with the terms and conditions of this Agreement and of the Alnylam Existing In-Licenses governing Alnylam’s rights under
the Alnylam Licensed Technology. 
 (b) The licenses granted to Alnylam in Section 2.2(a), Section 2.2(b) and
Section 2.2(c) include the right for Alnylam to grant sublicenses in the Alnylam Field, but only on a Alnylam Sublicensable Product-by-Alnylam Sublicensable Product basis, to Third Parties to Research, Develop and/or Commercialize Alnylam
Products that are Alnylam Sublicensable Products. Alnylam shall require that the terms of any sublicense under its rights in this Agreement are fully in compliance with the terms and conditions of this Agreement. 

(c) Any sublicense granted by a Party hereunder shall be subject and subordinate to the terms and conditions of this Agreement and shall
contain terms and conditions consistent with those in this Agreement. The sublicensing Party shall assume full responsibility for the performance of all obligations and observance of all terms herein under the licenses granted to it and will itself
pay and account to the other Party for all payments due under such licenses by reason of any such sublicense. If a sublicensing Party becomes aware of a material breach of any sublicense by a Sublicensee, the sublicensing Party shall promptly notify
the other Party of the particulars of same and take all reasonable efforts to enforce the terms of such sublicense. 
 (d)
Unless otherwise provided in this Agreement, the sublicensing Party will notify the other Party within [**] days after execution of a sublicense entered into hereunder and 

  
 13 

 
provide a copy of the fully executed sublicense agreement to the other Party within the same time frame (with such reasonable redactions as the sublicensing Party may make, provided
that such redactions do not include provisions necessary to demonstrate compliance with the requirements of this Agreement), which shall be treated as Confidential Information of the sublicensing Party under Article VI; and provided
further that the other Party may disclose such agreement(s) to Third Parties under confidence if and to the extent required in order to comply with such other Party’s contractual obligations under both this Agreement and Third Party
agreements. 
 (e) Tekmira hereby waives the foregoing sublicensing restrictions and requirements of Section 2.2(c),
Section 2.2(d) and this Section 2.3 with respect to the Alnylam Existing Sublicenses. In addition, to the extent that Alnylam as of the Effective Date has licensed or sublicensed any Patent or Know-How Controlled by Tekmira as of the
Effective Date to any Third Party pursuant to any Alnylam Existing Sublicense, or granted any Third Party pursuant to any Alnylam Existing Sublicense any option to obtain a license or sublicense under any Patent or Know-How Controlled by Tekmira,
the rights of the applicable Third Party shall not be affected by this Agreement, and if such Third Party Develops or Commercializes Alnylam Products, then Tekmira will be entitled to milestone payments and royalties with respect thereto as set
forth in this Agreement. Alnylam agrees that it will not grant any additional options, licenses or sublicenses under Alnylam Patents, Tekmira Combined Licensed Technology, UBC Patents or Category 1 Patents to AlCana to Research, Develop or
Commercialize siRNA Products without the prior written consent of Tekmira or enter into any additional contractual obligations to indemnify AlCana as to AlCana’s practice of the Alnylam Patents, Tekmira Combined Licensed Technology, UBC Patents
or Category 1 Patents to Research, Develop or Commercialize siRNA Products. 
 (f) Notwithstanding Sections 2.3(a) and 2.3(b),
either Party may utilize Permitted Contractors and Institutional Collaborators to Research and/or Develop their respective Products, whether or not such Products have become Sublicensable Products; provided that (i) such Party
does not grant any such Permitted Contractor or Institutional Collaborator any license to Commercialize Products that are not Sublicensable Products and (ii) no Party shall share any of the other Party’s Confidential Information with such
Permitted Contractor or Institutional Collaborator unless such Third Party shall have executed a binding confidentiality agreement containing reasonably customary terms and conditions. 

2.4 Coordination with Supplemental Agreement. Tekmira and Alnylam hereby agree that the terms of this Agreement and the Settlement
Agreement (and the Binding Term Sheet attached thereto) extinguish, supersede, and replace the rights and obligations of Tekmira, Alnylam, and AlCana under the Supplemental Agreement solely as between and among Tekmira, Alnylam, and AlCana;
provided, however, Alnylam’s payment obligations to UBC and AlCana under the Supplemental Agreement and Sponsored Research Agreement shall survive the execution of this Agreement and the Settlement Agreement (and the Binding Term
Sheet attached thereto), and shall also survive any termination of the Supplemental Agreement or Sponsored Research Agreement, in each case for the duration of the applicable Royalty Term (as defined in the Sponsored Research Agreement). Subject to
the terms and conditions of the Settlement Agreement and any subsequent agreement(s) among Alnylam, Tekmira, UBC and 

  
 14 

 
AlCana, the rights and obligations of UBC under the Supplemental Agreement and Sponsored Research Agreement shall be maintained. Notwithstanding any of the foregoing, nothing in this section 2.4
shall operate to relieve Alnylam of its obligation to comply with its payment or royalty obligations to UBC or AlCana, either directly or indirectly, under the Supplemental Agreement or Sponsored Research Agreement. 

2.5 Covenants Not to Sue. Alnylam hereby covenants that it and its Existing Affiliates will not initiate any legal suit against
Tekmira or any of its Existing Affiliates asserting that: 
 (a) any internal Research performed solely by Tekmira or its
Existing Affiliates (and not with any Third Party) and solely for the purpose of identifying a Target for selection as a Tekmira Additional Target hereunder during the period starting on the Effective Date and continuing until the earlier of
(i) the [**] anniversary of the Effective Date and (ii) such date that Tekmira completes its selection of the Tekmira Additional Targets pursuant to Article III; or 
 (b) the formulating in LNP Formulations by Tekmira or any of its Existing Affiliates of oligonucleotides controlled by any bona fide Third Party pharmaceutical collaborator on behalf of such Third
Party and solely for Research (but not Development or Commercialization); 
 constitutes infringement and/or misappropriation of the Alnylam
Licensed Technology. For clarity, the Parties agree that the covenants set forth in this Section 2.5 do not extend to any Third Party. 
 2.6 Retained Rights. Each Party expressly retains any rights not expressly granted to the other Party under this Article II (or otherwise under this Agreement). 

2.7 Rights in Bankruptcy. All licenses and rights to licenses granted under or pursuant to this Agreement by a Party to other
Party are, and shall otherwise be deemed to be, for purposes of Section 365(n) of the United States Bankruptcy Code (the “Code”), licenses of rights to “intellectual property” as defined under Section 101(35A) of the
Code. The Parties agree that each Party, as a licensee of such rights under this Agreement, shall retain and may fully exercise all of its rights and elections under the Code, and that upon commencement of a bankruptcy proceeding by or against the
other Party under the Code, such Party shall be entitled to a complete duplicate of, or complete access to (as such Party deems appropriate), any such intellectual property and all embodiments of such intellectual property. Such intellectual
property and all embodiments thereof shall be promptly delivered to such Party (a) upon any such commencement of a bankruptcy proceeding upon written request therefor by such Party, unless such other Party elects to continue to perform all of
its obligations under this Agreement or (b) if not delivered under (a) above, upon the rejection of this Agreement by or on behalf of such other Party upon written request therefor by such Party. The foregoing provisions are without
prejudice to any rights such Party may have arising under the Code or other applicable law. 

  
 15 

 ARTICLE III - SELECTION OF ADDITIONAL TARGETS 

3.1 Tekmira Additional Targets. Subject to Section 3.3, during the period beginning on the Effective Date and ending on the
[**] anniversary thereof, Tekmira may select (i) up to two (2) Targets (other than the Alnylam Exclusive Targets) that shall each become a “Tekmira Additional Exclusive Target” and (ii) up to five (5) Targets (other
than the Alnylam Exclusive Targets) that shall each become a “Tekmira Additional Non-Exclusive Target”. For clarity, the Parties acknowledge that such seven (7) Tekmira Additional Targets shall be in addition to the one
(1) Tekmira Exclusive Target and the five (5) Tekmira Non-Exclusive Targets selected as of the Effective Date. 
 3.2
Alnylam Additional Exclusive Targets. Subject to Section 3.3, during the period beginning on the Effective Date and ending on the [**] anniversary thereof, Alnylam may select up to five (5) Targets (other than the Tekmira Targets)
that shall each become an “Alnylam Additional Exclusive Target”. For clarity, the Parties acknowledge that the five (5) Alnylam Exclusive Additional Targets shall be in addition to the Alnylam Existing Exclusive Targets. 

3.3 Selection Process. The following process shall apply to the selection of Tekmira Additional Targets and Alnylam Additional
Exclusive Targets. 
 (a) As to Targets that are peptide entities, the selecting Party shall initially notify the other Party in
writing of the NCBI Gene ID number (or, if a NCBI Gene ID number is not available, the specific sequence of the proposed Target) of each Target nominated by the selecting Party for selection as an additional Target. As to Targets that are
non-peptide entities, the selecting Party shall initially notify the other Party in writing of the non-peptide entity. Within [**] Business Days following the other Party’s receipt of a notice nominating a Target, such other Party shall notify
the selecting Party in writing whether such Target is either: (i) subject to a binding contractual obligation to a Third Party that would be breached by the inclusion of such Target as an additional Target under these terms, or (ii) the
subject of an Active Internal Development Program at such other Party and such Active Internal Development Program was in existence as such prior to the receipt of such notice from the selecting Party and such other Party determines in good faith
that it intends to continue such Active Internal Development Program, and so notifies the selecting Party. If neither of these criteria applies, the Target shall be considered to have been successfully nominated as a Tekmira Additional Non-Exclusive
Target, Tekmira Additional Exclusive Target, or Alnylam Additional Exclusive Target, as applicable. 
 (b) If a Target submitted
to Alnylam is not available for license as a Tekmira Additional Target pursuant to subsection (a) above, then Tekmira may nominate an additional Target as a Tekmira Additional Target, until two (2) Tekmira Additional Exclusive Targets and
five (5) Tekmira Additional Non-Exclusive Targets have been identified and successfully nominated pursuant to the foregoing procedure. Any Target successfully nominated pursuant to the foregoing procedure shall be a Tekmira Additional Target.

 (c) If a Target submitted to Tekmira is not available for license as an Alnylam Additional Exclusive Target pursuant to
subsection (a) above, then Alnylam may nominate an 

  
 16 

 
additional Target as an Alnylam Additional Exclusive Target, until five (5) Alnylam Additional Exclusive Targets have been identified and successfully nominated pursuant to the foregoing
procedure. Any Target successfully nominated pursuant to the foregoing procedure shall be an Alnylam Exclusive Additional Target. 
 ARTICLE IV - FINANCIAL PROVISIONS 
 4.1 Manufacturing Opt-Out
Payment. Within ten (10) Business Days after the Effective Date, Alnylam shall pay Tekmira a fee of thirty million U.S. dollars ($30,000,000), which amount shall constitute full consideration for the termination of and release of Alnylam
from all of Alnylam’s obligations under the Manufacturing Agreements, including without limitation the obligations to obtain materials and/or services from Tekmira, and the rights to Manufacture and have Manufactured Alnylam Products included
in the Development and Commercialization rights granted to Alnylam pursuant to Sections 2.2(a) and 2.2(b). Based on Tekmira’s provision to Alnylam of a completed Form W-8BEN, Alnylam agrees that it will not withhold taxes from the payment under
this Section 4.1. 
 4.2 Restructuring Payment. Within ten (10) Business Days after the Effective Date, Alnylam
shall pay Tekmira a fee of thirty-five million U.S. dollars ($35,000,000), which amount shall constitute payment for the termination of the Prior Cross-License Agreements and the Parties’ rights and obligations thereunder, as well as the
restructuring of certain milestone payments and royalty rates for certain Alnylam Products as set forth in Sections 4.6 and 4.9(d). Based on Tekmira’s provision to Alnylam of a completed Form W-8BEN, Alnylam agrees that it will not withhold
taxes from the payment under this Section 4.2. 
 4.3 Milestones with Respect to Tekmira Milestone Products. On a
Tekmira Milestone Product-by-Tekmira Milestone Product basis, payments will be payable by Tekmira to Alnylam based upon the achievement of certain milestone events as set forth in the table below (all references are to U.S. dollars). Tekmira will
provide written notice to Alnylam of the occurrence of a milestone event within [**] Business Days, and pay the indicated milestone fee to Alnylam within [**] days, after the occurrence of the relevant event. 

