LICENSE AND COLLABORATION AGREEMENT

Exhibit 10.1

Confidential
Execution Copy

LICENSE AND COLLABORATION AGREEMENT
by and among
Takeda Pharmaceutical Company Limited
and
Alnylam Pharmaceuticals, Inc.
Dated as of May 27, 2008

Table of Contents

Schedules

Confidential
Execution Copy

LICENSE AND COLLABORATION AGREEMENT

          This LICENSE AND COLLABORATION AGREEMENT (this “ Agreement ”) is entered into as of May 27, 2008 (the “ Effective Date ”), by and among Takeda Pharmaceutical Company Limited, a Japanese corporation, having a place of business at 1-1, Doschomachi 4-chome, Chuo-ku, Osaka 540-8645, Japan (“ Takeda ”), and Alnylam Pharmaceuticals, Inc., a Delaware corporation, having a place of business at 300 Third Street, 3rd Floor, Cambridge, Massachusetts 02142, USA (“ Alnylam ”).

INTRODUCTION

          1. Takeda is engaged in the business of Developing, Commercializing and Manufacturing therapeutic products.

          2. Alnylam has developed, acquired and licensed technology useful for the Development, Manufacture, characterization and use of therapeutic products that function through the mechanism of RNAi.

          3. Alnylam desires to grant licenses to such technology to Takeda, and the Parties desire to collaborate on certain Development activities, in each case upon the terms and conditions set forth in this Agreement.

          NOW, THEREFORE, in consideration of the respective representations, warranties, covenants and agreements contained herein, and for other valuable consideration, the receipt and adequacy of which are hereby acknowledged, Alnylam and Takeda agree as follows:

ARTICLE I

DEFINITIONS

           1.1 Definitions. For the purpose of this Agreement, the following terms, whether used in singular or plural form, shall have the respective meanings set forth below:

          “ Abandoned Product ” shall mean a Licensed Product with respect to which Alnylam has exercised its Abandoned Product Option or Takeda has exercised the Early Opt-Out Option or Opt-Out Option.

          “ Abandoned Product Option ” shall have the meaning set forth in Section 4.4.

          “ Accounting Period ” shall have the meaning set forth in Section 7.7.

          “ Acquirer ” shall have the meaning set forth in Section 12.4.

          “ Acquisition ” shall have the meaning set forth in Section 12.4.

          “ Additional Field ” shall mean the treatment, palliation or prophylaxis of all Indications in a Supplemental Therapeutic Area.

          “ Affiliate ” shall mean any Person who directly or indirectly controls or is controlled by or is under common control with another Person. For purposes of this definition, “control” or “controlled” shall mean, with respect to a Person, (a) any corporation or business entity of which fifty percent (50%) or more of the securities or other ownership interests representing the equity, the voting stock or general partnership interest are owned, controlled or held, directly or indirectly, by such Person; (b) any corporation or business entity which, directly or indirectly, owns, controls or holds fifty percent (50%) (or the maximum ownership interest permitted by Law) or more of the securities or other ownership interests representing the equity, the voting stock or, if applicable, the general partnership interest, of such Person; or (c) any corporation or business entity, of which fifty percent (50%) or more of the securities or other ownership interests representing the equity of such corporation or business entity is directly or indirectly owned, controlled or held by the same corporation, business entity or security holders, or holders of ownership interests, that own, control or hold fifty percent (50%) or more of the securities or other ownership interests representing the equity or the voting stock of such Person. For purposes of this Agreement, [**], shall not be deemed an Affiliate of Alnylam.

          “ Agreement ” shall have the meaning set forth in the Preamble, and shall include, for the avoidance of doubt, all Exhibits and Schedules attached hereto.

          “ Alnylam ” shall have the meaning set forth in the Preamble.

          “ Alnylam Change of Control ” shall be deemed to occur upon the closing of (a) a merger, tender offer, share exchange, reorganization, consolidation or other similar transaction involving Alnylam in which its shareholders immediately prior to such transaction would hold fifty percent (50%) or less of the securities or other ownership or voting interests representing the equity of the surviving entity immediately after such transaction, (b) a merger, tender offer, share exchange, reorganization, consolidation or other similar transaction involving Alnylam in which the individuals who, as of the Effective Date, constitute the board of directors of Alnylam (the “ Incumbent Board” ) ceasing for any reason to constitute fifty percent (50%) or more of the board of directors of Alnylam; provided , that any individual becoming a director subsequent to the Effective Date whose election, or nomination for election by Alnylam’s stockholders, was approved by a vote of at least a majority of the directors then comprising the Incumbent Board shall be considered as though such individual were a member of the Incumbent Board, but excluding, for this purpose, any such individual whose initial assumption of office occurs as a result of an actual or threatened election contest with respect to the election or removal of directors or other actual or threatened solicitation of proxies or consents by or on behalf of a Person other than the board of directors of Alnylam or (c) a sale or other transfer to a Third Party of all or substantially all of Alnylam’s assets or business relating to this Agreement.

          “ Alnylam Delivery Intellectual Property ” shall mean Alnylam Delivery Know-How and Alnylam Delivery Patent Rights.

          “ Alnylam Delivery Know-How ” shall mean Delivery Know-How Controlled by Alnylam or its Affiliates (a) as of the Effective Date, (b) at any time during the [**] period following the Effective Date and arising outside the Delivery Collaboration or (c) arising under the Delivery Collaboration during the Delivery Collaboration Term. For purposes of clarity, Alnylam Delivery Know-How shall not include (i) Know-How included in Takeda Delivery Intellectual Property or (ii) Joint Delivery Collaboration Know-How.

          “ Alnylam Delivery Patent Rights ” shall mean Delivery Patent Rights Controlled by Alnylam or its Affiliates (a) as of the Effective Date, (b) at any time during the [**] period following the Effective Date and arising outside the Delivery Collaboration or (c) arising under the Delivery Collaboration during the Delivery Collaboration Term, but excluding such Delivery Patent Rights to the extent such Delivery Patent Rights fall within Alnylam [**] Specific Patent Rights. For purposes of clarity, Alnylam Delivery Patent Rights shall not include (i) Patent Rights included in Takeda Delivery Intellectual Property or (ii) Joint Delivery Collaboration Patent Rights.

          “ Alnylam Indemnified Parties ” shall have the meaning set forth in Section 12.1(b).

          “ Alnylam Intellectual Property ” shall mean (a) Broad RNAi Intellectual Property, (b) Alnylam Delivery Intellectual Property, and (c) Alnylam Research Collaboration Intellectual Property.

          “ Alnylam Patent Rights ” shall mean the Patent Rights falling within Alnylam Intellectual Property. As of the Effective Date, the list of the Alnylam Patent Rights worldwide, including the current status of such Patent Rights (pending, issued, challenged), is set forth in Schedule A , which Schedule shall be updated by Alnylam semi-annually during the term of this Agreement on or before June 30 and December 31 of each year. For the avoidance of doubt, Alnylam’s omission of any applicable Patent Rights contained in Alnylam Intellectual Property from Schedule A shall not limit the license granted to Takeda pursuant to Section 3.1(a).

          “ Alnylam Research Collaboration Intellectual Property ” shall mean the Know-How and Patent Rights arising under the Research Collaboration and Controlled by Alnylam or its Affiliates, but excluding Alnylam [**] Specific Patent Rights. For purposes of clarity, Alnylam Research Collaboration Intellectual Property excludes (a) Takeda Collaboration Target Specific Intellectual Property, (b) Takeda Research Collaboration Intellectual Property and (c) Joint Research Collaboration Intellectual Property.

          “ Alnylam [**] Specific Patent Rights ” shall mean such claim or claims contained in Patent Rights Controlled by Alnylam or its Affiliates that are specifically directed to particular [**] of RNAi Products against a particular individual Target (other

than Patent Rights included in Takeda Collaboration Target Specific Intellectual Property).

          “ Alnylam Third Party Obligations ” shall mean Alnylam’s or its Affiliates’ obligations to, and the rights of, Pre-Existing Alliance Parties and Listed Counterparties with respect to the Alnylam Intellectual Property under Pre-Existing Alliance Agreements and/or Listed Alnylam Third Party Agreements, respectively, including without limitation Listed Alnylam Third Party Payment obligations, as set forth in Schedule B .

          “ Annual Net Sales ” shall mean, with respect to a Licensed Product (other than a Shared Product in the United States), the Net Sales of such Licensed Product during a Fiscal Year.

          “ Applicable Accounting Standards ” shall mean, in the case of Alnylam, U.S. GAAP, and in the case of Takeda, Japanese GAAP.

          “ Asia ” shall mean Japan, China (including Hong Kong and Macao), Taiwan, South Korea, Thailand, Malaysia, North Korea, Philippines, Vietnam, Cambodia, Laos, Indonesia, Singapore, Mongolia, and Timor-Leste.

          “ Asian Pharmaceutical Company ” shall mean any corporation or entity (a) organized and existing under the Laws of a country in Asia, (b) having its principal worldwide headquarters in Asia, or (c) any Affiliate of a corporation or entity referred to in the foregoing clauses (a) or (b). Notwithstanding the foregoing, a corporation or entity referred to in the foregoing clauses (a), (b) and (c) shall not constitute an Asian Pharmaceutical Company if such corporation or entity is an Affiliate of a multinational company, the ultimate parent of which is neither (i) organized and existing under the Laws of a country in Asia nor (ii) substantially operating (on a consolidated basis) in a country in Asia as measured by (1) such corporation or entity generating at least fifty percent (50%) of its sales from Asia; or (2) such corporation or entity conducting more than fifty percent (50%) of its discovery and research activities in Asia. Notwithstanding the foregoing, Asian Pharmaceutical Companies shall include, but are not limited to, companies listed on Schedule C .

          “ Auction Banking Firm ” shall have the meaning set forth in Section 12.5(c)(ii)(A).

          “ Auction Option ” shall have the meaning set forth in Section 12.5(c)(ii).

          “ Bankruptcy Code ” shall have the meaning set forth in Section 3.3.

          “ Bid ” shall have the meaning set forth in Section 12.5(c)(ii)(B).

          “ Bid Notice ” shall have the meaning set forth in Section 12.5(c)(ii)(B).

          “ Blocked Target ” shall mean any Target that is subject to a contractual obligation of a Pre-Existing Alliance Agreement that would be breached by the inclusion of such Target as a Designated Target under this Agreement.

          “ Bona Fide Collaboration ” of a Party shall mean a collaboration by such Party with a Third Party for the Development and/or Commercialization of a particular RNAi Product, in which such Party satisfies each of the following requirements: (a) is responsible for [**] percent ([**]%) or more of the Development and Commercialization costs; (b) is entitled to receive [**] percent ([**]%) or more of the profits/potential value expected from such Development or Commercialization; and (c) plays a significant role in the decision-making processes with respect to the Development and Commercialization of such RNAi Product.

          “ Bona Fide Delivery Collaboration ” shall have the meaning set forth in Section 3.1(b)(ii).

          “ Bona Fide Delivery Collaboration Intellectual Property ” shall have the meaning set forth in Section 3.1(b)(ii).

          “ Broad RNAi Intellectual Property ” shall mean Broad RNAi Know-How and Broad RNAi Patent Rights.

          “ Broad RNAi Know-How ” shall mean Know-How Controlled by Alnylam or its Affiliates (a) as of the Effective Date, (b) at any time during the [**] period following the Effective Date, (c) during the term of this Agreement, if such Know-How Controlled by Alnylam or its Affiliates is licensed from Sirna Therapeutics, Inc., or (d) at any time if such Know-How is within the Takeda Collaboration Target Specific Intellectual Property and not assigned to Takeda pursuant to Section 6.3(b), in each case that is necessary or useful for the Development, Commercialization or Manufacture of RNAi Compounds, RNAi Products, and/or Licensed Products; but excluding (i) any scientific, regulatory, pre-clinical or clinical information or data relating and useful solely to specific Indications of particular RNAi Products, (ii) any marketing, financial, commercial or personnel information and plans or (iii) Delivery Know-How. For purposes of clarity, Broad RNAi Know-How shall not include Know-How to the extent specifically and solely related to and useful for microRNAs, microRNA antagonists, or microRNA mimics. Notwithstanding the foregoing or anything to the contrary in this Agreement, except as otherwise expressly provided in Section 6.3, in the Research Collaboration Plan, in the Delivery Collaboration Plan or in the Technology Transfer Plan, Alnylam shall not have any obligation to disclose to Takeda particular [**] of RNAi Products.

          “ Broad RNAi Patent Rights ” shall mean the Patent Rights Controlled by Alnylam or its Affiliates (a) as of the Effective Date, (b) at any time during the [**] period following the Effective Date, (c) during the term of this Agreement, if such Patent Rights Controlled by Alnylam or its Affiliates are licensed from Sirna Therapeutics, Inc., or (d) at any time if such Patent Rights are within the Takeda Collaboration Target Specific Intellectual Property and not assigned to Takeda pursuant to Section 6.3(b), in

each case that Cover RNAi technology, products or processes (including compositions, methods and uses of RNAi Compounds), including: (i) the general structure, architecture, or design of RNAi Compounds; (ii) chemical modifications of such RNAi Compounds (including any modifications to the bases, sugars or internucleoside linkages, nucleotide mimetics, conjugates and any end modifications); (iii) all uses or applications of RNAi Compounds referred to in the foregoing clause (i) or (ii); and (iv) manufacturing techniques for RNAi Compounds referred to in the foregoing clauses (i) and (ii); but excluding (A) Alnylam [**] Specific Patent Rights, or (B) Delivery Patent Rights. For purposes of clarity, Broad RNAi Patent Rights shall not include Patent Rights to the extent specifically and solely related to and useful for microRNAs, microRNA antagonists, or microRNA mimics.

          “ Business Day ” shall mean a day on which banking institutions in both Boston, Massachusetts and Osaka, Japan are open for business.

          “ Calendar Quarter ” shall mean each successive period of three (3) months commencing on January 1, April 1, July 1 and October 1.

          “ Cancer ” shall mean oncologic disease, including, but not limited to, hematologic or solid tumor malignancy, excluding complications of chemotherapy such as neutropenia, anemia, thrombocytopenia and mucositis, and excluding oncologic diseases of infectious pathogen origin or hosted by pathogen infection.

          “[**] Agreement ” shall have the meaning set forth in Section 3.6(b)(ii).

          “ Cold Spring Harbor ” shall mean Cold Spring Harbor Laboratory.

          “ Cold Spring Harbor Agreement ” shall mean the License Agreement between Cold Spring Harbor Laboratory and Alnylam dated December 30, 2003.

          “ Collaboration Target ” shall mean a Research Collaboration Target or a Delivery Collaboration Target.

          “ Combination Product ” shall mean a Licensed Product that consists of an RNAi Compound and any other clinically active therapeutic or prophylactic ingredient, mechanism or device.

          “ Commercialization ” or “ Commercialize ” shall mean activities directed to marketing, promoting, detailing, distributing, importing, having imported, exporting, having exported, selling or offering to sell, or seeking to obtain reimbursement for, an RNAi Product, whether before or after Regulatory Approval for such product has been obtained.

          “ Commercialization Costs ” shall have the meaning set forth in Schedule D .

          “ Commercially Reasonable Efforts ” shall mean, with respect to a Party, the efforts and resources that such Party would use as part of an active and continuing

program of development and/or commercialization of a pharmaceutical or biologic product owned by it or to which it has rights, of similar market potential and similar stage of product life, taking into account the competitiveness of the marketplace, the proprietary position of the product, the regulatory status involved, the pricing and launching strategy, the relative safety and efficacy of the product, and the projected profitability of the product.

          “ Confidential Information ” of a Party shall mean the terms of this Agreement and all Know-How and other information that is of a confidential and proprietary nature to such Party and that is disclosed to the other Party under this Agreement. Confidential Information includes Know-How or other information (whether or not patentable) regarding a Party’s technology, products, business information or objectives and reports and audits under Sections 7.8 and 7.9, and all proprietary biological materials (and data and information associated therewith) of a Party. Notwithstanding the foregoing, Confidential Information shall not include Know-How or other information that:

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

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

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

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

          “ Control ” or “ Controlled ” shall mean, with respect to any (a) Know-How or other information or materials or (b) other intellectual property right, the possession (whether by license, other than a license granted under this Agreement, or ownership) by a Party of the ability to grant to the other Party access and/or a license as provided herein without violating the terms of any agreement with any Third Party existing as of the Effective Date or thereafter during the term of this Agreement; provided , however , that any Know-How or Patent Rights licensed or acquired by Alnylam after the Effective Date pursuant to an agreement with a Third Party shall only be deemed to be Controlled by Alnylam if, and after, Takeda agrees in writing (subject to Alnylam summarizing in writing to Takeda the material burdens and obligations under such agreement) that such subsequent Third Party agreement shall be deemed a Listed Alnylam Third Party

Agreement and the Third Party counterparty(ies) to such agreement shall be deemed Listed Counterparties, in which case Schedules A , B and E shall be amended accordingly.

