EX-10.1 2 alny2023q310-qex101.htm EX-10.1 Document
Exhibit 10.1

CERTAIN CONFIDENTIAL INFORMATION CONTAINED IN THIS DOCUMENT, MARKED BY [****], HAS BEEN OMITTED BECAUSE IT IS BOTH (I) NOT MATERIAL AND (II) THE TYPE THAT THE REGISTRANT TREATS AS PRIVATE OR CONFIDENTIAL.


COLLABORATION AND LICENSE AGREEMENT
by and between
ALNYLAM PHARMACEUTICALS, INC.
on the one hand
and
F. Hoffmann-La Roche Ltd.
and
Genentech, Inc.
on the other hand.

EFFECTIVE DATE: July 21, 2023





TABLE OF CONTENTS



    
ii


    
iii



Schedules and Exhibits

Schedule 1.72
Co-Commercialization Costs Cap
Schedule 1.114
Development Costs Cap
Schedule 1.134
Exclusivity Period
Schedule 1.175
KARDIA-6 Preliminary Key Elements and Considerations
Schedule 1.190
KARDIA-3 Study Design Overview
Schedule 1.254
Primary Indication Target Product Profile
Schedule 1.351
Zilebesiran
Schedule 3.7(b)Development Data
Schedule 4.2(c)(i)Major Regulatory Communications
Schedule 6.2Technology Transfer Documentation
Schedule 6.3(b)Preliminary Manufacturing Budget
Schedule 6.13Approved Roche CMOs
Schedule 8.2(a)Financial Appendix
Exhibit AInitial Development Plan
Exhibit BCo-Promotion Term Sheet
Exhibit C[Intentionally deleted]
Exhibit DCommercial Supply Term Sheet
    
iv


Exhibit EAlnylam Patents
Exhibit FPress Release

    
v


COLLABORATION AND LICENSE AGREEMENT
This COLLABORATION AND LICENSE AGREEMENT (this “Agreement”) is entered into as of July 21, 2023 (the “Effective Date”) by and between ALNYLAM PHARMACEUTICALS, INC., a Delaware corporation having its principal place of business at 675 West Kendall Street, Cambridge, Massachusetts 02142 USA (“Alnylam”), on the one hand, and F. HOFFMANN-LA ROCHE LTD., having an office and place of business at Grenzacherstrasse 124, 4070 Basel, Switzerland (“Roche Basel”) and GENENTECH, INC., with an office and place of business at 1 DNA Way, South San Francisco, California 94080, (“Genentech”; each of Roche Basel and Genentech individually and collectively, “Roche”), on the other hand. Alnylam and Roche are sometimes referred to herein individually as a “Party” and collectively as the “Parties.”
RECITALS
WHEREAS, Roche is a fully integrated pharmaceutical company with expertise in the development, manufacture and commercialization of human therapeutic products;
WHEREAS, Alnylam is a biotechnology company with expertise and experience in the development of product candidates for multiple indications, including cardiovascular indications;
WHEREAS, Alnylam is developing Zilebesiran (as defined below), an investigational, subcutaneously administered siRNA therapeutic targeting liver-expressed angiotensinogen (“AGT”), which is in Phase 2 Clinical Trials for the treatment of hypertension; and
WHEREAS, Roche and Alnylam desire to establish a broad, worldwide, strategic collaboration for the joint continued development and, if successful, regulatory approval for, and commercialization of, Zilebesiran in hypertension and additional indications.
NOW THEREFORE, in consideration of the foregoing premises and the mutual promises, covenants and conditions contained in this Agreement, the Parties agree as follows:
ARTICLE 1

DEFINITIONS
1.1General. Capitalized terms used in this Agreement, whether used in the singular or plural, shall have the meanings ascribed to such terms in this Agreement, including as specified in this Article 1.
1.2Accounting Standards” has the meaning set forth in the Financial Appendix.
1.3Account Management Activities” has the meaning set forth in Section 5.10.
1.4Acquired Party” has the meaning set forth in Section 7.8(a)(i).