Capitalized terms in the chart below shall be read in context to apply to Tekmira Milestone Products; provided, however, that each
milestone payment will be payable no more than once in respect of any given Tekmira Milestone Product. 
  

					
	 Milestone Event
	  	Milestone Fee	 
		
	 [**]
	  	 	[**	] 
		
	 [**]
	  	 	[**	] 
		
	 [**]
	  	 	[**	] 
		
	 [**]
	  	 	[**	] 

  
 17 

					
	 Milestone Event
	  	Milestone Fee	 
		
	 [**]
	  	 	[**	] 
		
	 [**]
	  	 	[**	] 

 If one or more milestone events set out above are skipped for any reason, the payment for such skipped milestone event(s)
will be due at the same time as the payment for the next achieved milestone event. The milestone payments described above shall be payable only once in relation to each Tekmira Milestone Product that achieves Regulatory Approval in a Major Market
(each, a “Successful Tekmira Milestone Product”). Therefore, unless and until there is a Successful Tekmira Milestone Product directed to a particular Target, any of the milestone payments made by Tekmira under this Section in connection
with a Tekmira Milestone Product directed to such Target shall be fully creditable against the repeated achievement of such milestone event by any other Tekmira Milestone Product directed to such Target. However, in the event that there is a
Successful Tekmira Milestone Product directed to a Target and Tekmira subsequently begins to Develop or continues to develop a Follow-On Product then, if and when any of the milestone events set out above is thereafter achieved for such Follow-On
Product, in addition to the milestone payment for such milestone event, there will also be due and payable all of the milestone payment(s) for any such milestones that were achieved but not paid for such Follow-On Product prior to the achievement of
Regulatory Approval in a Major Market of a Successful Tekmira Milestone Product with respect to such Target. 
 4.4
Milestones with Respect to Biodefense Targets. The milestone fees payable by Alnylam to Tekmira with respect to Alnylam Products directed to Biodefense Targets that are not intended for sale, directly or indirectly, to a Funding Authority
shall be as set forth in Section 4.4. The milestone fees payable by Alnylam to Tekmira with respect to Alnylam Products Covered by a Valid Claim within the Tekmira Royalty-Bearing Patents that are directed to Biodefense Targets which are
intended for sale, directly or indirectly, to a Funding Authority shall be payable on an Alnylam Product-by-Alnylam Product basis as follows, subject to Section 4.6: 

 

					
	 Milestone Event
	  	Milestone Fee	 
		
	 [**]
	  	 	[**	] 
		
	 [**]
	  	 	[**	] 
		
	 [**]
	  	 	[**	] 

 In the event one or more milestone events set out above are skipped for any reason, the payment for such skipped
milestone event(s) will be due at the same time as the payment for the next achieved milestone event. The milestone payments described above shall be payable only once in relation to each Alnylam Royalty Product directed to a Biodefense Target that
achieves First 

  
 18 

 
Commercial Sale in a Major Market (each, a “Successful Biodefense Product”). Therefore, unless and until there is a Successful Biodefense Product directed to a particular Biodefense
Target, any of the milestone payments made by Alnylam under this Section in connection with an Alnylam Product directed to such Biodefense Target shall be fully creditable against the repeated achievement of such milestone event by any other Alnylam
Product directed to such Biodefense Target. However, in the event that there is a Successful Biodefense Product directed to a Biodefense Target and Alnylam subsequently begins to Develop or continues to Develop a Follow-On Product, then, if and when
any of the milestone events set out above is thereafter achieved for such Follow-On Product directed to such Biodefense Target, in addition to the milestone payment for such milestone event, there will also be due and payable all of the milestone
payment(s) for any such milestones that were achieved but not paid for such Follow-On Product prior to the achievement of Approval in a Major Market of a Successful Biodefense Product with respect to such Biodefense Target. 

4.5 Milestones with Respect to Alnylam Products. On an Alnylam Product-by-Alnylam Product basis, and except as otherwise set forth
in Sections 4.4 and 4.6, payments will be payable by Alnylam to Tekmira based on the achievement of certain milestone events as set forth in the table below (all references are to U.S. dollars) with respect to any Alnylam Product that is Covered by
a Valid Claim within the Tekmira Royalty-Bearing Patents. Alnylam will provide written notice to Tekmira of the occurrence of a milestone event within [**] Business Days, and pay the indicated milestone fee to Tekmira within [**] days, after the
occurrence of the relevant event. 
 Capitalized terms in the chart below shall be read in context to apply to Alnylam Products;
provided, however, that each milestone payment will be payable no more than once in respect of any given Alnylam Product. 
  

					
	 Milestone Event
	  	Milestone Fee	 
		
	 [**]
	  	 	[**	] 
		
	 [**]
	  	 	[**	] 
		
	 [**]
	  	 	[**	] 
		
	 [**]
	  	 	[**	] 
		
	 [**]
	  	 	[**	] 
		
	 [**]
	  	 	[**	] 

 If one or more milestone events set out above are skipped for any reason, the payment for such skipped milestone event(s)
will be due at the same time as the payment for the next achieved milestone event. The milestone payments described above shall be payable only once in relation to each Alnylam Product that achieves Regulatory Approval in a Major Market (each, a

  
 19 

 
“Successful Alnylam Product”). Therefore, unless and until there is a Successful Alnylam Product directed to a particular Target, any of the milestone payments made by Alnylam under
this Section in connection with an Alnylam Product directed to such Target shall be fully creditable against the repeated achievement of such milestone event by any other Alnylam Product directed to such Target. However, in the event that there is a
Successful Alnylam Product directed to a Target and Alnylam subsequently begins to Develop or continues to Develop a Follow-On Product, if and when any of the milestone events set out above is thereafter achieved for such Follow-On Product directed
to such Target, in addition to the milestone payment for such milestone event, there will also be due and payable all of the milestone payment(s) for any such milestones that were achieved but not paid for such Follow-On Product prior to the
achievement of Regulatory Approval in a Major Market of a Successful Alnylam Product directed to such Target. 
 4.6
Milestones for Certain Alnylam Existing Exclusive Targets. In lieu of any milestone payments under Sections 4.4 and 4.5 with respect to all Alnylam Products that are directed to any of the Alnylam Existing Exclusive Targets, a milestone
payment will be due by Alnylam to Tekmira solely for the first achievement of each of the corresponding milestone events set forth in the table below (all references are to U.S. dollars) by the applicable Alnylam Product identified below. Alnylam
will provide written notice to Tekmira of the occurrence of a milestone event within [**] Business Days, and pay the indicated milestone fee to Tekmira within [**] days, after the occurrence of the relevant milestone event. For the avoidance of
doubt, each milestone fee set forth below will be payable no more than once. 
  

					
	 Milestone Event
	  	Milestone Fee	 
		
	 Dosing of first patient in a Phase III Clinical Trial for ALN-TTR; provided that such ALN-TTR is Covered by a Valid
Claim within the Tekmira Royalty-Bearing Patents
	  	$	5,000,000	  
		
	 Tekmira has [**] for clinical development of ALN-VSP in China either by (i) provision of direct Manufacturing services, including
but not limited to the clinical trial drug product material and associated manufacturing and regulatory information necessary and sufficient for the initiation of a clinical trial in China or Korea, or (ii) the transfer of necessary Manufacturing
process technology used to produce batch [**] of ALN-VSP for Alnylam clinical trials and sufficient to produce at least one (1) batch of ALN-VSP suitable for clinical trials in China or Korea.
	  	$	5,000,000	  

  
 20 

 In addition to the corresponding milestone fee, all expenses actually incurred by Tekmira for the activities
set forth in clauses (i) and (ii) in the second milestone listed in the above table shall be paid by [**]. 
 4.7
Royalty Term. Royalties shall be payable hereunder on a Product-by-Product and country-by-country basis commencing on the First Commercial Sale of a Product in a country and continuing during any period in which (a) in the case of
Alnylam Products, a Valid Claim within the Tekmira Royalty-Bearing Patents Covers the applicable Alnylam Product in such country of sale, or (b) in the case of Tekmira Products, a Valid Claim within the Alnylam Patents Covers the applicable
Tekmira Product in such country of sale (such period, as applicable, the “Royalty Term”). Upon the expiration of the Royalty Term applicable to a given Product and country, the license granted under Section 2.1(a),
Section 2.1(b), Section 2.2(a) or Section 2.2(b), as applicable, shall become fully paid-up, royalty-free, non-exclusive, perpetual and irrevocable with respect to such Product in such country. 

4.8 Royalties Payable by Tekmira. During the applicable Royalty Term, Tekmira shall pay running royalties on Net Sales of Tekmira
Products Covered by one or more Valid Claims of any Alnylam Patent in the applicable country of sale in accordance with the applicable running royalty rates set out in the table below (all references are to U.S. dollars): 

 

					
	 Aggregate Annual Net Sales
	  	Royalty Rate	 
		
	 [**]
	  	 	[**	]% 
		
	 [**]
	  	 	[**	]% 
		
	 [**]
	  	 	[**	]% 
		
	 [**]
	  	 	[**	]% 

 No royalties will be payable more than once by Tekmira with respect to any single unit of Tekmira Product. 

4.9 Royalties on Alnylam Products. During the applicable Royalty Term, Alnylam shall pay running royalties on Net Sales of Alnylam
Products Covered by one or more Valid Claims of the Tekmira Royalty-Bearing Patents in the applicable country of sale, as follows (all references are to U.S. dollars), whether or not such Alnylam Products are directed to Biodefense Targets, subject
to Section 4.9(d): 
 (a) Where the Net Sales are those of, and are invoiced by, any one of the following: 

(i) Alnylam or its Affiliate; 

  
 21 

 (ii) Roche; 
 (iii) Regulus Therapeutics under a sub-license granted by Alnylam; or 
 (iv)
another sub-licensee under a sub-license granted by Alnylam in connection with, and solely for the purpose of, a Bona Fide Collaboration; 
 the
applicable running royalty rates shall be as set out in the table below: 
  

					
	 Aggregate Annual Net Sales
	  	Royalty Rate	 
		
	 [**]
	  	 	[**	]% 
		
	 [**]
	  	 	[**	]% 
		
	 [**]
	  	 	[**	]% 

 (b) In all other cases, the applicable running royalty rates shall be set out in the table below:

  

					
	 Aggregate Annual Net Sales
	  	Royalty Rate	 
		
	 [**]
	  	 	[**	]% 
		
	 [**]
	  	 	[**	]% 
		
	 [**]
	  	 	[**	]% 
		
	 [**]
	  	 	[**	]% 

 (c) No royalties will be payable more than once by Alnylam with respect to any single unit of Alnylam
Product. 
 (d) The royalty rate payable on Net Sales of Alnylam Products Covered by one or more Valid Claims of the Tekmira
Royalty-Bearing Patents in the applicable country of sale that are directed to any of the Alnylam Existing Exclusive Targets shall be reduced by [**] percent ([**]%) of Aggregate Annual Net Sales at all tiers set forth in the tables in subsections
(a) and (b) above (e.g., where such a table indicates a royalty rate of [**]%, the royalty rate that would apply instead with respect to Net Sales of Alnylam Products directed to any of the Alnylam Existing Exclusive Targets shall
be [**]%). 