          “ Co-Promotion ” or “ Co-Promote ” shall mean those Commercialization activities jointly undertaken by Takeda and Alnylam to implement a Joint Commercialization Plan in accordance with the terms of the Profit-Sharing Agreement with respect to a Shared Product in the United States.

          “ Cover ”, “ Covered ” or “ Covering ” shall mean, with respect to an RNAi Product, but for a license granted to a Person under an issued Valid Claim included in the Patent Rights under which such license is granted, that the commercial Manufacture or Commercialization of such RNAi Product by such Person would infringe such Valid Claim or, subject to Section 3.5, with respect to a pending Valid Claim included in the Patent Rights under which such license is granted, the commercial Manufacture or Commercialization of such RNAi Product by such Person would infringe such Valid Claim if such patent application were to issue as a patent.

          “ 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.

          “ Delivery Collaboration ” shall mean the collaboration between the Parties regarding certain Delivery Technology toward certain Targets and RNAi Products which the Parties agree to pursue pursuant to the terms of Section 6.2.

          “ Delivery Collaboration Plan ” shall have the meaning set forth in Section 6.2(b).

          “ Delivery Collaboration Target ” shall have the meaning set forth in Section 6.2(b).

          “ Delivery Collaboration Term ” shall mean the period commencing upon the Parties’ agreement to a definitive Delivery Collaboration Plan pursuant to Section 6.2(b) and ending in accordance with the Delivery Collaboration Plan, but, in any event, no later than the [**] anniversary of the Effective Date.

          “ Delivery Know-How ” shall mean Know-How that relates to (a) Delivery Technologies or (b) manufacturing techniques for the Delivery Technologies.

          “ Delivery Patent Rights ” shall mean Patent Rights that Cover any (a) Delivery Technologies or (b) manufacturing techniques for the Delivery Technologies.

          “ Delivery Technology ” shall mean the Patent Rights and Know-How that are necessary or useful for delivering or administering any pharmaceutical formulation containing an RNAi Compound for treatment, palliation or prophylaxis of an Indication.

          “ Designated Target ” shall mean (a) at any time during the Novartis Exclusivity Term, any Target which is (i) identified by Takeda pursuant to Section 3.7(a) which is not a Blocked Target, (ii) submitted to Novartis pursuant to Takeda’s exercise of the Designated Target Option pursuant to Section 3.9, and (iii) rejected or waived by Novartis, as evidenced by Alnylam’s written notice to Takeda pursuant to Section 3.9; and (b) at any time following the end of the Novartis Exclusivity Term, any Target identified by Takeda pursuant to Section 3.7(a) which is not a Blocked Target. For the avoidance of doubt, (x) if Takeda selects any Target prior to the end of the Novartis Exclusivity Term for submission to Novartis, but such Target is not submitted to Novartis until after the end of the Novartis Exclusivity Term, or (y) if Takeda selects any Target prior to the end of the Novartis Exclusivity Term for submission to Novartis and such Target is submitted to Novartis prior to the end of the Novartis Exclusivity Term, but the time period during which Novartis is obligated to reply does not end until after the end of the Novartis Exclusivity Term, then such Target shall not be deemed a “Designated Target” hereunder until such Target has been actually rejected or deemed waived by Novartis pursuant to the terms of the Novartis Agreement.

          “ Designated Target Option ” shall have the meaning set forth in Section 3.9.

          “ Develop ” or “ Development ” shall mean discovery, research, preclinical development, clinical development, and regulatory activities with respect to an RNAi Product, including test method development and stability testing, design, compatibility testing, toxicology, animal efficacy studies, formulation, quality assurance/quality control development, statistical analysis, clinical studies, regulatory affairs, product approval and registration, chemical development and Manufacturing development, packaging development and Manufacturing and development documentation efforts in support of development activities anywhere in the world, whether before or after Regulatory Approval for such product has been obtained.

          “ Development Costs ” shall have the meaning set forth in Schedule D .

          “ Early Opt-Out Option ” shall have the meaning set forth in Section 4.3(a).

          “ Effective Date ” shall have the meaning set forth in the Preamble.

          “ Executive Officer ” shall mean, with respect to Takeda, Takeda’s General Manager of Pharmaceutical Research Division (or an officer or employee of Takeda then serving in a substantially equivalent capacity), and, with respect to Alnylam, Alnylam’s President (or an officer or employee of Alnylam then serving in a substantially equivalent capacity).

          “ Failed Product ” shall have the meaning set forth in Section 7.2(a)(iii).

          “ FDA ” shall mean the United States Food and Drug Administration or any successor agency thereto.

          “ Field ” shall mean the Primary Fields and, subject to the exercise by Takeda of a Field Option with respect to any Additional Field(s) pursuant to Section 3.8, any such Additional Field(s).

          “ Field Definition Panel ” shall have the meaning set forth in Section 3.8(a).

          “ Field Option ” shall have the meaning set forth in Section 3.8(b).

          “ Field Option Fee ” shall have the meaning set forth in Section 7.4.

          “ First Commercial Sale ” shall mean the first commercial sale of a Licensed Product by Takeda, its Affiliates and/or its sublicensees in a country following Regulatory Approval of such Licensed Product in that country or, if no such Regulatory Approval or similar marketing approval is required, the date upon which such Licensed Product is first commercially sold in such country to end users. Sales for test marketing or clinical trial purposes shall not constitute a First Commercial Sale.

          “ Fiscal Year ” shall mean Takeda’s fiscal year, which starts from April 1 of any calendar year and lasts until March 31 of the subsequent calendar year.

          “ Follow-On Product ” shall have the meaning set forth in Section 7.2(a)(iii).

          “ FTE ” shall mean the number of full-time-equivalent person-years (each consisting of a total of 1,840 hours) of scientific, technical, regulatory, marketing or managerial work by each Party’s personnel on or directly related to the applicable activity conducted hereunder.

          “ FTE Cost ” shall mean the amount obtained by multiplying (a) the number of FTEs by (b) [**] United States dollars ($[**]), increased or decreased annually by the percentage increase or decrease in the CPI as of December 31 of the then most recently ended Fiscal Year over the level of the CPI on December 31, 2007 ( i.e. , the first such increase or decrease would occur on January 1, 2009).

          “ Future Technology ” shall have the meaning set forth in Section 5.2(b)(i)

          “ Gatekeepers ” shall have the meaning set forth in Section 3.7(c).

          “ GLP Toxicology Study ” shall mean a toxicology study that is conducted in compliance with the then-current good laboratory practice standards promulgated or endorsed by the FDA, as defined in U.S. 21 C.F.R. Part 58 (or such other comparable regulatory standards in jurisdictions outside the U.S. to the extent applicable to the relevant toxicology study, as they may be updated from time to time) (“ GLP ”) and is required to meet the requirements for filing an IND.

          “ IND ” shall mean an application submitted to a Regulatory Authority to initiate human clinical trials, including (a) an Investigational New Drug application or any successor application or procedure filed with the FDA, (b) any equivalent of a U.S.

Investigational New Drug application in any country outside the United States, and (c) all supplements and amendments that may be filed with respect to the foregoing.

          “ Indication ” shall mean any human disease or condition, or sign or symptom of a human disease or condition.

          “ Initiation ” shall mean the first dosing of a human subject participating in a clinical study.

          “ Isis Agreement ” means the Strategic Collaboration and License Agreement dated March 11, 2004 between Alnylam and Isis Pharmaceuticals, Inc., as amended and supplemented.

          “ Isis Intellectual Property ” shall mean the Patent Rights and Know-How Controlled by Alnylam pursuant to the Isis Agreement.

          “ JDCC ” shall have the meaning set forth in Section 2.1(b)(i).

          “ Japanese GAAP ” shall mean the then current Japanese generally accepted accounting principles, consistently applied.

          “ Joint Commercialization Plan ” shall have the meaning set forth in Schedule D .

          “ Joint Delivery Collaboration Intellectual Property ” shall mean Joint Delivery Collaboration Know-How and Joint Delivery Collaboration Patent Rights.

          “ Joint Delivery Collaboration Know-How ” shall mean Know-How that is conceived, discovered, developed or otherwise made or created jointly by employees, agents and consultants of Takeda, on the one hand, and employees, agents and consultants of Alnylam, on the other hand, in the course of the Delivery Collaboration. For purposes of clarity, Joint Delivery Collaboration Know-How shall not include Know-How included in Takeda Collaboration Target Specific Intellectual Property.

          “ Joint Delivery Collaboration Patent Rights ” shall mean Patent Rights with at least one (1) Valid Claim of such Patent Rights having at least one (1) Takeda employee, agent or consultant as an inventor, and at least one (1) Alnylam employee, agent or consultant as an inventor, and claiming any invention that is conceived, discovered, developed or otherwise made or created in the course of the Delivery Collaboration. For purposes of clarity, Joint Delivery Collaboration Patent Rights shall not include Patent Rights included in Takeda Collaboration Target Specific Intellectual Property.

          “ Joint Development Plan ” shall have the meaning set forth in Schedule D .

          “ Joint Research Collaboration Intellectual Property ” shall mean Joint Research Collaboration Know-How and Joint Research Collaboration Patent Rights.

          “ Joint Research Collaboration Know-How ” shall mean Know-How that is conceived, discovered, developed or otherwise made or created jointly by employees, agents and consultants of Takeda, on the one hand, and employees, agents and consultants of Alnylam, on the other hand, in the course of the Research Collaboration. For purposes of clarity, Joint Research Collaboration Know-How shall not include Know-How included in Takeda Collaboration Target Specific Intellectual Property.

          “ Joint Research Collaboration Patent Rights ” shall mean Patent Rights with at least one (1) Valid Claim of such Patent Rights having at least one (1) Takeda employee, agent or consultant as an inventor, and at least one (1) Alnylam employee, agent or consultant as an inventor, and claiming any invention that is conceived, discovered, developed or otherwise made or created in the course of the Research Collaboration. For purposes of clarity, Joint Research Collaboration Patent Rights shall not include Patent Rights included in Takeda Collaboration Target Specific Intellectual Property.

          “ JRCC ” shall have the meaning set forth in Section 2.1(a)(i).

          “ JTTC ” shall have the meaning set forth in Section 5.2(b)(i).

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

          “ Law ” shall mean any law, statute, rule, regulation, ordinance or other pronouncement having the effect of law of any federal, national, multinational, state, provincial, county, city or other political subdivision, domestic or foreign.

          “ Licensed Product ” shall mean any RNAi Product (a) Covered by one or more Valid Claims of Alnylam Patent Rights in a particular country or (b) which embodies Alnylam Know-How. For avoidance of doubt, Licensed Product includes any Shared Product.

          “ Listed Alnylam Third Party Agreement ” shall mean an agreement pursuant to which Alnylam has in-licensed any intellectual property licensed to Takeda hereunder, which is set forth on Schedule E , as such Schedule may be amended from time to time only with Takeda’s prior written consent in accordance herewith.

          “ Listed Alnylam Third Party Payment ” shall have the meaning set forth in Section 7.3(d).

          “ Listed Counterparties ” shall mean the Third Party counterparties to Listed Alnylam Third Party Agreements and their respective successors in interest.

          “ Losses ” shall have the meaning set forth in Section 12.1(a).

          “ Major European Country ” shall mean any of France, Germany, Italy, Spain or the United Kingdom.

          “ Major Market ” shall mean each of Japan, the United States and the Major European Countries.

          “ Manufacture ” or “ Manufacturing ” shall mean, as applicable, all activities associated with the production, manufacture, supply, processing, filling, packaging, labeling, shipping, and storage of an RNAi Product and/or any components thereof, including process and formulation development, process validation, stability testing, manufacturing scale-up, preclinical, clinical and commercial manufacture and analytical development, product characterization, quality assurance and quality control development, testing and release.

          “ Metabolic Disease ” shall mean diseases of metabolism, including, but not limited to, diabetes, obesity and Syndrome X, and excluding metabolic diseases of infectious pathogen origin or hosted by pathogen infection.

          “ Minimum FTE Commitment ” means the commitment of [**] per Calendar Quarter).

          “ MIT ” shall mean the Massachusetts Institute of Technology.

          “ MIT Agreement ” shall mean the Amended and Restated Exclusive Patent License Agreement dated May 9, 2007 between the Massachusetts Institute of Technology and Alnylam.

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

          “ Net Profits/Losses ” shall have the meaning set forth in Schedule D .

          “ Net Sales ” shall mean the gross amount invoiced by Takeda, its Affiliates and/or its sublicensees on sales or other dispositions (excluding sales or dispositions for use in clinical trials or other scientific testing, or other similar cases for which Takeda, its Affiliates and/or its sublicensees receive no revenue) of the Licensed Product to unrelated Third Parties, less the following deductions:

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

          (b) Tariffs, duties, excises, sales taxes or other taxes imposed upon and paid directly with respect to the delivery, sale or use of the Licensed Product and

included and separately stated in the applicable invoice (excluding national, state or local taxes based on income);

          (c) Amounts repaid or credited by reason of rejections, defects, recalls or returns or because of reasonable and customary chargebacks, refunds, rebates (including rebates to managed care organizations or social and welfare systems) or retroactive price reductions (including any discounts granted later than at the time of invoicing), government mandated rebates and similar types of rebates (e.g., Pharmaceutical Price Regulation Scheme and Medicaid, and with respect to any Net Sales in Japan, any sales-based contribution for “Drug Induced Suffering” and any sales-based contribution for “Contribution for Measure for Drug Safety,” in the amount determined by and payable to the Pharmaceuticals and Medical Devices Agency (so-called “KIKO”) each as consistently applied by Takeda to its products), or cash sales incentives, or deductions for items of a nature or substance similar to that of the foregoing deductions in this clause (c) that may become customary;

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

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

Such amounts shall be determined from the books and records of Takeda, its Affiliates and/or its sublicensees, maintained in accordance with Applicable Accounting Standards, consistently applied.

In the case of pharmacy incentive programs, hospital performance incentive program chargebacks, disease management programs, similar programs or discounts on “bundles” of products, all discounts and the like shall be allocated among products in proportion to the respective list prices of such products or such other reasonable allocation method as the Parties shall agree.

In the case where a Licensed Product (other than a Shared Product) is a Combination Product, royalties with respect to a Combination Product in a country shall be equal to the rates set forth in Section 7.3(a), multiplied by a fraction whose numerator is the average published sales price in such country for an equivalent dosage of RNAi Compound (sold separately as a stand alone product) contained in a given Combination Product, and whose denominator is the sum of the average published sale prices in such country for all components (sold separately as a stand alone product) that are equivalent to all components contained in the Combination Product. If the numerator or denominator cannot be determined in the manner set forth above, the Parties shall negotiate in good faith and agree to an appropriate adjustment to Net Sales to reflect the relative significance of the RNAi Compound and the other components contained in the

Combination Product, which agreement shall not be unreasonably withheld, conditioned or delayed. If the Parties are unable to reach agreement regarding such issue within [**] after commencing good faith negotiations, the issue shall be referred to the Executive Officers in accordance with Section 12.2.

Notwithstanding the foregoing, with respect to Shared Products that are Combination Products, Net Sales shall not be reduced as set forth in the immediately preceding paragraph and the costs of acquiring any other clinically active therapeutic or prophylactic ingredient, mechanism or device shall be included in the calculation of the cost of goods for purposes of calculating Net Profits/Losses for such Shared Product.

          “ Novartis ” shall mean Novartis Institutes for BioMedical Research, Inc.

          “ Novartis Agreement ” shall mean the Research Collaboration and License Agreement, effective as of October 12, 2005, by and between Alnylam and Novartis, as amended by the Addendum Re: Influenza Program effective as of December 13, 2005, Amendment No. 1 to such Addendum effective as of March 14, 2006, and Amendment No. 2 to such Addendum effective as of May 5, 2006, and as the same may be amended from time to time after the Effective Date in accordance with Section 3.10(c).

          “ Novartis Exclusivity Term ” shall mean the “Exclusivity Term” as defined in the Novartis Agreement.

          “ Novartis Selection Term ” shall mean the “Selection Term” as defined in the Novartis Agreement, which, in any event, shall not be extended beyond October 10, 2010.

          “[**]” shall have the meaning set forth in Section 3.10(b).

          “[**]” shall have the meaning set forth in Section 3.10(b)(ii).

          “ Option Exercise Payment ” shall have the meaning set forth in Section 7.5(a).

          “ Option Exercise Period ” shall have the meaning set forth in Section 4.2(c).

          “ Opt-Out Option ” shall have the meaning set forth in Section 4.3(b).

          “ Paragraph IV Notice ” shall have the meaning set forth in Section 8.4.

          “ Partially Blocked Target ” shall have the meaning set forth in Section 3.7(a).

          “ Party ” shall mean Alnylam or Takeda; “ Parties ” shall mean Alnylam and Takeda.

          “ Past Development Milestone ” shall have the meaning set forth in Section 7.5(b).

          “ Patent Rights ” shall mean patents, patent applications and/or provisional patent applications, utility models and utility model applications, design patents or registered industrial designs and design applications or applications for registration of industrial designs, and all substitutions, divisionals, continuations, continuation-in-part applications, continued prosecution applications, requests for continued examinations, reissues, reexaminations and extensions thereof, in any country of the world. For clarity, any Patent Rights shall include any future Patent Rights that claim priority to or common priority with such Patent Rights.