1.5Acquiring Party” has the meaning set forth in Section 7.8(a)(ii).
1.6Acquiror” has the meaning set forth in Section 7.8(a)(i).
1.7Additional Indication” has the meaning set forth in Section 3.5(b)(i).
1.8Additional Program Plan” has the meaning set forth in Section 3.5(b)(i).
1.9Additional Study” has the meaning set forth in Section 3.5(b)(i).
1.10Administration Device” has the meaning set forth in Section 3.5(c)(i).
1.11Affiliate” means, with respect to a particular Person, another Person that directly or indirectly controls, is controlled by, or is under common control with such Person. For the purposes of this definition, the word “control” (including, with correlative meaning, the terms “controlled by” or “under the common control with”) means the possession, either directly or indirectly through one or more intermediaries, of (a) power to control or cause the control of the management or policies of such entity (whether through ownership of securities or other ownership interests, by contract or otherwise), or (b) beneficial ownership of at least fifty percent (50%) of the voting securities or other ownership interest (whether directly or pursuant to any option, warrant or other similar arrangement) or other comparable equity interests of an entity. Notwithstanding the foregoing, neither the following entities nor their respective subsidiaries shall be Affiliates of Roche hereunder, unless and until Roche provides written notice to Alnylam stating that one or more of such entities or their respective subsidiaries are Affiliates of Roche hereunder: (i) Chugai, or its subsidiaries, [****] the “Roche Excluded Affiliates”).
1.12Affiliate Sublicense Agreement” has the meaning set forth in Section 7.3(c)(i).
1.13Agreement” has the meaning set forth in the preamble.
1.14AGT” has the meaning set forth in the Recitals.
1.15AGT EMO” means [****].
1.16AGT EMO Acquisition” has the meaning set forth in Section 7.8(a)(ii).
1.17AGT EMO Program” has the meaning set forth in Section 7.8(a)(i).
1.18Alliance Manager” has the meaning set forth in Section 2.6.
1.19Allowable Commercialization Expenses” has the meaning set forth in the Financial Appendix.
1.20Alnylam” has the meaning set forth in the preamble.
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1.21Alnylam Background Know-How” means any and all Know-How to the extent Controlled by Alnylam or any of its Affiliates as of the Effective Date or during the Term, which Know-How has been used prior to the Effective Date in, or is otherwise necessary or reasonably useful for, the Development, Manufacture or Commercialization of any Products for use in the Field in the Territory in accordance with the terms of this Agreement, other than Alnylam Collaboration Know-How and Alnylam’s interest in Joint Know-How. For clarity, “Alnylam Background Know-How” (a) includes Alnylam Core Know-How and Alnylam Product-Specific Know-How and (b) excludes any and all Patent Rights and Alnylam Excluded IP.
1.22Alnylam Background Patents” means any and all Patents Rights to the extent Controlled by Alnylam or any of its Affiliates as of the Effective Date or during the Term that Cover Alnylam Background Know-How. For clarity, the “Alnylam Background Patents” (a) includes Alnylam Core Patents and Alnylam Product-Specific Patents and (b) excludes Alnylam Excluded IP.
1.23Alnylam Collaboration Know-How” means any and all Know-How to the extent Controlled by Alnylam or any of its Affiliates after the Effective Date and during the Term that (a) is necessary or reasonably useful for the Development, Manufacture or Commercialization of Products for use in the Field in the Territory in accordance with the terms of this Agreement and (b) is conceived or reduced to practice (in whole or in part) or otherwise identified, developed, made, or discovered solely by or on behalf of (including by subcontractors) Alnylam or any of its Related Parties in its conduct of the Collaboration activities under this Agreement. For clarity, “Alnylam Collaboration Know-How” (i) may include Alnylam Core Know-How and Alnylam Product-Specific Know-How and (ii) excludes any and all Patent Rights and Alnylam Excluded IP.
1.24Alnylam Collaboration Patents” means any and all Patents Rights to the extent Controlled by Alnylam or any of its Affiliates during the Term that Cover any Alnylam Collaboration Know-How. For clarity, “Alnylam Collaboration Patents” (a) excludes Alnylam’s interest in Joint Patents and Alnylam Excluded IP and (b) may include Alnylam Core Patents and Alnylam Product-Specific Patents.
1.25Alnylam Core Improvements” has the meaning set forth in Section 1.182.
1.26Alnylam Core Know-How” means any and all Alnylam Know-How other than (a) Alnylam Product-Specific Know-How, (b) Alnylam’s interest in Joint Know-How and (c) Alnylam Excluded IP.
1.27Alnylam Core Patents” means any and all Alnylam Patents other than Alnylam Product-Specific Patents, excluding any (a) Alnylam Excluded IP and (b) Alnylam’s interest in Joint Patents.
1.28Alnylam Excluded IP” means any and all [****] and (c) Know-How and Patent Rights specifically related to any active pharmaceutical ingredient, but not Zilebesiran or REVERSIR.
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1.29Alnylam Indemnitee” has the meaning set forth in Section 11.2.
1.30Alnylam Know-How” means any and all Alnylam Background Know-How, Alnylam Collaboration Know-How and Alnylam’s interest in Joint Know-How.
1.31Alnylam Lead Study” has the meaning set forth in Section 3.6(a).
1.32Alnylam Licensed IP” means the Alnylam Know-How and Alnylam Patents, in each case, excluding any Alnylam Excluded IP.
1.33Alnylam Manufacturing Change” has the meaning set forth in Section 6.10(c)(i).
1.34Alnylam-Originated Transfer Activities” has the meaning set forth in Section 13.8(e)(iii).
1.35Alnylam Patents” means any and all Alnylam Background Patents, Alnylam Collaboration Patents and Alnylam’s interest in Joint Patents. For clarity, Alnylam Patents include the Patent Rights disclosed in Exhibit E.
1.36Alnylam Product-Specific Know-How” means, on a Product-by-Product basis, [****].
1.37Alnylam Product-Specific Patents” means any and all Patent Rights to the extent Controlled by Alnylam or any of its Affiliates as of the Effective Date or during the Term that Cover Alnylam Product-Specific Know-How.
1.38Anti-Corruption Laws” means any and all anti-bribery and anti-corruption Applicable Laws, including the U.S. Foreign Corruption Practices Act of 1977, the U.S. Travel Act, the U.K. Bribery Act 2010, and Applicable Laws implementing the OECD Convention on Combating Bribery of Foreign Public Officials in International Business Transactions.
1.39APAC” means, collectively, [****].
1.40API” means active pharmaceutical ingredient.
1.41Applicable Data Protection Laws” has the meaning set forth in Section 15.16.
1.42Applicable Laws” means, individually and collectively, all laws, statutes, ordinances, codes, regulations, rules, orders, writs, judgments, injunctions, decrees, stipulations or rulings of any kind of any Governmental Authority that may be in effect from time to time and applicable to the activities contemplated by this Agreement.
1.43[****].
1.44Assigning Party” has the meaning set forth in Section 9.2(d).
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1.45Auditor” has the meaning set forth in Section 8.12(a).
1.46Bankruptcy Code” has the meaning set forth in Section 13.12.
1.47[****].
1.48[****].
1.49[****].
1.50Breaching Party” has the meaning set forth in Section 13.5(a).
1.51Bridging Study” means any Non-Clinical Study or human clinical trial conducted in the Roche Territory for the purpose of providing country or region-specific Development Data on safety, efficacy, dosage, or dosing regimen to permit the extrapolation of other Development Data to a population in the Roche Territory or in relation to Regulatory Approvals of a Product in such country, or any other Non-Clinical Study or Clinical Trial designed to demonstrate equivalency by extrapolating results from a different study.
1.52Business Day” means a day other than a Saturday, Sunday, or a bank or other public or federal holiday in Boston, Massachusetts; San Francisco, California; or Basel, Switzerland.
1.53Calculated Amounts” has the meaning given such term in Section 8.12(a).
1.54Calendar Quarter” means for each Calendar Year, each of the three (3)-month periods ending March 31, June 30, September 30 and December 31; provided that (a) the first Calendar Quarter of the Term shall begin on the Effective Date and end on the first to occur of March 31, June 30, September 30 or December 31 thereafter and the last Calendar Quarter of the Term shall end on the last day of the Term, and (b) the first Calendar Quarter of a Royalty Term for a Product in a country shall begin on the First Commercial Sale of such Product in such country and end on the first to occur of March 31, June 30, September 30 or December 31 thereafter.
1.55Calendar Quarter Report” has the meaning set forth in Section 8.7(d).
1.56Calendar Year” means each successive period of twelve (12) months commencing on January 1 and ending on December 31; provided that (a) the first Calendar Year of the Term shall begin on the Effective Date and end on the first December 31 thereafter and the last Calendar Year of the Term shall end on the last day of the Term, and (b) the first Calendar Year of a Royalty Term for a Product in a country shall begin on the First Commercial Sale of such Product in such country and end on the first December 31 thereafter.
1.57Certification Notice” has the meaning set forth in Section 9.8.
1.58Certification Notice Party” has the meaning set forth in Section 9.8.
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1.59Change of Control” means, with respect to a Party (or its ultimate parent), (a) a merger, acquisition, consolidation or reorganization of such Party (or its ultimate parent) with a Third Party that results in the voting securities of such Party (or its ultimate parent) outstanding immediately prior thereto, or any securities into which such voting securities have been converted or exchanged, ceasing to represent more than fifty percent (50%) of the combined voting power of the outstanding securities of the surviving entity or the parent of the surviving entity immediately after such transaction, or (b) a transaction or series of related transactions in which a Third Party or group, together with their respective Affiliates, becomes the “beneficial owner” (as such term is used in Section 13(d) of the Securities Exchange Act of 1934 and Rule 13d-3 thereunder, except that a Person shall be deemed to have “beneficial ownership” of all shares that any such Person or its Affiliates has the right to acquire, whether such right may be exercised immediately or only after the passage of time), directly or indirectly, of more than fifty percent (50%) of the combined voting power of the outstanding securities of such Party (or its ultimate parent), or (c) the sale or other transfer to a Third Party or group, whether directly or indirectly by a Party or an Affiliate thereof, of all or substantially all of such Party’s (or its ultimate parent’s) business to which the subject matter of this Agreement relates.
1.60Chugai” means Chugai Pharmaceutical Co. Ltd., a Japanese corporation having an address at 1-1 Nihonbashi-Muromachi 2-chome, Chuo-ku Tokyo, 103-8324, Japan.
1.61[****].
1.62Chugai Sublicense Agreement” has the meaning set forth in Section 7.3(b)(ii).
1.63Clinical Supply Agreement” has the meaning set forth in Section 6.7(b).
1.64Clinical Supply Costs” has the meaning set forth in the Financial Appendix.
1.65Clinical Trial” means any Phase 1 Clinical Trial, Phase 2 Clinical Trial, Phase 3 Clinical Trial, Bridging Study that is not a Non-Clinical Study, or Phase 4 Clinical Trial.
1.66CMC” means chemistry, manufacturing, and controls.
1.67CMC Manufacturing Development” means the activities to enable development of the design of the Manufacturing process for the supply of clinical and commercial quantities of a pharmaceutical product or device, which includes, as applicable, Manufacturing process development and Manufacturing process scale-up (but excluding manufacturing facilities scale-up), test method development and stability testing, bulk production and fill/finish work associated with the supply of such pharmaceutical product (including for Non-Clinical Studies, Clinical Trials and commercial sale) and related quality assurance technical support activities as well as validation and qualification of commercial Manufacturing processes.
1.68CMO” means a Third Party contract manufacturing organization contracted by a Party or any of its Affiliates to Manufacture Product to fulfill certain of such Party’s Manufacturing obligations under this Agreement.
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1.69[****].
1.70Co-Commercialization Budget” has the meaning set forth in Section 5.4.
1.71Co-Commercialization Costs” has the meaning set forth in the Financial Appendix.
1.72[****].
1.73[****].
1.74Co-Commercialization Opt-Out Notice” has the meaning set forth in Section 13.9(a).
1.75Co-Commercialization Plan” has the meaning set forth in Section 5.3.
1.76Co-Commercialization Term” means, with respect to the Co-Commercialization Territory, the period commencing on the start of the Launch Preparation Period and continuing until a Co-Commercialization Termination Date determined in accordance with Section 13.9.
1.77Co-Commercialization Termination Date” has the meaning set forth in Section 13.9(a).
1.78Co-Commercialization Territory” means the U.S.
1.79Co-Promotion” or “Co-Promote” means, on a Product-by-Product basis, the detailing, marketing and promotional activities (including performing sales calls) for such Product for use in the Field performed by personnel of one or both Parties in the Co-Commercialization Territory in accordance with the Co-Promotion Agreement, Co-Promotion Plan and Co-Commercialization Plan.
1.80Co-Promotion Agreement” has the meaning set forth in Section 5.10.
1.81Co-Promotion Plan” has the meaning set forth in Section 5.10.
1.82Co-Promotion Term Sheet” has the meaning set forth in Section 5.10.
1.83Code” means the U.S. Internal Revenue Code of 1986.
1.84Collaboration” means the Development, Manufacturing, and Commercialization activities undertaken by the Parties under this Agreement.
1.85Combination Product” means a product that includes Zilebesiran or REVERSIR (for clarity, or both) as an active pharmaceutical ingredient combined with or comprised of (whether co-formulated, co-packaged or packaged separately but sold together for a single price) one (1) or more other active pharmaceutical ingredient(s) or pharmaceutical product(s).
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1.86Commercial Medical Affairs Activities” means Medical Affairs Activities for the Commercialization of a Product in the Field, including the coordination of medical information requests and field-based medical science liaisons, and activities of medical science liaisons, (a) with respect to the Co-Commercialization Territory, following the start of the Launch Preparation Period, and (b) with respect to the Roche Territory, following the First Commercial Sale of such Product in the Roche Territory.
1.87Commercial Supply Agreement” has the meaning set forth in Section 6.9(b).
1.88Commercial Supply Costs” has the meaning set forth in the Financial Appendix.
1.89Commercial Supply Term Sheet” has the meaning set forth in Section 6.9(b)
1.90Commercialization” means, with respect to a pharmaceutical product, the conduct of all activities relating to the promotion, sales, marketing and distribution (including importing, exporting, transporting, customs clearance, warehousing, invoicing, handling, and delivering products to customers) of such product, including sales force efforts, detailing, advertising, marketing, sales force training, market research and market access (including price setting and reimbursement activities); provided that, with respect to a Product, Commercialization shall refer to such activities (x) with respect to the Co-Commercialization Territory, following the start of the Launch Preparation Period for such Product and (y) with respect to the Roche Territory, following the First Commercial Sale of such Product for use in the Field in the Roche Territory, including Commercial Medical Affairs Activities. “Commercialize” has a correlative meaning.
1.91Commercialization Records” has the meaning set forth in Section 5.15.
1.92Commercialization Report” has the meaning set forth in Section 5.15.
1.93Commercially Reasonable Efforts” means with respect to the obligations of a Party under this Agreement that relate to the Development, Manufacture or Commercialization of a Product, the carrying out of such obligations [****] products of similar market potential at a similar stage in development or product life, taking into account, to the extent reasonable and relevant and measured by the facts and circumstances at the time such efforts are due, all relevant factors, including issues of safety and efficacy, product labeling or anticipated labeling, competitiveness of the applicable Product and other competitive products in the marketplace or under development, the patent or other proprietary position of the applicable Product, the regulatory structure involved and the potential profitability of the applicable Product marketed or to be marketed, [****].
1.94Committee” means the Joint Steering Committee, any Operating Committee, or the JPT, as applicable.
1.95Compulsory Sublicense” has the meaning set forth in Section 1.96.
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1.96Compulsory Sublicense Compensation” means for a given country or region in the Territory, [****] through the order, decree or grant of a Governmental Authority having competent jurisdiction in such country or region, authorizing such Third Party to manufacture, use, sell, offer for sale, import or export a Product in the Field in such country or region.
1.97Compulsory Sublicensee” has the meaning set forth in Section 1.96.
1.98Confidential Information” has the meaning set forth in Section 12.1.
1.99Confirmatory Clinical Trial” means a clinical trial, irrespective of phase, of a drug product in human subjects required to be conducted as part of a contingent Regulatory Approval of such drug product.
1.100Continuation Election Notice” has the meaning set forth in Section 13.8(c).
1.101Continuing Party” has the meaning set forth in Section 13.9(a).
1.102Control” means, with respect to any intellectual property right that a Party, directly or through an Affiliate, (a) owns such intellectual property right, or (b) has a license or right to use such intellectual property right (but without taking into account any rights granted by one Party to the other Party pursuant to this Agreement), in each case with the ability to grant to the other Party access, a right to use, a license, or a sublicense (as applicable) to such intellectual property right on the terms and conditions set forth herein, without violating the terms of any agreement or other arrangement with any Third Party or any Applicable Laws.
1.103Core Disease Awareness Materials” has the meaning set forth in Section 5.11(a)(i).
1.104Core Promotional Materials” means core visual aids for healthcare providers, patient brochures, value proposition for payors, and direct-to-consumer healthcare provider and patient campaigns for Non-Personal Digital Promotions, in each case, with respect to Products.
1.105Cover” means (a) as to any product and Patent Right, that, in the absence of a license granted under, or ownership of, such Patent Right, the Development, Manufacture, Commercialization or other exploitation of such pharmaceutical product would infringe a Valid Claim of such Patent Right (or, in the case of any pending claim included in such Patent Right, would infringe such Patent Right if such pending claim were to issue in an issued patent without modification), (b) as to Know-How and a Patent Right, that, in the absence of a license granted under, or ownership of, such Patent Right, the use or practice of such Know-How would infringe a Valid Claim of such Patent Right (or, in the case of any pending claim included in such Patent Right, would infringe such Patent Right if such pending claim were to issue in an issued patent without modification), and (c) as to a pharmaceutical product or technology and Know-How, that the exploitation of such pharmaceutical product or technology incorporates, uses, employs, embodies, or practices such Know-How. The determination of whether any of the foregoing, as applicable, are Covered by a particular Valid Claim shall be made on a country-by-country basis.
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1.106Covered Indications” means all Indications, provided that [****]. For clarity, the Hypertension Indication and subsets of the Hypertension Indication (e.g., primary hypertension or secondary hypertension) shall remain Covered Indications at all times during the Term.
1.107Damages” has the meaning set forth in Section 11.1.
1.108Data Subjects” has the meaning set forth in Section 15.16.
1.109Derivative Disease Awareness Materials” has the meaning set forth in Section 5.11(a)(i).
1.110Derivative Promotional Materials” has the meaning set forth in Section 5.11(a)(i).
1.111Development” means, with respect to a pharmaceutical product or device, as applicable, all activities related to the discovery, research, preclinical development, clinical development, and Regulatory Activities with respect to such product or device, toxicology, design, compatibility testing, animal efficacy studies, formulation, quality assurance/quality control development and support activities, statistical analysis and report writing, Clinical Trials, and Development Medical Affairs Activities, preparing and submitting Regulatory Materials (including applications for Regulatory Approval), together with Regulatory Activities with respect thereto, whether before or after Regulatory Approval for such product has been obtained; provided that “Development” shall exclude Commercialization (including, for the avoidance of doubt, the conduct of Post-Approval Studies) and Manufacture (including, for the avoidance of doubt, the conduct of CMC Manufacturing Development). “Develop” has a correlative meaning.
1.112Development Budget” has the meaning set forth in Section 3.3.
1.113Development Costs” has the meaning set forth in the Financial Appendix.
1.114[****].
1.115[****].
1.116Development Data” means any and all scientific, technical, test, or other data related to any Product that is generated by or on behalf of either Party or any of its Related Parties (or subcontractors acting on their behalf), under the Development Plan, including research data, clinical pharmacology data, CMC data (including analytical and quality control data and stability data), preclinical data, clinical data, clinical study reports, and all data used in connection with submissions and approvals of an IND or NDA in the Territory.
1.117Development Lead Option” has the meaning set forth in Section 3.6(b)(ii).
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1.118Development Medical Affairs Activities” means Medical Affairs Activities for a Product conducted to support the Development of such Product in the Field in the Territory (for clarity, excluding Commercialization and Manufacturing activities for such Product), (a) with respect to the Co-Commercialization Territory prior to the start of the Launch Preparation Period, and (b) with respect to the Roche Territory prior to the First Commercial Sale of such Product in the Roche Territory.
1.119Development Milestone” has the meaning set forth in Section 8.5(a).
1.120Development Milestone Payment” has the meaning set forth in Section 8.5(a).
1.121Development Plan” has the meaning set forth in Section 3.1.
1.122Development Records” has the meaning set forth in Section 3.9.
1.123Development Report” has the meaning set forth in Section 3.9.
1.124Device Program Plan” has the meaning set forth in Section 3.5(c)(i).
1.125Direct Costs” has the meaning set forth in the Financial Appendix.
1.126Directed to” means, with respect to siRNA and a target, that such siRNA binds to and interferes with the function of any messenger RNA encoded by such target. For clarity, in the event a siRNA has been engineered to bind to and interfere with the function of any messenger RNA encoded by a particular target other than AGT (and has not be engineered to bind to and interfere with the function of any messenger RNA encoded by AGT) but such siRNA additionally binds to or interferes with the function of the messenger RNA encoded by AGT, either directly or indirectly, then such product will not be deemed to be Directed to AGT.
1.127Discloser” has the meaning set forth in Section 12.1.
1.128Disease Awareness Materials” means any and all disease awareness and disease education materials to be used by a Party, its Related Parties or its subcontractors acting on their behalf in connection with Commercial Medical Affairs Activities for Products for use in the Field.
1.129Disputed Matter” has the meaning set forth in Section 14.1.
1.130Divestment Period” has the meaning set forth in Section 7.8(c)(i).
1.131e-Signature” has the meaning set forth in Section 15.17.
1.132Effective Date” has the meaning set forth in the preamble.
1.133Europe” means, collectively, [****].
1.134Exclusivity Period” has the meaning set forth in [****].
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1.135Executive Officer” means (a) in the case of Roche, the Chief Executive Officer of the Roche Pharmaceuticals Division for Development, Manufacturing, Regulatory and Commercialization related issues, and for all other issues the Head of Pharma Partnering for the Roche Pharmaceuticals Division, or, in each case his or her designee; and (b) in the case of Alnylam, its Chief Executive Officer or his or her designee.
1.136Existing Confidentiality Agreement” means that certain Mutual Confidential Disclosure Agreement, by and between Roche Ltd. and Alnylam, dated as of [****], as amended by that certain Amendment No. 1 to Mutual Confidential Disclosure Agreement, dated as of Effective Date.
1.137Existing Process Technology Transfer” has the meaning set forth in Section 6.8(a).
1.138Existing Process Technology Transfer Plan” has the meaning set forth in Section 6.8(a).
1.139Expanded Access Program” means the use of investigational new drug products outside of Clinical Trials to treat patients with serious or immediately life-threatening disease or conditions when there are no comparable or satisfactory alternative treatment options, as described in 21 CFR Section 312.305 or comparable Applicable Laws in jurisdictions outside the U.S. “Expanded Access Program” includes so-called “treatment IND sales,” “named patient sales,” and “compassionate use sales.”
1.140Expiration Condition” has the meaning set forth in Section 13.9(a).
1.141[****].
1.142FD&C Act” means the U.S. Federal Food, Drug and Cosmetic Act.
1.143FDA” means the U.S. Food and Drug Administration or its successor.
1.144Field” means all uses; provided that “Field” shall exclude [****].
1.145Financial Appendix” has the meaning set forth in Section 8.2(a).
1.146First Commercial Sale” means, on a country-by-country basis, the first commercial sale of a Product in a country by or on behalf of Roche or any of its Related Parties (or subcontractors acting on their behalf) to a Third Party (other than a Related Party of Roche) or Governmental Authority following Regulatory Approval of such Product in such country. If no such Regulatory Approval or similar marketing approval is required in a country for marketing and sale of a Product, First Commercial Sale means the date upon which such Product is first commercially sold in such country to end users. Sales or transfers of reasonable quantities of a Product for research or Development, including proof of concept studies or other Clinical Trial purposes, or for compassionate or similar use, shall not be considered a First Commercial Sale; provided that [****].
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1.147First Patient In” or “FPI” means, with respect to a Clinical Trial of Product, the date that the first subject is dosed in such Clinical Trial.
1.148Flash Sales Report” has the meaning set forth in Section 8.7(d)(i).
1.149force majeure” has the meaning set forth in Section 15.2.
1.150GCPs” means the then-current standards, practices and procedures promulgated or endorsed by FDA for the design, conduct, performance, monitoring, auditing, recording, analyses, and reporting of clinical trials as set forth in the guidelines titled “Guidance for Industry E6 Good Clinical Practice: Consolidated Guidance,” (which also titled by FDA as “E6(R2) Good Clinical Practice: Integrated Addendum to ICH E6(R1)”), including related regulatory requirements imposed by FDA, including 21 CFR Parts 50, 54, and 56, as well as comparable Applicable Laws in jurisdictions outside the U.S. that provide assurance that the data and reported results are credible and accurate, and that the rights, integrity, and confidentiality of trial subjects are protected.
1.151Genentech” has the meaning set forth in the preamble.
1.152Generic Product” means, with respect to a particular Product, any pharmaceutical product that (a) contains (i) if such Product is a Therapeutic Product, Zilebesiran, or (ii) if such Product is a REVERSIR Product, REVERSIR, in each case as an active pharmaceutical ingredient, (b) is not distributed or sold by, with respect to the Co-Commercialization Territory, either Party or any of its Related Parties (or subcontractors acting on their behalf), or with respect to the Roche Territory, Roche or any of its Related Parties (or subcontractors acting on their behalf) and (c) is distributed or sold under a separate Regulatory Approval application approved by a Regulatory Authority in reliance, in whole or in part, on a Party’s or any of its Related Party’s (or a subcontractor’s acting on their behalf) Regulatory Approval application for the applicable Product in such country (or on safety or efficacy data submitted by any such Person in support of the Regulatory Approval application for the applicable Product in such country), including any product authorized for sale (i) in the U.S. pursuant to Section 505(b)(2) or Section 505(j) of the FFDCA (21 U.S.C. § 355(b)(2) and 21 U.S.C. § 355(j), respectively), (ii) in the European Union pursuant to a provision of Articles 10, 10a or 10b of Parliament and Council Directive 2001/83/EC (including an application under Article 6.1 of Parliament and Council Regulation (EC) No. 726/2004 that relies for its content on any such provision) or (iii) in any other country or jurisdiction pursuant to comparable Applicable Laws or if no such comparable Applicable Laws exist in such country or jurisdiction, is approved by an expedited process that relies in whole or in part on safety and efficacy data generated for the first Regulatory Approval of the Product.
1.153Generic Product Entry” means, in a given country in the Territory, if one or more Generic Products with respect to a given Product is sold in any Calendar Quarter.
1.154Global Brand Strategy” has the meaning set forth in Section 5.2.
1.155GLPs” means the then-current good laboratory practice standards promulgated or endorsed by FDA as defined in 21 C.F.R. Part 58, and comparable Applicable Laws in jurisdictions outside the U.S.
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1.156GMPs” means the then-current good manufacturing practices required by FDA under section 501(a) of the FD&C Act or other applicable statutes, including 21 C.F.R. Parts 210 and 211 and other Applicable Laws promulgated thereunder, for the manufacture and testing of pharmaceutical materials, and comparable Applicable Laws applicable to the manufacture and testing of pharmaceutical materials in jurisdictions outside the U.S. For clarity, GMPs shall include applicable quality guidelines promulgated under the International Conference on Harmonization.
1.157Governmental Authority” means any multi-national, federal, state, local, municipal or other government authority of any nature (including any governmental division, subdivision, department, agency, bureau, branch, office, commission, council, court or other tribunal).
1.158H-W Suit Notice” has the meaning set forth in Section 9.8.
1.159[****].
1.160[****].
1.161Hypertension Indication” means any of the following Indications: (a) the Primary Indication or (b) treatment of essential (primary) or secondary hypertension to lower blood pressure [****].
1.162ICC” has the meaning set forth in Section 14.2(a).
1.163ICC Court” has the meaning set forth in Section 14.2(c).
1.164ICD-11” means the Eleventh Revision of the International Statistical Classifications of Diseases and Related Health Problems, as may be revised or amended from time to time, or a successor classification.
1.165Idle Capacity” has the meaning set forth in the Financial Appendix.
1.166IND” means (a) an Investigational New Drug Application as defined in the FD&C Act and applicable regulations promulgated thereunder by FDA, or (b) any comparable submission to the applicable Regulatory Authority in any other regulatory jurisdiction that is required to initiate or conduct clinical testing of a pharmaceutical product in humans in such jurisdiction (including any Clinical Trial Authorizations (“CTA”) submitted to the EMA).
1.167Indemnification Claim Notice” has the meaning set forth in Section 11.3(a).
1.168Indemnifying Party” has the meaning set forth in Section 11.3(a).
1.169Indemnitee” has the meaning set forth in Section 11.3(a).
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1.170Indication” means any distinct indication or patient population in the Field, determined as follows: (a) to distinguish one indication from another indication, the two indications have to be either (i) listed in two different blocks of the ICD-11 (as a way of example, any essential hypertension under BA00 is in a different block from any hypertensive disease under block BA01, whereas BA00.0 and BA00.1 belong to the same block) or (ii) Developed by the Parties (as applicable) under separate Clinical Trials, and (b) to distinguish one patient population from another patient population, the two patient populations must be investigated in separate Phase 2 Clinical Trials or Phase 3 Clinical Trials (e.g., recently diagnosed treatment naive hypertension would be distinct from high-risk patients with uncontrolled hypertension); provided that, with respect to the foregoing (i) and (ii), if a Phase 2 Clinical Trial or Phase 3 Clinical Trial is conducted with patients with two (2) or more indications or patients consisting of two (2) or more patient populations (e.g., such Clinical Trial includes both recently diagnosed treatment naïve hypertension patients with high cardiovascular risk and recently diagnosed treatment naïve hypertension patients without cardiovascular risk) and a Phase 2 Clinical Trial or Phase 3 Clinical Trial is separately conducted with only one of those indications or patient populations (e.g., treatment naïve hypertension patients with high cardiovascular risk), then such indication or patient population for which the second Phase 2 Clinical Trial or Phase 3 Clinical Trial (i.e., recently diagnosed treatment naïve hypertension patients without cardiovascular risk) shall be deemed to be a distinct indication or patient population from the first Phase 2 Clinical Trial or Phase 3 Clinical Trial for purposes of this definition. By way of example and without limiting the foregoing, each of the following shall be deemed [****].
1.171Indirect Costs” has the meaning set forth in the Financial Appendix.
1.172Indirect Taxes” has the meaning set forth in Section 8.8(d).
1.173Information Security Incident” means, with respect to Confidential Information, any unauthorized use, unauthorized disclosure, corruption (including ransomware attack) or similar loss of such Confidential Information.
1.174Initial Co-Commercialization Plan” has the meaning set forth in Section 5.5.
1.175Initial CVOT Study” means any cardiovascular outcomes Phase 3 Clinical Trial of the Therapeutic Product as an add-on to standard of care in patients with uncontrolled hypertension and who are at high risk of cardiovascular events[****].
1.176Initial Development Plan” has the meaning set forth in Section 3.4.
1.177Initial Manufacturing Plan” has the meaning set forth in Section 6.4.
1.178[****].
1.179[****].
1.180Joint Commercialization Committee” or “JCC” has the meaning set forth in Section 2.4(a).
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1.181Joint Development Committee” or “JDC” has the meaning set forth in Section 2.2(a).
1.182Joint Know-How” means any and all Know-How first conceived, reduced to practice or otherwise identified, developed made or discovered, jointly by or on behalf of (including by subcontractors) Roche or any of its Related Parties, on the one hand, and (including by subcontractors) Alnylam or any of its Related Parties, on the other hand, in the course of conducting the Collaboration; provided, however, that notwithstanding the foregoing, any invention or discovery first conceived or reduced to practice or, with respect to any invention or discovery other than patentable inventions, otherwise identified, developed, made or discovered, jointly by or on behalf of employees or consultants of Roche or any of its Related Parties, on the one hand, and Alnylam or any of its Related Parties, on the other hand in the course of conducting the Collaboration that (a) is an improvement to, or modification of, Alnylam Core Know-How, including any Patent Rights that Cover such inventions or discoveries (the “Alnylam Core Improvements”), shall be Alnylam Collaboration Know-How or Alnylam Collaboration Patents, as applicable, and owned by Alnylam pursuant to Section 9.2(a); or (b) is an improvement to, or modification of, Roche Core Know-How, including any Patent Rights that Cover such inventions or discoveries (the “Roche Core Improvements”), shall be Roche Collaboration Know-How or Roche Collaboration Patents, as applicable, and owned by Roche pursuant to Section 9.2(b).
1.183Joint Manufacturing Committee” or “JMC” has the meaning set forth in Section 2.3(a).
1.184Joint MLRB” has the meaning set forth in Section 5.11(a)(ii).
1.185Joint Patents” means any and all Patents Rights Covering Joint Know-How to the extent Controlled by the Parties. For clarity, “Joint Patents” does not include: (a) Alnylam Background Patents, (b) Alnylam Collaboration Patents, (c) Roche Background Patents or (d) Roche Collaboration Patents.
1.186Joint Program Team” or “JPT” means the cross-functional joint program team described in Section 2.9.
1.187Joint Steering Committee” or “JSC” has the meaning set forth in Section 2.1(a).
1.188KARDIA-1” means the Phase 2 Clinical Trial entitled “A Study to Evaluate Efficacy and Safety of ALN-AGT01 in Patients with Mild To-Moderate Hypertension” (NCT04936035). For clarity, KARDIA-1 is an Alnylam Lead Study and is set forth in the Initial Development Plan.
1.189KARDIA-2” means the Phase 2 Clinical Trial entitled “Zilebesiran as an Add-on Therapy in Patients With Hypertension Not Adequately Controlled by a Standard of Care Antihypertensive Medication” (NCT05103332). For clarity, KARDIA-2 is an Alnylam Lead Study and is set forth in the Initial Development Plan.
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1.190KARDIA-3” means the Phase 2 Clinical Trial of Therapeutic Product in patients with uncontrolled hypertension and at high cardiovascular risk. For clarity, KARDIA-3 is an Alnylam Lead Study and is set forth in the Initial Development Plan, and [****].
1.191Know-How” means all technical, scientific, regulatory, business and other information, results, knowledge, techniques and data, in whatever form and whether or not patented or patentable, including inventions, invention disclosures, discoveries, plans, processes, practices, methods, knowledge, trade secrets, know-how, instructions, skill, experience, ideas, concepts, drawings, data (including biological, chemical, pharmacological, toxicological, pharmaceutical, physical and analytical, safety, quality control, and preclinical and clinical data), manufacturing documentation (including manufacturing batch records and documentation supporting cGMP), formulae, formulations, compositions, specifications, marketing, pricing, distribution, costs, sales and manufacturing data or descriptions, cells, cell lines, assays, chemical structures, chemical sequences and other physical, biological, and chemical materials, expertise, and technology that are confidential and necessary or useful in the discovery, manufacture, research, development and/or commercialization of Products, and all derivatives, modifications, and improvements of the foregoing. For clarity, “Know-How” does not include Patent Rights Covering any of the foregoing.
1.192Launch Preparation Period” has the meaning set forth in the Financial Appendix.
1.193Lead Development Party” has the meaning set forth in Section 3.6.
1.194Lead Regulatory Party” has the meaning set forth in Section 4.2.
1.195Long Term Development Budget” has the meaning set forth in Section 3.3.
1.196Long Term Development Plan” has the meaning set forth in Section 3.2(d).
1.197Major Markets” means [****].
1.198[****].
1.199Major Regulatory Communication” has the meaning set forth in Section 4.2(c)(i).
1.200Manufacture” and “Manufacturing” means all activities related to the production, manufacturing, processing, filling, finishing, packaging, labeling, assembling, shipping, and holding of any product, or any intermediate or component thereof, and any placebo, as the case may be (including any devices or other delivery technologies that are packaged or distributed with such product), including process development, process qualification and validation, scale-up (including manufacturing facility scale-up), preclinical, clinical and commercial manufacture and analytic development, product characterization, stability testing, quality assurance, and quality control, and management of any Third Parties conducting such activities.
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1.201Manufacturing Budget” has the meaning set forth in Section 6.3(a).
1.202Manufacturing Changes” has the meaning set forth in Section 6.10.
1.203Manufacturing Plan” has the meaning set forth in Section 6.2.
1.204Manufacturing Records” has the meaning set forth in Section 6.12.
1.205Manufacturing Reports” has the meaning set forth in Section 6.12.
1.206Medical Affairs Activities” means with respect to the Product in the Field in the Territory activities of medical science liaisons, activities involving key opinion leaders and professional societies, the provision of medical information services, evidence and real world evidence generation strategy, coordination and development of content to address medical information requests, health economics and outcomes research, publication and congress planning and continuing medical education.
1.207MicroRNA” or “miRNA” means a structurally defined functional RNA molecule usually between nineteen (19) and twenty-five (25) nucleotides in length, which is derived from an endogenous, genetically encoded RNA which is predicted to fold into a hairpin RNA structure that is a substrate for the double-stranded RNA-specific ribonuclease drosha and subsequently is predicted to serve as a substrate for the enzyme dicer, a member of the ribonuclease III enzyme family.
1.208MicroRNA Mimic” means a single-stranded or double-stranded oligonucleotide with the same base composition and sequence (including chemically modified bases) [****] as a particular natural miRNA and which is designed to mimic the activity of such miRNA. For clarity, MicroRNA Mimic excludes a double-stranded oligonucleotide which functions or is designed to function as a siRNA.
1.209[****].
1.210NDA” means (a) a New Drug Application or supplemental New Drug Application, as defined in the FD&C Act and applicable regulations promulgated thereunder by FDA, or (b) any comparable submission to the applicable Regulatory Authority in any other regulatory jurisdiction that is required to sell a pharmaceutical product in such jurisdiction. including any Marketing Authorization Application (“MAA”) in any jurisdiction.
1.211NDC” means the FDA National Drug Code.
1.212Net Profits and Net Losses” has the meaning set forth in the Financial Appendix.
1.213Net Sales” means [****].
1.214Net Sales Deduction” has the meaning set forth in Section 1.213.
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1.215New Manufacturing Process” has the meaning set forth in Section 6.8(b).
1.216New Manufacturing Process Technology Transfer” has the meaning set forth in Section 6.8(b).
1.217New Manufacturing Process Technology Transfer Plan” has the meaning set forth in Section 6.8(b).
1.218New York Court” has the meaning set forth in Section 14.2(g).
1.219Non-Acquiring Party” has the meaning set forth in Section 7.8(a).
1.220Non-breaching Party” has the meaning set forth in Section 13.5(a).
1.221Non-Clinical Studies” means all non-human studies of pharmaceutical products.
1.222Non-Personal Digital Promotions” means any non-personal promotional materials using digital channels to promote Products including search engines, social media, email, websites, digital advertisements, and television and radio advertisements.
1.223[****].
1.224Notice Date” has the meaning set forth in Section 13.2.
1.225Notice Period” has the meaning set forth in Section 13.2.
1.226Operating Committee” means the Joint Development Committee, the Joint Manufacturing Committee, the Joint Commercialization Committee, or any other subcommittee of the JSC, or any of the foregoing committees, which may be established by the JSC from time to time in accordance with the terms hereof; provided that neither the JPT nor any working group formed hereunder are “Operating Committees.”
1.227Opt-Out Party” has the meaning set forth in Section 13.9(a).
1.228Other Manufacturing Costs” has the meaning set forth in the Financial Appendix.
1.229Other Outcomes Trial” means, other than the Initial CVOT Study, any Phase 3 Clinical Trial that is a cardiovascular or renal outcomes trial of a Therapeutic Product.
1.230Party” has the meaning set forth in the preamble.
1.231Patent Challenge” has the meaning set forth in Section 13.3.
1.232Patent Costs” has the meaning set forth in Section 9.5.
1.233Patent Dispute” has the meaning set forth in Section 14.1.
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1.234Patent Rights” means (a) all national, regional and international patents, priority patent filings, and patent applications, including provisional patent applications and rights to claim priority from any of these patents or applications, (b) any renewals, divisions, continuations (in whole or in part), or requests for continued examination of any of such patents and patent applications, and any and all patents issuing thereon, (c) any and all reissues, reexaminations, extensions, supplementary protection certificates, divisions, renewals, substitutions, confirmations, registrations, revalidations, revisions, and additions of or to any of the foregoing and (d) any foreign equivalents of each of the foregoing (a) through (c).
1.235PCD Strategy” has the meaning set forth in Section 5.9.
1.236Person” means an individual, firm, corporation, partnership, trust, incorporated or unincorporated association, joint venture, limited liability company, joint stock company, Governmental Authority or other entity of any kind.
1.237Personal Data” has the meaning set forth in Section 15.16.
1.238Pharmacovigilance Agreement” has the meaning set forth in Section 4.5.
1.239Phase 1 Clinical Trial” means a clinical trial of a drug product in human subjects that is designed to satisfy the requirements for a Phase 1 study as described in 21 C.F.R. § 312.21(a), regardless of where such clinical trial is conducted.
1.240Phase 2 Clinical Trial” means a clinical trial of a drug product in human subjects that is designed to satisfy the requirements for a Phase 2 study as described in 21 C.F.R. § 312.21(b), regardless of where such clinical trial is conducted. [****].
1.241Phase 3 Clinical Trial” means a clinical trial of a drug product in human subjects designed to satisfy the requirements for a Phase 3 study as defined in 21 C.F.R. § 312.21(c), regardless of where such clinical trial is conducted [****].
1.242Phase 4 Clinical Trial” means a clinical trial of a drug product in human subjects conducted after Regulatory Approval of such drug product has been obtained from an appropriate Regulatory Authority, including a Confirmatory Clinical Trial.
1.243PhRMA Code” means the Pharmaceutical Research and Manufacturers of America Code on Interactions with Health Care Professionals.
1.244PII/Samples” has the meaning set forth in Section 13.8(e)(ii).
1.245PIP Trial” means any Clinical Trial of Product in pediatric patients, including any such Clinical Trial that is part of a pediatric investigation plan or pediatric study plan required by a Regulatory Authority.
1.246Post-Approval Study” means any Phase 4 Clinical Trial, real-world evidence study, non-interventional study, investigator-initiated study, or disease registry
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conducted following Regulatory Approval for the applicable Product for use in the Field in the applicable country or jurisdiction.
1.247Pre-Approval Trial” means a Phase 1 Clinical Trial, Phase 2 Clinical Trial or Phase 3 Clinical Trial.
1.248Pre-Existing Affiliates” means (a) with respect to an Acquired Party, the Affiliates of such Acquired Party that exist immediately prior to the effective date of the applicable Change of Control (not including, for clarity, the Acquiror or any of its Affiliates that exist immediately prior to the effective date of the applicable Change of Control) and any successors thereto and (b) with respect an Acquiror Party, the Affiliates of such Acquiror Party that exist immediately prior to the effective date of the applicable Change of Control (not including, for clarity, the Acquired Party or any of its Affiliates that exist immediately prior to the applicable Change of Control) and any successors thereto.
1.249Preliminary Manufacturing Budget” has the meaning set forth in Section 6.3(b).
1.250Presiding Arbitrator” has the meaning set forth in Section 14.2(c).
1.251Price Approval” means, in any country where a Governmental Authority authorizes reimbursement for, or approves or determines pricing for, pharmaceutical products, receipt (or, if required to make such authorization, approval or determination effective, publication) of such reimbursement authorization or pricing approval or determination (as the case may be).
1.252Primary Indication” means the reduction of one or more major adverse cardiovascular events in high-risk patients with hypertension [****].
1.253Primary Indication Program” means any and all Development activities directed to obtaining Regulatory Approval of the Therapeutic Product for the Primary Indication as contemplated in, or in furtherance of, the Primary Indication TPP and the Development Plan (including the initiation and conduct of KARDIA-3, the Initial CVOT Study and any PIP Trial).
1.254Primary Indication Target Product Profile” or “Primary Indication TPP” has the meaning set forth in Schedule 1.254.
1.255Primary Indication TPP Failure” means that the criteria set forth in both of the following clauses (a) and (b) are satisfied for the Therapeutic Product in [****].
1.256Product” means any pharmaceutical product (including any Combination Product) that is comprised of or contains (a) Zilebesiran as an active pharmaceutical ingredient (the “Therapeutic Product”) or (b) a REVERSIR (a “REVERSIR Product”), in each case ((a) and (b)), in any form, presentation, dosage and formulation; provided that any such form, presentation, dosage or formulation comprises or contains either Zilebesiran or REVERSIR as an active pharmaceutical ingredient. For clarity, the Development,
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Manufacture and/or Commercialization of any Combination Product under this Agreement will be subject, as applicable, to Section 3.5 and [****].
1.257Product Action Concern” has the meaning set forth in Section 4.4(a).
1.258Product Trademarks” means any trademarks, service marks, trade names and related trade dress, designs, logos, domain names or symbols used in connection with the Commercialization of Products (a) by Roche in the Roche Territory or (b) by the Parties in the Co-Commercialization Territory, in each case (the foregoing (a) and (b)), that is not a corporate name or logo of either Party or any of its Related Parties.
1.259Promotional Materials” means any and all promotional materials to be used in promoting the Products for use in the Field, including all forms of Non-Personal Digital Promotions, non-personal print promotions, print promotions, and any materials presented to congresses in the U.S. or any other congresses in the Territory with global reach.
1.260Quality Agreement” has the meaning set forth in Section 6.10.
1.261Recipient” has the meaning set forth in Section 12.1.
1.262Redacted Agreement” has the meaning set forth in Section 12.4(c).
1.263[****].
1.264[****].
1.265[****].
1.266[****].
1.267Region” means one or more of the following: [****].
1.268Register” has the meaning set forth in Section 9.6.
1.269Regulatory Activities” means preparing, obtaining, or maintaining Regulatory Materials and Regulatory Approvals for the Product or activities otherwise relating to Pre-Approval Trials or Post-Approval Studies for the Product for use in the Field in the Territory, in each case to the extent consistent with the Development Plan or Co-Commercialization Plan, as applicable.
1.270Regulatory Approval” means all approvals (other than Price Approval) necessary for the Manufacture, Commercialization or other exploitation of a pharmaceutical product for one or more Indications in a country or regulatory jurisdiction, which may include satisfaction of all applicable regulatory and notification requirements. For avoidance of doubt, “Regulatory Approval” shall include (a) accelerated approval as such term is described in 21 C.F.R. Part 314 Subpart H or an equivalent conditional approval of a Regulatory Authority outside the United States and (b) any label expansion or an approval by the applicable
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Regulatory Authority to include Development Data pertaining to such Indication in the label of such pharmaceutical product.
1.271Regulatory Authority” means, in a particular country or regulatory jurisdiction, any applicable Governmental Authority involved in granting Regulatory Approval or, to the extent required in such country or regulatory jurisdiction, Price Approval of a pharmaceutical product in such country or regulatory jurisdiction and any successor thereto.
1.272Regulatory Exclusivity” means any exclusive marketing rights or data exclusivity rights conferred by any Regulatory Authority under Applicable Laws with respect to a Product in a country or jurisdiction in the Territory that generally have the effect of preventing or delaying all or some Third Parties from selling such Product in such country or jurisdiction during such period of exclusivity, other than Patent Rights, including rights conferred in the U.S. under the Hatch-Waxman Act or the FDA Modernization Act of 1997 (including pediatric exclusivity), or rights similar thereto outside the U.S.
1.273Regulatory Materials” means regulatory applications, submissions, notifications, correspondences, registrations, Regulatory Approvals or other filings made to or with, or other approvals granted by, a Regulatory Authority that are necessary or reasonably desirable in order to Develop, Manufacture, Commercialize or otherwise exploit a Product in a particular country or regulatory jurisdiction. “Regulatory Materials” include INDs and NDAs.
1.274Related Party” means, with respect to a Party, such Party’s Affiliates and Sublicensees.
1.275Representatives” has the meaning set forth in Section 12.3(f).
1.276Required Manufacturing Change” has the meaning set forth in Section 6.10(a).
1.277Reversion Product” has the meaning set forth in Section 13.8(c).
1.278REVERSIR” means ATG01-RVR or any other siRNA designed to reverse Zilebesiran-mediated AGT knockdown that is developed in accordance with and subject to the terms of this Agreement.
1.279REVERSIR Product” has the meaning set forth in Section 1.256.
1.280Reviewing Party” has the meaning set forth in Section 12.5.
1.281RNA” means ribonucleic acid.
1.282Roche” has the meaning set forth in the preamble.
1.283Roche Background Know-How” means any and all Know-How to the extent Controlled by Roche or any of its Affiliates as of the Effective Date or during the Term, which Know-How is necessary or reasonably useful for the Development, Manufacture or Commercialization of any Products for use in the Field in the Territory in accordance with the
23