  
 22 

 4.10 Royalty Reduction. The royalties due under Section 4.8 or 4.9 above, as
applicable, may be reduced on a country-by-country basis in the Territory by the amount of royalties paid or payable with respect to Necessary Third Party IP; provided, however, that royalties due under Section 4.8 or 4.9 above,
as applicable, may not be reduced by more than [**] of the royalties otherwise due (and will not in any case be reduced below [**] of the amount of royalties that would otherwise be due, e.g., for Net Sales of a Tekmira Product up to and
including $[**], the minimum effective royalty rate would be [**]%). For purposes of illustration only, if Aggregate Annual Net Sales of a Tekmira Product are $[**] and royalties due to Third Parties in respect of the sale of such product total [**]
percent ([**]%) of Net Sales (or $[**]), royalties due to Alnylam may be reduced only by $[**] which is determined as follows: maximum reduction is [**] of the royalty due on Net Sales of $[**], calculated by [**]. For the avoidance of doubt,
royalties paid or payable by Alnylam pursuant to the Supplemental Agreement or the Sponsored Research Agreement shall constitute royalties paid or payable to Third Parties with respect to Necessary Third Party IP for purposes of this
Section 4.10, notwithstanding any assignment or transfer of the rights to receive such payments to Tekmira or any of its Affiliates; provided, however, that royalties paid or payable pursuant to the Supplemental Agreement or the
Sponsored Research Agreement on Aggregate Annual Net Sales greater than $[**] of any Alnylam Product, where such royalties are paid or payable only because such Alnylam Product is Covered by a Valid Claim within the Category 1 Patents (i.e.,
where such royalties would not be paid or payable based on other patent rights in the absence of such Category 1 Patents), shall not result in a reduction to royalties under this Agreement pursuant to this Section 4.10 of more than [**]% of
such Aggregate Annual Net Sales greater than $[**] in respect of any such Alnylam Product. 
 4.11 Third Party License
Payments. Tekmira shall pay 100% of all royalties, license fees, milestones and similar payments (if any) payable to any Third Party under its existing in-licenses, if any, for the rights to Tekmira Combined Licensed Technology licensed to
Alnylam under this Agreement. In addition, notwithstanding the differences between the milestones and royalties payable by Alnylam under this Agreement and the milestones and royalties that were payable under the Alnylam-Tekmira LCA, Tekmira remains
solely responsible for, and agrees to pay to UBC, any and all amounts payable to UBC pursuant to the Tekmira-UBC License Agreement, including, without limitation, any and all amounts payable to UBC in connection with Alnylam’s exercise of its
rights under the UBC Sublicense and any and all amounts paid by Alnylam to Tekmira under this Agreement or the UBC Sublicense. Alnylam shall pay 100% of all royalties, license fees, milestones and similar payments (if any) payable to any Third Party
under any Alnylam Existing In-License for the rights to Alnylam Licensed Technology licensed to Tekmira under this Agreement. 

4.12 Reports. As to each Royalty Quarter commencing with the Royalty Quarter during which the First Commercial Sale occurs with
respect to a Tekmira Product, in the case of Tekmira as the reporting Party, or with respect to an Alnylam Product, in the case of Alnylam as the reporting Party, within [**] days after the end of such Royalty Quarter (if the reporting Party has not
entered into an agreement with a Sublicensee) and within [**] days after the receipt by the reporting Party from a Sublicensee of such Sublicensee’s report, as required by such Sublicensee’s sublicense for each Royalty Quarter (if the
applicable Party has entered into an agreement with a Sublicensee), each reporting Party will deliver to the other Party to this 

  
 23 

 
Agreement a written report showing, on a country-by-country basis, the Net Sales of Products calculated under GAAP and its royalty obligation for such quarter with respect to such Net Sales under
this Agreement together with wire transfer of an amount equal to such royalty obligation. All Net Sales will be segmented in each such report according to sales by the selling Party and each of its Affiliates and Sublicensees, as well as on a
product-by-product basis, including the rates of exchange used to convert Net Sales to United States Dollars from the currency in which such sales were made. For the purposes of this Agreement, the rates of exchange to be used for converting Net
Sales to United States Dollars will be the simple average of the selling and buying rates of U.S. dollars published in The Wall Street Journal East Coast Edition for the last Business Day of the Royalty Quarter covered by the report.

 4.13 Tax Withholding. Each paying Party will use all reasonable and legal efforts to reduce tax withholding with
respect to payments to be made to the other Party under this Agreement. Notwithstanding such efforts, subject to Sections 4.1 and 4.2, if the paying Party concludes that tax withholdings under the laws of any country are required with respect to
payments, the paying Party will make the full amount of the required payment to such other Party after any tax withholding. In any such case, the paying Party shall provide such other Party with a written explanation of such withholding and original
receipts or other evidence reasonably desirable and sufficient to allow it to document such tax withholdings for purposes of claiming foreign tax credits and similar benefits. 
 4.14 Payments. Unless otherwise agreed by the Parties, all payments required to be made under this Agreement will be made in United States Dollars via wire transfer to an account designated in
advance by the receiving Party. 
 4.15 Audits. At any given point in time, each Party will have on file and will require
its Affiliates and Sublicensees to have on file complete and accurate records for the last [**] years of all Net Sales of Products for which it is the paying Party. The other Party to this Agreement will have the right, [**] during each twelve
(12) month period, to retain at its own expense an independent qualified certified public accountant reasonably acceptable to such Party to review such records solely for accuracy and for no other purpose upon reasonable notice and under a
written obligation of confidentiality, during regular business hours. If the audit demonstrates that the payments owed under this Agreement have been understated, the audited Party will pay the balance to such other Party together with interest on
such amounts from the date on which such payment obligation accrued at a rate equal to the then current [**]-day United States dollar LIBOR rate plus [**] percent per annum. If the underpayment is greater than five percent of the amount owed, then
the audited Party will reimburse such other Party for its reasonable out-of-pocket costs of the audit. If the audit demonstrates that the payments owed under this Agreement have been overstated, such other Party to this Agreement will credit the
balance against the next payment due from the audited Party (without interest). 

  
 24 

 ARTICLE V - INTELLECTUAL PROPERTY 

5.1 Category 1, 2 and 3 Patents. Subject to the terms and conditions set forth in the Exhibit A attached hereto (the “IP
Management Terms”): 
 (a) Alnylam hereby assigns to Tekmira all of Alnylam’s right, title and interest in and to the
Category 1 Patents, subject to any existing rights granted by Alnylam to Third Parties under the Category 1 Patents, including but not limited to such rights granted by Alnylam to UBC and AlCana under the Supplemental Agreement and rights granted
under the Alnylam Existing Sublicenses; provided, however, that such assignment shall exclude any right to enforce the Category 1 Patents with respect to any alleged infringing activities by Alnylam and/or any of its licensees that
occurred prior to the Effective Date. 
 (b) In the event that Tekmira obtains any ownership interest in any Category 2 Patent
or Category 3 Patent pursuant to the inventorship determination made under Sections 5 and 6 of the IP Management Terms, Tekmira shall and hereby does assign to Alnylam all of Tekmira’s right, title and interest in and to such Category 2 Patent
or Category 3 Patent, as applicable. 
 (c) Each Party agrees to execute such further documents and take such further actions as
the other Party may reasonably request in order to give effect to the assignments contemplated under subsections (a) and (b) above. 
 (d) The filing, prosecution and maintenance of Category 1 Patents, Category 2 Patents and Category 3 Patents shall be governed by the applicable provisions of the IP Management Terms. 

5.2 Prosecution and Maintenance of Other Patents. Subject to the IP Management Terms, Alnylam will have the sole right and
responsibility, at Alnylam’s discretion and at its expense, to file, prosecute and maintain patent protection in the Territory for all Patents (other than Category 2 Patents, and Category 3 Patents) within the Alnylam Licensed Technology.
Tekmira will have the sole right and responsibility, at Tekmira’s discretion and at its expense, to file, prosecute and maintain patent protection in the Territory for all Patents (other than Category 1 Patents) within the Tekmira Combined
Licensed Technology. 
 5.3 Third Party Infringement of Alnylam’s Patents. 

(a) Each Party will promptly report in writing to the other Party during the Term any known or suspected infringement by a Third Party of
any of the Alnylam Patents of which such Party becomes aware, as such infringement relates to Research, Development or Commercialization of Products directed at any Tekmira Target, or any Tekmira Product, and will provide the other Party with all
available evidence supporting such infringement. 
 (b) Alnylam will have the sole and exclusive right to initiate an
infringement or other appropriate suit in the Territory with respect to infringements or suspected infringements of any of the Alnylam Patents and to any and all recoveries obtained in connection therewith. 

(c) Alnylam will have the sole and exclusive right to select counsel for any suit referred to in subsection 5.3(b) above initiated by it
and will pay all expenses of the suit, including without limitation attorneys’ fees and court costs. 

  
 25 

 5.4 Competitive Infringement of Category 1 Patents. 

(a) Each Party will promptly report in writing to the other Party during the Term any known or suspected infringement by a Third Party of
any of the Category 1 Patents of which such Party becomes aware. If any such infringement relates to the development, making, using, selling, offering for sale or importing of a product that is directed against an Alnylam Exclusive Target
(“Competitive Infringement”), then Alnylam will have the first right to initiate an infringement or other appropriate suit in the Territory with respect to such Competitive Infringement; provided, that if Alnylam fails to
initiate a suit or take other appropriate action with respect to such Competitive Infringement within [**] days after becoming aware of the basis for such suit or action, then Tekmira may, in its discretion, provide Alnylam with written notice of
Tekmira’s intent to initiate a suit or take other appropriate action with respect to such Competitive Infringement. If Tekmira provides such notice and Alnylam fails to initiate a suit or take such other appropriate action within [**] days
after receipt of such notice from Tekmira, then Tekmira shall have the right to initiate a suit or take other appropriate action that it believes is reasonably required to protect its interests with respect to such Competitive Infringement.