          “ Patent Term Extension ” shall have the meaning set forth in Section 8.5.

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

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

          “ Phase II Study ” shall mean a study of a Licensed Product to evaluate preliminary efficacy and establish safety, appropriate dosage and pharmacological activity in the target patient population.

          “ Phase III Study ” shall mean a human clinical trial that is prospectively designed to demonstrate statistically whether a product is safe and effective for use in humans in a manner sufficient to obtain Regulatory Approval to market such product in patients having the disease or condition being studied as described in U.S. 21 C.F.R. § 312.21(c), or a similar clinical study in a country other than the United States.

          “ Pre-Existing Alliance Agreements ” shall mean the agreements set forth on Schedule F .

          “ Pre-Existing Alliance Parties ” shall mean the Third Party counterparties to Pre-Existing Alliance Agreements and their respective successors in interest.

          “ Primary Fields ” shall mean the treatment, palliation or prophylaxis of all Indications in the Primary Therapeutic Areas.

          “ Primary Therapeutic Areas ” shall mean Cancer and Metabolic Disease.

          “ Product Liability Claim ” shall mean, with respect to an RNAi Product, any Third Party claim, suit, action, proceeding, liability or obligation involving any actual

or alleged death or bodily injury arising out of or resulting from the use of such RNAi Product.

          “ Profit-Sharing Agreement ” shall have the meaning set forth in Section 4.2(a).

          “ Profit-Sharing Option ” shall have the meaning set forth in Section 4.2(a).

          “ Profit-Share Term ” shall mean, as to any Shared Product, the period commencing with the effective date of the Profit-Sharing Agreement until such time as Takeda exercises the Early Opt-Out Option or either Party exercises the Opt-Out Option.

          “ Region ” shall mean each of (a) North America (the United States and Canada, collectively), (b) the countries of the European Union collectively as of the relevant time hereunder or (c) all countries of the world other than North America (the United States and Canada, collectively) and the countries of the European Union.

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

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

          “ Required Third Party Payments ” shall mean milestone payments, royalty payments and other payments, or portions thereof (in the case of any such milestone payment or other non-royalty payment, appropriately allocated to a Licensed Product, if the whole payment includes an amount that should be attributed to Patent Rights that Cover technology or products other than such Licensed Product) to a Third Party made by Takeda under Third Party agreements (other than Listed Alnylam Third Party Agreements or Pre-Existing Alliance Agreements) to license Patent Rights Covering such Third Party’s technology if, in the absence of such license, the licensed use by Takeda of the Alnylam Patent Rights in respect of a Licensed Product for which royalties are payable hereunder would infringe such Patent Rights; provided , however , that Required Third Party Payments with respect to a Licensed Product shall not include any milestone payments, royalties or other payments to the extent payable to obtain access to a specific Target or Targets so that such Target or Targets can be the subject of Development efforts, but shall include such milestone payments (or portions thereof), royalties and other payments (or portions thereof) to the extent necessary to obtain access to Third Party Delivery Technologies for delivery of such Licensed Product, or manufacturing techniques for such Delivery Technologies.

          “ Research Collaboration ” shall mean the collaboration between the Parties regarding the Development of potential RNAi Compounds directed to at least one (1)

mutually agreed Research Collaboration Target, which the Parties shall conduct pursuant to the terms of Section 6.1(a).

          “ Research Collaboration Plan ” shall have the meaning set forth in Section 6.1(a).

          “ Research Collaboration Target ” shall have the meaning set forth in Section 6.1(a).

          “ Research Collaboration Term ” shall mean the period commencing on the date during the first [**] after the Effective Date on which Takeda proposes the Collaboration Target(s) pursuant to Section 6.1(a) and ending [**] thereof; provided , that , Alnylam may in its reasonable discretion extend the term of the Research Collaboration [**]; provided , further , that , in the event of any such extension at Alnylam’s discretion, Takeda shall not be obligated to reimburse Alnylam for any FTE Cost in connection with such extended term.

          “ RNAi Compound ” shall mean any compound that functions to reduce RNA through the mechanism of RNAi and consists of or encodes double-stranded RNA, and which double-stranded RNA is optionally chemically modified (including any modifications to bases, sugars or internucleoside linkages, conjugates, nucleotide mimetics, and any end modifications) to contain modified nucleotide bases or non-RNA nucleotides and optionally may be administered in association or conjugation with a delivery vehicle or vector. For purposes of clarity, RNAi Compounds shall not include microRNAs, microRNA antagonists, or microRNA mimics.

          “ RNAi Product ” shall mean any pharmaceutical product that contains or is comprised of one or more RNAi Compounds as an active ingredient.

          “ ROFN Banking Firm ” shall have the meaning set forth in Section 12.5(d)(i).

          “ ROFN Call Notice ” shall have the meaning set forth in Section 12.5(d).

          “ ROFN Call Option ” shall have the meaning set forth in Section 12.5(d).

          “ ROFN Call Price ” shall have the meaning set forth in Section 12.5(d).

          “ ROW ” means all countries in the world other than the United States.

          “ Royalty Term ” shall mean, with respect to a given Licensed Product (other than Shared Products) sold commercially in a particular country, the period of time commencing on the First Commercial Sale of such Licensed Product ( provided that the Royalty Term shall not commence unless or until either (a) the commercial Manufacture or Commercialization of such Licensed Product is Covered by a Valid Claim of an Alnylam Patent Right in such country or (b) the actual commercial Manufacture of such Licensed Product is Covered by a Valid Claim of an Alnylam Patent Right in the country or countries in which such Licensed Product was actually commercially Manufactured),

and concluding on the later of (i) the last to expire Alnylam Patent Right in the country of sale containing a Valid Claim Covering the commercial Manufacture or Commercialization of such Licensed Product in such country, (ii) the last to expire Alnylam Patent Right in the country of actual commercial Manufacture containing a Valid Claim Covering the commercial Manufacture in such country of such Licensed Product, or (iii) [**] from the date of First Commercial Sale of such Licensed Product in such country.

          “[**]” shall have the meaning set forth in Section 3.1(d).

          “ SEC ” shall have the meaning set forth in Section 9.1.

          “ Severed Clause ” shall have the meaning set forth in Section 12.13.

          “ Shared Product ” shall have the meaning set forth in Section 4.2(d).

          “ SPC ” shall have the meaning set forth in Section 4.2(f).

          “ Submitted Target ” shall have the meaning set forth in Section 3.9.

          “ Supplemental Therapeutic Area ” shall mean each of the disease area fields set forth on Schedule G .

          “ Takeda ” shall have the meaning set forth in the Preamble.

          “ Takeda Collaboration Target Specific Intellectual Property ” shall mean any Know-How or Patent Rights that are specifically and solely directed to a Collaboration Target, as opposed to being of general applicability to a range of Targets, and developed solely by a Party or jointly by the Parties either (i) in the course of conducting the Research Collaboration or the Delivery Collaboration; or (ii) during the Research Collaboration Term or Delivery Collaboration Term, and outside the conduct of the Research Collaboration and the Delivery Collaboration; provided that , Alnylam’s obligation to assign such Know-How and Patent Rights described in the foregoing clause (ii) to Takeda pursuant to Section 6.3(b) shall only apply to such Know-How and Patent Rights that Alnylam solely owns and Controls.

          “ Takeda Delivery Intellectual Property ” shall mean Takeda New Delivery Intellectual Property and Takeda Licensed Pre-Existing Delivery Patent Rights.

          “ Takeda Delivery Reserved Target List ” shall mean a list of Targets provided by Takeda to the Gatekeepers for purposes of Section 3.2(a)(i) of up to [**] Targets per Field (i.e., up to [**] Targets in the aggregate for the Primary Fields), which list is maintained by the Gatekeepers and updated by Takeda from time to time in accordance with Section 3.7(b).

          “ Takeda Indemnified Parties ” shall have the meaning set forth in Section 12.1(a).

          “ Takeda Intellectual Property ” means Takeda Know-How and Takeda Patent Rights, collectively.

          “ Takeda Know-How ” means (a) Takeda New Delivery Know-How, (b) Takeda Licensed Pre-Existing Delivery Know-How and (c) Know-How falling within the Takeda Research Collaboration Intellectual Property.

          “ Takeda Licensed Pre-Existing Delivery Patent Rights ” shall mean any Takeda Patent Rights included in the Takeda Pre-Existing Delivery Intellectual Property, without a license under which Alnylam’s practice of any Alnylam Delivery Intellectual Property that is generated by Alnylam during the [**] after the Effective Date would infringe such Takeda Patent Rights; but excluding such Patent Rights to the extent such Patent Rights fall within Takeda [**] Specific Patent Rights.

          “ Takeda New Delivery Intellectual Property ” shall mean Takeda New Delivery Know-How and Takeda New Delivery Patent Rights.

          “ Takeda New Delivery Know-How ” shall mean Delivery Know-How that Takeda or those Affiliates of Takeda that have received a sublicense pursuant to Section 3.1(b)(iv) or that have generated new Patent Rights or Know-How from practicing Alnylam Intellectual Property without a sublicense from Takeda thereto, (a) first come to Control at any time during the [**] period following the Effective Date and that arises outside of the Delivery Collaboration or (b) first come to Control during the Delivery Collaboration Term and that arises under the Delivery Collaboration. For purposes of clarity, Takeda New Delivery Know-How shall not include Know-How that is based on, directly or indirectly, or constitutes Takeda Pre-Existing Delivery Intellectual Property or any Know-How that constitutes improvements to Takeda Pre-Existing Delivery Intellectual Property (i.e., to the extent that practicing such Know-How without a license would infringe any Takeda Pre-Existing Delivery Intellectual Property).

          “ Takeda New Delivery Patent Rights ” shall mean Delivery Patent Rights that Takeda or those Affiliates of Takeda that have received a sublicense pursuant to Section 3.1(b)(iv) or that have generated new Patent Rights or Know-How from practicing Alnylam Intellectual Property without a sublicense from Takeda thereto, (a) first come to Control at any time during the [**] period following the Effective Date and that arises outside of the Delivery Collaboration or (b) first come to Control during the Delivery Collaboration Term and that arises under the Delivery Collaboration, but excluding such Patent Rights to the extent such Patent Rights fall within Takeda [**] Specific Patent Rights. For purposes of clarity, Takeda New Delivery Patent Rights shall not include Patent Rights that are based on, directly or indirectly, or constitute Takeda Pre-Existing Delivery Intellectual Property or any Patent Right that constitutes improvements to Takeda Pre-Existing Delivery Intellectual Property (i.e., to the extent that practicing such Patent Rights without a license would infringe any Takeda Pre-Existing Delivery Intellectual Property).

          “ Takeda Patent Rights ” shall mean all (a) Takeda New Delivery Patent Rights, (b) Takeda Licensed Pre-Existing Delivery Patent Rights and (c) Patent Rights falling within the Takeda Research Collaboration Intellectual Property.

          “ Takeda Pre-Existing Delivery Intellectual Property ” shall mean Delivery Know-How and Delivery Patent Rights Controlled by Takeda as of the Effective Date.

          “ Takeda Research Collaboration Intellectual Property ” shall mean the Know-How and Patent Rights arising under the Research Collaboration and Controlled by Takeda or its Affiliates, including Takeda Collaboration Target Specific Intellectual Property and any portion of Takeda [**] Specific Patent Rights that arise under the Research Collaboration. For purposes of clarity, Takeda Research Collaboration Intellectual Property excludes Alnylam Research Collaboration Intellectual Property and Joint Research Collaboration Intellectual Property.

          “ Takeda Reserved Target ” shall mean a Target Takeda has submitted under Section 3.7(a) and that is not a Blocked Target pursuant to the process set forth in Section 3.7(a). Takeda shall have the right to terminate a Target’s designation as a Takeda Reserved Target upon written notification to the Gatekeepers.

          “ Takeda [**] Specific Patent Rights ” shall mean claims contained in Patent Rights Controlled by Takeda that are specifically directed to particular [**] of RNAi Products against a particular individual Target (including such Patent Rights assigned by Alnylam to Takeda pursuant to Section 6.3(b)).

          “ Takeda Third Party Obligations ” shall mean Takeda’s obligations to, and the rights of, Third Parties with respect to Takeda Intellectual Property, including, without limitation, payment obligations to such Third Parties.

          “ Target ” shall mean (a) a polypeptide that is a site or potential site of therapeutic intervention by a therapeutic agent, or a nucleic acid which is required for expression of such polypeptide; (b) variants of a polypeptide (including any splice variant thereof), cellular entity or nucleic acid described in the foregoing clause (a); or (c) a defined non-peptide entity, including a microorganism, virus, bacterium or single-cell parasite; provided that the entire genome of a virus shall be regarded as a single Target.

          “ Technology Milestone I ” shall mean the technology transfer milestone relating to Alnylam Intellectual Property Controlled by Alnylam as of the Effective Date that is identified as “Technology Transfer Milestone I” and further defined in Schedule J .

          “ Technology Milestone II ” shall mean the technology transfer milestone relating to Alnylam Intellectual Property Controlled by Alnylam as of the Effective Date that is identified as “Technology Transfer Milestone II” and further defined in Schedule J .

          “ Technology Milestone III ” shall mean the technology transfer milestone relating to Alnylam Intellectual Property Controlled by Alnylam as of the Effective Date

that is identified as “Technology Transfer Milestone III” and further defined in Schedule J .

          “ Technology Transfer Period ” shall have the meaning set forth in Section 5.1.

          “ Technology Transfer Plan ” shall have the meaning set forth in Section 5.1.

          “ Tekmira ” shall mean Tekmira Pharmaceuticals Corporation (formerly INEX Pharmaceuticals Corporation).

          “ Tekmira License Agreement ” shall mean the License and Collaboration Agreement between Tekmira and Alnylam Pharmaceuticals, Inc., dated January 8, 2007.

          “ Tekmira Selection Term ” shall mean the “Selection Term” as defined in the Tekmira License Agreement, which in any event shall not extend beyond January 8, 2014.

          “ Territory ” shall mean all countries of the world.

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

          “ Third Party Infringement Claim ” shall have the meaning set forth in Section 8.3(a).

          “ UBC ” shall mean the University of British Columbia.

          “ United States ” or “ U.S. ” shall mean the United States of America and its territories and possessions.

          “ U.S. GAAP ” shall mean the then current United States generally accepted accounting principles, consistently applied.

          “ Valid Claim ” shall mean a claim (a) of any issued, unexpired patent that has not been revoked or held unenforceable or invalid by a decision of a court or governmental agency of competent jurisdiction from which no appeal can be taken, or with respect to which an appeal is not taken within the time allowed for appeal, and that has not been disclaimed or admitted to be invalid or unenforceable through reissue, disclaimer or otherwise or (b) subject to Section 3.5, of any patent application that has not been cancelled, withdrawn or abandoned, nor been pending for more than [**] from the filing date of the earliest patent application from which such patent application claims priority.

ARTICLE II

GOVERNANCE

           2.1 Committees.

          (a)  Joint Research Collaboration Committee .

               (i) Within [**] after the Effective Date the Parties shall establish a Joint Research Collaboration Committee (the “ JRCC ”) that shall oversee the research activities of the Parties under the Research Collaboration. The JRCC shall be comprised of three (3) representatives designated by Alnylam and three (3) representatives designated by Takeda. Takeda shall appoint a Chairperson from among its representatives. Each Party’s JRCC representatives shall be of the seniority and experience appropriate for service on the JRCC in light of the functions, responsibilities and authority of the JRCC. Each Party may replace any or all of its representatives on the JRCC with individual(s) of appropriate experience and seniority at any time upon written notice to the other Party.

               (ii) The JRCC will perform the following functions: (A) managing and overseeing the performance of the Research Collaboration, (B) reviewing and amending, if necessary, the Research Collaboration Plan, (C) managing the performance of the Research Collaboration Plan prepared by the Parties pursuant to Sections 6.1(a) and (b), including overseeing the allocation and assignment of tasks with respect to the Research Collaboration, and (D) assuming such other responsibilities as may be assigned to the JRCC pursuant to this Agreement or as may be mutually agreed upon in writing by the Parties from time to time.

          (b) Joint Delivery Collaboration Committee .

               (i) Within [**] after Takeda exercises its option to pursue the Delivery Collaboration with Alnylam pursuant to Section 6.2, the Parties shall establish a Joint Delivery Collaboration Committee (the “ JDCC ”) that shall oversee the research activities of the Parties under the Delivery Collaboration. The JDCC shall be comprised of three (3) representatives designated by Alnylam and three (3) representatives designated by Takeda. Takeda shall appoint a Chairperson from among its representatives. Each Party’s JDCC representatives shall be of the seniority and experience appropriate for service on the JDCC in light of the functions, responsibilities and authority of the JDCC. Each Party may replace any or all of its representatives on the JDCC with individual(s) of appropriate experience and seniority at any time upon written notice to the other Party.