terms of this Agreement, other than Roche Collaboration Know-How and Roche’s interest in Joint Know-How. For clarity, “Roche Background Know-How” (a) includes Roche Core Know-How and (b) excludes any and all Patent Rights and Roche Excluded IP. For purposes of this definition only, “Controlled” means Know-How to the extent actually used by Roche or any of its Affiliates as part of the Collaboration activities hereunder.
1.284Roche Background Patents” means any and all Patents Rights to the extent Controlled by Roche or any of its Affiliates as of the Effective Date or during the Term that Cover Roche Background Know-How, other than Roche Excluded IP.
1.285Roche Basel” has the meaning set forth in the preamble.
1.286Roche Collaboration Know-How” means any and all Know-How to the extent Controlled by Roche or any of its Affiliates after the Effective Date and during the Term that (a) is necessary or reasonably useful for the Development, Manufacture or Commercialization of Products for use in the Field in the Territory in accordance with the terms of this Agreement and (b) is conceived or reduced to practice (in whole or in part) or otherwise identified, developed, made, or discovered solely by or on behalf of (including by subcontractors) Roche or any of its Related Parties in its conduct of Collaboration activities under this Agreement. For clarity, “Roche Collaboration Know-How” (a) includes Roche Core Know-How and Roche Product-Specific Know-How, and (b) excludes any and all Patent Rights and Roche Excluded IP.
1.287Roche Collaboration Patents” means any and all Patents Rights to the extent Controlled by Roche or any of its Affiliates during the Term that Cover any Roche Collaboration Know-How. For clarity, “Roche Collaboration Patents” excludes Roche’s interest in Joint Patents and Roche Excluded IP.
1.288Roche Commercialization Costs” has the meaning set forth in the Financial Appendix.
1.289Roche Core Improvements” has the meaning set forth in Section 1.182.
1.290Roche Core Know-How” means any and all Roche Know-How other than (a) Roche Product-Specific Know-How, (b) Roche’s interest in Joint Know-How and (c) Roche Excluded IP.
1.291Roche Core Patents” means any and all Roche Patents other than Roche Product-Specific Patents, excluding Roche’s interest in Joint Patents and Roche Excluded IP.
1.292[****].
1.293Roche Excluded IP” means any and all [****]; (b) Know-How and Patent Rights specifically related to any active pharmaceutical ingredient, but not Zilebesiran or REVERSIR; [****].
1.294Roche Indemnitee” has the meaning set forth in Section 11.1.
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1.295Roche Know-How” means any and all Roche Background Know-How, Roche Collaboration Know-How and Roche’s interest in Joint Know-How.
1.296Roche Lead Study” has the meaning set forth in Section 3.6(b)(i).
1.297Roche Licensed IP” means the Roche Know-How and Roche Patents.
1.298Roche Manufacturing Change” has the meaning set forth in Section 6.10(c)(ii).
1.299[****].
1.300Roche Patents” means any and all Roche Background Patents, Roche Collaboration Patents and Roche’s interest in Joint Patents.
1.301Roche Product-Specific Know-How” means, on a Product-by-Product basis, [****].
1.302Roche Product-Specific Patents” means any and all Patent Rights to the extent Controlled by Roche or any of its Affiliates during the Term that Cover Roche Product-Specific Know-How.
1.303Roche-Requested Manufacturing Change” has the meaning set forth in Section 6.10(b).
1.304Roche Territory” means, subject to Section 7.3(b) and Section 13.10 with respect to Japan, all countries and regulatory jurisdictions throughout the world other than the Co-Commercialization Territory.
1.305Roche Territory Compulsory Sublicense Compensation” means Compulsory Sublicense Compensation paid to Roche for the Roche Territory.
1.306Roche Transfer Activities” has the meaning set forth in Section 13.8(c)(xii).
1.307Royalty Payment” has the meaning set forth in Section 8.7(a).
1.308Royalty Rate” has the meaning set forth in Section 8.7(a).
1.309Royalty Term” has the meaning set forth in Section 8.7(b).
1.310Rules” has the meaning set forth in Section 14.2(a).
1.311Sales” means [****].
1.312Sales Milestone” has the meaning set forth in Section 8.6(a).
1.313Sales Milestone Payments” has the meaning set forth in Section 8.6(a).
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1.314Sanctioned Jurisdiction” means a country or territory that is itself the subject or target of any Sanctions and Export Control Laws (as of the date of this Agreement, Cuba, Iran, North Korea, Syria, and the Crimea, the so-called Luhansk People’s Republic, and the so-called Donetsk People’s Republic regions of Ukraine, and the non-government controlled areas of Ukraine in the oblasts of Kherson and Zaporizhzhia).
1.315Sanctioned Person” means any Person targeted by Sanctions and Export Control Laws, including as a result of being (a) listed in any list of sanctioned Persons, including those maintained by the U.S. (including the Department of the Treasury’s Office of Foreign Assets Control and the Department of State), the United Kingdom, or the European Union; (b) located, organized, or resident in a Sanctioned Jurisdiction; (c) directly or indirectly owned fifty percent (50%) or more or controlled, individually or in the aggregate, by one or more Persons described in the foregoing clauses (a) and/or (b); or identified on the U.S. Department of Commerce’s Entity List, Denied Persons List, Unverified List or Military End User List, or the U.S. Department of State’s Debarred List.
1.316Sanctions and Export Control Laws” means any and all Applicable Laws related to (a) import and export controls, including the U.S. Export Administration Regulations, (b) economic or financial sanctions and trade embargoes, including those administered by the Office of Foreign Assets Control of the U.S. Department of the Treasury, the U.S. Department of State, the European Union, and the United Kingdom or (c) anti-boycott measures.
1.317SEC” means the U.S. Securities and Exchange Commission or any successor thereof.
1.318Shared Development Costs” has the meaning set forth in the Financial Appendix.
1.319Short Term Development Budget” has the meaning set forth in Section 3.3.
1.320Short Term Development Plan” has the meaning set forth in Section 3.2.
1.321siRNA” means an oligonucleotide composition of native or chemically modified RNA that targets a gene through activation of the RNA interference pathway, and that is not a MicroRNA, MicroRNA antagonist or MicroRNA Mimic.
1.322Sublicense Agreement” has the meaning set forth in Section 7.3(c)(ii).
1.323Sublicensee” means a Third Party that is granted a sublicense (through one or multiple tiers) by either Party under the licenses granted in Section 7.1, with respect to Roche, or Section 7.2, with respect to Alnylam, in each case other than through a Compulsory Sublicense.
1.324Supply Agreements” has the meaning set forth in Section 6.9(b).
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1.325Tax” means any tax (including any income tax, franchise tax, capital gains tax, gross receipts tax, VAT, surtax, excise tax, ad valorem tax, transfer tax, stamp tax, sales tax, use tax, property tax, business tax, withholding tax or payroll tax), levy, assessment, tariff, duty (including any customs duty) and any related charge or amount (including any fine, addition, penalty or interest), imposed, assessed or collected by any Governmental Authority.
1.326Tax Representative” means the “partnership representative” as such term is defined in Section 6223 of the Code.
1.327Technology Transfer” means the Existing Process Technology Transfer and the New Manufacturing Process Technology Transfer.
1.328Technology Transfer Completion Date” has the meaning set forth in Section 6.2.
1.329Technology Transfer Costs” means all Direct Costs and Indirect Costs incurred by or on behalf of a Party or any of its Affiliates in conducting any (a) Technology Transfer pursuant to Section 6.8 or (b) activities to enable Roche, its Affiliates or [****] to obtain the authorization or ability to Manufacture Products.
1.330Technology Transfer Plans” means the Existing Process Technology Transfer Plan and the New Manufacturing Process Technology Transfer Plan.
1.331Term” has the meaning set forth in Section 13.1.
1.332Terminated Territory” has the meaning set forth in Section 13.8(c).
1.333Termination Effective Date” has the meaning set forth in Section 13.8(c).
1.334Termination Notice Period” has the meaning set forth in Section 13.8(a).
1.335Territory” means, collectively, the Co-Commercialization Territory and the Roche Territory.
1.336Therapeutic Product” has the meaning set forth in Section 1.256.
1.337Third Party” means any entity other than Alnylam or Roche or any of their respective Affiliates.
1.338Third Party Claim” has the meaning set forth in Section 11.1.
1.339Third Party Infringement” has the meaning set forth in Section 9.10(a).
1.340Third Party License” means any agreement entered into after the Effective Date in accordance with Section 7.6 by and between a Party or its Affiliate, on the one hand, and a Third Party on the other hand, pursuant to which such Party or its Affiliates are granted a license to intellectual property rights of such Third Party or its Affiliates (excluding
27



any such agreement which relates solely to an active pharmaceutical ingredient of a Combination Product that is not Zilebesiran or a REVERSIR).
1.341Third Party Payment” has the meaning set forth in Section 7.6(b).
1.342Third Party Sublicense Agreement” has the meaning set forth in Section 7.3(c)(ii).
1.343Trademark Costs” mean those out-of-pocket costs and expenses incurred by or on behalf of a Party or any of its Affiliates for outside counsel and other Third Parties, and filing and maintenance, in each case incurred in connection with the establishment and maintenance of rights under Product Trademarks, including costs of trademark filings and registration fees, and actions to enforce or maintain the applicable trademarks.
1.344Transition Agreement” has the meaning set forth in Section 13.8(c)(ii).
1.345U.S.” or “United States” means the United States of America (including all possessions and territories thereof).
1.346U.S. Territory Partnership” has the meaning set forth in Section 8.8(e).
1.347Valid Claim” means (a) a claim (including a process, use, or composition of matter claim) of an issued and unexpired Patent Right, which has not been held invalid or unenforceable by a patent office, court or other Governmental Authority of competent jurisdiction, which holding is unappealable or unappealed within the time allowed for appeal, and which has not been admitted to be invalid by the owner through reissue, disclaimer or otherwise, or (b) a claim (including a process, use, or composition of matter claim) within a patent application that is pending for no more [****] years and that has not been revoked, cancelled, withdrawn, or affirmatively abandoned, or held invalid, unenforceable, unpatentable, or abandoned by a patent office, court or other Governmental Authority of competent jurisdiction, which holding is unappealable or unappealed within the time allowed for appeal.
1.348VAT” has the meaning set forth in Section 8.8(b).
1.349Withholding” has the meaning set forth in Section 8.8(c).
1.350Withholding Action” has the meaning set forth in Section 8.8(c).
1.351Zilebesiran” means the molecule designated by Alnylam as AD-85481 [****], and any modification thereto developed in accordance with and subject to the terms of this Agreement.
ARTICLE 2