 (b) The Party bringing the enforcement action with respect to such Competitive Infringement shall have the right to defend
against any claim arising during such action asserting that the Category 1 Patent that is subject of such Competitive Infringement is invalid or unenforceable. 
 (c) Regardless of which Party brings such the enforcement action with respect to such Competitive Infringement, the Party not bringing the enforcement action shall (i) provide all reasonable
assistance to the Party bringing the action, at the expense of the Party bringing the action, and (ii) have the right to join and participate in such action at its own expense with its own counsel and to share equally all expenses of such suit
if it so elects. If required under applicable law in order for the initiating Party to initiate and/or maintain such suit, or if the initiating Party is unable to initiate or prosecute such suit solely in its own name or it is otherwise advisable to
obtain an effective legal remedy, in each case, the other Party shall, at the expense of the initiating Party, join as a party to the suit and will execute all documents necessary for the initiating Party to initiate litigation to prosecute and
maintain such action. 
 (d) Any damages or other recovery, whether by settlement or otherwise, from an action under this
Section 5.4 to enforce the Category 1 Patent against Competitive Infringement shall first be applied pro rata to reimburse the Parties for the costs and expenses of litigation in such action, and [**] percent ([**]%) of any remaining
amount shall be paid to or retained by the Party conducting the litigation and [**] percent ([**]%) of such remaining amount shall be paid to or retained by the other Party. 
 5.5 Third Party Infringement of Tekmira’s Patents. 
 (a) Each Party
will promptly report in writing to the other Party during the Term any known or suspected infringement by a Third Party of any Patents within the Tekmira Combined Licensed Technology of which such Party becomes aware, as such infringement relates to
the Research, Development or Commercialization of Products directed at any Alnylam Target, or any Alnylam Product, and will provide the other Party with all available evidence supporting such infringement. 

  
 26 

 (b) Tekmira will have the sole and exclusive right to initiate an infringement or other
appropriate suit in the Territory with respect to infringements or suspected infringements of any of the Patents within the Tekmira Combined Licensed Technology, and of any of the Category 1 Patents that does not constitute Competitive Infringement
and to any and all recoveries obtained in connection therewith. 
 (c) Tekmira will have the sole and exclusive right to select
counsel for any suit referred to in subsection 5.5(b) above initiated by it and will pay all expenses of the suit, including without limitation attorneys’ fees and court costs. 

5.6 Patent Certification. To the extent required by law or permitted by law, the Parties shall use reasonable efforts to maintain
with the applicable regulatory authorities during the Term correct and complete listings of applicable Patents for Alnylam Products or Tekmira Products, as the case may be, being Commercialized, including but not limited to all so-called
“Orange Book” listings required under the Hatch-Waxman Act. 
 ARTICLE VI - CONFIDENTIAL INFORMATION AND PUBLICITY

 6.1 Non-Disclosure of Confidential Information. Each Party agrees that all Confidential Information of a Party
that is disclosed by a Party to the other Party (a) will not be used by the receiving Party except in connection with the activities contemplated by this Agreement, (b) will be maintained in confidence by the receiving Party, and
(c) will not be disclosed by the receiving Party to any Third Party without the prior written consent of the disclosing Party. Notwithstanding the foregoing, the receiving Party will be entitled to use and disclose Confidential Information of
the disclosing Party that (i) was known by the receiving Party or its Affiliates prior to its date of disclosure by the disclosing Party to the receiving Party as demonstrated by legally admissible evidence available to the receiving Party,
(ii) either before or after the date of the disclosure such Confidential Information is lawfully disclosed to the receiving Party or its Affiliates by sources other than the disclosing Party, (iii) either before or after the date of the
disclosure by the disclosing Party or its Affiliates to the receiving Party such Confidential Information becomes published or otherwise part of the public domain through no fault, act or omission on the part of the receiving Party or its
Affiliates, (iv) is independently developed by or for the receiving Party or its Affiliates without reference to or in reliance upon the Confidential Information as demonstrated by legally admissible evidence available to the receiving Party or
its Affiliates, (v) is reasonably necessary to conduct clinical trials or to obtain regulatory approval of Products, or for the prosecution and maintenance of Patents, and such Patents shall include without limitation claims to the nucleic acid
component of the Products, the Products as formulated with an LNP including excipients, as well as methods of use and manufacture of the foregoing, along with any other claims that are usual and customary to obtain maximum protection for a
pharmaceutical, (vi) is reasonably required in order for a Party to obtain financing or conduct discussions with existing or potential Development and/or Commercialization partners so long as such Third Party recipients are bound by an
obligation of confidentiality, or (vii) in the reasonable judgment of the receiving Party is required to be disclosed by the receiving Party to comply with applicable laws or regulations or legal process, including without limitation by the
rules or regulations of the United States Securities and Exchange Commission or similar regulatory agency in a country other than the United States or 

  
 27 

 
of any stock exchange or NASDAQ, provided that the receiving Party provides prior written notice of such disclosure to the disclosing Party and takes reasonable and lawful actions
to avoid or minimize the extent of such disclosure, or (viii) solely with respect to Confidential Information comprising Alnylam Know-How, Tekmira Know-How or Protiva Know-How, is otherwise reasonably necessary to disclose in connection with
the Research, Development or Commercialization of Products hereunder. 
 Alnylam and its Affiliates shall not provide the Tekmira Manufacturing
Documents or copies thereof to any Third Party, and shall not reproduce such Tekmira Manufacturing Documents in any patent application, publication or other public disclosure; provided, however, that Alnylam and its Affiliates shall be
permitted to provide such Tekmira Manufacturing Documents to (1) on a need-to-know basis, Third Party contract manufacturers and other Permitted Contractors that are engaged to manufacture Alnylam Products or to provide services in connection
with Development, Manufacturing or regulatory matters for Alnylam Products and/or (2) Sublicensees (who shall also be permitted to provide such Tekmira Manufacturing Documents on a need-to-know basis to Third Party contract manufacturers and
other Permitted Contractors that are engaged to manufacture Alnylam Products or to provide services in connection with Development, Manufacturing or regulatory matters for Alnylam Products), in each of the foregoing clauses (1) or (2), that are
subject to binding confidentiality agreements containing reasonably customary terms and conditions and, in the case of Third Party contract manufacturers and other Permitted Contractors, restricting such Third Parties from providing the Tekmira
Manufacturing Documents to further Third Parties other than in accordance with clause (3) below, and/or (3) regulatory authorities to the extent reasonably necessary to obtain Regulatory Approval for, or comply with regulatory requirements
applicable to the Development or Commercialization of, any Alnylam Product. 
 Notwithstanding anything to the contrary in this Agreement, the
confidentiality and non-use obligations under this Agreement and the restrictions set forth in the immediately preceding paragraph shall not apply to Confidential Information consisting of Alnylam Know-How, Tekmira Know-How or Protiva Know-How,
including such Confidential Information comprised by the Tekmira Manufacturing Documents, that is mentally retained in the unaided memories of the receiving Party’s and its Affiliates’ employees, consultants and advisors. 

For the avoidance of doubt, information received by a Party solely as a result of the litigation settled pursuant to the Settlement Agreement shall not
be governed by this Agreement and therefore shall not be subject to the exceptions set forth in the immediately preceding paragraphs permitting the use and disclosure of Confidential Information hereunder (i.e., nothing in this Agreement shall
lessen any restrictions on the use and disclosure of such information imposed in such litigation proceedings). 
 If a Party is required by
judicial or administrative process to disclose Confidential Information that is subject to the non-disclosure provisions of this Section 6.1, such Party shall promptly inform the other Party of the disclosure that is being sought in order to
provide the other Party an opportunity to challenge or limit the disclosure obligations. Confidential Information that is disclosed by judicial or administrative process shall remain otherwise subject to the confidentiality and non-use provisions of
this Section 6.1, and the Party disclosing Confidential 

  
 28 

 
Information pursuant to law or court order shall take all steps reasonably practical, including without limitation seeking an order of confidentiality, to ensure the continued confidential
treatment of such Confidential Information. In addition to the foregoing restrictions on public disclosure, if either Party concludes that a copy of this Agreement must be filed with the United States Securities and Exchange Commission or similar
regulatory agency in a country other than the United States, such Party shall seek the maximum confidential treatment available under applicable law, provide the other Party with a copy of this Agreement showing any sections as to which the Party
proposes to request confidential treatment, provide the other Party with an opportunity to comment on any such proposal and to suggest additional portions of this Agreement for confidential treatment, and take such Party’s reasonable comments
into consideration before filing this Agreement. 
 6.2 Limitation on Disclosures. Each Party agrees that it will provide
Confidential Information received from the other Party solely to its employees, consultants and advisors, and the employees, consultants and advisors of its or its Affiliates or existing or potential Sublicensees, as applicable, who have a
legitimate business need to know and an obligation to maintain in confidence the Confidential Information of the disclosing Party. The receiving Party is liable for any breach of the non-disclosure obligation of, as applicable, (a) its and its
Affiliates’ employees, consultants and advisors, (b) existing or potential Sublicensees and (c) the employees, consultants and advisors of any existing or potential Sublicensees. 

6.3 Publicity. 
 (a) No disclosure of the existence of, or the terms of, this Agreement may be made by either Party or its Affiliates, and no Party or its Affiliates shall use the name, trademark, trade name or logo of
the other Party or its employees in any publicity, news release or disclosure relating to this Agreement or its subject matter, without the prior express written permission of the other Party, except as may be required by law or as set forth in this
Section 6.3. Either Party may issue press releases or otherwise make public statements or disclosures (such as in annual reports to stockholders or filings with the Securities and Exchange Commission) as it determines, based on advice of
counsel, are reasonably necessary to comply with applicable laws and regulations. In addition, following any press release(s) announcing this Agreement or any other public disclosure by the Parties, either Party shall be free to disclose, without
the other Party’s prior written consent, the existence of this Agreement, the identity of the other Party and those terms of the Agreement which have already been publicly disclosed in accordance herewith. 

Any reference made by Alnylam in a press release to LNP technology shall include the following statement: 

“About LNP Technology 
 Alnylam has licenses to Tekmira LNP intellectual property for use in RNAi therapeutic products.” 

  
 29 

 Any reference made by Tekmira in a press release to siRNA programs shall include the
following statement: 
 “About Alnylam RNAi Technology 

Tekmira has licenses to Alnylam RNAi intellectual property for certain RNAi programs.” 

ARTICLE VII - INDEMNIFICATION AND INSURANCE 
 7.1 Tekmira Indemnification. Tekmira agrees to indemnify and hold harmless Alnylam and its Affiliates, and their respective agents, directors, officers and employees and their respective successors
and permitted assigns (the “Alnylam Indemnitees”) from and against any and all losses, costs, damages, fees or expenses (“Losses”) incurred by an Alnylam Indemnitee arising out of or in connection with any claim, suit, demand,
investigation or proceeding brought by a Third Party based on (a) any claim made against Alnylam by Third Parties regardless of the form or forum in which any such claim is made alleging (i) infringement or misappropriation of Third Party
intellectual property, or (ii) personal injury, or death occurring to any person claimed to result, directly or indirectly, from the possession, use or consumption of, or treatment with, any Tekmira Product Covered by an Alnylam Patent, whether
claimed by reason of breach of warranty, negligence or product defect, and (b) any breach of any representation, warranty or covenant of Tekmira in this Agreement. 
 The above indemnification shall not apply to the extent that any Losses are due to a breach of any of Alnylam’s representations, warranties, covenants and/or obligations under this Agreement.