               (ii) The JDCC will perform the following functions: (A) managing and overseeing the performance of the Delivery Collaboration, (B) reviewing and amending, if necessary, the Delivery Collaboration Plan prepared by the Parties pursuant to Sections 6.2(b) and (c), (C) managing the performance of the Delivery Collaboration Plan, including overseeing the allocation and assignment of tasks with respect to the

Delivery Collaboration, and (D) assuming such other responsibilities as may be assigned to the JDCC pursuant to this Agreement or as may be mutually agreed upon in writing by the Parties from time to time.

           2.2 Meetings. The JRCC and JDCC shall each meet at least once per Calendar Quarter, and more frequently as Alnylam and Takeda deem appropriate or as reasonably requested by either Party, on such dates, and at such places and times, as the Parties shall agree; provided that the Parties shall endeavor to have the first meeting of the JRCC and JDCC within [**] after the establishment of the respective committee. Meetings of the JRCC and JDCC in person shall alternate between the offices of Alnylam and Takeda, or such other place as the Parties may agree, with the first such meeting for the JRCC and JDCC being at Takeda’s offices. The members of the JRCC or JDCC also may convene or be polled or consulted from time to time by means of telecommunications, video conferences, electronic mail or correspondence, as deemed necessary or appropriate. A JRCC or JDCC member of the Party hosting the meeting shall serve as secretary of that meeting and shall be responsible for preparing the minutes of the meeting. Such minutes shall be in English and 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 JRCC or JDCC, as applicable. The Parties agree that they shall endeavor to ensure that draft minutes of each meeting shall be distributed within [**] of the meeting, and final minutes shall be approved by both Parties within [**] of the meeting. Final minutes of each meeting shall be distributed to the members of the JRCC or JDCC by the chairperson of the JRCC or JDCC, as the case may be.

           2.3 Decision-Making Authority.

          (a) Subject to the remainder of this Section 2.3, all decisions of the JRCC or JDCC, as the case may be, shall be made by majority vote, with each Party’s JRCC representatives or JDCC representatives, as applicable, collectively having one vote. The Parties shall use reasonable good faith efforts to reach consensus on all issues within the responsibility of the JRCC and JDCC. Upon [**] prior written notice, either Party may convene a special meeting of the JRCC or JDCC, as the case may be, for the purpose of resolving any failure to reach agreement on a matter within the scope of the authority and responsibility of the JRCC or JDCC, as the case may be.

          (b) If the JRCC or JDCC is unable to reach agreement on any matter so referred to it for resolution by one or more of the Parties within [**] after the matter is so referred to it, such dispute shall be referred to the Executive Officers (or their designees) in accordance with Section 12.2, provided that if such dispute is not resolved by the Executive Officers, then Takeda shall have the right to decide the matter; provided further that Takeda shall not have any authority to assign obligations to Alnylam beyond those set forth in the Research Collaboration Plan or the Delivery Collaboration Plan without Alnylam’s written consent, which consent shall not be unreasonably withheld, conditioned or delayed.

           2.4 Limitation on JRCC and JDCC Authority. Neither the JRCC nor the JDCC shall have the power to (a) amend or modify the Parties’ respective rights

and obligations under this Agreement or (b) resolve any dispute between the Parties regarding such rights and obligations.

           2.5 Reports to Committees. Each Party shall provide the JRCC and JDCC on a Calendar Quarter basis with reports regarding the activities performed by such Party under the Research Collaboration and Delivery Collaboration, as applicable. Each such report shall summarize in reasonable detail the activities undertaken by such Party during the prior Calendar Quarter, as well as the results of such activities. Such reports will be accurate and, where appropriate, will contain raw data from studies carried out by or on behalf of such Party.

           2.6 Expenses. Each Party shall be responsible for all costs and expenses for its members and other representatives to attend meetings of, and otherwise participate on, a committee, including all travel and related costs and expenses.

ARTICLE III

GRANT OF RIGHTS;
INTELLECTUAL PROPERTY MATTERS

           3.1 Rights Granted by Alnylam to Takeda.

          (a)  License Grant . Subject to the terms and conditions of this Agreement and Alnylam Third Party Obligations, Alnylam hereby grants to Takeda a non-exclusive, worldwide, royalty-bearing (“royalty bearing” here meaning only with respect to Licensed Products, other than Shared Products, during the Royalty Term) right and license under the Alnylam Intellectual Property, to Develop, Manufacture, Commercialize, use, offer for sale, sell, export and import RNAi Products in the Field.

          (b)  Sublicense Rights .

               (i) Subject to Alnylam Third Party Obligations, Takeda shall have the right to grant sublicenses within the scope of the licenses under Alnylam Intellectual Property granted to Takeda in Section 3.1(a), on an RNAi Product-by-RNAi Product basis, to Third Parties in the Field (as applicable) solely for purposes of (x) Developing and/or Commercializing an RNAi Product Developed by Takeda, which has achieved at the time of such sublicense grant, at a minimum, completion of a [**] (which, for clarity, needs to be completed with respect to the lead candidate only for such RNAi Product and not for any backup candidates for such RNAi Product), (y) a Bona Fide Collaboration, or (z) engaging contract research organizations, contract manufacturers, contract sales forces and academic institutions in connection with Development and/or Commercialization of an RNAi Product; provided , however , that, with respect to the foregoing clause (z), Takeda shall only sublicense such Third Party the right to use the Alnylam Intellectual Property in connection with the performance of such services.

               (ii) Notwithstanding Section 3.1(b)(i), as to a Bona Fide Delivery Collaboration (as defined below), the following shall apply. Subject to Alnylam Third Party Obligations, Takeda shall have the right to grant sublicenses within the scope of the licenses under Alnylam Intellectual Property granted to Takeda in Section 3.1(a) to a Third Party collaborator (other than any Third Party listed on Schedule H ) solely for purposes of discovering Delivery Technology for RNAi Products (a “ Bona Fide Delivery Collaboration ”); provided that Takeda shall either maintain Control (it being understood and agreed that a non-exclusive license shall be satisfactory as long as Takeda has the right to sublicense such license to Alnylam with the same scope (i.e. non-commercial vs. commercial, territory, etc.) as the terms of the license granted by such Third Party collaborator to Takeda), or a similar license is available to Alnylam from such Third Party collaborator on terms that, in the aggregate are materially the same as the terms of such license to Takeda, of, in either case, all Delivery Know-How and Delivery Patent Rights generated in the course of such Delivery Technology collaborations that use Alnylam Intellectual Property (excluding improvements on pre-existing Delivery Know-How and Delivery Patent Rights of such collaborator that do not incorporate and are not improvements on Alnylam Intellectual Property) (collectively, the “ Bona Fide Delivery Collaboration Intellectual Property ”). For the avoidance of doubt, such sublicense shall not include any rights under Alnylam Intellectual Property to offer for sale, sell or otherwise Commercialize any Delivery Technology or RNAi Products. In order to facilitate Takeda entering into the foregoing Delivery Technology collaboration with Third Party collaborators, at Takeda’s request, Alnylam agrees to negotiate in good faith with such Third Party collaborators regarding the terms and conditions on which Alnylam would be willing to grant a non-exclusive, royalty-bearing license to Develop, Manufacture, Commercialize, use, offer for sale, sell, export and import RNAi Products under Alnylam Intellectual Property to the extent such license is necessary to practice such Bona Fide Delivery Collaboration Intellectual Property without infringing Alnylam Intellectual Property.

               (iii) All sublicenses granted pursuant to Section 3.1(b)(i) and (ii) shall be subject to the following conditions:

               (A) Such sublicense shall be consistent with the requirements of this Agreement;

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

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

               (D) To the extent required under any applicable Listed Alnylam Third Party Agreement, if such sublicense is granted pursuant to a written sublicense agreement, Takeda shall provide a copy of such sublicense

agreement to Alnylam (with redactions to the fullest extent permitted under the applicable Listed Alnylam Third Party Agreement(s)).

               (iv) Notwithstanding the foregoing, subject to Alnylam Third Party Obligations, Takeda shall have the right to grant sublicenses to any of its Affiliates within the scope of the licenses under Alnylam Intellectual Property granted to Takeda in Section 3.1(a), with the same right to further grant sublicenses granted to Takeda pursuant to Sections 3.1(b)(i), (ii) and (iii), to Develop, Manufacture, Commercialize use, offer for sale, sell, export and import RNAi Products in the Field; provided that the provisions of Sections 3.1(b)(iii)(A), (C) and (D) shall apply to any such sublicense granted by Takeda to any of its Affiliates.

          (c)  Exclusivity in Asia . During the five (5) year period following the Effective Date, Alnylam shall not grant any Asian Pharmaceutical Company a license under Alnylam Intellectual Property in any therapeutic area, provided , however , that (i) Alnylam may grant such a license(s) to contract research organizations, contract manufacturers, contract sales forces or academic institutions engaged by Alnylam in connection with Development and/or Commercialization of an Alnylam RNAi Product, (ii) this limitation shall in no way affect licenses granted to Third Parties prior to the Effective Date under a Pre-Existing Alliance Agreement, and (iii) Alnylam may grant such a license(s) subject to Takeda’s first negotiation right under Section 3.1(d).

          (d)  Preferred Asian Territory Partner . If at any time or times during the first five (5) years after the Effective Date, Alnylam, or any of its Affiliates, desires to enter into a transaction with a Third Party to Develop and/or Commercialize, in a territory consisting primarily of Asia (or any portion thereof), an RNAi Product of Alnylam that has completed a [**], Alnylam shall promptly notify Takeda of its intent to enter into such a transaction, identifying the RNAi Product and Target therefor that will be the subject of such transaction and a summary of any other relevant terms applicable to such transaction. Within [**] after receipt of such notification, Takeda shall notify Alnylam in writing either that (i) Takeda is interested in negotiating an agreement with respect to such transaction or (ii) Takeda has no interest and therefore waives such right of first negotiation with respect to such RNAi Product. If Takeda notifies Alnylam within [**] that Takeda desires to negotiate an agreement with respect to such transaction, the Parties shall negotiate in good faith for up to [**] from the date of such notification, or such longer period as agreed between the Parties, regarding the terms pursuant to which the Parties would enter into such transaction. Failure by Takeda to give notice of its interest or lack of interest in negotiating for such agreement within [**] after receipt of written notice from Alnylam as described in the first sentence of this Section 3.1(d) shall be deemed to constitute a waiver by Takeda of its right of first negotiation with respect to such transaction. In addition, failure of the Parties to agree within such [**] negotiation period (or such longer period as agreed between the Parties) shall result in the termination of such right of first negotiation with respect to such RNAi Product. If Takeda waives its right of first negotiation or such right of first negotiation terminates with respect to any such transaction and such RNAi Product is not against a Target for which Takeda has, prior to or concurrent with such waiver or termination, provided Alnylam written notice that Takeda is Developing an RNAi Product that has achieved, at a minimum, completion

of a [**] in the Field, then Alnylam shall be free to enter into a transaction for such RNAi Product with a Third Party; provided , however , that , no individual Asian Pharmaceutical Company shall be granted a license to RNAi Products directed against more than [**], and Alnylam shall not grant such permitted licenses to more than [**] Asian Pharmaceutical Companies; further provided that if such right of first negotiation with respect to such RNAi Product terminates after Takeda notifies Alnylam that Takeda desires to negotiate an agreement with respect to such transaction, then for a period of [**] following the termination of such right of first negotiation, Alnylam shall not negotiate or enter into a transaction for such RNAi Product with a Third Party on terms that, in the aggregate, are materially more favorable to the Third Party than those last offered by Alnylam to Takeda, taking into consideration the stage of Development for such RNAi Product at the time of negotiation with Alnylam. For clarity, the waiver or termination of the foregoing right of first negotiation with respect to one RNAi Product shall not affect Takeda’s right of first negotiation with respect to other RNAi Products during the five (5) year period after the Effective Date. Notwithstanding the foregoing, Takeda hereby acknowledges and agrees that Takeda has waived its right of first negotiation pursuant to this Section 3.1(d) with respect to Alnylam’s Development of RNAi Product(s) related to [**] and that Alnylam may, at any point during the term of this Agreement, enter into transaction(s) with any Third Party(ies) with respect to such [**] related RNAi Product(s) without providing notice to or engaging in negotiations with Takeda pursuant to this Section 3.1(d).

          (e)  Most Favored Licensee . Subject to Alnylam’s obligations to Third Parties, during the [**] period following the Effective Date, in the event that Alnylam enters into an agreement with a Third Party (other than pursuant to Listed Third Party Agreements or Pre-Existing Alliance Agreements) granting such Third Party any rights substantially similar in scope and substance as any of the rights granted to Takeda under this Agreement, including a non-exclusive license under the Alnylam Intellectual Property to Develop, Manufacture or Commercialize RNAi Products under [**] that are, with respect to such rights, more favorable in the aggregate to such Third Party than the [**], then the [**] shall be reduced or adjusted to such more favorable Third Party [**] on a prospective basis from the effective date of Alnylam’s agreement with such Third Party with respect to such rights.

           3.2 Rights Granted by Takeda to Alnylam.

          (a)  License Grants .

               (i)  Delivery Intellectual Property .

               (A) Subject to the terms and conditions of this Agreement and Takeda Third Party Obligations, Takeda hereby grants to Alnylam and its Affiliates a non-exclusive, worldwide right and license, under Takeda New Delivery Intellectual Property, to Develop, Manufacture, Commercialize, make, have made, use, offer for sale, sell and import RNAi Products.

               (B) Subject to the terms and conditions of this Agreement and Takeda Third Party Obligations, Takeda hereby grants to Alnylam and its Affiliates a non-exclusive, worldwide right and license, under Takeda Licensed Pre-Existing Delivery Patent Rights, solely for the purpose of practicing any Delivery Patent Rights that Alnylam first comes to Control during the [**] period following the Effective Date only to Develop, Manufacture, Commercialize, make, have made, use, offer for sale, sell and import RNAi Products Developed by Alnylam solely to the extent that practicing such Delivery Patent Rights of Alnylam without a license to such Takeda Licensed Pre-Existing Delivery Patent Rights would infringe such Takeda Licensed Pre-Existing Delivery Patent Rights; and

               (C) Notwithstanding the foregoing, the license grants under Sections 3.2(a)(i)(A) and 3.2(a)(i)(B) shall not apply to a given RNAi Product unless Alnylam personnel have devoted at least [**] of an FTE of effort to such Target, and Alnylam, in accordance with Section 3.7(b), confirms in writing through the Gatekeepers that the Target to which such RNAi Product is directed is not on the Takeda Delivery Reserved Target List. For purposes of clarity, Takeda’s addition of a Target to the Takeda Delivery Target List after the date Alnylam has cleared such Target through the Gatekeepers in accordance with Section 3.7(b) shall not terminate or in any way restrict the license granted to Alnylam under this Section 3.2(a)(i).

               (ii)  License Grant with Respect to Abandoned Product . Effective as of Alnylam’s election of the Abandoned Product Option or Takeda’s election of the Early-Opt-Out Option or Opt-Out Option with respect to an Abandoned Product, subject to the terms and conditions of this Agreement and Takeda Third Party Obligations, Takeda hereby grants Alnylam and its Affiliates an exclusive, worldwide, royalty bearing right and license, under the Know-How and Patent Rights Controlled by Takeda or its Affiliates and incorporated by Takeda or its Affiliates into such Abandoned Product, or included in the Development plan approved by Takeda or its Affiliates, as of the effective date of Alnylam’s election of the Abandoned Product Option or Takeda’s election of the Early-Opt-Out Option or Opt-Out Option to the extent that is necessary for Alnylam to Develop, Manufacture, Commercialize, make, have made, use, offer for sale, sell and import such Abandoned Product; provided , however , that Takeda shall not be obligated to transfer any Know-How which falls within Takeda Pre-Existing Delivery Intellectual Property.

          (b) Sublicense Rights .

               (i) Subject to Takeda Third Party Obligations, Alnylam shall have the right to grant sublicenses within the scope of the licenses granted to Alnylam in Sections 3.2(a)(i)(A) and 3.2(a)(ii), on an RNAi Product-by-RNAi Product basis or Abandoned Product-by-Abandoned Product basis (x) to Third Parties (other than any Person listed on Schedule I-1 ) solely for purposes of Developing and/or Commercializing an RNAi Product that has been Developed by Alnylam or Abandoned Product, as applicable, that has achieved at the time of such sublicense grant, at a minimum,

completion of a [**] (which, for clarity, need only be completed with respect to the lead candidate for such RNAi Product or Abandoned Product and not for any backup candidates for such RNAi Product or Abandoned Product), (y) to Third Parties (other than any Person listed on Schedule I-2 ) solely for purposes of a Bona Fide Collaboration or (z) to Third Parties solely for purposes of engaging contract research organizations, contract manufacturers, contract sales forces and academic institutions in connection with the performance of services related to the Development and/or Commercialization of an RNAi Product; provided that , with respect to the foregoing clause (z), Alnylam shall only sublicense such Third Party the right to use the Takeda New Delivery Intellectual Property or Takeda Intellectual Property, as applicable, in connection with the performance of such services.