GOVERNANCE
2.1Joint Steering Committee.
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(a)Purpose; Formation. Within [****] days after the Effective Date, the Parties shall establish a joint steering committee (the “Joint Steering Committee” or “JSC”) to monitor and oversee the activities under this Agreement and facilitate communication between the Parties with respect to the Development, Manufacture and Commercialization of Products for use in the Field in the Territory under this Agreement.
(b)Composition. Each Party shall initially appoint [****] representatives to serve as JSC members. Each JSC member shall have appropriate seniority and functional expertise to make decisions arising within the JSC’s responsibilities. The JSC may change its size from time to time by mutual written agreement of its members; provided that the JSC shall consist at all times of an equal number of members of each of Alnylam and Roche. Each Party may replace its JSC members at any time upon written notice to the other Party; provided that the applicable replacement has the requisite expertise and seniority for JSC members hereunder. The JSC may invite non-members to participate in the discussions and meetings of the JSC; provided that such participants (i) are subject to confidentiality obligations (whether in writing or by operation of law) consistent with this Agreement, (ii) are participating in or supporting activities conducted under this Agreement and (iii) for clarity, have no voting rights at the JSC. Each Party shall appoint one of its JSC members as its chairperson, and the JSC shall be co-chaired by such chairpersons. Each Party may replace its chairperson at any time upon written notice to the other Party. The role of each chairperson shall be to convene and preside at meetings of the JSC, but neither chairperson shall have any additional powers or rights beyond those held by the other JSC members.
(c)Specific Responsibilities of the JSC. In addition to its overall responsibility for monitoring and providing a forum to discuss and coordinate the Parties’ activities under this Agreement, the JSC shall in particular:
(i)oversee the collaborative activities of the Parties under this Agreement;
(ii)review and approve any amendments, changes or other updates to the Development Plan, Manufacturing Plan, Co-Commercialization Plan, PCD Strategy and each Global Brand Strategy, including all budget recommendations from any Operating Committee and the adoption of, or any amendments, changes or other updates to, any Additional Program Plans or Device Program Plans proposed by a Party to be included in the Development Plan;
(iii)review and discuss the Parties’ activities under the Development Plan, the Manufacturing Plan and the Co-Commercialization Plan and set the overall strategy for coordination of activities among the Parties relating to Products for use in the Field within the Territory;
(iv)oversee the establishment, termination and activities of additional subcommittees as it deems necessary to achieve the objectives and intent of this Agreement;
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(v)delegate duties to Operating Committees, direct particular projects or activities at an appropriate time and agree on operating procedures of such Operating Committees;
(vi)approve plans brought forth by the Operating Committees to the JSC;
(vii)approve termination of the JPT if so proposed by the Operating Committees;
(viii)attempt to resolve issues presented to it by, and disputes within, any Operating Committee; and
(ix)perform such other functions as may be appropriate to further the purposes of this Agreement, as mutually agreed upon and directed by the Parties in writing or as expressly specified in this Agreement.
For clarity, the JSC shall have no responsibility or authority other than that expressly set forth in this Agreement.
(d)Meetings. The Parties shall endeavor to have their first meeting of the JSC within [****] days after the establishment of the JSC; provided that such meeting shall be no later than [****] days after the Effective Date. The JSC shall meet at least [****] per Calendar Quarter during the Term (spaced at regular intervals) unless the JSC mutually agrees in writing to a different frequency for such meetings. Either Party may also call a special meeting of the JSC (by videoconference or teleconference) by providing at least [****] Business Days’ prior written notice to the other Party in the event such Party reasonably believes that a significant matter must be addressed prior to the next scheduled meeting of the JSC, and such Party shall provide the JSC no later than [****] Business Days prior to the special meeting with materials that such Party reasonably believes in good faith are sufficient to enable the JSC members to make an informed decision; provided that for time sensitive matters, a Party may call a special meeting of the JSC on less than [****] Business Days’ prior written notice if the Parties, as confirmed in writing by the Alliance Managers, agree that an issue warrants an expedited meeting. No later than [****] Business Days prior to any meeting of the JSC, the Alliance Managers (or their respective designees) shall prepare and circulate an agenda for such meeting and each Party shall be permitted to propose additional topics to be included on such agenda. The JSC may meet in person, by videoconference or by teleconference. In-person JSC meetings will be held at locations alternately selected by Alnylam and by Roche. Each Party will bear the expense of its respective JSC members’ participation in JSC meetings. Meetings of the JSC shall be effective only if at least one (1) member of each Party is present or participating in such meeting. The Alliance Managers (or their respective designees) will be responsible for the preparation of written minutes of all JSC meetings that reflect material decisions and actions made at such meetings. The Alliance Managers (or their respective designees) shall deliver draft meeting minutes to each member of the JSC for their review within [****] Business Days after each JSC meeting. Such minutes will be deemed approved unless one or more members of the JSC objects in writing to the accuracy of such minutes within [****] Business Days after receipt thereof.
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(e)Decision-Making. In addition to resolving issues within the scope of the JSC’s express responsibilities hereunder, the JSC shall have the authority in accordance with Section 2.5(b) to resolve any disputes not resolved by any Operating Committee in accordance with Section 2.5. Subject to the remainder of this Section 2.1(e) and Section 2.7, the JSC shall act by consensus, with each Party having, collectively, one (1) vote on behalf of that Party. If the JSC cannot reach consensus on an issue that comes before the JSC and over which the JSC has responsibility, then such matter shall be resolved in accordance with Section 2.5(c) or Section 2.5(d), as applicable.
2.2Joint Development Committee.
(a)Purpose; Formation. Within [****] days after the Effective Date, the Parties shall establish a joint development committee to oversee and coordinate, and facilitate communication regarding, Development of Products for use in the Field in the Territory under this Agreement (the “Joint Development Committee” or “JDC”).
(b)Composition. Each Party shall initially appoint [****] representatives to serve as JDC members. Each JDC member shall have appropriate seniority and sufficient expertise in the Development of pharmaceutical products similar to the Products to make decisions arising within the scope of the JDC’s responsibilities. The JDC may change its size from time to time by mutual written agreement of its members; provided that the JDC shall consist at all times of an equal number of members of each of Alnylam and Roche and in no event shall the JDC consist of less than [****] members of each Party. Each Party may replace its JDC members at any time upon written notice to the other Party; provided that the applicable replacement has the requisite expertise and seniority for JDC members hereunder. The JDC may invite non-members to participate in the discussions and meetings of the JDC; provided that such participants (i) are subject to confidentiality obligations (whether in writing or by operation of law) consistent with this Agreement, (ii) are participating in or supporting Development activities conducted with respect to the Products under this Agreement and (iii) for clarity, have no voting rights at the JDC. Each Party shall appoint one of its JDC members as its chairperson, and the JDC shall be co-chaired by such chairpersons. Each Party may replace its chairperson at any time upon written notice to the other Party. The role of each chairperson shall be to convene and preside at meetings of the JDC, but neither chairperson shall have any additional powers or rights beyond those held by the other JDC members.
(c)Specific Responsibilities of the JDC. In addition to its general responsibilities, the JDC shall in particular:
(i)monitor, implement, and oversee the Development of the Products through Regulatory Approval in accordance with, and compare Development progress against, the Development Plan;
(ii)discuss and approve, for submission to the JSC, any proposed changes, amendments, or other updates to the Development Plan (including the Development Budget) no less than [****], including amendments regarding whether to: conduct additional Pre-Approval Trials of Products for use in the Field in the Territory; develop Products for use in the Field in combination (whether co-administered or co-formulated) with any other
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active pharmaceutical ingredient or other pharmaceutical product; or discuss and amend the Development Plan (including the Development Budget) to include any Additional Program Plan or Device Program Plan;
(iii)discuss and approve a template clinical trial agreement for use in connection with Clinical Trials conducted in accordance with the Development Plan or Co-Commercialization Plan;
(iv)review and discuss the Development Reports submitted by each Party;
(v)discuss and approve a regulatory strategy to meet the objectives of the target product profile for Products in the Field in the Territory;
(vi)approve the Indication, overall study design and dosing, as applicable, for any Post-Approval Study for any Product in the Territory;
(vii)prior to initiation of any Phase 3 Clinical Trial for a Product for use in the Field, [****];
(viii)approve (subject to the timing requirement set forth in the last sentence of Section 3.7(b)) the initiation of [****];
(ix)following completion of the Phase 3 Clinical Trial for a Product or Indication in the Field, review and approve the Regulatory Approval strategy (including label strategy, label negotiation strategy and any proposed changes thereto, for use in the Co-Commercialization Territory) therefor;
(x)approve the initial submission of an NDA and major labeling updates for a Product for use in the Field to the FDA;
(xi)if applicable, develop a plan for an Expanded Access Program with respect to Products for use in the Field in the Territory;
(xii)[****]; and
(xiii)perform such other functions as may be appropriate to further the purposes of this Agreement, as directed by the JSC or as expressly specified in this Agreement.
For clarity, the JDC shall have no responsibility or authority other than that expressly set forth in this Agreement.
(d)Meetings. The JDC shall meet at least [****] per Calendar Quarter during the Term (spaced at regular intervals) unless the Parties mutually agree in writing to a different frequency for such meetings. Either Party may also call a special meeting of the JDC (by videoconference or teleconference) by providing at least [****] Business Days’ prior written notice to the other Party in the event such Party reasonably believes that a significant matter must
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be addressed prior to the next scheduled meeting of the JDC, and such Party shall provide the JDC no later than [****] Business Days prior to the special meeting with materials that such Party reasonably believes in good faith are sufficient to enable the JDC members to make an informed decision; provided that for time sensitive matters, a Party may call a special meeting of the JDC on less than [****] Business Days’ prior written notice if the Parties, as confirmed in writing by the Alliance Managers, agree that an issue warrants an expedited meeting. No later than [****] Business Days prior to any meeting of the JDC, the Alliance Managers (or their respective designees) shall prepare and circulate an agenda for such meeting and each Party shall be permitted to propose additional topics to be included on such agenda. The JDC may meet in person, by videoconference or by teleconference. In-person JDC meetings will be held at locations alternately selected by Alnylam and by Roche. Each Party will bear the expense of its respective JDC members’ participation in JDC meetings. Meetings of the JDC shall be effective only if at least one (1) member of each Party is present or participating in such meeting. The Alliance Managers (or their respective designees) will be responsible for the preparation of written minutes of all JDC meetings that reflect material decisions and actions made at such meetings. The Alliance Managers (or their respective designees) will deliver draft meeting minutes to each member of the JDC for their review within [****] Business Days after each JDC meeting. Such minutes will be deemed approved unless one or more members of the JDC objects in writing to the accuracy of such minutes within [****] Business Days after receipt thereof.
(e)Decision-Making. Subject to the remainder of this Section 2.2(e) and Section 2.7, the JDC shall act by consensus, with each Party having, collectively, one (1) vote on behalf of that Party. If the JDC cannot reach consensus on an issue that comes before the JDC and over which the JDC has oversight within [****] days after such issue having come before the JDC, then such matter shall be resolved in accordance with Section 2.5.
2.3Joint Manufacturing Committee.
(a)Purpose; Formation. Within [****] days after the Effective Date, the Parties shall establish a joint manufacturing committee to oversee, and facilitate communication regarding, Manufacturing of clinical and commercial supplies of Products (the “Joint Manufacturing Committee” or “JMC”).
(b)Composition. Each Party shall initially appoint [****] representatives to serve as members of the JMC. Each JMC member shall have appropriate seniority and sufficient expertise in the Manufacturing of pharmaceutical products similar to the Products to make decisions within the scope of the JMC’s responsibility. The JMC may change its size from time to time by mutual written agreement of its members; provided that the JMC shall consist at all times of an equal number of members of each of Alnylam and Roche. Each Party may replace its JMC members at any time upon written notice to the other Party; provided that the applicable replacement has the requisite expertise and seniority for JMC members hereunder. The JMC may invite non-members to participate in the discussions and meetings of the JMC; provided that such participants (i) are subject to confidentiality obligations (whether in writing or by operation of law) consistent with this Agreement, (ii) are involved in or supporting Manufacturing activities related to Products under this Agreement and (iii) for clarity, have no voting rights at the JMC. Each Party shall appoint one of its JMC members as its chairperson, and the JMC shall be co-chaired by such chairpersons. Each Party may replace its chairperson at any time upon
33



written notice to the other Party. The role of each chairperson shall be to convene and preside at meetings of the JMC, but neither chairperson shall have any additional powers or rights beyond those held by the other JMC members.
(c)Specific Responsibilities of the JMC. In addition to its general responsibilities, the Joint Manufacturing Committee shall in particular:
(i)discuss and approve, for submission to the JSC, the Manufacturing Plan (including the Manufacturing Budget) for each Product, including any amendments thereto;
(ii)oversee and coordinate implementation of the Manufacturing Plan and Supply Agreements, including [****] as further described in the Commercial Supply Term Sheet;
(iii)oversee Technology Transfers to Roche with respect to the Manufacture of Products in the Roche Territory in accordance with and subject to the terms hereof and the applicable Technology Transfer Plan;
(iv)oversee the exchange of information between the Parties relating to Manufacturing Changes or other Manufacturing improvements;
(v)[****];
(vi)discuss and approve, for submission to the JSC, amendments to the Manufacturing Plan (including the Manufacturing Budget) with respect to [****];
(vii)review and discuss Manufacturing Reports submitted by each Party;
(viii)discuss and approve, for submission to the JSC, amendments to the Development Plan (including the Development Budget) solely for any CMC Manufacturing Development activities;
(ix)discuss CMOs to be used to Manufacture Product in the Field for the Territory (including applicable contractual terms), [****];
(x)perform such other functions as may be appropriate to further the purposes of this Agreement, as directed by the JSC or as expressly specified in this Agreement.
For clarity, the JMC shall have no responsibility or authority other than that expressly set forth in this Agreement.
(d)Meetings. The JMC shall meet at least [****] time per Calendar Quarter during the Term (spaced at regular intervals) unless the Parties mutually agree in writing to a different frequency for such meetings. Either Party may also call a special meeting of the JMC (by videoconference or teleconference) by providing at least [****] Business Days’ prior written
34



notice to the other Party in the event such Party reasonably believes that a significant matter must be addressed prior to the next scheduled meeting of the JMC, and such Party shall provide the JMC no later than [****] Business Days prior to the special meeting with materials that such Party reasonably believes in good faith are sufficient to enable the JMC members to make an informed decision; provided that for time sensitive matters, a Party may call a special meeting of the JMC on less than [****] Business Days’ prior written notice if the Parties, as confirmed in writing by the Alliance Managers, agree that an issue warrants an expedited meeting. No later than [****] Business Days prior to any meeting of the JMC, the Alliance Managers (or their respective designees) shall prepare and circulate an agenda for such meeting and each Party shall be permitted to propose additional topics to be included on such agenda. The JMC may meet in person, by videoconference or by teleconference. In-person JMC meetings will be held at locations alternately selected by Alnylam and by Roche. Each Party will bear the expense of its respective JMC members’ participation in JMC meetings. Meetings of the JMC shall be effective only if at least one (1) member of each Party is present or participating in such meeting. The Alliance Managers (or their respective designees) will be responsible for the preparation of minutes of all JMC meetings that reflect material decisions made and actions at such meetings. The Alliance Managers (or their respective designees) will deliver draft meeting minutes to each member of the JMC for their review within [****] Business Days after each JMC meeting. Such minutes will be deemed approved unless one or more members of the JMC objects in writing to the accuracy of such minutes within [****] Business Days after receipt thereof.
(e)Decision-Making. Subject to the remainder of this Section 2.3(e) and Section 2.7, the JMC shall act by consensus, with each Party having, collectively, one (1) vote on behalf of that Party. If the JMC cannot reach consensus on an issue that comes before the JMC and over which the JMC has oversight within [****] days after such issue having come before the JMC, then such matter shall be resolved in accordance with Section 2.5.
2.4Joint Commercialization Committee.
(a)Purpose; Formation. By no later than [****] years prior to the anticipated launch of the first Product under this Agreement, the Parties shall establish a joint commercialization committee to oversee and coordinate, and facilitate communication regarding, Commercialization of Products (other than commercial Manufacture of Products, which shall be overseen by the JMC) (the “Joint Commercialization Committee” or “JCC”).
(b)Composition. Each Party shall initially appoint [****] representatives to serve as members of the JCC. Each JCC member shall have appropriate seniority and sufficient expertise in the Commercialization of pharmaceutical products similar to the Products to make decisions within the scope of the JCC’s responsibilities. The JCC may change its size from time to time by mutual written agreement of its members; provided that the JCC shall consist at all times of an equal number of members of each of Alnylam and Roche. Each Party may replace its JCC members at any time upon written notice to the other Party; provided that the applicable replacement has the requisite expertise and seniority for JCC members hereunder. The JCC may invite non-members to participate in the discussions and meetings of the JCC; provided that such participants (i) are subject to confidentiality obligations (whether in writing or by operation of law) consistent with this Agreement, (ii) are involved in or supporting Manufacturing activities related to Products under this Agreement and (iii) for clarity, have no voting rights at the JCC. Each Party shall appoint one of its JCC members as its chairperson, and the JCC shall be co-
35



chaired by such chairpersons. Each Party may replace its chairperson at any time upon written notice to the other Party. The role of each chairperson shall be to convene and preside at meetings of the JCC, but neither chairperson shall have any additional powers or rights beyond those held by the other JCC members.
(c)Specific Responsibilities of the Joint Commercialization Committee. In addition to its general responsibilities, the Joint Commercialization Committee shall in particular:
(i)monitor Commercialization of Products in the Roche Territory and coordinate Commercialization of Products in the Co-Commercialization Territory, in accordance with the Co-Commercialization Plan;
(ii)discuss and approve, for submission to the JSC, the Co-Commercialization Plan (including the Co-Commercialization Budget) sufficiently in advance so that it may be approved at least [****] years prior to the anticipated launch of the first Product for use in the Field in the Co-Commercialization Territory, and any amendments thereto, which amendments shall be discussed, prepared and approved no less than [****] in accordance with and subject to the terms hereof;
(iii)review Commercialization strategies and plans of the Parties, including with respect to the specified activities (and performance thereof) and priorities with respect to the Commercialization of Products in the Field in the Territory;
(iv)review and discuss Commercialization Reports submitted by each Party;
(v)discuss and approve, for submission to the JSC, the PCD Strategy and the Global Brand Strategy for each Product;
(vi)[****];
(vii)discuss and approve the conduct of any Post-Approval Study (subject to Section 2.2(c)(vi)) and discuss the status and results of such Post-Approval Study;
(viii)discuss whether to sell any Product [****]; and
(ix)perform such other functions as may be appropriate to further the purposes of this Agreement, as directed by the JSC or as expressly specified in this Agreement.
The JCC shall have no responsibility or authority other than that expressly set forth in this Agreement.
(d)Meetings. The JCC shall meet at least [****] per Calendar Quarter during the Term (spaced at regular intervals) unless the Parties mutually agree in writing to a different
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frequency for such meetings. Either Party may also call a special meeting of the JCC (by videoconference or teleconference) by providing at least [****] Business Days’ prior written notice to the other Party in the event such Party reasonably believes that a significant matter must be addressed prior to the next scheduled meeting of the JCC, and such Party shall provide the JCC no later than [****] Business Days prior to the special meeting with materials that such Party reasonably believes in good faith are sufficient to enable the JCC members to make an informed decision; provided that for time sensitive matters, a Party may call a special meeting of the JCC on less than [****] Business Days’ prior written notice if the Parties, as confirmed in writing by the Alliance Managers, agree that an issue warrants an expedited meeting. No later than [****] Business Days prior to any meeting of the JCC, the Alliance Managers (or their respective designees) shall prepare and circulate an agenda for such meeting and each Party shall be permitted to propose additional topics to be included on such agenda. The JCC may meet in person, by videoconference or by teleconference. In-person JCC meetings will be held at locations alternately selected by Alnylam and by Roche. Each Party will bear the expense of its respective JCC members’ participation in JCC meetings. Meetings of the JCC shall be effective only if at least one (1) member of each Party is present or participating in such meeting. The Alliance Managers (or their respective designees) will be responsible for the preparation of written minutes of all JCC meetings that reflect material decisions made at such meetings. The Alliance Managers (or their respective designees) will deliver draft meeting minutes to each member of the JCC for their review within [****] Business Days after each JCC meeting. Such minutes will be deemed approved unless one or more members of the JCC objects in writing to the accuracy of such minutes within [****] Business Days after receipt thereof.
(e)Decision-Making. Subject to the remainder of this Section 2.4(e) and Section 2.7, the JCC shall act by consensus, with each Party having, collectively, one (1) vote on behalf of that Party. If the JCC cannot reach consensus on an issue that comes before the JCC and over which the JCC has oversight within [****] days after such issue having come before the JCC, then such matter shall be resolved in accordance with Section 2.5.
2.5Resolution of Committee Disputes.
(a)Within Operating Committees. Subject to the exceptions specified in this Section 2.5, if any Operating Committee fails to reach consensus on a matter properly before such Operating Committee in accordance with Section 2.2(e), 2.3(e) or 2.4(e), as applicable, then any member of such Operating Committee shall have the right to refer such matter to the JSC for resolution by providing the JSC with written notice of such matter within [****] days. Such matter shall be resolved in accordance with Section 2.5(b).
(b)Within The JSC. If a matter is referred by an Operating Committee to the JSC in accordance with Section 2.5, the JSC shall use good faith efforts to promptly address such matter within [****] Business Days after the matter is first referred to the JSC in accordance with Section 2.5 with the goal to resolve such matter within [****] days after the matter is first referred to the JSC in accordance with Section 2.5. If the JSC is unable to reach consensus on (i) any matter referred to the JSC in accordance with Section 2.5 or (ii) any other matter within the scope of the JSC’s express responsibilities hereunder, in each case ((i) and (ii)) within [****] days after such matter having come before the JSC, then either Party’s JSC members shall have the right to submit (by way of such Party’s Alliance Manager) such matter for resolution to the Parties’ Executive Officers within [****] days of such matter being referred to the JSC or
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otherwise arising within the JSC. Such matter shall be resolved in accordance with Section 2.5(c).
(c)Referral To Executive Officers. If a matter is referred by the JSC to the Executive Officers in accordance with Section 2.5(b), each Party shall promptly submit in writing the respective positions of such Party’s JSC members to each Party’s Executive Officers. Such Executive Officers shall use good faith efforts to promptly resolve such matter, and in no event later than [****] Business Days after each Party’s submission of the respective positions of the Parties with respect to such matter to the Executive Officers (which submissions shall be provided within [****] Business Days of the matter first being referred to the Executive Officers under Section 2.5(b)). If the Executive Officers are unable to reach consensus on any matter referred to the Executive Officers in accordance with Section 2.5(b), then such matter shall be resolved in accordance with Section 2.5(d).
(d)Final Decision-Making Authority.
(i)Alnylam Final Decision-Making Authority. Subject to Section 2.5(d)(iii), in the event that the Executive Officers are unable to reach consensus on any matter referred to the Executive Officers in accordance with Section 2.5(b) for a period of [****] Business Days as described in Section 2.5(c), Alnylam shall have final decision-making authority regarding the following matters:
[****].
(ii)Roche Final Decision-Making Authority. Subject to Section 2.5(d)(iii), in the event that the Executive Officers are unable to reach consensus on any matter referred to the Executive Officers in accordance with Section 2.5(b) for a period of [****] Business Days, Roche shall have final decision-making authority regarding the following matters:
[****].
(iii)Mutual Consent. Notwithstanding anything to the contrary herein, unless otherwise agreed by the Parties in writing, in the event that the Executive Officers are unable to reach consensus on any matter referred to the Executive Officers in accordance with Section 2.5(b) for a period of [****] Business Days, no decision shall be made, and the status quo shall be maintained regarding the following matters:
[****].
2.6Appointment of Alliance Managers. Each Party shall appoint an appropriately qualified individual to serve as alliance manager under this Agreement (each such individual, an “Alliance Manager”). Such individuals shall endeavor to assure clear and responsive communication between the Parties and the effective exchange of information, and may serve as a single point of contact for any matters arising under this Agreement. The Alliance Managers shall strive to facilitate resolution of potential and pending issues and
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potential disputes to reach consensus and avert escalation of such issues or potential disputes. Alliance Managers may attend all Committee meetings; provided, however, that the Alliance Managers shall not be members of any Committee established pursuant to this Agreement and shall not have final decision-making authority with respect to any matter. Each Party may change its designated Alliance Manager from time to time upon written notice to the other Party; provided that the applicable replacement has the requisite expertise and seniority for Alliance Managers hereunder.
2.7General Committee Authority. Each Committee shall only have those powers expressly assigned to it in this Article 2 and elsewhere in this Agreement. Notwithstanding anything to the contrary herein, and for clarity, (a) no Committee shall have any power to amend, modify, or waive compliance with the terms of this Agreement and (b) the Parties expressly acknowledge and agree that the decision-making authority granted to Alnylam and Roche pursuant to Section 2.5 shall not be used to authorize a Party to (i) perform any function not delegated to a Committee, (ii) unilaterally modify or amend, or waive its own compliance with, the terms of this Agreement, or (iii) impose any additional material performance obligations on the other Party, other than those for which such other Party is expressly responsible hereunder. Notwithstanding anything to the contrary in this Agreement, neither Party nor any of its Affiliates shall be required to take, or shall be penalized for not taking, any action that is not in compliance with such Party’s ethical business practices and policies or that such Party reasonably believes is not in compliance with Applicable Laws.
2.8Discontinuation of Participation on a Committee. Each Committee shall continue to exist until the Parties mutually agree to disband such Committee, except that the JDC shall disband upon the conclusion of all Development activities hereunder, the JMC will disband following the Technology Transfer Completion Date, and the JCC will disband at the end of the Co-Commercialization Term. If any Committee is disbanded in accordance with the foregoing, all decisions formerly made within or by such Committee shall become a decision that shall be made by the JSC.
2.9Joint Program Team.
(a)Composition; Responsibilities. The Parties shall establish a cross-functional Joint Program Team that is composed of representatives designated by each Party. Representatives must be appropriate for the tasks then being undertaken and the stage of Development, Manufacturing or Commercialization, as the case may be, in terms of their seniority, availability, function in their respective organizations, training and experience. Each Party shall designate one of its representatives as its primary JPT contact. Each Party may replace its representatives from time to time upon written notice to the other Party; provided, however, if a Party’s representative is unable to attend a meeting, such Party may designate a knowledgeable alternate to attend such meeting and perform the functions of such representative. The JPT will, subject to the oversight of the applicable Operating Committee, undertake the following activities: (i) preparing proposed changes, amendments, or other updates to the Development Plan (including the Development Budget) for submission to the JDC (other than those changes, amendments and updates with respect to CMC Manufacturing Development activities, which are addressed below in (iii)), (ii) preparing the regulatory strategy for Products in the Field in the Territory for submission to the JDC, (iii) preparing the Manufacturing Plan
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and any proposed changes, amendments, or other updates to the Manufacturing Plan for submission to the JMC, (iv) preparing any amendment to the Development Plan for CMC Manufacturing Development activities for submission to the JMC, (v) preparing the Co-Commercialization Plan and any proposed changes, amendments, or other updates to the Co-Commercialization Plan for submission to the JCC, (vi) preparing the PCD Strategy and the Global Brand Strategy for each Product, (vii) any other responsibilities delegated to the JPT by an Operating Committee, and (viii) discuss and coordinate any desired or planned publications or presentations (or other public disclosure of any Development Data, or any other results of any Clinical Trial or analysis therefor) relating to Product in the Territory and coordinate publications in either Party’s clinical trials registry. The JPT shall meet at least [****] by audio or video teleconference or as otherwise agreed by such JPT. The JPT shall not have the authority to interpret or otherwise amend this Agreement.
(b)Working Groups. To facilitate the accomplishment of the JPT’s responsibilities, the JPT may agree to establish working groups composed of representatives designated by each Party to interact on a more frequent and shorter-term basis on specific projects and tasks assigned to them by the JPT; provided that the authority of such working groups shall not expand beyond the authority of the JPT. Any such working group shall have no decision-making authority, but may make recommendations to the JPT for review and as applicable, submission to the relevant Operating Committee(s) for their review and as applicable, approval. Following the Effective Date, the JPT shall assess the need to establish any working groups based on the needs of any Collaboration activities.
ARTICLE 3