 7.2 Alnylam Indemnification. Alnylam agrees to indemnify and hold harmless Tekmira, its Affiliates, and their
respective agents, directors, officers and employees and their respective successors and permitted assigns (the “Tekmira Indemnitees”) from and against any and all Losses incurred by a Tekmira Indemnitee arising out of or in connection
with any claim, suit, demand, investigation or proceeding brought by a Third Party based on (a) any claim made against Tekmira by Third Parties regardless of the form or forum in which any such claim is made alleging (i) infringement or
misappropriation of Third Party intellectual property, or (ii) personal injury, or death occurring to any person claimed to result, directly or indirectly, from the possession, use or consumption of, or treatment with, any Alnylam Product
Covered by a Tekmira Patent, whether claimed by reason of breach of warranty, negligence or product defect, and (b) any breach of any representation, warranty or covenant of Alnylam in this Agreement. 

The above indemnification shall not apply to the extent that any Losses are due to a breach of any of Tekmira’s representations, warranties,
covenants and/or obligations under this Agreement. 
 7.3 Tender of Defense; Counsel. The obligation to indemnify
pursuant to this Article shall be contingent upon timely notification by the indemnitee to the indemnitor of any claims, suits or service of process; the tender by the indemnitee to the indemnitor of full control over the conduct and disposition of
any claim, demand or suit; and reasonable cooperation by the 

  
 30 

 
indemnitee in the defense of the claim, demand or suit. No indemnitor will be bound by or liable with respect to any settlement or admission entered or made by any indemnitee without the prior
written consent of the indemnitor. The indemnitee will have the right to retain its own counsel to participate in its defense in any proceeding hereunder. The indemnitee shall pay for its own counsel except to the extent it is determined that
(a) one or more legal defenses may be available to it which are different from or additional to those available to the indemnitor, or (b) representation of both Parties by the same counsel would be inappropriate due to actual or potential
differing interests between them. In any such case and to such extent, the indemnitor shall be responsible to pay for the reasonable costs and expenses of one separate counsel retained to participate in the defense of the indemnitee, provided that
such expenses are otherwise among those covered by the indemnitor’s indemnity obligations under this Article VII. Notwithstanding the foregoing, if the indemnitor reasonably believes that any of the exceptions to its obligation of
indemnification of the indemnitee set forth in Sections 7.1 or 7.2 may apply, the indemnitor shall promptly notify the indemnitee, which shall then have the right to be represented in any such action or proceeding by separate counsel at the
indemnitee’s expense; provided, that the indemnitor shall be responsible for payment of such expenses if the indemnitee is ultimately determined to be entitled to indemnification from the indemnitor. 

7.4 Tekmira Insurance. With respect to its activities under this Agreement, Tekmira will secure and maintain in full force and
effect throughout the term of the licenses set out in Section 2.1 (and for at least [**] years thereafter for claims-made coverage), the following types and amounts of insurance coverage with carriers having a minimum AM Best rating of A, with
per claim deductibles that do not exceed [**] U.S. dollars ($[**]): 
 Comprehensive General Liability and Personal Injury, including coverage
for contractual liability assumed by Tekmira and coverage for Tekmira independent contractor(s), with limits of at least [**] U.S. dollars ($[**]) per occurrence and a general aggregate limit of t[**] U.S. dollars ($[**]). 

Prior to, at, and following the dosing of the first patient in a Phase I Clinical Trial of any Tekmira Product by Tekmira, its Affiliates or
Sublicensees, Umbrella Liability, exclusive of the coverage provided by the policies listed above, with a limit of at least [**] U.S. dollars ($[**]). 
 Prior to, at, and following the First Commercial Sale of any Tekmira Product by Tekmira, its Affiliates or Sublicensees, Products/Clinical/Professional Liability, exclusive of the coverage provided by the
Comprehensive General Liability policy, with limits of at least [**] U.S. dollars ($[**]) per occurrence and an aggregate limit of at least [**] dollars ($[**]), with Alnylam to be named as an additional insured party with respect to each Tekmira
Product under such coverage. 
 7.5 Alnylam Insurance. With respect to its activities under this Agreement, Alnylam will
secure and maintain in full force and effect throughout the term of the licenses set out in Sections 2.2(a) and 2.2(b) (and for at least [**] years thereafter for claims-made coverage), the following types and amounts of insurance coverage with
carriers having a minimum AM Best rating of A, with per claim deductibles that do not exceed [**] U.S. dollars ($[**]): 
 Comprehensive General
Liability and Personal Injury, including coverage for contractual liability assumed by Alnylam and coverage for Alnylam independent contractor(s), with limits of at least [**] U.S. dollars ($[**]) per occurrence and a general aggregate limit of [**]
U.S. dollars ($[**]). 

  
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 Prior to, at, and following the dosing of the first patient in a Phase I Clinical Trial of any Alnylam
Product by Alnylam, its Affiliates or Sublicensees, Umbrella Liability, exclusive of the coverage provided by the policies listed above, with a limit of at least [**] U.S. dollars ($[**]). 
 Prior to, at, and following the First Commercial Sale of any Alnylam Product by Alnylam, its Affiliates or Sublicensees, Products/Clinical Liability, exclusive of the coverage provided by the
Comprehensive General Liability policy, with limits of at least [**] U.S. dollars ($[**]) per occurrence and an aggregate limit of at least [**] U.S. dollars ($[**]), with Tekmira to be named as an additional insured party with respect to each
Alnylam Product under such coverage. 
 ARTICLE VIII - EXPORT 

8.1 General. The Parties acknowledge that the exportation from the United States of materials, products and related technical data
(and the re-export from elsewhere of United States origin items) may be subject to compliance with United States export laws, including without limitation the United States Bureau of Export Administration’s Export Administration Regulations,
the Act and regulations of the FDA issued thereunder, and the United States Department of State’s International Traffic and Arms Regulations which restrict export, re-export, and release of materials, products and their related technical data,
and the direct products of such technical data. The Parties agree, under this Agreement, to comply with all applicable exports laws and to commit no act that, directly or indirectly, would violate any United States law, regulation, or treaty, or any
other international treaty or agreement, relating to the export, re-export, or release of any materials, products or their related technical data to which the United States adheres or with which the United States complies. 

8.2 Delays. The Parties acknowledge that they cannot be responsible for any delays attributable to export controls which are
beyond the reasonable control of either Party. 
 8.3 Assistance. The Parties agree to provide reasonable assistance to
one another in connection with each Party’s efforts to fulfill its obligations under this Article VIII. 
 ARTICLE IX -
TERM AND TERMINATION 
 9.1 Term; Expiration. The term of this Agreement shall begin on the Effective Date and,
unless terminated earlier as provided herein, the licenses granted under Sections 2.1(a), 2.1(b), 2.2(a), 2.2(b) and 2.2(c) of this Agreement will become fully paid-up, perpetual, non-exclusive and irrevocable at the end of the period set forth in
Section 4.7, as applicable to each of such licenses. The term of this Agreement shall expire upon the expiration of the last-to-expire Royalty Term. 

  
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 9.2 Material Breach. 

(a) Alnylam, as the licensor under Section 2.1, will have the right to terminate the licenses granted thereunder, upon written
notice to Tekmira, on a Tekmira Product-by-Tekmira Product basis in the event Tekmira materially breaches its obligations under this Agreement related to the licenses granted under Section 2.1 with respect to a particular Tekmira Product(s), or
such licenses in their entirety if such breach is not specific to particular Tekmira Product(s), and Tekmira does not remedy such breach within ninety (90) days after receipt of written notice from Alnylam specifically identifying the breach
and stating that Alnylam intends to terminate such licenses if Tekmira fails to remedy the breach within the ninety (90)-day time period; provided, however, that if Tekmira disputes in good faith that the claimed breach exists, such
90-day period will not start to run until such dispute has been resolved or can no longer be maintained in good faith. 
 (b)
Tekmira, as the licensor under Section 2.2, will have the right to terminate the licenses granted thereunder, upon written notice to Alnylam, on an Alnylam Product-by-Alnylam Product or technology-by-technology basis in the event Alnylam
materially breaches its obligations under this Agreement related to the licenses granted under Section 2.2 with respect to a particular Alnylam Product(s) or technology(-ies), or such licenses in their entirety if such breach is not specific to
particular Alnylam Product(s) or technology(-ies), and does not remedy such breach within ninety (90) days after receipt of written notice from Tekmira specifically identifying the breach and stating that Tekmira intends to terminate such
licenses if Alnylam fails to remedy the breach within the ninety (90)-day time period; provided, however, that if Alnylam disputes in good faith that the claimed breach exists, such 90-day period will not start to run until such
dispute has been resolved or can no longer be maintained in good faith. 
 9.3 Challenges of Alnylam’s Patents. In
the event that Tekmira or any of its Affiliates shall (a) commence or participate in any action or proceeding (including, without limitation, any patent opposition or re-examination proceeding), or otherwise assert in writing any claim,
challenging or denying the validity of any of the Alnylam Patents or any claim thereof or (b) actively assist any other Person in bringing or prosecuting any action or proceeding (including, without limitation, any patent opposition or
re-examination proceeding) challenging or denying the validity of the Alnylam Patents or any claim thereof, Alnylam will have the right to give notice to Tekmira (which notice must be given, if at all, within sixty (60) days after Alnylam first
learns of the foregoing) that the licenses granted by Alnylam to such Patent will terminate in thirty (30) days following such notice, and, unless Tekmira withdraws or causes to be withdrawn all such challenge(s) within such thirty-day period,
such licenses will so terminate. 
 9.4 Challenges of Tekmira Patents. In the event that Alnylam or any of its Affiliates
shall (a) commence or participate in any action or proceeding (including, without limitation, any patent opposition or re-examination proceeding), or otherwise assert in writing any claim, challenging or denying the validity of any of the
Category 1 Patents or Patents within the Tekmira Combined Licensed Technology, or any claim thereof or (b) actively assist any other Person in bringing or prosecuting any action or proceeding (including, without limitation, any patent
opposition or re-examination proceeding) challenging or denying the validity of any of the Category 1 Patents or Patents within the Tekmira Combined Licensed Technology, or any claim thereof, Tekmira will have the right to give notice to Alnylam
(which notice must be given, if at all, within sixty (60) days after Tekmira first learns of the foregoing) that Alnylam’s license 

  
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under such Patent will terminate in thirty (30) days following such notice, and, unless Alnylam withdraws or causes to be withdrawn all such challenge(s) within such thirty-day period, such
licenses will so terminate. 
 9.5 Consequences of Termination; Survival. 

(a) In the event of termination by Alnylam under Section 9.2(a) above, all licenses and rights granted by Alnylam to Tekmira under
Section 2.1 of this Agreement will terminate with respect to the particular Tekmira Product(s), or in their entirety, as provided in Section 9.2(a); provided, however, that to the extent such licenses and rights are required
in respect of clinical trials that are ongoing and cannot reasonably be terminated promptly due to health or safety reasons or the requirements of applicable law, such licenses and rights will continue in effect until such clinical trials are
properly terminated; provided, further, that any license that has become fully paid-up and perpetual pursuant to Section 9.1 shall survive. 
 (b) In the event of termination by Tekmira under Section 9.2(b) above, all licenses and rights granted by Tekmira to Alnylam under Section 2.2 of this Agreement will terminate with respect to
the particular Alnylam Product(s) and/or technology(-ies), or in their entirety, as provided in Section 9.2(b); provided, however, that to the extent such licenses and rights are required in respect of clinical trials that are
ongoing and cannot reasonably be terminated promptly due to health or safety reasons or the requirements of applicable law, such licenses and rights will continue in effect until such clinical trials are properly terminated; provided,
further, that any license that has become fully paid-up and perpetual pursuant to Section 9.1 shall survive. 
 (c)
Expiration or termination of this Agreement shall not relieve the Parties of any obligation accruing prior to such expiration or termination. Any expiration or termination of this Agreement shall be without prejudice to the rights of either Party
against the other accrued or accruing under this Agreement prior to expiration or termination, including without limitation the obligation to pay royalties for Products sold prior to such expiration or termination. The provisions of Sections 6.1,
6.2 and 6.3(a) shall survive the expiration or termination of this Agreement for a period of five (5) years. In addition, the provisions of Sections 2.2(c) (to the extent the license in such section extends outside of Alnylam Products in the
Alnylam Field), 2.2(d), 2.4, 2.6, 2.7, 4.7, 4.11, 4.12, 4.13, 4.14, 4.15, 5.1(d), 5.4, Article VII, 9.1, 9.5, 9.6, 10.1(d), 10.2, 10.4, 10.6, 10.8 and 10.16, and any license that has become fully paid-up and perpetual pursuant to Section 9.1,
shall survive any expiration or termination of this Agreement. 
 9.6 Licenses upon Termination. 