               (ii) Subject to Takeda Third Party Obligations, Alnylam shall have the right to grant sublicenses within the scope of the licenses granted to Alnylam in Section 3.2(a)(i)(B), on an RNAi Product-by-RNAi Product basis (x) to Third Parties (other than any Person listed on Schedule I-1 ) solely for purposes of Developing and/or Commercializing an RNAi Product that has been Developed by Alnylam and that has achieved at the time of such sublicense grant, at a minimum, completion of a [**] (which, for clarity, need only be completed with respect to the lead candidate for such RNAi Product and not for any backup candidates for such RNAi Product) or (y) to Third Parties solely for purposes of engaging contract research organizations, contract manufacturers, contract sales forces and academic institutions in connection with Development and/or Commercialization of an RNAi Product; provided that , with respect to the foregoing clause (y), Alnylam shall only sublicense such Third Party the right to use the Takeda Licensed Pre-Existing Delivery Patent Rights in connection with the performance of such services.

               (iii) All sublicenses granted pursuant to Sections 3.2(b)(i) and 3.2(b)(ii) shall be subject to the following conditions:

               (A) Such sublicense shall be consistent with the requirements of this Agreement;

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

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

               (D) To the extent required under any applicable Takeda Third Party Obligations, if such sublicense is granted pursuant to a written sublicense agreement, Alnylam shall provide a copy of such sublicense agreement to Takeda (with redactions to the fullest extent permitted under the applicable Takeda Third Party Obligation(s)).

          (c)  Alnylam’s Right of First Negotiation in the United States . From the Effective Date until the [**] of the Effective Date, if Takeda seeks to license to a Third Party the right to Develop and/or Commercialize a Licensed Product in (i) the United States or (ii) the United States and other countries, provided that such license does not also include any country in Asia or Europe, Takeda shall provide Alnylam written notice of its intent to enter into such a transaction, identifying the Licensed Product that will be the subject of such transaction. Within [**] after receipt of such notice, Alnylam shall notify Takeda in writing either that (x) Alnylam is interested in negotiating an agreement with respect to such Licensed Product or (y) Alnylam has no interest and therefore waives such right of first negotiation. If Alnylam notifies Takeda within [**] that Alnylam desires to negotiate an agreement with respect to such Licensed Product, the Parties shall negotiate in good faith for up to [**] from the date of such notification, or such longer period as agreed between the Parties, regarding the terms pursuant to which the Parties would enter into such transaction. Failure by Alnylam to give notice of its interest or lack of interest in negotiating for such agreement within [**] after receipt of written notice from Takeda as described in the first sentence of this Section 3.2(c) shall be deemed to constitute a waiver by Alnylam of its right of first negotiation with respect to such Licensed Product. In addition, failure of the Parties to agree within such [**] negotiation period (or such longer period as agreed between the Parties) shall result in the termination of such right of first negotiation. If Alnylam waives its right of first negotiation or such right of first negotiation terminates with respect to such Licensed Product, then Takeda shall be free to enter into a transaction for such Licensed Product with a Third Party; provided that if such right of first negotiation terminates after Alnylam notifies Takeda that Alnylam desires to negotiate an agreement with respect to such transaction, then for a period of [**] following the termination of such right of first negotiation Takeda shall not enter into a transaction for such Licensed Product with a Third Party on terms that, in the aggregate, are materially more favorable to the Third Party than those last offered by Takeda to Alnylam, taking into consideration the stage of Development for such Licensed Product at the time of negotiation with Alnylam. For clarity, the waiver or termination of the foregoing right of first negotiation with respect to one Licensed Product shall not affect Alnylam’s right of first negotiation with respect to other Licensed Products during the [**] period after the Effective Date.

           3.3 Section 365(n) of the Bankruptcy Code. All rights and licenses granted under or pursuant to any section of this Agreement are and will otherwise be deemed to be for purposes of Section 365(n) of the United States Bankruptcy Code (Title 11, U.S. Code), as amended (the “ Bankruptcy Code ”), licenses of rights to “intellectual property” as defined in Section 101(35A) of the Bankruptcy Code. The Parties will retain and may fully exercise all of their respective rights and elections under the Bankruptcy Code. Each Party agrees that the other Party, as licensee of such rights under this Agreement, will retain and may fully exercise all of its rights and elections under the Bankruptcy Code or any other provisions of applicable Law outside the United States that provide similar protection for “intellectual property.” The Parties further agree that, in the event of the commencement of a bankruptcy proceeding by or against a Party under the U.S. Bankruptcy Code or analogous provisions of applicable Law outside the United States, the other Party will be entitled to a complete duplicate of (or complete access to,

as appropriate) such intellectual property and all embodiments of such intellectual property, which, if not already in such Party’s possession, will be promptly delivered to it upon such Party’s written request thereof. Any agreements supplemental hereto will be deemed to be “agreements supplementary to” this Agreement for purposes of Section 365(n) of the Bankruptcy Code.

           3.4 No Other Rights. Only the licenses granted to Takeda under Section 3.1 and Schedule D and to Alnylam under Section 3.2 and Schedule D hereof shall be of legal force and effect and are limited to the scope expressly granted. Accordingly, except for the rights expressly granted under Section 3.1, Section 3.2 and Schedule D hereof, no license, right, title or interest of any nature whatsoever is granted hereunder by implication, estoppel, reliance or otherwise, by either Party to the other Party, and any of Alnylam’s rights to Alnylam Intellectual Property not specifically granted to Takeda under Section 3.1 and Schedule D on the one hand or any of Takeda’s rights to Takeda Delivery Intellectual Property not specifically granted to Alnylam under Section 3.2 and Schedule D on the other hand, shall be retained by the licensor Party. For purposes of clarity, subject to the provisions of Sections 3.1(c) and 3.1(d) with respect to Alnylam and Section 3.2(c) with respect to Takeda, nothing contained in this Agreement shall prevent or restrict (a) Alnylam from granting to any Third Party any non-exclusive licenses under any Alnylam Intellectual Property, or (b) Takeda from granting to any Third Party any non-exclusive licenses under any Takeda Delivery Intellectual Property, in each case either within or outside the Field.

           3.5 [**]. If at any time with respect to a Licensed Product (a) royalties would not be required hereunder but for [**] and (b) Takeda believes in good faith that [**], then Takeda may notify Alnylam in writing to request an [**] pursuant to the procedures as set forth in this Section 3.5 of its good faith belief that such [**] hereunder. Within thirty (30) days after Alnylam’s receipt of Takeda’s notice, the Parties shall meet to discuss Takeda’s questions. If the Parties are unable to reach agreement regarding such issue within thirty (30) days after such meeting, the Parties shall engage three (3) independent Third Party [**] attorneys to [**], with each Party appointing one of such Third Party [**] attorneys and the two (2) [**] attorneys so appointed selecting the third such Third Party [**] attorney. All three Third Party [**] attorneys shall be jointly engaged by the Parties, with the Parties sharing equally in the fees of such attorneys. The standard on which any such determination shall be based is whether all such [**] require payment of royalties hereunder for such Licensed Product in such country. Prior to such determination, each Party shall have an opportunity to present to such Third Party [**] attorneys a written summary of its position with respect to the issue (including factual and documentary evidence with respect to the issue). The Third Party attorneys will establish appropriate rules for such proceeding. The issue shall be determined by majority vote of the three (3) Third Party [**] attorneys; provided that the Third Party [**] attorneys shall not issue a written decision regarding such vote. The determination of the three (3) Third Party [**] attorneys shall be binding on the Parties. All proceedings and determinations pursuant to this Section 3.5 and information disclosed in connection therewith, whether or not written, shall remain the Confidential Information of both Parties and shall not be used by either Party for any purpose other than the

proceedings set forth in this Section 3.5; provided that Alnylam shall have the right to use any such information in the [**]. If the majority of such attorneys determines that each such [**] require payment of royalties hereunder for such Licensed Product in such country, [**] and, subject to the provisions of this Section 3.5 below, no royalties shall be owed on the sales of such Licensed Product in such country by Takeda or its Affiliates or sublicensees. If royalties would not be required hereunder in accordance with the foregoing provisions of this Section 3.5, but [**] in such country and, within thirty (30) days after Alnylam notifies Takeda of such [**], Takeda shall pay Alnylam all past royalties that were not paid by Takeda on account of the determination pursuant to this Section 3.5. If a [**] require payment of royalties hereunder for a Licensed Product in a country, then [**] Takeda shall not thereafter have the right to seek additional determinations pursuant to this Section 3.5 with respect to such counterpart [**]. Alnylam hereby acknowledges and agrees that the foregoing questioning process shall not constitute a [**] and shall not give rise to [**].

           3.6 Certain License Limitations.

          (a)  Pre-Existing Alliance Agreements .

               (i) The grants by Alnylam under Alnylam Intellectual Property set forth in Section 3.1(a) are subject to, and are limited to the extent of, the rights that Alnylam has previously granted and is required to grant under Alnylam Intellectual Property to Pre-Existing Alliance Parties under the terms of the Pre-Existing Alliance Agreements to the extent disclosed in the copies of such agreements provided to Takeda prior to the Effective Date. As and to the extent that such rights previously granted to Pre-Existing Alliance Parties under Alnylam Intellectual Property (whether such rights are previously or subsequently exercised) lapse, terminate or otherwise revert to Alnylam, they shall be automatically included in the non-exclusive rights under Alnylam Intellectual Property granted to Takeda under Section 3.1(a).

               (ii) Takeda acknowledges that, other than with respect to Designated Targets, [**] until the expiration of the [**], and [**] until the expiration of the [**], may under their respective Pre-Existing Alliance Agreement from time to time request rights under Broad RNAi Intellectual Property with respect to a particular Target that Alnylam is required, pursuant to the terms of the applicable Pre-Existing Alliance Agreement, to grant such rights to such Pre-Existing Alliance Party with respect to such Target. Notwithstanding the foregoing, in no event shall Takeda’s non-exclusive rights granted with respect to any Designated Target hereunder be restricted in any way or at any time by any Pre-Existing Alliance Agreement.

          (b) Contractual Obligations Under Listed Alnylam Third Party Agreements .

               (i) For the avoidance of doubt, the grants by Alnylam under Alnylam Intellectual Property set forth in Section 3.1(a) include, subject to this Section 3.6(b)(i), the sublicense of Alnylam Intellectual Property that is not owned by Alnylam. Takeda’s rights and licenses under such Alnylam Intellectual Property are limited to the

rights granted by Listed Counterparties to Alnylam under the Listed Alnylam Third Party Agreements, and Takeda shall comply, and cause its Affiliates and sublicensees to comply, with those restrictions and other terms applicable to sublicensees under such agreements. True and correct redacted copies of such Listed Alnylam Third Party Agreements have been made available to Takeda.

               (ii) Notwithstanding anything to the contrary herein, the licenses to Alnylam Patent Rights hereunder initially shall not include licenses to Patent Rights licensed by Alnylam or its Affiliates under the Non-Exclusive License Agreement between [**] (the “[**] Agreement ”). Takeda shall have the option, exercisable upon written notice to Alnylam hereunder, to license any of such Patent Rights on a Licensed Product-by-Licensed Product basis. Upon such election, which shall indicate the Patent Rights to be licensed, (x) the license granted to Takeda under Alnylam’s rights to Patent Rights pursuant to Section 3.1(a) shall include such Patent Rights with respect to the designated Licensed Product(s), (y) Schedule A shall be amended to include such Patent Rights, and (z) the [**] Agreement shall be deemed a Listed Alnylam Third Party Agreement, [**] shall be deemed a Listed Counterparty and Schedule E shall be amended accordingly.

           3.7 Gatekeepers.

          (a)  Takeda Target Clearance .

               (i) From time to time during the term of this Agreement and, except as set forth in clauses (ii), (iii) and (iv) of this Section 3.7(a), with respect to no more than [**] Targets in any [**] and no more than [**] total Targets in any Fiscal Year, which Takeda reasonably believes are likely to be implicated in an Indication in the Field, Takeda may inquire [**] (except as provided below) of the Gatekeepers in writing (specifying the Target common name, GenBank accession number and nucleotide sequence thereof, but in no event shall Takeda be required to disclose the Indications or particular RNAi Compound) whether such Target is (A) a Blocked Target, (B) a Target for which the [**] Intellectual Property is not available but which is not otherwise a Blocked Target (a “ Partially Blocked Target ”), or (C) a Takeda Reserved Target; provided , however , that, prior to reporting to Takeda that a Target is a Partially Blocked Target, Alnylam shall (x) inquire of Takeda as to whether Takeda would like Alnylam to use its best efforts to encourage [**] to undertake any actions available to [**] which would have the effect of causing such Partially Blocked Target to become a Takeda Reserved Target, which would require Alnylam to disclose the identity of such Partially Blocked Target, but not the identity of Takeda and (y) if so requested by Takeda, Alnylam shall use its best efforts to encourage [**] to undertake any actions available to [**] which would have the effect of causing such Partially Blocked Target to become a Takeda Reserved Target. The Gatekeepers shall, within the time periods specified below, notify Takeda in writing which of the three categories described in clauses (A), (B) and (C) of the previous sentence such Target falls in to; provided , however , that in no event will the Gatekeepers directly or indirectly notify or communicate to any other Alnylam employee or consultant or any Alnylam Affiliate or Third Party the contents or the existence of Takeda’s inquiry hereunder without Takeda’s prior written consent, which may be withheld at Takeda’s sole discretion. With respect to each [**] request, the Gatekeepers shall provide the foregoing notification to Takeda as soon as possible, but no later than [**] days after receipt of such request. For purposes of clarity, a Partially Blocked Target shall be considered a Takeda Reserved Target for all purposes under this Agreement except that Takeda shall have no right hereunder to use [**] Intellectual Property with respect to such Partially Blocked Target.

               (ii) Notwithstanding the foregoing, from the Effective Date until achievement of [**], the limitation on the number of Takeda’s inquiries as set forth in Section 3.7(a)(i) shall not apply until such time as at least [**] Targets submitted by Takeda are determined not to be Blocked Targets.

               (iii) Notwithstanding the foregoing, the limitation on the number of Takeda’s inquiries as set forth in Section 3.7(a)(i) shall not be exhausted until [**] included in such inquiry is determined not to be a Blocked Target.

               (iv) If the Gatekeepers become aware of the removal of any Target previously identified to Takeda as a Blocked Target from the Blocked Target List,

Alnylam shall notify Takeda the identity of such Target that was removed from the Blocked Target List.

               (v) Notwithstanding the foregoing, the Parties acknowledge that, to the extent permitted as of the Effective Date (A) under the [**] Agreement, [**] may during the [**] request exclusive rights from Alnylam with respect to a particular Target other than a Designated Target and (B) under the [**] License Agreement, [**] may during the [**] request exclusive rights from Alnylam with respect to a particular Target other than a Takeda Reserved Target.

          (b) Alnylam Target Clearance .

               (i) From time to time during the term of this Agreement, with respect to no more than [**] in any [**] and no more than [**] total Targets in any Fiscal Year, Alnylam may inquire of the Gatekeepers in writing (specifying the Target common name, GenBank accession number and nucleotide sequence thereof) whether or not a Target is on the Takeda Delivery Reserved Target List. The Gatekeepers shall notify Alnylam in writing whether or not such Target is on the Takeda Delivery Reserved Target List; provided , however , that in no event will the Gatekeepers directly or indirectly notify or communicate to Takeda or any Third Party the contents or the existence of Alnylam’s inquiry hereunder without Alnylam’s prior written consent, which may be withheld at Alnylam’s sole discretion. Notwithstanding the limitation on the number of Targets as set forth in this Section 3.7(b)(i), Alnylam’s inquiry right shall not be exhausted until at least [**] per [**], or [**] Targets per Fiscal Year, are determined not to be on the Takeda Delivery Reserved Target List.

               (ii) If the Gatekeepers become aware of the removal of any Target previously identified to Alnylam as on the Takeda Delivery Reserved Target List from the applicable list, the Gatekeepers shall notify Alnylam of such removal (but not the identity of the Target that was removed) and Alnylam shall have the right to inquire of the Gatekeepers pursuant to, and in compliance with, Section 3.7(b)(i), whether or not a Target previously identified to Alnylam as on the Takeda Delivery Reserved Target List remains on the applicable list; provided , however , that the inquiries made under this Section 3.7(b)(ii) shall not be counted towards the [**] per [**] and [**] Target per year limits set forth in Section 3.7(b)(i).

          (c)  Gatekeepers . The inquiries and responses made in connection with Sections 3.7(a) and 3.7(b) shall be made in writing, including via e-mail. Such inquiries shall be directed to the attention of [**] designated employees of Alnylam (the “ Gatekeepers ”) who will be bound by confidentiality obligations to both Parties. Each Party agrees to provide the Gatekeepers with full and complete copies of all records and information (including un-redacted copies of the relevant Third Party agreements) that are necessary for the Gatekeepers to render their determination.