DEVELOPMENT
3.1Overview. The Parties agree to collaborate with respect to the Development of Products for use in the Field in the Territory as provided in this Article 3 under the direction of the JDC and the JSC (if applicable), and pursuant to a development plan, which shall include the level of detail specified in this Article 3 (the “Development Plan”) to be prepared by the JPT for approval of the JDC and JSC.
3.2Development Plans. The Development of all Products for use in the Field for the Territory shall be conducted pursuant to the comprehensive (including all timelines, objectives and planned tasks for the conduct of Development activities hereunder), worldwide Development Plan which shall describe, for a rolling period of three (3) Calendar Years (broken down by Calendar Quarter for the first Calendar Year, and by Calendar Year for the following two (2) Calendar Years), beginning with the Effective Date (such portion of the Development Plan, the “Short Term Development Plan”):
(a)the proposed overall program of Development for Products for use in the Field in the Territory, including Non-Clinical Studies and Pre-Approval Trials [****], Product label strategy (including the timing of transition of ownership of the core data sheets to Roche), Product label negotiations strategy and proposed Product label content, and regulatory plans and other Regulatory Activities to obtain Regulatory Approval for Products for use in the Field in the Territory;
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(b)the anticipated start dates and Development Data availability dates of such Non-Clinical Studies and Pre-Approval Trials, and anticipated timelines for filing applications for Regulatory Approvals in the Territory;
(c)subject to Section 3.6, the respective roles and responsibilities of each Party (including designation of a Lead Development Party), in connection with such activities; and
(d)the Development Budget.
Together with the Short Term Development Plan, the Development Plan shall include a high-level description of the activities in each Calendar Year subsequent to the period covered by the Short Term Development Plan through the expected first filing of an NDA in the Territory for Products for use in the applicable Indications in the Field (“Long Term Development Plan”).
3.3Development Budget. The Development Plan will include a budget for all Development activities for the Products for use in the Field in the Territory (the “Development Budget”), comprising a detailed rolling budget for the Development activities to be performed under the Development Plan during the [****]; provided that only [****]. Notwithstanding anything to the contrary herein, unless the Parties agree in writing (in each of their sole discretion), in no event shall the amount allocated to a Party under the Development Budget exceed such Party’s share of the [****]. For clarity, no Party shall have any obligation, to incur Development Costs in the Territory in excess of such Party’s share of the [****].
3.4Initial Development Plan. An initial high-level outline of the Development activities currently contemplated as needed to obtain Regulatory Approval in the Territory for the Therapeutic Product as described in the Primary Indication Target Product Profile and for the REVERSIR Product, an initial outline of the Short Term Development Budget, which includes the Development Costs anticipated to be incurred in the conduct of the activities outlined in the Initial Development Plan (other than KARDIA-1 and KARDIA-2) during the three (3) Calendar Year-period beginning on the Effective Date. and an initial outline of the Long Term Development Budget, including high-level, non-binding and preliminary estimates of the long term Development Costs through Regulatory Approval is attached hereto as Exhibit A (the “Initial Development Plan”). Within [****] days after the Effective Date, the JPT shall prepare, for review and approval by the JDC in accordance with Section 2.2(c)(ii), and the JSC in accordance with Section 2.1(c)(ii), a Development Plan (for clarity, including a Short Term Development Plan and a Long Term Development Plan, and a Short Term Development Budget and a Long Term Development Budget), which shall be consistent with the Initial Development Plan (including with the Primary Indication Target Product Profile, clinical development plans and Clinical Trials designs therein) and the initial draft of the Short Term Development Budget, including all timelines set forth therein, and shall set forth the objectives and planned tasks for the conduct of Development activities hereunder, including regulatory strategy. The Initial Development Plan shall be effective from the Effective Date until amended and updated by the JPT and approved by the JDC and JSC in accordance with Section 3.5.
3.5Amendments to the Development Plan.
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(a)Annual Updates. On a Calendar Year basis (no later than [****] days prior to the start of the following Calendar Year), or more often as the Parties may agree upon in writing from time to time, the JSC and the JDC shall review and as it determines appropriate, update and approve any changes, amendments or other updates to the Development Plan prepared by the JPT (including the Development Budget contained therein). For clarity, such updated and amended Development Plan shall reflect any changes, re-prioritization of studies within, reallocation of resources with respect to, and additions to the then-current Development Plan and shall include a Short Term Development Plan (including a Short Term Development Budget) and a Long Term Development Plan (including a Long Term Development Budget). Once approved in accordance with Article 2, the amended Development Plan shall become effective for the applicable period commencing January 1st (or such other date that the JSC may specify) and any amended Development Plan so approved shall supersede the previous Development Plan for the applicable period. If the JSC (or, for clarity, a Party, in accordance with Article 2) decides to discontinue Developing a Product for use in one or more Indications upon recommendation by the JDC, the Development Plan shall terminate with respect to such Product for use in such Indication(s) upon such decision.
(b)Additional Program Plans.
(i)From time to time, during the Term, each Party shall have the right to propose to the JDC that the Development Plan be amended to include (1) any new Indication in the Field (including any Hypertension Indication) for the Product other than the Primary Indication (each, an “Additional Indication”), (2) any additional Non-Clinical Studies or Pre-Approval Trials needed to Develop the Products in an Additional Indication that was previously added to the Development Plan under this Section 3.5 (each, an “Additional Study”), or (3) any Combination Product or any other co-administration of the Product with another pharmaceutical product, in each case (the foregoing (1) through (3)), by submitting a written proposal to the JDC describing the proposed Additional Indication (including its proposed target product profile), Additional Study, or Combination Product (including its proposed target product profile), as applicable, and anticipated costs and timelines with respect thereto, in sufficient detail for the JDC to consider such Additional Indication, Additional Study or Combination Product for inclusion in the Development Plan (each such proposal, an “Additional Program Plan”).
(ii)Following a Party’s submission of an Additional Program Plan to the JDC in accordance with Section 3.5(b)(i), the JDC shall, at its next regularly scheduled meeting, review and determine whether to modify or amend such Additional Program Plan. In the event that the JDC accepts such Additional Program Plan (as modified or amended, as applicable), then the JDC shall recommend such Additional Program Plan (with any modifications or amendments agreed upon by the JDC) for consideration by the JSC for inclusion in the Development Plan by providing the JSC with such Additional Program Plan. Following the JDC’s submission of an Additional Program Plan to the JSC in accordance with this
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Section 3.5(b)(ii), the JSC shall, at its next regularly scheduled meeting, review and determine whether to approve such Additional Program Plan, either in the form provided by the JDC or with such modifications or amendments agreed upon by the JSC. If the JSC approves such Additional Program Plan (with any modifications or amendments agreed upon by the JSC), such Additional Program Plan shall be incorporated in the Development Plan. If the JSC fails to approve the applicable Additional Program Plan, then neither Party may, directly or indirectly, itself or through any Affiliate or Third Party, conduct the applicable Additional Program Plan or any activities therein.
(c)Device Program Plans.
(i)The Parties agree that, as of the Effective Date, the Development Plan for the Therapeutic Product will include Development activities [****]. From time to time, during the Term, each Party shall have the right to propose to the JDC that the Development Plan be amended to include a device, [****], for administration of any Product for use in the Field (each such device, an “Administration Device”) in the Co-Commercialization Territory or in the Roche Territory by submitting a written proposal to the JDC describing the proposed Administration Device and anticipated costs and timelines with respect thereto, in sufficient detail for such Party to consider for inclusion in the Development Plan (each such proposal, a “Device Program Plan”).
(ii)Following a Party’s submission of a Device Program Plan to the JDC in accordance with Section 3.5(c)(i), the JDC shall, at its next regularly scheduled meeting, review and determine whether to modify or amend such Device Program Plan. In the event that the JDC accepts such Device Program Plan (as modified or amended, as applicable), then the JDC shall recommend such Device Program Plan for consideration by the JSC for inclusion in the Development Plan (with any modifications or amendments agreed upon by the JDC) by providing the JSC with such Device Program Plan. Following the JDC’s submission of a Device Program Plan to the JSC in accordance with this Section 3.5(c)(ii), the JSC shall, at its next regularly scheduled meeting, review and determine whether to approve such Device Program Plan, either in the form provided by the JDC or with such modifications or amendments agreed upon by the JSC. If the JSC approves such Device Program Plan (with any modifications or amendments agreed upon by the JSC), such Device Program Plan shall be incorporated in the Development Plan. If the JSC fails to approve the Device Program Plan in accordance with Section 2.5, then (1) for the Co-Commercialization Territory, neither Party may, directly or indirectly, itself or through any Affiliate or Third Party, Develop or Commercialize the applicable Administration Device for the Co-Commercialization Territory and (2) for the Roche Territory, Roche may, at its sole cost and expense, Develop the applicable Administration
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Device for the administration of a Product Developed for use in the Field pursuant to the Development Plan for use solely in the Roche Territory.
3.6Lead Development Party. One Party shall have primary responsibility for the day-to-day operational activities and decision-making with respect to each Non-Clinical Study and Pre-Approval Trial in connection with Development of Products hereunder, as further described in this Section 3.6 (such Party, the “Lead Development Party”).
(a)Alnylam as Lead Development Party. Alnylam shall be the Lead Development Party and shall have primary operational responsibility for leading the conduct and execution of (i) all Non-Clinical Studies and Pre-Approval Trials of the Therapeutic Product for the Hypertension Indications (except as provided in Section 3.6(b)(i)(2) below), including KARDIA-1, KARDIA-2, KARDIA-3, the Initial CVOT Study, and any PIP Trial for the Primary Indication Program, (ii) all Non-Clinical Studies and Pre-Approval Trials of the REVERSIR Product, and (iii) all Non-Clinical Studies and Pre-Approval Trials of Products for any Additional Program Plan for an Additional Indication for which Roche does not exercise its Development Lead Option and for which Alnylam elects to do so by providing written notice to Roche (as described in Section 3.6(b)(ii) below) (each of the foregoing (i) through (iii), an “Alnylam Lead Study”).
(b)Roche as Lead Development Party.
(i)Roche shall be the Lead Development Party and shall have primary operational responsibility for (1) all Non-Clinical Studies and Pre-Approval Trials of any Product for any Additional Program Plan for which Roche exercises its Development Lead Option pursuant to Section 3.6(b)(ii) below, and (2) subject to Section 3.6(a)(i), all Non-Clinical Studies and Pre-Approval Trials of any Product that are conducted primarily to support Regulatory Approval of the applicable Product in the Roche Territory (which shall be deemed to include any Bridging Studies) (each of the foregoing (i) and (ii), a “Roche Lead Study”).
(ii)For a period of [****] Business Days after the date on which the JSC approves the first Additional Program Plan for an Additional Indication, and every Additional Program Plan for an Additional Indication thereafter, Roche shall have the right, but not the obligation, to elect to be the Lead Development Party for such Additional Program Plans (the “Development Lead Option”) by providing Alnylam with written notice of such election during such time period. For clarity, upon providing such notice in accordance with the foregoing, Roche shall become the Lead Development Party for the Non-Clinical Studies and Pre-Approval Trials set forth in the applicable Additional Program Plan. For clarity, in the event that Roche does not provide such notice in accordance with the foregoing, Alnylam shall have the right, but not the obligation, to be the Lead Development Party for the applicable Additional Program Plan by providing Roche with written notice thereof.
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(c)Rights and Responsibilities. The rights and responsibilities of the Lead Development Party shall include managing operationalization of the applicable study, negotiating and entering into contracts with participating clinical sites and investigators (using a clinical trial agreement template previously agreed upon by the Parties in accordance with Section 2.2(c)(iii) that includes terms (including intellectual property ownership, assignment and confidentiality principles) mutually agreed upon that are consistent with this Agreement). The Party that is not the Lead Development Party for a specific Non-Clinical Study or Pre-Approval Trial shall perform those activities related to such study that are allocated to it under the Development Plan, shall reasonably cooperate with the Lead Development Party in the conduct of such study, and shall have the right to provide the Lead Development Party with input and feedback regarding the conduct of such study (which input and feedback the Lead Development Party will consider in good faith).
3.7Transfer of Development Data.
(a)Alnylam will provide Roche with the data included in [****], and any other Development Data generated by or on behalf of Alnylam with respect to [****] to the extent not provided to Roche pursuant to the foregoing; and
(b)without limiting the foregoing clause (a), the Lead Development Party will provide the other Party with a copy of all Development Data generated in any Clinical Trial or other Development activity conducted by the Lead Development Party under the Development Plan, including as set forth on Schedule 3.7(b). For each delivery of [****].
3.8Development Diligence and Standards of Conduct. Each Party shall use Commercially Reasonable Efforts to carry out the tasks assigned to it under the Development Plan. Without limiting the foregoing, each Party shall conduct its activities under the Development Plan in a good scientific manner and in compliance with all Applicable Laws.
3.9Development Records and Reports. Each Party shall maintain complete and accurate records (in the form of technical notebooks or electronic files where appropriate) of all work conducted by it under the Development Plan and all information and Development Data resulting from such work (such records, “Development Records”). Such Development Records, including any electronic files where such information or Development Data may also be contained, shall fully and properly reflect all work done and results achieved in the performance of the Development Plan in sufficient detail and in good scientific manner appropriate for patent and regulatory purposes. Each Party shall have the right to review and copy Development Records maintained by the other Party at reasonable times and to the extent needed for patent or regulatory purposes, to obtain access to originals. Within [****] days after the end of each Calendar Quarter, each Party shall provide the JDC with reports detailing its Development activities under the Development Plan for the immediately preceding Calendar Quarter (each such report, a “Development Report”) and the results of such activities as the JDC requests.
3.10Subcontracts. Each Party may perform any of its Development obligations under this Agreement through one or more subcontractors or consultants in accordance with, and subject to, Section 7.3.
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ARTICLE 4

REGULATORY MATTERS
4.1Overview. The Parties agree to collaborate with respect to the Regulatory Materials (including Regulatory Approvals and regulatory label negotiation strategy) for Products for use in the Field in the Territory as provided in this Agreement (including this Article 4) under the direction of the JDC and the JSC, and pursuant to the Development Plan. The Development Plan shall set forth the regulatory strategy (including the label strategy, and the content of the initially submitted label, and the content of any major labeling updates) for seeking Regulatory Approvals in the Territory of all Products being Developed under the terms of this Agreement.
4.2Lead Regulatory Party. One Party shall have primary responsibility for the day-to-day operational activities and decision-making with respect to certain Regulatory Materials and interactions with the applicable Regulatory Authorities for a Product, as further described in this Section 4.2 (such Party, the “Lead Regulatory Party”).
(a)Alnylam as Lead Regulatory Party.
(i)As between the Parties, Alnylam will be the Lead Regulatory Party, and in furtherance thereof, will be responsible for, (1) preparing and submitting any IND, and any related Regulatory Materials necessary or desirable for conducting any Alnylam Lead Study (and Alnylam will be the sponsor of such Non-Clinical Trial or Clinical Trial); (2) preparing and submitting any NDA and other application for Regulatory Approval, and any other related Regulatory Materials necessary or desirable for obtaining, registering, listing and maintaining Regulatory Approval for any Product for use in the Field in the Co-Commercialization Territory; and (3) performing those day-to-day activities (including corresponding and participating in any meetings with the applicable Regulatory Authorities) required to obtain or maintain any of the foregoing. All such Regulatory Materials will be in Alnylam’s or its designee’s name and owned by Alnylam; provided that (x) Roche shall be responsible for, and hold in its or its Affiliate’s name, the NDC that is affixed to the Product packaging for Product in the Co-Commercialization Territory, and (y) to the extent Applicable Laws or Regulatory Authorities in the relevant jurisdiction require such Regulatory Materials to be in Roche’s name, such Regulatory Materials shall be in Roche’s name to such extent (with Alnylam as the responsible party or owner to the extent permitted by Applicable Laws), and following Alnylam’s reasonable written request, Roche shall cooperate with Alnylam to transfer such Regulatory Materials to Alnylam as and to the extent permitted by Applicable Laws. Notwithstanding anything to the contrary herein, for clarity, Alnylam shall also hold, in its or its Affiliate’s or other designee’s name, one or more NDCs with respect to Products.
(ii)Notwithstanding Section 4.2(b), prior to the Technology Transfer Completion Date, Alnylam will be responsible for authoring the core
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CMC dossier of any Regulatory Materials for the Product for use in the Field and providing Roche with a copy of such core CMC dossier for Roche to include in those Regulatory Materials for which it is responsible pursuant to the terms hereof. Roche shall use such sections [****].
(b)Roche as Lead Regulatory Party. Subject to Section 4.2(a)(ii), as between the Parties, Roche will be the Lead Regulatory Party and in furtherance thereof, will be responsible for (i) preparing and submitting any IND, and any related Regulatory Materials necessary or desirable for conducting any Roche Lead Study (and Roche will be the sponsor of such study); (ii) preparing and submitting any NDA and other application for Regulatory Approval, any related Regulatory Materials necessary or desirable for obtaining, registering, listing and maintaining such Regulatory Approval for any Product for use in the Field in the Roche Territory in accordance with the terms hereof; (iii) holding in its (or its Affiliate’s) name and maintaining the NDC that is affixed to the Product packaging and (iv) performing those day-to-day activities (including corresponding and participating in any meetings with the applicable Regulatory Authorities) required to obtain or maintain any of the foregoing. All such Regulatory Materials will be in Roche’s or its designee’s name and owned by Roche; provided that to the extent Applicable Laws or Regulatory Authorities in the relevant jurisdiction require such Regulatory Materials to be in Alnylam’s name, such Regulatory Materials shall be in Alnylam’s name to such extent (with Roche as the responsible party or owner to the extent permitted by Applicable Laws), and following Roche’s reasonable written request, Alnylam shall cooperate with Roche to transfer such Regulatory Materials to Roche as and to the extent permitted by Applicable Laws.
(c)Additional Lead Regulatory Party Responsibilities.
(i)Submissions to Regulatory Authorities. The Lead Regulatory Party will provide the other Party with a copy of any [****] and to the extent set forth on Schedule 4.2(c)(i), other significant filings or communications, in each case, for submission to any Regulatory Authority (each, a “Major Regulatory Communication”), in each case (the foregoing (1)-(3)), in English and reasonably in advance of submission of such Major Regulatory Communication to the applicable Regulatory Authority and reasonably consider (to the extent reasonably practicable) comments promptly provided by the other Party in good faith. If following such consideration, any disagreement remains between the Parties as to the content of a Major Regulatory Communication, such matter shall be [****].
(ii)Communications with Regulatory Authorities. Within [****] Business Days of receipt, the Lead Regulatory Party shall provide the other Party with copies of all written or electronic Major Regulatory Communications received by it from any Regulatory Authority. To the extent the other Party receives any communication from a Regulatory Authority that addresses, in whole or in part, a study for which it is not the Lead Regulatory Party, such other Party shall provide the Lead Regulatory Party with copies of any such written or electronic communications within [****] Business Days of receipt.
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(iii)Regulatory Meetings. With respect to those matters for which a Lead Regulatory Party is responsible in accordance with the terms hereof, such Lead Regulatory Party shall provide the other Party with reasonable (but no less than [****]) prior written notice of any requested or scheduled meeting with any Regulatory Authority including engagements with OPDP, [****]. Representatives of the Lead Regulatory Party will be the primary spokespeople at any such meeting [****]. The Lead Regulatory Party shall reasonably consider any proposed input for the meeting provided by the other Party in good faith; provided that, for clarity and notwithstanding anything to the contrary herein, the Lead Regulatory Party shall have final decision-making authority in the event of a dispute with respect to the content and information to be discussed at a meeting with a Regulatory Authority.
4.3Right of Reference.
(a)Subject to the terms and conditions of this Agreement (including the licenses granted pursuant to Section 7.1), Alnylam hereby grants to Roche, its Affiliates and Sublicensees a right to cross-reference, file or incorporate by reference any Regulatory Materials (including Regulatory Approvals) for any Product for use in the Field in the Co-Commercialization Territory, and Development Data and other Know-How included or referenced therein or filed in support thereof, to the extent such Regulatory Materials, Development Data and other Know-How are Controlled by Alnylam or any of its Affiliates, solely for Roche or its Related Parties to Develop Products in accordance with the Development Plan, Manufacture Products for use in the Field for the Roche Territory after completion of Technology Transfer by Alnylam pursuant to Section 6.8 and obtain and maintain Regulatory Approvals for Products in the Roche Territory, in each case, to the extent permitted under this Agreement and to otherwise enable Roche to fulfill its obligations with respect to Products hereunder.
(b)Subject to the terms and conditions of this Agreement (including the licenses granted pursuant to Section 7.2), Roche hereby grants to Alnylam, its Affiliates and Sublicensees a right to cross-reference, file or incorporate by reference any Regulatory Materials (including Regulatory Approvals) for any Product, and Development Data and other Know-How included or referenced therein or filed in support thereof, to the extent such Regulatory Materials, Development Data and other Know-How are Controlled by Roche or any of its Affiliates, solely for Alnylam or its Related Parties (or subcontractors acting on their behalf) to Develop Products for use in the Field, Manufacture Products for use in the Territory and obtain and maintain Regulatory Approvals for Products in the Co-Commercialization Territory, in each case, to the extent permitted under this Agreement and to otherwise enable Alnylam to fulfill its obligations with respect to Products hereunder.
(c)Each Party shall duly execute and deliver, or cause to be duly executed and delivered, such instruments and shall do and cause to be done such reasonable acts and things, as may be necessary under, or as the other Party may reasonably request, to effectuate the rights granted under Section 4.3(a) and 4.3(b).
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(d)Neither Party will grant any right of reference or other access to Regulatory Materials (including Regulatory Approvals) or Development Data with respect to Product in the Territory to any Third Party other than as necessary to Related Parties (or subcontractors acting on their behalf) for the Development, Manufacture or Commercialization of Product in the Field in the Territory hereunder, or as otherwise permitted herein.
4.4Product Withdrawals and Recalls.
(a)Co-Commercialization Territory. If either Party becomes aware of any Regulatory Authority that (i) has threatened, initiated or advised any action to remove any Product for use in the Field from the market or (ii) has required or advised Alnylam, Roche, or any of their Related Parties to distribute a “Dear Doctor” letter or its equivalent regarding use of such Product in the Field (collectively, a “Product Action Concern”), in each case ((i) and (ii)) with respect to, or in, the Co-Commercialization Territory, then such Party shall notify the other Party in writing of such event within [****] Business Days (or sooner if required by Applicable Laws) after such Party becomes aware of the Product Action Concern. Following receipt of such written notice, the Parties will discuss and attempt to agree upon whether to recall or withdraw the applicable Product for use in the Field in the Co-Commercialization Territory in response to such Product Action Concern; provided, however, that if the Parties fail to agree within an appropriate time period [****].
(b)Roche Territory. If either Party becomes aware of any Regulatory Authority that raises a Product Action Concern with respect to, or in, the Roche Territory, then such Party shall notify the other Party in writing of such event within [****] Business Days (or sooner if required by Applicable Laws) after such Party becomes aware of the Product Action Concern. Following receipt of such written notice, the Parties will discuss and attempt to agree upon whether to recall or withdraw the applicable Product for use in the Field in the Roche Territory; provided, however, that if the Parties fail to agree within an appropriate time period [****].
4.5Safety Reporting. As soon as practicable after the Effective Date, the Parties shall mutually agree and execute a separate agreement (a “Pharmacovigilance Agreement”) specifying the procedures and timeframes for compliance with Applicable Laws pertaining to safety reporting of the Products and their related activities. The Pharmacovigilance Agreement will set forth each Party’s responsibilities and obligations pertaining to safety collection, assessment and reporting for the Product based on Applicable Laws, including a timeline and procedures for transfer of the global safety database from Alnylam to Roche.
4.6Regulatory Standards of Conduct. Each Party shall make regulatory filings, seek Regulatory Approvals and conduct all other Regulatory Activities under this Agreement (including this Article 4) in compliance with all Applicable Laws, including any Anti-Corruption Laws.
4.7Subcontracts. Each Party may perform any of its Regulatory Activities under this Agreement through one or more Sublicensees or subcontractors in accordance with, and subject to, Section 7.3.
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ARTICLE 5