(a) Upon any termination of this Agreement, Alnylam shall enter into an agreement containing substantially the same provisions as this
Agreement with any Sublicensees of Tekmira existing at the time of such termination, covering the Tekmira Products that had been licensed to such Sublicensee by Tekmira in compliance with this Agreement, provided that at the time of
any termination of this Agreement, such Sublicensees are in full compliance with the terms and conditions of the sublicense agreement. Alnylam acknowledges that such Sublicensees of Tekmira that are then in full compliance with the terms and
conditions of their respective sublicense agreement are third party beneficiaries of this Agreement, including this Section 9.6(a). 

  
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 (b) Upon any termination of this Agreement, Tekmira shall enter into an agreement containing
substantially the same provisions as this Agreement with any Sublicensees of Alnylam existing at the time of such termination, covering the Alnylam Products that had been licensed to such Sublicensee by Alnylam in compliance with this Agreement,
provided that at the time of any termination of this Agreement, such Sublicensees are in full compliance with the terms and conditions of the sublicense agreement. Tekmira acknowledges that such Sublicensees of Alnylam that are then in
full compliance with the terms and conditions of their respective sublicense agreement are third party beneficiaries of this Agreement, including this Section 9.6(b). 
 ARTICLE X - MISCELLANEOUS 
 10.1 Representations and Warranties.

 (a) Mutual Representations and Warranties by Tekmira and Alnylam. 

(i) Each Party hereby represents and warrants to the other Party as of the Effective Date: 

(a) It is duly organized and validly existing under the laws of the jurisdiction of its incorporation or formation, and has all
necessary power and authority to conduct its business in the manner in which it is currently being conducted, to own and use its assets in the manner in which its assets are currently owned and used, and to enter into and perform its obligations
under this Agreement. 
 (b) The execution, delivery and performance of this Agreement has been duly authorized by all
necessary action on the part of such Party and its Board of Directors and no consent, approval, order or authorization of, or registration, declaration or filing with any Third Party or governmental authority is necessary for the execution, delivery
or performance of this Agreement. 
 (c) This Agreement constitutes the legal, valid and binding obligation of such Party,
enforceable against it in accordance with its terms, subject to (A) laws of general application relating to bankruptcy, insolvency and the relief of debtors, and (B) rules of law governing specific performance, injunctive relief and other
equitable remedies. 
 (d) It has never approved or commenced any proceeding, or made any election contemplating, the winding
up or cessation of its business or affairs or the assignment of material assets for the benefit of creditors. To such Party’s knowledge, no such proceeding is pending or threatened. 

(ii) Each Party acknowledges and agrees that the other Party has not made any representation or warranty that it has or can provide all
the rights that are necessary or useful to Research, Develop or Commercialize a Product. 

  
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 (iii) Each Party represents and warrants to the other Party that as of the Effective Date it
has the right to grant to such other Party, its Affiliates and Sublicensees the licenses granted hereunder and has not granted any conflicting rights to any other Person. Each Party shall maintain any applicable in-licenses in effect and shall not
amend any such in-licenses in a manner that is detrimental to the rights of the other Party under this Agreement without the prior written consent of such other Party. 
 (b) Alnylam Representations and Warranties. Alnylam hereby represents and warrants to Tekmira that: 
 (i) to Alnylam’s knowledge, the conception, development and reduction to practice of the Alnylam Licensed Technology licensed to Tekmira under this Agreement did not constitute or involve the
misappropriation of trade secrets or other rights or property of any Person; 
 (ii) it has not assigned, transferred, conveyed
or otherwise encumbered its right, title and interest in the Alnylam Licensed Technology in a manner that conflicts with any rights granted to Tekmira hereunder. 
 (c) Tekmira Representations and Warranties. Tekmira hereby represents and warrants to Tekmira that: 
 (i) to Tekmira’s knowledge, the conception, development and reduction to practice of the Tekmira Combined Licensed Technology licensed to Alnylam under this Agreement did not constitute or involve
the misappropriation of trade secrets or other rights or property of any Person; and 
 (ii) it has not assigned, transferred,
conveyed or otherwise encumbered its right, title and interest in the Tekmira Combined Licensed Technology in a manner that conflicts with any rights granted to Alnylam hereunder. 

(d) Warranty Disclaimer. EXCEPT AS OTHERWISE EXPRESSLY PROVIDED IN THIS AGREEMENT, NEITHER PARTY MAKES ANY REPRESENTATION OR
EXTENDS ANY WARRANTY OR CONDITIONS OF ANY KIND, EITHER EXPRESS OR IMPLIED, TO THE OTHER PARTY WITH RESPECT TO ANY INTELLECTUAL PROPERTY, PRODUCTS, GOODS, RIGHTS OR OTHER SUBJECT MATTER OF THIS AGREEMENT AND HEREBY DISCLAIMS ALL IMPLIED CONDITIONS,
REPRESENTATIONS, AND WARRANTIES, INCLUDING WITHOUT LIMITATION, WARRANTIES OF MERCHANTABILITY, FITNESS FOR A PARTICULAR PURPOSE AND NONINFRINGEMENT OR VALIDITY OF PATENT RIGHTS WITH RESPECT TO ANY AND ALL OF THE FOREGOING. EACH PARTY HEREBY DISCLAIMS
ANY REPRESENTATION OR WARRANTY THAT THE DEVELOPMENT, MANUFACTURE OR COMMERCIALIZATION OF ANY PRODUCT PURSUANT TO THIS AGREEMENT WILL BE SUCCESSFUL OR THAT ANY PARTICULAR SALES LEVEL WITH RESPECT TO ANY SUCH PRODUCT WILL BE ACHIEVED. 

  
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 10.2 Dispute Resolution; Arbitration Procedures. The Parties agree that any disputes
that arise under this Agreement between them during the period starting on the Effective Date and ending on the third anniversary of the Effective Date, including without limitation, claims relating to the enforcement of this Agreement, shall be
resolved by binding arbitration conducted in accordance with the Commercial Arbitration Rules and Supplementary Procedures for Large Complex Disputes of the American Arbitration Association (“AAA”). The arbitration shall be conducted by a
panel of three persons experienced in large commercial disputes who are independent of the arbitrating Parties and neutral with respect to the dispute presented for arbitration. Within [**] days after initiation of arbitration, each arbitrating
Party shall select one person to act as an arbitrator and the Party-selected arbitrators shall select an additional arbitrator within [**] days of their appointment. If the arbitrators selected by the Parties are unable or fail to agree on the third
arbitrator, the additional arbitrator shall be appointed by the AAA. The place of the arbitration shall be in Chicago, Illinois, USA, and all proceedings and communications shall be in English. Except to the extent necessary to confirm an award or
as may be required by law, neither a Party nor an arbitrator may disclose the existence, content, or results of an arbitration without the prior written consent of both Parties. 

10.3 Force Majeure. No failure or omission by the Parties in the performance of any obligation of this Agreement will be deemed a
breach of this Agreement or create any liability if the same will arise from any cause or causes beyond the control of the Parties, including, but not limited to, the following: acts of God; acts or omissions of any government; any rules,
regulations or orders issued by any governmental authority or by any officer, department, agency or instrumentality thereof; fire; flood; storm; earthquake; accident; war; rebellion; insurrection; riot; and invasion. The affected Party shall notify
the other Party of such force majeure circumstances as soon as reasonably practical, and shall promptly undertake all reasonable efforts necessary to cure such force majeure circumstances. 

10.4 Consequential Damages. NEITHER PARTY (INCLUDING ITS AFFILIATES AND SUBLICENSEES) SHALL BE LIABLE UNDER THIS AGREEMENT FOR ANY
SPECIAL, INCIDENTAL, OR CONSEQUENTIAL DAMAGES OR FOR LOSS OF PROFIT OR LOST REVENUE, EVEN IF SUCH PARTY HAS BEEN ADVISED OF THE POSSIBILITY OF SUCH DAMAGES. NOTWITHSTANDING THE FOREGOING, NOTHING IN THIS SECTION 10.4 IS INTENDED TO OR SHALL LIMIT OR
RESTRICT THE INDEMNIFICATION RIGHTS OF A PARTY OR DAMAGES AVAILABLE FOR A PARTY’S BREACH OF CONFIDENTIALITY OBLIGATIONS IN ARTICLE VI. 
 10.5 Assignment. 
 (a) This Agreement, and any of its rights and
obligations, may not be assigned or otherwise transferred by either Party without the prior written consent of the other Party, which consent shall not be unreasonably withheld, delayed or conditioned; provided, however, that either
Party may assign this entire Agreement, without the consent of the other Party, in connection with such Party’s merger, consolidation or transfer or sale of all or substantially all of the assets of such Party; and provided
further that the successor, surviving entity, purchaser of assets, or transferee, as applicable, expressly assumes in writing such Party’s obligations under this Agreement, if any. 

  
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 (b) Any purported transfer or assignment in contravention of this Section 10.5 shall,
at the option of the non-assigning Party, be null and void and of no effect. 
 (c) This Agreement shall be binding upon and
inure to the benefit of the Parties and their permitted successors and assigns. 
 10.6 Notices. 

Notices to Alnylam will be addressed to: 
 Alnylam Pharmaceuticals, Inc. 
 300 Third Street 

Cambridge, Massachusetts 02142 
 U.S.A. 
 Attention: Senior Vice President, Chief Business Officer 

Facsimile No.: (617) 812-0353 
 With copy to: 
 WilmerHale LLP 

60 State Street 

Boston, Massachusetts 02109 

			
	Attention:	  	Steven D. Singer, Esq.
		  	Steven D. Barrett, Esq.

 Facsimile No.: (617) 526-5000 

Notices to Tekmira will be addressed to: 
 Tekmira Pharmaceuticals Corporation 
 100-8900 Glenlyon Parkway 

Burnaby, B.C. 