           3.8 Additional Fields; Field Option.

          (a)  Additional Fields . Takeda shall initially conduct Development, Commercialization and Manufacturing activities directed to Targets only with respect to Indications in the Field. Based on the results of [**] with respect to any Licensed Product directed to a specific Target in the Field, Takeda may engage in Development, Commercialization and/or Manufacturing activities directed to such Target for any additional or replacement Indication (each, an “ Additional Indication ”) in any Additional Field not previously the subject of Takeda’s exercise of a Field Option, without having to pay a Field Option Fee; provided , however , that (i) Takeda shall notify Alnylam of its extension of Development, Commercialization and/or Manufacturing activities directed to such Target for such Additional Indication in such Additional Field, and (ii) Takeda shall pay Alnylam the following amounts (which shall be in addition to any event payments which may be owed under Section 7.2) upon achievement of the following events by Takeda, its Affiliates or sublicensees with respect to each such Additional Indication in such Additional Field:

With respect to the first Licensed Product for each such Additional Indication in such Additional Field:

With respect to the second and each subsequent Licensed Product for such Additional Indication in such Additional Field:

          The amounts paid under this Section 3.8(a) for Additional Indications within a given Additional Field shall be fully creditable against Field Option Fees which may be paid by Takeda pursuant to Section 7.4 for such Additional Field. In the event that the total event payments made under this Section 3.8(a) reach Fifty Million United States dollars ($50,000,000) for a given Additional Field, such Additional Field shall automatically be included in the Field hereunder. Amounts paid under this Section 3.8(a) with respect to Shared Products will be reduced by [**] percent ([**]%); provided that , for purposes of the credit against Field Option Fees described above in this paragraph to which Takeda is entitled with respect to any such reduced payment for a Shared Product, the credit amount shall be the [**] amount of the applicable event payment (i.e., [**] percent ([**]%) of the amount that would have been payable if a Licensed Product other than a Shared Product had achieved the applicable event) notwithstanding that Takeda only paid [**] percent ([**]%) of such amount.

          For the avoidance of doubt, in no event shall Takeda conduct Development, Commercialization or Manufacturing activities directed to any Target in any Additional Field other than as permitted in this Section 3.8. In the event that the Parties are unable to agree on whether Takeda’s activities fall within or outside the Primary Fields or any Additional Field in a manner prohibited by this Agreement, the Parties shall comply with Section 12.2, except that if the dispute is not resolved thereby, then either Party may submit such dispute to a panel (the “ Field Definition Panel ”) consisting of three (3) independent experts in clinical development, with each Party having the right to select a single expert and the two (2) selected experts selecting the third expert by mutual agreement. Such third expert shall serve as the chairperson of the Field Definition Panel. The selection of the experts for the Field Definition Panel shall occur within [**] following the Parties’ decision to submit such dispute to such a panel, and the Parties shall consult with such Field Definition Panel for a period not to exceed [**] from the selection of such experts. The Field Definition Panel shall render a decision with respect to such dispute, based on a majority vote, with each expert having one (1) vote, within [**] following the end of such consultation period, which decision shall be binding on the Parties. In the event that the Field Definition Panel determines that Takeda’s Development, Commercialization or Manufacturing activities are being conducted in any Additional Field in a manner which is prohibited hereunder, Takeda shall, within [**] after such determination by the Field Definition Panel, cease such proscribed activity or exercise the Field Option with respect to such Additional Field, if the Field Option is then exercisable as to such Additional Field and such activity would not be prohibited upon such exercise.

          (b)  Field Option . During the term of this Agreement, Alnylam or its Affiliates may not grant any Third Party any exclusive license or right under Alnylam Intellectual Property to any Field or Additional Field. From time to time during the term of this Agreement, Takeda shall have the right, upon written notice to Alnylam, to request the extension of the license granted under Section 3.1(a) to include one or more

Additional Field(s) (“ Field Option ”) in which Takeda has a good faith intention to seek to Develop, Commercialize and Manufacture RNAi Compounds or RNAi Products, which right shall be subject to any agreement which Alnylam may have entered into with a Third Party with respect to such Additional Field(s). Upon Takeda’s payment of the Field Option Fee for each such Additional Field pursuant to Section 7.4, the Field shall include such Additional Field(s).

          (c)  Inquiries Regarding Targets in Additional Field . Notwithstanding the foregoing, prior to Takeda requesting to extend the Field as provided in Section 3.8(b) above, Takeda may inquire, with respect to any Additional Field in which Takeda has a bona fide interest in exercising a Field Option, from time to time, from the Gatekeepers whether selected Targets are available in such Additional Field for license under the Alnylam Intellectual Property until at least [**] Targets have been identified as available in such Additional Field, which inquires shall not be subject to those limitations set forth in Section 3.7(a)(i).

           3.9 Designated Target Option. No more frequently than [**] during the Novartis Exclusivity Term, Takeda shall have the right, upon written notice to Alnylam, to select up to [**] Targets in the Field, which have been confirmed by the Gatekeeper pursuant to Section 3.7(a)(i) not to be Blocked Targets, for submission by the Gatekeepers to Novartis pursuant to the terms of the Novartis Agreement (a “ Submitted Target ”); provided that such [**] Target limit shall not apply until such time as such process has identified at least [**] Targets as Designated Targets. The Gatekeepers shall provide notice to Novartis of the Submitted Target(s) as promptly as practicable, but no later than [**] after its receipt of Takeda’s request, and Takeda shall cooperate with the Gatekeepers in providing any information reasonably requested by Novartis (but not the identity of Takeda or any of Takeda’s RNAi Compounds and Indications thereof) in order for Novartis to determine whether or not to pursue Development and/or Commercialization activities directed to a Submitted Target. During the period of time between Alnylam providing notice to Novartis of such Submitted Targets until Alnylam receives a response from Novartis, Alnylam shall not, other than to Novartis, (a) grant any exclusive rights to any Third Party in or to such Submitted Target or (b) disclose any information regarding such Submitted Target to any Third Party, including, without limitation, any Pre-Existing Alliance Party. If Novartis notifies the Gatekeepers that it wishes (as such term is used in the Novartis Agreement) to pursue Development and/or Commercialization activities directed to a Submitted Target, then the Gatekeepers shall so notify Takeda and Alnylam promptly upon the Gatekeepers’ receipt of such notification, and such Target shall be deemed a Blocked Target for purposes of this Agreement. If the Gatekeepers receive notice from Novartis that Novartis has no interest in pursuing Development and/or Commercialization activities directed to a Submitted Target, or if Novartis otherwise waives its right to a Submitted Target under the terms of the Novartis Agreement, then the Gatekeepers shall notify Takeda and Alnylam promptly upon the Gatekeepers’ receipt of such notification or waiver. In such event, such rejected or waived Submitted Target shall be deemed a “Designated Target” for all purposes under this Agreement, Takeda shall be deemed to have exercised the option with respect to such Submitted Target (each, a “ Designated Target Option ”), and any Designated

Target will not thereafter become a Blocked Target (i.e., once a Target becomes a Designated Target, Alnylam shall not grant any exclusive license with respect to such Target to any Third Party, including Novartis). Takeda shall be free to Develop, Commercialize and Manufacture RNAi Compounds and RNAi Products in the Field directed to any Designated Target in accordance with the terms hereof without further risk of such Target becoming a Blocked Target. Further, after expiration of the Novartis Exclusivity Term, no Takeda Reserved Target shall become a Blocked Target and all Takeda Reserved Targets shall henceforth be deemed Designated Targets.

           3.10 Special Provisions Relating to Novartis.

          (a)  Compliance with Novartis Agreement . It is the intent of the Parties that, subject to Section 3.10(b)(i), this Agreement shall be construed in a manner which is consistent with and in compliance with the terms of the Novartis Agreement, as provided to Takeda prior to the Effective Date, in all respects.

          (b)  Alnylam Change of Control . In the event that, at any time during the [**], an Alnylam Change of Control occurs in which [**] is the acquiring entity (a “[**]”), it shall be a condition precedent to such [**] that:

               (i) Section 3.7(c) of this Agreement shall be amended to provide that the “Gatekeepers” shall not be designated employees of Alnylam but instead (A) shall be Third Parties who shall have no material relationship (other than as Gatekeepers) with Alnylam, [**], (B) shall be mutually agreeable to both Parties and (C) shall be bound by confidentiality obligations to both Parties, and to the extent that the consent of [**] shall be required for such amendment, such consent shall have been obtained;

               (ii) [**], to the extent required, shall have agreed [**] that the [**] contained therein ( i.e. , [**] thereof) shall terminate upon such [**] and that [**], as a result of any obligations under the [**] or as a result of any other actions [**] in connection with [**] hereunder after the date of the agreement providing for such [**] or, if there is no [**], after the date of such [**]; and

               (iii) Alnylam agrees that the [**] shall include the consent of [**], as applicable, required by clause (i) above and the agreement of [**], as applicable, to the amendment required by clause (ii) above, and to comply with all the terms and conditions of this Agreement.

          (c) No Adverse Amendments . Alnylam agrees not to enter into any amendment or modification to the [**] which would have an adverse impact on Takeda’s rights under this Agreement without the prior written consent of Takeda. Without limiting the foregoing, the Parties acknowledge and agree that the following amendments/modifications would have an adverse impact on Takeda’s rights under this Agreement: [**]; (iv) any amendment that would require Alnylam to provide to [**] any Confidential Information of Takeda; and (v) any provision that is inconsistent with the obligations of Alnylam to Takeda hereunder.

          (d) Specific Performance . The Parties hereto agree that irreparable damage would occur if any provision of this Section 3.10 were not performed in accordance with the terms hereof and that, notwithstanding anything to the contrary contained in this Agreement, Takeda shall be entitled to equitable relief (including an injunction or injunctions or the ordering of specific performance) to prevent breaches of this Agreement or to enforce specifically the performance of the terms and provisions hereof in any federal court located in the State of New York or any New York state court, in addition to any other remedy to which it is entitled at law or in equity.

           3.11 Notice of Changes. Within [**] after each anniversary of the Effective Date, Alnylam shall provide to Takeda an updated Schedule A that reflects any changes to the list of Broad RNAi Patent Rights set forth on Schedule A which have occurred during the prior year.

ARTICLE IV

DEVELOPMENT OF LICENSED PRODUCTS;

OPT-IN AND OPT-OUT RIGHTS

           4.1 Diligence. Subject to the exercise by Takeda of the Early Opt-Out Option or the Opt-Out Option, during the first [**] after the Effective Date, Takeda shall use Commercially Reasonable Efforts to Develop and Commercialize Licensed Products in the Field. For purposes of clarity, Alnylam acknowledges and agrees that Takeda is not required to use Commercially Reasonable Efforts to Develop or Commercialize Licensed Products with respect to every Takeda Reserved Target or Designated Target nor to do so in each country in the Territory.

           4.2 Alnylam Profit-Sharing Option.

          (a) Profit-Sharing Option . From the Effective Date until the [**] of the Effective Date, Alnylam shall have the right, on a Licensed Product-by-Licensed Product basis, to elect to participate with Takeda in the Development and Commercialization in the United States, in accordance with an initial Development plan established by Takeda, for up to [**] Licensed Products for which an IND has been filed; provided that if the Field is expanded to include an Additional Field pursuant to Section 3.8(a), Alnylam may exercise the Profit-Sharing Option for up to [**] additional Licensed Products within each such Additional Field (the “ Profit-Sharing Option ”) in accordance with the terms and conditions set forth in an agreement (the “ Profit-Sharing Agreement ”) to be negotiated in good faith between the Parties, which agreement shall be based on the terms and conditions substantially the same as those set forth on Schedule D and consistent with this Agreement. For clarity, Alnylam shall have no Profit-Sharing Option with respect to any Abandoned Product. Notwithstanding the foregoing, unless and until the Parties enter into a Profit-Sharing Agreement, the provisions of Schedule D and this Section 4.2, as such terms may be modified by mutual written agreement of the Parties, shall apply and shall be deemed to be the Profit-Sharing Agreement and in the event of any inconsistency between Schedule D and this Agreement, this Agreement shall govern.

Notwithstanding anything to the contrary in this Agreement, the Profit-Sharing Option and the provisions of this Section 4.2 shall only be applicable with respect to a Licensed Product that is being Developed against a Designated Target; provided that , after the end of the Novartis Exclusivity Term, the Profit-Sharing Option and the provisions of this Section 4.2 shall be applicable with respect to all Licensed Products that are not Blocked Targets.

          (b) Access to Information Regarding Licensed Products . On a Licensed Product-by-Licensed Product basis, until the earlier of the [**] of the Effective Date or the earlier expiration of the Profit-Sharing Option, (i) at the time of [**], (ii) [**] prior to Initiation of a [**] or (iii) promptly following Takeda’s receipt of FDA feedback following the [**] meeting with the FDA (or in the event there is no [**] meeting with the FDA, not earlier than [**] before the planned commencement date and not later than [**] after the commencement of the [**] designed to provide a basis for seeking Regulatory Approval in a Major Market), for each Licensed Product, Takeda shall provide Alnylam with information on the historical Development Costs, payments associated with Takeda Third Party Obligations, regulatory information submitted to the FDA prior to the applicable time-period mentioned above, Takeda’s then current Development plans and budgets and then-current Commercialization plans and budgets (to the extent available) with respect to such Licensed Product and other information pertinent to the Development and Commercialization of such Licensed Product in the United States to the extent Takeda reasonably believes such information is useful. In addition, Alnylam may, by written notice to Takeda, request such additional information that will significantly impact the value of such Licensed Products in the United States (x) after the [**] for a Licensed Product, (y) after the Initiation of a [**] and (z) following Takeda’s receipt of FDA feedback following the [**] meeting (or in the event there is no [**] meeting with the FDA, within [**] after receiving the information from Takeda pursuant to Section 4.2(b)(iii)). Takeda shall provide such additional report as promptly as practicable after receipt of Alnylam’s written request for such report.

          (c)  Exercising Profit-Sharing Option . Alnylam may exercise its Profit-Sharing Option with respect to a Licensed Product with written notice to Takeda and upon payment of the Profit-Sharing Option Payment for each such Licensed Product pursuant to Section 7.5, at any time within: (i) [**] after the [**] for such Licensed Product; (ii) [**] days after the Initiation of a [**] with respect to such Licensed Product; or (iii) [**] after the date of Takeda’s receipt of FDA feedback following the [**] meeting (or in the event there is no [**] meeting with the FDA, [**] after receiving the information from Takeda pursuant to Section 4.2(b)(iii)) (each an “ Option Exercise Period ”). Notwithstanding the foregoing, if Takeda fails to provide Alnylam information, (including reasonable additional information requested by Alnylam pursuant to Section 4.2(b)) on a particular Licensed Product on or before the time specified in clause (i), (ii) or (iii) set forth in Section 4.2(b), as applicable, then, (x) the corresponding Option Exercise Period with respect to such Licensed Product and (y) the related time frame set forth in Section 7.5(a) for Alnylam to pay Takeda the applicable Option Exercise Payment for the relevant Option Exercise Period, shall each be extended by an amount of

time equal to the amount of time of Takeda’s delay in delivering to Alnylam such information regarding such Licensed Product pursuant to Section 4.2(b).

          (d) Effects of Exercising Profit-Sharing Option . Subject to Section 4.3, if Alnylam exercises the Profit-Sharing Option as to a Licensed Product and after Takeda receives all payments due from Alnylam pursuant to Section 7.5, then (i) such Licensed Product in the United States shall be deemed a “ Shared Product ” and Alnylam and Takeda shall jointly Develop and Commercialize such Shared Product in the United States during the Profit-Share Term in accordance with the Profit-Sharing Agreement, (ii) Takeda’s obligation to pay the royalty set forth in Section 7.3 with respect to the applicable Shared Product in the United States shall terminate and the Parties shall share the Net Profits/Losses with respect to such Shared Product as set forth in Section 7.5 and (iii) all future milestone payments, whether with respect to the United States or the ROW, that become payable by Takeda pursuant to Sections 3.8(a) and 7.2 with respect to such Licensed Product which becomes a Shared Product will be reduced by [**] percent ([**]%).

          (e) Expiration of Profit-Sharing Option; Effectiveness of Profit-Sharing Agreement . Failure by Alnylam to give written notice of exercise within the applicable time period set forth in Section 4.2(c) above, or waiver of its rights of first negotiation under Section 3.2(c), shall result in the expiration of the Profit-Sharing Option with respect to the applicable Licensed Product at the applicable stage. Notwithstanding the foregoing, if Alnylam’s rights of first negotiation under Section 3.2(c) is waived or terminated and on the first day of the next applicable Option Exercise Period Takeda is actively negotiating a license with a Third Party with respect to the relevant Licensed Product in the United States, Alnylam’s Profit-Sharing Option and such Option Exercise Period shall be suspended until the earlier of: (i) Takeda enters into a licensing transaction with such Third Party with respect to the relevant Licensed Product in the United States (in which case the Profit-Sharing Option shall terminate with respect to such Licensed Product), or (ii) Takeda is no longer in active negotiations with such Third Party. If Takeda ceases to be engaged in active negotiations with such Third Party without Takeda entering into a licensing transaction, Takeda shall notify Alnylam in writing of such termination, and Alnylam’s suspended Option Exercise Period shall commence on the date of such notice from Takeda and continue for a [**] period, as applicable, pursuant to Section 4.2(c). The Profit-Sharing Agreement shall not become effective until after Takeda receives all payments due from Alnylam in accordance with Section 7.5.