COMMERCIALIZATION
5.1Overview. The Parties agree to collaborate with respect to the Commercialization of Products for use in the Field in the Co-Commercialization Territory as provided in this Agreement (including this Article 5) under the direction of the JCC and the JSC, and pursuant to the Co-Commercialization Plan and the Global Brand Strategy (each of which shall be prepared by the JPT for approval of JSC following the review and approval by the JCC). Roche shall have the sole right and responsibility for Commercializing Products for use in the Field in the Roche Territory in accordance with the Global Brand Strategy and this Agreement.
5.2Global Brand Strategy. For each Product, the JPT will prepare for review and approval of the JSC (following the review and approval by the JCC), and thereafter update from time to time, in each case with the approval of the JSC) a global brand strategy, including global positioning and global brand elements, for such Product for use in the Field in the Territory (each, a “Global Brand Strategy”).
5.3Co-Commercialization Plan. The Commercialization of all Products for use in the Field for the Co-Commercialization Territory shall be conducted pursuant to a comprehensive, worldwide co-commercialization plan that is consistent with the Global Brand Strategy(ies) (the “Co-Commercialization Plan”) that describes [****] for a rolling period of [****], beginning at [****] (as agreed by the Parties in writing):
(a)pre-launch, launch and subsequent Commercialization activities for such Product in the Co-Commercialization Territory [****];
(b)[****];
(c)the relative responsibilities of the Parties, including which Party will lead the operationalization of any Post-Approval Study (subject to Sections 2.5(d)(i)(6) and 2.5(d)(i)(7)); and
(d)the Co-Commercialization Budget.
5.4Co-Commercialization Budget. In accordance with Section 5.3(d), the Co-Commercialization Plan shall include an overall budget for the anticipated Co-Commercialization Costs for each Product in the Co-Commercialization Territory during the Co-Commercialization Term, which budget shall comprise a rolling budget for the Commercialization activities to be performed under the Co-Commercialization Plan during the following [****] (each such budget, and any revisions thereto, the “Co-Commercialization Budget”). Notwithstanding anything to the contrary hereunder, unless the Parties agree in writing (in each of their sole discretion), in no event shall the amount allocated to a Party under the Co-Commercialization Budget with respect to Therapeutic Product [****]. [****].
5.5Initial Co-Commercialization Plan. At least [****] prior to the anticipated First Commercial Sale of a Product for use in the Field in the Co-Commercialization Territory (as agreed upon by the Parties or such other time period that the Parties agree is sufficiently in advance of such anticipated First Commercial Sale to ensure approval of Co-
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Commercialization Plan prior to start of the Launch Preparation Period for such Product in the Co-Commercialization Territory), the JPT shall prepare, for the JSC’s review and approval (following the review and approval by the JCC), the initial Co-Commercialization Plan for such Product for use in the Field in the Co-Commercialization Territory (including the initial Co-Commercialization Budget, the “Initial Co-Commercialization Plan”). The Initial Co-Commercialization Plan shall be effective from the date it is approved by the JSC or otherwise in accordance with the terms hereof until amended and updated by the JCC and approved by the JSC in accordance with the terms hereof.
5.6Amendments to the Co-Commercialization Plan. On a [****] basis (on timing to be coordinated with Roche’s then typical internal commercial plan review and approval processes used for Roche’s other pharmaceutical products), or more often as the Parties may agree upon in writing from time to time, the JSC shall review and as it determines appropriate, update and approve, any amendments to the Co-Commercialization Plan (including the Co-Commercialization Budget contained therein) as prepared by the JPT and submitted to the JCC for review and approval for further submission to the JSC for approval. [****]. Once approved by the JSC, the amended Co-Commercialization Plan shall become effective for the applicable period and any JSC-approved amended Co-Commercialization Plan shall supersede the previous Co-Commercialization Plan for the applicable period. If the JSC decides to discontinue Commercializing a Product for use in one or more Indications upon recommendation by the JCC, the Co-Commercialization Plan shall terminate with respect to such Product for use in such Indication(s) upon such decision.
5.7Roche Territory. Roche shall at all times conduct Commercialization of Products in the Field in the Roche Territory in accordance with the Global Brand Strategy. Roche shall provide informational updates to the JCC of its plans for Commercialization activities for Products for use in the Roche Territory on an annual basis (no later than once every [****], and shall respond in a timely fashion to any reasonable requests of Alnylam with respect to such plans and Commercialization activities in the Roche Territory. Roche will consider in good faith Alnylam’s input on such plans; provided that for clarity, Roche shall have final decision making authority at the JCC with respect to Commercialization of Products in the Roche Territory in accordance with Section 2.5(d)(ii)(3).
5.8Names and Logos of the Parties. The JPT (for review and approval of the JCC) shall determine the manner in which the Parties will be presented and described in (1) any Promotional Materials, Disease Awareness Materials, Product packaging or other materials related to a particular Product, and the placement of the names and logos of the Parties (provided that all such Promotional Materials, Disease Awareness Materials and Product packaging shall include, with equal prominence, the names and logos of both Parties), in each case to the extent permitted by Applicable Laws and (2) the labeling for the applicable Product approved by the applicable Regulatory Authority.
5.9PCD Strategy. The JPT will prepare a global pricing, contracting and distribution strategy (the “PCD Strategy”) and submit it to the JCC for review and approval prior to Product Regulatory Approval in the Territory. The PCD Strategy will provide [****]. For clarity, if the JCC and JSC cannot agree, [****]. Roche will update the JCC at each regularly scheduled JCC meeting with respect to all such pricing, contracting and distribution activities which Roche shall conduct in a manner consistent with the PCD Strategy in accordance
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with, and subject to, Section 2.5(d). Roche shall also be solely responsible for handling all returns, recalls or withdrawals (as finally determined to be undertaken pursuant to Section 4.4(a)), order processing, invoicing and collection, and receivables using the appropriate Roche (or its Affiliate’s) NDC that is affixed to the Product packaging for Product sales and distribution in the Co-Commercialization Territory. Alnylam shall not accept orders for Products or sell Products for its own account or for Roche’s account, in the Field in the Territory, and if Alnylam receives any order for Products for use in the Field in the Territory, it shall refer such orders to Roche for acceptance or rejection. Roche shall book all sales of Product for use in the Field in the Territory.
5.10Co-Promotion of Products. Alnylam shall participate with Roche in Co-Promoting each Product in the Field in the Co-Commercialization Territory on the terms and conditions set forth in this Agreement and the Co-Promotion Agreement. Beginning upon the start of the Launch Preparation Period for the Product for use in the Field in the Co-Commercialization Territory, the Parties shall (a) negotiate in good faith and execute a co-promotion agreement (the “Co-Promotion Agreement”), which shall set forth the terms and conditions applicable to such Co-Promotion and (b) prepare a marketing and sales plan (the “Co-Promotion Plan”) consistent with the Commercialization Plan for each such Product for use in the Field in the Co-Commercialization Territory, each of which (the foregoing (a) and (b)), shall incorporate the terms set forth on Exhibit B (the “Co-Promotion Term Sheet”) and other applicable relevant co-promotion terms and conditions set forth hereunder, and such other customary or appropriate terms and conditions agreed upon in writing by the Parties. Notwithstanding the foregoing, unless otherwise agreed by the Parties, the Co-Promotion Agreement shall specify that [****]. For clarity, Roche shall not have the right to use its [****] under Section 2.5(d)(ii)(3) to modify the Co-Promotion Term Sheet or finalize or modify the Co-Promotion Agreement.
5.11Promotional Materials and Disease Awareness Materials.
(a)Co-Commercialization Territory.
(i)Creation of Promotional Materials and Disease Awareness Materials. With respect to the Co-Commercialization Territory, as may be more specifically set forth in the Co-Promotion Term Sheet and agreed in the Co-Promotion Agreement, the JPT (for clarity, including representatives of both Parties) will co-create promotional strategies, key claims, key messages and Core Promotional Materials, and either Party may create Promotional Materials consisting of derivative marketing and promotional materials from, and consistent with, the Core Promotional Materials for the Co-Commercialization Territory (“Derivative Promotional Materials”). The Parties will [****]. The JPT (for clarity, including representatives of both Parties) will co-create Disease Awareness Materials for Products for use in the Field for use in the Co-Commercialization Territory consisting of disease awareness and disease education materials to increase knowledge and understanding of a specific disease in the Field and its symptoms and causes (collectively, the “Core Disease Awareness Materials”) and either Party may create Disease Awareness Materials consisting of derivative disease awareness materials
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from, and consistent with, the Core Disease Awareness Materials for the Co-Commercialization Territory (“Derivative Disease Awareness Materials”). The Parties will [****]. All Promotional Materials, Disease Awareness Materials and all related promotional practices, including detailing, distribution of study reprints, interactions with healthcare practitioners, sample distribution, voucher programs, and any payments made to healthcare practitioners to serve as speakers or on advisory boards, shall comply with all Applicable Laws and be consistent with the applicable Product labeling and the Global Brand Strategy. No Promotional Material or Disease Awareness Material will be [****]. All Promotional Materials and Disease Awareness Materials will be used by the Parties [****].
(ii)Approval of Core Promotional Materials and Disease Awareness Materials. Subject to [****] each Core Promotional Material and Core Disease Awareness Material to be utilized by either Party for Products for use in the Field in the Co-Commercialization Territory must be submitted in writing to, and reviewed and approved in writing prior to use by, a joint medical, legal, regulatory review board comprised of an equal number of representatives from each Party who have sufficient expertise and seniority to fulfill their obligations as set forth herein (“Joint MLRB”). The Joint MLRB also shall be responsible for [****]. The Joint MLRB shall meet [****]. The representative members from each Party on the Joint MLRB will have, collectively, [****] vote on behalf of that Party, and all decision-making shall be [****]. If the Joint MLRB cannot [****] with respect to any Core Promotional Materials and Core Disease Awareness Materials, then the matter will be escalated to [****]; provided that the Parties shall [****].
(iii)Approval of Derivative Promotional Materials and Derivative Disease Awareness Materials. The Joint MLRB shall establish processes and procedures [****] to approve [****] Derivative Promotional Materials and Derivative Disease Awareness Materials [****]. If such lead representatives cannot [****] with respect to the approval of any Derivative Promotional Material or Derivative Disease Awareness Material, or reasonably disagree as to whether such Promotional Material is a Derivative Promotional Material or Derivative Disease Awareness Material, then the review and approval of such Promotional Material shall be [****]; provided that the Parties shall [****].
(iv)Omnichannel Infrastructure/Tools and Non-Personal Digital Promotions. Each Party’s responsibilities with respect to Omnichannel infrastructure/tools and Non-Personal Digital Promotions for Product in the Co-Commercialization Territory shall be as specified in the Co-Promotion Term Sheet.
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(v)Use Only of Approved Promotional Materials. For clarity, each Party shall only utilize Promotional Materials and Disease Awareness Materials approved by, or on behalf of the, the Joint MLRB in accordance with clause (ii) or clause (iii) above, in each case in Commercializing the Products for use in the Field in the Co-Commercialization Territory. Neither Party shall, and each Party shall cause its Related Parties (and subcontractors acting on their behalf) to not, change the Promotional Materials or Disease Awareness Materials approved by the Joint MLRB in any way, including by: [****]. Notwithstanding anything to the contrary herein, neither Party shall be required to use any Promotional Materials or Disease Awareness Materials, which, in such Party’s reasonable judgment, are not compliant with Applicable Laws, the PhRMA Code or such Party’s internal compliance policies.
(vi)Discontinued Promotional Materials. If the Joint MLRB informs the Parties that a particular Promotional Material or Disease Awareness Material may no longer be used or distributed in the Co-Commercialization Territory for use with the Product in the Field, each Party shall, and shall cause its sales force and medical liaisons to, cease using and distributing such Promotional Material or Disease Awareness Materials (as applicable) after the no-use date specified by the Joint MLRB. If, as of such no-use date, either Party has any remaining inventory of the applicable Promotional Material or Disease Awareness Material, such Party shall, within [****] days after such date, destroy in accordance with Applicable Laws such Promotional Materials or Disease Awareness Materials (as applicable) in its possession, except for a reasonable, limited number of copies which may be retained for archival purposes or as required by Applicable Laws.
(vii)Submission to Regulatory Authorities. To the extent any Promotional Materials (as approved by, or on behalf of, the MLRB in accordance with this Section 5.11(a)) are required by Applicable Laws to be submitted to any Regulatory Authority in the Co-Commercialization Territory, as between the Parties, [****].
(b)Roche Territory. Roche shall be solely responsible for developing the Promotional Materials and Disease Awareness Materials for use by Roche in the Commercialization of the Products for use in the Field in the Roche Territory. Roche may develop the Promotional Materials and Disease Awareness Materials for the Products for use in the Field in the Roche Territory that are different than the Promotional Materials and Disease Awareness Materials used in the Co-Commercialization Territory; provided that such Promotional Materials, Disease Awareness Materials, and all related promotional practices, including detailing, distribution of study reprints, interactions with healthcare practitioners, sample distribution, voucher programs, and any payments made to healthcare practitioners to serve as speakers or on advisory boards (i) include, with equal prominence, the names and logos of both Parties, (ii) are consistent with the applicable Product labeling, the Global Brand Strategy and the Core Promotional Materials and Core Disease Awareness Materials, as applicable,
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(iii) do not have an adverse effect on the Commercialization activities with respect to any Products in the Co-Commercialization Territory and (iv) notwithstanding anything to the contrary herein, comply with all Applicable Laws.
5.12Medical Information. After the First Commercial Sale of the Product for use in the Field in the Co-Commercialization Territory, Roche shall be responsible for maintaining a medical information call center for responding to medical information requests from healthcare professionals and consumers with respect to Product in the Field in the Territory consistent with its standard practice for such activity. Alnylam and Roche shall discuss and agree upon procedures for responding via medical science liaisons in a consistent manner to medical information requests on Products for use in the Field from healthcare professionals and consumers received after the First Commercial Sale of a Product for use in the Field in the Co-Commercialization Territory.
5.13Medical Affairs Activities.
(a)Co-Commercialization Territory. Subject to the oversight of the JCC and Section 2.5(d), and as further agreed upon by the Parties in the Co-Promotion Agreement, Alnylam and Roche shall each be responsible for undertaking Commercial Medical Affairs Activities for Products for use in the Field in the Co-Commercialization Territory in accordance with the Co-Commercialization Plan upon the start of the Launch Preparation Period. Each of the Parties shall use Commercially Reasonable Efforts to perform Commercial Medical Affairs Activities in support of Products for use in the Field in the Co-Commercialization Territory, and to carry out the tasks assigned to it under the Co-Commercialization Plan in a timely and effective manner and in compliance in all material respects with all Applicable Laws and applicable industry codes, including the PhRMA Code. The number of medical affairs personnel and roles shall be set forth in the Co-Promotion Agreement (which, for clarity, shall be consistent with the terms and conditions set forth in the Co-Promotion Term Sheet).
(b)Roche Territory. Roche shall have the sole right and responsibility for Commercial Medical Affairs Activities in support of the Products for use in the Field in the Roche Territory. Roche shall use Commercially Reasonable Efforts to perform such Commercial Medical Affairs Activities in support of Products for use in the Roche Territory and shall conduct its activities in compliance in all material respects with all Applicable Laws.
5.14Commercialization Diligence and Standards of Conduct. Roche and Alnylam each shall use Commercially Reasonable Efforts to Commercialize each Product for use in the Field in the Co-Commercialization Territory upon Regulatory Approval. Roche shall use Commercially Reasonable Efforts to Commercialize each Product for use in the Field in [****], in each case, following Regulatory Approval for such Product for use in the Field for such country. Without limiting the foregoing, each Party shall use Commercially Reasonable Efforts to carry out the tasks assigned to it under the Co-Commercialization Plan in compliance with all Applicable Laws.
5.15Commercialization Records and Reports. Each Party shall maintain complete and accurate records (in the form of electronic files where appropriate) of all Commercialization activities conducted by such Party in connection with this Agreement
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(including the Co-Commercialization Plan, as applicable) (such records, “Commercialization Records”). Such Commercialization Records, including any electronic files where such information may also be contained, shall fully and properly reflect all work done in connection with the Commercialization of Products under this Agreement (including the Co-Commercialization Plan, applicable) in sufficient detail for regulatory purposes. To the extent needed for regulatory and patent purposes, or as otherwise reasonably necessary for purposes of either Party fulfilling its obligations under this Agreement, each Party shall have the right to review and copy Commercialization Records maintained by the other Party upon reasonable request at reasonable times and to the extent needed for regulatory and patent purposes, to obtain access to originals. Within [****] days after the end of each Calendar Quarter during which a Party performs any Commercialization activities under this Agreement in the Territory, each Party shall provide the JCC with a report or presentation summarizing (at the level of detail normally prepared internally by such Party) its Commercialization activities pursuant to this Agreement (including the Co-Commercialization Plan, as applicable) during the immediately preceding Calendar Quarter (each such report, a “Commercialization Report”) and the results of such activities as the JCC requests.
5.16Subcontracts. Each Party may perform any of its obligations under the Co-Commercialization Plan through one or more Sublicensees or subcontractors in accordance with, and subject to, Section 7.3.
ARTICLE 6