Canada V5J 5J8 

Attention: President & CEO 
 Facsimile No.: (604) 630-5103 
 With copy to: 

Orrick, Herrington & Sutcliffe LLP 
 1000 Marsh Road 
 Menlo Park, CA 94025-1015 

			
	Attention:	  	Elizabeth A. Howard
		  	R. King Milling

 Facsimile No.: (650) 614-7401 
 Either Party may change its address by giving notice to the other Party in the manner provided in this Section 10.6. Any notice required or provided for by the terms of this Agreement will be in

  
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writing and will be (a) sent by certified mail, return receipt requested, postage prepaid, (b) sent via a reputable international express courier service, or (c) sent by facsimile
transmission, with a copy by regular mail. The effective date of the notice will be the actual date of receipt by the receiving Party. 
 10.7 Independent Contractors. It is understood and agreed that the relationship between the Parties is that of independent contractors and that nothing in this Agreement will be construed as
authorization for either Party to act as the agent for the other Party. 
 10.8 Governing Law; Jurisdiction. This
Agreement will be governed and interpreted in accordance with the substantive laws of the State of Delaware, U.S.A., notwithstanding the provisions governing conflict of laws under such law of the State of Delaware to the contrary, provided
that (a) matters of intellectual property law, if any, will be determined in accordance with the national intellectual property laws relevant to the intellectual property in question, and (b) the application of the 1980 United
Nations Convention on Contracts for the International Sale of Goods is expressly excluded from this Agreement. 
 10.9
Severability. In the event that any provision of this Agreement is held by a court of competent jurisdiction to be unenforceable because it is invalid or in conflict with any law of the relevant jurisdiction, the validity of the remaining
provisions will not be affected and the rights and obligations of the Parties will be construed and enforced as if the Agreement did not contain the particular provisions held to be unenforceable, provided that the Parties will
negotiate in good faith a modification of this Agreement with a view to revising this Agreement in a manner which reflects, as closely as is reasonably practicable, the commercial terms of this Agreement as originally signed. 

10.10 No Implied Waivers. The waiver by either Party of a breach or default of any provision of this Agreement by the other Party
will not be construed as a waiver of any succeeding breach of the same or any other provision, nor will any delay or omission on the part of either Party to exercise or avail itself of any right, power or privilege that it has or may have hereunder
operate as a waiver of any right, power or privilege by such Party. 
 10.11 Headings. The headings of articles and
sections contained this Agreement are intended solely for convenience and ease of reference and do not constitute any part of this Agreement, or have any effect on its interpretation or construction. 

10.12 Entire Agreement. This Agreement constitutes the entire agreement between the Parties with respect to its subject matter and
supersedes all previous written or oral representations, agreements and understandings between the Parties including, without limitation, the Prior Cross-License Agreements and the Manufacturing Agreements, but excluding the Settlement Agreement,
the Supplemental Agreement (subject to Section 2.4) and the UBC Sublicense. The Parties specifically agree that the corresponding provisions of this Agreement shall supersede in their entirety any surviving provisions of the Prior Cross-License
Agreements. This Agreement (including the attachments hereto) may be amended only by a writing signed by both Parties. 

  
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 10.13 Waiver of Rule of Construction. Each Party has had the opportunity to consult
with counsel in connection with the review, drafting and negotiation of this Agreement. Accordingly, the rule of construction that any ambiguity in this Agreement shall be construed against the drafting Party shall not apply. 

10.14 No Third Party Beneficiaries. Except as expressly contemplated herein, no Third Party, including any employee of any Party
to this Agreement, shall have or acquire any rights by reason of this Agreement. 
 10.15 Further Assurances. Each Party
will provide such further documents or instruments required by the other Party as may be reasonably necessary or desirable to give effect to the purpose of this Agreement and carry out its provisions. 

10.16 Performance by Affiliates. Either Party may use one or more of its Affiliates to perform its obligations and duties
hereunder and Affiliates of a Party are expressly granted certain rights herein; provided that each such Affiliate shall be bound by the corresponding obligations of such Party and the relevant Party shall remain liable hereunder for
the prompt payment and performance of all their respective obligations hereunder. 
 10.17 Counterparts. This Agreement
may be executed in any number of counterparts, each of which will be deemed an original, and all of which together will constitute one and the same instrument. 
 [Signature Page Follows] 

  
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 IN WITNESS WHEREOF, Alnylam, Tekmira and Protiva have set their hands to this Cross-License Agreement as of
the date first written above. 
  

			
	ALNYLAM PHARMACEUTICALS, INC.
		
	By:	 	 /s/ Barry Greene

	Name:	 	Barry Greene
	Title:	 	President and Chief Operating Officer
	
	TEKMIRA PHARMACEUTICALS CORPORATION
		
	By:	 	 /s/ Mark J. Murray

	Name:	 	Mark J. Murray
	Title:	 	President & CEO
	
	PROTIVA BIOTHERAPEUTICS INC.
	solely with respect to Section 10.12
		
	By:	 	 /s/ Mark J. Murray

	Name:	 	Mark J. Murray
	Title:	 	President & CEO

  
 41 

 EXHIBIT A - IP MANAGEMENT TERMS 

Management of Category 1, 2, and 3 Patents 
 1. The Category 1 Patents shall be assigned to Tekmira pursuant to Section 5.1(a) of this Agreement. Within [**] days of the Effective Date, representative(s) of each Party shall meet in the offices
of Blank Rome in NY, NY to coordinate the transition of prosecution control from Alnylam to Tekmira. Within [**] business days of the Effective Date, Alnylam will determine which priority applications, in whole or in part, within the [**] family
will be assigned to Tekmira and shall record such assignments with the U.S. Patent and Trademark Office. For clarity, all priority applications, in whole or in part, to which [**] family members that have been assigned to Tekmira are entitled, or
are necessary to effect a valid priority claim shall be assigned to Tekmira according to the procedure set forth above. 
 2. The Category 2
Patents and the Category 3 Patents shall be owned by Alnylam. If Tekmira obtains any ownership interest in any Category 2 Patents or any Category 3 Patents as a result of any inventorship determination pursuant to this Agreement, Tekmira shall
assign such interest to Alnylam as set forth in Section 5.1(b) of this Agreement. 
 3. If it is determined that a novel lipid, or novel
lipid formulation is disclosed for the first time in a Category 2 Patent application or a Category 3 Patent application, then a divisional or continuation will be filed to isolate this subject matter. The division or continuation will be assigned to
Tekmira, and for the purposes of this Agreement will be treated as Category 1 IP. 
 4. Prosecution and Maintenance of Category 1 Patents.

 a. Within [**] days following the Effective Date, each Party shall provide to the other Party the name of the person responsible for
prosecution and maintenance of Category 1 Patents within such Party’s company. 
 b. The Parties agree that current outside US counsel
utilized by Alnylam prior to the Effective Date shall continue to handle US prosecution and coordinate rest of world prosecution of Category 1 Patents for a period of at least [**] month from the Effective Date. For [**]. 

c. If the outside counsel identified in 3.b above are not acceptable to Tekmira due to a bona fide conflict of interest, the Parties shall agree on
mutually acceptable outside counsel and the cost of transferring such cases shall be divided equally between Alnylam and Tekmira. If after [**] months from the effective date Tekmira wishes to transfer any of the above cases to an outside firm of
their choosing and is such firm is acceptable to Alnylam, Tekmira shall be free to do so but the cost of transferring such cases shall be borne by Tekmira 100%. 
 d. If the Parties cannot agree on choice of outside counsel, each Party shall provide the names of three (3) law firms they find acceptable, excluding those firms the other Party found unacceptable,
to the third party arbitrator as provided below and agree to abide by the decision of the arbitrator. 

  
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 e. Starting on the Effective Date Tekmira shall control prosecution with input and agreement from Alnylam
and shall diligently prosecute the Category 1 Patents claims in the broadest reasonable manner possible. Alnylam shall be copied on any correspondence with the respective patent offices related to the prosecution of the Category 1 Patents, and
Tekmira shall consult Alnylam prior to any proposed filing, response or claim additions, deletions or amendments with sufficient time to allow for review, comment and agreement by Alnylam. 
 f. Alnylam shall be consulted and must agree on any inventorship determinations or any changes to inventorship prior to filing such changes with any patent office. In the event, however, that there is a
disagreement between the Parties as to inventorship determinations, the Parties agree that they will be bound by the inventorship determinations made pursuant to the procedure outlined in paragraph 4.k below. 

g. Except as otherwise set forth in 3.c above or 3.h below, prosecution and maintenance costs shall be divided equally between Alnylam and Tekmira for
Category 1 Patents. 
 h. If for whatever reason Tekmira wishes to abandon an application for or cease to maintain any Category 1 Patents in a
jurisdiction, Tekmira will provide Alnylam with [**] days advance notice and, if Alnylam wishes to maintain such application or patent, it will be at Alnylam’s expense and such application or patent shall be assigned back to Alnylam, and
Tekmira shall have no further rights in such application or patent and such application or patent shall cease to constitute Category 1 Patents. 

i. Tekmira shall not have the right to utilize, refer to, incorporate or any way use to support claims, any subject matter that is explicitly disclosed
in a patent application to which any of the Category 1 Patents claims priority that is also not explicitly disclosed in the Category 1 IP application in question or that is also not explicitly disclosed in other Tekmira owned or controlled patents
or patent applications having an earlier filing date than the Category 1 Patent priority application containing such subject matter. For clarity, subject matter that is incorporated by reference or incorporated by virtue of a priority claim in the
Category 1 Patents in question shall not in any way be used by Tekmira unless that subject matter is also explicitly disclosed in the Category 1 Patent in question or was explicitly disclosed in other Tekmira owned or controlled patent or patent
applications having an earlier filing date than the Category 1 Patent or Category 1 Patent priority application in question. 
 j. Alnylam shall
not have the right in any patent or patent application that it owns or controls, to utilize, refer to, incorporate or any way use to support claims in such patent or patent application, any subject matter that was explicitly disclosed in any of the
Category 1 Patents by virtue of having a common priority document with any of the Category 1 Patents, unless it was explicitly disclosed in such Alnylam owned or controlled patent or patent application . 

k. In the event there is a disagreement between the Parties on any prosecution matter (including new patent application filings, claims, claim
amendments, deletions or additions), or any inventorship determination or correction they agree to utilize the dispute resolution mechanism as set forth in paragraph 7 below. 

  
 43 

 5. Prosecution and Maintenance of Category 2 Patents. 

a. Prosecution and maintenance of Category 2 Patents shall be controlled by Alnylam and as to Category 2 Patents Alnylam shall have sole discretion in
any decisions regarding patent prosecution and all prosecution and maintenance costs shall be borne by Alnylam. 
 b. Within [**] days of
Tekmira providing the names of Tekmira inventors to be added to patent application [**] in Alnylam patent family [**], Alnylam shall add such inventors by filing with the US Patent and Trademark Office a corresponding correction, and the added
inventors shall assign their rights in this application to Alnylam upon their addition to the application. Alnylam will similarly correct the inventorship in related US and foreign applications or patents where a claim or claims of similar scope
exist. 
 c. Within [**] days of the Effective Date an inventorship determination shall be performed on all Category 2 Patents at Alnylam’s
expense. 
 d. If it is determined that Tekmira inventors should be added any application(s) or patent(s), Alnylam shall add such inventors by
filing with the respective patent office a corresponding correction, and the added inventors shall assign their rights in this application to Alnylam upon their addition to the application. 
 e. If Tekmira disagrees with the above inventorship determination the Parties agree to utilize the dispute resolution mechanism as set forth in paragraph 7 below. 

f. Tekmira shall be provided [**] days advance notice on any material claim amendments, additions or deletions in any Category 2 Patents that utilize or
relate to disputed subject matter or if it decides to abandon any patent or patent application. 
 g. Tekmira shall be copied on all
correspondence with the respective patent offices related to the prosecution of Category 2 Patents for which an inventorship determination referenced above results in the addition of a Tekmira inventor. 