          (f)  Shared-Product Committee . Within [**] after the effective date of the Profit-Sharing Agreement, the Parties shall establish a Shared Product Committee (the “ SPC ”). The Profit-Sharing Agreement shall set forth the specific details governing the composition and conduct of the SPC. The SPC shall have responsibilities for overseeing activities of the Parties with respect to Shared Product(s) in the United States provided that Takeda shall have the authority to ensure that the Development and Commercialization of Shared Product(s) in the United States is consistent with Takeda’s global strategic plan for such Shared Product(s) in the ROW. The initial Development plan and budget and the initial Commercialization plan and budget shall be the plans and

budgets provided by Takeda to Alnylam pursuant to Section 4.2(b) most recently prior to Alnylam exercising the Profit-Sharing Option and thereafter. From time to time as reasonably necessary, Takeda shall have the right, in its sole reasonable discretion, to modify a Joint Development Plan and Joint Commercialization Plan (including the Development budget and Commercialization budget contained therein) after consultation with Alnylam and giving good faith consideration of all reasonable comments or suggestions proposed by Alnylam. Any material changes to development timeline or budget set forth in the applicable Joint Development Plan or Commercialization Plan which (i) are reasonably likely to delay the filing of the NDA for the applicable Shared Product by more than [**] or (ii) will increase the applicable Development or Commercialization budget by more than [**] percent ([**]%) of the most recent applicable budget set forth in the Joint Development Plan or Joint Commercialization Plan shall require the mutual agreement of the Parties. Notwithstanding the foregoing, Takeda (x) shall have the right to increase the budget by more than [**] percent ([**]%) by paying all Development Costs or Commercialization Costs that exceed [**] percent ([**]%) of the applicable Development budget or Commercialization budget, whether or not such increase is based on matters that could have substantial impact on Takeda’s global development and marketing strategies for such Shared Product, and (y) otherwise shall have the final authority in deciding matters that could have substantial impact on Takeda’s global development and marketing strategies for such Shared Product, even if such matters delay the filing of the NDA for the applicable Shared Product by more than [**]; provided that Takeda shall provide Alnylam with a reasonable explanation of the reasons for such budget increases and decisions and Takeda shall consider Alnylam’s reasonable opinion in good faith before increasing such budget or making such final decision. The SPC’s responsibilities shall include:

               (i) Reviewing and updating the Joint Development Plan and the Joint Commercialization Plan,

               (ii) Planning, coordinating and monitoring the Development and Commercialization of Shared Product(s) in the United States, and

               (iii) Coordinating regulatory activities with respect to Shared Product(s) in the United States and the ROW.

          (g)  Joint Development and Commercialization Plans . The Parties shall perform Development and Commercialization of Shared Product(s) in accordance with a Joint Development Plan and budget, a Joint Commercialization Plan and budget, the Profit-Sharing Agreement and any additional terms agreed to by the Parties. Subject to amendments in accordance with Section 4.3(b), the Joint Development Plan and budget and Joint Commercialization Plan and budget shall be the plans and budgets provided to Alnylam pursuant to Section 4.2(b) most recently prior to Alnylam exercising the Profit-Sharing Option.

          (h)  Diligence . If Alnylam exercises the Profit-Sharing Option, and subject to the exercise by either Party of the Opt-Out Option, each Party shall use Commercially Reasonable Efforts to Develop and Commercialize Shared Product(s) in the United States

during the Profit-Share Term in accordance with the Joint Development Plan, the Joint Commercialization Plan and the Profit-Sharing Agreement.

           4.3 Opt-Out.

          (a)  Takeda Early Opt-Out . Within [**] of Alnylam exercising the Profit-Sharing Option with respect to a particular Licensed Product, Takeda shall have the right to opt-out from participating in the Development and Commercialization worldwide of such Licensed Product by providing Alnylam written notice (“ Early Opt-Out Option ”); provided , however , that, subject to Section 4.5(b), Takeda shall continue through completion, at Alnylam’s expense, any clinical trials with respect to such Licensed Product that are in progress as of the date of the exercise of Takeda’s Early Opt-Out Option.

               (i) If Takeda exercises the Early Opt-Out Option pursuant to this Section 4.3(a), Alnylam may, within [**] of Takeda’s exercise of such option, rescind Alnylam’s election of the Profit-Sharing Option by providing written notice to Takeda, in which case, all rights with respect to the applicable Licensed Product shall be deemed to revert to Takeda and Takeda may, at its sole option, continue its Development or Commercialization unilaterally with respect to such Licensed Product at any time thereafter and the provisions of this Agreement shall apply to such Licensed Product on a going-forward basis as if such Licensed Product had never been a Shared Product.

               (ii) If Takeda exercises the Early Opt-Out Option and Alnylam does not rescind its Profit-Sharing Option, then (A) such Licensed Product shall cease to be a Licensed Product and shall become an Abandoned Product and (B) Alnylam shall make payments to Takeda in accordance with Section 7.6(a).

          (b)  Opt-Out by Either Party . At any time after the [**] of Alnylam’s exercise of its Profit- Sharing Option, either Party, by written notice to the other Party, shall have the right, in its sole discretion, to opt-out of the Development and Commercialization of a Shared Product (“ Opt-Out Option ”), which notice shall take effect with respect to such Shared Product [**] after such written notice. Notwithstanding the foregoing, a Party that exercises the Opt-Out Option shall (x) continue to be responsible for its share of Development Costs for any clinical trial with respect to such Shared Product that is in progress as of the date such Party exercises its Opt-Out Option through the earlier of (I) completion of such clinical trials, (II) the first anniversary of such Party’s exercise of the Opt-Out Option, or (III) the Development Costs paid by such Party for the Shared Product with respect to the continued conduct of such clinical trials after such Party has exercised the Opt-Out Option meet or exceed [**] United States dollars ($[**]), and (y) subject to foregoing [**] United States dollars ($[**]), remain liable for [**] percent ([**]%) of any other Development Costs for such Shared Product that cannot be cancelled after the Parties’ good-faith efforts to cancel such activity under the Joint Development Plan as of the date of the opt-out.

               (i)  Alnylam Opt-Out . If Alnylam exercises the Opt-Out Option with respect to a Shared Product, then, subject to Section 4.3(c): (A) the Parties shall

perform a final reconciliation of applicable Net Profits/Losses with respect to such Shared Product, through the effective date of such discontinued participation, and, subject to clauses (x) and (y) of Section 4.3(b), thereafter, Alnylam shall have no further right or obligation to share in the Net Profits/Losses with respect to such Shared Product; (B) the SPC shall cease to have oversight over such Shared Product; (C) Alnylam shall have no further Development or Commercialization responsibilities in connection with such Shared Product; (D) the Profit-Sharing Agreement with respect to such Shared Product(s) shall terminate; and (E) Takeda may elect to continue unilaterally Developing and Commercializing such Shared Product subject to Takeda’s payment of [**] percent ([**]%) of applicable future milestone payments and [**] percent ([**]%) of royalty payments set forth in Sections 7.2 and 7.3. If, upon Alnylam’s exercising of the Opt-Out Option with respect to a Shared Product, Takeda determines not to continue unilaterally Developing and Commercializing the Shared Product, then Section 4.3(c) shall apply.

               (ii)  Takeda Opt-Out . If Takeda exercises the Opt-Out Option with respect to a Shared Product, then, subject to Section 4.3(c): (A) the Parties shall perform a final reconciliation of applicable Net Profits/Losses with respect to such Shared Product through the effective date of such discontinued participation, and, subject to clauses (x) and (y) of Section 4.3(b), thereafter, Takeda shall have no further right or obligation to share in Net Profits/Losses with respect to such Shared Product(s); (B) the SPC shall cease to have oversight over such Shared Product; (C) Takeda shall have no further Development or Commercialization responsibilities in connection with such Shared Product; (D) the Profit-Sharing Agreement with respect to such Shared Product shall terminate; and (E) Alnylam may elect to continue unilaterally Developing and Commercializing such Shared Product subject to Alnylam’s payment of the applicable milestone and royalty payments set forth in Section 7.6(a). If, upon Takeda’s exercising of the Opt-Out Option with respect to a Shared Product, Alnylam determines not to continue unilaterally Developing and Commercializing the Shared Product, then Section 4.3(c) shall apply.

          (c)  Discontinuation by Both Parties . If a Party elects to discontinue its participation in a Shared Product Development program pursuant to this Section 4.3, and thereafter the other Party determines not to continue unilaterally Developing and Commercializing such Shared Product, then all rights with respect to such Shared Product shall be deemed to revert to Takeda, and Takeda shall have sole right and discretion in any further actions with respect to such Shared Product, including sublicensing such Shared Product. For purposes of clarity, the Parties acknowledge and agree that Alnylam’s sublicensing or partnering of the Development and/or Commercialization of a Shared Product shall not constitute discontinuation by Alnylam after opt out by Takeda.

           4.4 Abandoned Product Option.

          (a)  Abandoned Product Option . Until the [**] of the Effective Date, if (i) Takeda determines to terminate Development and/or Commercialization throughout the Territory of a Licensed Product for which Takeda has [**], (ii) Alnylam has not exercised the Profit-Sharing Option with respect to such Licensed Product, and (iii)

Takeda does not have another Licensed Product directed to the same Target being actively Developed that has reached, [**], then subject to Takeda Third Party Obligations with respect to Takeda Intellectual Property licensed from Third Parties that is incorporated into such Abandoned Product, Takeda shall provide Alnylam with a written notice of such determination and such Licensed Product shall be considered an Abandoned Product. Alnylam shall have the right, within [**] of its receipt of such notice from Takeda, to assume the Development and Commercialization, subject to applicable Takeda Third Party Obligations, of such Abandoned Product (the “ Abandoned Product Option ”) by providing Takeda written notice. For purposes of clarity, the Parties acknowledge and agree that (x) Takeda’s sublicensing or partnering relating to the Development and/or Commercialization of a Licensed Product or (y) Takeda’s decision to Develop a Licensed Product in a formulation, using a route of administration or for an Indication, in each case, that is different from the formulation, route of administration or Indication as set forth in the original IND, shall not constitute abandonment.

          (b)  Exercise of Abandoned Product Option . If Alnylam exercises the Abandoned Product Option with respect to a particular Abandoned Product, then: (i) the license grant to Takeda under Section 3.1(a) shall terminate with respect to such Abandoned Product; (ii) Takeda shall provide Alnylam with schedules identifying the Patent Rights Controlled by Takeda or its Affiliates that are licensed pursuant to Section 3.2(a)(ii); provided that Takeda’s omission of any applicable Patent Rights Controlled by Takeda or its Affiliates from such schedule shall not limit the license granted to Alnylam pursuant to Section 3.2(a)(ii); and (iii) Alnylam shall make payments to Takeda with respect to Net Sales of such Abandoned Product in accordance with Section 7.6(b) and any payment for, or triggered by, such Abandoned Product under Takeda Third Party Obligations.

          (c)  Discontinuation by Alnylam . If Alnylam, together with its Affiliates and sublicensees, elects to discontinue its Development and Commercialization of an Abandoned Product, then (i) the license grant to Alnylam under Section 3.2(a)(ii) shall terminate with respect to such Abandoned Product, (ii) all rights with respect to such Abandoned Product shall be deemed to revert to Takeda, and (iii) Takeda shall have sole right and discretion in any further actions with respect to such Abandoned Product, including sublicensing such Abandoned Product.

           4.5 Effect of Election of Early Opt-Out Option, Opt-Out Option or Abandoned Product Option.

          (a)  Effects of Election . If (x) Takeda exercises the Early Opt-Out Option for a Licensed Product and Alnylam does not rescind its exercise of the Profit-Sharing Option with respect to such Licensed Product, (y) either Party exercises the Opt-Out Option pursuant to Section 4.3 and the other Party continues unilateral Development and Commercialization of such Licensed Product, or (z) Alnylam exercises the Abandoned Product Option pursuant to Section 4.4 for a Licensed Product, then the Party that has elected to opt-out of or abandon the Development and Commercialization of such Licensed Product shall:

               (i) transfer and assign to the other Party all right, title and interest in any regulatory filings made by such Party or any of its Affiliates relating to the relevant Licensed Product, all regulatory materials with respect to the relevant Licensed Product, and all non-clinical, clinical and other reports, records, data and other information developed or generated by or for the opt-out Party or any of its Affiliates in respect of such Licensed Product that are reasonably required for the other Party to continue Development and Commercialization and to satisfy requirements imposed by applicable Regulatory Authorities;

               (ii) cooperate with the other Party to effect an orderly transfer of Development and regulatory responsibilities with respect to the relevant Licensed Product as promptly as practicable, including by continuing to perform the Development activities assigned to such opt-out Party under the Joint Development Plan for [**] following the date of the opt-out, subject to the Parties’ respective obligations with respect to Development Costs pursuant to Section 4.3(b);

               (iii) to the extent assignable and at the other Party’s written request (and at no cost to the opt-out Party), assign to the other Party the opt-out Party’s rights in any or all Third Party agreements for licenses, services or supplies necessary for the Development, Manufacture or Commercialization of such Licensed Product to the extent such agreement(s) are specifically and solely related to such Licensed Product;

               (iv) to the extent that the opt-out Party is responsible for Manufacturing the Shared Product prior to opting-out, pursuant to a supply agreement to be negotiated in good faith by the Parties at the transfer price paid by the opt-out Party for the applicable Licensed Product, if the opt-out Party sources such product from a Third Party, or at [**] percent ([**]%) of the opt-out Party’s Cost of Goods (as defined in Schedule D ), if the opt-out Party or any of its Affiliates Manufactures the applicable Licensed Product, supply the other Party with commercial quantities of the applicable Licensed Product in the dosage strength, formulation and presentation under Development or being Commercialized by the opt-out Party, in either case, as of the effective date of termination of the Agreement in its entirety until the earlier of [**] after the effective date of the opt-out or establishment by the other Party of an alternative supply for such Licensed Product. Subject to Section 3.2(a)(ii), the opt-out Party shall also within [**] after the other Party’s request, provide to the other Party or its designee all information in its possession with respect to the Manufacture of such Licensed Product or intermediate. Notwithstanding the foregoing or anything to the contrary in Section 3.2(a)(ii), at the request of Alnylam, if Takeda is the opt-out Party with respect to a Shared Product that incorporates Know-How falling within the Takeda Pre-Existing Delivery Intellectual Property and for which the Parties have completed a [**] at the time of such opt-out, at Takeda’s election at the time of such opt-out, Takeda shall either (A) transfer the Manufacture of such Abandoned Product to Alnylam or a mutually agreed upon contract manufacturer organization, or (B) commit to ongoing Manufacture of such Abandoned Product as provided above in this Section 4.5(a)(iv), on an ongoing basis for the life of such Shared Product (i.e., the [**] time limit set forth above shall not apply). Notwithstanding the foregoing or anything to the contrary in Section 3.2(a)(ii), at the request of Alnylam, if Takeda is the opt-out Party with respect to a Shared Product that

incorporates Know-How falling within the Takeda Pre-Existing Delivery Intellectual Property and for which the Parties have not completed a [**] at the time of such opt-out, the Parties will negotiate an agreement pursuant to which, at Takeda’s election at the time of such opt-out, Takeda will either (I) commercially Manufacture such Abandoned Product for Alnylam at [**] percent ([**]%) of Takeda’s Cost of Goods or (II) transfer the Manufacture of such Abandoned Product to Alnylam or a mutually agreed upon contract manufacturer organization.

               (v) in the event that an NDA for such Licensed Product has already been submitted to the FDA, negotiate in good faith with the other Party whether and under what conditions the opt-out Party will transfer or grant a license to Product Trademarks associated with such Licensed Product to the other Party; and

               (vi) transfer and assign to the other Party copies of all reports, records, regulatory correspondence and other documents and/or materials in the opt-out Party’s or its Affiliates’ or sublicensees’ possession or control reasonably relating to process conditions, in-process controls, analytical methodology and formulation, in each case as developed by the opt-out Party or its Affiliates or sublicensees and relating to the Manufacture of the Licensed Product.

               (vii) Subject to Sections 4.3(b)(x) and 4.3(b)(y), the other Party shall (A) compensate the opt-out Party for the FTE Cost for the actual time spent after the exercise of the opt-out with respect to such Licensed Product by the opt-out Party personnel fulfilling its obligations under this Section 4.5 and (B) reimburse the opt-out Party for all costs and expenses incurred in fulfilling its obligations under this Section 4.5. The opt-out Party shall provide the other Party with an invoice at the end of each Calendar Quarter for the FTE Cost and out-of-pocket costs and expenses accrued with respect to the foregoing following each Calendar Quarter. The other Party shall pay such invoices in full within [**].