MANUFACTURE AND SUPPLY
6.1Overview. The Parties agree to collaborate with respect to the Manufacture of Products for use in the Field in the Territory as provided in this Agreement (including this Article 6) under the direction of the JMC and the JSC, and pursuant to the Manufacturing Plan.
6.2Manufacturing Plan. The Manufacture of all Products for use in the Field for the Territory shall be conducted pursuant to a comprehensive, worldwide manufacturing plan (each and any revisions thereto, the “Manufacturing Plan”) that describes, for a rolling period of three (3) Calendar Years, beginning with the Effective Date:
(a)[****];
(b)subject to the remainder of this Article 6, the respective roles and responsibilities of each Party;
(c)the Existing Process Technology Transfer Plan and any New Manufacturing Process Technology Transfer Plan, as applicable;
(d)anticipated Manufacturing Changes;
(e)the Manufacturing Budget;
(f)based upon information from then current Development Plan and Commercialization Plan, as applicable, [****]; and
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(g)planned and anticipated CMO supply chain, including with respect to Product packaging and labeling;
provided that, except for any New Manufacturing Process Technology Transfer Plan or anticipated Manufacturing Changes, the Manufacturing Plan (including the Manufacturing Budget) shall only address Manufacturing for Products for use in the Field for use in the Roche Territory until the date upon which Roche is able to Manufacture the first GMP batch of Therapeutic Product and finalization of the relevant documentation related to the Technology Transfer as set forth in Schedule 6.2 (such date, the “Technology Transfer Completion Date”).
6.3Manufacturing Budget.
(a)In accordance with Section 6.2(e), the Manufacturing Plan shall include an overall budget for the anticipated Clinical Supply Costs, Commercial Supply Costs and Other Manufacturing Costs for each Product in the Co-Commercialization Territory, and prior to the Technology Transfer Completion Date, in the Roche Territory, which budget shall comprise a rolling budget for the Manufacturing activities to be performed under the Manufacturing Plan during the following three (3) Calendar Years (broken down by Calendar Quarter for the first Calendar Year), and a forecast of the annual budgets for each subsequent Calendar Year (each such budget, and any revisions thereto, the “Manufacturing Budget”)
(b)A preliminary Manufacturing Budget [****] (the “Preliminary Manufacturing Budget”) and includes an initial outline of the preliminary, non-binding Clinical Supply Costs and Other Manufacturing Costs anticipated to be incurred in the conduct of the activities outlined in the Initial Development Plan (other than KARDIA-1 and KARDIA-2) during the three (3) Calendar Year-period beginning on the Effective Date, as well as a high-level, non-binding and preliminary estimate of the long term Clinical Supply Costs and Other Manufacturing Costs through Regulatory Approval.
6.4Initial Manufacturing Plan. Within [****] days after the Effective Date, the Parties shall develop through the JPT for the JMC’s and JSC’s review and as it determines appropriate, approval of, the initial Manufacturing Plan for the Therapeutic Product for use in the Field in the Territory (including the initial Manufacturing Budget, the “Initial Manufacturing Plan”). The Initial Manufacturing Plan shall be effective from the date it is approved by the JSC or otherwise in accordance with the terms hereof until amended and updated by the JMC and approved by the JSC in accordance with the terms hereof.
6.5Amendments to the Manufacturing Plan. On a [****] basis (no later than [****] days prior to the start of the next following Calendar Year), or more often as the Parties may agree upon in writing from time to time or as necessary to incorporate any Existing Process Technology Transfer Plan, New Manufacturing Process Technology Transfer Plan, Manufacturing Change or other amendment, update or change, the JSC shall review and as it determines appropriate, update and approve, any amendments to the Manufacturing Plan (including the Manufacturing Budget contained therein) as prepared by the JPT and reviewed by the JMC. Once approved by the JSC, the amended Manufacturing Plan shall become effective for the applicable period on the date approved by the JSC (or such other date as the JSC shall specify) and any JSC-approved amended Manufacturing Plan shall supersede the previous
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Manufacturing Plan for the applicable period. If the JSC decides to discontinue Developing or Commercializing a Product upon recommendation by the JDC or JCC, respectively, the Manufacturing of such Product pursuant to such Manufacturing Plan and this Agreement shall terminate, except to the extent necessary to supply any then ongoing Clinical Trial.
6.6API Process Development and Scale-Up. The Parties shall collaborate through the JPT with respect to [****].
6.7Clinical Supply.
(a)Overview. Subject to the remainder of this Article 6, as between the Parties, Alnylam (itself or through an Affiliate or one or more CMOs) shall have the responsibility for Manufacture of Products (for clarity, including REVERSIR Product) for Non-Clinical Studies and Pre-Approval Trials under the Development Plan for the Co-Commercialization Territory, and, prior to the Technology Transfer Completion Date, for the Roche Territory; provided that Alnylam (itself or through an Affiliate or one or more CMOs) shall have the responsibility for Manufacture of REVERSIR Product for Non-Clinical Studies and Pre-Approval Trials under the Development Plan for the Roche Territory. Following the Technology Transfer Completion Date, Roche shall be responsible for Manufacture of Therapeutic Products for (i) Non-Clinical Studies and Pre-Approval Trials under the Development Plan that are primarily to support Regulatory Approval of a Product for use in the Field in the Roche Territory and (ii) any Post-Approval Studies conducted only for the Roche Territory, unless any such Non-Clinical Study, Pre-Approval Trial or Post-Approval Study under (i) or (ii) above have been initiated prior to the Technology Transfer Completion Date, in which case Alnylam shall continue the supply of Therapeutic Product for such Non-Clinical Study, Pre-Approval Trial or Post-Approval Study until Roche can switch to its own supply and Roche shall use Commercially Reasonable Efforts to switch to its own supply for Therapeutic Product for the Roche Territory as soon as practicable following the Technology Transfer Completion Date.
(b)Clinical Supply Agreement. Within [****] following the Effective Date (unless mutually agreed otherwise), the Parties shall negotiate in good faith and enter into a clinical supply agreement (the “Clinical Supply Agreement”) for the Manufacture and supply by Alnylam of quantities of Products for the conduct of Non-Clinical Studies and Pre-Approval Trials of Products under this Agreement in accordance with the Development Plan for the Co-Commercialization Territory and prior to the Technology Transfer Completion Date, for the Roche Territory, and for the Roche Territory following the Technology Transfer Completion Date for REVERSIR Product. The Clinical Supply Agreement shall include terms consistent with the allocation of Clinical Supply Costs as Shared Development Costs, as set forth in Section 8.2 and the Financial Appendix, and such other reasonable and customary terms (including terms identified in the Commercial Supply Term Sheet that expressly refer to applying to the Clinical Supply Agreement) agreed upon by the Parties. For clarity, the Clinical Supply Agreement will contain the terms applicable to Alnylam’s supply of Product for the Roche Lead Studies; provided that Alnylam will have no obligation to supply Product for Roche Lead Studies prior to the execution of the Clinical Supply Agreement.
6.8Technology Transfer.
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(a)Existing Process Technology Transfer. The Parties will, under the oversight of the JMC, and subject to Section 6.9(a), use commercially reasonable efforts to collaborate and complete a one-time transfer by Alnylam (or any of its applicable CMOs) to Roche or [****] designated by Roche of the Know-How within the Alnylam Licensed IP that is necessary, or that Alnylam determines (in good faith) is reasonably useful, to Manufacture drug substance and drug product for the Products for use in the Field using the Manufacturing process in use at such time by Alnylam or its CMO (as applicable) in order for Roche (or such [****]) to Manufacture the Products for clinical and commercial supply in the Roche Territory in accordance with, and subject to, the terms of this Agreement (the “Existing Process Technology Transfer”). For clarity, the Existing Process Technology Transfer will include the transfer of those analytical methods included in the Alnylam Licensed IP that are necessary to ensure quality control and release of the Product. Prior to initiation of the Existing Process Technology Transfer, the Parties, through the JMC, shall submit to the JSC for approval, as part of the Manufacturing Plan, a technology transfer plan, defining the scope, timeline and conditions of the Existing Process Technology Transfer (the “Existing Process Technology Transfer Plan”), which technology transfer shall continue until the Technology Transfer Completion Date. The Parties shall use commercially reasonable efforts to (i) initiate the Existing Process Technology Transfer within [****] after the start of the Launch Preparation Period for such Product, and (ii) complete the Existing Process Technology Transfer as soon as reasonably practicable following initiation in accordance with the foregoing clause (i); provided that if, despite the Parties’ commercially reasonable efforts, the Technology Transfer Completion Date has not occurred as of the First Commercial Sale of Product in the Roche Territory, Alnylam, at Roche’s request, shall Manufacture Product for Commercialization (for clarity, including for Post-Approval Studies) in the Roche Territory until the earlier of: [****]; provided in each case, that the relevant quantities of Product are set forth in Roche’s binding forecast under the applicable Supply Agreement. Following the Technology Transfer Completion Date, Roche shall use commercially reasonable efforts to obtain and maintain the capability to Manufacture Products for use in the Field in the Roche Territory and for which Roche is otherwise responsible hereunder, either itself or through an Affiliate or one or more [****], in sufficient quantities to meet Roche’s Development and Commercialization obligations for the Roche Territory hereunder.
(b)New Manufacturing Process Technology Transfer. In the event that, after the Technology Transfer Completion Date, Alnylam develops an alternative Manufacturing process [****] for Zilebesiran drug substance for use in the Field throughout the Territory (such process, the “New Manufacturing Process”), Alnylam will, reasonably promptly following implementation of such New Manufacturing Process in Alnylam’s, or its Affiliate’s or CMO’s facilities, provide Roche with written notice thereof. Within [****] days after such written notice, Roche shall have the right to provide Alnylam with written notice electing that the Parties will, under the oversight of the JMC, use commercially reasonable efforts to collaborate and complete a one-time transfer by Alnylam (or its applicable CMOs) to Roche or [****] designated by Roche of the Know-How within the Alnylam Licensed IP that is necessary, or that Alnylam determines (in good faith) is reasonably useful, to Manufacture the Products for clinical and commercial supply in the Roche Territory using such New Manufacturing Process in accordance with, and subject to, the terms of this Agreement (the “New Manufacturing Process Technology Transfer” and, together with the Existing Process Technology Transfer, the “Technology Transfers”). Prior to initiation of the New Manufacturing Process Technology Transfer, the Parties, through the JMC, shall submit to the JSC for approval, as part of the
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Manufacturing Plan, a technology transfer plan, defining the scope, timeline and conditions of such technology transfer (the “New Manufacturing Process Technology Transfer Plan”). The Parties shall use commercially reasonable efforts to complete any New Manufacturing Process Technology Transfer within a reasonable time period after the approval of the New Manufacturing Process Technology Transfer Plan.
(c)Additional Studies/Clarifications. For clarity, following the Technology Transfer Completion Date, Roche shall be solely responsible for completing any additional studies or testing required to obtain and maintain any qualifications and other Regulatory Approvals (including manufacturing licenses) from any Regulatory Authorities or other Governmental Authorities necessary to Manufacture a Product for use in the Field in the Roche Territory and for which Roche is otherwise responsible hereunder. Prior to conducting any such additional studies or testing, Roche shall submit a reasonably detailed plan of such studies and testing to the JMC for approval, as part of the Manufacturing Plan. Upon completion of any such studies or testing, Roche shall promptly provide to the JMC copies of reports from any such additional studies or testing (including any clinical study reports, as applicable) in English.
6.9Commercial Supply.
(a)Roche Territory. Following the Technology Transfer Completion Date, Roche will be responsible (either itself or through an Affiliate or one or more [****]) for the Manufacture of all quantities of Therapeutic Product for Commercialization of the Product for use in the Field in the Roche Territory. Alnylam shall Manufacture and supply the REVERSIR Product for Commercialization for use in the Field in the Roche Territory which shall be included in the Commercial Supply Agreement, and the REVERSIR Product will not be part of the Technology Transfer to Roche under Section 6.8.
(b)Co-Commercialization Territory. Alnylam shall be responsible, either itself or through any of its Affiliates or CMOs, for the Manufacture of quantities of Products required for Commercialization (for clarity, including Post-Approval Studies) in the Co-Commercialization Territory pursuant to the Commercial Supply Agreement. No later than [****] years prior to the anticipated date of First Commercial Sale of the Product for use in the Field in the Co-Commercialization Territory (as agreed upon by the Parties through the JCC), the Parties shall negotiate in good faith and enter into a commercial supply agreement (the “Commercial Supply Agreement” and, together with the Clinical Supply Agreement, the “Supply Agreements”), for the Manufacture and supply by or on behalf of Alnylam or any of its Affiliates (including a CMO) to Roche of quantities of Products for Commercialization of the Products for use in the Field in the Co-Commercialization Territory. The Commercial Supply Agreement shall contain those terms set forth on Exhibit D (the “Commercial Supply Term Sheet”), terms consistent with the allocation of Commercial Supply Costs as part of shared Net Profits and Net Losses as set forth in Section 8.3 and the Financial Appendix, and such other reasonable customary terms agreed upon by the Parties in writing. For the avoidance of doubt, the terms and conditions to be included in the Commercial Supply Agreement shall not be subject to Roche’s or Alnylam’s final decision-making authority under Section 2.5(d)(i) or Section 2.5(d)(ii), as applicable.
6.10Manufacturing Changes. Changes to the specifications or the processes or methods used, for the Manufacture of any Product for use in the Field in the Territory (such
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changes, if any, “Manufacturing Changes”) shall be implemented in accordance with this Agreement and the relevant quality agreement to be entered into between the Parties pursuant to the Supply Agreements (each, a “Quality Agreement”).
(a)Required Manufacturing Changes. In the event that a Manufacturing Change is requested or required (i) due to a requirement of a Regulatory Authority, or (ii) as necessary to obtain or maintain Regulatory Approval for a Product for use in the Field (each, a “Required Manufacturing Change”), the Parties shall work together in good faith, and Alnylam, or, in the case of the Roche Territory following the Technology Transfer Completion Date, Roche, as applicable, shall use commercially reasonable efforts to make, or cause the applicable CMO to make, such Manufacturing Change.
(b)Manufacturing Changes Requested by Roche. Subject to Section 6.10(a), if, with respect to the Roche Territory prior to the Technology Transfer Completion Date, or with respect to the Co-Commercialization Territory, Roche requests any Manufacturing Changes (any such requested change, a “Roche-Requested Manufacturing Change”), then Alnylam shall, in consultation with the applicable Alnylam CMO (if any), consider such Roche-Requested Manufacturing Change in good faith, including meeting with Roche upon Roche’s reasonable request to discuss such Roche-Requested Manufacturing Change, and, to the extent Alnylam determines in its sole discretion to make such Roche-Requested Manufacturing Change, shall use commercially reasonable efforts to, or to cause its applicable CMO to, make such Roche-Requested Manufacturing Change.
(c)Other Manufacturing Changes.
(i)Manufacturing Changes by Alnylam. Alnylam (itself or through its Affiliates and CMOs) may make Manufacturing Changes for the Co-Commercialization Territory or Territory (but that do not apply solely to the Manufacture of Products for the Roche Territory) that Alnylam reasonably believes are needed to support the development or implementation of any (1) new dosage, form or formulation of any Product or (2) process development, process improvement, manufacturing lifecycle management, or other Manufacturing activities to improve the yield, efficiency or proprietary nature of the Manufacturing process for any Product (each, an “Alnylam Manufacturing Change”); provided that (x) to the extent an Alnylam Manufacturing Change would require a filing with a Regulatory Authority, Alnylam shall propose such Alnylam Manufacturing Changes to the JMC for its review and approval, and (y) any such proposed Alnylam Manufacturing Changes that are not covered by the foregoing clause (x) shall be discussed by the JPT (but, for clarity, shall not be subject to any escalation to, or decision-making of, the JMC or JSC). Alnylam shall not make any such Alnylam Manufacturing Changes covered by clause (x) until approved in accordance with Article 2. For clarity, and notwithstanding anything to the contrary herein, “Alnylam Manufacturing Changes” shall not include Required Manufacturing Changes.
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(ii)Manufacturing Changes by Roche. Following the Technology Transfer Completion Date, Roche (itself or through its Affiliates and [****]) may make Manufacturing Changes for the Roche Territory that Roche reasonably believes are needed to support the development or implementation of any (1) new dosage, form or formulation of any Product or (2) process development, process improvement, manufacturing lifecycle management, or other Manufacturing activities to improve the yield, efficiency or proprietary nature of the Manufacturing process for any Product (each, a “Roche Manufacturing Change”); provided that (x) to the extent a Roche Manufacturing Change would require a filing with a Regulatory Authority, Roche shall propose such Roche Manufacturing Changes to the JMC for its review and approval, and (y) any such proposed Roche Manufacturing Changes that are not covered by the foregoing clause (x) shall be discussed by the JPT (but, for clarity, shall not be subject to any escalation to, or decision-making of, the JMC or JSC). For clarity, and notwithstanding anything to the contrary herein, “Roche Manufacturing Changes” shall not include Required Manufacturing Changes.
(d)Change Control Procedures. Alnylam shall have, and shall cause its CMOs to have, a change control procedure with respect to the Manufacturing of the Product in connection with this Agreement, which procedure shall be operated and maintained in accordance with the terms of the applicable Quality Agreement.
6.11Manufacturing Diligence and Standards of Conduct. Each Party shall use Commercially Reasonable Efforts to conduct its activities under the Manufacturing Plan and shall conduct such activities in a good scientific manner and in compliance with all Applicable Laws.
6.12Manufacturing Records and Reports. Each Party shall maintain complete and accurate records (in the form of technical notebooks or electronic files where appropriate) of all work conducted by or on behalf of such Party or any of its Affiliates (including any applicable CMOs) with respect to Manufacturing Products and all information resulting from such work (such records, “Manufacturing Records”). Such Manufacturing Records, including any electronic files where such information may also be contained, shall fully and properly reflect all work done and results achieved in the performance of the Manufacturing Plan in sufficient detail and in good scientific manner appropriate for patent and regulatory purposes. Each Party shall have the right to review and copy Manufacturing Records maintained by the other Party at reasonable times following reasonable notice and to the extent needed for patent or regulatory purposes, to obtain access to originals. Within [****] days after the end of each Calendar Quarter during which a Party performs any Manufacturing activities under the Manufacturing Plan, such Party shall provide the JMC with a report detailing its Manufacturing activities under the Manufacturing Plan for the immediately preceding Calendar Quarter (each such report, a “Manufacturing Report”) and the results of such activities as the JMC requests.
6.13Subcontracts. Each Party may perform any of its manufacturing and supply obligations under the Manufacturing Plan or Supply Agreements through its Affiliates or
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one or more CMOs in accordance with, and subject to, Section 7.3; provided that in the case of [****].
ARTICLE 7

LICENSES AND EXCLUSIVITY
7.1License to Roche under Alnylam Licensed IP. Subject to the terms and conditions of this Agreement, Alnylam hereby grants, and shall cause its Affiliates to grant, to Roche:
(a)an exclusive (even as to Alnylam and its Affiliates), royalty-bearing, sublicensable (solely to the extent permitted in accordance with Section 7.3) license, under the Alnylam Licensed IP solely to Commercialize Products solely for use in the Field in the Roche Territory (for clarity, the Commercialization of Products under this license grant shall be subject to the Global Brand Strategy);
(b)a co-exclusive (with Alnylam and its Affiliates), sublicensable (solely to the extent permitted in accordance with Section 7.3) license under the Alnylam Licensed IP solely to (i) Develop Products solely for use in the Field in the Territory in accordance with the Development Plan and (ii) Commercialize Products solely for use in the Field in the Co-Commercialization Territory. For clarity, the Development and Commercialization of Product under this license grant shall be subject to the terms and conditions of this Agreement including the Co-Commercialization Plan, the Co-Promotion Agreement and the Global Brand Strategy; and
(c)a non-exclusive, sublicensable (solely to the extent permitted in accordance with Section 7.3) license under the Alnylam Licensed IP solely to Manufacture Products in the Territory solely for permitted Development and Commercialization of such Products for use in the Field in the Roche Territory following Technology Transfer to Roche in accordance with Section 6.8.
(d)For clarity, the licenses granted to Roche under this Section 7.1 do not include any licenses or other rights to (i) any Know-How or Patent Rights related to (1) any active pharmaceutical ingredient other than Zilebesiran and REVERSIR, or (2) any siRNA, MicroRNA, MicroRNA antagonist, MicroRNA Mimic, or single or double-stranded oligonucleotide Controlled by Alnylam or any of its Affiliates as of the Effective Date or during the Term that is Directed to, or otherwise modulates the expression of, a target other than AGT or (iii) any Alnylam Excluded IP. Notwithstanding anything to the contrary herein, Alnylam and its Related Parties retain the right to use the Alnylam Licensed IP for any research and development purpose, other than clinically Developing, Commercializing, or Manufacturing for clinical Development or Commercialization, any Products for use in the Field in the Territory.
7.2Licenses to Alnylam under Roche Licensed IP. Subject to the terms and conditions of this Agreement, Roche hereby grants, and shall cause its Affiliates to grant, to Alnylam:
(a)a co-exclusive (with Roche and its Affiliates), sublicensable (solely to the extent permitted in accordance with Section 7.3), royalty-free license, under Roche Licensed IP solely to (i) Develop Products solely for use in the Field in the Territory in accordance with the
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Development Plan and (ii) Commercialize Products solely for use in the Field in the Co-Commercialization Territory (for clarity, the Development and Commercialization of Product under such license shall be subject to the terms and conditions of this Agreement including the Co-Commercialization Plan, the Co-Promotion Agreement and the Global Brand Strategy);
(b)a non-exclusive, sublicensable (solely to the extent permitted in accordance with Section 7.3) royalty-free license under the Roche Licensed IP to Manufacture Products in the Territory solely for use in the Field for Alnylam to fulfill its supply obligations with respect to Product under this Agreement; and
(c)if and solely to the extent permitted under Section 7.3(b), an exclusive, sublicensable (solely to the extent permitted in accordance with Section 7.3) license under the Roche Licensed IP solely to Develop and Commercialize Products solely for use in the Field in Japan.
(d)For clarity, the foregoing licenses granted to Alnylam do not include any rights to any Know-How or Patent Rights related to any (i) active pharmaceutical ingredient other than Zilebesiran and REVERSIR, (ii) any siRNA, MicroRNA, Micro RNA antagonist, MicroRNA Mimic, or single or double-stranded oligonucleotide Controlled by Roche or any of its Affiliates as of the Effective Date or during the Term that is Directed to, or otherwise modulates the expression of, a target other than AGT or (iii) any Roche Excluded IP. Notwithstanding anything to the contrary herein, Roche and its Related Parties retain the right to use the Roche Licensed IP for any research and development purpose, other than clinically Developing, Commercializing, or Manufacturing for clinical Development or Commercialization, any Products for use in the Field in the Territory.
7.3Sublicensing and Subcontracting.
(a)Scope of Permissible Sublicensing.
(i)By Roche. The licenses granted by Alnylam to Roche under Section 7.1 may be sublicensed by Roche solely following receipt of Alnylam’s prior written consent (not to be unreasonably withheld, conditioned or delayed); provided that such consent shall not be required for sublicenses granted by Roche to: [****].
(ii)By Alnylam. The licenses granted by Roche to Alnylam under Section 7.2 may be sublicensed by Alnylam solely following receipt of Roche’s prior written consent (not to be unreasonably withheld, conditioned or delayed); provided that (1) such consent shall not be required for sublicenses granted by Alnylam to [****].
(b)Sublicense to Chugai for Japan.
(i)Roche shall use commercially reasonable efforts to notify and engage Chugai as a Sublicensee with respect to performance of Roche’s obligations hereunder in Japan as soon as reasonably practicable following the Effective Date.
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(ii)Without limiting the foregoing Section 7.3(b)(i), in the event that Chugai [****], then Japan shall cease to be included in the Roche Territory as of the earlier of [****].
(iii)Notwithstanding anything to the contrary herein, and for clarity, commencing on the earlier of [****], in each case only if there is not a Chugai Sublicense Agreement prior to such time period, (A) Alnylam shall be permitted, itself or through a Related Party or subcontractor, to Develop, Manufacture, and Commercialize Products in Japan, (B) Alnylam shall have final decision-making authority with respect to the Development, Manufacture, Commercialization and other exploitation of Products for Japan, (C) Alnylam shall make Royalty Payments to Roche on Net Sales of Products in Japan [****], (D) Japan shall cease to be included in the Roche Territory for purposes of this Agreement, and (E) Roche shall not be obligated to make any Royalty Payments, Development Milestone Payments or Sales Milestone Payments related to Japan to Alnylam, and Alnylam shall be responsible for all costs associated with the Development, Manufacture and Commercialization of Product for Japan. In addition, the Parties agree that during the period prior to the earlier of the preceding clauses (1) and (2), Alnylam shall have the right to conduct Development activities for the Therapeutic Product in Japan as needed to meet the timelines in the Initial Development Plan and during such time any costs associated with such Development activities in Japan shall be Alnylam’s sole responsibility; provided that if Chugai shall enter into a Chugai Sublicense Agreement with Roche [****], then Roche shall reimburse Alnylam for such costs.
(iv)Subject in all cases to Section 7.3(b)(iii), and without limiting the Parties’ rights and obligations hereunder, if Japan is no longer part of the Roche Territory in accordance with this Section 7.3, then the Parties shall reasonably cooperate in good faith to establish necessary and appropriate procedures to coordinate the Development, Manufacturing and Commercialization of Product in the Field in Japan with the Development, Manufacturing and Commercialization of Product in the Field in the Co-Commercialization Territory and the Roche Territory.
(c)Sublicenses.
(i)Sublicense to an Affiliate. With respect to an agreement under which a Party grants a sublicense to an Affiliate (or, in the case of Roche to Chugai under a Chugai Sublicense Agreement pursuant to Section 7.3(b)) under any license granted to such Party pursuant to Section 7.1 or Section 7.2 (each, an “Affiliate Sublicense Agreement”), such Party shall ensure that all of the applicable terms and conditions of this Agreement shall apply to such Affiliate (or Chugai as applicable) to the same extent as they apply to such Party for all applicable purposes; provided that in accordance with [****]. The grant of any sublicense in compliance with this Section 7.3
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shall not relieve the granting Party of its obligations under this Agreement, and as between Alnylam and Roche, the Party granting such sublicense assumes full responsibility for the performance of all obligations to be performed by, and observance of all terms so imposed on, such Affiliate (or Chugai as applicable). For clarity, if a Sublicensee ceases to be an Affiliate, then any Affiliate Sublicense Agreements with such sublicensee shall automatically become, and shall be subject to the terms of this Agreement applicable to, Third Party Sublicense Agreements as set forth in Section 7.3(c)(ii), and shall thereafter not constitute an Affiliate Sublicense Agreement; provided that such Sublicensee and the corresponding Sublicense Agreement comply with the terms and conditions set forth herein with respect to Sublicensees that are Third Parties and Third Party Sublicense Agreements (including that any consent required to be obtained in connection with such Third Party Sublicensee and Third Party Sublicense Agreement has been granted by the other Party). For clarity, if such Sublicensee (as a Third Party Sublicensee) or the corresponding Sublicense Agreement does not comply with the terms hereof as described in the foregoing sentence, such Sublicense Agreement shall automatically terminate upon the applicable Sublicensee ceasing to be an Affiliate.
(ii)Sublicenses to a Third Party. Each Party shall, in each agreement under which it grants a sublicense to a Third Party under a license granted to such Party pursuant to Section 7.1 or 7.2 (each, a “Third Party Sublicense Agreement” and, together with any Affiliate Sublicense Agreement, a “Sublicense Agreement”):
(1)ensure that all of the terms and conditions applicable to a Sublicensee of this Agreement apply to the Third Party in the applicable Third Party Sublicense Agreement; provided that [****]; and
(2)require such Sublicensee to provide the following to such Party: (A)  the assignment and transfer of sponsorship and ownership and all Regulatory Materials held or possessed by such Sublicensee with respect to a Product, as applicable; (B) the assignment of, or a freely sublicensable exclusive license to, all intellectual property Controlled by such Sublicensee, as the case may be, that Covers a Product or its respective Development, Manufacture, Commercialization or other exploitation that was created by or on behalf of such Sublicensee during the exercise of its rights or fulfillment of its obligations pursuant to such Sublicense Agreement, (C) the assignment and transfer of ownership and possession of any Product Trademarks created during the exercise of such Sublicensee’s rights or fulfillment of its obligations pursuant to such Sublicense Agreement and all goodwill associated therewith, and (D) confidentiality and non-use obligations
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regarding Confidential Information, that are at least as protective as those undertaken by the Parties pursuant to Article 12 hereof.
(iii)Each Sublicense Agreement shall be subject to the applicable terms and conditions of this Agreement and any applicable Third Party License sublicensed to the Sublicensee. Any Sublicense Agreement entered into by a Party with a Third Party shall be in writing. A copy of any Sublicense Agreement executed by a Party with a Third Party shall be provided to the other Party within [****] days after its execution; provided that the terms of any such Sublicense Agreement may be redacted to the extent not pertinent to an understanding of a Party’s obligations or benefits under this Agreement. Each Party shall remain responsible for the work allocated to, and payment to, its Sublicensees to the same extent it would if it were doing such work itself.
(d)Subcontractors.
(i)Each Party shall have the right to subcontract the work performed by it under this Agreement without the prior approval of the other Party; provided that (i) Roche shall only be able to subcontract its Manufacturing obligations under this Agreement with respect to Product for the Roche Territory solely following receipt of Alnylam’s prior written consent (not to be unreasonably withheld, conditioned or delayed) or [****], and (ii) (A) each Party shall obtain the prior written consent of the other Party to [****]; and (B) the Parties shall discuss though the JPT, any of its planned subcontracting out of any of its field force obligations under the Co-Commercialization Plan. Any subcontract entered into by either Party shall be consistent with the applicable terms and conditions of this Agreement, and such Party shall be responsible for the actions or omissions of its subcontractors in performing work hereunder and the compliance of its subcontractors with the terms and conditions of this Agreement. Each Party shall remain responsible for the work allocated to, and payment to, its subcontractors to the same extent it would if it were doing such work itself.
(ii)If Roche engages the services of any Roche Excluded Affiliate to conduct Collaboration activities on behalf of Roche under the Agreement, such Roche Excluded Affiliate will be considered a subcontractor for the purposes of this Section 7.3(d) [****].
7.4[****].
7.5No Implied Licenses. Except to the extent expressly provided hereunder, each Party reserves its and its Affiliates’ rights in and to all intellectual property rights that is not expressly licensed or otherwise granted hereunder. Without limiting the foregoing, this Agreement and the licenses and rights granted herein do not, and shall not be construed to, confer any rights upon either Party or its Related Parties by implication, estoppel, or otherwise as to any of the other Party’s or its Affiliates’ intellectual property rights, except to the extent expressly set forth herein.
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7.6Third Party Licenses.
(a)The Parties acknowledge that, during the Term, it may be beneficial to obtain a Third Party License and in furtherance thereof the Parties agree that:
(i)With respect to Third Party intellectual property that is necessary or useful to Develop, Manufacture, Commercialize or otherwise exploit Products for use in the Field in the Co-Commercialization Territory, as soon as reasonably practicable following either Party’s written request, the Parties shall discuss whether to enter into a Third Party License with respect thereto; provided that in the event that the Parties fail to agree on whether to enter into any Third Party License [****]; and
(ii)with respect to Third Party intellectual property that is necessary or useful to Develop, Manufacture, Commercialize or otherwise exploit Products for use in the Field solely in the Roche Territory, as soon as reasonably practicable following either Party’s written request, the Parties shall discuss whether to enter into a Third Party License with respect thereto [****].
(b)The Parties agree that the payments to any Third Party in respect of any Third Party License entered into in accordance with Section 7.6(a) shall be deemed a “Third Party Payment” and subject to this Section 7.6(b). If such Third Party License is necessary or useful for Development, Manufacture, Commercialization or other exploitation of a Product [****].
7.7Exclusive Efforts. Except to the extent (a) permitted pursuant to this Section 7.7 or Section 7.8, or (b) necessary for a Party to satisfy its obligations or exercise its rights with respect to Product under this Agreement, in each case ((a) - (b)), with respect to the Field in the Territory for the Covered Indications [****]. In the event that a Governmental Authority of competent jurisdiction determines that the restrictions under this Section 7.7 are too broad or otherwise unreasonable under any Applicable Laws, including with respect to scope, duration or geographic territory, the court is hereby requested and authorized by the Parties to revise the foregoing restriction to include the maximum restrictions within such scope, duration or geographic territory allowable under Applicable Laws. Notwithstanding the foregoing, each of the Parties acknowledges and agrees that this Section 7.7 has been negotiated by the Parties and that the scope, duration and geographic territory of the restrictions herein are reasonable in light of the circumstances pertaining to the Parties. For clarity, the Parties intend that the foregoing covenants should not extend to diagnostic products or services, software, or clinical trial services provided to Third Parties in the ordinary course of a party’s business that are independent of, and do not involve the use of (x) in the case of Roche, any Alnylam Licensed IP or Alnylam’s Confidential Information, or (y) in the case of Alnylam, any Roche Licensed IP or Roche’s Confidential Information. For purposes of this Section 7.7, [****].
7.8Change of Control and Other Acquisition Transactions.
(a)Notice. If [****],
(i)there is a Change of Control of a Party (such Party, the “Acquired Party”) with a Third Party (the “Acquiror”) and as of the effective date of
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such Change of Control, such Third Party or any of its Affiliates (other than the Acquired Party or the Acquired Party’s Affiliates immediately prior to the closing of such Change of Control) is engaged, directly or indirectly, in any activities with respect to an AGT EMO in the Field in the Territory that, if carried out by the Acquired Party, would be a breach of such Party’s obligations under Section 7.7 (such activities, an “AGT EMO Program”), or
(ii)a Party (such Party, the “Acquiring Party”) or any of its Affiliates (including in the case of Roche, any Roche Excluded Affiliate) acquires a Third Party (other than a Roche Excluded Affiliate), or a Third Party’s assets (other than a Roche Excluded Affiliate's), and beginning as of the closing of such transaction, the Acquiring Party or any of its Affiliates is engaged in a [****] (each transaction described in the foregoing subsections (i) and (ii), an “AGT EMO Acquisition”),
(iii)then, in each case (the foregoing (i) and (ii)), the Acquired Party or Acquiring Party, as applicable, shall provide the other Party (the “Non-Acquiring Party”) with written notice thereof within [****] Business Days after the closing of such AGT EMO Acquisition and shall comply with the remainder of this Section 7.8.
(b)Permitted Alternatives. By the later of (i) [****] months after the closing of any AGT EMO Acquisition, and (ii) [****], the Acquired Party or Acquiring Party, as applicable, shall, if not prohibited by Applicable Laws, comply with the following (for clarity, the option selected to be in the sole discretion of the Acquired Party or Acquiring Party; provided that such Person complies with the terms and conditions thereof):
(i)use commercially reasonable efforts to divest (whether by sale, license or otherwise) its rights in [****] pursuant to Section 7.8(c); provided that if such divestiture does not occur in accordance with, and subject to, Section 7.8(c), such Acquired Party or Acquiring Party shall comply with option (iii) below;
(ii)if the applicable Party is the Acquired Party (and not the Acquiring Party), elect to continue the Development, Manufacture and Commercialization of the AGT EMO to which the AGT EMO Program relates in accordance with, and subject to, Section 7.8(d); or
(iii)only if (x) the Acquired Party’s or the Acquiring Party’s efforts (as applicable) to divest under the foregoing clause (ii) are unsuccessful, (y) to the extent permitted under Section 7.8(d), the Acquired Party or Acquiring Party, as applicable, does not elect to continue the Development, Manufacture and Commercialization of the AGT EMO to which the AGT EMO Program relates in accordance with, and subject to, Section 7.8(d) or (z) the Acquired Party or the Acquiring Party, as applicable, determines in good faith those options are [****].
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(c)Divestiture.
(i)If the Acquired Party or Acquiring Party, as applicable, chooses to divest (whether by sale, license or otherwise) its rights in the AGT EMO in the Field in the Territory to which the AGT EMO Program relates to a Third Party, in accordance with Section 7.8(b)(i), the Acquired Party or Acquiring Party, as applicable, shall notify the Non-Acquiring Party of such desire in writing within [****] days of the closing of the applicable AGT EMO Acquisition. In the event that the Acquired Party or Acquiring Party, as applicable, provides such notice to the Non-Acquiring Party, the Acquired Party or Acquiring Party, as applicable, shall divest such AGT EMO in the Field in the Territory to a Third Party (other than, for clarity, a Roche Excluded Affiliate) within [****] days after such notice; provided that if the Acquired Party or Acquiring Party, as applicable, fails to complete such divestiture within such [****]-day period, but can demonstrate to the Non-Acquiring Party’s reasonable satisfaction that it used good faith to effect such divestiture on commercially reasonable terms within such [****]-day period, then, unless otherwise required by any Applicable Laws, such [****]-day period shall be extended for such additional reasonable period thereafter as is necessary to enable such AGT EMO, as applicable, to be divested, not to exceed an additional [****] days; provided, however, that such period shall be extended for such period as is necessary to obtain any governmental or regulatory approvals required to complete such divestiture, and provided, further, that the Acquired Party or Acquiring Party, as applicable, is using good faith efforts to obtain such approvals (such period, the “Divestment Period”).
(ii)In the event that the Acquired Party or Acquiring Party, as applicable, does not complete the applicable divestiture within the Divestment Period, then (1) the Acquired Party or Acquiring Party, as applicable, shall comply with Section 7.8(b)(iii).
(iii)Any divestiture under this Section 7.8(c) shall not permit the Acquired Party or Acquiring Party, as applicable, or its Affiliates, to [****]. If the Acquired Party or Acquiring Party, as applicable, elects to divest the applicable AGT EMO in the Field in the Territory, the Acquired Party or Acquiring Party, as applicable, shall not be precluded under Section 7.7 from conducting any activities (either directly, or with or through any Third Party) with respect to such AGT EMO during the applicable Divestment Period; provided no Confidential Information of the Non-Acquiring Party and no other information (to the extent it is not yet generally available to the public) generated under this Agreement is used in connection with such AGT EMO Program.
(d)Continued Competing Program; Separation for Collaboration Activities. To the extent not prohibited by Applicable Laws, either Party as the Acquired Party in an AGT EMO Acquisition shall have the right to elect to continue the Development, Manufacture or
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Commercialization of the AGT EMO to which the AGT EMO Program relates, and in the event the Acquired Party makes such election then, (1) such Party shall notify the Non-Acquiring Party in writing of such election [****].
(e)Notwithstanding the foregoing, the foregoing restrictions will not prevent senior management or members of the board of directors of the Acquiror from receiving financial or other information about activities under this Agreement; provided that such employees or members of the board of directors do not perform any day-to-day responsibilities in connection with this Agreement or for the AGT EMO Program and that such employees and members of the board of directors understand and comply with the Acquired Party’s obligations of confidentiality and non-use as set forth herein. Notwithstanding anything to the contrary in this Agreement, following the closing of any Change of Control, the Parties agree that (1) the Non-Acquiring Party shall not obtain rights or access to any Patent Rights or Know-How Controlled by the Acquiror and its Pre-Existing Affiliates and (2) the Acquiror and its Affiliates (other than the Acquired Party and its Pre-Existing Affiliates) shall not obtain rights or access to the Patent Rights or Know-How Controlled by the Non-Acquiring Party or any of its Affiliates pursuant to this Agreement; provided that clause (1) of this Section 7.8(e) shall not apply to any Patent Rights or Know-How Controlled by the Acquiror or any of its Affiliates to the extent such Patent Right or Know-How (A) is used by or on behalf of the Acquired Party or any of its Affiliates in performing any of the Acquired Party’s obligations under this Agreement or (B) is incorporated into any Product by or on behalf of the Acquired Party or any of its Affiliates. Without limiting the foregoing, the Non-Acquiring Party’s rights in all Patent Rights and Know-How Controlled by the Acquired Party or any of its Pre-Existing Affiliates or any of their respective successors, shall remain licensed to such Non-Acquiring Party after the date of the closing of such Change of Control in accordance with and subject to the terms and conditions of this Agreement and shall not be affected in any manner by virtue of such Change of Control.
(f)Exceptions. Notwithstanding the foregoing Sections 7.7 and 7.8, [****] Alnylam and its Affiliates and Roche and its Affiliates shall each be permitted to, directly or indirectly, whether by itself or with or through a Third Party, conduct pre-clinical research activities and non-clinical Development of AGT EMOs for use in the Field in the Territory, and Manufacturing therefor.
ARTICLE 8

FINANCIALS
8.1Upfront Payment. No later than [****] days after the Effective Date, and receipt of an invoice therefor from Alnylam, Roche shall pay, or cause to be paid, to Alnylam a nonrefundable, non-creditable fee of three hundred ten million dollars ($310,000,000).
8.2Development Costs.
(a)Development Costs Sharing for Territory. The Parties shall share Shared Development Costs incurred for Product for the Territory in the performance of the Development Plan and in accordance with the Development Budget as determined in accordance with Schedule 8.2(a) (the “Financial Appendix”) and the [****].
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(b)[****].
8.3Profit and Loss Sharing in the Co-Commercialization Territory. The Parties shall share Net Profits and Net Losses with respect to each Product that is Commercialized for use in the Field for the Co-Commercialization Territory during the Co-Commercialization Term as determined in accordance with the Financial Appendix. For clarity, Alnylam shall have no right to share revenue, and no obligation to bear any Roche Commercialization Costs, and Alnylam shall instead be entitled to receive from Roche the applicable payments pursuant to Sections 8.5, 8.6, and 8.7.
8.4Manufacturing Related Costs.
(a)Technology Transfer Costs. Roche shall be responsible for one hundred percent (100%) of Technology Transfer Costs. Roche shall pay, or cause to be paid, Technology Transfer Costs on a Calendar Quarter basis, within [****] days after receipt of an invoice from Alnylam therefor.
(b)Other Manufacturing Costs. The Parties shall share Other Manufacturing Costs in accordance with the Financial Appendix.
8.5Development Milestone Payments.
(a)Roche shall pay, or cause to be paid, to Alnylam the payments set forth in the table below (each, a “Development Milestone Payment”) upon the first achievement of the corresponding development milestone event by the Therapeutic Product to achieve such development milestone in the Field (each, a “Development Milestone”) in accordance with Section 8.5(b) and Section 8.5(c) up to a maximum amount of [****].
No.Development MilestoneDevelopment Milestone Payment
1FPI for KARDIA-3$65 million
2[****][****]
3FPI for the Initial CVOT Study for the first Therapeutic Product for use in the Field in the Primary Indication$300 million
4[****][****]
[****][****]
[****][****]
5[****]*[****]
6[****][****]
7[****]**[****]
8[****][****]
9[****][****]
[****][****]
* [****].
**[****].
(b)Clarifications. [****].
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(c)Notice and Payment. Roche shall provide written notice to Alnylam within [****] days of achievement by or on behalf of Roche of any Development Milestone, and Alnylam shall provide written notice to Roche (and if not already notified, the JSC) within [****] days of achievement by or on behalf of Alnylam of any Development Milestone. After Alnylam’s receipt of a notice of the achievement of a Development Milestone from Roche, or as applicable the delivery by Alnylam to Roche of a notice of the achievement of a Development Milestone by or on behalf of Alnylam, in each case in accordance with this Section 8.5(c), Alnylam shall submit an invoice to Roche with respect to the corresponding Development Milestone Payment and Roche shall pay the corresponding Development Milestone Payment within [****] days after receipt of such invoice. For clarity, each such Development Milestone Payment is nonrefundable and non-creditable against any other payments due hereunder.
8.6Sales Milestone Payments.
(a)Roche shall pay to Alnylam the one-time payments set forth in the table below (the “Sales Milestone Payments”) up to a maximum amount of [****] based on aggregate Net Sales of all Products in the Territory made during (i) the Co-Commercialization Term (for Net Sales in the Co-Commercialization Territory) and (ii) the Term until expiration of the applicable Royalty Term for a given Product and country (for Net Sales in the Roche Territory) in a Calendar Year (each, a “Sales Milestone”) in accordance with Section 8.6(c). Sales Milestone Payments shall be payable one-time only upon the first achievement of the corresponding Sales Milestone (for clarity, regardless of how many times such sales threshold may be reached in any subsequent Calendar Year).
No.Sales MilestoneSales Milestone Payment
1Aggregate Net Sales of Products [****][****]
2Aggregate Net Sales of Products [****][****]
3Aggregate Net Sales of Products [****][****]
4Aggregate Net Sales of Products [****][****]
5Aggregate Net Sales of Products [****][****]
(b)Concurrent Achievement of Sales Milestones. For clarity, each Sales Milestone Payment shall be payable one time only, however, there shall be no restriction on the number of Sales Milestone Payments that are payable with respect to a given Calendar Year. For example, if aggregate Net Sales of the Products subject to payment under this Section 8.6 in the Territory are [****] in the first Calendar Year, and then [****] in the next Calendar Year, then Roche will owe Alnylam [****] with respect to the first Calendar Year and a [****].
(c)Notice and Payment. Roche shall notify Alnylam in writing of achievement of any Sales Milestone pursuant to the applicable Calendar Quarter Report in accordance with Section 8.7(d). After receipt of such written notice from Roche of the achievement of a Sales Milestone in accordance with Section 8.7(d), Alnylam shall submit an invoice to Roche with respect to the corresponding Sales Milestone Payment, and Roche shall pay the corresponding Sales Milestone Payment within [****] days after receipt of such invoice. For clarity, each such Sales Milestone Payment is nonrefundable and non-creditable against any other payments due hereunder.
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8.7Royalty Payments.
(a)Roche Territory. Subject to the remainder of this Section 8.7, Roche shall pay to Alnylam nonrefundable, non-creditable (except with respect to ordinary course adjustments made consistent with the calculation of Net Sales or otherwise made in accordance with the procedures set forth in the Financial Appendix) tiered royalties on aggregate Calendar Year Net Sales of Products for use in the Field in the Roche Territory during the Royalty Term thereof (“Royalty Payment”) at the applicable royalty rate set forth below (each, a “Royalty Rate”):
Portion of Aggregate Calendar Year Net Sales in the Roche TerritoryRoyalty Rate
Portion of Net Sales [****][****]
Portion of Net Sales [****][****]
Portion of Net Sales [****][****]
Portion of Net Sales [****][****]
Portion of Net Sales [****][****]
[****].
(b)Royalty Term. The period during which Royalty Payments under this Section 8.7 are payable for a given Product and country in the Roche Territory on Net Sales of such Product commences upon the First Commercial Sale of such Product in such country and continues on a Product-by- Product, and country-by-country basis until the latest of (i) [****] from the anniversary of the First Commercial Sale of such Product in such country, (ii) expiration of the last Valid Claim included in any Alnylam Patent that Covers the Manufacture, use or sale of such Product, in such country, and (iii) the expiration of Regulatory Exclusivity for such Product in such country (each such period, a “Royalty Term”).
(c)Royalty Rate Reductions.
(i)Generic Product Entry. On a Product-by-Product and country-by-country basis, if, prior to the end of the Royalty Term for such Product, in any Calendar Quarter at any time after Generic Product Entry for such Product for such country,
(1)subject to Section 8.7(c)(iv), the Net Sales in a Calendar Quarter of such Product in such country has declined [****], then the applicable Royalty Rates for such Product in such country shall be reduced by [****]; and
(2)if the Net Sales in a Calendar Quarter of such Product in such country has declined [****], then the applicable Royalty Rates for such Product in such country shall be reduced [****].
(ii)Exclusivity Expiry. On a Product-by-Product and country-by-country basis, if prior to the end of the Royalty Term in any Calendar Quarter (and subject to Section 8.7(c)(iv)), if (1) the time period set forth in Section 8.7(b)(ii) has expired or continues solely on the basis of [****],
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and (2) [****], then the applicable Royalty Rate for such Product in such country shall be reduced by [****] for the remainder of the Royalty Term therefor.
(iii)