6. Prosecution and Maintenance of Category 3 Patents. 
 a. Prosecution and maintenance of Category 3 Patents shall be controlled by Alnylam and as to Category 3 Patents Alnylam shall have sole discretion in any decisions regarding patent prosecution and all
prosecution and maintenance costs shall be borne by Alnylam. 
 b. Upon claim allowance an independent inventorship determination shall be made
by Alnylam at its cost and inventorship shall be corrected if warranted. If Tekmira inventors are added to any applications, such inventors shall assign their rights to such patent applications to Alnylam. 

c. In the event that Tekmira wishes to determine inventorship for any claim prior to allowance it may do so at its expense. If as a result of such
determination Tekmira inventors are added to any applications, such inventors shall assign their rights to such patent applications to Alnylam 

  
 44 

 d. If Tekmira disagrees with the above inventorship determination, the Parties agree to utilize the dispute
resolution mechanism as set forth in paragraph 7 below. 
 e. Tekmira shall be provided [**] days advance notice on any material claim
amendments, additions or deletions in any Category 3 Patents that utilize or relate to disputed subject matter or if it decides to abandon any patent or patent application. 
 f. In addition to 6e above, Tekmira shall be copied on all correspondence with the respective patent offices related to the prosecution of such Tekmira Category 3 Patents for which an inventorship
determination referenced above results in the addition of a Tekmira inventor. 
 7. Dispute Resolution Mechanism. 

a. A third party gatekeeper/arbiter shall be identified along with a simple, speedy dispute resolution mechanism in the event of any disagreement among
the Parties regarding the matters set forth in this Exhibit A. 
 b. The arbiter shall be mutually agreed to by the Parties. When a dispute
arises among the Parties, the arbiter shall consider in good faith the position(s) of each Party in the dispute which the Parties shall have [**] business days to submit to such arbiter. The arbiter shall render his/her decision in an unbiased
manner in accordance with the patent laws of the jurisdiction of the patent application as to which such disagreement pertains within [**] business days of receiving all relevant documentation from the Parties and, at the arbiter’s discretion,
discussion with the Parties; provided, however, that the arbiter shall hold no ex parte meetings or substantive conversations with a Party without the consent of the other Party. 

c. In the event that the arbiter is no longer willing or capable of serving in this function a replacement shall be selected or if the Parties cannot
agree to a replacement arbiter, one will be selected as follows: 
 i. Each of the Parties shall nominate five (5) potential arbiters and
any potential arbiter appearing on both Parties’ lists shall be the arbiter and the Parties shall attempt in good faith to secure such arbiter’s services. In the event that there is more than one (1) arbiter that appears on both such
lists, the Parties shall agree in good faith which arbiter to approach first. In the event that there are no arbiters in common, the Parties shall repeat the process until an arbiter appears on both such lists or until the Parties can otherwise
agree on an arbiter. 
 d. The costs of the arbiter shall be divided equally between the Parties. 

8. Cooperation. 
 a. The Parties hereby agree
as to Category 1 Patents, Category 2 Patents, Category 3 Patents: 
 i. to make its employees, agents and consultants reasonably available to
the other Party (or the other Party’s authorized attorneys, agents or representatives), to the extent reasonably necessary to enable such Party to undertake patent prosecution as contemplated by this Exhibit A; 

  
 45 

 ii. to cooperate, if necessary and appropriate, with the other Party in gaining patent term extensions
wherever applicable to patent rights; 
 iii. to endeavor in good faith to coordinate its efforts wherever possible or reasonable with the other
Party to minimize or avoid interference with the prosecution and maintenance of the other Party’s patent applications; 
 iv. in the event
one Party receives an obviousness-type double patenting rejection in an application such Party controls over an application controlled by the other Party, the Parties will enter into good faith discussions to take steps necessary to allow both sets
of claims to issue, such steps potentially including assigning an ownership interest in the patent application in question to the other party so that common ownership is established allowing for the filing of a terminal disclaimer. In the event that
such common ownership is established the Party receiving the ownership interest will license all of its rights back in such application to the other Party; and 
 v. Unless otherwise explicitly provided in this Agreement the Parties shall have rights with respect to the enforcement of Category 1 Patents, Category 2 Patents, Category 3 Patents according to their
respective ownership interests in such patent rights as provided under applicable law. 
 9. For the avoidance of doubt, the Parties agree that,
despite Tekmira’s prior identification of the following patent families as being subject to an inventorship challenge by Tekmira, Tekmira does not challenge Alnylam’s inventorship or sole ownership of the following patent families: [**].

  
 46 

 SCHEDULE 1.9 - ALNYLAM EXISTING IN-LICENSES 

 

	1.	Co-Exclusive License Agreement between Max Planck Innovation GmbH (formerly Garching Innovation GmbH) and Alnylam Pharmaceuticals, Inc., dated December 20, 2002,
as amended by Amendment dated July 2, 2003, the Requirements Amendment effective June 15, 2005, the Waiver Amendment effective August 9, 2007 and the Amendment to the Alnylam Co-Exclusive License Agreement dated as of March 14,
2011, by and between Alnylam Pharmaceuticals, Inc., on the one hand, and Whitehead Institute for Biomedical Research, Massachusetts Institute of Technology and Max-Planck-Innovation GmbH, on the other hand; and Co-Exclusive License Agreement between
Max Planck Innovation GmbH (formerly Garching Innovation GmbH) and Alnylam Europe AG (formerly Ribopharma AG), dated July 30, 2003 

  
 47 

 SCHEDULE 1.10 - ALNYLAM EXISTING SUBLICENSES 

 

	1.	InterfeRx Option Agreement between AlCana Technologies, Inc., and Alnylam Pharmaceuticals, Inc., dated December 9, 2009 

 

	2.	License and Collaboration Agreement between Alnylam Pharmaceuticals, Inc. and Ascletis Pharmaceuticals (Hangzhou) Co., Ltd., dated June 29, 2012

  

	3.	License and Collaboration Agreement between Alnylam Pharmaceuticals, Inc. and Genzyme Corporation, dated October 18, 2012 

 

	4.	License and Collaboration Agreement between Monsanto Company and Alnylam Pharmaceuticals, Inc., dated August 27, 2012 

 

	5.	Research Collaboration and License Agreement between Novartis Institutes for BioMedical Research, Inc. and Alnylam Pharmaceuticals, Inc., dated October 12, 2005,
as amended by letter amendment dated May 1, 2011 

  

	6.	Amended and Restated License and Collaboration Agreement among Alnylam Pharmaceuticals, Inc., Isis Pharmaceuticals, Inc., and Regulus Therapeutics Inc. (formerly
Regulus Therapeutics LLC), dated January 1, 2009, as amended by amendments dated June 10, 2010 and October 25, 2011 

  

	7.	License and Collaboration Agreement among F. Hoffmann-La Roche Ltd, Hoffman-La Roche Inc., and Alnylam Pharmaceuticals, Inc., dated July 8, 2007, as amended by
letter amendment dated May 29, 2008 (assigned to Arrowhead Research Corporation in October 2011) 

  

	8.	Collaboration Agreement among Alnylam Pharmaceuticals, Inc., F. Hoffmann-La Roche Ltd., and Hoffman-La Roche Inc., dated October 29, 2009 (assigned to Arrowhead
Research Corporation in October 2011) 

  

	9.	License and Collaboration Agreement between Takeda Pharmaceutical Company Limited and Alnylam Pharmaceuticals, Inc., dated May 27, 2008, as supplemented or amended
by letter agreements dated August 18, 2009 and March 16, 2011 

  

	10.	Supplemental Agreement among Alnylam Pharmaceuticals, Inc., Tekmira Pharmaceuticals Corporation, Protiva Biotherapeutics Inc., the University of British Columbia, and
AlCana Technologies, Inc., dated July 27, 2009 

  
 48 

 SCHEDULE 1.15 - CERTAIN ALNYLAM PATENTS 

 

															
	 Case Number
	  	 Country

Name
	  	Case
Type	  	Application
Status	  	Application
Number	  	Filing
Date	  	Patent
Number	  	Issue
Date
	[**]	  	[**]	  	[**]	  	[**]	  	[**]	  	[**]	  		  	

 A total of 19 pages were omitted and filed separately with the Securities and Exchange Commission pursuant to a request
for confidential treatment. [**] 

  
 49 

 SCHEDULE 1.19 - CERTAIN BIODEFENSE TARGETS 

Category A Pathogens: 
 BACTERIA: 

[**] 
 VIRUSES: 

[**] 
 Category B Pathogens: 

BACTERIA: 
 [**] 

VIRUSES: 
 [**] 

Category C Pathogens 
 BACTERIA: 

[**] 
 VIRUSES: 

[**] 

  
 50 

 SCHEDULE 1.22 - CATEGORY 1 PATENTS 

 

																	
	 Case Number
	  	 Country
Name
	  	Law
Firm	  	Case
Type	  	Application
Status	  	Application
Number	  	Filing
Date	  	Patent
Number	  	Issue
Date
	[**]	  	[**]	  	[**]	  	[**]	  	[**]	  	[**]	  	[**]	  	[**]	  	[**]

 A total of 8 pages were omitted and filed separately with the Securities and Exchange Commission pursuant to a request
for confidential treatment. [**] 

  
 51 

 SCHEDULE 1.23 - CATEGORY 2 PATENTS 

 

																	
	 Case Number
	  	 Country
Name
	  	Law
Firm	  	Case
Type	  	Application
Status	  	Application
Number	  	Filing
Date	  	Patent
Number	  	Issue
Date
	[**]	  	[**]	  	[**]	  	[**]	  	[**]	  	[**]	  	[**]	  		  	

 A total of 4 pages were omitted and filed separately with the Securities and Exchange Commission pursuant to a request
for confidential treatment. [**] 

  
 52 

 SCHEDULE 1.24 - CATEGORY 3 PATENTS 

 

																	
	 Case Number
	  	 Country
Name
	  	Law
Firm	  	Case
Type	  	Application
Status	  	Application
Number	  	Filing
Date	  	Patent
Number	  	Issue
Date
	[**]	  	[**]	  	[**]	  	[**]	  	[**]	  	[**]	  	[**]	  		  	

 A total of 6 pages were omitted and filed separately with the Securities and Exchange Commission pursuant to a request
for confidential treatment. [**] 

  
 53 

 SCHEDULE 1.70 - TEKMIRA MANUFACTURING DOCUMENTS 

Tekmira Manufacturing Documents are limited to the following documents provided to Alnylam by Tekmira: 

 

	1.	Batch records or master batch records for [**] 

  

	2.	The following technical protocols and reports: [**] 

  

	3.	Specifications for raw materials, components and final products for [**] 

  

	4.	The following technical presentations: [**] 

  

	6.	Production Plans for [**] 

  

	7.	Technical transfer plans for [**] 

  

	8.	[**] 

  

	9.	Minutes of Production Meeting telecons [**] 

  
 54

Source: [{"source": "alea-institute/alea-institute/kl3m-data-edgar-agreements/train-00212-of-00352.parquet"}, [{"source": "alea-institute/alea-institute/kl3m-data-edgar-agreements/train-00212-of-00352.parquet"}]]