          (b)  Shared Product Safety Concerns . Notwithstanding the foregoing, in the event that in either Party’s reasonable judgment, a Shared Product presents safety concerns, such Party shall promptly notify the other Party of such concerns and the Parties shall meet to discuss such concerns. In the event that the Parties agree that a Shared Product presents a safety concern, the Parties shall cease Development of such Shared Product and shall share the costs associated with winding-down such Development. If, however, either Party objects to discontinuing Development of such Shared Product, and the other Party continues to have good faith safety concerns with the continuation of such trial, to the extent permitted under the Law, the Party that wishes to discontinue the clinical trial shall have the right to (i) notwithstanding the [**] requirement under Section 4.3(b), wind down such trial immediately or (ii) at the other Party’s written request, diligently transfer the conduct of such clinical trial to the other Party.

ARTICLE V

TECHNOLOGY TRANSFER AND UPDATES

           5.1 Technology Transfer.

          (a)  Technology Milestones . The Parties shall use Commercially Reasonable Efforts to complete the activities under the technology transfer plan set forth on Schedule J (as it may be amended from time to time by mutual agreement of the Parties, the “ Technology Transfer Plan ”), to effect the transfer to Takeda (or its designated Affiliate(s)) of Alnylam Intellectual Property Controlled by Alnylam or its Affiliates existing as of the Effective Date that is reasonably necessary or useful for the exercise of Takeda’s rights under the licenses granted pursuant to Section 3.1(a) in accordance with the Technology Transfer Plan (the [**] period under the Technology Transfer Plan for performance of the activities set forth therein being referred to as the “ Technology Transfer Period ”). Alnylam shall make available to Takeda such number of technical personnel as are reasonably necessary to accomplish the activities set forth in the Technology Transfer Plan, to answer any questions or provide instruction as reasonably requested by Takeda concerning the items delivered pursuant to this Section 5.1, in connection with Takeda’s Development, Commercialization and Manufacture of Licensed Products hereunder. In the event there are any conflicts or inconsistencies between this Agreement and the Technology Transfer Plan, this Agreement shall govern.

          (b)  Technology Transfer Plan . The Technology Transfer Plan is attached hereto as Schedule J . The Technology Transfer Plan: (i) specifies goals and time lines for the achievement of the technology transfer; (ii) identifies specific technology to be transferred; (iii) specifies criteria for successful achievement of the technology transfer (including, without limitation, the Technology Milestones); and (iv) sets forth those obligations assigned to each Party with respect to technology transfer. The Technology Transfer Plan may be amended from time to time through written amendments unanimously approved by both Parties’ JTTC representatives.

          (c)  Diligence Obligations .

               (i) Each Party shall use Commercially Reasonable Efforts to complete the tasks assigned to such Party under the Technology Transfer Plan in a timely manner and in accordance with the Technology Transfer Plan.

               (ii) Alnylam shall, subject to Takeda satisfying the Takeda obligations as set forth in the Technology Transfer Plan, be primarily responsible for Technology Milestones I and II and the Parties shall be jointly responsible for Technology Milestone III within the time frames set forth in the Technology Transfer Plan. Alnylam shall, to the extent reasonably practicable prior to the initiation of any technology transfer with respect to any element of technology transfer, and otherwise during the Technology Transfer Period with respect to any such elements: (i) provide to Takeda a written description of personnel and scientific qualifications, facility, and equipment requirements for achieving such technology transfer, (ii) identify any known

Third Party encumbrances or limitations on such technology transfer and (iii) identify specific technology which should be included within such technology transfer, but could not be included as a result of restrictions or limitations imposed by Third Parties.

               (iii) If an assessment by Takeda reveals an insufficiency in any technology that has already been transferred, upon Takeda’s request, Alnylam shall disclose any new and/or more detailed documents and SOPs that it may have related to any such insufficiencies, but nothing contained herein shall require Alnylam to seek or obtain technology which it does not already possess.

           5.2 Management of Transition Activities.

          (a)  Cooperation . Each Party shall designate qualified personnel having the necessary skill, expertise, and experience to facilitate such technology transfer and who shall be responsible for coordinating the technology transfer activities under the Technology Transfer Plan. Each Party shall cooperate with the other Party in such other Party’s conduct of technology transfer activities under the Technology Transfer Plan.

          (b)  Joint Technology Transfer Committee .

               (i)  Formation of Joint Technology Transfer Committee . Within [**] after the Effective Date, the Parties shall establish a Joint Technology Transfer Committee (the “ JTTC ”) that shall, until the [**] of the Effective Date, (A) oversee the activities of the Parties under the Technology Transfer Plan and (B) facilitate the transfer of technology (and information related thereto) by Alnylam to Takeda with respect to Alnylam Intellectual Property, and by Takeda to Alnylam with respect to Takeda New Delivery Intellectual Property, in each case arising during the [**] period following the Effective Date and that is licensed hereunder (“ Future Technology ”). The JTTC shall be comprised of two (2) representatives designated by Alnylam and two (2) representatives designated by Takeda, provided that the Parties shall appoint additional representatives as appropriate with respect to subject area-specific subteams. Each Party’s JTTC representatives shall be of the seniority and experience appropriate for service on the JTTC in light of the functions, responsibilities and authority of the JTTC. Takeda shall select from its representatives a chairperson for the JTTC. Each Party may replace any or all of its representatives on the JTTC with individual(s) of appropriate experience and seniority at any time upon written notice to the other Party. The JTTC chairperson shall call a meeting of the JTTC as required by this Agreement or promptly upon the written request of either Party. The JTTC shall remain in existence and shall not cease functioning until the [**] of the Effective Date.

               (ii)  JTTC Responsibilities .

                    (A) With respect to the transfer of technology under the Technology Transfer Plan, the JTTC will perform the following functions: (1) managing and overseeing the performance of the Technology Transfer Plan, (2) providing updates to the Parties regarding the Technology Transfer Plan, (3) reviewing and approving any updates, amendments or modifications to the

Technology Transfer Plan, (4) determining whether or not a specific technology area has been successfully transferred, delayed or not transferred, (5) developing and adopting remediation plan(s) specifically designed to facilitate the successful achievement of any technology area transfers that have not been successfully transferred, including amendments to the Technology Transfer Plan with respect to the achievement of the applicable timelines set forth therein with respect thereto, (6) coordinating with the JRCC or JDCC as appropriate, (7) providing an initial forum for resolving disputes arising under the Technology Transfer Plan, and (8) such other responsibilities as may be assigned to the JTTC pursuant to this Agreement or as may be mutually agreed upon by the Parties from time to time.

                    (B) With respect to the transfer of Future Technology, the JTTC shall perform the following functions: (1) exchanging information and facilitating discussions between the Parties concerning any Future Technology, (2) reviewing and approving the plan for Future Technology transfer periodically, but no less than once semi-annually, (3) coordinating and supervising the transfer of Future Technology to Takeda, (4) providing an initial forum for Future Technology transfer-related dispute resolution and (5) such other responsibilities as may be assigned to the JTTC pursuant to this Agreement or as may be mutually agreed upon by the Parties from time to time.

               (iii)  Operation of Joint Technology Transfer Committee .

                    (A) The JTTC shall meet in person or hold video conferences on a Calendar Quarter basis until the completion of the Future Technology transfer; provided , that two (2) such meetings shall occur in person and two (2) such meetings shall occur by video conference. Meetings of the JTTC in person shall alternate between the offices of Alnylam and Takeda, or such other place as the Parties may agree, with the first such meeting for the JTTC being at Takeda’s offices. The members of the JTTC also may convene or be polled or consulted from time to time by means of telecommunications, video conferences, electronic mail or correspondence, as deemed necessary or appropriate. Except as set forth in this Section 5.2(b), meetings of the JTTC shall be held in accordance with the same rules as for the other committees as set forth in Sections 2.2 to 2.6, inclusive.

                    (B) If the JTTC is unable to reach agreement on any matter referred to it for resolution by one or more of the Parties within [**] after the matter is so referred to it, such dispute shall be referred to the Executive Officers (or their designees) in accordance with Section 12.2.

                    (C) For purposes of clarity, the JTTC shall not have the authority to modify the terms of this Agreement.

           5.3 Technology to be Transferred.

          (a)  Table I of Schedule J contains a complete list of the documents and materials that Alnylam will transfer to Takeda (the “ Technology List ”).

          (b) Until the completion of technology transfer under the Technology Transfer Plan, Alnylam shall use Commercially Reasonable Efforts to transfer Alnylam Intellectual Property to Takeda in accordance with the Technology Transfer Plan.

           5.4 Additional Services. Following the termination of the Technology Transfer Period, provided that Takeda has exercised Commercially Reasonable Efforts in performing the activities assigned to it under the Technology Transfer Plan, (a) at Takeda’s option, Alnylam shall, at no cost to Takeda, continue to provide technology transfer services with respect to Alnylam Intellectual Property for [**] following the termination of the Technology Transfer Period (which services may include additional document transfer, additional training sessions, phone conferences, and email support), and (b) if Takeda desires Alnylam to provide technology transfer services beyond such additional [**] period, then Alnylam shall continue to provide technology transfer services on commercially reasonable terms to be agreed upon by the Parties, including payment to Alnylam for the number of Alnylam FTEs agreed upon by the Parties for such continued services, and the Parties will amend the Technology Transfer Plan accordingly.

ARTICLE VI

RESEARCH AND DELIVERY COLLABORATIONS

           6.1 Research Collaboration.

          (a)  Research Collaboration Plan . Within [**] months following the Effective Date, Takeda shall select, subject to Alnylam’s consent, such consent not to be unreasonably withheld, one (1) or two (2) Designated Targets with respect to which Takeda has an interest in entering into a Research Collaboration with Alnylam (each, a “ Research Collaboration Target ”). The Parties shall thereafter develop a mutually agreeable research plan within [**] after agreement on the Research Collaboration Targets, which plan shall set forth each Party’s obligations and responsibilities during the Research Collaboration Term in connection with the Research Collaboration (“ Research Collaboration Plan ”) which shall be attached as Schedule K . The activities set forth in the Research Collaboration Plan shall, [**] with respect to at least [**].

          (b)  Adoption and Amendment of Research Collaboration Plan . In accordance with Section 2.1(a), the JRCC may propose amendments to the Joint Research Collaboration Plan. The adoption of and any amendments to the Research Collaboration Plan shall require the written approval of the Parties; provided that with respect to amendments to the Joint Research Collaboration Plan, Takeda shall have the final authority in the event mutual agreement cannot be reached, except that Takeda shall not have any authority to change the Research Collaboration Targets or materially change the scope of Alnylam’s obligations under the Research Collaboration Plan without

Alnylam’s written consent, which consent shall not be unreasonably withheld, conditioned or delayed.

          (c)  Research Collaboration FTEs . During the Research Collaboration Term, subject to Section 6.1(b), the Parties shall prepare annual updates to the Research Collaboration Plan setting forth the number of FTEs each Party will commit to the Research Collaboration during the next Fiscal Year. During the Research Collaboration Term, Alnylam shall provide such number of FTEs as specified in the Research Collaboration Plan to perform the activities allocated to Alnylam under the Research Collaboration Plan. Takeda may, at any time during the Research Collaboration Term, request that the Parties amend the Research Collaboration Plan to reduce or increase on a [**] basis the number of Alnylam’s FTEs, and the Research Collaboration Plan shall be amended to account for the reallocation of Research Collaboration activities; provided that (i) Takeda may not reduce the number of FTEs for a [**] to a level below the Minimum FTE Commitment; and (ii) Takeda may not change the number of Alnylam FTEs [**] during any [**]. Takeda shall reimburse Alnylam for all FTE Costs incurred by Alnylam in accordance with Section 7.14.

           6.2 Delivery Collaboration.

          (a)  Delivery Collaboration Option . Takeda shall have the option, which may be exercised at any time during the [**] after the Effective Date, to collaborate with Alnylam on the research and development of RNAi drug Delivery Technology on the Target(s) and/or RNAi Product(s) selected by Takeda, subject to Alnylam’s consent in accordance with Section 6.2(b). In the event that Takeda elects to exercise its option for the Delivery Collaboration, Takeda shall notify Alnylam in writing of such decision.

          (b)  Delivery Collaboration Plan . If Takeda exercises its option pursuant to Section 6.2(a), Takeda will discuss with Alnylam in good faith to prepare and adopt a research plan within [**] of the date of Takeda’s notice. Such research plan shall identify the focus of the collaboration, the Delivery Technology being Developed and each Party’s obligations and responsibilities in connection with the Delivery Collaboration during the Delivery Collaboration Term (“ Delivery Collaboration Plan ”), and shall be subject to Alnylam’s consent, such consent not to be unreasonably withheld. Takeda shall select, subject to Alnylam’s consent, such consent not to be unreasonably withheld, the Designated Targets that will be the subject of such Delivery Collaboration (each, a “ Delivery Collaboration Target ”), and such Delivery Collaboration Targets shall be reflected in such Delivery Collaboration Plan.

          (c)  Adoption and Amendments to Delivery Collaboration Plan . In accordance with Section 2.1(b)(ii), the JDCC may propose amendments to the Joint Delivery Collaboration Plan. The adoption of and any amendments to the Joint Delivery Collaboration Plan shall require the written approval of the Parties; provided that with respect to any amendments to the Delivery Collaboration Plan, Takeda shall have the final authority in the event mutual agreement cannot be reached, except that Takeda shall not have any authority to change the Delivery Collaboration Target(s) or the Delivery Technology Developed under the Delivery Collaboration, or materially change the scope

of Alnylam’s obligations under the Delivery Collaboration Plan without Alnylam’s written consent, which consent shall not be unreasonably withheld, conditioned or delayed.

          (d)  Delivery Collaboration FTEs . During the Delivery Collaboration Term, subject to Section 6.2(c), the Parties shall prepare annual updates to the Delivery Collaboration Plan setting forth the number of FTEs each Party will commit to the Delivery Collaboration during the next Fiscal Year. Alnylam shall provide such number of FTEs as specified in the Delivery Collaboration Plan to perform the activities allocated to Alnylam under the Delivery Collaboration Plan. Takeda may, at any time during the Delivery Collaboration Term, request that the Parties amend the Delivery Collaboration Plan to reduce or increase on a [**] basis the number of Alnylam FTEs, and the Delivery Collaboration Plan shall be amended to account for the reallocation of Delivery Collaboration activities, provided that Takeda may not change the number of Alnylam FTEs [**] during any [**]. Takeda shall [**] Alnylam for [**] incurred by Alnylam in accordance with Section 7.14.

           6.3 Intellectual Property Developed Under Research Collaboration and Delivery Collaboration.

          (a)  Ownership of Intellectual Property . Subject to Section 6.3(b), all Joint Research Collaboration Intellectual Property and Joint Delivery Collaboration Intellectual Property shall be owned jointly by the Parties. All Know-How and Patent Rights that are conceived, discovered, developed or otherwise made or created solely by employees, agents and consultants of Takeda during the Research Collaboration Term or the Delivery Collaboration Term shall be solely owned by Takeda. All Know-How and Patent Rights that are conceived, discovered, developed or otherwise made or created solely by employees, agents and consultants of Alnylam during the Research Collaboration Term or the Delivery Collaboration Term shall be solely owned by Alnylam.

          (b)  Takeda Collaboration Target Specific Intellectual Property . Notwithstanding anything to the contrary contained in this Agreement, all Takeda Collaboration Target Specific Intellectual Property shall be assigned to Takeda and thus become solely owned by Takeda. In furtherance of the foregoing, Alnylam hereby assigns to Takeda all of its rights and interest in the foregoing Takeda Collaboration Target Specific Intellectual Property and shall execute and have its employees, agents and consultants execute all assignments and other documents as Takeda may reasonably request in order to confer upon Takeda ownership in and to Patent Rights within the Takeda Collaboration Target Specific Intellectual Property. Notwithstanding the foregoing, Alnylam shall not have any obligation pursuant to this Section 6.3(b) to assign, in whole or in part, (i) any patent or patent application containing claim(s) that are not specifically and solely related to a Collaboration Target; provided that , during the Research Collaboration Term and the Delivery Collaboration Term, Alnylam shall use Commercially Reasonable Efforts to consult with Takeda regarding the prosecution of patent applications that contain any claim that is specifically and solely related to a Collaboration Target and, if consistent with a reasonable patent prosecution strategy, to pursue the prosecution of such patent applications in a manner that results in issued

patents that are assignable to Takeda pursuant to this Section 6.3(b); or (ii) any Takeda Collaboration Target Specific Intellectual Property described in clause (ii) of the definition of Takeda Collaboration Target Specific Intellectual Property that Alnylam does not solely own and Control.

          (c)  Ownership of Pre-Existing Intellectual Property . Any Know-How and Patent Rights developed by Takeda or Alnylam prior to the Effective Date or outside the Research Collaboration or Delivery Collaboration shall remain the sole property of such Party.

ARTICLE VII

FINANCIAL PROVISIONS

           7.1 License Grant Consideration. In consideration of the rights granted to Takeda and the transfer of technology to Takeda under this Agreement, and in accordance with the allocation set forth in Schedule L , Takeda shall pay, or cause to be paid, to Alnylam, in connection with the following events, One Hundred Fifty Million United States dollars ($150,000,000), conditioned, as applicable, on reaching the specified events, set forth below: