Document:

exv10w1

Exhibit 10.1

Confidential

Execution Copy

Confidential Materials omitted and filed separately with the

Securities and Exchange Commission. Asterisks denote omissions.

LICENSE AND COLLABORATION AGREEMENT

by and among

Takeda Pharmaceutical Company Limited

and

Alnylam Pharmaceuticals, Inc.

Dated as of May 27, 2008

 

 

Table of Contents

	 	 	 	 	 	 	 	 	 	 	 
	 	 	 	 	Page	 	 	 	 	 
	 
	 	 	 	 	 	 	 	 	 	 
	ARTICLE I
	 	DEFINITIONS	 	 	1	 	 	 	 	 
	 
	 	 	 	 	 	 	 	 	 	 
	ARTICLE II
	 	GOVERNANCE	 	 	22	 	 	 	 	 
	 
	 	 	 	 	 	 	 	 	 	 
	2.1
	 	Committees	 	 	22	 	 	 	 	 
	2.2
	 	Meetings	 	 	23	 	 	 	 	 
	2.3
	 	Decision-Making Authority	 	 	24	 	 	 	 	 
	2.4
	 	Limitation on JRCC and JDCC Authority	 	 	24	 	 	 	 	 
	2.5
	 	Reports to Committees	 	 	24	 	 	 	 	 
	2.6
	 	Expenses	 	 	25	 	 	 	 	 
	 
	 	 	 	 	 	 	 	 	 	 
	ARTICLE III
	 	GRANT OF RIGHTS;  INTELLECTUAL PROPERTY MATTERS	 	 	25	 	 	 	 	 
	 
	 	 	 	 	 	 	 	 	 	 
	3.1
	 	Rights Granted by Alnylam to Takeda	 	 	25	 	 	 	 	 
	3.2
	 	Rights Granted by Takeda to Alnylam	 	 	28	 	 	 	 	 
	3.3
	 	Section 365(n) of the Bankruptcy Code	 	 	31	 	 	 	 	 
	3.4
	 	No Other Rights	 	 	32	 	 	 	 	 
	3.5
	 	[**]	 	 	32	 	 	 	 	 
	3.6
	 	Certain License Limitations	 	 	33	 	 	 	 	 
	3.7
	 	Gatekeepers	 	 	35	 	 	 	 	 
	3.8
	 	Additional Fields; Field Option	 	 	37	 	 	 	 	 
	3.9
	 	Designated Target Option	 	 	39	 	 	 	 	 
	3.10
	 	Special Provisions Relating to Novartis	 	 	40	 	 	 	 	 
	3.11
	 	Notice of Changes	 	 	41	 	 	 	 	 
	 
	 	 	 	 	 	 	 	 	 	 
	ARTICLE IV
	 	DEVELOPMENT OF LICENSED PRODUCTS; OPT-IN AND OPT-OUT RIGHTS	 	 	41	 	 	 	 	 
	 
	 	 	 	 	 	 	 	 	 	 
	4.1
	 	Diligence	 	 	41	 	 	 	 	 
	4.2
	 	Alnylam Profit-Sharing Option	 	 	41	 	 	 	 	 
	4.3
	 	Opt-Out	 	 	45	 	 	 	 	 
	4.4
	 	Abandoned Product Option	 	 	47	 	 	 	 	 
	4.5
	 	Effect of Election of Early Opt-Out Option, Opt-Out Option or	 	 	 	 	 	 	 	 
	 
	 	Abandoned Product Option	 	 	48	 	 	 	 	 
	 
	 	 	 	 	 	 	 	 	 	 
	ARTICLE V
	 	TECHNOLOGY TRANSFER AND UPDATES	 	 	50	 	 	 	 	 
	 
	 	 	 	 	 	 	 	 	 	 
	5.1
	 	Technology Transfer	 	 	50	 	 	 	 	 
	5.2
	 	Management of Transition Activities	 	 	51	 	 	 	 	 
	5.3
	 	Technology to be Transferred	 	 	53	 	 	 	 	 
	5.4
	 	Additional Services	 	 	53	 	 	 	 	 
	 
	 	 	 	 	 	 	 	 	 	 
	ARTICLE VI
	 	RESEARCH AND DELIVERY COLLABORATIONS	 	 	54	 	 	 	 	 
	 
	 	 	 	 	 	 	 	 	 	 
	6.1
	 	Research Collaboration	 	 	54	 	 	 	 	 
	6.2
	 	Delivery Collaboration	 	 	55	 	 	 	 	 
	6.3
	 	Intellectual Property Developed Under Research Collaboration and	 	 	 	 	 	 	 	 
	 
	 	Delivery Collaboration	 	 	56	 	 	 	 	 

 

 

	 	 	 	 	 	 	 	 	 	 	 
	 	 	 	 	Page	 	 	 	 	 
	 	 	 	 		 	 	 	 	 
	ARTICLE VII
	 	FINANCIAL PROVISIONS	 	 	56	 	 	 	 	 
	 
	 	 	 	 	 	 	 	 	 	 
	7.1
	 	License Grant Consideration	 	 	56	 	 	 	 	 
	7.2
	 	Milestone Payments	 	 	57	 	 	 	 	 
	7.3
	 	Royalties	 	 	60	 	 	 	 	 
	7.4
	 	Field Option Fee	 	 	63	 	 	 	 	 
	7.5
	 	Profit-Sharing	 	 	63	 	 	 	 	 
	7.6
	 	Alnylam Payments	 	 	65	 	 	 	 	 
	7.7
	 	Payments	 	 	65	 	 	 	 	 
	7.8
	 	Reporting	 	 	66	 	 	 	 	 
	7.9
	 	Audits	 	 	66	 	 	 	 	 
	7.10
	 	Currency Exchange	 	 	66	 	 	 	 	 
	7.11
	 	Manner of Payment	 	 	66	 	 	 	 	 
	7.12
	 	Tax Withholding	 	 	67	 	 	 	 	 
	7.13
	 	Late Payments	 	 	67	 	 	 	 	 
	7.14
	 	[**]	 	 	67	 	 	 	 	 
	 
	 	 	 	 	 	 	 	 	 	 
	ARTICLE VIII
	 	INTELLECTUAL PROPERTY OWNERSHIP, PROTECTION AND RELATED MATTERS	 	 	68	 	 	 	 	 
	 
	 	 	 	 	 	 	 	 	 	 
	8.1
	 	Prosecution and Maintenance of Patent Rights	 	 	68	 	 	 	 	 
	8.2
	 	Third Party Infringement	 	 	69	 	 	 	 	 
	8.3
	 	Claimed Infringement	 	 	70	 	 	 	 	 
	8.4
	 	Paragraph IV Notice	 	 	71	 	 	 	 	 
	8.5
	 	Patent Term Extension	 	 	71	 	 	 	 	 
	8.6
	 	Listing of Patents	 	 	71	 	 	 	 	 
	8.7
	 	Cooperation	 	 	72	 	 	 	 	 
	8.8
	 	Trademarks	 	 	72	 	 	 	 	 
	 
	 	 	 	 	 	 	 	 	 	 
	ARTICLE IX
	 	CONFIDENTIAL INFORMATION	 	 	72	 	 	 	 	 
	 
	 	 	 	 	 	 	 	 	 	 
	9.1
	 	Confidential Information	 	 	72	 	 	 	 	 
	9.2
	 	Disclosures to Employees, Consultants and Advisors	 	 	73	 	 	 	 	 
	9.3
	 	Term	 	 	73	 	 	 	 	 
	9.4
	 	Publicity	 	 	73	 	 	 	 	 
	 
	 	 	 	 	 	 	 	 	 	 
	ARTICLE X
	 	REPRESENTATIONS, WARRANTIES AND COVENANTS	 	 	74	 	 	 	 	 
	 
	 	 	 	 	 	 	 	 	 	 
	10.1
	 	Mutual Representations and Warranties	 	 	74	 	 	 	 	 
	10.2
	 	Representations, Warranties and Covenants of Alnylam	 	 	74	 	 	 	 	 
	10.3
	 	Representations and Warranties of Takeda	 	 	78	 	 	 	 	 
	10.4
	 	No Warranties	 	 	78	 	 	 	 	 
	 
	 	 	 	 	 	 	 	 	 	 
	ARTICLE XI
	 	TERM AND TERMINATION	 	 	78	 	 	 	 	 
	 
	 	 	 	 	 	 	 	 	 	 
	11.1
	 	Term	 	 	78	 	 	 	 	 
	11.2
	 	Termination for Cause	 	 	78	 	 	 	 	 
	11.3
	 	Patent Validity Challenges	 	 	79	 	 	 	 	 
	11.4
	 	Termination at Will	 	 	80	 	 	 	 	 
	11.5
	 	Effect of Expiration or Termination	 	 	80	 	 	 	 	 
	 
	 	 	 	 	 	 	 	 	 	 
	ARTICLE XII
	 	MISCELLANEOUS	 	 	81	 	 	 	 	 
	 
	 	 	 	 	 	 	 	 	 	 
	12.1
	 	Indemnification	 	 	81	 	 	 	 	 

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	 	 	 	 	Page	 	 	 	 	 
	 	 	 	 		 	 	 	 	 
	12.2
	 	Dispute Resolution	 	 	83	 	 	 	 	 
	12.3
	 	Governing Law and Waiver of Jury Trial	 	 	83	 	 	 	 	 
	12.4
	 	Assignment	 	 	84	 	 	 	 	 
	12.5
	 	Alnylam Change of Control	 	 	84	 	 	 	 	 
	12.6
	 	Entire Agreement; Amendments	 	 	87	 	 	 	 	 
	12.7
	 	Notices	 	 	88	 	 	 	 	 
	12.8
	 	Force Majeure	 	 	89	 	 	 	 	 
	12.9
	 	Independent Contractors	 	 	89	 	 	 	 	 
	12.10
	 	No Strict Construction	 	 	89	 	 	 	 	 
	12.11
	 	Headings	 	 	89	 	 	 	 	 
	12.12
	 	No Implied Waivers; Rights Cumulative	 	 	89	 	 	 	 	 
	12.13
	 	Severability	 	 	89	 	 	 	 	 
	12.14
	 	Execution in Counterparts; Facsimile Signatures	 	 	90	 	 	 	 	 
	12.15
	 	No Consequential or Punitive Damages	 	 	90	 	 	 	 	 
	12.16
	 	Interpretation	 	 	90	 	 	 	 	 
	12.17
	 	Actions of Affiliates	 	 	90	 	 	 	 	 
	12.18
	 	No Third Party Beneficiaries	 	 	91	 	 	 	 	 
	12.19
	 	Further Assurances	 	 	91	 	 	 	 	 

Schedules

	 	 	 	 	 
	Schedule A

	 	Alnylam Patent Rights
	 	 
	Schedule B

	 	Description of Alnylam Third Party Obligations	 	 
	Schedule C

	 	Asian Pharmaceutical Companies	 	 
	Schedule D

	 	Profit-Sharing Agreement Term Sheet	 	 
	Schedule E

	 	Listed Alnylam Third Party Agreements	 	 
	Schedule F

	 	Pre-Existing Alliance Agreements	 	 
	Schedule G

	 	Supplemental Therapeutic Areas	 	 
	Schedule H

	 	Prohibited Collaborators	 	 
	Schedule I

	 	Prohibited Sublicensees	 	 
	Schedule J

	 	Summmary of Technology Transfer Plan	 	 
	Schedule K

	 	Summary of Research Collaboration Plan	 	 
	Schedule L

	 	Allocation	 	 
	Schedule M

	 	Joint Press Release	 	 
	Schedule N

	 	Prohibited Partners	 	 

-iii-

 

Confidential
Execution Copy

LICENSE AND COLLABORATION AGREEMENT

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

INTRODUCTION

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

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

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

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

ARTICLE I

DEFINITIONS

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

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

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

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

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

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

 

 

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

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

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

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

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

-2-

 

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

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

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

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

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

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

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

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

-3-

 

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

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

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

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

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

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

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

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

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

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

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

-4-

 

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

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

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

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

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

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

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

-5-

 

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

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

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

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

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

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

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

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

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

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

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

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

-6-

 

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

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

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

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

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

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

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

-7-

 

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

-12-

 

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

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

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

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

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

          “MIT” shall mean the Massachusetts Institute of Technology.

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

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

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

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

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

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

-13-

 

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

          “Territory” shall mean all countries of the world.

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

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

          “UBC” shall mean the University of British Columbia.

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

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

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

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ARTICLE II

GOVERNANCE

          2.1 Committees.

          (a) Joint Research Collaboration Committee.

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

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

          (b) Joint Delivery Collaboration Committee.

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

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

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

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

          2.3 Decision-Making Authority.

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

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

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

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

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

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

ARTICLE III

GRANT OF RIGHTS;

INTELLECTUAL PROPERTY MATTERS

          3.1 Rights Granted by Alnylam to Takeda.

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

          (b) Sublicense Rights.

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

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

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

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

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

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

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

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

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

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

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

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

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

          3.2 Rights Granted by Takeda to Alnylam.

          (a) License Grants.

               (i) Delivery Intellectual Property.

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

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

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

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

          (b) Sublicense Rights.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

          3.6 Certain License Limitations.

          (a) Pre-Existing Alliance Agreements.

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

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

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

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

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

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

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          3.7 Gatekeepers.

          (a) Takeda Target Clearance.

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

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

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

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

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

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

          (b) Alnylam Target Clearance.

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

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

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

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          3.8 Additional Fields; Field Option.

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

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

	 	 	 	 	 
	 	 	Payment for
	Development Event:	 	Licensed Products:
	Initiation of Phase III for each Additional Indication
	 	$	[**]	 
	Acceptance of NDA filing in a Major Market for each
Additional Indication
	 	$	[**]	 
	First Commercial Sale in a Major Market for each
Additional Indication
	 	$	[**]	 

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

	 	 	 	 	 
	 	 	Payment for
	Development Event:	 	Licensed Products:
	Initiation of Phase III for each Additional Indication
	 	$	[**]	 
	Acceptance of NDA filing in a Major Market for each
Additional Indication
	 	$	[**]	 
	First Commercial Sale in a Major Market for each
Additional Indication
	 	$	[**]	 

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

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

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

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

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

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

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

          3.10 Special Provisions Relating to Novartis.

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

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

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

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

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

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

-40-

 

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

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

ARTICLE IV

DEVELOPMENT OF LICENSED PRODUCTS;

OPT-IN AND OPT-OUT RIGHTS

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

          4.2 Alnylam Profit-Sharing Option.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

          4.3 Opt-Out.

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

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

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

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

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

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

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

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

          4.4 Abandoned Product Option.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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ARTICLE V

TECHNOLOGY TRANSFER AND UPDATES

          5.1 Technology Transfer.

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

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

          (c) Diligence Obligations.

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

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

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

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

          5.2 Management of Transition Activities.

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

          (b) Joint Technology Transfer Committee.

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

               (ii) JTTC Responsibilities.

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

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

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

               (iii) Operation of Joint Technology Transfer Committee.

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

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

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

          5.3 Technology to be Transferred.

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

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

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

ARTICLE VI

RESEARCH AND DELIVERY COLLABORATIONS

          6.1 Research Collaboration.

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

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

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

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

          6.2 Delivery Collaboration.

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

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

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

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

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

          6.3 Intellectual Property Developed Under Research Collaboration and Delivery Collaboration.

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

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

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

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

ARTICLE VII

FINANCIAL PROVISIONS

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

	 	 	 	 	 
	Event:	 	Payment Trigger:	 	Payment:
	Execution of this
Agreement
	 	Due within [**] after the Effective Date.	 	$100,000,000
	 
	 	 	 	 
	Technology Milestone I
	 	Due within [**] after achievement of	 	$[**]
	 
	 	Technology Milestone I which shall be	 	 
	 
	 	deemed to be the completion of	 	 
	 
	 	transferring the items described in	 	 
	 
	 	Column J of Table 1 of Schedule J, which	 	 
	 
	 	are items intended to be transferred	 	 
	 
	 	within [**] after the Effective Date.	 	 
	 
	 	 	 	 
	Technology Milestone II
	 	Due within [**] after the earlier of (i)	 	$[**]
	 
	 	achievement of Technology Milestone II	 	 
	 
	 	or (ii) the [**] of the Effective Date	 	 
	 
	 	if Alnylam has exercised its	 	 
	 
	 	Commercially Reasonable Efforts in the	 	 
	 
	 	performance of its obligations under the	 	 
	 
	 	Technology Transfer Plan; provided that	 	 
	 
	 	no such payment shall be made until	 	 
	 
	 	after the [**] of the Effective Date.	 	 

	 	 	 	 	 
	Technology Milestone III
	 	Due within [**] after the earlier of (i)	 	$[**]
	 
	 	achievement of Technology Milestone III	 	 
	 
	 	or (ii) the [**] of the Effective Date	 	 
	 
	 	if Alnylam has exercised its	 	 
	 
	 	Commercially Reasonable Efforts in the	 	 
	 
	 	performance of its obligations under the	 	 
	 
	 	Technology Transfer Plan; provided that	 	 
	 
	 	no such payment shall be made until	 	 
	 
	 	after the [**] of the Effective Date.	 	 

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          7.2 Milestone Payments.

          (a) Event Payments. In connection with the Development and Commercialization of
Licensed Products directed against a given Target hereunder Takeda shall provide Alnylam written
notice within [**] after the achievement by or on behalf of Takeda, its Affiliates or sublicensees
of the events set forth below. If at such time that the milestone is achieved there is a Valid
Claim included in the Alnylam Patent Rights that Covers the relevant Licensed Product, Takeda
shall, concurrent with such written notice, pay, or cause to be paid, to Alnylam the following
payments:

               (i) For the first Licensed Product against each Target:

	 	 	 	 	 
	 	 	Payment for
	Development Event:	 	Licensed Products:
	Initiation of [**]
	 	$	[**]	 
	Initiation of the first Phase I Study
	 	$	[**]	 
	Initiation of the first Phase II Study
	 	$	[**]	 
	Initiation of the first Phase III Study for the first Indication
	 	$	[**]	 
	First acceptance of an NDA in the United States
	 	$	[**]	 
	First acceptance of an NDA in a Major European Country
	 	$	[**]	 
	First Commercial Sale in the United States
	 	$	[**]	 
	First Commercial Sale in a Major European Country
	 	$	[**]	 

               (ii) For the second Licensed Product against the same Target for which payments were made
pursuant to Section 7.2(a)(i) above:

	 	 	 	 	 
	 	 	Payment for
	Development Event:	 	Licensed Products:
	Initiation of [**]
	 	$	[**]	 

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	 	 	Payment for
	Development Event:	 	Licensed Products:
	Initiation of the first Phase I Study
	 	$	[**]	 
	Initiation of the first Phase II Study
	 	$	[**]	 
	Initiation of the first Phase III Study for the first Indication
	 	$	[**]	 
	First acceptance of an NDA in the United States
	 	$	[**]	 
	First acceptance of an NDA in a Major European Country
	 	$	[**]	 
	First Commercial Sale in the United States
	 	$	[**]	 
	First Commercial Sale in a Major European Country
	 	$	[**]	 

               (iii) Event Payments Payable Only Once; Follow-On Product. Each event payment under
Sections 7.2(a)(i) and 7.2(a)(ii) shall be payable only once in relation to each Target,
irrespective of dosage, formulation forms, route of administration or Indications. For purposes of
clarity, (A) if Development of a Licensed Product directed to a particular Target ceases prior to
acceptance of an NDA in a Major Market (a “Failed Product”), and Development of the next
Licensed Product directed to the same Target (a “Follow-On Product”) subsequently commences
or continues, then any of the milestone payments previously made by Takeda under Section 7.2(a)(i)
or 7.2(a)(ii) above in connection with such Failed Product shall be fully creditable against the
repeated achievement of such milestone event by such Follow-On Product to achieve such milestone
event, and (B) if for any reason a milestone event relating to the Initiation of [**], Phase I
Study, Phase II Study or Phase III Study and corresponding to a milestone payment under Section
7.2(a)(i) or 7.2(a)(ii) does not occur prior to the occurrence of the next milestone event listed
in the table above in Sections 7.2(a)(i) and 7.2(a)(ii) for such Licensed Product, then such prior
non-occurring milestone event shall be deemed to occur concurrently with the occurrence of the next
milestone event.

               (iv) No Valid Claim Upon Achievement of Milestone Event. In the event that on the
date a milestone event set forth in this Section 7.2(a) is achieved there is no Valid Claim
Covering the relevant Licensed Product in the applicable country (or, in the case of milestones
that are not country-specific, in the U.S.), the associated milestone payment shall not become due
until such time as there is a Valid Claim that Covers such Licensed Product in a manner that would
permit the commencement of the Royalty Term for such Licensed Product in such country. Alnylam
shall notify Takeda of such Valid Claim and the applicable milestone payment(s) shall be paid
within [**] of such notice unless Takeda has ceased Developing and Commercializing such Licensed
Product before Alnylam obtains such Valid Claim.

          (b) Sales Milestones. Takeda shall pay, or cause to be paid, to Alnylam the following
payments concurrently with Takeda’s payment of royalties pursuant to

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Section 7.7 for the Calendar
Quarter during which the achievement of the events set forth below occurs:

	 	 	 	 	 
	 	 	Payment for Licensed
	Annual Net Sales of a Licensed Product (other	 	Product (other than a
	than a Shared Product in the United States)	 	Shared Product in the
	during the applicable Fiscal Year:	 	United States):
	Worldwide Annual Net Sales greater than $[**]
	 	$	[**]	 
	Worldwide Annual Net Sales greater than $[**]
	 	$	[**]	 

For purposes of clarity, Net Sales of a Licensed Product (other than a Shared Product in the United
States) shall only be included in the calculation of worldwide Annual Net Sales for the purposes of
this Section 7.2(b) if royalties are payable by Takeda to Alnylam on such Net Sales pursuant to
Section 7.3 other than pursuant to Section 7.3(b) (i.e., excluding Net Sales that are only entitled
to Know-How-based royalties pursuant to Section 7.3(b)).

          7.3 Royalties.

          (a) Royalty Rate. Subject to Sections 7.3(b), (c), (d), (e) and (f) during each
relevant Royalty Term, Takeda shall pay, or cause to be paid, to Alnylam the following royalties on
Annual Net Sales of each Licensed Product on a Region-by-Region basis:

	 	 	 	 	 
	 	 	Royalty Rate
	 	 	Applicable to Such
	 	 	Annual Net Sales
	Annual Net Sales of a Licensed Product on a Region-by-Region basis:	 	of Such Licensed Product:
	Less than or equal to $[**]:
	 	 	[**]	%
	Greater than $[**], but less than or
equal to $[**]:
	 	 	[**]	%
	Greater than $[**], but less than or
equal to $[**]:
	 	 	[**]	%
	Greater than $[**]:
	 	 	[**]	%

By way of example, if Annual Net Sales of a Licensed Product are [**] United States dollars ($[**])
in a given Region and no reductions or deductions were to apply under

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Sections 7.3(b), (c), (d),
(e) and (f), then the royalty payable by Takeda to Alnylam in such Region would be as follows:

	 	 	 	 	 
	[**]
	 	 	 	 
	 
	 	 	 	 
	Total Royalty Due
	 	=	 	$[**]

For the avoidance of doubt, Takeda’s obligation to pay royalties under this Section 7.3 is imposed
only once with respect to the same unit of Licensed Product, including by reason of such Licensed
Product being Covered by more than one Valid Claim of Alnylam Patent Rights.

          (b) Know-How Royalty. If, at some future date, after the Royalty Term for a given
Licensed Product in a given country begins, neither (i) any Valid Claim of the Alnylam Patent
Rights in such country Covers the commercial Manufacture or Commercialization of the Licensed
Product in the country of sale, nor (ii) any Valid Claim of the Alnylam Patent Rights Covers the
commercial Manufacture of the Licensed Product in the country or countries where such Licensed
Product was commercially Manufactured, then the royalty rate applicable to such Licensed Product in
such country shall be reduced to [**] percent ([**]%) of the rate set forth in Section 7.3(a) above for any
remaining portion of the Royalty Term which applies to such Licensed Product in such country. For
purposes of clarity, the Royalty Term shall not commence unless and until a Valid Claim exists,
which may occur, at the time of First Commercial Sale or any time thereafter.

          (c) Royalty Stacking.

               (i) Licensed Products Other Than Shared Products. Takeda shall be entitled to deduct,
from the royalty payments payable by Takeda under Sections 7.3(a) and 7.3(b) for a reporting
period, [**] percent ([**]%) of Required Third Party Payments paid by Takeda with respect to
Licensed Products (excluding Shared Products Commercialized in the U.S.) during the applicable
reporting period. In no event shall aggregate deductions under this Section 7.3(c) reduce any
quarterly royalty payment by Takeda in respect of Net Sales of a Licensed Product to less than [**]
percent ([**]%) of the royalty otherwise payable to Alnylam under Sections 7.3(a) and 7.3(b) with
respect to such Licensed Product.

               (ii) Shared Products. All royalty, milestone and other payments to a Third Party made
by either Party under Third Party agreements (including Listed Alnylam Third Party Agreements or
Pre-Existing Alliance Agreements) with respect to Shared Products in the United States shall be
deemed expenses of such Party and deducted in calculating Net Profits/Losses pursuant to
Schedule D.

          (d) Payments in Respect of In-Licenses.

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               (i) In addition to any royalty set forth in Sections 7.3(a) and 7.3(b), Takeda shall reimburse
Alnylam for [**] of all royalty payments payable to Third Parties pursuant to Listed Alnylam Third
Party Agreements applicable to sales of Licensed Products (other than Shared Products in the United
States), after applicable royalty reduction thereunder, which royalty payments are summarized in
Schedule B (each such payment, a “Listed Alnylam Third Party Payment,”
collectively, the “Listed Alnylam Third Party Payments”); provided that the
cumulative amount payable by Takeda under this Section 7.3(d) shall not exceed [**] percent ([**]%)
of Net Sales. Notwithstanding the foregoing, if (A) the sum of (i) the royalties payable by Takeda
to Alnylam under Sections 7.3(a) and 7.3(b) with respect to any Licensed Product for any Calendar
Quarter expressed as a percentage of Net Sales, after any reduction to such royalties pursuant to
Section 7.3(c), and (ii) the lower of (x) [**] of the Listed Alnylam Third Party Payments expressed
as a percentage of Net Sales, and (y) [**] percent ([**]%) is less than (B) the sum of (i) [**]
percent ([**]%) of Net Sales and (ii) the Listed Alnylam Third Party Payments expressed as a
percentage of Net Sales, then Takeda shall pay to Alnylam such additional royalty amounts as are
necessary for Alnylam to realize a net royalty amount equal to [**] percent ([**]%) of Net Sales of
such Licensed Product for such Calendar Quarter, after it makes the Listed Alnylam Third Party
Payments to the Listed Alnylam Third Parties.

               (ii) The Parties shall cooperate to coordinate such reimbursements by Takeda hereunder in a
manner that ensures all amounts payable by Alnylam with respect to the Licensed Products pursuant
to Listed Alnylam Third Party Agreements are paid in a timely manner and otherwise in compliance
with such Listed Alnylam Third Party Agreements. Takeda shall have the right to have an
independent public accountant reasonably acceptable to Alnylam audit Alnylam’s books and records
solely for purposes of verifying such Listed Alnylam Third Party Payments, which right shall be
exercisable [**] per year solely with respect to records covering up to the [**] Fiscal Years prior
to audit notification, upon reasonable advance notice and during Alnylam’s business hours, subject
to the confidentiality provisions of Article IX hereof. Audit results and findings shall be shared
by Takeda and Alnylam. If the audit reveals an overpayment by Takeda under this Section 7.3(d),
the amount of such overpayment shall be credited towards any future reimbursement amounts payable
by Takeda under this Section 7.3(d). If the audit reveals an underpayment by Takeda, Takeda shall
make up such underpayment within [**]. The failure of Takeda to request verification of any Listed
Alnylam Third Party Payments hereunder within the [**] Fiscal Year period set forth above shall be
deemed acceptance of the calculation of such Listed Alnylam Third Party Payments. Notwithstanding
the foregoing, in no event shall the Listed Alnylam Third Party Payments include any payment to
[**] under Section 7.4 of the [**] Agreement.

          (e) Loss of Listed Alnylam Third Party Agreements. If Alnylam ceases to be a licensee
of Alnylam Patent Rights licensed hereunder (as such, “Terminated Patent Rights”) under any
Listed Alnylam Third Party Agreement (other than as a result of any action or omission by Takeda),
Alnylam shall within [**] of such termination provide Takeda written notice of such Terminated
Patent Rights. If Takeda directly licenses such

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Terminated Patent Rights from that Third Party, then Takeda may, except as provided below, deduct the full amount of any [**] paid to such Third Party for such license(s) that is
attributable to Licensed Products Covered by such Terminated Patent Rights from any royalties
otherwise payable to Alnylam hereunder; provided, that prior to Takeda entering
into any such license of such Terminated Patent Rights from such Third Party, Takeda shall notify
Alnylam of its intent to do so and shall provide to Alnylam an opportunity to explain its rationale
for ceasing to license such Terminated Patent Rights and Takeda shall consider in good faith such
rationale. If Takeda does not agree with Alnylam’s rationale, then, at Takeda’s request, Alnylam
shall use Commercially Reasonable Efforts to reinstate the license for such Terminated Patent
Rights within a [**] period. If Alnylam is unable to reinstate the license, then Takeda may obtain
a direct license for such Terminated Patent Rights from such Third Party and make such full
deductions as provided herein; provided, that, in no event, shall such total
deductions under this Section 7.3(e) reduce any quarterly royalty payment by Takeda in respect of
Net Sales of the applicable Licensed Product to less than [**]; provided, further,
that Takeda may offset any excess portion of the full amount of any [**] paid to any such Third
Party for any such license (that was not able to be deducted in accordance with the preceding
proviso) from any other milestone or royalty payment to Alnylam under this Agreement.

          (f) Duration of Royalty Payments; First Commercial Sale. The royalties payable under
Section 7.3(a) or 7.3(b), as applicable, shall be paid on a country-by-country basis on each
Licensed Product during the applicable Royalty Term for such Licensed Product. Takeda shall notify
Alnylam of the occurrence of the First Commercial Sale of each Licensed Product within [**] of its
occurrence.

          7.4 Field Option Fee. If Takeda exercises the Field Option with respect to any Additional
Field pursuant to Section 3.8(b), Takeda shall pay Alnylam a fee (the “Field Option Fee”)
of Fifty Million United States dollars ($50,000,000) for each such Additional Field. Takeda shall
pay such Field Option Fee, less any amounts creditable pursuant to Section 3.8(a), within [**]
following receipt of Takeda’s notice of exercise of such Field Option pursuant to Section 3.8(b).

          7.5 Profit-Sharing.

          (a) Alnylam may exercise its Profit-Sharing Option for each Licensed Product upon payment of
the applicable option exercise amount during the applicable Option Exercise Period, pursuant to
Section 4.2(c), set forth in the table below (“Option Exercise Payment”):

	 	 	 	 	 	 	 	 	 
	 	 	Exercise Payment Shall be
	 	 	the Greater of the Two
	Timing of Notice of Exercise:	 	Amounts Set Forth Below*:
	Any time within [**] after the [**] for such Licensed Product
	 	$	[**]	 	 	 	[**]	 

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	 	 	Exercise Payment Shall be
	 	 	the Greater of the Two
	Timing of Notice of Exercise:	 	Amounts Set Forth Below*:
	Any time within [**] after the Initiation of a [**] with respect to such Licensed Product
	 	$	[**]	 	 	 	[**]	 
	 
	 	 	 	 	 	 	 	 
	Any time within [**] after the date of Takeda’s receipt of FDA feedback following the [**]
meeting (or in the event there is no [**]
meeting, [**] after receiving the information
from Takeda pursuant to Section 4.2(b)(iii)
with respect to such Licensed Product
	 	$	[**]	 	 	 	[**]	 

 

			
	*	 	For purposes of this Section 7.5(a), “PDC” or “Past Development Costs” shall mean the past
Development Costs reasonably allocated to seeking or maintaining Regulatory Approval in the United
States with respect to the applicable Licensed Product prior to the effective date of the
Profit-Sharing Agreement.

Payment to Takeda shall be made within [**] after Alnylam exercises the Profit-Sharing Option. For
purposes of clarity, only one Option Exercise Payment, determined in accordance with the table
above based on the point at which Alnylam exercises the Profit-Sharing Option, shall apply for each
Shared Product.

          (b) If Alnylam exercises the Profit-Sharing Option, in addition to the applicable Option
Exercise Payment for a Shared Product, Alnylam shall (i) refund [**] percent ([**]%) of the
milestone payments for such Shared Product which Takeda paid to Alnylam pursuant to Section 7.2(a)
prior to the effective date of the Profit-Sharing Agreement (“Past Development
Milestones”), and (ii) permit Takeda to fully credit [**] percent ([**]%) of the past
Development Costs reasonably allocated to seeking or maintaining Regulatory Approval in the United
States for such Shared Product against any future payments to be paid by Takeda to Alnylam for such
Shared Product in the United States pursuant to this Article VII. Alnylam shall refund such [**]
percent ([**]%) of the Past Development Milestones concurrent with its payment of the Option
Exercise Payment.

          (c) Within [**] of Alnylam exercising the Profit-Sharing Option, Takeda shall provide to
Alnylam a report detailing the past Development Costs reasonably allocated to seeking or
maintaining Regulatory Approval in the United States for such Shared Product. Alnylam shall have
the right to have an independent public accountant reasonably acceptable to Takeda audit Takeda’s
books and records solely for purposes of verifying such past Development Costs, which right shall
be exercisable [**] per Shared Product, upon reasonable advance notice and during Takeda’s business
hours, subject to the confidentiality provisions of Article IX hereof. Thereafter, each Party
shall, no more frequently than [**] per Fiscal Year, have the right to have an independent public
accountant reasonably acceptable to the other Party audit the other Party’s books and records for
purposes of verifying subsequent Development Costs in accordance with Section 7.9. Audit results
and findings shall be shared by Takeda and Alnylam.

          (d) In the event Alnylam exercises the Profit-Sharing Option, (i) all future milestone
payments, whether with respect to the United States or the ROW, that become payable by Takeda
pursuant to Sections 3.8(a) and 7.2 with respect to such Shared

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Product will be reduced by [**] percent ([**]%), and (ii) the royalty set forth in Section 7.3(a) with respect to Net Sales of such Shared Product in the United States shall no longer
be due.

          (e) The payments to Alnylam or Takeda, as applicable, with respect to Net Profits/Losses,
shall be made in accordance with the Profit-Sharing Agreement and such other terms as the Parties
may agree.

          7.6 Alnylam Payments.

          (a) If Takeda exercises the Early Opt-Out Option or Opt-Out Option and Alnylam does not
rescind its Profit-Sharing Option then, with respect to such Abandoned Product, (i) Alnylam shall
pay Takeda (A) [**] percent ([**]%) of the milestone payments under Sections 7.2(a)(i), 7.2(a)(ii)
and 7.2(b) that Takeda would have paid to Alnylam for future milestone events for such Abandoned
Product and (B) royalties during the applicable Royalty Term with respect to Net Sales of such
Abandoned Product (for such purposes, substituting Alnylam for Takeda, Alnylam Patent Right for
Patent Right controlled by Takeda and “Abandoned Product” for “Licensed Product” in the definitions
of Royalty Term and Net Sales respectively) at [**] percent ([**]%) of the rates set forth in
Section 7.3(a), with reductions and deductions as set forth in Sections 7.3(b) and 7.3(c) (for such
purpose, substituting Alnylam for Takeda and substituting “Abandoned Product” for “Licensed
Product” in such sections and vice versa), and (ii) Takeda shall not be obligated to pay Alnylam
any future milestone payments with respect to such Abandoned Product under Sections 7.2(a)(i),
7.2(a)(ii) and 7.2(b) or the royalty on future sales of such Abandoned Product set forth in Section
7.3(a). In addition, Sections 3.5, 7.7, 7.8, 7.12 and 7.13 shall apply to any payments under this
Section 7.6 (for such purpose, substituting Alnylam for Takeda and substituting “Abandoned Product”
for “Licensed Product” in such sections and vice versa).

          (b) If Alnylam exercises the Abandoned Product Option for an Abandoned Product under Section
4.4, Alnylam shall pay Takeda (i) royalties with respect to Net Sales of such Abandoned Product
(for such purposes, substituting Alnylam for Takeda and substituting “Abandoned Product” for
“Licensed Product” in the definition of Net Sales) at [**] set forth in Section 7.3(a), with
reductions and deductions as set forth in Sections 7.3(b) and 7.3(c) (for such purpose,
substituting Alnylam for Takeda and substituting “Abandoned Product” for “Licensed Product” in such
sections and vice versa) and (ii) milestone payments with respect to such Abandoned Products as are
set forth in Sections 7.2(a)(i), 7.2(a)(ii) and 7.2(b) (for such purpose, substituting Alnylam for
Takeda and substituting “Abandoned Product” for “Licensed Product” in such sections and vice
versa). In addition, Sections 3.5, 7.7, 7.8, 7.12 and 7.13 shall apply to any payments under this
Section 7.6 (for such purpose, substituting Alnylam for Takeda and substituting “Abandoned Product”
for “Licensed Product” in such sections and vice versa).

          7.7 Payments. Takeda shall calculate royalties on Net Sales quarterly as of March 31, June
30, September 30 and December 31 (each being the last day of an “Accounting Period”) and
shall pay royalties on Net Sales of Licensed Products (other

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than Shared Product in the United States) within the [**] after the end of each Accounting Period in which such Net Sales occur. Royalties on applicable Net Sales shall be
paid by Takeda in U.S. Dollars.

          7.8 Reporting. With each payment Takeda shall provide in writing for the relevant Accounting
Period the following information, on a Region-by-Region basis: (a) Net Sales (including the
deductions used in determining Net Sales), (b) the basis for any deductions from gross amounts
received to determine Net Sales, (c) the applicable royalty rates for such Product, (d) the
exchange rates used in calculating any of the foregoing, and (e) the total royalties payable for
the applicable period.

          7.9 Audits. Each Party shall keep, and shall require its Affiliates and sublicensees to keep,
complete and accurate records of the latest [**] years relating to Net Sales sufficient to allow
amounts payable hereunder pursuant to Sections 7.2, 7.3 and 7.5 to be determined, and each Party
shall keep and require its Affiliates to keep complete and accurate records of the latest [**]
years relating to Net Profits/Losses and all information relevant to calculating the foregoing.
For the sole purpose of verifying amounts payable hereunder or for calculating Net Profits/Losses,
as applicable, each Party shall have the right [**], at such Party’s expense, to retain an
independent certified public accountant selected by the auditing Party and reasonably acceptable to
the audited Party, to review such records in the location(s) where such records are maintained by
the audited Party, its Affiliates and sublicensees upon [**] prior written notice and during
regular business hours. The right to audit any royalty report or payment shall extend for [**]
years from the end of the Accounting Period to which such royalty report or such payment relates.
Such audit right shall not be exercised by Alnylam more than [**] in any Fiscal Year. All records
made available for audit shall be deemed to be Confidential Information of the audited Party. The
results of each audit, if any, shall be binding on both Parties. The audited Party shall promptly
pay the auditing Party the amount of any underpayment revealed by such audit together with interest
calculated in the manner provided in Section 7.13. If the underpayment is equal to or greater than
[**] percent ([**]%) of the amount that was otherwise due, the auditing Party shall be entitled to
have the audited Party reimburse the auditing Party’s reasonable out-of-pocket costs of such
review. The auditing Party shall promptly return to the audited Party any overpayment revealed by
such audit.

          7.10 Currency Exchange. With respect to sales of Licensed Products invoiced in U.S. Dollars,
the sales and royalties payable shall be expressed in U.S. Dollars. With respect to sales of
Licensed Products invoiced in a currency other than U.S. Dollars, the sales and any amounts payable
hereunder on such sales shall be expressed in their U.S. Dollar equivalent calculated using a
Party’s own standard currency translation methodology for the conversion of foreign sales
currencies into U.S. Dollars, which methodology shall be in accordance with the Applicable
Accounting Standards and shall be the methodology generally used by a Party for currency
conversions in such Party’s audited financial statements.

          7.11 Manner of Payment. Any payment to be made by one Party to the other under this Agreement
shall be payable in United States dollars and shall be paid

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by wire transfer in immediately available funds to the bank account designated by the relevant Party. Either Party shall have the right to change such information at any time by
providing written notice to the other Party; provided that such new bank information shall not be
deemed effective until the date that is [**] after the receipt of such new information.

          7.12 Tax Withholding. Each Party shall use reasonable efforts to minimize tax withholding on
payments made to the other Party. Notwithstanding such efforts, if such Party concludes that tax
withholdings under the Laws of any country are required with respect to payments to the other
Party, such Party shall first notify the other Party and provide such Party with [**] to determine
whether there are actions such receiving Party can undertake to avoid such withholding. The paying
Party shall refrain from making such payment until the receiving Party instructs the paying Party
that (i) the paying Party intends to take actions that will obviate the need for such withholding,
in which case the paying Party shall make such payment only after it is instructed to do so by the
receiving Party, or (ii) the paying Party should make such payment and withhold the required amount
and pay it to the appropriate governmental authority. In such case, the withholding Party shall
promptly provide the other Party with copies of receipts or other evidence reasonably required and
sufficient to allow the other Party to document such tax withholdings adequately for purposes of
claiming foreign tax credits and similar benefits. The Parties will cooperate reasonably in
completing and filing documents required under the provisions of any applicable tax laws or under
any other applicable Law, in connection with the making of any required tax payment or withholding
payment, or in connection with any claim to a refund of or credit for any such payment. The
Parties will cooperate to minimize such taxes in accordance with applicable Laws. Notwithstanding
the foregoing, Alnylam represents that zero percent (0%) withholding shall be required in respect
of the payments to be paid by Takeda to Alnylam pursuant to Section 7.1 hereof, because of the
eligibility of Alnylam as a publicly traded U.S. tax resident for purposes of the U.S.-Japan Income
Tax Treaty. Alnylam shall be solely responsible for its costs incurred in registering under such
treaty.

          7.13 Late Payments. Takeda shall pay interest to Alnylam on the aggregate amount of any
payments (except for those payments which are the subject of a reasonable, good faith dispute) that
are not paid on or before the date such payments are due under this Agreement at a rate of [**]
percent ([**]%) per month from the due date until paid in full or the highest rate permitted by
applicable Law, calculated on the number of days such payments are paid after the date such
payments are due. In the event that Takeda in reasonable good faith disputes any amounts due under
this Agreement, the interest rate in the preceding sentence shall not apply to the amounts so
disputed and Takeda shall instead pay interest to Alnylam at [**] plus [**] percent ([**]%) on any
such disputed payments which are found to be owed to Alnylam.

          7.14 [**]. Takeda shall [**] Alnylam its [**] in accordance with the Research Collaboration
Plan and the Delivery Collaboration Plan, as applicable. Alnylam shall invoice Takeda [**] for
such [**] and payment shall be due and payable within [**] of the invoice date.

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ARTICLE
VIII

Intellectual Property Ownership, Protection and Related Matters

          8.1 Prosecution and Maintenance of Patent Rights.

          (a) Alnylam Patent Rights. Alnylam shall have the initial right to file, prosecute
and maintain all Alnylam Patent Rights, at Alnylam’s expense; provided that,
subject to Alnylam Third Party Obligations, in the event that Alnylam declines the option to file
and prosecute any such patent applications or maintain any such patents that Cover a Licensed
Product, it shall give Takeda reasonable notice to this effect, sufficiently in advance to permit
Takeda to undertake such filing, prosecution and maintenance without a loss of rights, and
thereafter Takeda may, upon written notice to Alnylam, file and prosecute such patent applications
and maintain such patents in Alnylam’s name with respect to Alnylam Patent Rights at Takeda’s
expense.

          (b) Takeda Patent Rights and Joint Patent Rights. Takeda shall have the initial right
to file, prosecute and maintain all Takeda Patent Rights, Joint Research Collaboration Patent
Rights and Joint Delivery Collaboration Patent Rights, at Takeda’s expense; provided
that, in the event that Takeda declines the option to file, prosecute or maintain any such
Patent Rights that Cover a Shared Product or an Abandoned Product, it shall give Alnylam reasonable
notice to this effect, sufficiently in advance to permit Alnylam to undertake such filing,
prosecution and maintenance without a loss of rights, and thereafter Alnylam may, upon written
notice to Takeda, file, prosecute and maintain such Patent Rights in Takeda’s name with respect to
Takeda Patent Rights and in Alnylam’s and Takeda’s names with respect to Joint Research
Collaboration Patent Rights and Joint Delivery Collaboration Patent Rights, at Alnylam’s expense.
Notwithstanding the foregoing, the portion of Takeda’s foregoing expenses that are allocated to
filing, prosecuting or maintaining any Takeda Patent Rights that specifically and solely Cover a
Shared Product in the U.S. shall be included as cost in calculating Net Profits/Losses pursuant to
the Profit-Sharing Agreement and the Parties shall share such expenses in accordance with the
Profit-Sharing Agreement.

          (c) Cooperation. Each Party agrees to cooperate with the other with respect to the
filing, prosecution and maintenance of Patent Rights pursuant to this Section 8.1, including the
execution of all such documents and instruments and the performance of such acts as may be
reasonably necessary in order to permit the other Party to undertake any filing, prosecution or
maintenance of Patent Rights that such Party has elected not to pursue, as provided for in Sections
8.1(a) and (b). With respect to Joint Research Collaboration Patent Rights and Joint Delivery
Collaboration Patent Rights, the Party filing, prosecuting and maintaining such Patent Rights shall
provide the other Party, within [**] after submitting or receiving such filings or correspondence,
with copies of all filings and correspondence submitted to and received from patent offices and,
with respect to substantive filings and correspondence to be submitted to patent offices, shall use
reasonable efforts to provide the other Party with drafts of such filings and correspondence
reasonably in advance of submission and shall consider in good faith any

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comments regarding such filings and correspondence that the other Party may timely provide.

          8.2 Third Party Infringement.

          (a) Notice. Each Party shall promptly report in writing to the other Party during the
term of this Agreement any (i) known or suspected infringement of Alnylam Patent Rights, Takeda
Patent Rights, Joint Research Collaboration Patent Rights or Joint Delivery Collaboration Patent
Rights or (ii) known or suspected unauthorized use or misappropriation of Alnylam Know-How, Takeda
Know-How, Joint Research Collaboration Know-How or Joint Delivery Collaboration Know-How of which
such Party becomes aware, and shall provide the other Party with all available evidence supporting
such infringement, suspected infringement, unauthorized use or misappropriation or suspected
unauthorized use or misappropriation.

          (b) Infringement Actions.

               (i) Alnylam’s Enforcement Rights. Alnylam shall have the sole and exclusive right and
not the obligation to initiate a suit or take other appropriate action that it believes is
reasonably required to enforce Alnylam Intellectual Property. To the extent that any such suit or
action pertains to Licensed Products, Alnylam shall give Takeda advance notice of its intent to
file any such suit or take any such action and the reasons therefor, and shall provide Takeda with
an opportunity to make suggestions and comments regarding such suit or action. Thereafter, to the
extent any such suit or action pertains to Licensed Products, Alnylam shall keep Takeda promptly
informed, and shall from time to time consult with Takeda regarding the status of any such suit or
action and shall provide Takeda with copies of all material documents (e.g., complaints, answers,
counterclaims, material motions, orders of the court, memoranda of law and legal briefs,
interrogatory responses, depositions, material pre-trial filings, expert reports, affidavits filed
in court, transcripts of hearings and trial testimony, trial exhibits and notices of appeal) filed
in, or otherwise relating to, such suit or action.

               (ii) Takeda’s Enforcement Rights.

          (A) Takeda shall have the sole and exclusive right and not the obligation to initiate
a suit or take other appropriate action that it believes is reasonably required to enforce
Takeda Intellectual Property. To the extent that any such suit or action pertains to
Shared Products or Abandoned Products, Takeda shall give Alnylam advance notice of its
intent to file any such suit or take any such action and the reasons therefor, and shall
provide Alnylam with an opportunity to make suggestions and comments regarding such suit or
action.

          (B) Takeda shall have the first right, but not the obligation, to initiate a suit or
take other appropriate action with regard to Joint Research Collaboration Intellectual
Property and Joint Delivery Collaboration Intellectual Property. If Takeda declines to
initiate a suit or take other appropriate action to enforce such Joint Research
Collaboration Intellectual Property or Joint Delivery

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Collaboration Intellectual Property within [**] of such notice, Alnylam may, upon
written notice to Takeda, initiate a suit or take other appropriate action to enforce such
Joint Research Collaboration Intellectual Property and Joint Delivery Collaboration
Intellectual Property.

          (C) The enforcing Party under the foregoing Clause (A) or (B) shall keep the other
Party promptly informed, and shall from time to time consult with the other Party regarding
the status of any such suit or action and shall provide the other Party with copies of all
material documents (e.g., complaints, answers, counterclaims, material motions, orders of
the court, memoranda of law and legal briefs, interrogatory responses, depositions,
material pre-trial filings, expert reports, affidavits filed in court, transcripts of
hearings and trial testimony, trial exhibits and notices of appeal) filed in, or otherwise
relating to, such suit or action.

          (c) Conduct of Action; Costs. The Party initiating suit shall have the sole and
exclusive right to select counsel for any suit initiated by it under this Section 8.2. If required
under applicable Law in order for such Party to initiate and/or maintain such suit, the other Party
shall join as a party to the suit. If requested by the Party initiating suit, the other Party
shall provide reasonable assistance to the Party initiating suit in connection therewith at no
charge to such Party except for reimbursement of reasonable out-of-pocket expenses incurred in
rendering such assistance. The Party initiating suit shall assume and pay all of its own
out-of-pocket costs incurred in connection with any litigation or proceedings described in this
Section 8.2, including the fees and expenses of the counsel selected by it. The other Party shall
have the right to participate and be represented in any such suit by its own counsel at its own
expense.

          (d) Recoveries. Any recovery obtained as a result of any proceeding described in this
Section 8.2 or from any counterclaim or similar claim asserted in a proceeding described in Section
8.3, by settlement or otherwise, shall be applied in the following order of priority:

               (i) first, the Party initiating the suit or action shall be reimbursed for all costs in
connection with such proceeding paid by such Party;

               (ii) second, the other Party shall be reimbursed for all costs in connection with such
proceeding paid by such other Party; and

               (iii) third, any remainder shall be (A) treated as Recovery (as defined in Schedule D)
in calculating Net Profits/Losses in accordance with the Profit-Sharing Agreement to the extent
related to a Shared Product in the United States; or (B) retained by the Party that initiated the
suit or action to the extent not related to a Shared Product in the United States.

          8.3 Claimed Infringement.

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          (a) In the event that a Third Party at any time asserts a claim, or brings an action, suit or
proceeding against a Party or any of its Affiliates or, with respect to Takeda, sublicensees,
claiming infringement of such Third Party’s Patent Rights or unauthorized use or misappropriation
of such Third Party’s Know-How, based upon an assertion or claim arising out of any of the
activities taken in respect of the Development, Commercialization or Manufacture of Licensed
Products, where such claim, action, suit or proceeding and/or the defense thereof involves, or is
likely to involve, the validity, scope and/or enforceability of the Alnylam Intellectual Property
(“Third Party Infringement Claim”), such Party shall promptly notify the other Party in
writing of the claim or the commencement of such action, suit or proceeding, enclosing a copy of
the claim and all papers served.

          (b) Within [**] after delivery of the notification required to be delivered under Section
8.3(a) above, as between Alnylam and Takeda and subject to Alnylam Third Party Obligations, Alnylam
shall, upon written notice thereof to Takeda, assume control of the defense of solely those aspects
of any such Third Party Infringement Claim that involve the validity, scope and/or enforceability
of Alnylam Intellectual Property, and Takeda shall assume control of the defense of all other
aspects thereof. Takeda and Alnylam shall keep the other Party advised of the status of such
action, suit, proceeding or claim and the defense thereof and shall consider in good faith
recommendations made by the other Party with respect thereto.

          (c) Alnylam shall not agree to any settlement of such action, suit, proceeding, claim or
defense without the prior written consent of Takeda, which shall not be unreasonably withheld,
conditioned or delayed.

          8.4 Paragraph IV Notice. If either Party receives a notice under 21 U.S.C. §355(b)(2)(A)(iv)
or 355(j)(2)(A)(vii)(IV) from a Third Party filing an Abbreviated New Drug Application in which a
Licensed Product is the subject listed product (a “Paragraph IV Notice”), then it shall
provide a copy of such notice to the other Party within [**] after its receipt thereof. The
Parties’ rights to initiate patent infringement litigation based on such Paragraph IV Notice shall
be as set forth in Section 8.2.

          8.5 Patent Term Extension. Takeda shall have sole and exclusive control regarding selecting
which Patent Rights, if any, are relied upon for obtaining term extensions, supplementary
protection certificates and equivalents thereof (collectively, “Patent Term Extensions”)
offering patent protection beyond the initial term with respect to Licensed Products;
provided that Takeda shall not have the right to seek any Patent Term Extension
with respect to Alnylam Patent Rights without Alnylam’s prior written consent, which shall not be
unreasonably withheld, conditioned or delayed.

          8.6 Listing of Patents. Takeda shall, with respect to Licensed Products, have the right to
determine which of the Alnylam Patent Rights, Joint Research Collaboration Patent Rights, Joint
Delivery Collaboration Patent Rights or Takeda Patent Rights, if any, shall be submitted for
inclusion in the Approved Drug Products with Therapeutic Equivalence Evaluations pursuant to 21
U.S.C. Section 355, or any successor

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Law in the United States, together with any comparable Laws in any other country. Takeda
shall notify Alnylam at least [**] prior to the deadline for any such submission, and Alnylam shall
submit the designated Alnylam Patent Rights, if any, in accordance with applicable Law.

          8.7 Cooperation. Subject to Alnylam Third Party Obligations, to the extent Alnylam Patent
Rights are owned by Alnylam’s Affiliates or Listed Counterparties, Alnylam shall use best efforts
to cause such Affiliates or Listed Counterparties to comply with the provisions set forth in this
Article VIII.

          8.8 Trademarks. Each Party and its Affiliates shall retain all right, title and interest in
and to its and their respective housemarks. Takeda shall not acquire any rights under this
Agreement in any trademark, service mark or Internet domain name including the word “Alnylam” or
any other trademarks or trade dress of Alnylam or its Affiliates, and Alnylam shall not acquire any
rights under this Agreement in any trademark, service mark or Internet domain name including the
word “Takeda” or any other trademarks or trade dress of Takeda or its Affiliates. Takeda shall
solely own and be solely responsible for selecting, filing, prosecuting, maintaining, defending and
enforcing all Licensed Product (including any Shared Product) trademarks and copyrights at Takeda’s
sole expense.

ARTICLE IX

CONFIDENTIAL INFORMATION

          9.1 Confidential Information. With respect to any Confidential Information of a Party
disclosed by it or its Affiliates to the other Party during the term of this Agreement, such
receiving Party agrees: (a) not to use any Confidential Information in connection with activities
other than those contemplated by this Agreement, (b) that any Confidential Information shall not be
used in conjunction with any Third Party who is not a consultant of, or an advisor to, the
receiving Party or its Affiliates without the prior written consent of the disclosing Party, (c)
that Confidential Information shall be maintained in confidence by the receiving Party and its
Affiliates, and (d) that Confidential Information shall not be disclosed by the receiving Party or
its Affiliates to any Third Party who is not a consultant of, or an advisor to, the receiving Party
or its Affiliates without the prior written consent of the disclosing Party. Notwithstanding the
foregoing provisions of this Section 9.1, either Party may disclose Confidential Information of the
other Party or the terms of this Agreement if such Party reasonably determines, based on advice
from its counsel, that it is required to make such disclosure by applicable Law or legal process,
including by the rules or regulations of the United States Securities and Exchange Commission (the
“SEC”) or similar regulatory agency in a country other than the United States or of any
stock exchange, in which event such Party shall provide prior notice of such intended disclosure to
such other Party sufficiently in advance (to the extent practicable) to enable the other Party to
seek confidential treatment or other protection for the Confidential Information subject to such
requirement unless the disclosing Party is prevented by Law from providing such advance notice,
shall disclose only such Confidential Information of such other Party as

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such disclosing Party reasonably determines is required to be disclosed, and shall seek
confidential treatment of any terms of this Agreement that such other Party considers particularly
sensitive from the SEC, similar regulatory agencies in countries other than the United States, or
any stock exchange.

          9.2 Disclosures to Employees, Consultants and Advisors. Each Party agrees that it and its
Affiliates shall provide Confidential Information received from the other Party only to the
receiving Party’s respective employees, consultants and advisors, and to the employees, consultants
and advisors of the receiving Party’s Affiliates, who have a need to know such Confidential
Information to assist the receiving Party in fulfilling its obligations under this Agreement,
provided that each Party shall remain responsible for any failure by its and its
Affiliates’ respective employees, consultants and advisors to treat such information and materials
as required under Section 9.1.

          9.3 Term. All obligations imposed under this Article IX shall expire five (5) years after the
expiration or termination of this Agreement.

          9.4 Publicity. Upon execution of this Agreement, the Parties shall jointly issue a press
release announcing the execution of this Agreement in form and substance substantially as attached
hereto as Schedule M. During the term of this Agreement, the content of any press release
or public announcement relating to this Agreement and/or Licensed Products shall be mutually agreed
upon by the Parties, which agreement shall not be unreasonably withheld, delayed or conditioned,
except that a Party may, without the other Party’s consent, (a) issue such press release or public
announcement if the contents of such press release or public announcement have previously been made
public other than through a breach of this Agreement by the issuing Party or its Affiliates, or (b)
issue such press release or public announcement if such Party is advised by its counsel that it is
required to issue such a press release or public announcement by applicable Law or legal process,
including by the rules or regulations of the SEC or similar regulatory agency in a country other
than the United States or of any stock exchange, in which event such Party shall provide prior
notice of such intended press release or public announcement to the other Party unless the
disclosing Party is prevented by Law or legal process from providing such advance notice and shall
include in such press release or public announcement only such information relating to this
Agreement and/or the Licensed Product as it reasonably determines is required by such applicable
Law or legal process. The Party subject to the requirement to issue such press release or public
announcement shall, if reasonably practicable under the circumstances, consider in good faith all
comments provided by the other Party prior to such press release or public announcement and
incorporate all comments that are reasonable. Notwithstanding anything to the contrary in this
Agreement, each Party may disclose the terms of this Agreement to existing and prospective
investors, acquirers and lenders in connection with such Party’s financing activities,
provided that, each such Third Party is subject to an obligation of confidentiality
with respect to such information no less strict than the disclosing Party’s obligation of
confidentiality with respect to the other Party’s Confidential Information hereunder.

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ARTICLE X

REPRESENTATIONS, WARRANTIES AND COVENANTS

          10.1 Mutual Representations and Warranties.

          (a) Representations of Authority. Each Party represents and warrants to the other
Party that, as of the Effective Date, it has full corporate right, power and authority to enter
into this Agreement and to perform its obligations under this Agreement.

          (b) Consents. Each Party represents and warrants to the other Party that all
necessary consents, approvals and authorizations of all government authorities and other Persons
required to be obtained by it as of the Effective Date in connection with the execution, delivery
and performance of this Agreement have been obtained.

          (c) No Conflict. Each Party represents and warrants to the other Party that the
execution and delivery of this Agreement and the performance of its obligations hereunder (i) does
not violate or conflict with the provisions of its certificate of incorporation or by-laws, (ii)
does not conflict with or violate any requirement of applicable Law effective as of the Effective
Date, and (iii) does not and will not conflict with, violate, breach or constitute a default under
any contractual obligations of it or any of its Affiliates existing as of the Effective Date.

          (d) Authorization and Binding Nature. Each Party represents and warrants to the other
Party that the execution, delivery and performance of this Agreement and the performance of all
obligations hereunder have been duly authorized by all requisite corporate action on the part of
such Party and this Agreement constitutes valid and legally binding obligations of such Party,
limited by applicable bankruptcy, insolvency, reorganization, moratorium and other Laws of general
application affecting the enforcement of creditors’ rights generally and as may be limited by Laws
relating to the availability of specific performance, injunctive relief or other equitable
remedies.

          (e) Employee Obligations. Each Party represents and warrants that all of its
employees, officers and consultants have executed agreements or have existing obligations under Law
requiring assignment to such Party of all intellectual property and proprietary rights made during
the course of and as the result of their association with such Party, and obligating such
individuals to maintain as confidential the Confidential Information of such Party and of a Third
Party which such Party may receive.

          10.2 Representations, Warranties and Covenants of Alnylam. Alnylam represents and warrants to
Takeda that, as of the Effective Date:

          (a) Organization and Good Standing. Alnylam is a corporation duly organized, validly
existing and in good standing under the Laws of the State of Delaware.

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          (b) Non-Infringement. To the best of Alnylam’s knowledge, (i) no Third Party is
currently infringing or misappropriating any Alnylam Intellectual Property, it being understood
that there may be Third Parties that are conducting research or clinical development under the
“safe harbor” exemption from patent infringement under 35 U.S.C. § 271(e)(1) or similar exemptions
in other jurisdictions, and (ii) the practice of the Alnylam Intellectual Property licensed under
this Agreement does not violate the intellectual property rights of any Third Party.

          (c) Validity. All Alnylam Intellectual Property that is owned by Alnylam, and, to the
best of Alnylam’s knowledge, all Alnylam Intellectual Property that is licensed by Alnylam pursuant
to Listed Alnylam Third Party Agreements, is in full force and effect and all necessary
registration, maintenance, and renewal fees for such Alnylam Intellectual Property have been paid
on time and Alnylam shall take all reasonable steps to ensure that its obligations with respect to
all administrative procedures of any governmental authority relating to the Alnylam Patent Rights
are fully complied with in a timely manner in all material respects. Except for those oppositions
or challenges which are publicly disclosed in Alnylam’s filings with the SEC, no Third Party has
initiated a suit or other proceedings to challenge the validity of the Alnylam Patent Rights.
Alnylam has no reason to believe that the issued Alnylam Patent Rights are other than valid and
enforceable.

          (d) Litigation. There is no pending, and Alnylam and its Affiliates are not aware of
any threatened, claim or litigation (nor has Alnylam received notice of a potential claim or
litigation) (i) which alleges that any issued patents of a Third Party would be infringed by the
Development and Commercialization of any Licensed Product hereunder or (ii) that questions the
validity of this Agreement or the right of Alnylam to enter into this Agreement, or to consummate
the transactions contemplated hereby. To Alnylam’s knowledge, there are no legal actions or
investigations pending, or to the best of Alnylam’s knowledge threatened, involving the employment
by or with Alnylam of any of Alnylam’s current or former officers, their use in connection with
Alnylam’s business or any information or techniques allegedly proprietary to any of their former
employers, or their obligations under any agreements with prior employers or alleging a violation
of Law. Alnylam is not a party to any order, writ, injunction, judgment or decree of any court.
There is no action, suit, proceeding or investigation by Alnylam currently pending or that Alnylam
intends to initiate.

          (e) Authority. Alnylam and its Affiliates have the right and authority to grant the
license to Takeda set forth in Section 3.1(a) or other rights as contemplated under this Agreement.
Alnylam and its Affiliates shall not grant any right or enter into any agreement with any Third
Party that would prevent or have a material adverse effect on Takeda’s exercise of its rights under
this Agreement or Alnylam’s performance of its obligations under this Agreement.

          (f) Alnylam Patent Rights. Schedule A provides a complete listing of the
Alnylam Patent Rights as of the Effective Date. Except as set forth on Schedule A, Alnylam
does not Control as of the Effective Date, any other Patent Rights licensed hereunder that Cover
RNAi technology, products or processes (including compositions,

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methods and uses of RNAi Compounds), including: (i) the general structure, architecture, or
design of RNAi Compounds; (ii) chemical modifications of such RNAi Compounds (including any
modifications to the bases, sugars or internucleoside linkages, nucleotide mimetics, conjugates and
any end modifications); (iii) all uses or applications of RNAi Compounds referred to in the
foregoing clause (i) or (ii); (iv) Delivery Technologies; and (e) manufacturing techniques for RNAi
Compounds or Delivery Technologies; but excluding Patent Rights to the extent such
Patent Rights fall within Alnylam [**] Specific Patent Rights.

          (g) Listed Alnylam Third Party Agreements. Schedule E identifies all Listed
Alnylam Third Party Agreements existing as of the Effective Date. All Listed Alnylam Third Party
Agreements are in full force and effect, and no dispute presently exists between Alnylam and any of
such Listed Counterparties and Pre-Existing Alliance Parties that would adversely affect any of the
licenses granted by Alnylam under this Agreement. Alnylam shall use its best efforts to maintain
its good standing under each Listed Alnylam Third Party Agreement (including, without limitation,
by not initiating any patent challenges which could result in the termination of any in-license in
accordance with its terms). Alnylam shall not (i) breach any of its material obligations or waive
any of its rights under, (ii) amend in any manner that would be materially adverse to the rights
granted to Takeda hereunder (including, but not limited to, amending the [**] Agreement in any
manner prohibited by Section 3.10(c) or extending the [**] or increasing the number of exclusive
Targets under the [**] License Agreement or amending the [**] License Agreement in a manner similar
to those prohibited by Section 3.10(c)) or (iii) terminate any Listed Alnylam Third Party
Agreement, including by failure to satisfy any of its diligence obligations thereunder. If a
Listed Alnylam Third Party Agreement provides Alnylam with the opportunity to assume prosecution of
any Alnylam Patent Right or risk that such right will be abandoned, then Alnylam shall take
reasonable measures to prosecute such Alnylam Patent Right in the Field, consistent with prudent
commercial practices in the biotechnology industry.

          (h) Pre-Existing Alliance Agreements. Schedule F identifies all Pre-Existing
Alliance Agreements and other license agreements granted by Alnylam to Third Parties existing as of
the Effective Date which could adversely impact any of the rights granted by Alnylam under this
Agreement.

          (i) Alnylam Third Party Obligations. Schedule B summarizes all relevant
Alnylam Third Party Obligations under Listed Alnylam Third Party Agreements, including obligations
and restrictions that are imposed on sublicensees of the sublicensed Alnylam Intellectual Property,
and summarizes and identifies all Listed Alnylam Third Party Payment obligations. Alnylam has used
its best efforts to completely and accurately identify all obligations and restrictions to which
Takeda is subject as a sublicensee of Alnylam under the Listed Alnylam Third Party Agreements. To
Alnylam’s knowledge, there is no information which is not summarized on Schedule B and
which would materially affect the obligations of Takeda under the Listed Alnylam Third Party
Agreements.

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          (j) Payments to Listed Counterparties. As between Takeda and Alnylam, Alnylam will be
solely responsible for all sublicense income payable to the Listed Counterparties in connection
with the upfront payments set forth in Section 7.1, the milestones set forth in Section 7.2, and
subject to Section 7.3(d), all royalty payments to the Listed Counterparties in accordance with the
Listed Third Party Agreements.

          (k) Representations, Warranties and Covenants Regarding Certain Listed Alnylam Third Party
Agreements and Pre-Existing Alliance Agreements.

               (i) In the event that Takeda is required to make any payments in accordance with Section [**]
Agreement dated [**], Alnylam shall, at Takeda’s election, reimburse Takeda for such payment within
[**] or permit Takeda to offset such payment against any amounts owed to Alnylam under this
Agreement.

               (ii) In accordance with Section [**] of the [**] Agreement, Alnylam shall ensure that Takeda
will be able to qualify as one of the [**] Alnylam Collaborators (as defined in the [**] Agreement)
and, upon Takeda’s written request, Alnylam shall request that [**] promptly enter into
negotiations in good faith with Takeda for a license under [**] Licensed Patents (as defined in the
[**] Agreement).

          (l) Protecting IP Rights. Alnylam and its Affiliates have taken reasonable measures
to protect the Alnylam Intellectual Property, consistent with prudent commercial practices in the
biotechnology industry.

          (m) Targets.

               (i) Alnylam represents and warrants that as of the Effective Date there are no more than [**]
Blocked Targets.

               (ii) Alnylam covenants that once a Target becomes a Designated Target Takeda shall have, with
respect to Alnylam Intellectual Property, the full and unlimited right to exploit the licenses
granted to Takeda in the Field under this Agreement with respect to such Target(s).

               (iii) Prior to the expiration of the [**], Alnylam may grant certain exclusive rights with
respect to a Target(s) (other than a Designated Target) to [**] pursuant to the [**] as existing as
of the Effective Date. Prior to the expiration of the [**], Alnylam may grant certain exclusive
rights with respect to up to [**] Target(s) (other than (x) a Designated Target or (y) a Target
with respect to which the Gatekeepers have informed Takeda that it is not a Blocked Target) to [**]
pursuant to the [**] License Agreement as existing as of the Effective Date. Except as set forth
in this Section 10.2(m)(iii) above, during the term of this Agreement Alnylam covenants that it
will not grant any Third Party any exclusive rights to any Target.

          (n) Forthrightness. Alnylam has not misstated any information in any written
representation provided by Alnylam to Takeda, and has not intentionally or negligently withheld or
omitted any information from Takeda, which would reasonably

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be expected to be material to Takeda’s decision to enter into this Agreement or which is
necessary in order to make information disclosed by Alnylam not misleading.

          10.3 Representations and Warranties of Takeda. Takeda represents and warrants to Alnylam
that, as of the Effective Date, Takeda is not engaged in a dispute with [**].

          10.4 No Warranties. EXCEPT AS OTHERWISE EXPRESSLY SET FORTH IN SECTION 10.1, 10.2 or 10.3,
NEITHER PARTY MAKES ANY REPRESENTATION OR EXTENDS ANY WARRANTIES OF ANY KIND, EITHER EXPRESS OR
IMPLIED, TO THE OTHER PARTY, INCLUDING ANY WARRANTIES OF MERCHANTABILITY OR FITNESS FOR A
PARTICULAR PURPOSE.

ARTICLE XI

TERM AND TERMINATION

          11.1 Term. This Agreement shall be effective as of the Effective Date and shall continue,
subject to Sections 11.2, 11.3 and 11.4, in accordance with its terms until the later of (a) the
expiration of the last-to-expire Royalty Term, or (b) the expiration of the last-to-expire
Profit-Share Term. Without prejudice to any other rights or remedies available at Law or in
equity, neither Party shall have the right to terminate any right or obligation under this
Agreement except pursuant to Section 11.2, 11.3 or 11.4.

          11.2 Termination for Cause.

          (a) Termination As A Result of Alnylam’s Breach. Takeda may terminate this Agreement
on a Licensed Product-by-Licensed Product basis or solely as it relates to the Research
Collaboration or the Delivery Collaboration, or in its entirety, in each case upon [**] prior
written notice to Alnylam upon the material breach by Alnylam of any of its representations,
warranties or obligations under this Agreement relating to such Licensed Product, the Research
Collaboration or the Delivery Collaboration, respectively, or this Agreement in its entirety;
provided that such termination shall become effective only if (i) Alnylam fails to
remedy or cure the breach within such [**] period, or (ii) such breach cannot be remedied or cured
through the application of Commercially Reasonable Efforts within such [**] period, and Alnylam has
(within such time period) submitted a plan for cure as promptly as is reasonably practicable (but
in no event beyond an additional [**] period) through the application of Commercially Reasonable
Efforts with a remedy or cure period reasonably acceptable to Takeda, then after the earlier of the
remedy or cure date accepted by Takeda or the date Alnylam ceases to use Commercially Reasonable
Efforts to remedy or cure such breach.

          (b) Termination As A Result of Takeda’s Breach. Alnylam may terminate this Agreement,
at its sole discretion, on a Licensed Product-by-Licensed Product basis, or solely as it relates to
the Research Collaboration or the Delivery Collaboration, or in its

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entirety, in each case upon [**] prior written notice to Takeda upon the material breach by
Takeda of any of its representations, warranties or obligations under this Agreement relating to
such Licensed Product, the Research Collaboration or the Delivery Collaboration, respectively, or
this Agreement in its entirety; provided that such termination shall become
effective only if (i) Takeda fails to remedy or cure the breach within such [**] period, or (ii)
such breach cannot be remedied or cured through the application of Commercially Reasonable Efforts
within such [**] period, and Takeda has (within such time period) submitted a plan for cure as
promptly as is reasonably practicable (but in no event beyond an additional [**] period) through
the application of Commercially Reasonable Efforts with a remedy or cure period reasonably
acceptable to Alnylam, then after the earlier of the remedy or cure date accepted by Alnylam or the
date Takeda ceases to use Commercially Reasonable Efforts to remedy or cure such breach.

          (c) Termination As A Result of Insolvency. Subject to Section 3.3, either Party may
terminate this Agreement effective upon written notice to the other Party, upon the filing or
institution of bankruptcy, reorganization, liquidation or receivership proceedings, or upon an
assignment of a substantial portion of the assets for the benefit of creditors by the other Party;
provided, however, in the case of any involuntary bankruptcy or receivership
proceeding such right to terminate shall only become effective if the Party consents to the
involuntary bankruptcy or receivership or such proceeding is not dismissed within ninety (90) days
after the filing thereof.

          11.3 Patent Validity Challenges.

          (a) By Takeda. Without prejudice and subject to Takeda’s rights under Section 3.5, if
Takeda or any of its Affiliates or sublicensees initiates any legal action seeking a determination
that any of the Alnylam Patent Rights in any country are invalid, unenforceable, and/or not
infringed (including a request for reexamination of any such Patent Rights), to the extent
permitted by the applicable Law of such country, Alnylam may terminate this Agreement with the
effects provided under Section 11.5(b) upon sixty (60) days’ prior written notice to Takeda,
provided, however, that if, prior to the end of such sixty (60) day period Takeda
is able to obtain a full and complete withdrawal of such action, the termination shall not become
effective and this Agreement shall remain in full force and effect. For clarity, Takeda’s
initiation of a legal action with regard to a particular claim of any Patent Right Controlled by
Alnylam that is not licensed to Takeda under Section 3.1(a) at the time such legal action is
initiated shall not constitute a basis for Alnylam to terminate this Agreement under this Section
11.3(a).

          (b) By Alnylam. If Alnylam or any of its Affiliates or sublicensees initiates any
legal action seeking a determination that any of the Takeda New Delivery Patent Rights or the
Takeda Licensed Pre-Existing Delivery Patent Rights (or other applicable Patent Rights of Takeda
licensed hereunder in connection with any Shared Product or Abandoned Product) in any country are
invalid, unenforceable, and/or not infringed (including a request for reexamination of any such
Patent Rights), to the extent permitted by the applicable Law of such country, Takeda may terminate
this Agreement with the effects provided under Section 11.5(c) upon sixty (60) days’ prior written
notice

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to Alnylam, provided, however, that if, prior to the end of such sixty (60)
day period Alnylam is able to obtain a full and complete withdrawal of such action, the termination
shall not become effective and this Agreement shall remain in full force and effect.

          11.4 Termination at Will. Takeda shall have the right to terminate this Agreement on a
Licensed Product-by-Licensed Product or country-by-country basis after the first (1st) anniversary
of the Effective Date for any reason upon one hundred eighty (180) days prior written notice to
Alnylam, provided, however, that if the Royalty Term has not expired as of the date
of such termination with respect to such Licensed Product in such country and Takeda continues to
sell such Licensed Product in such country after the date of such termination, Takeda shall
continue to comply with the terms of this Agreement with respect to such Licensed Product in such
country until the expiration of the Royalty Term as if the Agreement had not terminated hereunder,
as such terms relate to the payment of royalties and event payments with respect to such Licensed
Product in such country, and the related accounting provisions of this Agreement.

          11.5 Effect of Expiration or Termination.

          (a) Effect of Expiration. Upon the expiration of the Royalty Term applicable to any
Licensed Product in a country, Takeda’s and its Affiliates’ license under Section 3.1(a) with
respect to such Licensed Product in such country shall become a fully paid-up, royalty-free
license, with the right to sublicense, to Develop, Commercialize or Manufacture such Licensed
Product in such country. Notwithstanding the foregoing, Takeda shall continue to provide Alnylam
with information regarding Licensed Product only to the extent necessary for Alnylam to comply with
its obligations under any relevant Alnylam Third Party Agreement.

          (b) Termination by Alnylam for Cause or Patent Challenge; Termination by Takeda for
Convenience. If (i) Alnylam terminates this Agreement pursuant to Section 11.2(b), 11.2(c) or
11.3(a) or (ii) Takeda terminates this Agreement pursuant to Section 11.4, then the licenses
granted to Takeda under Section 3.1(a) shall terminate with respect to the particular Licensed
Product, or the Research Collaboration or Delivery Collaboration, or this Agreement in its
entirety, as the case may be, that is the subject matter of such termination; provided,
however, that, in the event such termination is with respect to a Shared Product, Takeda
will be deemed to have opted-out of the joint Development and Commercialization of such Shared
Product, and such Shared Product shall be treated as an Abandoned Product in accordance with
Section 4.5. For purposes of clarity, (x) except to the extent this Agreement is terminated in its
entirety, Takeda shall retain its rights and obligations with respect to Licensed Products or
collaboration activities that are not the subject of the termination and (y) termination of this
Agreement in accordance with Section 11.3 shall be deemed termination of this Agreement in its
entirety.

          (c) Termination by Takeda for Cause or Patent Challenge. If Takeda terminates this
Agreement pursuant to Section 11.2(a), 11.2(c) or 11.3(b) then the license granted to Alnylam under
Section 3.2(a), and all other rights granted to Takeda under this Agreement shall terminate with
respect to the particular Licensed Product, or the

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Research Collaboration or Delivery Collaboration, or this Agreement in its entirety, as the
case may be, that is the subject matter of such termination; provided that upon
such termination Takeda may elect to retain the licenses granted to Takeda under Section 3.1(a), in
which case Takeda shall (subject to the offset right set forth below) continue to comply with its
payment obligations under Article VII; provided, however, that, in the event such
termination is with respect to a Shared Product, Alnylam will be deemed to have opted-out of the
joint Development and Commercialization of such Shared Product, and the applicable Profit-Sharing
Agreement shall terminate and the applicable effects of termination set forth in the Profit-Sharing
Agreement shall govern. If Takeda terminates this Agreement as contemplated by this Section
11.5(c), Takeda may offset against any unpaid amounts owed to Alnylam pursuant to Article VII by
the amount of Takeda’s damages determined by any court having jurisdiction over such matter to have
resulted from Alnylam’s breach of this Agreement.

          (d) Survival. The expiration or termination of any right or obligation under this
Agreement for any reason will not affect obligations, including the payment of any royalties and
event payments, that have accrued as of the date of such expiration or termination, as the case may
be, and the provisions set forth in Sections 3.8(a), 7.2-7.4 and 7.6 -7.13 (with respect to each
of the foregoing Sections, solely to the extent that any amounts are due but unpaid thereunder),
Section 3.1(a) (solely in accordance with Section 11.5(c)), Section 4.5 (solely in accordance with
Section 11.5(b)), Section 6.3, Section 8.1 and Section 8.2 (solely with respect to Joint Research
Collaboration Patent Rights and Joint Delivery Collaboration Patent Rights), this Section 11.5,
Sections 12.1, 12.2, 12.3, 12.6, 12.7 and 12.9 — 12.18, inclusive, and ARTICLE I, ARTICLE IX and
ARTICLE X hereof, shall survive such expiration or termination.

ARTICLE XII

MISCELLANEOUS

          12.1 Indemnification.

          (a) By Alnylam. Alnylam shall defend, indemnify and hold harmless Takeda, its
Affiliates and their respective directors, officers, employees and agents (“Takeda Indemnified
Parties”), at Alnylam’s cost and expense, from and against any liabilities, losses, costs,
damages, fees or expenses (including reasonable fees and expenses of legal counsel)
(“Losses”) arising out of any Third Party claim based on (i) any breach by Alnylam of any
of its representations, warranties or obligations pursuant to this Agreement, (ii) the negligence
or willful misconduct of Alnylam or its Affiliates or sublicensees, or any of their respective
directors, officers, employees and agents, in the performance of obligations or exercise of rights
under this Agreement or (iii) any Product Liability Claim relating to an Abandoned Product or other
RNAi Product (other than a Shared Product) licensed under this Agreement which is Developed and/or
Commercialized by Alnylam or its Affiliates or sublicensees, except to the extent that such claims
arise out of any negligence or willful misconduct of the Takeda Indemnified Parties.

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          (b) By Takeda. Takeda shall defend, indemnify and hold harmless Alnylam, its
Affiliates and their respective directors, officers, employees and agents (“Alnylam Indemnified
Parties”) at Takeda’s cost and expense, from and against any Losses arising out of any Third
Party claim based on (i) any breach by Takeda of any of its representations, warranties or
obligations pursuant to this Agreement, (ii) the negligence or willful misconduct of Takeda or its
Affiliates or sublicensees, or any of their respective directors, officers, employees and agents,
in the performance of obligations or exercise of rights under this Agreement, or (iii) any Product
Liability Claim relating to a Licensed Product (other than an Abandoned Product or a Shared
Product) or other RNAi Product (other than an Abandoned Product or a Shared Product) licensed under
this Agreement which is Developed and/or Commercialized by Takeda or its Affiliates or
sublicensees; except to the extent that such claims arise out of any negligence or willful
misconduct of the Alnylam Indemnified Parties.

          (c) Liability Contribution for Shared Products. With respect to any Licensed Product
that is a Shared Product, the following shall apply:

               (i) U.S. Product Liability. Each of Alnylam and Takeda shall be responsible for [**]
percent ([**]%) of the amount of any Losses resulting from the Product Liability Claim caused by
the applicable Shared Product sold in the U.S. except to the extent Alnylam is obligated to
indemnify Takeda or Takeda is obligated to indemnify Alnylam pursuant to Section 12.1(a) or
12.1(b), respectively.

               (ii) U.S. IP Liability. Each of Alnylam and Takeda shall be responsible for [**]
percent ([**]%) of the amount of any and all Losses arising out of or resulting from any Third
Party claim involving any actual or alleged infringement, misappropriation or other violation of a
Third Party’s intellectual property rights arising out of or related to the Alnylam Intellectual
Property or the Takeda Intellectual Property, caused by the use, Manufacture, or Commercialization
of a Shared Product in the U.S. except to the extent Alnylam is obligated to indemnify Takeda or
Takeda is obligated to indemnify Alnylam pursuant to Section 12.1(a) or 12.1(b), respectively.

               (iii) Procedures. The Parties shall use the indemnification procedures set forth in
Section 12.1(d) for executing the liability contribution as provided in Section 12.1(c) and Takeda
shall be the Indemnifying Party solely for purposes of determining which Party has the right to
control the defense of the relevant Third Party claim and Alnylam shall have the rights, to which
an Indemnified Party is entitled, to participate in the indemnification procedures pursuant to
Section 12.1(d).

          (d) Claims for Indemnification with Respect to Third Parties.

               (i) With regard to any Third Party claim for which indemnification may be sought under this
Section 12.1 against a person entitled to indemnification under this Section 12.1 (an
“Indemnified Party”), the Indemnified Party shall give prompt written notification to the
person from whom indemnification is sought (the “Indemnifying Party”) of the commencement
of any action, suit or proceeding relating to such Third Party claim or, if earlier, upon the
assertion of any such claim by a

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Third Party (it being understood and agreed, however, that the failure by an Indemnified Party
to give notice of a Third Party claim as provided in this Section 12.1(d) shall not relieve the
Indemnifying Party of its indemnification obligation under this Agreement except and only to the
extent that such Indemnifying Party is actually prejudiced as a result of such failure to give
notice).

               (ii) Within [**] after delivery of such notification, the Indemnifying Party may, upon written
notice thereof to the Indemnified Party, assume control of the defense of such action, suit,
proceeding or claim with counsel reasonably satisfactory to the Indemnified Party. If the
Indemnifying Party does not assume control of such defense, the Indemnified Party shall control
such defense.

               (iii) The Party not controlling such defense may participate therein at its own expense;
provided that if the Indemnifying Party assumes control of such defense and the
Indemnified Party reasonably concludes, based on advice from counsel, that the Indemnifying Party
and the Indemnified Party have conflicting interests with respect to such action, suit, proceeding
or claim, the Indemnifying Party shall be responsible for the reasonable fees and expenses of
counsel to the Indemnified Party solely in connection therewith; provided further,
however, that in no event shall the Indemnifying Party be responsible for the fees and expenses of
more than one counsel in any one jurisdiction for all Indemnified Parties.

               (iv) The Party controlling such defense shall keep the other Party advised of the status of
such action, suit, proceeding or claim and the defense thereof and shall consider recommendations
made by the other Party with respect thereto.

               (v) The Indemnified Party shall not agree to any settlement of such action, suit, proceeding
or claim without the prior written consent of the Indemnifying Party, which shall not be
unreasonably withheld. The Indemnifying Party shall not, without the prior written consent of the
Indemnified Party, agree to any settlement of such claim or consent to any judgment in respect
thereof that does not include a complete and unconditional release of the Indemnified Party from
all liability with respect thereto or that imposes any liability or obligation on the Indemnified
Party.

          12.2 Dispute Resolution. Subject to the exceptions set forth in Sections 2.3(b), 3.5 and 3.8,
should a dispute arise under this Agreement that the Parties are not initially able to resolve,
such dispute shall be referred to the Executive Officers (or their designees), who shall promptly
initiate discussions in good faith to resolve such dispute. If such dispute is not resolved by the
Executive Officers within [**] after the date the Executive Officers first met to consider such
dispute, such dispute shall be resolved in accordance with Section 12.3.

          12.3 Governing Law and Waiver of Jury Trial. This Agreement shall be construed and the
respective rights of the Parties determined according to the substantive laws of the State of New
York, USA, excluding (a) any of its conflicts of laws principles to the contrary; (b) the United
Nations Conventions on Contracts for the International Sale of Goods; (c) the 1974 Convention on
the Limitation Period in the

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International Sale of Goods; and (d) the Protocol amending the 1974 Convention on the
Limitation Period in the International Sale of Goods, done at Vienna, April 11, 1980. The Parties
hereby (A) irrevocably submit to the jurisdiction of the state and federal courts in the State of
New York and agree that all claims shall be heard and determined in any such court; (B) waive any
defense of inconvenient forum to the maintenance of any such claims and further agree not to bring
any such claims in any other court; (C) irrevocably consent to service of process by certified
mailing, postage prepaid, or delivering such service to the Party at its respective notice address
set forth in Section 12.7; (D) waive any right to a trial by jury in any action or proceeding to
enforce or defend any rights under this Agreement or under any amendment, instrument, document or
agreement delivered in connection herewith or hereafter and agree that any such action or
proceeding shall be tried before a court and not before a jury; and (E) agree that a final judgment
shall be conclusive and may be enforced by suit on the judgment or in any other manner provided by
law or at equity. Notwithstanding anything to the contrary in this Section 12.3, either Party may
seek injunctive relief in any court in any jurisdiction where appropriate.

          12.4 Assignment. Neither Alnylam nor Takeda may assign this Agreement in whole or in part
without the consent of the other Party, except if such assignment is to an Affiliate of the
assigning Party, or subject to Section 12.5, occurs in connection with the sale or transfer of all
or substantially all of the business or assets of the assigning Party to which the subject matter
of this Agreement pertains. In the event that either Party is acquired (whether by merger or
otherwise) (an “Acquisition”) by a Third Party (the “Acquirer”), the other Party
shall not obtain any rights or access under this Agreement to any Know-How or Patent Rights
Controlled by such Acquirer which were not already within the Alnylam Intellectual Property or
Takeda Delivery Intellectual Property licensed to the relevant Party pursuant to Section 3.1(a) or
Section 3.2(a), as applicable, immediately prior to the consummation of such Acquisition.

          12.5 Alnylam Change of Control. In the event of an Alnylam Change of Control, Alnylam shall
notify Takeda promptly, but in no event later than [**], following final approval by Alnylam’s
board of directors of any transaction that constitutes an Alnylam Change of Control, or the
occurrence of an Alnylam Change of Control that does not require such approval. Within [**]
following consummation of the Alnylam Change of Control, Takeda may elect to exercise one or more
of the following options by notifying Alnylam in writing of such election(s):

          (a) Collaborations. At Takeda’s election, Takeda may terminate the Research
Collaboration and/or Delivery Collaboration, in which case the JRCC and/or the JDCC shall be
permanently disbanded, as applicable, in each case immediately upon written notice to Alnylam.

          (b) Licenses and Other Rights. Takeda shall have the right, at its sole discretion,
to terminate all licenses and rights granted to Alnylam pursuant to Sections 3.2(a) and 3.2(b);
provided that such license and right under Section 3.2(a) or 3.2(b) shall survive
if Alnylam is using Takeda Delivery Intellectual Property to Develop and/or

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Commercialize an RNAi Product that at the time of such termination, has, at a minimum,
completed a [**].

          (c) Alnylam’s Profit-Sharing Option. Takeda shall have the option, at its sole
discretion, to terminate Alnylam’s Profit-Sharing Option with respect to any Licensed Products
that, as of the exercise by Takeda of such option, are not Shared Products. In addition, Takeda
shall have the option, with respect to any Shared Product, to terminate certain joint aspects of
the joint Development and Commercialization of such Shared Product or initiate the Auction Option
(as defined below), as set forth below:

               (i) if no NDA has been filed with respect to such Shared Product at the time such Alnylam
Change of Control is consummated, Takeda may (A) continue with the Shared Product collaboration
pursuant to the Profit-Sharing Agreement or (B) terminate the rights and obligations of Alnylam to
conduct Development and/or Commercialization activities, perform Co-Promotion activities or have
other active involvement with respect to such Shared Product, and in connection therewith terminate
the SPC and any Joint Development Plan and/or any Joint Commercialization Plan with respect to such
Shared Product, other than (x) Alnylam’s right and obligation to pay or receive, as applicable,
fifty percent (50%) of the Net Profits/Losses of such Shared Product and (y) Alnylam’s right to
receive [**] percent ([**]%) of future Development milestones as set forth in Section 7.2(a) with
respect to such Shared Product. Notwithstanding the foregoing, if Alnylam exercises its Opt-Out
Option pursuant to Section 4.3(b)(i), Alnylam shall be entitled to receive [**] percent ([**]%) of
future Development milestones as set forth in Section 7.2(a) and one hundred percent (100%) of
royalty payments as set forth in Section 7.3;

               (ii) if an NDA has been filed with respect to such Shared Product at the time an Alnylam
Change of Control occurs, Takeda may (x) continue with the Shared Product collaboration pursuant to
the Profit-Sharing Agreement or (y) exercise its “auction option” to evaluate and conduct an
internal auction between Takeda and Alnylam whereby each Party may bid for the other Party’s fifty
percent (50%) interest in the Net Profits/Losses of such Shared Product pursuant to the procedures
set forth in Sections 12.5(c)(ii)(A) and (B) below (the “Auction Option”).

                    (A) Takeda shall, within [**] after the consummation of the Alnylam Change of
Control, notify Alnylam in writing if it elects to initiate the Auction Option. Within
[**] after Takeda’s written notice, the Parties shall engage a mutually agreed upon
internationally recognized investment banking firm (the “Auction Banking Firm”) to
evaluate the fair market value of a fifty percent (50%) interest in the Net Profits/Losses
of such Shared Product. Within [**] (or such other period of time as agreed to by the
Parties) after its engagement, the Auction Banking Firm shall provide a report to the
Parties, setting forth (i) its determination of such fair market value and (ii) its
underlying rationale in making such determination. Within [**] after its receipt of the
report, Takeda shall notify Alnylam in writing whether it elects to continue such Auction
Option.

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                    (B) Within [**] after Takeda’s written notice, each Party may deliver to the Auction
Banking Firm a written sealed bid stating the cash price it is willing to pay to acquire
the entire interest in the Net Profits/Losses of such Shared Product controlled by the
other Party (each, a “Bid”). Within [**] after the expiration of such [**] period,
or earlier upon receipt of a Bid from both Parties, the Auction Banking Firm shall notify
each Party in writing if only one (1) Bid was received, or if two (2) Bids were received
which Bid is higher (the “Bid Notice”). The Party who has submitted the Bid, if
only one (1) Bid was received, or the higher Bid, if two (2) Bids were received, shall
purchase the entire interest in the Net Profits/Losses of such Shared Product controlled by
the other Party, which purchase shall be consummated within [**] following the Bid Notice;
provided, that such period shall be extended as may be necessary in order
to obtain requisite governmental or regulatory approvals. The Parties shall execute and
deliver appropriate documentation, in form and substance that is reasonably acceptable, to
effect the transfer of the selling Party’s entire interest in the Shared Product and each
Party further agrees to reasonably cooperate to effect the orderly transition, the cost of
which shall be shared equally by the Parties, of any activities then being conducted by the
selling Party and its Affiliates for the Shared Product.

                    (C) The fees for the Auction Banking Firm for generating the report and conducting
the bidding process shall be [**]. The fees payable to the Auction Banking Firm in
connection with the successful sale of the selling Party’s interest in the Shared Product
shall be paid by the Party that [**]. Each Party shall be responsible for all of its own
legal and administrative fees and expenses incurred in the transfer of the Shared Product
and all of its costs incurred in connection with the transfer of technology and any
regulatory filings and related data and information related to such Shared Product.

          (d) Alnylam’s Right of First Negotiation. At Takeda’s election, Alnylam’s right of
first negotiation pursuant to Section 3.2(c) shall terminate. In the event that Alnylam and Takeda
have already entered into an exclusive license agreement for Alnylam to Develop and/or
Commercialize a Licensed Product in the United States, Takeda may not terminate such license
agreement, unless the acquirer of Alnylam is a Prohibited Partner (defined below), in which case
Takeda may require Alnylam to sell Alnylam’s entire interest in such Licensed Product (the
“ROFN Call Option”) to Takeda at a price equal to the fair market value of such Licensed
Product (the “ROFN Call Price”). Takeda may exercise the ROFN Call Option by delivering
written notice to Alnylam (the “ROFN Call Notice”). In the event Takeda exercises a ROFN
Call Option:

               (i) Within [**] after the ROFN Call Notice, each Party shall engage a mutually agreed upon
internationally recognized investment banking firm (each, a “ROFN Banking Firm”) to
evaluate the fair market value of Alnylam’s entire interest in the Licensed Product that is the
subject of the ROFN Call Option. Within [**] (or such other period of time as agreed to by the
Parties) after such engagement, each ROFN Banking Firm shall provide a report to each Party,
setting forth (i) its determination of such fair market value and (ii) its underlying rationale in
making such determination.

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The ROFN Call Price shall be the average of such fair market values determined by such two (2)
ROFN Banking Firms; provided, however, that, if the higher value is more than [**]
percent ([**]%) of the lower value, a third internationally recognized investment banking firm
(which is independent of both Parties) shall be engaged by the Parties (or if they are unable to
agree within [**], then by the two (2) ROFN Banking Firms) to determine such fair market value by
selecting one (1) (but only one (1)) of the two (2) values previously determined by the two (2)
ROFN Banking Firms. Such determination by the third investment banking firm, if any, shall be
provided to each Party within [**] after its engagement. The cost of each Party’s ROFN Banking
Firm shall be borne by such Party, and the cost of such third investment banking firm, if any,
shall be shared equally by the Parties.

               (ii) Within [**] after its receipt of the report (or determination by such third investment
banking firm, if any), Takeda shall notify Alnylam in writing whether it elects to continue such
ROFN Call Option. If Takeda notifies Alnylam in writing that it elects to continue such ROFN Call
Option, then such purchase shall be consummated within [**] days following such written notice;
provided, that such period shall be extended as may be necessary in order to obtain
requisite governmental or regulatory approvals. The Parties shall execute and deliver appropriate
documentation, in form and substance that is reasonably acceptable, to effect the transfer of
Alnylam’s entire interest in such Licensed Product and each Party further agrees to reasonably
cooperate to effect the orderly transition, the cost of which shall be shared equally by the
Parties, of any activities then being conducted by Alnylam and its Affiliates for such Licensed
Product.

               (iii) “Prohibited Partner” shall mean (i) any Person identified in Schedule N,
as such schedule may be updated from time-to-time by agreement of the Parties, such agreement not
to be unreasonably withheld, or (ii) any Person that is Developing and/or Commercializing a
pharmaceutical product against the same Target as the Licensed Product that is the subject of the
ROFN Call Option.

          (e) Necessary Amendments. Upon Takeda’s election of any of the foregoing, the Parties
shall enter into an appropriate and customary written amendment to this Agreement or, as
applicable, the Profit-Sharing Agreement, to reflect the specific changes to the Parties’ rights
and obligations made pursuant to this Section 12.5. For the avoidance of doubt, Takeda shall be
entitled, in its sole discretion, to make the elections provided for in this Section 12.5 upon each
occurrence of an Alnylam Change of Control.

          12.6 Entire Agreement; Amendments. This Agreement (including all attachments hereto)
constitutes the entire agreement between the Parties with respect to the subject matter hereof, and
supersedes all other previous arrangements with respect to the subject matter hereof, whether
written or oral. Any amendment or modification to this Agreement shall be made in writing signed
by both Parties.

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          12.7 Notices.

	 	 	 	 	 
	          Notices to Alnylam shall be

          addressed to:

	 	 
	 	 
	 
	 	 	 	 
	          Alnylam Pharmaceuticals, Inc.
	 	 	 	 
	          300 Third Street
	 	 	 	 
	          Cambridge, MA 02142
	 	 	 	 
	          Telefacsimile: (617) 551-8101
	 	 	 	 
	          Attention: Vice President-Legal
	 	 	 	 
	 
	 	 	 	 
	          with a copy which shall not
	 	 	 	 
	          constitute notice to:
	 	 	 	 
	 
	 	 	 	 
	          Wilmer, Cutler, Pickering, Hale
	 	 	 	 
	          and Dorr LLP
	 	 	 	 
	          60 State Street
	 	 	 	 
	          Boston, MA 02109
	 	 	 	 
	          Telefacsimile: (617) 526-5000
	 	 	 	 
	          Attention: Steven D. Singer, Esq.
	 	 	 	 
	 
	 	 	 	 
	          Notices to Takeda shall be

	 	with separate copies thereof	 	 
	          addressed to:

	 	addressed to:	 	 
	 
	 	 	 	 
	          Takeda Pharmaceutical Company

	 	Takeda Pharmaceutical Company	 	 
	          Limited

	 	Limited	 	 
	          17-85, Jusohonmachi 2-chome,

	 	1-1, Doshomachi 4-chome,
	 	 
	          Yodogawa-ku, Osaka 532-8686,

	 	Chuo-ku, Osaka 540-8645, Japan	 	 
	          Japan

	 	 	 	 
	 
	 	 	 	 
	 

	 	Telefacsimile: +81-6-6204-2328/2055
	 	 
	          Telefacsimile: +81-6-6300-6730

	 	Attention: General Manager of
	 	 
	          Attention: General Manager of

	 	Global Licensing & Business
	 	 
	          Pharmaceutical Research Division

	 	Development Department and
	 	 
	 

	 	General Counsel	 	 
	 
	 	 	 	 
	          with a copy which shall not
	 	 	 	 
	          constitute notice to:
	 	 	 	 
	 
	 	 	 	 
	          Morgan, Lewis & Bockius LLP

	 	Morgan, Lewis & Bockius LLP	 	 
	 
	 	 	 	 
	          One Market, Spear Street Tower

	 	502 Carnegie Center	 	 
	          San Francisco, CA 94105-1596

	 	Princeton, NJ 08540	 	 
	 
	 	 	 	 
	          Telefacsimile: (415) 442-1001

	 	Telefacsimile: (609) 919-6701	 	 
	          Attention: Robin M. Silva

	 	Attention: Randall B. Sunberg	 	 

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Either Party may change its address by giving notice to the other Party in the manner herein
provided. Any notices given under this Agreement shall be in writing and deemed to have been
sufficiently given when delivered by hand, by overnight courier, or by certified or registered
mail, postage and other charges prepaid, in each case to the address set forth above or any other
address provided in accordance with this Section 12.7. The date of mailing any written or
electronic notice will be deemed the date on which such notice is given unless otherwise specified
in the notice.

          12.8 Force Majeure. No failure or omission by the Parties in the performance of any
obligation of this Agreement shall be deemed a breach of this Agreement or create any liability if
the same shall arise from any cause or causes beyond the reasonable control of the Parties, which
may include the following: acts of God; acts or omissions of any government; any rules, regulations
or orders issued by any governmental authority or by any officer, department, agency or
instrumentality thereof; fire; storm; flood; earthquake; accident; war; rebellion; insurrection;
riot; and invasion, and provided that such failure or omission resulting from one
of the above causes is cured as soon as is practicable after the occurrence of one or more of the
above-mentioned causes.

          12.9 Independent Contractors. It is understood and agreed that the relationship between the
Parties hereunder is that of independent contractors and that nothing in this Agreement shall be
construed as authorization for either Alnylam or Takeda to act as agent for the other.

          12.10 No Strict Construction. This Agreement has been prepared jointly and shall not be
strictly construed against any Party.

          12.11 Headings. The captions or headings of the sections or other subdivisions hereof are
inserted only as a matter of convenience or for reference and shall have no effect on the meaning
of the provisions hereof.

          12.12 No Implied Waivers; Rights Cumulative. No failure on the part of Alnylam or Takeda to
exercise, and no delay in exercising, any right, power, remedy or privilege under this Agreement,
or provided by statute or at law or in equity or otherwise, shall impair, prejudice or constitute a
waiver of any such right, power, remedy or privilege or be construed as a waiver of any breach of
this Agreement or as an acquiescence therein, nor shall any single or partial exercise of any such
right, power, remedy or privilege preclude any other or further exercise thereof or the exercise of
any other right, power, remedy or privilege.

          12.13 Severability. If, under applicable Law, any provision of this Agreement is invalid or
unenforceable, or otherwise directly or indirectly affects the validity of any other material
provision(s) of this Agreement (such invalid or unenforceable provision, a “Severed
Clause”), the Parties shall consult one another and use reasonable efforts to agree upon a
valid and enforceable provision that is a reasonable substitute for the Severed Clause in view of
the intent of this Agreement. In the event

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such a valid and enforceable provision cannot be agreed upon, the invalidity of one or more
Severed Clauses shall not affect the validity of this Agreement as a whole, unless the Severed
Clauses are of such essential importance to this Agreement that it is to be reasonably assumed that
the Parties would not have entered into this Agreement without the Severed Clauses.

          12.14 Execution in Counterparts; Facsimile Signatures. This Agreement may be executed in
counterparts, each of which, when so executed and delivered, shall be deemed to be an original, and
all of which, taken together, shall constitute one and the same instrument even if both Parties
have not executed the same counterpart. Signatures provided by facsimile transmission shall be
deemed to be original signatures.

          12.15 No Consequential or Punitive Damages. NEITHER PARTY HERETO WILL BE LIABLE FOR INDIRECT,
INCIDENTAL, CONSEQUENTIAL, SPECIAL, EXEMPLARY, MULTIPLE OR PUNITIVE DAMAGES, OR FOR LOST PROFITS,
ARISING OUT OF THIS AGREEMENT OR RELATING TO ANY BREACH OF THIS AGREEMENT, REGARDLESS OF ANY NOTICE
OF SUCH DAMAGES. NOTHING IN THIS SECTION 12.15 IS INTENDED TO LIMIT OR RESTRICT THE
INDEMNIFICATION RIGHTS OR OBLIGATIONS OF EITHER PARTY WITH RESPECT TO THIRD PARTY CLAIMS.

          12.16 Interpretation. Whenever the context may require, any pronoun shall include the
corresponding masculine, feminine and neuter forms. The words “include”, “includes” and
“including” shall be deemed to be followed by the phrase “without limitation.” The word “will”
shall be construed to have the same meaning and effect as the word “shall.” Unless the context
requires otherwise, (a) any definition of or reference to any agreement, instrument or other
document herein shall be construed as referring to such agreement, instrument or other document as
from time to time amended, supplemented or otherwise modified (subject to any restrictions on such
amendments, supplements or modifications set forth herein or therein), (b) any reference to any
Laws herein shall be construed as referring to such Laws as they from time to time may be enacted,
repealed or amended, (c) any reference herein to any Person shall be construed to include the
Person’s successors and assigns, (d) the words “herein”, “hereof’ and “hereunder”, and words of
similar import, shall be construed to refer to this Agreement in its entirety and not to any
particular provision hereof, (e) any reference herein to the words “mutually agree” or “mutual
written agreement” shall not impose any obligation on either Party to agree to any terms relating
thereto or to engage in discussions relating to such terms except as such Party may determine in
such Party’s sole discretion; (f) all references herein to Articles, Sections, Exhibits or
Schedules shall be construed to refer to Articles, Sections, Exhibits and Schedules of this
Agreement; and (g) all references to the “knowledge” of a Party shall refer to the actual knowledge
of any of such Party’s officer or director level employees or members of its Board of Directors, or
the knowledge which any such person would reasonably be expected to have assuming reasonable
inquiry in light of such person’s position with such Party.

-89-

 

          12.17 Actions of Affiliates. Each Party shall be liable for any failure by its Affiliates to
comply with the restrictions, limitations and obligations set forth in this Agreement. Neither
Party shall permit any of its Affiliates to commit any act (including any act of omission) that
such Party is prohibited hereunder from committing directly. To the extent that the rights granted
to a Party hereunder may be and are exercised by an Affiliate of such Party, such Affiliate shall
be bound by the corresponding obligations of such Party.

          12.18 No Third Party Beneficiaries. Except as expressly set forth in this Agreement, no
Person other than the Parties and their respective Affiliates and permitted assignees hereunder
shall be deemed an intended third party beneficiary hereunder or have any right to enforce any
obligation of this Agreement. Notwithstanding the foregoing, the Parties agree that [**] shall be
deemed a Third Party beneficiary of, and shall have the right to enforce directly against Takeda,
its Affiliates and/or its sublicensees, those rights set forth in the subsection titled
“Restrictions on Sublicensing by Alnylam” of Section 7 of Schedule B hereto.

          12.19 Further Assurances. Each Party agrees to duly execute and deliver, or cause to be duly
executed and delivered, such further instruments and do and cause to be done such further acts and
things, including, without limitation, the filing of such additional assignments, agreements,
documents and instruments, as the other Party may at any time and from time to time reasonably
request in connection with this Agreement or to carry out more effectively the provisions and
purposes of, or to better assure of and confirm unto such other Party its rights and remedies
under, this Agreement.

[Remainder of This Page Intentionally Left Blank]

-90-

 

Confidential

Execution Copy

          IN WITNESS WHEREOF, Alnylam and Takeda have caused this Agreement to be duly executed by their
authorized representatives, as of the date first written above.

	 	 	 	 	 
	 	TAKEDA PHARMACEUTICAL COMPANY LIMITED

 	 
	 	By:  	/s/ Yasuchika Hasegawa
 	 
	 	 	Name:  	Yasuchika Hasegawa 	 
	 	 	Title:  	President 	 
	 
	 	ALNYLAM PHARMACEUTICALS, INC.

 	 
	 	By:  	/s/ John Maraganore
 	 
	 	 	Name:  	John Maraganore 	 
	 	 	Title:  	Chief Executive Officer 	 

-92-

 

	 	 	 	 	 

SCHEDULE A

ALNYLAM PATENT RIGHTS 

[**]

A total of 100 pages have been omitted pursuant to a request for confidential treatment. Asterisks
denote omissions.

[**]

 

 

Schedule B

Description of Alnylam Third Party Obligations

(including Alnylam Third Party Payments)

          This Schedule B summarizes obligations of Alnylam or its Affiliates to, and the rights
of, Pre-Existing Alliance Parties and Listed Counterparties with respect to the Alnylam
Intellectual Property under Pre-Existing Alliance Agreements (as listed on Schedule E) and
Listed Alnylam Third Party Agreements (as listed on Schedule D), respectively, including
without limitation Listed Alnylam Third Party Payment obligations (marked with “***”), which are
applicable to Takeda under this Agreement, in each case subject to the terms and conditions of such
Pre-Existing Alliance Agreements and Listed Alnylam Third Party Agreements in the form as provided
to Takeda on or before the Effective Date.

          Unless otherwise expressly stated, capitalized terms not otherwise defined in this
Schedule B shall have the meanings ascribed to them in the applicable Pre-Existing Alliance
Agreement or Listed Alnylam Third Party Agreement, and references to sections, articles, schedules
or exhibits made in this Schedule B shall be to sections, articles, schedules or exhibits,
as the case may be, in or to such applicable Pre-Existing Alliance Agreement or Listed Alnylam
Third Party Agreement.

          This Schedule B also contains a “Brief Summary of Technology Covered by License” at the
beginning of the summary of each agreement. Such Brief Summaries of Technology Covered by License
are provided for informational purpose only and shall in no way affect the scope or nature of the
licenses granted to Takeda by Alnylam pursuant to this Agreement.

Page 1 of 93, Schedule B

 

MAX PLANCK (US)

	1.	 	Co-Exclusive License Agreement between Max Planck Innovation (formerly Garching Innovation
GmbH) (“Max Planck”) and Alnylam Pharmaceuticals, Inc. (“Alnylam”), dated
December 20, 2002, as amended by Amendment dated July 2, 2003 and the Requirement Amendment
(“Requirement Amendment”) effective June 15, 2005, and the Waiver Amendment dated
August 9, 2007 (as amended, “Max Planck US License Agreement”)

Brief Summary of Technology Covered by License:

Max Planck granted Alnylam a co-exclusive (with Alnylam Europe AG) license to develop and
commercialize RNAi therapeutics under certain patent rights developed by Dr. Thomas Tuschl relating
to “RNA Interference Mediating Small RNA Molecules”.

Limitations on Scope of License (Section 2.1)

	•	 	The license granted to Alnylam is limited to (1) a worldwide, co-exclusive (co-exclusive
with Alnylam Europe AG) license, with the right to sublicense, under the Patent Rights to
develop, make, have made, use, sell and import Licensed Products in the Field, which rights
are sublicenseable, and (2) a worldwide, non-exclusive license, without the right to grant
sublicenses, under the Patent Rights to develop, make, have made, use, sell and import
Licensed Products for all diagnostic uses other than for purposes of therapeutic monitoring.
	 
	•	 	Owners retain the right to practice under the Patent Rights for research, teaching,
education, non-commercial collaboration and publication purposes. The German and the U.S.
federal government retain a royalty-free, non-exclusive, non-transferable license to practice
any government-funded invention claimed in any Patent Rights for government purposes.

Restrictions on Sublicensing by Alnylam (Sections 2.4 and 11.8)

	•	 	Alnylam is prohibited from granting sublicenses under the Patent Rights to develop, make,
have made, use, sell and import Licensed Products for any diagnostic uses other than for
purposes of therapeutic monitoring.
	 
	•	 	Sublicensees are required to perform their sublicense agreement in accordance with the Max
Planck US License Agreement. If Max Planck determines that Alnylam or any of its Sublicencees
has failed to fulfill any of its obligations under Section 4 (Company Diligence Obligations
and Report) of the Max Planck US License Agreement, then Max Planck may treat such failure as
a material breach.
	 
	•	 	If any license granted to Alnylam under the Max Planck US License Agreement is terminated,
any sublicense under such license granted prior to termination of said license will remain in
full force and effect, provided that (i) the Sublicensee is not then in breach
of its sublicense agreement; and (ii) the Sublicensee agrees to be bound

Page 2 of 93, Schedule B

 

	 	 	to Max Planck as licensor under the terms and conditions of the sublicense agreement, provided
that Max Planck will have no other obligation than to leave the sublicense granted by Alnylam
in place.
	 
	•	 	Immediately after the signature of each sublicense granted under the Max Planck US License
Agreement, Alnylam is required to provide Max Planck with a copy of the signed sublicense
agreement.

Diligence and Reporting (Sections 4.1 and 4.2; Sections 1 and 3 of Requirement Amendment)

	•	 	Sublicensees are required to use commercially reasonable efforts to develop and to
introduce into the commercial market Licensed Products at the earliest practical date.
	 
	•	 	Sublicensees are required to furnish information to Alnylam for inclusion in its reports to
Max Planck, which reports are due within 30 days after the end of each calendar quarter with
Alnylam’s standard R&D report, on the progress of its efforts during the immediately preceding
calendar quarter to develop and commercialize Licensed Products for each indication and
sub-indication within the Field. The report shall also contain a discussion of intended R&D
efforts for the calendar quarter in which the report is submitted.

***Royalty Payment Obligation (Sections 5.2 and 5.3)

	•	 	The following running royalties are payable to Max Planck by Alnylam on Net Sales of
therapeutic and prophylactic Licensed Products by Alnylam and its Sublicensees:

	 	(i)	 	[**]% of the first US$[**] of annual accumulated Net Sales of all Licensed
Products;
	 
	 	(ii)	 	[**]% of annual accumulated Net Sales of all Licensed Products between
US$[**] and US$[**];
	 
	 	(iii)	 	[**]% of annual accumulated Net Sales of all Licensed Products between
US$[**] and US$[**];
	 
	 	(iv)	 	[**]% of annual accumulated Net Sales of all Licensed Products between
US$[**] and US$[**];
	 
	 	(v)	 	[**]% of annual accumulated Net Sales of all Licensed Products between
US$[**] and US$[**]; and
	 
	 	(vi)	 	[**]% of annual accumulated Net Sales of all Licensed Products above US$[**].

	•	 	If the sale of any Licensed Product is covered by more than one of the Patent Rights,
multiple royalties shall not be due. Alnylam or a Sublicensee develops diagnostic Licensed
Products, Alnylam will initiate negotiations with Max Planck at least [**]

Page 3 of 93, Schedule B

 

	 	 	prior to the intended first commercial sale of each diagnostic Licensed Product. Alnylam and
Max Planck will negotiate in good faith [**] for such diagnostic Licensed Product.
	 
	•	 	Non-cash consideration will not be accepted by any Sublicensee for Licensed Products
without the prior written consent of Max Planck.
	 
	•	 	If any Sublicensee takes, for objective commercial and/or legal reasons, a license from any
third party under any patent applications or patents that dominate the Patent Rights or is
dominated by the Patent Rights in order to develop, make, use, sell or import any Licensed
Product (explicitly excluding, without limitation, any third party patents and patent
applications for formulation, stabilization and delivery), then up to [**]% of any additional
running royalties to be paid to such third party may be deducted, up to [**]% of the running
royalties stated in Section 5.2 of the Max Planck US License Agreement, from the date such
running royalties must be paid to such third party. However, the running royalties stated in
Section 5.2 of the Max Planck US License Agreement will not be reduced to less than a minimum
of [**]% of Net Sales in any case. No deduction is allowed from running royalties due to Max
Planck for any license fees for patents and patent applications for formulation stabilization
and delivery. For avoidance of doubt, if a Sublicensee takes a license to a third party
target, in no event is a deduction allowed on any license fees for such target from running
royalties due to Max Planck under the Max Planck US License Agreement.
	 
	•	 	If (i) Sublicensees sell a Licensed Product in a country where no Patent Rights are issued
and no patent applications that are part of the Patent Rights are pending that have not been
pending for less than [**] after filing national patent applications in the country in
question, and (ii) such Licensed Product is manufactured in a country where Patent Rights are
issued or patent applications that are part of the Patent Rights are pending that have not
been pending for more than [**] after filing national patent applications in the country in
question, the royalties stated in Section 5.2 of the Max Planck US License Agreement will be
reduced by [**]% for such Licensed Product, until the expiration or abandonment of all issued
patents and filed patent applications within the Patent Rights in the country in which the
Licensed Product is manufactured.

Payments and Reports (Sections 5.4 and 5.5)

	•	 	Within 30 days after the end of each calendar half year, Alnylam is required to deliver a
detailed report to Max Planck for the immediately preceding calendar half year showing at
least (i) the number of Licensed Products sold by Alnylam and its Sublicensees in each
country, (ii) the gross price charged by Alnylam and its Sublicensees for each Licensed
Products in each country, (iii) the calculation of Net Sales, and (iv) the resulting running
royalties due to Max Planck according to those figures. If no running royalties are due to
Max Planck, the report shall so state.
	 
	•	 	Running royalties shall be payable for each calendar half year, and shall be due to Max
Planck within 60 days after the end of each calendar half year.

Page 4 of 93, Schedule B

 

Bookkeeping and Auditing (Sections 5.6 and 5.7)

	•	 	Sublicensees are obliged to keep complete and accurate books on any reports and payments
due to Max Planck under the Max Planck US License Agreement, which books shall contain
sufficient information to permit Max Planck to confirm the accuracy of any reports and
payments made to Max Planck. Upon Max Planck’s request, Alnylam, or agents appointed by Max
Planck for Alnylam, shall check the books of its Sublicensees for Max Planck, once a year.
This right of auditing by Max Planck shall expire five years after each report or payment has
been made. Alnylam shall have the right to check the books of its Sublicensees according to
Section 5.6. All payments made by Sublicensees under the Max Planck US License Agreement are
nonrefundable and noncreditable against each other.

Prosecution and Enforcement (Article 6)

	•	 	The Owners have the first right to prosecute the Patent Rights. If all Owners wish to
cease prosecution or abandon any of the Patent Rights, Alnylam will have the right to continue
prosecution or maintenance of such Patent Rights in its discretion, in its name and at its
expense. Max Planck will inform and offer Alnylam Europe AG, respectively. If Alnylam does
not accept Max Planck’s offer within 30 days after receiving it, the Owners will be free to
cease prosecution or abandon such Patent Rights.
	 
	•	 	The Owners will have the right, but not the obligation, to prosecute in their own
discretion and at their own expense, all infringements of the Patent Rights. The total cost
of any such sole infringement action will be borne by the Owners, and the Owners will keep any
resulting recovery or damages. In any such infringement suits, Alnylam will, at the Owners’
expense, cooperate in all respects.
	 
	•	 	Alnylam will have the right to join the Owners’ prosecution of any infringements of the
Patent Rights. In any such joint infringement suits, the Owners and Alnylam will cooperate in
all respects. The Owners and Alnylam will agree in good faith on the sharing of the total
cost of any such joint infringement action and the sharing of any recovery or damages derived
therefrom.
	 
	•	 	If the Owners decide not to prosecute infringements of the Patent Rights, neither solely
nor jointly with Alnylam, Max Planck will offer to Alnylam to prosecute any such infringement
in its own discretion and at its own expense. Max Planck will offer Alnylam Europe AG
respectively. The Owners will, at Alnylam’s expense, cooperate. The total cost of any such
sole infringement action will be borne by Alnylam, and Alnylam will keep any resulting
recovery or damages.

Certain Termination Rights (Sections 11.2, 11.3 and 11.5)

	•	 	Alnylam has the right to terminate the Max Planck US License Agreement for any reason upon
at least 6 months’ prior written notice to Max Planck and payment of all amounts due to Max
Planck through the effective date of termination.

Page 5 of 93, Schedule B

 

	•	 	If Alnylam ceases to carry on its business related to the Max Planck US License Agreement,
Alnylam must inform Max Planck immediately. Alnylam and Max Planck have the right to
terminate the agreement immediately upon written notice to the other.
	 
	•	 	To the extent legally enforceable, if any Sublicensee attacks, or has attacked or supports
an attack through a third party, the validity of any of the Patent Rights, Alnylam will have
the right to terminate the sublicense agreement immediately; upon request of Max Planck,
Alnylam will have the obligation to terminate such sublicense agreement.

Definitions:

“Field” means all uses other than the commercial sale or use of the Licensed Products as a
research reagent, including in a kit format, for research or educational purposes, including
without limitation, (a) Alnylam’s internal and collaborative research use, and (b) all therapeutic
and prophylactic uses, and (c) diagnostic uses for purposes of therapeutic monitoring, but
excluding all other diagnostic uses, specifically including human and veterinary diseases for all
indications.

“Joint Patent Rights” means the Tuschl patent applications entitled “RNA Sequence-Specific
Mediators of RNA Interference” listed on Appendix A to the Max Planck US License Agreement,
and resulting patents and patent applications.

“Licensed Products” means any product or part thereof the manufacture, use or sale of which
would, absent the license granted hereunder, infringe one or more issued claims of the Patent
Rights or one or more pending claims of the Patent Rights that have not been pending for more than
5 years after filing national patent applications in the country in question.

“Max Planck Patent Rights” means the Tuschl patent applications entitled “RNA Interference
Mediating Small RNA Molecules” listed on Appendix B to the Max Planck US License Agreement,
and resulting patents and patent applications.

“Owners” means MIT, Whitehead, UMass and Max Planck, collectively.

“Patent Rights” means the Joint Patent Rights and Max Planck Patent Rights together.

Page 6 of 93, Schedule B

 

CANCER RESEARCH TECHNOLOGY

	2.	 	Licence Agreement between Cancer Research Technology Ltd. (“CRT”) and Alnylam, dated
July 18, 2003 (“CRT Agreement”)

Brief Summary of Technology Covered by License:

CRT granted Alnylam exclusive rights to develop and commercialize RNAi therapeutics under certain
patent rights relating to “Inhibiting Gene Expression with dsRNA”.

Scope of License Grant (Sections 2.1 — 2.3, 2.5)

	•	 	The license granted to Alnylam and its Affiliate(s) is limited to an exclusive, worldwide
license in the Field under the CRT Patent Rights to research, develop, have developed, use,
keep, make, have made, import, have imported, sell, have sold and otherwise dispose or offer
to dispose of Licensed Products. Except as necessary for the development and/or sale of
Licensed Products in the Field, Alnylam does not have rights to make use of the CRT Patent
Rights for any diagnostic application, as research tools or reagents, for target validation,
or for small molecule drug discovery.
	 
	•	 	CRT and Cancer Research UK have the right to use, and CRT has the right to consent to the
use by academic research institutions (including for the sake of clarity those in receipt of
Cancer Research UK funding) of, the CRT Patent Rights in the Field for internal, or in
collaboration with another academic research institution, non-commercial, non-commercially
sponsored research. For the sake of clarity, Cancer Research UK-funded Researchers are
permitted under the CRT Patent Rights to conduct clinical trials of potential dsRNA
therapeutic agents as part of their Cancer Research UK-funded academic research.
	 
	•	 	CRT grants an option to Alnylam and its Affiliates to enter into non-exclusive,
non-sublicenseable and non-assignable licenses under the CRT Patent Rights in the fields of
either or both of [**] and [**] on terms to be agreed in good faith between CRT and Alnylam,
the payment terms in respect of each license which shall be no more than annual payments of
[**] pounds sterling (£[**]) or any (lesser) sum that may be agreed between CRT and a Third
Party licensee after the Commencement Date in the same field (other than a license pursuant to
which, or under the terms of a related agreement, significant resources are provided by the
Third Party in respect of a collaboration in the field).

Restrictions on Sublicensing by Alnylam (Section 2.4) 

	•	 	Any Sub-license entered into by Alnylam must be limited to the Field and contain
restrictions in equivalent terms to those set out in Clause 2.1 of the CRT Agreement.
	 
	•	 	Any Sub-license shall terminate automatically on the expiry or termination for whatever
reason of the CRT Agreement. If the CRT Agreement is terminated pursuant to Clause 10 of the
CRT Agreement, CRT has agreed to enter into a direct

Page 7 of 93, Schedule B

 

	 	 	licensing arrangement with any Sub-licensee on terms substantially similar to those contained
in the CRT Agreement save that any license granted by CRT to any Sub-licensee shall be
consistent with the terms of the Sub-license granted by Alnylam (or its Affiliate) in relation
to field, territory, exclusivity, rights to sub-license and payment provisions. However, if
the CRT Agreement is terminated by Alnylam pursuant to Clause 10.2 of the CRT Agreement, the
foregoing shall apply save that the granting of such license by CRT shall be subject to CRT’s
consent. Nothing in Clause 2.4 of the CRT Agreement shall confer upon CRT any obligation to
enter into a direct licensing arrangement with the Sub-licensee where the Sub-licensee is in
default of its obligations under the Sub-license. CRT shall not be expected to take any
responsibility for any disputes between Alnylam (or its Affiliate) and its Sub-licensees
relating to the terms of the Sub-license(s) and notwithstanding the foregoing, CRT shall not be
obliged to enter into a direct license with a Sub-licensee in circumstances in which the
Sub-licensee reserves any right to maintain a claim against CRT where such claim was previously
maintained against Alnylam (or its Affiliate).
	 
	•	 	Sublicensees are required to undertake to CRT directly to allow the same access to the
books and records as CRT has to Alnylam’s books and records under the CRT Agreement.
	 
	•	 	Sublicensees are restricted with respect to rights to assign in equivalent terms to those
set out in Clause 15 of the CRT Agreement and any further sublicensing must be subject to the
terms of Clause 2.4 of the CRT Agreement.
	 
	•	 	Alnylam or its Affiliate shall (subject to Alnylam’s and its Affiliate’s right to redact
confidential information not related to CRT’s rights hereunder) provide to CRT in confidence a
copy of each and every Platform Sub-license entered into.

***Royalty Payment Obligation (Sections 3.2.1 and 3.3)

	•	 	Royalties of [**]% of Net Sales of Royalty Licensed Products in the Field are payable to
CRT.
	 
	•	 	If at any time prior to or during the period for the payment of royalties under the CRT
Agreement in relation to any particular territory, a Sub-licensee elects in its reasonable
opinion to take a license from a Third Party to any Blocking IP to develop, make, sell, or
otherwise dispose of Licensed Products, the royalties set forth in Clause 3.2.1 shall be
reduced by [**]% of the amount paid to such Third Party to access said Blocking IP. In no
event shall the royalty payable to CRT be reduced below [**]%.

Royalty Reports and Payment (Sections 4.2.1 and 5.1)

	•	 	Royalty payments are required to be made to CRT within 30 days of the end of the Quarter in
which sales of the relevant Licensed Products took place.

Page 8 of 93, Schedule B

 

	•	 	Following the earlier of first commercial sale of a Licensed Product in the Field by
Alnylam or its Affiliate or the grant of a Sub-license, Alnylam is required to prepare an
annual statement showing all monies due to CRT under the CRT Agreement for the previous
calendar year, on a country by country basis. The statement shall include the number of units
of each Royalty Licensed Product sold in each country in which sales occurred, and shall be
submitted to CRT within 60 Business Days of March 31st of each year. If CRT gives notice
pursuant to the CRT Agreement that it does not accept the statement, Alnylam shall make
available to an independent accountant all books and records required for the purpose of
certifying such statement.

Books and Records (Section 5.2)

	•	 	Sub-licensees are required to keep true and accurate records and books of account
containing all data necessary for calculating amounts payable to CRT. Such records and books
of account shall be kept for 5 years following the end of the calendar year to which they
relate, and shall, upon reasonable notice having been given by CRT, be open at all reasonable
times on Business Days for inspection by an independent firm of accountants.

Diligence and Reporting (Article 6)

	•	 	Alnylam shall use reasonable efforts to develop, make, market, sell, and otherwise dispose
of Licensed Products in all therapeutic areas within the Field and market each Licensed
Product in the Field throughout the United States, Europe and Japan.
	 
	•	 	CRT shall provide notice to Alnylam of its knowledge of a willing potential sub-licensee.
Without prejudice to Clause 6.1 of the CRT Agreement, in the event that Alnylam (itself or
through Affiliates or Sub-licensees) declines to develop, make, market, sell or otherwise
dispose of Licensed Products in any therapeutic area or any indication within the cancer
therapeutic area within the Field or any territory within the Territory in the Field, Alnylam
shall (save as hereinafter provided) upon direct approach made by, or receipt of notice from
CRT of a willing potential sublicensee in respect of a Licensed Product that has demonstrated
clinical efficacy be obliged to enter into negotiations in good faith with such Third Party to
enter into a Sub-license in relation to such therapeutic area, indication, or territory. The
preceding provisions of Clause 6.2 of the CRT Agreement shall not apply in respect of any
therapeutic area, indication, or territory in respect of which Alnylam provides to CRT’s
reasonable satisfaction evidence that the conclusion of a Sub-license would:
	 
	•	 	(a) be contrary to sound and reasonable business practice applicable to pharmaceutical
development; or
	 
	•	 	(b) not materially increase the availability of therapeutic products covered by the CRT
Patent Rights.

Page 9 of 93, Schedule B

 

	•	 	If CRT believes that Alnylam has failed to meet the diligence requirements set forth in
Clause 6 of the CRT Agreement, but Alnylam fails to reestablish diligence within [**] of
receipt of notice from CRT, CRT’s remedy is limited to, at CRT’s discretion, termination of
Alnylam’s license under the CRT Patent Rights in the particular territory or therapeutic area
or, with respect to Clause 6.2 of the CRT Agreement, indication within the cancer therapeutic
area for which Alnylam has failed to meet the diligence requirements. For the sake of
clarity, should Alnylam’s license be terminated in respect of a therapeutic area or territory
pursuant to Clause 6.3 of the CRT Agreement, CRT shall be free to offer such therapeutic area
or territory to a potential licensee.
	 
	•	 	Within 30 days of the end of each Year, Alnylam shall provide CRT with a written report of
the steps taken by Alnylam, its Affiliates and Sub-licensees to comply with the performance
obligations of Clause 6.1 and Clause 6.2 of the CRT Agreement. Alnylam’s annual statement
shall also include a detailed description of therapeutic areas and territories under
development and an overview of Alnylam’s development plans for the forthcoming year (itself or
through Affiliates or Sub-licensees).
	 
	•	 	If Alnylam intends to undertake a Phase I Clinical Trial of any Licensed Product in the UK,
Alnylam shall, at its option, notify CRT with the particulars of the proposed investigation,
and allow Cancer Research UK the opportunity of conducting or procuring the conduct of the
investigation on behalf of Alnylam or participate in such an investigation, subject to the
agreement of terms acceptable to Alnylam, CRT and Cancer Research UK.

Prosecution and Enforcement (Sections 7.1, 7.2, 7.4 and 7.5)

	•	 	CRT shall or shall procure in consultation with and (except as set forth in Clause 7.2) at
the reasonable expense of Alnylam the filing, prosecution, and maintenance of any patents and
patent applications comprised within the CRT Patent Rights. Alnylam shall bear (except as set
forth in Clause 7.2) the full expense and shall reimburse in full and hold CRT harmless in
respect of any and all reasonable fees, charges, costs, levies or expenses incurred by CRT or
its agents after the Commencement Date in relation to such applications.
	 
	•	 	The reasonable costs of opposition and interference proceedings in relation to the CRT
Patent Rights (together “Challenges”) shall be borne equally by the Parties. In the
event that the total aggregate costs of Challenges in any year exceed $[**], CRT shall be free
to make no further contribution to the costs of Challenges and all further costs incurred
during that year (“Further Challenge Costs”) and, at Alnylam’s option, the future
control of such Challenge(s) shall be borne by Alnylam solely. CRT shall give credit for
[**]% of Further Challenge Costs actually paid by Alnylam against sums due from Alnylam to CRT
pursuant to Clause 3 of the CRT Agreement from that time forward. In the event that one or
more of the CRT Patent Rights are the subject of a declaration of interference by the USPTO as
interfering with claims in a patent or patent application which is owned by or licensed by
Alnylam or its Affiliate, CRT and Alnylam shall negotiate in good faith to reasonably agree on
a mechanism

Page 10 of 93, Schedule B

 

	 	 	outside the USPTO which simplifies the issues involved in determining priority and which awards
priority to the appropriate party to the interference.

	•	 	In any country where Alnylam elects not to have a patent application included in CRT Patent
Rights filed or to pay expenses associated with filing, prosecuting, interference or
equivalent proceedings, or maintaining a patent application or patent included in CRT Patent
Rights, CRT may file, prosecute, continue with interference or equivalent proceedings, and/or
maintain such patent application or patent at its own expense and for its own exclusive
benefit and Alnylam (and its Affiliates) thereafter shall not be licensed under such patent or
patent application. For the sake of clarity, should Alnylam elect not to continue with
interference or equivalent proceedings and CRT elect to continue with such proceedings,
Alnylam (and its Affiliates) shall cease to be licensed for the patent subject to interference
for that territory.
	 
	•	 	Alnylam shall, at its option and at its own cost, defend and enforce or shall procure the
defense or enforcement of the rights under the CRT Patent Rights. If Alnylam opts not to
defend or enforce the relevant CRT Patent Rights, Alnylam shall grant to CRT (if CRT so
requests) any and all rights that would be necessary for CRT to undertake the enforcement or
defense. If Alnylam is unable to grant such rights, then it shall, at CRT’s request, grant to
CRT the right to conduct such an action in its name. Alnylam shall provide, at CRT’s request
and CRT’s reasonable expense, such reasonable assistance as CRT may reasonably request in any
such proceedings.

Termination for Patent Challenge (Section 10.5)

	•	 	CRT may terminate the CRT Agreement upon 30 days’ written notice to Alnylam if Alnylam or
its Affiliate commences legal proceedings, with the exception of interference proceedings
declared by the USPTO or any other patent office, contesting the validity of the CRT Patent
Rights; or commences itself, or provides any material assistance to a Third Party in relation
to, legal proceedings contesting the ownership of the CRT Patent Rights. Any actions taken
concerning determination of priority of invention under US patent law between a CRT Patent
Right and claims in a patent or patent application which is owned by or licensed by Alnylam or
its Affiliate shall not be considered a contest of validity or ownership under Clause 10.5 of
the CRT Agreement.

Termination by Alnylam at Will (Section 10.2)

	•	 	Alnylam may terminate the CRT Agreement by written notice to CRT, and the CRT Agreement
will terminate 90 days after receipt by CRT of such notice

Definitions:

“Blocking IP” means any and all Patent Rights (other than that licensed under the CRT Agreement)
which, if claims covering subject matter of such Patent Rights issue, would render the use,
development, manufacture, sale, or other disposal of a Licensed Product unlawful in the absence of
a license to such Patent Rights from a Third Party.

Page 11 of 93, Schedule B

 

“CRT Patent Rights” means the patent applications referred to in Schedule 1 (entitled “Inhibiting
Gene Expression with dsRNA”) and all Patent Rights deriving priority from them and all Patent
Rights deriving priority from such Patent Rights.

“Field” means the development of RNAi therapeutic products for the treatment of human disease
(including by means of gene therapy).

“Licensed Products” means product or products which, or the process of production of which, or the
use of which falls within the scope of a Valid Claim of the CRT Patent Rights and Licensed Product
shall be construed as any one of them.

Page 12 of 93, Schedule B

 

STANFORD

	3.	 	Agreement between the Board of Trustees of the Leland Stanford Junior University
(“Stanford”) and Alnylam, dated September 17, 2003 (“Stanford Agreement”)

Brief Summary of Technology Covered by License:

Stanford granted Alnylam co-exclusive rights under an invention relating to “Efficient RNA
Transfection in the Livers of Living Mice” from the laboratory of Mark Kay, and certain patent
rights relating to “Methods and Compositions for In Vivo Delivery of a Naked Ribonucleic Acid Into
a Target Cell,” and “Methods and Compositions for RNAi Mediated Inhibition of Viral Gene Expression
in Mammals”, for the delivery of ex-vivo synthesized siRNA Molecules for research, development and
therapeutic uses.

Limitations on Scope of License (Articles 3 and 4; Sections 6.10, 13.2 and 13.7)

	•	 	The license granted to Alnylam is limited to a worldwide license under the Invention and
Licensed Patents in the Licensed Field of Use to make, have made, use, have used, sell, have
sold, import, and have imported Licensed Product.
	 
	•	 	The license to Alnylam is Co-Exclusive, including the right to sublicense in the Licensed
Field of Use. If the other Co-Licensee discontinues licensing this Field of Use, then the
Field of Use will become exclusive for Alnylam. If the other Co-Licensee discontinues any
other therapeutic license under the Licensed Patents, Stanford will so inform Alnylam and
Alnylam will have the option to obtain an exclusive, worldwide sublicensable license to such
therapeutic field. The terms of any such license will be negotiated in good faith by Stanford
and Alnylam. This option may be exercised by Alnylam by written notice to Stanford at any
time during a period of 90 days after notification by Stanford.
	 
	•	 	Stanford may practice the Invention and use the Technology for its own bona fide research,
including sponsored research and collaborations. Stanford has the right to publish any
information included in the Technology and Licensed Patents.
	 
	•	 	The Stanford Agreement is subject to all of the terms and conditions of Title 25 USC
200-204, including an obligation that Licensed Product sold or produced in the U.S. be
“manufactured substantially in the U.S.” Alnylam will take all reasonable action necessary on
its part as licensee to enable Stanford to satisfy its obligations to the U.S. Government
under Title 35.
	 
	•	 	If Alnylam or its sublicensee(s) is unable or unwilling to serve or develop a potential
market or market territory for which there is a willing sublicensee, Alnylam will, at
Stanford’s request, negotiate in good faith a sublicense under the Licensed Patents, provided
that the same request has been made of the other Co-Exclusive licensee. Bona fide business
concerns of Alnylam will be considered in any good faith negotiations for a sublicense under
the Stanford Agreement and Alnylam will not be

Page 13 of 93, Schedule B

 

	 	 	required to license/sublicense any other intellectual property to such sublicensee. If the
other Co-Exclusive licensee itself or through its sublicensees is already developing a product
in the market or market territory for which there is a willing sublicensee, Alnylam will not be
required to sublicense to such party. If any other issue arises in the context of such
required sublicensing, Stanford will discuss and try to resolve such issue with Alnylam in good
faith.
	 
	•	 	Alnylam may grant royalty-free or noncash sublicenses or cross-licenses only if Alnylam
pays all royalties due Stanford from sublicensee’s Net Sales.

Diligence and Reporting (Article 5)

	•	 	Alnylam is required to use all commercially reasonable efforts and diligence to develop,
manufacture, and sell or lease Licensed Product and to diligently develop markets for the
Licensed Product. In particular, Alnylam is required to meet the following milestones, which
will satisfy Alnylam’s diligence obligations: (1) By the end of the year 2005, Alnylam will
select the method of delivery. (2) By the end of the year 2006, Alnylam will optimize the
lead. (3) By the end of the year 2008, Alnylam will conclude preclinical development. If
Alnylam in good faith fails to meet a milestone set forth above, and Alnylam fails to
reestablish diligence within [**], Stanford may terminate the Stanford Agreement. Stanford
may also terminate the Stanford Agreement if Alnylam has not sold Licensed Product for any
[**] period after Alnylam’s first commercial sale of Licensed Product. Efforts of Alnylam’s
sublicensees or Affiliates will be considered efforts of Alnylam.
	 
	•	 	On or before September 30 of each year until Alnylam markets a Licensed Product, Alnylam is
required to make a written annual report covering the preceding year ending June 30, regarding
progress toward commercialization of Licensed Product. The report must include, as a minimum,
information (e.g., summary of work completed, key scientific discoveries, summary of work in
progress, current schedule of anticipated events or milestones and market plans for
introduction of Licensed Product) sufficient to enable Stanford to satisfy reporting
requirements of the U.S. Government, and for Stanford to ascertain progress by Alnylam toward
meeting the diligence requirements of Article 5 of the Stanford Agreement.

***Royalty Payment Obligation (Article 6)

	•	 	On each anniversary of the Effective Date, a minimum yearly royalty of $[**] must be paid
to Stanford, which payments are non-refundable but creditable against earned royalties to the
extent provided in Section 6.4.
	 
	•	 	Earned royalties of [**]% of Net Sales for Licensed Product are payable to Stanford,
subject to the following:

	 	(i)	 	Royalty Payments are reduced up to [**]% (from [**]% of Net Sales down to
[**]% of Net Sales) by the amount of royalty paid to access

Page 14 of 93, Schedule B

 

	 	 	 	additional intellectual property necessary in order to sell Licensed Products
(“Additional Earned Royalties”).
	 
	 	(ii)	 	Such royalty payments shall be reduced as follows:

	 	(1)	 	[**]% if Additional Earned Royalties are [**]% or less.
	 
	 	(2)	 	[**]% if Additional Earned Royalties are greater than [**]%
but less than [**]%.
	 
	 	(3)	 	[**]% if Additional Earned Royalties are equal to or greater
than [**]% but less than [**]%.
	 
	 	(4)	 	[**]% if Additional Earned Royalties are equal to or greater
than [**]% but less than [**]%.
	 
	 	(5)	 	[**]% if Additional Earned Royalties are equal to or higher
than [**]%.

	 	(iii)	 	Only one royalty is due on each Licensed Product, regardless of whether its
manufacture, use, importation, or sale is covered by more than one patent or patent
application included in Licensed Patents, and no further royalties will be due for use
of such Licensed Product by Alnylam or its sublicensee’s customers.

	•	 	Creditable payments under the Stanford Agreement will be an offset against each earned
royalty payment which is required to be paid under Section 6.3 until the entire credit is
exhausted.
	 
	•	 	If the Stanford Agreement is not terminated in accordance with other provisions, royalties
must continue to be paid on all Licensed Products that are either sold or produced under the
license granted in Article 3, whether or not such Licensed Products are produced before the
Effective Date or sold after the Licensed Patents have expired.

Restrictions on Sublicensing by Alnylam (Sections 13.1, 13.3-13.5 and 13.7)

	•	 	Alnylam may grant sublicenses in the Co-exclusive Licensed Field of Use during the
Co-Exclusive period (a) only in conjunction with intellectual property under Alnylam’s
control; and (b) only if Alnylam is developing or selling Licensed Products in the
Co-Exclusive Licensed Field of Use.
	 
	•	 	Any sublicense granted by Alnylam under the Stanford Agreement must be subject and
subordinate to the terms and conditions of the Stanford Agreement.
	 
	•	 	Any sublicense will expressly include the provisions of Articles 7 (Royalty Reports,
Payments and Accounting), 8 (Negation of Warranties) and 9 (Indemnity) for the benefit of
Stanford.

Page 15 of 93, Schedule B

 

	•	 	If a sublicensee desires that its sublicense survive the termination of the Stanford
Agreement, Stanford has agreed that the sublicense will revert to Stanford subject to the
transfer of all obligations, including the payment of royalties specified in the sublicense,
to Stanford or its designee, if the Stanford Agreement is terminated.
	 
	•	 	Alnylam will provide Stanford in confidence a copy of all relevant portions of any
sublicenses granted under the Stanford Agreement.

Restrictions on Further Sublicensing by Sublicensee (Section 13.3)

	•	 	Sublicensees may not further sublicense, except that Sublicensees may further sublicense
rights under Licensed Patents only as needed or implied in the course of distribution or
performance of service as required for the sale to an end user of Licensed Products.

Royalty Reports, Payments, and Accounting (Article 7)

	•	 	Beginning with the first sale of a Licensed Product, Alnylam is required to make written
reports (even if there are no sales) and earned royalty payments within 30 days after the end
of each calendar quarter. The report must be in the form of Appendix B to the
Stanford Agreement and state the number, description, and aggregate Net Sales of Licensed
Product during the completed calendar quarter, and calculation of earned royalty payment due.
With each report, royalty payments due for the completed calendar quarter must be paid.
	 
	•	 	A written report is due within 90 days after the license expires under Section 3.2 of the
Stanford Agreement. Alnylam is required to continue to make reports after the license has
expired, until all Licensed Product produced have been sold or destroyed. Royalty payments
must also continue to be made, concurrent with the submittal of each post-termination report.
	 
	•	 	Records must be kept and maintained for 3 years showing the manufacture, sale, use, and
other disposition of products sold or otherwise disposed of under the license, including
general-ledger records of cash receipts and expenses, as well as other information sufficient
to determine royalties due, including production records, customers, and serial numbers, and
related information in sufficient detail to enable Alnylam to determine the royalties payable
under the Stanford Agreement.
	 
	•	 	An independent certified public accountant selected by Stanford and acceptable to Alnylam
is permitted to examine such books and records from time to time (but no more than once a
year) to the extent necessary to verify the royalty and termination reports as detailed in the
Stanford Agreement.

Prosecution and Enforcement (Section 6.9; Article 12)

	•	 	Stanford will be responsible for the filing, prosecution and maintenance of the Licensed
Patents. Throughout the term of the Stanford agreement, Alnylam will

Page 16 of 93, Schedule B

 

	 	 	retain rights to any claims that have support in the Licensed Patents, whether or not they are
in a CIP. If Stanford elects not to continue to seek or maintain patent prosecution on any
Licensed Patent in any country during the co-exclusive term despite Alnylam’s willingness to
pay its share of the prosecution costs, Alnylam will have the right, at its expense, to
procure, maintain and enforce in any country such Licensed Patent.
	 
	•	 	Stanford, Alnylam and the other Co-Exclusive licensee will meet to discuss any suspected
infringement of any Licensed Patent by a third party during the Co-Exclusive period of the
Stanford Agreement. If the Field-of-Use becomes Exclusive for Alnylam, Stanford and Alnylam
will meet to discuss the matter during the Exclusive period of the Stanford Agreement.
	 
	•	 	If Stanford does not choose to institute suit against said third party within 60 days of
notification, then the suit may be brought in both Alnylam’s and the other Co-Exclusive
licensee’s names, and Stanford’s name if necessary, and Alnylam and Co-Exclusive licensee will
share equally the out-of-pocket costs thereof and any recovery or settlement. In such
situation, Alnylam and the other Co-Exclusive licensee will agree to the manner in which they
exercise control over such action and if either party desires to also be represented by
separate counsel of its own selection, such party will pay the fees for such counsel.
	 
	•	 	If both Stanford and the other Co-Exclusive licensee, or Stanford if there is no other
Co-Exclusive Licensee, choose not to institute suit against said third party within 60 days of
notification, then Alnylam will have the right to institute suit in its own name or if
necessary, in Stanford’s name, to enjoin such infringement. Alnylam will bear the entire cost
of such litigation and will be entitled to retain the entire amount of any recovery or
settlement. However, any recovery in excess of litigation/settlement costs will be considered
Net Sales and Alnylam must pay Stanford royalties as indicated in Article 6 of the Stanford
Agreement.

Negation of Warranties (Article 8)

	•	 	Stanford has represented and warranted to Alnylam that, to the best of Stanford’s OTL
knowledge, Stanford is the sole owner of Stanford Licensed Patents and has the right to enter
into the Stanford Agreement and to grant the rights and licenses set forth therein.
	 
	•	 	Notwithstanding the foregoing, nothing in the Stanford Agreement or any sublicense
agreement shall be construed as:

(i) Stanford’s warranty or representation as to the validity or scope of any Licensed
Patent;

(ii) A warranty or representation that anything made, used, sold, or otherwise disposed of
under any license granted under the Stanford Agreement or any

Page 17 of 93, Schedule B

 

sublicense agreement is or will be free from infringement of patents, copyrights, and other
rights of third parties;

(iii) An obligation to bring suit against third parties for infringement, except as
described in Article 12 of the Stanford Agreement;

(iv) Granting by implication, estoppel, or otherwise any licenses or rights under patents
or other rights of Stanford or other persons other than Licensed Patents, regardless of
whether the patents or other rights are dominant or subordinate to any Licensed Patents; or

(v) An obligation to furnish any technology or technological information.

Except as expressly set forth in the Stanford Agreement, it is acknowledged and agreed that
Stanford makes no representations and extends no warranties of any kind, either express or
implied. There are no express or implied warranties of merchantability or fitness for a
particular purpose, or that Licensed Products will not infringe any patent, copyright,
trademark, or other rights, or any other express or implied warranties.

	•	 	Nothing in the Stanford Agreement or any sublicense agreement grants any sublicensee any
express or implied license or right under or to U.S. Patent 4,656,134 entitled “Amplification
of Eucaryotic Genes” or any patent application corresponding thereto.

Indemnification and Insurance (Article 9) 

	•	 	Alnylam is required to indemnify, hold harmless, and defend Stanford and Stanford Hospitals
and Clinics, and their respective trustees, officers, employees, students, and agents against
all claims for death, illness, personal injury, property damage, and improper business
practices arising out of the manufacture, use, sale, or other disposition of Invention,
Licensed Patents, Licensed Products, by Alnylam or any sublicensee, or their customers except
to the extent such claims are due to the gross negligence or willful misconduct of Stanford.
Upon notification to Alnylam in writing of any such claim, Alnylam shall manage and control,
at its own expense, the defense of such claim and its settlement. Alnylam agrees not to settle
any such claim against Stanford without Stanford’s written consent where such settlement would
include any admission of liability on the part of Stanford, where the settlement would impose
any restriction on the conduct by Stanford of any of its activities, or where the settlement
would not include an unconditional release of Stanford from all liability for claims that are
the subject matter of such claim.
	 
	•	 	Subject to Section 9.1, neither Stanford nor Alnylam shall be liable to each other for any
loss profit, expectation, punitive or other indirect, special, consequential, or other damages
whatsoever, in connection with any claim arising out of or related to the Stanford Agreement
whether grounded in tort (including negligence), strict liability, contract, or otherwise.

Page 18 of 93, Schedule B

 

	•	 	Alnylam shall at all times comply, through insurance or self-insurance, with all statutory
workers’ compensation and employers’ liability requirements covering all employees with
respect to activities performed under the Stanford Agreement.
	 
	•	 	Alnylam shall maintain, during the term of the Stanford Agreement, Comprehensive General
Liability Insurance, including Product Liability Insurance prior to commercialization, with a
reputable and financially secure insurance carrier to cover the activities of Alnylam and its
sublicensees. Upon initiation of human clinical trials of any Licensed Product, such insurance
will provide minimum limits of liability of Five Million Dollars and will include Stanford and
Stanford Hospitals and Clinics, and their respective trustees, directors, officers, employees,
students, and agents as additional insureds. Insurance will be written to cover claims
incurred, discovered, manifested, or made during or after the expiration of the Stanford
Agreement and must be placed with carriers with ratings of at least A- as rated by A.M. Best.
Alnylam will furnish a Certificate of Insurance evidencing primary coverage and additional
insured requirements and requiring thirty (30) days prior written notice of cancellation or
material change to Stanford. Alnylam will advise Stanford, in writing, that it maintains
excess liability coverage (following form) over primary insurance for at least the minimum
limits set forth above. All insurance of Alnylam will be primary coverage; insurance of
Stanford and Stanford Hospitals and Clinics will be excess and noncontributory.

Certain Termination Rights (Section 14.1)

	•	 	Alnylam has the right to terminate the Stanford Agreement by giving Stanford at least 30
days’ prior written notice.

Definitions:

“Co-Exclusive” means that Stanford will only grant one further license in the Licensed
Territory in the Licensed Field of Use.

“Invention” means “Efficient RNA Transfection in the Livers of Living Mice” from the
laboratory of Mark Kay, as described in Stanford Docket S00-012.

“Licensed Field of Use” means delivery of ex-vivo synthesized siRNA Molecules for research,
development and therapeutic uses (including a diagnostic necessary for development, sale or
reimbursement of a therapeutic Licensed Product). The Licensed Field of Use specifically excludes
delivery of any system producing in vivo expressed siRNAs for therapeutic use,
including but not limited to episomal and integrated vectors, and recombinant viruses.

“Licensed Patents” means all patent applications filed on the Invention and all patents
issuing thereon, including certain patent applications entitled [**] and [**], and any divisions,
continuations and any foreign patent application or equivalent corresponding thereto, and any
Letters patent or equivalent thereof issuing thereon or reissue, reexamination or extension
thereof. Continuation-in-part applications that are offered to

Page 19 of 93, Schedule B

 

the other co-exclusive licensee will also be offered to Alnylam for licensing in the Licensed Field
of Use.

“Licensed Product” means any product or part in the Licensed Field of Use, the manufacture,
use or sale of which (a) is covered by a valid claim of an issued, unexpired Licensed Patent
directed to the Invention in the country in which it is made, used or sold; or (b) is covered by
any claim being prosecuted in a pending application of Licensed Patents in the country in which it
is made, used or sold unless such claim has been pending in such application or an earlier
application of Licensed Patents for greater than [**] years.

“siRNA Molecule” means an agent that modulates expression of a target gene by an RNA
interference mechanism.

Page 20 of 93, Schedule B

 

ISIS

	4.	 	Strategic Collaboration & License Agreement between Isis Pharmaceuticals, Inc.
(“Isis”), and Alnylam, dated March 11, 2004, as supplemented or amended by letter
agreements dated March 9, 2004 (as amended by letter agreement dated October 28, 2005), March
11, 2004, June 10, 2005 and two letter agreements dated January 31, 2008 (as amended,
“Isis Agreement”)

Brief Summary of Technology Covered by License:

Isis granted Alnylam co-exclusive rights to develop and commercialize certain double-stranded RNAi
products under certain patent rights and know-how, including Isis Current Motif and Mechanism
Patents, Isis Current Chemistry Patents, Isis Future Motif and Mechanism Patents and Isis Future
Chemistry Patents.

Alnylam granted Isis non-exclusive rights (including options) to research and develop certain
single-stranded and double-stranded RNAi products, and to develop and commercialize certain
single-stranded RNAi products, under certain patent rights and know-how, including Alnylam Current
Motif and Mechanism Patents, Alnylam Current Chemistry Patents, Alnylam Future Motif and Mechanism
Patents and Alnylam Future Chemistry Patents.

Limitations on Scope of License (Section 5.1 and 5.3; Article 6, as amended on March 11, 2004
and January 31, 2008; Sections 10.2 and 11.7)

	•	 	Alnylam is granted co-exclusive (with Isis) licenses under Isis Current Motif and Mechanism
Patents and Isis Current Chemistry Patents and subject to Section 11.8 under Isis Future Motif
and Mechanism Patents, Isis Future Chemistry Patents and Isis’ rights in Joint Patents to
research, develop, make, have made, use, import, offer to sell and sell Double Stranded RNA
and Double Stranded RNA Products.
	 
	•	 	The licenses granted to Alnylam exclude the right to practice the Isis Excluded Technology.
	 
	•	 	Isis retains its rights in the Isis Patent Rights and in the Joint Patents (x) exclusively
for the Isis Exclusive Targets and (y) exclusively for the Isis Encumbered Targets.
	 
	•	 	Licenses to Isis Patent Rights that are joint patents with Third Parties (i.e., invented by
one or more Isis inventors and one or more non-Isis inventors) are licensed subject to the
retained rights of any non-Isis inventors and their assignees and licensees. Any such
retained rights of non-Isis inventors and their assignees and licensees existing as of the
Effective Date are set forth in Exhibit 5.3(c) attached to the Addendum Transmittal to the
Isis Agreement.
	 
	•	 	Licenses to Isis Patent Rights that are subject to contractual obligations between Isis and
Third Parties in effect as of the Effective Date are licensed subject to the restrictions and
other terms described in Exhibit 5.3(d) attached to the Addendum

Page 21 of 93, Schedule B

 

	 	 	Transmittal to the Isis Agreement. Alnylam’s sublicensees are required to comply with such
restrictions and other terms.
	 
	•	 	Alnylam is granted a non-exclusive license, with no right to sublicense, to practice any
Know-How disclosed to Alnylam during the performance of the Isis Agreement, subject to the
non-disclosure obligations set forth in Article 12 of the Isis Agreement.

In addition, any licenses granted by Alnylam to a Third Party under Alnylam Patent Rights would be
subject to the following:

	•	 	Isis is granted non-exclusive licenses to research, develop, make, have made, use and
import Isis Products for Research Use, and to research, develop, make, have made, use, import,
offer to sell and sell Isis Single Stranded Products.
	 
	•	 	For each Gene Target in the Isis Target Pool, Isis is granted an option, exercisable during
a specified period, to obtain a non-exclusive license to research, develop, make, have made,
use, import, offer for sale and sell Double Stranded RNA and Double Stranded RNA Products.
	 
	•	 	The foregoing non-exclusive licenses, and options to obtain non-exclusive licenses, exclude
the right to practice the Alnylam Excluded Technology.
	 
	•	 	The licenses to Alnylam Patent Rights initially shall not include licenses to Patents
licensed by Alnylam from Stanford University, provided, that, if any such licensed Patent
become issued Patents, Isis shall have the option of expanding its licenses to Alnylam Patent
Rights to include such issued Patents.
	 
	•	 	Isis is granted an option to sublicense certain patent rights licensed by Alnylam from
Cancer Research Technology Limited pursuant to the CRT License.
	 
	•	 	Isis is also granted a non-exclusive license to practice any Know-How disclosed to Isis
during the performance of the Isis Agreement, subject to the non-disclosure obligations set
forth in Article 12 of the Isis Agreement.
	 
	•	 	If Alnylam grants to any Third Party that is not a Major Pharmaceutical Company a license
under the Alnylam Patent Rights to develop and commercialize Double Stranded RNA Products,
then if (a) either (i) the [**] terms of such license are more favorable to the Third Party
than the [**] terms under the Isis Agreement with respect to Isis Products are to Isis, or
(ii) the [**] covered by such license exceeds the [**] potentially licensed to Isis under the
Isis Agreement for development and commercialization of Double Stranded RNA Products, and (b)
the roles to be played by Alnylam and such Third Party in the development and
commercialization of Double Stranded RNA Products under such Third Party license, the nature
of the Gene Targets covered by such Third Party license and any other relevant terms of such
Third Party license do not collectively justify the conditions described in the preceding
clauses (a)(i) and/or (a)(ii), then Alnylam shall modify the terms of its

Page 22 of 93, Schedule B

 

	 	 	licenses to Isis under the Isis Agreement with respect to such conditions so that they are
reasonably equivalent to those granted to the Third Party.
	 
	•	 	The Parties are obligated to consult about the need to license any patents Controlled by
Third Parties that would be useful or necessary for either Party to research, develop, make,
have made, use, sell, offer for sale or import Double Stranded RNA Products. If it is agreed
that there is a desire to obtain a license or to acquire any such patent, the Parties will
negotiate in good faith regarding (i) the share of the financial obligations relating to the
license or acquisition that each Party will bear; (ii) the compensation of any acquisition
costs incurred in connection with obtaining the patent rights; and (iii) an agreement by the
Parties to abide by all terms of the agreement under which the patent rights are granted.

Certain Sublicense Terms (Sections 5.2, 5.3 and 14.4)

	•	 	Alnylam is not permitted to grant sublicenses under its co-exclusive licenses, except Naked
Sublicenses or in connection with a Bona Fide Drug Discovery Collaboration or a Development
Collaboration.
	 
	•	 	Alnylam cannot sublicense its right to grant Naked Sublicenses under the Isis Agreement
except that Alnylam may permit its sublicensees to grant further sublicenses in connection
with an Alnylam Product.
	 
	•	 	The rights of any sublicensee under any permitted sublicense granted in accordance with
Section 5.2 will survive the termination of the Isis Agreement.

***Royalty Payment Obligations (Section 7.2)

	•	 	Royalties are payable to Isis on sales of Alnylam Products, equal to [**]% of Net Sales.
	 
	•	 	The royalty may be reduced by [**]% of any additional royalties that Alnylam owes to Third
Parties on such Alnylam Product that arise from Alnylam acquiring access to new technologies
after the Effective Date (as defined in the Isis Agreement); provided, however that (a) the
royalty due under this section can never be less than a floor of [**]% and (b) additional
royalties arising as the result of the addition, pursuant to Section 11.8, of Isis Future
Chemistry Patents or Isis Future Motif and Mechanism Patents to the Isis Patent Rights
licensed to Alnylam cannot be used to reduce the royalty.

Payment Terms and Reports (Section 9.1)

	•	 	Royalties payable under the Isis Agreement are payable on a quarterly basis within 45 days
after the end of each calendar quarter. Alnylam is required to provide Isis with a report
setting forth (i) gross sales of Alnylam Products by Alnylam, its Affiliates and sublicensees,
(ii) all deductions from such gross sales taken in calculating Net Sales, (iii) Net Sales of
Alnylam Products by Alnylam, its Affiliates and sublicensees, (iv)

Page 23 of 93, Schedule B

 

	 	 	royalties payable based on such Net Sales and (v) all other information relevant to the
calculation of such royalties, on a product-by-product and country-by-country basis, for each
calendar quarter within [**] after the end of such calendar quarter.

Prosecution; Enforcement (Article 11)

	•	 	Isis will be responsible for preparing, filing, prosecuting, maintaining and taking such
other actions as are reasonably necessary or appropriate with respect to the Isis Patent
Rights. Alnylam will be responsible for preparing, filing, prosecuting, maintaining and
taking such other actions as are reasonably necessary or appropriate with respect to the
Alnylam Patent Rights. The RMC will designate the Party responsible for prosecuting and
maintaining any Joint Patents.
	 
	•	 	Alnylam will have the sole and exclusive right to assert and enforce any Isis Patent
Rights, Alnylam Patent Rights or Joint Patents against any party engaging in an unlicensed or
unauthorized making, having made, using, selling, offering for sale or importing of any
allegedly infringing Double Stranded RNA; provided, however, that Isis
will actively participate in the planning and conduct of any enforcement by Alnylam that
includes Isis Patent Rights covering a [**] chemical modification and will take the lead of
such enforcement to the extent that the scope or validity of any such Isis Patent Rights
covering a [**] chemical modification is at risk. Otherwise, Isis will have sole and
exclusive right to assert and enforce any Isis Patent Rights, Alnylam will have sole and
exclusive right to assert and enforce any Alnylam Patent Rights, and the RMC will agree in
advance on the enforcement of any Joint Patent. A Party’s enforcement rights are further
limited under the Addendum Transmittal.
	 
	•	 	If the Enforcing Party fails to initiate proceedings against any actual or suspected
infringement within [**] and if the infringer is directly competing with the Nonenforcing
Party’s Affected Product, then either (a) the Nonenforcing Party has step-in rights if the
license granted to such Party is exclusive or co-exclusive or (b) the Nonenforcing Party will
not be obligated to pay royalties during the period for which the Enforcing Party fails to
take action to eliminate the infringement if the license granted to such Party is
non-exclusive; provided, that clause (b) shall not apply if the Enforcing party elects to
grant the Nonenforcing Party enforcement rights with respect to such infringement. The
Enforcing Party will not grant a license to any such infringing Third Party with respect to
any directly competitive infringing product on terms materially more favorable (milestones and
royalties) than the terms of the license granted hereunder to the Nonenforcing Party or,
solely with respect to the Affected Product, will adjust the terms of such license so that
they are not materially less favorable than the terms of the license granted to the infringing
Third Party.

Definitions:

“Alnylam Excluded Technology” means inhibitors to specific genes or gene families, manufacturing
and analytical technologies, formulation and delivery technologies and the specific technology
listed on Schedule 1-6 attached to the Addendum Transmittal.

Page 24 of 93, Schedule B

 

“Alnylam Patent Rights” means Alnylam Current Motif and Mechanism Patents, Alnylam Future Motif and
Mechanism Patents, Alnylam Current Chemistry Patents and Alnylam Future Chemistry Patents.

“Alnylam Product” means a Double Stranded RNA Product or MicroRNA Product discovered or developed
by Alnylam, its Affiliates or sublicensees, the manufacture, sale or use of which is covered by a
Valid Claim within the Isis Patent Rights.

“Bona Fide Drug Discovery Collaboration” means a collaboration involving the discovery and
development of Double Stranded RNA Products in which a Party plays an integral role in the
experimentation and an important, though not necessarily dominant or co-equal, role in the
decision-making, relating to the discovery and development of Double Stranded RNA Products from the
point in time at which the relevant Gene Target has been designated through the initiation of [**].
A Bona Fide Drug Discovery Collaboration may continue beyond the initiation of such [**]. For Isis
Products that are Double Stranded RNA Products, a Bona Fide Drug Discovery Collaboration must be an
Antisense Drug Discovery Program. For each Party, collaborations that do not include or involve
Patents licensed from the other Party hereunder shall not constitute Bona Fide Drug Discovery
Collaborations. A Party’s experimentation relating to the discovery and development of Double
Stranded RNA Products that modulate a relevant Gene Target prior to the commencement of a
collaboration shall be deemed to have been conducted in the course or the collaboration for
purposes or detennining whether the collaboration is a Bona Fide Drug Discovery collaboration. A
series of related collaborations and/or license agreements involving the discovery and development
of Double Stranded RNA Products with the same sublicensee or related sublicensees that includes a
Bona Fide Drug Discovery Collaboration agreement will be aggregated to constitute a single Bona
Fide Drug Discovery Collaboration.

“Development Collaboration” means a collaboration by either Party with a Third Party whose purpose
is the further development and/or commercialization of a Double Stranded RNA Product and that
begins at or after the initiation of IND-Enabling Studies for such Product. For each Party,
collaborations that do not include or involve Patents licensed from the other Party hereunder shall
not constitute Development Collaborations.

“Double Stranded RNA” means a composition designed to act primarily through an RNAi mechanism that
is not a MicroRNA Construct and which consists of either (a) two separate oligomers of native or
chemically modified RNA that are hybridized to one another along a substantial portion (greater
than or equal to [**]%) of their lengths, or (b) a single oligomer of native or chemically modified
RNA that is hybridized to itself by self-complementary base-pairing along a substantial portion
(greater than or equal to [**]%) of its length to form a hairpin.

“Double Stranded RNA Product” means a pharmaceutical composition that contains a Double Stranded
RNA.

“Gene Target” means a transcriptional unit of a gene, including any protein product of such
transcriptional unit, and including all splice variants.

Page 25 of 93, Schedule B

 

“Isis Encumbered Targets” means a Gene Target (a) to which Isis has a contractual obligation to a
Third Party existing as of the Effective Date that precludes Isis from granting a license under
Section 5 with respect to such Gene Target and (b) that is identified and described on a [**] (as
defined in the letter agreement date March 9, 2004 between Alnylam and Isis).

“Isis Excluded Technology” means (a) RNase H mechanisms, RNase H motifs and RNase H
oligonucleotides when utilized in an RNase H mechanism, assays and methods thereof; (b) modulators
of specific genes, gene families or proteins; (c) manufacturing technologies; (d) analytical
technologies, kits and assays, including without limitation methods, systems and compositions of
matter for amplifying, quantifying, detecting, characterizing or identifying nucleic acids or
nonoligomeric ligands thereto; (e) formulation and delivery technologies; and (f) the specific
technology listed on Schedule 1-30 attached to the Addendum Transmittal.

“Isis Exclusive Targets” refer to the Reserved Targets which are designated by Isis as Isis
Exclusive Targets.

“Isis Patent Rights” means Isis Current Motif and Mechanism Patents, Isis Future Motif and
Mechanism Patents, Isis Current Chemistry Patents and Isis Future Chemistry Patents.

“Isis Products” means any Isis Single Stranded Product, MicroRNA Product or Double Stranded RNA
Product, discovered or developed by Isis, its Affiliates or sublicensees, the manufacture, sale or
use of which is covered by a Valid Claim within the Alnylam Patent Rights.

“Isis Single Stranded Product” means any single stranded oligomeric compound (a) that hybridizes in
whole or in part with a target RNA and modulates the Gene Target, (b) is not a Double Stranded RNA
or Double Stranded RNA Product and (c) the manufacture, sale or use of which is covered by a Valid
Claim within the Alnylam Patent Rights.

“Naked Sublicense” means a license for Double Stranded RNA that includes rights to the Isis Patent
Rights that is not a license in connection with (a) a Development Collaboration or (b) a Bona Fide
Drug Discovery Collaboration. A series of Naked Sublicenses to the same sublicensee or related
sublicensees will be aggregated to constitute a single Naked Sublicense. For the avoidance of
doubt, where this Agreement grants Alnylam exclusive rights to grant Naked Sublicenses, such
exclusive rights preclude Isis from granting licenses to the Isis Patent Rights to Third Parties
for Double Stranded RNA even though such license grants by Isis would technically be license grants
and not sublicense grants. Licenses that do not include or involve rights to Isis Patents shall not
constitute Naked Sublicenses.

Page 26 of 93, Schedule B

 

MIT

	5.	 	Amended and Restated Exclusive Patent License Agreement between Massachusetts Institute of
Technology (“MIT”) and Alnylam, dated May 9, 2007, as amended by Amendment No. 1 dated
May 7, 2008 and Amendment No. 2 dated May 20, 2008 (“MIT Agreement”)

Brief Summary of Technology Covered by License:

MIT granted Alnylam exclusive rights to develop and commercialize for human RNAi therapeutics
certain technology relating to novel lipid compositions that are potential components of cationic
liposomal formulations for cellular delivery of oligonucleotides. The technology was developed in
the laboratory of Professor Robert Langer.

Limitations on Scope of License (Sections 2.1, 2.3 and 2.5)

	•	 	The license granted to Alnylam is limited to an exclusive (for the Exclusive Period),
worldwide license under the Patent Rights to develop, make, have made, use and import Library
Products and Licensed Processes to develop, make, have made, use, sell, offer to sell, lease,
and import Licensed Products in the Field and to develop and perform Licensed Processes in the
Field.
	 
	•	 	Alnylam does not have the right to sell or offer for sale the Library Products separately
from a sale or offer for sale of a Licensed Product.
	 
	•	 	MIT retains the right to practice under the Patent Rights for research, teaching, and
educational purposes. The U.S. federal government retains a royalty-free, non-exclusive,
non-transferable license to practice any government-funded invention claimed in any Patent
Rights as set forth in 35 USC 201-211, and the regulations promulgated thereunder, including
the requirement that Library Products, whether or not part of Licensed Products, used or sold
in the U.S. must be manufactured substantially in the U.S.
	 
	•	 	The Patent Rights may not be asserted against non-for-profit research institutions that
practice the Patent Rights for research funded by (i) the institutions themselves, (ii)
not-for profit foundations, or (iii) any federal, state or municipal government. Alnylam may
assert the Patent Rights against not-for-profit research institutions only if the infringement
activity of the not-for-profit research institution was performed in the fulfillment of
research sponsored by a for-profit entity and the assertion of infringement must be limited to
those specific activities.

Restrictions on Sublicensing by Alnylam (Sections 2.1 and 2.3; Section 4.1(g) as amended by
Amendment No. 1 and Amendment No. 2)

	•	 	Alnylam may grant sublicenses under commercially reasonable terms and conditions only
during the Exclusive Period. Any sublicenses by Alnylam may extend past the

Page 27 of 93, Schedule B

 

	 	 	expiration date of the Exclusive Period, but any exclusivity of such sublicense will expire
upon the expiration of the Exclusive Period.
	 
	•	 	The sublicense must incorporate terms and conditions sufficient to enable Alnylam and its
Affiliates to comply with the MIT Agreement. Such sublicenses will also include provisions to
provide that if Sublicensee brings a Patent Challenge against MIT (except as required under a
court order or subpoena), Alnylam may terminate the sublicense.
	 
	•	 	Upon termination of the MIT Agreement, any Sublicensee not then in default will have the
right to seek a license from MIT, and MIT agrees to negotiate such licenses in good faith
under reasonable terms and conditions.
	 
	•	 	Alnylam may permit third parties (i) to use Library Products and Licensed Processes for the
purpose of research with academic or nonprofit institutions and contract research, including
for the conduct of clinical trials of a Licensed Product, and (ii) to sell Licensed Products
under an agency, consignment or equivalent arrangement, wherein such rights are not sublicense
rights.
	 
	•	 	Alnylam will promptly furnish MIT with a fully signed photocopy of any sublicense
agreement, which copy may be redacted except with respect to terms directly relevant to
Alnylam’s obligations under the MIT Agreement.
	 
	•	 	Non-monetary consideration may not be accepted by Alnylam or an Affiliate for any
sublicense of the Patent Rights without the prior written consent of M.I.T. Consideration for
any and all sublicenses of the Patent Rights shall be on commercially reasonable terms and
conditions consistent with amounts paid for similar technology in the industry.
	 
	•	 	Upon termination of the Agreement for any reason, and at the written request of any
sublicensee, M.I.T. will assume Alnylam’s duties and obligations solely with respect to the
Patent Rights under each sublicense agreement granted by Alnylam to such Sublicensee,
effective as of the termination date of the Agreement, provided that:

     (i) such Sublicensee is not in default of its sublicense agreement with Alnylam at
the date of such termination;

     (ii) such Sulicensee agrees in writing to M.I.T. within thirty (30) days of the
termination date of the Agreement to be bound to M.I.T. for all obligations, including the
payment of license maintenance fees (Section 4.1(b)), royalties (Section 4.1(c)) and
clinical milestone payments (Section 4.1(f)(ii)), specified in the Agreement;

     (iii) M.I.T. shall not assume any obligation of Alnylam to such Sublicensee pursuant
to any representation, warranty or indemnification provision;

Page 28 of 93, Schedule B

 

     (iv) notwithstanding anything to the contrary in the sublicense agreement with
Alnylam, such Sublicensee agrees in writing to M.I.T. within thirty (30) days of the
termination date of the Agreement to be bound to M.I.T. by the terms and conditions of
specified provisions of the Agreement.; and

     (v) such Sublicensee pays to M.I.T. a fee of [**] dollars ($[**]) within thirty (30)
days of the termination date of this Agreement.

Diligence and Reporting (Sections 3.1 and 3.2)

	•	 	Sublicensees are required to use diligent efforts to develop Library Products and Licensed
Products and to introduce Licensed Products into the commercial market; thereafter
Sublicensees are required to make Licensed Products reasonably available to the public.
Specifically, the following obligations must be fulfilled:

(a) Written reports are due within [**] days after the end of each calendar year on the
progress of efforts during the immediately preceding calendar year to develop and
commercialize Licensed Products. Such reports shall include the number of [**], a
description of [**], and the [**] that have been tested. The report shall also contain a
discussion of intended efforts and sales projections for the year in which the report is
submitted.

(b) Funding for research at MIT pursuant to the Budget set forth in Attachment C of the
Research Agreement.

(c) By [**] will be evaluated for use in [**] of RNAi Products.

(d) Prior to the [**], at least [**] will be advanced to [**] studies in support of [**]
for [**] studies.

(e) Filing of [**] for Licensed Product by [**].

(f) Commencement of [**] trial for a Licensed Product within [**] for such Licensed
Product.

(g) First Commercial Sale of a Licensed Product within [**] for each such Licensed Product.

	•	 	If Alnylam, an Affiliate of Alnylam or any Sublicensee is determined to have failed to
fulfill any obligation under Sections 3.1(a) and 3.1(c) — (g) above, MIT may treat such
failure as a material breach, subject to any changes to such diligence requirements as may be
mutually-agreed by the parties below.
	 
	•	 	If Alnylam anticipates a failure to meet an obligation set forth in Section 3.1(c), (d),
(e), (f) or (g) above will occur, Alnylam will promptly advise MIT, and representatives of
each party will meet to review the reasons for anticipated failure. Alnylam and MIT will
enter into a written amendment to the MIT Agreement with respect to any mutually agreed upon
change(s) to the relevant obligation. If, after

Page 29 of 93, Schedule B

 

	 	 	good faith discussion, Alnylam and MIT are unable to agree upon an amendment to the obligation,
Alnylam, at its discretion, may elect to extend the due date to meet the obligation for such
diligence obligation by one year by providing written notice to MIT along with payment in the
amount of $[**]. Alnylam may extend the due date of each diligence obligation set forth in
Section 3.1(c), (d), (e), (f) or (g) of the MIT Agreement only once during the term.

***Royalty Payment Obligations (Section 4.1)

	•	 	Running royalties of [**]% of Net Sales of Licensed Products and Licensed Processes are due
within [**] days of the end of each calendar quarter.
	 
	•	 	If Alnylam or an Affiliate is legally required to pay royalties to one or more third
parties in order to obtain a license or similar right necessary to practice the Patent Rights,
Alnylam shall be entitled to a credit up to [**] percent ([**]%) of the amounts payable to
such third parties against the royalties due to MIT for the same Reporting Period; provided,
however, that (i) in no event will royalties due to MIT under Section 4.1(c), when aggregated
with any other offsets and credits allowed under the MIT Agreement, be less than [**]% of Net
Sales in any Reporting Period, and (ii) royalties due to third parties with respect to [**]
patents (see Appendix B to MIT Agreement) shall not qualify for purposes of the offset against
royalties under Section 4.1(d).
	 
	•	 	Multiple royalties are not due if the manufacture, use, lease, or sale of any Licensed
Product or the performance of any Licensed Process is covered by more than one of the Patent
Rights.

Royalty Payment and Reports (Sections 5.1 and 5.2)

	•	 	Royalties are payable for each Reporting Period and are due to MIT within [**] days of the
end of each Reporting Period.
	 
	•	 	Prior to the First Commercial Sale of a Licensed Product or first commercial performance of
a Licensed Process, Alnylam is required to deliver annual reports within [**] days of the end
of each calendar year, containing information concerning the immediately preceding year, as
further described in Section 5.2. The date of First Commercial Sale of a Licensed Product or
commercial performance of a Licensed Process must be reported to MIT within [**] days of its
occurrence.
	 
	•	 	After First Commercial Sale of a Licensed Product or commercial performance of a Licensed
Process, reports are required to be delivered to MIT within [**] days of the end of each
Reporting Period containing information concerning the immediately preceding Reporting Period,
as further described in Section 5.2.
	 
	•	 	Section 5.2 states that reports must include at least the following information for the
immediately preceding reporting period: the number of Licensed Products sold, leased, or
distributed, the number of [**], a description of Licensed Processes

Page 30 of 93, Schedule B

 

	 	 	performed in each country as may be pertinent to a royalty accounting, gross price charged in
each country, calculation of Net Sales in each country (including a listing of applicable
deductions), total royalty payable on Net Sales, the exchange rate used for conversion, [**]
categorized by rights relating to [**], milestones achieved and the [**]. If no amounts are
due to MIT for any Reporting Period, the report shall so state.

Recordkeeping and Audit Rights (Section 5.4)

	•	 	Sublicensees are required to maintain complete and accurate records reasonably relating to
(i) the rights and obligations under the MIT Agreement, and (ii) any amounts payable to MIT in
relation to the MIT Agreement to the extent customarily maintained in the biopharmaceutical
industry, which records will contain sufficient information to permit MIT to confirm the
accuracy of any reports and payments delivered to MIT and compliance in other respects with
the MIT Agreement. Such records will be retained for at least [**] years following the end of
the calendar year to which they pertain, during which time a certified public accountant
selected by MIT (who will be required to enter into a confidentiality obligation with
Sublicensee) may inspect such records upon advance notice and during normal business hours
solely for the purpose of verifying any reports and payments or compliance in other respects
with the MIT Agreement.

Prosecution and Enforcement (Sections 6.1, 7.1-7.3 and 7.7)

	•	 	MIT will prepare, file, prosecute, and maintain all of the Patent Rights. Alnylam will
cooperate with MIT in such filing, prosecution and maintenance.
	 
	•	 	So long as Alnylam remains the exclusive licensee of the Patent Rights in the Field,
Alnylam, to the extent permitted by law, will have the right, under its own control and at its
own expense, to prosecute any third party infringement of the Patent Rights in the Field,
subject to Sections 2.5(c) (Non-assert), 7.4 (Offsets) and 7.5 (Recovery) of the MIT
Agreement. Prior to commencing any such action, Alnylam will consult with MIT and will
consider the views of MIT regarding the advisability of the proposed action and its effect on
the public interest.
	 
	•	 	If Alnylam is unsuccessful in persuading the alleged infringer to desist or fails to have
initiated an infringement action within a reasonable time after Alnylam first becomes aware of
the basis for such action, MIT will have the right, at its sole discretion, to prosecute such
infringement under its sole control and at its sole expense, and to keep any recovery.
	 
	•	 	If a Patent Challenge is brought against Alnylam by a third party, MIT, at its option, will
have the right within 20 days after commencement of such action to take over the sole defense
of the action. If MIT does not exercise this right, Alnylam may take over the sole defense of
such action.

Page 31 of 93, Schedule B

 

	•	 	So long as Alnylam remains the exclusive licensee of the Patent Rights in the Field,
Alnylam will have the sole right to sublicense any alleged infringer in the Field for future
use of the Patent Rights in accordance with Alnylam’s rights under and the terms and
conditions of this Agreement. Any upfront fees as part of such sublicense will be shared
equally between Alnylam and MIT; other revenues to Alnylam pursuant to such sublicense will be
treated as set forth in Article 4 of the MIT Agreement.

Consequences of a Patent Challenge by Sublicensee (Sections 12.5 and 4.3)

	•	 	If a Sublicensee brings a Patent Challenge against MIT (except as required under a court
order or subpoena), MIT may send a written demand to Alnylam to terminate the sublicense. If
Alnylam fails to so terminate such sublicense within 30 days of MIT’s demand, MIT may
immediately terminate the MIT Agreement and/or the license granted thereunder.
	 
	•	 	Notwithstanding the foregoing, if MIT decides not to terminate the MIT Agreement and the
Patent Challenge is successful, Alnylam will have no right to recoup any royalties paid during
the period of challenge. If the Patent Challenge is unsuccessful, Alnylam will reimburse MIT
for all of its costs and expenses it incurred as a result of such Patent Challenge, including
without limitation attorneys fees, court costs, litigation related disbursements, and third
party and expert witness fees (collectively, “Litigation Costs”). Reimbursement for
Litigation Costs will be made within thirty (30) days of receipt of one or more invoices from
MIT for such Litigation Costs.

Certain Termination Rights (Sections 12.1, 12.2 and 12.4)

	•	 	Alnylam has the right to terminate the MIT Agreement for any reason upon at least 6 months’
prior written notice to MIT and payment of all amounts due to MIT through the effective date
of termination.
	 
	•	 	If Alnylam ceases to carry on its business related to the MIT Agreement, MIT will have the
right to terminate the MIT Agreement immediately upon written notice to Alnylam.
	 
	•	 	MIT, at its sole discretion, may terminate the Exclusive Period upon ten (10) days written
notice to Alnylam if any of the following events occurs: (a) Alnylam is in uncured material
default under the Research Agreement, including uncured failure to make any payments due
thereunder; or (b) the Research Agreement is terminated for any reason other than for (i)
material breach by MIT, (ii) the inability of Dr. Robert Langer to continue to serve as
Principal Investigator, and the inability of the parties to agree upon a replacement Principal
Investigator, an interim Principal Investigator, or an alternate arrangement for the
performance of the Research after Dr. Langer is no longer able to serve as Principal
Investigator (capitalized terms used in the foregoing clause have the meanings ascribed to
them in the Research Agreement); or (iii) circumstances beyond MIT’s reasonable control that
preclude the continuation of the Research, as provided for under the Research Agreement.

Page 32 of 93, Schedule B

 

Definitions:

“Development Candidate” means a pre-clinical Licensed Product which possesses desirable
properties of a therapeutic agent for the treatment of a clinical condition based on in vitro and
animal proof-of-concept studies.

“Exclusive Period” means the term of the MIT Agreement.

“Field” means therapeutic use in humans.

“Library Component” means a Library Product which is a set of reaction products formed by
an addition reaction between two individual monomers, which set will include all reaction products
and combinations within such set, including all isomers; and any compounds identical to any of the
foregoing, including individual reaction products within such set, regardless of the means by which
said compounds are prepared, manufactured or synthesized.

“Library Product” means any product that, in whole or in part: (i) absent the license
granted hereunder, would infringe one or more Valid Claims of the Patent Rights; or (ii) is
manufactured by using a Licensed Process or that, when used, practices a Licensed Process.

“Licensed Process” means any process that, in whole or in part: (i) absent the license
granted hereunder, would infringe one or more Valid Claims of the Patent Rights; or (ii) when
practiced, uses a Library Product.

“Licensed Product” means, generally, any product that contains both (i) an RNAi Product and
(ii) a Library Product.

“Patent Rights” means the patent applications listed on Appendix A to the MIT
Agreement entitled [**], and resulting patents and patent applications.

“RNAi Product” means, generally, a product containing one or more siRNA Therapeutics and/or
miRNA Therapeutics towards one or more Targets.

“siRNA Therapeutic” means a therapeutic containing, composed of or based on siRNA and
designed to modulate the function of particular genes or gene products by causing degradation of a
messenger RNA to which such siRNA is complementary, and that is not an miRNA Therapeutic.

“Target” means (a) a single gene, as defined in the NCBI Entrez Gene database or any
successor database thereto, or a product of such gene, that is a site or potential site of
therapeutic intervention by an siRNA Therapeutic and/or an miRNA Therapeutic; (b) naturally
occurring variants of a gene or gene product described in clause (a); or (c) a naturally occurring
interfering RNA or miRNA or precursors thereof; provided that for the purposes of this definition a
viral genome will be regarded as a single gene, and that the DNA sequence encoding a specific miRNA
precursor will also be regarded as a single gene.

Page 33 of 93, Schedule B

 

TEKMIRA

	6.	 	License and Collaboration Agreement between Tekmira Pharmaceuticals Corporation (formerly
INEX Pharmaceuticals Corporation) (“Tekmira”) and Alnylam, dated January 8, 2007
(“Tekmira Agreement”)

Brief Summary of Technology Covered by License:

Tekmira granted Alnylam a license relating to liposomal delivery of siRNA and miRNA products.
Alnylam granted Tekmira (i) an option to obtain exclusive, royalty-bearing, worldwide licenses
under its fundamental siRNA intellectual property for 3 targets and (ii) an exclusive,
royalty-bearing license to certain intellectual property relating to immunostimulatory RNA
oligonucleotide compositions (“IOC Technology”). Alnylam retained certain rights to participate
with Tekmira in commercialization of IOC Technology. In addition, Alnylam provided funding for a
2-year formulation development collaboration with Tekmira, a multi-year loan for capital
expenditure purposes, and Tekmira will provide exclusive manufacturing services for Alnylam’s
development programs up until completion of Phase 2 clinical studies.

Limitations on Scope of License (Sections 6.1 and 6.4)

	•	 	The license granted to Alnylam is limited to an exclusive, royalty-bearing, worldwide
license under Inex Technology, Inex Collaboration IP and Tekmira’s interest in Joint
Collaboration IP to Develop, Manufacture and Commercialize Alnylam Royalty Products in the
Alnylam Field, subject to (a) Tekmira’s non-exclusive license under Alnylam’s rights in Inex
Technology and Collaboration IP for purposes of performing Tekmira’s obligations under the
Collaboration with respect to Alnylam Royalty Products, and the Manufacturing Activities, and
(b) Tekmira’s exclusive, worldwide license under Alnylam’s rights in Inex Technology and
Collaboration IP to Develop, Manufacture and Commercialize Inex Development Products (as
defined below) in the Alnylam Field.
	 
	•	 	Any license granted by Alnylam to a Third Party under Alnylam RNAi Technology and Alnylam
Collaboration IP would be subject to a non-exclusive, worldwide license granted to Tekmira for
purposes of performing Tekmira’s obligations under the Collaboration with respect to Alnylam
Royalty Products, and the Manufacturing Activities.
	 
	•	 	Any license granted by Alnylam to a Third Party under Alnylam Core Patent Rights, Alnylam
Lipidoid Patent Rights, Alnylam Collaboration IP and Alnylam’s interest in Joint Collaboration
IP would be subject to an exclusive, worldwide license granted to Tekmira to Develop,
Manufacture and Commercialize RNAi Products directed to up to three (3) Targets (each such
Target, an “Inex Development Target,” and such RNAi Products, the “Inex
Development Products”) which Tekmira may select (as described below) in the Alnylam Field.
During the Selection Term, Tekmira has the right to nominate a Target, subject to (a)
Alnylam’s contractual obligation to a Third Party that would be breached by the inclusion of
such Target as an Inex Development

Page 34 of 93, Schedule B

 

	 	 	Target under the Tekmira Agreement, and (b) Alnylam’s determination after good faith review of
its ongoing or planned scientific and/or business activities that such Target is a Target of
interest to Alnylam. If neither of these criteria apply, the Target is deemed to have been
successfully nominated as an “Inex Development Target” and Alnylam is obligated to use
Commercially Reasonable Efforts consistent with the terms of the Novartis Agreement to obtain
Novartis’ consent to such selection. If an Inex Development Target is not available for
license, then Tekmira may nominate an additional Target, until an aggregate of 3 Inex
Development Targets have been identified and approved for selection. If all 3 Inex Development
Targets have not been approved for selection by the expiration of the Selection Term, the
Selection Term will be extended until the earlier of (i) the date on which an aggregate of 3
such Inex Development Targets have been identified and approved for selection, and (ii) January
8, 2014.
	 
	•	 	Any license granted by Alnylam to a Third Party under Alnylam IOC Technology, Alnylam
Collaboration IP and Alnylam’s interest in Joint Collaboration IP would be subject to an
exclusive license granted to Tekmira to Develop, Manufacture and Commercialize IOC Products in
the Inex IOC Field in and for the United States.

Restrictions on Sublicensing by Alnylam (Sections 6.2 and 6.4)

	•	 	Alnylam may grant sublicenses to Third Parties to Develop, Manufacture and Commercialize
Alnylam Royalty Products; provided, that (i) with respect to any sublicense of
Alnylam’s rights under Section 6.1.1(a) (i.e., the exclusive license under Inex Technology to
develop and commercialize Alnylam Royalty Products in the Alnylam Field) of the Tekmira
Agreement in respect of any Alnylam Royalty Product for which Tekmira has not initiated
Manufacturing of batches of finished dosage form for GLP toxicology studies, Alnylam is
required to use Commercially Reasonable Efforts to facilitate a business discussion between
Tekmira and Alnylam’s Sublicensee (other than Tekmira or its Affiliates) with respect to the
provision of manufacturing services by Tekmira to such Sublicensee; and (ii) with respect to
any sublicense of Alnylam’s rights under Section 6.1.1(a) of the Tekmira Agreement in respect
of any Alnylam Royalty Product for which Tekmira has initiated Manufacturing of batches of
finished dosage form for GLP toxicology studies, Alnylam’s Sublicensee (other than Tekmira or
its Affiliates) will be required to obtain its requirements of the bulk finished dosage form
of such Alnylam Royalty Product from Tekmira on the terms set forth in Article 5 of the
Tekmira Agreement. However, Tekmira agrees to negotiate in good faith with Alnylam and/or
Alnylam’s Sublicensee either an alternate or modified supply arrangement or the release of
such Sublicensee from such exclusive supply obligation in return for reasonable compensation
to Tekmira.
	 
	•	 	Each license and/or sublicense granted by Alnylam under the Tekmira Agreement to develop,
manufacture and commercialize Alnylam Royalty Products must be subject and subordinate to the
terms and conditions of the Tekmira Agreement and must contain terms and conditions consistent
with those in the Tekmira Agreement, including, without limitation, the requirements of
Section 6.4 of the Tekmira

Page 35 of 93, Schedule B

 

	 	 	Agreement (see below). Commercializing Sublicensees are also required to: (i) submit
applicable sales or other reports consistent with those required under the Tekmira Agreement;
(ii) comply with an audit requirement similar to the requirement set forth in Section 7.6 of
the Tekmira Agreement; and (iii) comply with the confidentiality and non-use provisions of
Article 8 of the Tekmira Agreement with respect to both Parties’ Confidential Information. If
Alnylam becomes aware of a material breach of any sublicense by a Third Party Sublicensee,
Alnylam is required to promptly notify Tekmira of the particulars of same and take all
Commercially Reasonable Efforts to enforce the terms of such sublicense.
	 
	•	 	Any sublicense granted by Alnylam shall survive termination of the licenses or other rights
granted to Alnylam under the Tekmira agreement in accordance with Section 6.2.6, and be
assumed by Tekmira as long as (i) the Sublicensee is not then in breach of its license and/or
sublicense agreement, (ii) the Sublicensee agrees in writing to be bound to Tekmira as a
licensor under the terms and conditions of the license and/or sublicense agreement, and (iii)
the Sublicensee agrees in writing that in no event shall Tekmira assume any obligations or
liabilities, or be under any obligation or requirement of performance, under any such license
and/or sublicense extending beyond Tekmira’s obligations and liabilities under the Tekmira
Agreement.
	 
	•	 	Section 6.4 of the Tekmira Agreement states that all licenses and other rights granted to
Alnylam with respect to Inex Technology under Article 6 of the Tekmira Agreement are subject
to (i) the rights granted to Tekmira, and to Tekmira’s ability to grant rights to Alnylam
under the Inex In-Licenses, and (ii) the provisions of the UBC Sublicense Documents governing
or relating to the rights sublicensed to Alnylam.

Diligence and Annual Reports (Section 6.7)

	•	 	Alnylam is required to use Commercially Reasonable Efforts to Develop and Commercialize an
Alnylam Royalty Product.
	 
	•	 	Alnylam is required to deliver to Tekmira an annual report, due no later than December 31
of each Contract Year during the Agreement Term, which summarizes the major activities
undertaken by Alnylam during the preceding 12 months to Develop and Commercialize its Royalty
Products in the applicable field. The report will include an outline of the status of any
such Royalty Products in clinical trials and the existence of any sublicenses with respect to
such Royalty Products which have not been previously disclosed.

***Royalty Payment Obligations (Sections 7.3 and 7.4; Section 6.1.3)

	•	 	Royalties are payable to Tekmira on Net Sales of Alnylam Royalty Products in the Territory
as follows:

	 	 	 
	Aggregate Calendar Year Net Sales of the	 	Royalty
	Alnylam Royalty Product in the Territory	 	(as a percentage of Net Sales)
	on the first $[**] — $[**]

	 	[**]%
	On the subsequent $[**] — $[**]

	 	[**]%
	Greater than $[**]

	 	[**]%

Page 36 of 93, Schedule B

 

	•	 	Notwithstanding the foregoing, in the event that an Alnylam Royalty Product is comprised of
a formulation Covered by or employing any Third Party Liposome Patent Rights then subject to
the terms and conditions of the Tekmira Agreement, royalties on Net Sales of Alnylam Royalty
Products in the Territory shall be calculated as follows:

	 	 	 
	Aggregate Calendar Year Net Sales of the	 	Royalty
	Alnylam Royalty Product in the Territory	 	(as a percentage of Net Sales)
	on the first $[**]

	 	[**]%
	On the subsequent $[**] — $[**]

	 	[**]%
	Greater than $[**]

	 	[**]%

	•	 	Royalties on Alnylam Royalty Products at the rates set forth above are payable on a
country-by-country and product-by-product basis commencing on the date of First Commercial
Sale of such Alnylam Royalty Product in a country and continuing until the later of the
expiration of the last Valid Claim Covering the Manufacture or Commercialization of such
Alnylam Royalty Product in the country of sale, subject to the following conditions:

	 	(i)	 	only one royalty shall be due with respect to the same unit of Alnylam
Royalty Product;
	 
	 	(ii)	 	no royalties shall be due upon the sale or other transfer among a Party and
its Related Parties, but in such cases the royalty shall be due and calculated upon
such Party’s or its Related Party’s Net Sales to the first independent Third Party;
	 
	 	(iii)	 	no royalties shall accrue on the sale or other disposition of the Alnylam
Royalty Product by a Party or its Related Parties for use in a clinical study
sponsored by such Party or under an IND prior to Regulatory Approval of such Alnylam
Royalty Product in the applicable jurisdiction; and
	 
	 	(iv)	 	no royalties shall accrue on the disposition of an Alnylam Royalty Product in
reasonable quantities by a Party or its Related Parties as samples (promotion or
otherwise) or as donations (for example, to non-profit institutions for a
non-commercial purpose).

	•	 	If the Development, Manufacture or Commercialization of an Alnylam Royalty Product in
accordance with the Tekmira Agreement infringes Necessary Third Party IP, the applicable
royalties in each country in the Territory payable to Tekmira will be reduced by [**] percent
([**]%) of the amount paid by Alnylam of any royalties under all licenses of such Necessary
Third Party IP that are reasonably allocable to the Development, Manufacture and
Commercialization of the Alnylam Royalty Product in or for such country in the Alnylam Field;
provided, however, that, on a

Page 37 of 93, Schedule B

 

	 	 	country-by-country basis, in no event shall the royalties payable to Tekmira with respect to
Net Sales in a country for any Calendar Quarter be reduced below the greater of: (i) [**]
percent ([**]%) of the royalties otherwise payable to Tekmira for such Calendar Quarter as
calculated pursuant to Section 7.3, and (ii) the amount of any royalties payable under the
In-licenses of Alnylam that are reasonably allocable to the Commercialization or Manufacture of
the Alnylam Royalty Product in or for such country in the Field (where the royalties are
calculated by adding one percentage point to the applicable royalty rate(s) in the applicable
In-License(s)).
	 
	•	 	In the event that Alnylam is required to make any payments to UBC in respect of the INEX
Technology or INEX Collaboration IP licensed to Alnylam pursuant to the UBC Sublicense
Agreement, then Alnylam shall be entitled to offset any amounts payable by Alnylam to Tekmira
under the Tekmira Agreement by the amount of Alnylam’s payments to UBC until such amounts have
been credited in full.

Royalty Reports; Payment and Audit Rights (Sections 7.3.4 and 7.6)

	•	 	Commencing upon the First Commercial Sale of an Alnylam Royalty Product, Alnylam is
required to provide to Tekmira a quarterly written report showing the quantity of Alnylam
Royalty Products sold in each country (as measured in saleable units of product), the gross
sales of such Alnylam Royalty Product in each country, total deductions for such Alnylam
Royalty Product for each country included in the calculation of Net Sales, the Net Sales in
each country of such Alnylam Royalty Product subject to royalty payments and the royalties
payable with respect to such Alnylam Royalty Product. Quarterly reports are due no later than
the 25th day following the close of each Calendar Quarter. Royalties shown to have accrued by
each royalty report are due and payable on the date such royalty report is due.
	 
	•	 	Complete and accurate records must be kept in sufficient detail to enable the royalties and
other payments payable under the Tekmira Agreement to be determined.
	 
	•	 	Upon the written request of Tekmira and not more than once in each Calendar Year, a
Sublicensee must permit an independent certified public accounting firm of nationally
recognized standing selected by Tekmira and reasonably acceptable to such Sublicensee to have
access during normal business hours to such of the records of Sublicensee as may be reasonably
necessary to verify the accuracy of the royalty and other financial reports required to be
delivered under the Tekmira Agreement for any Calendar Year ending not more than [**] months
prior to the date of such request, for the sole purpose of verifying the basis and accuracy of
payments made under Article 7 of the Tekmira Agreement.

Prosecution and Enforcement (Sections 10.2, 10.3 and 10.4)

	•	 	Alnylam is solely responsible, at Alnylam’s discretion, for filing, prosecuting, conducting
ex parte and inter partes proceedings (including the defense of any interference or opposition
proceedings) and maintaining all Patent Rights comprising

Page 38 of 93, Schedule B

 

	 	 	Alnylam RNAi Technology, Alnylam IOC Technology or Alnylam Collaboration IP, in Alnylam’s name.
	 
	•	 	Tekmira is sole responsible, at Tekmira’s discretion, for filing, prosecuting, conducting
ex parte and inter partes proceedings, (including the defense of any interference or
opposition proceedings), and maintaining all Patent Rights comprising Inex Technology or Inex
IOC Technology, in Tekmira’s name, or Inex Collaboration IP, in UBC’s name.
	 
	•	 	Subject to Tekmira’s continuing right to the prior review of, comment on, revision to and
approval of material documents, which will not be unreasonably delayed or withheld, Alnylam is
solely responsible, at Alnylam’s discretion, for filing, conducting ex parte and inter partes
prosecution, and maintaining (including the defense of any interference or opposition
proceedings) all Patent Rights comprising Joint Collaboration IP, in the names of both Tekmira
and Alnylam.
	 
	•	 	If Alnylam elects not to seek or continue to seek or maintain patent protection on any
Alnylam IOC Technology or Alnylam Collaboration IP which is subject to Tekmira’s licensed
rights under the Tekmira Agreement, or Joint Collaboration IP, then Tekmira will have step-in
rights. If Alnylam declines to file, prosecute and/or maintain Valid Claims at Tekmira’s
request in Joint Collaboration IP, then Tekmira will have step-in rights.
	 
	•	 	If Tekmira elects not to seek or continue to seek or maintain patent protection on any Inex
Technology or Inex Collaboration IP, which is subject to Alnylam’s licensed rights under the
Tekmira Agreement, then subject to the provisions of the UBC Sublicense Documents, Alnylam
will have rights (but not the obligation), at its expense, to prosecute and maintain in any
country patent protection on such Inex Technology in the name of Tekmira or Inex Collaboration
IP in the name of UBC.
	 
	•	 	Each Party agrees: (a) to make its employees, agents and consultants reasonably available
to the other Party (or to the other Party’s authorized attorneys, agents or representatives),
to the extent reasonably necessary to enable such Party to undertake patent prosecution; (b)
to provide the other Party with copies of all material correspondence pertaining to
prosecution with the patent offices; (c) to cooperate, if necessary and appropriate, with the
other Party in gaining patent term extensions wherever applicable to Patent Rights; and (d) to
endeavor in good faith to coordinate its efforts with the other Party to minimize or avoid
interference with the prosecution and maintenance of the other Party’s patent applications.
	 
	•	 	The patent filing, prosecution and maintenance expenses incurred after the Effective Date
with respect to Patent Rights comprised of Alnylam Core Patent Rights, Alnylam IOC Technology,
Alnylam Lipidoid Patent Rights, Inex Technology, Inex IOC Technology and Collaboration IP will
be borne by each Party having the right to file, prosecute and maintain such Patent Rights
under the Tekmira Agreement.

Page 39 of 93, Schedule B

 

	•	 	Subject to the provisions of any Inex In-License and the provisions of the UBC Sublicense
Documents, in respect of the Alnylam Royalty Products in the Alnylam Field, Alnylam will have
the sole and exclusive right to initiate an infringement or other appropriate suit anywhere in
the world against any Third Party who at any time has infringed, or is suspected of
infringing, any Patent Rights, or of using without proper authorization, any Know-How,
comprising any Inex Technology or Collaboration IP that is licensed to Alnylam under the
Tekmira Agreement.
	 
	•	 	Alnylam will have the sole and exclusive right to initiate an infringement or other
appropriate suit anywhere in the world against any Third Party who at any time has infringed,
or is suspected of infringing, any Patent Rights, or of using without proper authorization any
Know-How, comprising Alnylam RNAi Technology, Alnylam IOC Technology or Alnylam Collaboration
IP; provided, that if Alnylam fails to initiate a suit or take other appropriate action with
respect to Alnylam IOC Technology in the United States with respect to an IOC Product that it
has the initial right to initiate or take pursuant thereto within 90 days after becoming aware
of the basis for such suit or action, then Tekmira may, in its discretion, provide Alnylam
with written notice of Tekmira’s intent to initiate a suit or take other appropriate action
with respect to such IOC Product. If Alnylam fails to initiate a suit or take such other
appropriate action within 30 days after receipt of such notice from Tekmira, then Tekmira will
have the right to initiate a suit or take other appropriate action that it believes is
reasonably required to protect its licensed interests under the Alnylam IOC Technology and
Alnylam Collaboration IP with respect to such IOC Product.
	 
	•	 	Alnylam may defend any Infringement Claim brought against either Party or its Affiliates or
Sublicensees arising out of the Development, Manufacture or Commercialization of any Alnylam
Royalty Product in the Alnylam Field. Tekmira may defend any Infringement Claim brought
against either Party or its Affiliates or Sublicensees arising out of the Development,
Manufacture or Commercialization of any Inex Royalty Product and in (a) the Alnylam Field, in
the case of Inex Development Products or (b) the Inex IOC Field, in the case of Inex IOC
Products.
	 
	•	 	As the responsible party, Alnylam must keep Tekmira informed, and from time to time consult
with Tekmira regarding the status of any such claims and provide Tekmira with copies of all
documents filed in, and all written communications relating to, any suit brought in connection
with such claims. Tekmira also has the right to participate and to be presented in any such
claim or related suit. If Alnylam fails to exercise its right to assume such defense within
30 days following written notice of such Infringement Claim, Tekmira has the sole and
exclusive right to control the defense of such Infringement Claim.

Termination for Patent Challenge (Section 11.5)

	•	 	If any Sublicensee asserts in any court or other governmental agency of competent
jurisdiction that an Inex Patent Right or a Patent Right Controlled by Tekmira by virtue of
the Inex-UBC License Agreement and sublicensed to Alnylam pursuant to the UBC Sublicense (in
either case, an “Inex Patent”) is invalid, unenforceable, or

Page 40 of 93, Schedule B

 

	 	 	that no issued Valid Claim embodied in such Inex Patent excludes a Third Party from making,
having made, using, selling, offering for sale, importing or having imported an Alnylam Royalty
Product in such jurisdiction, then Tekmira may, upon written notice to Alnylam, terminate all
licenses granted to Alnylam for such Alnylam Royalty Product(s) covered by such Inex Patent
that is under challenge in the applicable jurisdiction; provided, however, that Tekmira will
not terminate such license if within 30 days of Alnylam’s receipt of Tekmira’s notification
under the Tekmira Agreement (a) it is confirmed by written notice to Tekmira that Sublicensee
no longer intends to challenge the validity or enforceability of such Inex Patent; or (b)
documentation is provided to Tekmira to confirm Sublicensee’s withdrawal of its filing,
submission, or other process commenced in any court or other governmental agency of competent
jurisdiction to challenge the validity or enforceability of any such Inex Patent.

Definitions:

“Alnylam Collaboration IP” means, generally (a) any improvement, invention, or Know-How
first discovered or developed by employees of Alnylam or its Affiliates or other persons not
employed by Tekmira acting on behalf of Alnylam, in the performance of the Collaboration, the
Manufacturing Activities, and/or Alnylam’s obligations under the Original Agreements, and (b) any
Patent Rights which claim, cover or relate to such Know-How. Alnylam Collaboration IP excludes
Alnylam’s interest in Joint Collaboration IP.

“Alnylam Core Patent Rights” means those Patent Rights set forth in Schedule 1.3 of the
Tekmira Agreement, including various [**] patents and patent applications, as such Schedule is
supplemented from time to time pursuant to Section 6.5.1 of the Tekmira Agreement.

“Alnylam Field” means the treatment, prophylaxis and diagnosis of diseases in humans using
an RNAi Product or miRNA Product.

“Alnylam IOC Technology” mean, generally (a) Know-How Controlled by Alnylam as of the
Effective Date that is useful or necessary to Develop, Commercialize and/or Manufacture an IOC
Product in the Inex IOC Field (excluding any Alnylam Collaboration IP and Alnylam’s interest in
Joint Collaboration IP), and (b) those Patent Rights set forth in Schedule 1.5 of the Tekmira
Agreement, including [**].

“Alnylam Lipidoid Patent Rights” means those Patent Rights Controlled by Alnylam under a
license from the Massachusetts Institute of Technology pursuant to the MIT License Agreement and
that are set forth in Schedule 1.6 of the Tekmira Agreement, including [**].

“Alnylam RNAi Know-How” means, generally, Know-How Controlled by Alnylam that Alnylam
determines in its reasonable judgment to be useful or necessary to Develop, Commercialize and/or
Manufacture an Alnylam Royalty Product in the Alnylam Field

Page 41 of 93, Schedule B

 

(excluding any Alnylam Collaboration IP and Alnylam’s interest in Joint Collaboration IP).

“Alnylam RNAi Patent Rights” means, generally, Patent Rights Controlled by Alnylam that
claim (a) Alnylam RNAi Know-How, or (b) the identification, characterization, optimization,
construction, expression, formulation, use or production of an Alnylam Royalty Product, as the case
may be, and which Alnylam determines in its reasonable judgment to be useful or necessary to
Develop, Commercialize and/or Manufacture an Alnylam Royalty Product in the Alnylam Field
(including, without limitation, the Alnylam Core Patent Rights and the Alnylam Lipidoid Patent
Rights, but specifically excluding Alnylam IOC Technology and any Patent Rights included in Alnylam
Collaboration IP or Alnylam’s interest in Joint Collaboration IP).

“Alnylam RNAi Technology” means, collectively, Alnylam RNAi Know-How and Alnylam RNAi
Patent Rights.

“Alnylam Royalty Product” means any RNAi Product or a miRNA Product that, but for the
licenses granted hereunder, would be Covered by one or more Valid Claims of the Inex Patent Rights.

“Biodefense Target” means (a) a Target within the genome of one or more Category A, B and C
pathogens, as defined by the National Institute of Allergy and Infectious Diseases, including
without limitation, pathogens listed on Schedule 1.12 of the Tekmira Agreement, but specifically
excluding influenza virus, or (b) an endogenous cellular Target against which Alnylam Develops
and/or Commercializes an Alnylam Royalty Product for commercial supply to one or more Funding
Authorities.

“Collaboration IP” means, collectively, Alnylam Collaboration IP, Inex Collaboration IP and
Joint Collaboration IP.

“Existing Inex In-Licenses” means the Third Party agreements listed on Schedule 1.30 to the
Tekmira Agreement.

“IOC” or “Immunostimulatory Oligonucleotide Composition” means a single-stranded or
double-stranded ribonucleic acid (“RNA”) composition, or derivative thereof, that has
activity solely through an immunostimulatory mechanism and has no RNAi activity against a human
gene transcript or viral genomic sequence.

"IOC Product” means a product containing, comprised of or based on IOCs or IOC derivatives.

“Inex Collaboration IP” means, generally (a) any improvement, invention or Know-How first
discovered or developed by employees of Tekmira or its Affiliates or other persons not employed by
Alnylam acting on behalf of Tekmira, in the performance of the Collaboration, the Manufacturing
Activities, and/or Tekmira’s obligations under the Original Agreements, and (b) any Patent Rights
which claim, cover or relate to such Know-How. Inex Collaboration IP excludes Tekmira’s interest
in Joint Collaboration IP.

Page 42 of 93, Schedule B

 

“Inex In-License” means an agreement between Tekmira or its Affiliates, and a Third Party,
pursuant to which Tekmira or any of its Affiliates Control(s) Inex Technology relating to the
Alnylam Field under a license or sublicense from such Third Party, including without limitation,
the Existing Inex In-Licenses.

“Inex IOC Field” means the treatment, prophylaxis and diagnosis of diseases in humans using
an IOC Product.

“Inex IOC Technology” means, generally (a) Know-How Controlled by Tekmira or its Affiliates
with respect to IOC Products and/or IOCs, and (b) Patent Rights Controlled by Tekmira and its
Affiliates that claim such Know-How or the identification, characterization, optimization,
construction, expression, formulation, delivery, use or production of an IOC Product and/or IOC,
and are useful or necessary to Develop, Commercialize and/or Manufacture IOC Products in the Field.

“Inex Know-How” means, generally, Know-How Controlled by Tekmira or its Affiliates with
respect to an RNAi Product or miRNA Product (excluding any Inex Collaboration IP, Tekmira’s
interest in Joint Collaboration IP and any such Know-How sublicensed to Alnylam pursuant to the UBC
Sublicense).

“Inex Patent Rights” means, generally, Patent Rights Controlled by Tekmira or its
Affiliates that claim (a) Inex Know-How or (b) the identification, characterization, optimization,
construction, expression, formulation, delivery, use or production of an RNAi Product or miRNA
Product, and are useful or necessary to Develop, Commercialize and/or Manufacture RNAi Products or
miRNA Products in the Alnylam Field (excluding any Patent Rights included in Inex Collaboration IP,
Tekmira’s interest in Joint Collaboration IP and any such Patent Rights licensed to Alnylam
pursuant to the UBC Sublicense).

“Inex Royalty Product” means any (a) Inex Development Product that, but for the licenses
granted hereunder, would be Covered by one or more Valid Claims under the Alnylam Core Patent
Rights or the Alnylam Lipidoid Patent Rights, or (b) IOC Product that but for the licenses granted
hereunder, would be Covered by one or more Valid Claims under the Alnylam IOC Technology.

“Inex Technology” means, collectively, Inex Know-How and Inex Patent Rights.

“Inex-UBC License Agreement” means that certain license agreement between Tekmira and the
University of British Columbia (“UBC”) dated effective July 1, 1998, as amended by
Amendment Agreement between Tekmira and UBC dated effective July 11, 2006, and Second Amendment
Agreement dated effective the Effective Date.

“Joint Collaboration IP” means, generally (a) any improvement, discovery or Know-How first
discovered or developed jointly by the Parties or their Affiliates or others acting on behalf of
Tekmira and Alnylam in the performance of the Collaboration, the Manufacturing Activities and/or
the obligations of the Parties under the Original Agreements, and (b) any Patent Rights which
claim, cover or relate to such Know-How.

Page 43 of 93, Schedule B

 

“Manufacturing Activities” means those activities performed by a party relating to the
manufacture and supply of Alnylam Royalty Products.

“Necessary Third Party IP” means, on a country-by-country basis, Know-How or Patent Rights
in such country owned or controlled by a Third Party that cover a Royalty Product.

“RNAi Product” means a product containing, comprised of or based on siRNAs or siRNA
derivatives or other moieties effective in gene function modulation and designed to modulate the
function of particular genes or gene products by causing degradation of a Target mRNA to which such
siRNAs or siRNA derivatives are complementary (“RNAi Interference Mechanism”), and that is
not an miRNA Product.

“Royalty Product” means, either (a) an Alnylam Royalty Product, or (b) an Inex Royalty
Product.

“Selection Term” means the period commencing on the Effective Date and continuing for five
(5) Contract Years thereafter, unless such period is extended pursuant to Section 2.2 of the
Tekmira Agreement.

“Target” means: (a) a polypeptide or entity comprising a combination of at least one
polypeptide and other macromolecules, that is a site or potential site of therapeutic intervention
by a therapeutic agent; or a nucleic acid which is required for expression of such polypeptide; (b)
variants of a polypeptide, cellular entity or nucleic acid described in clause (a); (c) a defined
non-peptide entity, including a microorganism, virus, bacterium or single cell parasite; provided
that the entire genome of a virus will be regarded as a single Target; or (d) a naturally occurring
interfering RNA or miRNA or precursor thereof.

“Third Party Liposome Patent Rights” means, with respect to an Alnylam Royalty Product, (a)
the Alnylam Lipidoid Patent Rights and/or (b) other technology comprising a lipid component or
liposomal formulation useful or necessary for the Development, Manufacture or Commercialization of
such Alnylam Royalty Product and Controlled by Alnylam under a license from a Third Party, and in
each case with respect to which Intellectual Property Rights Alnylam has granted to Tekmira a
non-exclusive, royalty- and milestone fee-bearing (on a pass-through basis) license to Develop,
Manufacture and Commercialize Inex Royalty Products in the Alnylam Field in the case of Inex
Development Product, and in the Inex IOC Field in the case of IOC Products.

“UBC Sublicense Documents” means the collective reference to (a) the Sublicense Agreement
dated as of the Effective Date between the Parties (the “UBC Sublicense”), (b) the Consent
and Agreement dated as of the Effective Date among the Parties and UBC, and (c) the Assignment
dated the Effective Date between Tekmira and UBC.

Page 44 of 93, Schedule B

 

TEKMIRA/UBC

	7.	 	The Sublicense Agreement between Tekmira and Alnylam, dated January 8, 2007 (“UBC
Sublicense Agreement”)

Brief Summary of Technology Covered by License: See Tekmira Agreement above.

Limitations on Scope of License (Sections 3.1 and 3.3)

	•	 	The sublicense granted to Alnylam is limited to an exclusive, worldwide license under the
rights granted to Tekmira in the University License Agreement (see below) with respect to
Technology to research, develop, manufacture, have made, distribute, import, use, sell and
have sold Products in and for the Alnylam Field. In addition, any sublicense granted by
Tekmira to Alnylam would be subject to Tekmira’s sublicense to Esperion Technologies, Inc. of
certain technology relating to liposome compositions and methods for the treatment of
atherosclerosis.
	 
	•	 	Under the University License Agreement, Tekmira obtained from the University an exclusive,
worldwide license to use and sublicense the Technology and to make, have made, distribute,
import and use goods, the manufacture, use or sale of which would, but for the license granted
herein, infringe a Valid Claim of any Patent, including a license to use and sublicense the
Technology for (a) the delivery of and use with nucleic acid constructs, and (b) the
treatment, prophylaxis and diagnosis of disease in humans using an RNAi Product or miRNA
Product, and to research, develop, make, have made, distribute, import, use, sell and have
sold RNAi Products and miRNA Products.
	 
	•	 	University retains the right to use the Technology without charge in any manner whatsoever
for non-commercial research, scholarly publication, educational or other non-commercial use.

Restrictions on Sublicensing by Alnylam (Sections 3.2 and 4.2)

	•	 	Any further sublicense granted by Alnylam to a third party would be subject to the grant of
the following licenses by Alnylam to Tekmira under Alnylam’s rights in the Technology: (a) to
perform Tekmira’s obligations under the Collaboration with respect to Products, and the
Manufacturing Activities, on a non-exclusive basis, and (b) to develop, manufacture and
commercialize Inex Royalty Products for the treatment, prophylaxis and diagnosis of diseases
in humans, on an exclusive basis.
	 
	•	 	Alnylam may grant sublicenses to third parties with respect to the Technology only upon
written notice to Tekmira and the University, and provided that the
Sublicensee agrees (i) to perform the terms of the UBC Sublicense Agreement as if such
Sublicensee were Alnylam under the UBC Sublicense Agreement; (ii) to represent that
Sublicensee is not, as of the effective date of the relevant sublicense agreement, engaged in
a dispute with the University; and (iii) to be subject to a written sublicense agreement that
contains terms consistent with “the terms of this Agreement”

Page 45 of 93, Schedule B

 

	 	 	described in Section 4.2(c) of the UBC Sublicense Agreement (see below) and that provides that
the University is a third party beneficiary of, and has the right to enforce directly against
the sublicensee, the terms in such sublicense agreement that are consistent with the terms
listed in Section 4.2(c)(ii) of the UBC Sublicense Agreement.

	•	 	Section 4.2(c)(ii) of the UBC Sublicense Agreement states that the “terms of this
Agreement” means (i) the terms set forth in the UBC Sublicense Agreement; (ii) terms in such
sublicense agreement consistent with Sections 1.3 (Alnylam Consent to Certain Disclosures to
the University), 1.7 (Rights of the University), 2.1 (Limited Warranties), 2.2 (Disclaimer of
Product Liability), 2.3 (Indemnification of the University), 2.4 (Monetary Cap Respecting UBC
License), 2.5 (Disclaimer of Consequential Losses by the University), 2.6 (Litigation), 2.7
(UBC Trademark), 2.8 (Confidentiality of Terms) and 2.13 (Alnylam Warranties) of the Consent
Agreement among Alnylam, Tekmira and the University of even date with the UBC Sublicense
Agreement (“Consent Agreement”); and (iii) other customary and reasonable terms,
including but not limited to terms relating to breach and termination, that are consistent
with Alnylam’s obligations to Tekmira under the UBC Sublicense Agreement and the Tekmira
Agreement.

The terms of the Consent Agreement referenced in clause (ii) above are set forth below:

	 	1.3	 	Alnylam Consent to Certain Disclosures to the University. Alnylam consents
to Tekmira disclosing to the University: (i) Alnylam’s report to Tekmira made pursuant
to Article 10.8 of the UBC Sublicense Agreement; and (ii) copies of Alnylam’s
sublicenses provided to Tekmira pursuant to Article 4.3 of the UBC Sublicense
Agreement; solely for the purposes of calculation of royalties under the UBC License,
determining compliance with Section 10.8 of the License Agreement between Tekmira and
University dated July 1, 1998, as amended by an Amendment Agreement dated July 11,
2006, and a Second Amendment Agreement dated January 8, 2007 (as amended, the “UBC
License”) and determining compliance with Article 5 of the UBC Sublicense
Agreement, and the University shall • use reasonable efforts to ensure that all
information provided to the University or its representatives pursuant to this Section
1.3 remains confidential and is treated as such by the University.
	 
	 	1.7	 	Rights of the University. In consideration of the University providing its
consent in the Consent Agreement, Tekmira and Alnylam agree that the University shall
be entitled to rely upon any rights provided to the University pursuant to the terms
of the UBC Sublicense Agreement, notwithstanding that the University is not a party to
the UBC Sublicense Agreement.
	 
	 	2.1	 	Limited Warranties. Alnylam and its Affiliates expressly acknowledge and
agree that:

Page 46 of 93, Schedule B

 

(a) Except as expressly set out in Section 2.1(c) of the Consent Agreement, the
University makes no representations, conditions, or warranties, either express or
implied, with respect to the Technology, Improvements, Patents or any Products.
Without limiting the generality of the foregoing, the University specifically
disclaims any implied warranty, condition, or representation that the Technology,
Improvements, Patents or Products: (i) shall correspond with a particular
description; (ii) are of merchantable quality; (iii) are fit for a particular
purpose; or (iv) are durable for a reasonable period of time.

(b) Except as expressly set out in Section 2.1(c) of the Consent Agreement, nothing
in the UBC License, the Consent Agreement, or the UBC Sublicense Agreement shall be
construed as: (i) a warranty or representation by the University as to title to the
Technology, the Patents or any improvement or that anything made, used, sold or
otherwise disposed of under the license granted in the Consent Agreement is or will
be free from infringement of patents, copyrights, trademarks, industrial design or
other intellectual property rights, (ii) an obligation by the University to bring
or prosecute or defend actions or suits against third parties for infringement of
patents, copyrights, trademarks, industrial designs or other intellectual property
or contractual rights, or (iii) the conferring by the University of the right to
use in advertising or publicity the name of the University or UBC Trademarks.

(c) The University agrees that the warranty set forth in Section 7.4 of the UBC
License will inure to the benefit of Alnylam and its sublicensees. For avoidance of
doubt, such warranty is exactly as stated in the UBC License and its inclusion in
the Consent Agreement will not change its terms in any way including, but not
limited to, changing the date of such warranty from June 30, 2001.

	 	2.2	 	Disclaimer of Product Liability. Alnylam and its Affiliates expressly
acknowledge and agree that the University shall not be liable for any damages, or any
other loss, whether direct, indirect consequential, incidental, or special which
Alnylam or its Affiliates, or any further sublicense, under any sublicense agreements
between Alnylam and such further sublicensee, suffer, arising from any defect, error,
fault, or failure to perform with respect to the Technology, Patents, Improvements or
any Products, even if the University has been advised of the possibility of such
defect, error, fault, or failure. Alnylam and its Affiliates acknowledge that they
have been advised by the University to undertake their own due diligence with respect
to the Technology, Patents, Improvements and Products.
	 
	 	2.3	 	Indemnification of the University. Alnylam and its Affiliates indemnify, hold
harmless and defend the University, its Board of Governors, officers, employees,
faculty, students, invitees and agents (the “UBC Indemnitees”)

Page 47 of 93, Schedule B

 

	 	 	 	against any and all claims (including all legal fees and disbursements incurred in
association therewith) arising out of the exercise of any rights under the Consent
Agreement, the UBC License or the UBC Sublicense Agreement, including, without
limiting the generality of the foregoing, against any damages or losses,
consequential or otherwise, arising from or out of the use of the Technology,
Patents, Improvements or Product(s) sublicensed under the UBC Sublicense Agreement
by Alnylam or its Related Parties, or their respective customers or end-users
howsoever the same may arise. For greater clarity, it is confirmed that, without
limiting the generality of the foregoing, the indemnification by Alnylam and its
Affiliates of the UBC Indemnitees set out in the Consent Agreement shall include an
obligation to indemnify the UBC Indemnitees against any and all subrogated claims
which may be brought against the UBC Indemnitees by any person(s) or entities
(including without limitation Alnylam, its Related Parties, their respective
customers or end-users, or their respective insurers) which may not have waived
their rights of subrogation against the UBC Indemnitees, and shall also include,
without limiting any of the foregoing, an obligation to indemnify the UBC
Indemnitees against any and all claims relating to any injury or death to any
person or damage to any property caused by any Product, whether claimed by reason
of breach of warranty, negligence, product defect or otherwise, and regardless of
the form in which any such claim is made.

	 	2.4	 	Monetary Cap Respecting UBC License. The University’s liability, whether
under the express or implied terms of the Consent Agreement, the UBC License or the
UBC Sublicense Agreement, in tort (including negligence), or at common law, for any
loss or damage suffered by Alnylam or its Related Parties, whether direct, indirect,
special, or any other similar or like damage, to the extent that such losses or damage
may arise or does arise from any breaches of the UBC License, the Consent Agreement or
the UBC Sublicense Agreement by UBC Indemnitees, shall be limited to the sum of [**].
	 
	 	2.5	 	Disclaimer of Consequential Losses by the University. In no event shall the
University be liable for consequential or incidental damages arising from any breach
or breaches of the UBC License, the UBC Sublicense Agreement or the Consent Agreement.
	 
	 	2.6	 	Litigation. Provided that Tekmira has obtained the University’s consent
required by Article 7 of the UBC License, Tekmira’s right to prosecute litigation in
Article 7 of the UBC License may be exercised by Alnylam pursuant to Sections 7.5 and
7.6 of the UBC Sublicense Agreement.
	 
	 	2.7	 	UBC Trademarks. Alnylam shall not use any of the University’s trademarks or
make reference to the University or its name in any advertising or publicity
whatsoever, without the prior written consent of the University, except as required by
law. Nothing in the Consent

Page 48 of 93, Schedule B

 

	 	 	 	Agreement shall prevent Alnylam from making or issuing factual statements to the
public regarding its business or use of the Patent. If Alnylam is required by law
to act in contravention of this provision, Alnylam shall provide the University
with sufficient advance notice in writing to permit the University to bring an
application or other proceeding to contest the requirement.

	 	2.8	 	Confidentiality of Terms. Alnylam requires of the University, and the
University agrees insofar as it may be permitted to do so at law, that the Consent
Agreement, the UBC Sublicense Agreement and each part of each of them, is confidential
and shall not be disclosed to third parties, as Alnylam claims that such disclosure
would or could reveal commercial, scientific or technical information and would
significantly harm Alnylam’s competitive position and/or interfere with Alnylam’s
negotiations with prospective sublicensees. Notwithstanding anything contained in this
Section 2.8, the parties to the Consent Agreement acknowledge and agree that the
University may identify the title of the Consent Agreement and/or the UBC Sublicense
Agreement, the parties to the Consent Agreement and/or the UBC Sublicense Agreement,
the inventors of the Technology, the term of the Consent Agreement and/or the UBC
Sublicense Agreement, and the consideration actually paid to the University pursuant
to the Consent Agreement and/or the UBC Sublicense Agreement.

	 	2.13	 	Alnylam Warranties. Alnylam warrants and represents to the University that:

(a) Alnylam is a corporation duly organized, existing, and in good standing under
the laws of Delaware and has the power, authority, and capacity to enter into the
Consent Agreement and to carry out the transactions contemplated by the Consent
Agreement, all of which have been duly and validly authorized by all requisite
corporate proceedings;

(b) the execution, delivery and performance by Alnylam of the Consent Agreement and
the UBC Sublicense Agreement do not contravene or constitute a default under any
provision of applicable law or its articles or by-laws (or equivalent documents) or
of any judgment, injunction, order, decree or other instrument binding upon
Alnylam; and

(c) the Consent Agreement constitutes a valid and binding agreement. of Alnylam,
enforceable against Alnylam in accordance with its terms.

	•	 	Any sublicense granted by Alnylam under the UBC Sublicense Agreement will survive
termination of the licenses or other rights granted to Alnylam under the UBC Sublicense
Agreement, and be assumed by Tekmira, as long as (i) the sublicensee is not then in breach of
its sublicense agreement, (ii) the sublicensee agrees in writing to be bound to Tekmira as a
sublicensor and to the University under the terms and

Page 49 of 93, Schedule B

 

	 	 	conditions of the UBC Sublicense Agreement, and (iii) the sublicensee agrees in writing that in
no event will Tekmira assume any obligations or liabilities, or be under any obligation or
requirement of performance, under any such sublicense extending beyond Tekmira’s obligations
and liabilities under the UBC Sublicense Agreement.

	•	 	Alnylam is required to furnish Tekmira with a copy of each sublicense granted within 30
days after execution. Any such copy may contain reasonable redactions as Alnylam may make,
provided that such redactions do not include provisions necessary to
demonstrate compliance with the requirements of the UBC Sublicense Agreement. If University
requests of Tekmira that a less redacted version of any sublicense be provided to University,
Alnylam agrees to discuss in good faith with Tekmira and the University the University’s
concerns.

Financial Obligations (Section 5.0)

	•	 	The consideration for the rights granted to Alnylam to the Technology under the UBC
Sublicense Agreement, and the consideration for the rights granted by Tekmira to Alnylam to
other technologies under the Tekmira Agreement, is the payment by Alnylam of milestones and
royalties in accordance with Article 7 of the Tekmira Agreement.

Prosecution and Enforcement (Sections 6.2, 7.5, 7.7)

	•	 	Tekmira will have the right, with reasonable input from Alnylam, to identify any process,
use or products arising out of the Technology that may be patentable and will take all
reasonable steps to apply for a patent in the name of the University, provided that Tekmira
pays all costs of applying for, registering, and maintaining the patent in those jurisdictions
in which Tekmira determines that a Patent is required.
	 
	•	 	On the issuance of a patent for the Technology, Tekmira will have the right to become, and
will become the licensee of the same, all pursuant to the terms contained in the University
License Agreement, and Alnylam will have the right to become, and will become the sublicensee
of such rights pursuant to the terms contained in the UBC Sublicense Agreement.
	 
	•	 	Should Tekmira:

(a) discontinue pursuing one or more patent applications, patent protection or patent
maintenance in relation to the Patent(s) or any continuation, continuation in-part, division,
reissue, re-examination or extension thereof; or

(b) not pursue patent protection in relation to the Patent(s) in any specific jurisdiction; or

(c) discontinue or not pursue patent protection in relation to any further process, use or
products arising out of the Technology in any jurisdiction;

Page 50 of 93, Schedule B

 

then Tekmira will provide Alnylam with notice of its decision to discontinue or not to pursue such
patent protection concurrently with the notice provided to the University by Tekmira pursuant
to Section 6.6 of the University License Agreement.

	•	 	In the event of an alleged infringement by a third party of the Technology or any right
with respect to the Technology, or any complaint by Alnylam alleging any infringement by a
third party with respect to the Technology or any right with respect to the Technology, in
each case that is licensed to Alnylam under the UBC Sublicense Agreement, Alnylam will,
subject to Tekmira having first obtained the University’s consent as required by Article 7 of
the University License Agreement, have the right to prosecute such litigation at Alnylam’s
expense.
	 
	•	 	In the event of any litigation, Alnylam will keep Tekmira fully informed of the actions and
positions taken or proposed to be taken by Alnylam (on behalf of itself or a sublicensee) and
actions and positions taken by all other parties to such litigation.
	 
	•	 	In the event of an alleged infringement of the Technology or any third party use of the
Technology which is Confidential Information, Alnylam and Tekmira agree that they will
reasonably cooperate to enjoin such third party’s use of the Technology.
	 
	•	 	If any complaint alleging infringement or violation of any patent or other proprietary
rights is made against Alnylam (or a sublicensee of Alnylam) with respect to the manufacture,
use or sale of Product, then:

(a) Alnylam will promptly notify Tekmira upon receipt of any such complaint and will keep
Tekmira fully informed of the actions and positions taken by the complainant and taken or
proposed to be taken by Tekmira (on behalf of itself or a sublicensee);

(b) Alnylam (or any sublicenseee, as the case may be) will pay all costs and expenses incurred
by Alnylam (or any sublicensee of Alnylam) in investigating, resisting, litigating and settling
such a complaint, including the payment of any award or damages and/or costs to any third
party; and

(c) if as a result of such suit it is decided that a Product infringes any valid claim on a
patent owned by another, Tekmira will consider fair distribution of Royalty Income.

Diligence and Reporting (Section 10.2)

	•	 	Alnylam is required to use its reasonable commercial efforts to promote, market and sell
the Products and utilize the Technology and to meet or cause to be met the market demand for
the Products and the utilization of the Technology.
	 
	•	 	Alnylam is required to deliver to Tekmira an annual report, due on December 31 of each
year, which summarizes the major activities Alnylam has undertaken in the course of the
preceding 12 months to develop and commercialize and/or market the

Page 51 of 93, Schedule B

 

	 	 	Technology. The report must include an outline of the status of any Products in clinical
trials and the existence of any sublicenses of the Technology.

Certain Termination Rights (Section 16.1)

	•	 	If Alnylam’s rights to Inex Technology are terminated under the Tekmira Agreement, the UBC
Sublicense Agreement and the license granted to Alnylam thereunder also terminates.

Definitions:

Capitalized terms not otherwise defined below have the meanings given to them under the Tekmira
Agreement.

“1999 CRA” means the Collaborative Research Agreement between Tekmira and the University
dated effective January 1, 1999 and successor agreements to such Know-How.

“2007 CRA” means the Collaborative Research Agreement between Tekmira and the University
dated effective January 1, 2007 and successor agreements to such Know-How.

“Alnylam Field” means the use of Products for the treatment, prophylaxis and diagnosis of
diseases in humans.

“Improvements” means, generally (i) any and all patents and any and all patent applications
that claim priority to Patents; and (ii) any and all inventions arising therefrom. Notwithstanding
anything to the contrary in the University License Agreement, ownership of all Improvements (A)
that fall within clause (i) above will be assigned to the University; and (B) that fall within
clause (ii) above will follow inventorship as determined by U.S. patent law, except that the
University will own all Improvements made by its employees, whether alone or jointly with Tekmira,
under the 1999 CRA or 2007 CRA.

“miRNA Product” means a product containing, comprised of or based on native or chemically
modified RNA oligomers designed to either modulate a micro RNA transcript and/or provide the
function of a micro RNA transcript.

“Patent(s)” means, generally, the patents and patent applications, including certain
“Wheeler Patents,” listed on Schedule A to the UBC Sublicense Agreement, and any claims of CIPs and
of resulting patents which are to the UBC Sublicense Agreement, and any reissues of such patents.

“Product(s)” means any RNAi Product or miRNA Product that, the manufacture, use or sale of
which would, but for the license granted herein, infringe a Valid Claim of one or more of the
Patent(s).

“RNAi Product” means a product containing, comprised of or based on small interfering RNAs
or small interfering RNA derivatives or other moieties effective in gene function modulation and
designed to modulate the function of particular genes or gene products by

Page 52 of 93, Schedule B

 

causing degradation of a target mRNA to which such small interfering RNAs or small interfering RNA
derivatives are complementary, and that is not an miRNA Product.

“Technology” means the Patent(s) and any and all knowledge, know-how and/or technique or
techniques invented, developed and/or acquired, being invented, developed and/or acquired by the
University solely or jointly with Tekmira relating to the Patent(s), including, without limitation,
all research, data, specifications, instructions, manuals, papers or other materials of any nature
whatsoever, whether written or otherwise, relating to same.

“University License Agreement” means the License Agreement dated effective July 1, 1998, as
amended, pursuant to which Tekmira is the exclusive licensee of certain Patents owned by the
University of British Columbia (the “University”).

Page 53 of 93, Schedule B

 

PROTIVA

	8.	 	Cross-License Agreement between Protiva Biotherapeutics Inc. (“Protiva”) and Alnylam
Pharmaceuticals, Inc., effective August 14, 2007 (“Protiva Cross-License Agreement”)

Brief Summary of Technology Covered by License:

PROTIVA grants Alnylam non-exclusive rights to develop and commercialize RNAi therapeutics, under
PROTIVA’s patent rights relating to “Lipid Encapsulated Interfering RNA” and “Method and Apparatus
for Producing Liposomes”.

Alnylam grants PROTIVA non-exclusive rights to develop and commercialize RNAi therapeutics directed
to specified target(s), some of which may be identified in the future, under certain of Alnylam’s
patent rights licensed from Max Planck relating to RNA interference.

Limitations on Scope of License (Sections 2 and 3; Section 4)

	•	 	Class 1: PROTIVA grants to Alnylam a non-exclusive, worldwide license under Class
1 PROTIVA Patent Rights, PROTIVA’s interest in Joint Patent Rights and Licensed Information to
Research, Develop and Commercialize RNAi Products for any Target in the Field (“Alnylam
Class 1 Development Products”). Subject to the restrictions set forth herein in respect
of the Merck Entities and the Tekmira Entities, such license includes the right to grant
sublicenses to one or more Third Parties in a Bona Fide Collaboration with Alnylam, but solely
within the scope of and for the purposes of such Bona Fide Collaboration, or with respect to
the Researching, Developing and/or Commercializing of Alnylam Class 1 Development Products
that meet one or more of the following: (i) such Alnylam Class 1 Development Product was
initially Developed at least to the point of preclinical proof-of-principle by Alnylam in an
Active Internal Development Program; (ii) such Alnylam Class 1 Development Product is an
Alnylam Partnered RNAi Product; or (iii) such Alnylam Class 1 Development Product is an R&D
Program RNAi Product.

	•	 	Class 2: PROTIVA grants to Alnylam a non-exclusive license under Class 2 PROTIVA
Patent Rights to Research, Develop and Commercialize RNAi Products for any Alnylam Target in
the Field in the Territory (“Alnylam Class 2 Development Products”). Subject to the
restrictions set forth herein in respect of the Merck Entities and the Tekmira Entities, such
license includes the right to grant sublicenses under the license granted in this Section
4.1(b); provided that:

	 	(i)	 	prior to the Class 2 Restrictions Reduction, such right to sublicense will
apply only with respect to the Researching, Developing and/or Commercializing of
Alnylam Class 2 Development Products that meet one or more of the following:

	 	(A)	 	such Alnylam Class 2 Development Product is an R&D Program
RNAi Product; or

Page 54 of 93, Schedule B

 

	 	(B)	 	such Alnylam Class 2 Development Product incorporates the
same Formulation as the Lead Formulation of an R&D Program RNAi Product, and
is directed at the same Alnylam Target as that R&D Program RNAi Product and
also meets one or more of the following: (1) such Alnylam Class 2 Development
Product was initially Developed at least to the point of preclinical
proof-of-principle by Alnylam in an Active Internal Development Program; or
(2) such Alnylam Class 2 Development Product is an Alnylam Partnered RNAi
Product; and

	 	(ii)	 	after the Class 2 Restrictions Reduction, such right to sublicense will apply
only with respect to the Researching, Developing and/or Commercializing of Alnylam
Class 2 Development Products that meet one or more of the following:

	 	(A)	 	such Alnylam Class 2 Development Product is an R&D Program
RNAi Product; or
	 
	 	(B)	 	such Alnylam Class 2 Development Product incorporates the
same Formulation as the Lead Formulation of an R&D Program RNAi Product,
whether or not it is directed at the same Alnylam Target as that R&D Program
RNAi Product, and also meets one or more of the following: (1) such Alnylam
Class 2 Development Product was initially Developed at least to the point of
preclinical proof-of-principle by Alnylam in an Active Internal Development
Program; or (2) such Alnylam Class 2 Development Product is an Alnylam
Partnered RNAi Product.

	•	 	Alnylam and PROTIVA agree that if any item listed in Exhibit A-3 as Class 2 PROTIVA Patent
Rights or claim thereunder meets the definition of Class 1 PROTIVA Patent Rights as described
in Section 1.43, such item or claim will become a Class 1 PROTIVA Patent Right. Only items or
claims under Class 2 PROTIVA Patent Rights may change to Class 1 PROTIVA Patent Rights, and
Class 1 PROTIVA Patent Rights will not change to Class 2 PROTIVA Patent Rights

In addition, any license granted by Alnylam to a Third Party under Alnylam Patent Rights would be
subject to the following:

	•	 	A non-exclusive, worldwide, sublicenseable (in accordance with Section 2.1(b)) license
granted to Protiva under the Alnylam Patent Rights and under Alnylam’s interest in Joint
Patent Rights, for purposes of Researching, Developing and Commercializing RNAi Products for a
specified target in the Field.

	•	 	Alnylam’s rights to co-develop and co-commercialize RNAi Products for a specified target
with Protiva.

Page 55 of 93, Schedule B

 

	•	 	PROTIVA’s right, during the first 4 years after the Effective Date, to select up to 3
Targets with respect to which PROTIVA shall have the non-exclusive right to Research, Develop
and Commercialize RNAi Products directed to such Target under the Alnylam Patent Rights (each,
a “PROTIVA Development Target”, and each such RNAi Product, a “PROTIVA Development
Product”).

	•	 	A non-exclusive license under the Alnylam Patent Rights and Alnylam’s interest in Joint
Patent Rights which will be granted to PROTIVA with respect to up to 3 PROTIVA Development
Targets, to Research, Develop and Commercialize PROTIVA Development Products covered by such
Alnylam Patent Rights in the Field in the Territory. Such license will include the right to
grant sublicenses to Third Parties to Research, Develop and Commercialize PROTIVA Development
Product(s), provided such PROTIVA Development Product(s) either (a) incorporate or exploit
material intellectual property rights (such as, without limitation, patents and/or
Confidential Information) owned or controlled by PROTIVA, other than the Alnylam Patent Rights
and/or (b) are substantially developed by PROTIVA in a Bona Fide Collaboration with such Third
Party.

	•	 	Prohibition on use or disclosures of any of PROTIVA’s Confidential Information to (1) Merck
Entities or (2) Tekmira Entities.

Restrictions on Sublicensing (Sections 4.4 and 4.5)

	•	 	In no event will Alnylam have the right to sublicense or agree to sublicense any PROTIVA
Patent Rights to any Merck Entity or any Tekmira Entity; provided, however, that PROTIVA will
notify Alnylam in writing when, in PROTIVA’s reasonable opinion, all litigation between either
(a) PROTIVA and any Merck Entity or (b) PROTIVA and any Tekmira Entity, as the case may be,
(x) has been settled or (y) a court has rendered a final, unappealable decision or order with
respect to such litigation, at which point, the provisions of this Section will no longer
apply to any Merck Entity or any Tekmira Entity, as the case may be.

	•	 	Alnylam shall assume full responsibility for the performance of all obligations and the
observance of all terms herein under a sublicense to the license granted for Alnylam
Development Products and will itself pay and account to PROTIVA for all payments due by reason
of such sublicense. Sublicenses under the licenses granted for Alnylam Development Products
will remain in full force and effect in the event of any termination of one or both of the
licenses, provided that sublicensee(s) are in compliance with the sublicense agreement (or are
in compliance within 30 days of the termination) and agree in writing with PROTIVA to the same
terms and conditions as in the sublicense agreement.

***Royalty Payment Obligations (Sections 4.9 and 4.10)

	•	 	Alnylam Development Products that are Licensed RNAi Products will bear the following
royalties: [

Page 56 of 93, Schedule B

 

	 	 	 	 	 
	Net Sales	 	Royalty Rate
	Up to and including $[**]
	 	 	[**]	%
	Greater than $[**] up to and including $[**]
	 	 	[**]	%
	Greater than $[**]
	 	 	[**]	%

	•	 	The royalties may be reduced on a country-by-country basis by the amount of royalties due
to Third Parties as a result of the in-license of intellectual property rights necessary or
useful in respect of the manufacture or sale of Alnylam Development Products; provided that
royalties due to PROTIVA may not be reduced by more than [**] of the royalties otherwise due
(and will not in any case be reduced below [**] of the amount of royalties that would
otherwise be due, e.g. for Net Sales up to and including $[**] the minimum effective royalty
rate would be [**]%).

Prosecution and Enforcement (Section 7)

	•	 	Alnylam will have the right and responsibility to file, prosecute and maintain patent
protection in the Territory for all Alnylam Patent Rights. PROTIVA will have the right and
responsibility to file, prosecute and maintain patent protection in the Territory for all
PROTIVA Patent Rights.

	•	 	Alnylam will have the sole and exclusive right to initiate an infringement or other
appropriate suit with respect to infringements or suspected infringements of any of the
Alnylam Patent Rights.

	•	 	PROTIVA will have the sole and exclusive right to initiate an infringement or other
appropriate suit with respect to infringements or suspected infringements of any of the
PROTIVA Patent Rights.

Term and Termination (Section 12)

	•	 	If Alnylam or any of its Affiliates shall (a) commence or participate in any action or
proceeding (including, without limitation, any patent opposition or re-examination
proceeding), or otherwise assert in writing any claim, challenging or denying the validity of
any of the PROTIVA Patent Rights or any claim thereof or (b) actively assist any other person
or entity in bringing or prosecuting any action or proceeding (including, without limitation,
any patent opposition or re-examination proceeding) challenging or denying the validity of any
of such PROTIVA Patent Rights or any claim thereof, PROTIVA will have the right to give notice
to Alnylam (within 60 days after PROTIVA first learns of the foregoing) that Alnylam’s
license under Class 1 PROTIVA Patent Rights and/or the license under Class 2 PROTIVA Patent
Rights will terminate in 30 days following such notice, and, unless Alnylam withdraws or
causes to be withdrawn all such challenge(s) within such 30-day period, such licenses will so
terminate.

Page 57 of 93, Schedule B

 

	•	 	Upon any termination of this Agreement, each Party shall enter into an agreement containing
substantially the same provisions as this Agreement with any Sublicensees of the other Party
existing at the time of such termination, covering the RNAi Products that had been licensed to
such Sublicensee by such other Party in compliance with this Agreement and with the first
Party’s consent, provided that at the time of any termination of this Agreement, such
Sublicensees are in full compliance with the terms and conditions of the sublicense agreement.
Sublicensees of each Party that are then in full compliance with the terms and conditions of
their respective sublicense agreement are third party beneficiaries of this Agreement.

Definitions:

“Active Internal Development Program”, with respect to a particular RNAi Product, means
that the following criteria have been satisfied, as of the relevant time under this Agreement:

     (a) an active program of Research, Development or Commercialization with respect to such RNAi
Product has been commenced and remains in effect internally at Alnylam or its Affiliates; and

     (b) if such program has not previously established preclinical proof-of-principle for such
RNAi Product, Alnylam or its Affiliates have committed to conduct such program at least through the
completion of significant preclinical proof-of-principle testing of a specific Formulation for such
RNAi Product

“Alnylam Development Products” means Alnylam Class 1 Development Products and Alnylam Class
2 Development Products.

“Alnylam Partnered RNAi Product” means an RNAi Product that is at the relevant time being
Researched, Developed, and/or Commercialized by Alnylam with the participation or sponsorship of
one or more Third Parties other than Merck Entities and Tekmira Entities. For clarity, it is
understood and agreed that no RNAi Product developed or to be developed in a project or arrangement
in which all or substantially all of Alnylam’s contributions or anticipated contributions are or
will be in the form of the grant by Alnylam of licenses or sublicenses to one or more intellectual
properties will be considered an Alnylam Partnered RNAi Product.

“Alnylam Patent Rights” means the patents and patent applications listed on Exhibit A-1 and
related patent family.

“Alnylam Target” means any Target that is neither the specified target nor a PROTIVA
Development Target; provided, however, that the exclusion of the specified target will not apply if
PROTIVA provides notice to Alnylam that PROTIVA is terminating its license rights under this
Agreement with respect to RNAi Products for the specified target.

“Bona Fide Collaboration” means, generally, a collaboration between a Party and one or more
Third Parties involving the Research and Development of one or more RNAi

Page 58 of 93, Schedule B

 

Products and established under a written agreement in which (i) the scope of the licenses granted,
and financial or other commitments of value, are of material value to such Party and (ii) such
Party undertakes and performs substantial, mutual research activity with the Third Party.

“Class 2 Restrictions Reduction” means the earlier of (i) the 4th anniversary of the
Effective Date and (ii) the first day following the day on which an aggregate of 3 PROTIVA
Development Targets have been identified and approved for selection and PROTIVA has thereby
obtained licenses with respect to such three PROTIVA Development Targets.

“Field” means the use of prophylactic or therapeutic RNAi Products against such Target for
the prevention or treatment of human disease.

“Generic Claim” means a claim in an issued or pending patent that meets the following
criteria: (a) the claim recites a nucleic acid-lipid particle comprising: an siRNA, at least one
cationic lipid, at least one non-cationic lipid, and a conjugated lipid that inhibits aggregation
of particles, and/or methods or uses of such particle in the delivery of siRNA; and (b) the claim
does not recite any particular or specific siRNA, cationic lipid, non-cationic lipid, or conjugated
lipid

“Joint Patent Rights” means all patents and patent applications to the extent specifically
claiming inventions or improvements discovered and reduced to practice jointly by PROTIVA and
Alnylam directly in the course of work conducted following the Effective Date under the relevant
Research Plan, together with the related patent family.

“Licensed Information” means the information disclosed to Alnylam in accordance with the
criteria in Appendix II and other requirements set forth in this Agreement that is not covered by
PROTIVA Patent Rights or Joint Patent Rights.

“Licensed RNAi Product” means (a) with respect to PROTIVA and its Affiliates and
Sublicensees, an RNAi Product, the identification, characterization, validation, synthesis,
development, use, formulation, manufacture, production or sale of which, where and when occurring,
would, but for the grant of a license or sublicense from Alnylam, infringe a Valid Claim of the
Alnylam Patent Rights; and (b) with respect to Alnylam and its Affiliates and Sublicensees, an RNAi
Product, the identification, characterization, validation, synthesis, development, use,
formulation, manufacture, production or sale of which, where and when occurring, would, but for the
grant of a license or sublicense from PROTIVA, infringe a Valid Claim of the PROTIVA Patent Rights.

“Merck Entities” means Merck & Co. or its affiliated companies (including without
limitation Sirna Therapeutics, Inc., whether or not it remains affiliated with Merck & Co.).

“PROTIVA Patent Rights” means the Class 1 PROTIVA Patent Rights and the Class 2 PROTIVA
Patent Rights, together with all claims (other than Generic Claims) in the related patent family.

Page 59 of 93, Schedule B

 

“R&D Program RNAi Product” means the Formulations that are related to RNAi Product(s)
developed under this Agreement for which Alnylam has established an Active Internal Development
Program.

“RNAi Product” means a product containing, comprised of or based on siRNAs or siRNA
derivatives or other double-stranded moieties effective in gene function modulation and designed to
modulate the function of particular genes or gene products by causing degradation through RNA
interference of a Target mRNA to which such siRNAs or siRNA derivatives are complementary.

“Target” means (a) a polypeptide or entity comprising a combination of at least one
polypeptide and other macromolecules, that is a site or potential site of therapeutic intervention
by a therapeutic agent; or a nucleic acid which is required for expression of such polypeptide,
together with all variants of such polypeptide, cellular entity or nucleic acid described above;
(b) a defined non-peptide entity, including a microorganism, virus, bacterium or single cell
parasite; provided that the entire genome of a microorganism, virus, bacterium, or single cell
parasite shall be regarded as a single Target; or (c) a naturally occurring interfering RNA or
miRNA or precursor thereof.

“Tekmira Entities” means Tekmira Pharmaceuticals Corporation or Inex Pharmaceuticals
Corporation or any of their affiliated companies.

Page 60 of 93, Schedule B

 

REGULUS (LICENSE AGREEMENT)

	9.	 	License and Collaboration Agreement among Alnylam Pharmaceuticals, Inc., Isis
Pharmaceuticals, Inc. (“Isis”) and Regulus Therapeutics LLC (“Regulus”),
effective as of September 6, 2007, as supplemented by letter agreement dated September 6, 2007
(“Regulus License Agreement”)

Brief Description of Technology Covered by License

	•	 	Alnylam granted Regulus a right to develop, manufacture and commercialize miRNA Compounds
and miRNA Therapeutics. Such right is exclusive with respect to miRNA Antagonists, and
non-exclusive with respect to certain other miRNA Compounds.

	•	 	Regulus granted Alnylam a license to develop, manufacture and commercialize double-stranded
oligonucleotides.

Scope of Rights

Rights granted by Alnylam to Regulus:

	•	 	Alnylam agreed to assign to Regulus a patent family for “Chemically Modified
Oligonucleotide Agents and Uses Thereof” and a License Agreement between The Rockefeller University
and Alnylam effective August 15, 2005. (Section 2.1)
	 
	•	 	Alnylam granted to Regulus a worldwide, sublicenseable license in the Field, under
Alnylam’s Licensed IP, (i) to Develop miRNA Compounds and miRNA Therapeutics, (ii) to Manufacture
miRNA Compounds and miRNA Therapeutics, and (iii) to Commercialize miRNA Therapeutics. Such rights
are (y) exclusive with respect to miRNA Compounds which are miRNA Antagonists and miRNA
Therapeutics containing such miRNA Compounds, and (z) non-exclusive with respect to miRNA Compounds
which are Approved Precursor Antagonists and miRNA Therapeutics containing such miRNA Compounds.
The exclusive license is subject to Alnylam’s retained right to use and exploit its Licensed IP
solely to support its own internal Research in the Alnylam Field. (Section 2.2)
	 
	•	 	The licenses and other rights granted to a Party are subject to, and are limited to
the extent of the terms of any Out-License Agreements and In-License Agreements.
	 
	•	 	The license does not initially include licenses to Patent Rights or Know-How licensed
by Alnylam under certain agreements (the “Optional In-Licenses”). Regulus has the option
of expanding its licenses to include Patent Rights and Know-How pursuant to Optional In-Licenses,
with respect to miRNA Compounds and related miRNA Therapeutics upon written notice.

Page 61 of 93, Schedule B

 

	•	 	Regulus may request a worldwide, sublicenseable, non-exclusive license in the Field, under
Alnylam’s Licensed IP, to Develop, Manufacture and Commercialize a specific miRNA Mimic or a
specific miRNA Precursor Antagonist that is not then an Approved Precursor Antagonist, and miRNA
Therapeutics containing such miRNA Mimic or miRNA Precursor Antagonist, by providing written notice
to Alnylam thereof. Such license is subject to (i) review and affirmative approval by Alnylam,
which approval may be withheld by Alnylam in its sole discretion, and (ii) compliance with relevant
Third Party Rights. (Section 2.2)

Rights granted by Regulus to Alnylam:

	•	 	Regulus granted Alnylam a worldwide, exclusive, royalty-free, perpetual and irrevocable
license, with the right to grant sublicenses, under the Regulus IP solely to the extent necessary
or useful to research, discover, develop, make, have made, use, sell, offer to sell and/or
otherwise commercialize double-stranded oligonucleotides (other than Approved Mimics) and any
product containing double-stranded oligonucleotides (other than Approved Mimics) (the “Alnylam
Field”). (Section 2.3)

Additional provisions applicable to both in-licenses and out-licenses:

	•	 	If a Party (the “Controlling Party”) invents or acquires rights or title to an
invention claimed by a Patent Right that would be included in the Licensed Patent Rights or Regulus
Patent Rights (the “Additional Rights”), then the Controlling Party must notify each other
Party (each, a “Non-Controlling Party”) of such acquisition or invention. If a
Non-Controlling Party wishes to include such Additional Rights under the licenses granted pursuant
to the Regulus License Agreement, such Non-Controlling Party will notify the Controlling Party of
its desire to do so, the Controlling Party will provide the Non-Controlling Party a summary of all
material restrictions on the scope of the licenses granted, and all material payment obligations
owed, under any Third Party Agreement applicable to such Additional Rights and the Non-Controlling
Party may, upon written notice to the Controlling Party, obtain a license under such Additional
Rights and will assume all financial and other obligations to, and be subject to all restrictions
imposed by, the Controlling Party’s licensors or collaborators, if any, arising from the grant to
such Non-Controlling Party of such license. Any Additional Rights that do not carry financial or
other obligations or restrictions will be automatically included under the licenses granted
pursuant to the Regulus License Agreement. (Section 2.4)

Technology Transfer: At each meeting of the Collaboration Working Group, (a) the
representatives will discuss new Know-How and Patent Rights of Isis and Alnylam that are included
in such Licensor’s Licensed Patents and Licensed Know-How and (b) Regulus will present a
description of all Regulus IP developed by it or on its behalf, or over which Regulus otherwise
acquired Control, since the last meeting. (Section 3)

Non-Compete: Under certain circumstances, if Regulus does not continue to pursue the
Development and Commercialization of a particular Development Project, either Alnylam or Isis may
take over such Development Project and become the “Opt-In Party”. The non-Opt-In Party
with respect to a Development Project will not, itself or through its

Page 62 of 93, Schedule B

 

Affiliates or with Third Parties, Develop, Manufacture or Commercialize Development Compounds or
Development Therapeutics with respect to such Development Project during a specified period of
time; provided, however that each Licensor may grant licenses to enable Third Parties to broadly
manufacture or formulate oligonucleotides under certain circumstances. (Section 5)

IP Ownership, Prosecution and Enforcement (Section 9)

	•	 	Regulus owns all Work Product, and the Intellectual Property therein.
	 
	•	 	Regulus has the sole right to file, prosecute and maintain Patent Rights covering any
Regulus IP, at Regulus’ own expense.
	 
	•	 	Subject to any Third Party Rights, Regulus has a step-in right to prosecute Licensed Patent
Rights.
	 
	•	 	With respect to any actual or suspected infringement of Licensed Patent Rights or Regulus
Patent Rights by a Third Party making, using or selling a therapeutic product that contains or
consists of (y) certain miRNA Compounds or (z) if clause (y) does not apply, an oligonucleotide(s)
that falls within the field of an exclusive license granted to Alnylam or Isis under the Regulus
License Agreement. In the case of (z) above, the Party with the exclusive license in the field
where the infringing product most reasonably falls will be considered the relevant “Commercializing
Party”.

	 	•	 	Each Party will promptly report in writing to the other Parties any such infringement
of which it becomes aware claiming that any of the Licensed Patent Rights or Regulus Patent Rights
is invalid, unenforceable or that no infringement will arise from the manufacture, use or sale of
such product.
	 
	 	•	 	The relevant Commercializing Party will have the initial right to protect the Regulus
Patent Rights and, if such Commercializing Party is a Licensor, such Commercializing Party’s
Licensed Patent Rights. Regulus has a step-in right with respect to the Regulus Patent Rights.

	•	 	Regulus otherwise has the sole right to protect Regulus Patent Rights and each Licensor
otherwise has the sole right to protect its Licensed Patent Rights.

Definitions

     “Development Project” means a project focused on one or more specific miRNA(s)
following agreement by the Parties that a sufficient portfolio of data exists to support the
initiation of certain preclinical activities on a miRNA Compound drug candidate targeting such
miRNA(s).

     “Field” means treatment and/or prophylaxis of any or all Indications.

Page 63 of 93, Schedule B

 

     “In-License Agreements” means agreements between Alnylam or Isis and Third Party
licensors or sellers that may contain restrictions on the scope of the licenses or trigger payment
or other material obligations or restrictions.

     “Isis Field” means single-stranded oligonucleotides (other than miRNA Antagonists,
Approved Precursor Antagonists, or Approved Mimics) and any product containing single-stranded
oligonucleotides (other than miRNA Antagonists, Approved Precursor Antagonists or Approved Mimics).

     “Licensed IP” means, with respect to a Licensor, such Licensor’s Licensed Know-How and
Licensed Patent Rights.

     “Licensed Know-How” means, with respect to a Licensor, all Know-How Controlled by such
Licensor on the Effective Date or during the term of the Regulus License Agreement that relates to
(a) miRNA Compounds or miRNA Therapeutics in general, (b) specific miRNA Compounds or miRNA
Therapeutics, (c) chemistry or delivery of miRNA Compounds or miRNA Therapeutics, (d) mechanism(s)
of action by which a miRNA Antagonist directly prevents the production of a specific miRNA, or (e)
methods of treating an Indication by modulating one or more miRNAs; provided, however, that in each
case, (i) for any such Know-How that include financial or other obligations to a Third Party, the
provisions of the Regulus License Agreement will govern whether such Know-How will be included as
Licensed Know-How and (ii) Licensed Know How does not include manufacturing technology (including
but not limited to analytical methods).

     “Licensed Patent Rights” means, with respect to a Licensor, (A) all Patent Rights
Controlled by such Licensor on the Effective Date and listed on a schedule to the Regulus License
Agreement and (B) all Patent Rights Controlled by such Licensor during the term of the Regulus
License Agreement that claim (a) miRNA Compounds or miRNA Therapeutics in general, (b) specific
miRNA Compounds or miRNA Therapeutics, (c) chemistry or delivery of miRNA Compounds or miRNA
Therapeutics, (d) mechanism(s) of action by which a miRNA Antagonist directly prevents the
production of the specific miRNA, or (e) methods of treating an Indication by modulating one or
more miRNAs; provided, however, that in each case, (i) for any such Patent Rights that include
financial or other obligations to a Third Party, the provisions of the Regulus License Agreement
will govern whether such Patent Right will be included as a Licensed Patent Right and (ii) Licensed
Patent Rights do not include manufacturing technology (including but not limited to analytical
methods).

     “Licensor” means Alnylam or Isis.

     “miRNA” means a structurally defined functional RNA molecule usually between 21 and 25
nucleotides in length, which is derived from genetically-encoded non-coding RNA which is predicted
to be processed into a hairpin RNA structure that is a substrate for the double-stranded
RNA-specific ribonuclease Drosha and subsequently is predicted to serve as a substrate for the
enzyme Dicer, a member of the RNase III enzyme family;

Page 64 of 93, Schedule B

 

including, without limitation, those miRNAs exemplified in miRBase (http://microrna.sanger.ac.uk/).

     “miRNA Antagonist” means a single-stranded oligonucleotide (or a single stranded
analog thereof) that is designed to interfere with or inhibit a particular miRNA. “miRNA
Antagonist” is not intended to include oligonucleotides that function predominantly through the
RNAi mechanism of action or the RNase H mechanism of action.

     “miRNA Compound” means a compound consisting of (a) a miRNA Antagonist, (b) a miRNA
Precursor Antagonist specified in the Regulus License Agreement or otherwise agreed upon by Regulus
and the relevant Licensor(s) pursuant to the Regulus License Agreement (an “Approved Precursor
Antagonist”), or (c) to the extent agreed upon by Regulus and the relevant Licensor(s) pursuant
to the Regulus License Agreement, a miRNA Mimic (an “Approved Mimic”).

     “miRNA Mimic” means a double-stranded or single-stranded oligonucleotide or analog
thereof with a substantially similar base composition as a particular miRNA and which is designed
to mimic the activity of such miRNA.

     “miRNA Precursor” means a transcript that originates from a genomic DNA and that
contains, but not necessarily exclusively, a non-coding, structured RNA comprising one or more
mature miRNA sequences, including, without limitation, (a) polycistronic transcripts comprising
more than one miRNA sequence, (b) miRNA clusters comprising more than one miRNA sequence, (c)
pri-miRNAs, and/or (d) pre-miRNAs.

     “miRNA Precursor Antagonist” means a single-stranded oligonucleotide (or a single
stranded analog thereof) that is designed to bind to a miRNA Precursor to prevent the production of
one or more miRNAs. “miRNA Precursor Antagonist” is not intended to include oligonucleotides that
function predominantly through the RNAi mechanism of action or the RNase H mechanism of action.

     “miRNA Therapeutic” means a therapeutic product having one or more miRNA Compounds as
an active ingredient(s).

     “Out-License Agreements” means agreements between Alnylam or Isis and a Third Party
pursuant to which Alnylam or Isis granted licenses, or owes other obligations, to such Third Party
prior to the Effective Date.

     “Regulus IP” means all Regulus Know-How and Regulus Patent Rights.

     “Regulus Know-How” means all Know-How conceived and/or developed by or on behalf of
Regulus (including by employees of a Licensor or its Affiliates in performance of the Services
Agreement), or over which Regulus otherwise acquires Control, but specifically excluding Licensed
IP.

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     “Regulus Patent Rights” means any Patent Right claiming an invention conceived and/or
developed by or on behalf of Regulus (including by employees of a Licensor or its Affiliates in
performance of the Services Agreement), or over which Regulus otherwise acquires Control, but
specifically excluding Licensed IP.

     “Research Program” means a project focused on one or more specific miRNA(s) until such
project becomes a Development Project.

     “Services” means certain research and development services and/or other services,
including, without limitation, general and administrative support services, business development
services, and intellectual property prosecution and enforcement services.

     “Services Agreement” means that certain Services Agreement by and between Regulus,
Alnylam and Isis dated September 6, 2007.

     “Third Party Agreement” means either (i) an Out-License Agreement, (ii) an In-License
Agreement, (iii) an Optional In-License or (iv) an agreement pursuant to which a Controlling Party
obtained Control over an Additional Right.

     “Third Party Rights” means, with respect to a Party, any rights of, and any
limitations, restrictions or obligations imposed by, Third Parties pursuant to Third Party
Agreements.

     “Work Product” means any data, documentation, inventions and other Know-How arising
from or made in the performance of the Services by a Licensor.

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REGULUS (LLC AGREEMENT)

	10.	 	Limited Liability Company Agreement of Regulus Therapeutics LLC among Alnylam
Pharmaceuticals, Inc., Isis Pharmaceuticals, Inc. (“Isis”) and Regulus Therapeutics
LLC (“Regulus”), effective as of September 6, 2007

Terms used, but not defined, in this summary have the meaning set forth in the summary of the
Regulus License Agreement.

Brief Description of Technology Covered by License

	•	 	Upon a Buy-Out, either Alnylam or Isis or a Third Party may obtain exclusive or
co-exclusive rights to Regulus’ assets including the Company Intellectual Property and
Regulus’ rights in Alnylam’s and Isis’s Licensed IP.

Scope of Rights (Section 9)

	•	 	Upon the occurrence of certain events, Alnylam or Isis may initiate the sale of Regulus or
the allocation of Regulus’ assets, including the Company Intellectual Property and Regulus’
rights in Alnylam’s and Isis’s Licensed IP (the “Buy-Out”). Regulus may be sold to
Alnylam, Isis or a Third Party.

	•	 	If Regulus is not sold to Alnylam, Isis or a Third Party, Regulus will distribute and
assign to the Members, in accordance with their percentage interest in Regulus, all of
Regulus’ assets.

Each Member will receive a royalty-bearing, co-exclusive license (a) under Company Intellectual
Property Controlled by Regulus at such time, for any and all purposes, and (b) under Licensed IP
licensed to Regulus at such time, for any and all purposes within the scope of the license granted
to Regulus (collectively, the “Distributed IP”); subject to (i) any licenses granted to a
Member pursuant to the Opt-In process under the Regulus License Agreement or as provided below and
(ii) any licenses granted to a Member in the Alnylam Field or Isis Field pursuant to the Regulus
License Agreement. “Co-exclusive” means that such license is exercisable by each Member or
its designated Affiliate, and that Regulus retains no rights to exercise any such licensed
Intellectual Property. Such licenses are sublicenseable solely (A) to such Member’s Affiliates or
(B) by such Member or its Affiliates to a Third Party pursuant to a Bona Fide Collaboration.

	 	•	 	Following such distribution of Regulus’ assets, the Members may initiate bidding
processes, pursuant to which the Members may alternate selecting Research Programs and Development
Projects, respectively, with respect to which the winning bidder with respect to each such Research
Program or Development Project (the “Buy-Out Party”) will be granted by the other Member an
exclusive sublicense under Distributed IP to Develop, Manufacture and Commercialize miRNA Compounds
and miRNA Therapeutics included in such Research Program or Development Project in the Field and
will have assigned to the Buy-Out Party by such other Member any other assets

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	 	 	 	distributed by Regulus to the extent solely related to such Research Program or Development
Project.
	 
	 	•	 	Non-Compete: With respect to any Research Program or Development Project, the
non-Opt-In Party or non-Buy-Out Party will not, itself or through its Affiliates or with Third
Parties, Discover, Develop, Manufacture or Commercialize Opt-In Products or Buy-Out Products during
the period (i) prior to first commercial sale of an Opt-In Product or Buy-Out Product with respect
to such Research Program or Development Project anywhere in the world, as long as the relevant
Opt-In Party or Buy-Out Party reasonably believes that the Opt-In Product or Buy-Out Product would
be a Royalty-Bearing Product upon first commercial sale, and (ii) after first commercial sale of a
Royalty-Bearing Product with respect to such Research Program or Development Project anywhere in
the world, until the expiration of all Royalty Terms for all Royalty-Bearing Products for such
Research Program or Development Project; provided, however, that each Party will be entitled to
grant Permitted Licenses; provided, however that each Licensor may grant licenses to enable Third
Parties to broadly manufacture or formulate oligonucleotides under certain circumstances.

Definitions

     “Bona Fide Collaboration” means a collaboration (pursuant to a written agreement)
between the relevant Member or one of its Affiliates, on the one hand, and a Third Party, on the
other hand, involving the Development of miRNA Compounds or miRNA Therapeutics in which such Member
or such Affiliate plays an integral, though not necessarily dominant or co-equal, role in the
decision-making, relating to the Development of miRNA Compounds or miRNA Therapeutics, and which
may, thereafter, involve the Commercialization of any such miRNA Compounds and miRNA Therapeutics.

     “Buy-Out Product” means any miRNA Therapeutic that is Developed, Manufactured or
Commercialized pursuant a Research Program or Development Project obtained by a Member pursuant to
the Buy-Out process.

     “Company Intellectual Property” means all Company Know-How and Company Patent Rights.

     “Company Know-How” means all Know-How conceived and/or developed by or on behalf of
the Company (including by employees of a Member or its Affiliates in performance of the Services
Agreement), or over which the Company otherwise acquires Control, including but not limited to any
Know-How assigned to the Company by a Member, but specifically excluding Licensed IP.

     “Company Patent Rights” means any Patent Right claiming an invention conceived and/or
developed by or on behalf of the Company (including by employees of a Member or its Affiliates in
performance of the Services Agreement), or over which the Company otherwise acquires Control,
including but not limited to any Patent Right assigned to Company by a Member, but specifically
excluding Licensed IP.

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     “Member” means Alnylam or Isis.

     “Opt-In Product” means any miRNA Therapeutic that is Developed, Manufactured or
Commercialized pursuant to a Development Project for which one and only one Member has exercised an
Opt-In Election and which the relevant Opt-In Party subsequently licensed.

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NOVARTIS

	11.	 	Research Collaboration and License Agreement between Novartis Institutes for BioMedical
Research, Inc. and Alnylam Pharmaceuticals, Inc., effective October 12, 2005, as amended by
the Addendum Re: Influenza Program effective as of December 13, 2005, Amendment No. 1 to such
Addendum effective as of March 14, 2006, and Amendment No. 2 to such Addendum effective as of
May 5, 2006 (“Novartis Agreement”)

Brief Description of Technology Covered by License

	•	 	Alnylam granted Novartis a right to exclusively develop a certain number of Targets using
intellectual property controlled by Alnylam during the term of the Agreement. Some of the
Targets would be developed through collaborative work between Novartis and Alnylam. In
addition, Novartis has the right to convert their license from an exclusive license with
respect to certain Targets to a broad, non-exclusive license.

Scope of Rights

	•	 	Novartis may select a specified number of Targets (“Selected Targets”). Alnylam
and Novartis entered into a Research Collaboration to identify and optimize RNAi Compounds
directed against Selected Targets and develop improved RNAi technology to enable and enhance
the utility of such RNAi Compounds. (Section 2)

	•	 	Alnylam granted Novartis and its Affiliates worldwide licenses under Alnylam Intellectual
Property to (i) perform Novartis’s obligations under the Research Collaboration, (ii) Discover
RNAi Compounds, (iii) Discover RNAi Compounds directed at the Selected Targets, and (iv)
Discover, Develop, Commercialize or Manufacture Discovered RNAi Compounds and Collaboration
Products. The rights under clauses (i) and (ii) are non-exclusive and non-sublicenseable,
under clause (iii) are exclusive and non-sublicenseable, and under clause (iv) are exclusive
and sublicenseable. (Sections 3.1(a) and (b))

	•	 	During the Research Term (following such time as the Collaboration Success Milestone has
been achieved), Novartis has an option, exercisable upon notice and payment of a fee, to
obtain for itself and its Affiliates a non-exclusive, non-sublicenseable (except to third
party contractors), worldwide, perpetual license under Broad RNAi Intellectual Property for
any human, veterinary or agricultural applications (the “Adoption License”). Alnylam
may not grant any exclusive rights or licenses under any Broad RNAi Intellectual Property
except with respect to an opportunity Novartis does not acquire under the ROFO or in
accordance with agreements existing before the effective date of the Novartis Agreement.
(Section 3.1(c) and (e))

	•	 	Exclusivity: Alnylam and its Affiliates may not, either alone or directly or
indirectly in conjunction with a Third Party, conduct Discovery of any RNAi Compound or

Page 70 of 93, Schedule B

 

	 	 	RNAi Products directed to a Selected Target, or Discovery, Development, Commercialization or
Manufacture of Discovered RNAi Compounds, Collaboration Products, or RNAi Compounds or RNAi
Products directed to Selected Targets. Alnylam and its Affiliates may not grant to any Third
Party any rights under Alnylam Intellectual Property to engage in any of the foregoing
activities. (Section 2.6(a))
	 
	•	 	ROFO: If Alnylam or any of its Affiliates seek, directly or indirectly in
conjunction with a Third Party (with limited exceptions), or to license a Third Party (with
limited exceptions) the right, to Discover, Develop, Commercialize or Manufacture any RNAi
Compounds or RNAi Products directed at a Target(s), during the Exclusivity Term, Alnylam must
first provide written notice to Novartis. Novartis has a period of time to accept or reject
the opportunity. If Novartis rejects an opportunity for a program for which no IND has been
filed in the US or Major Market Countries, or Novartis and Alnylam are unable to come to terms
on a post-IND program, Alnylam may, within a specified period of time, enter an agreement with
a Third Party, which can be no more favorable overall to such Third Party than those offered
to Novartis under Section 2.6(c)(i). (Sections 2.6(b) and (c))

	•	 	In-Licensing IP: To the extent applicable, Alnylam must comply with Sections
2.6(b) and (c) (the ROFO described above) when acquiring or licensing rights from Third
Parties. In the course of acquiring or licensing additional Broad RNAi Intellectual Property
or any other Alnylam Intellectual Property covering a Collaboration Product, Alnylam must use
its best efforts to ensure that such rights include the right to sublicense to Novartis such
Broad RNAi Intellectual Property or other Alnylam Intellectual Property. (Sections 2.6(d),
3.1(f))

	•	 	Technology Transfer: Alnylam will periodically deliver to Novartis all Alnylam
Intellectual Property specifically relating to the Discovered RNAi Compounds, relating to the
Research Collaboration, or otherwise necessary or useful to the Discovery, Development,
Commercialization or Manufacture of Discovered RNAi Compounds or Collaboration Products. Once
Novartis acquires the Adoption License, Alnylam will periodically deliver to Novartis all
Broad RNAi Intellectual Property. The deliveries will include un-redacted copies of
agreements that directly or indirectly grant or restrict rights in Alnylam Intellectual
Property, which may be redacted to comply with confidentiality obligations and to exclude
terms that do not relate to Novartis’s rights or obligations; provided, that Alnylam will use
commercially reasonable efforts to ensure that Novartis is granted access to un-redacted
copies of such agreements.

	•	 	Alnylam may not assign, license or otherwise grant any rights or dispose of any Broad RNAi
Intellectual Property or other Alnylam Intellectual Property covering a Collaboration Product
without making such disposition expressly subject to Novartis’s rights. (Section 3.1(g))

IP Ownership, Prosecution and Enforcement (Section 6)

Page 71 of 93, Schedule B

 

	•	 	Novartis owns all IP jointly created by the parties in the Research Collaboration.
Novartis grants Alnylam a worldwide, non-exclusive, sublicenseable (solely to Controlled
Contractors) license under such jointly-created IP that is Broad RNAi Intellectual Property,
to engage in any and all research activities directed to human, veterinary or agricultural
applications.

	•	 	Novartis has a step-in right to prosecute Alnylam Patent Rights that pertain to a
Discovered RNAi Compound or a Licensed Product.

	•	 	Alnylam will promptly report in writing to Novartis any known or suspected infringement or
misappropriation of Alnylam Intellectual Property and will provide Novartis with all available
evidence supporting such infringement or misappropriation.

	•	 	Alnylam has the right to protect the Alnylam Intellectual Property, and Alnylam will
consult with Novartis regarding the status of any such action and will provide Novartis with
copies of all material documents relating to such action. Notwithstanding the foregoing,
Novartis has the sole and exclusive right to initiate a suit under Alnylam Intellectual
Property to protect a Discovered RNAi Compound, a Licensed Product or IP created solely by
Novartis or jointly by Novartis and Alnylam in the Research Collaboration; Alnylam must
provide reasonable assistance at Novartis’ request. Recoveries will be shared in a specified
manner.

	•	 	Novartis and Alnylam will cooperate in responding to a claim challenging the validity of
any Alnylam Patent Right covering a Discovered RNAi Compound or a Licensed Product.

Definitions

“Adopted Product” means a product containing RNAi Compound(s) that are Discovered,
Developed, Commercialized or Manufactured pursuant to the Adoption License.

“Alnylam Intellectual Property” means Know-How and Patent Rights now or in the future owned
or licensed by Alnylam or its Affiliates, including Broad RNAi Intellectual Property.

“Broad RNAi Intellectual Property” means all Know-How and Patent Rights now or in the
future owned or licensed by Alnylam or its Affiliates that relate to RNAi technology, products or
processes, including (a) the general structure, architecture, or design of nucleic acid based
molecules which engage RNAi mechanisms in a cell; (b) chemical modifications of nucleic acids
(including any modification to the base, sugar or internucleoside linkage, nucleotide mimetics, and
any end modifications) which do not abolish the RNAi activity of the nucleic acid molecules in (a);
(c) manufacturing techniques for the nucleic acid based molecules or chemical modifications of (a)
and (b); and (d) all uses or applications of nucleic acid based molecules or chemical modifications
in (a) or (b); but excluding Patents which relates solely to (i) a specific Target or small

Page 72 of 93, Schedule B

 

group of Targets; or (ii) delivery technologies which may be broadly employed for delivery of
nucleic acid based molecules.

“Collaboration Product” means any product that contains one or more Discovered RNAi
Compound(s) as active ingredient(s).

“Discovered RNAi Compound” means an RNAi Compound directed to a Selected Target that is
Discovered during the course of a program under the Novartis Agreement, together with all
derivatives of such RNAi Compound, where “derivative” means a compound that may contain
modified nucleotides or may have been modified by chemical or molecular genetic means but which
still, at least in vitro, functions through an RNAi mechanism against the same Target.

“Licensed Products” means the Collaboration Products and the Adopted Products.

“RNAi Compound” means any compound that in vitro or otherwise functions through the
mechanism of RNAi and consists of or encodes double-stranded RNA, and which double-stranded RNA is
optionally chemically modified to contain modified nucleotide bases or non-RNA nucleotides, and
optionally may be administered in conjunction with a delivery vehicle or vector.

“RNAi Product” means any product that contains one or more RNAi Compounds as an active
ingredient.

“Target” means: (a) a polypeptide or entity comprising a combination of at least one
polypeptide and other macromolecules, that is a site or potential site of therapeutic intervention
by a therapeutic agent; or a nucleic acid which is required for expression of such polypeptide; (b)
variants of a polypeptide, cellular entity or nucleic acid described in clause (a); (c) a defined
non-peptide entity, including a microorganism, virus, bacterium or single cell parasite; provided
that the entire genome of a virus shall be regarded as a single Target; or (d) a naturally
occurring interfering RNA or microRNA or precursor thereof.

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MEDTRONIC

	12.	 	Amended and Restated Collaboration Agreement, dated July 27, 2007 (“Restatement
Date”), between Medtronic, Inc. and Alnylam Pharmaceuticals, Inc. (“Medtronic
Agreement”)

Brief Description of Technology Covered by License

	•	 	Alnylam granted Medtronic a right to develop and commercialize certain RNAi therapeutics in
combination with Medtronic’s implantable infusion device for the treatment of
neurodegenerative diseases.

Scope of Rights

	•	 	Alnylam granted to Medtronic the following worldwide licenses under Alnylam Intellectual
Property:

(a) Non-exclusive license to perform Medtronic’s obligations under the Medtronic Agreement and
to use Alnylam siRNAs to Discover and Develop Licensed Products in the Field.

(b) Exclusive license to Commercialize Licensed Products Developed in the course of the
Collaboration Program for which Medtronic is the Commercializing Party.

	•	 	During the Product Development Term, Alnylam is prohibited from, by itself or jointly with
or through any Affiliates or Third Parties, engaging in the Discovery, Development,
manufacture or Commercialization of any Product in the Exclusivity Field, other than pursuant
to the Medtronic Agreement.

	•	 	During the Royalty Term, Alnylam is prohibited from, by itself or jointly or through any
Affiliates or Third Parties, engaging in the Discovery, Development, manufacture or
Commercialization of any Product, with specified exceptions, for the gene target that is the
target of the Alnylam siRNA contained in the Licensed Products covered by the applicable
Royalty Term, other than pursuant to the Medtronic Agreement.

	•	 	Under certain circumstances set forth in Section 2.5(c), Medtronic has a right of first
negotiation if Alnylam desires to [**].

IP Enforcement

	•	 	Alnylam has the first right to enforce Alnylam Intellectual Property against third party
infringers, subject to consultation with Medtronic to the extent that any such suit pertains
to Licensed Products.

	•	 	With respect to claims by Third Parties that any Alnylam Patent Right is invalid or
unenforceable, Alnylam is obligated to cooperate with Medtronic to prepare and

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	 	 	formulate a response and may not settle or compromise such claim without Medtronic’s consent.

	•	 	With respect to claims by Third Parties that such Third Party’s Patent Rights are infringed
by a Party’s use of the Licensed Products outside the U.S., the Commercializing Party is
obligated to indemnify the other Party. Each Party is obligated to cross-indemnify the other
with respect to Third Party infringement claims based on use of Licensed Products within the
U.S.

Definitions

“Alnylam Intellectual Property” means Alnylam Know-How and Alnylam Patent Rights.

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

“Alnylam Patent Right” means any Patent Rights Controlled by Alnylam and Covering Alnylam Know-How,
including those Patent Rights set forth on Schedule 1.4, but excluding Alnylam’s interest
in Program Patent Rights.

“Alnylam siRNA” means, generally, any siRNA (a) the Discovery, Development, manufacture,
Commercialization or other use of which uses Alnylam Know-How or Program Know-How or is Covered by
Alnylam Patent Rights or Program Patent Rights and (b) that is made available or approved by
Alnylam’s JRDC Representatives for Development in the Collaboration Program.

“Exclusivity Field” means, generally, the treatment of Target Indications for which a Licensed
Product is to be Commercialized, using an implantable infusion device for the direct delivery of
siRNAs to the human nervous system.

“Field” means, generally, the treatment of Neurodegenerative Diseases using any implanted infusion
device for the direct delivery of siRNAs to the human nervous system.

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

“Medtronic Device” means, generally, any implanted infusion device for delivery of siRNAs to the
human nervous system that is made available or approved by Medtronic’s JRDC Representatives for use
in the Development of a Licensed Product in a Product Development Program.

Page 75 of 93, Schedule B

 

“Product” means, generally, a human therapeutic product that includes siRNA(s) as active
pharmaceutical ingredient(s) delivered or approved for delivery via an implantable infusion device,
together with such device, associated delivery hardware, and disposables whether or not uniquely
developed for exclusive delivery of such siRNA(s).

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

“Royalty Term”. Royalty Term, with respect to each Licensed Product in each country of the
Territory, shall mean the period of time commencing with the First Commercial Sale of such Licensed
Product in such country and ending on the later of (a) the latest date on which the use, offer for
sale, sale or importation of such Licensed Product in such country or the manufacture of such
Licensed Product in the country of manufacture is Covered by a Valid Claim of Alnylam Patent
Rights, Medtronic Patent Rights or Program Patent Rights, or (b) a specified number of years after
First Commercial Sale of such Licensed Product in such country, which number shall be fifteen (15)
years with respect to any Licensed Product resulting from the Initial Product Development Program.

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

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BIOGEN IDEC

	13.	 	Collaboration and License Agreement between Biogen Idec MA Inc. (“Biogen”) and
Alnylam Pharmaceuticals, Inc., effective September 20, 2006 (“Biogen Idec Agreement”)

Brief Description of Technology Covered by License

Alnylam granted Biogen Idec a right to develop and commercialize certain RNAi Therapeutics directed
to JCV in the Field.

Scope of Rights

	•	 	Alnylam granted Biogen Idec the following worldwide licenses under Alnylam Technology:

(a) co-exclusive (with Alnylam) license to discover RNAi Therapeutics directed to JCV, and to
develop Selected RNAi Therapeutics (i.e., the RNAi Therapeutics selected in accordance with the
Biogen Idec Agreement) in the Field.

(b) non-exclusive license to manufacture the Selected RNAi Therapeutics.

(c) exclusive license to commercialize Selected RNAi Therapeutics in the Field.

	•	 	Biogen Idec granted Alnylam a non-exclusive, royalty-free license, sublicenseable to
Affiliates, academic collaborators, service companies and manufacturers, under Blocking RNAi
Technology to research, develop, make, use and sell RNAi Therapeutics outside the Field

IP Ownership, Prosecution and Enforcement (Section 6)

	•	 	The following parties have the first right to prosecute the following IP, with the other
party having a step-in right:

	 	•	 	Biogen Idec: Blocking RNAi Technology and Joint Collaboration IP (other than Broad
RNAi Technology Collaboration IP)
	 
	 	•	 	Alnylam: Alnylam Technology, although Biogen Idec has a right to review and approve
prosecution of Core JCV Patents
	 
	 	•	 	Alnylam: Broad RNAi Technology Collaboration IP in the names of Alnylam and Biogen
Idec

	•	 	The following parties have the first right to enforce the following IP, with the other
party having a step-in right:

	 	•	 	Biogen Idec: Joint Collaboration IP relating to the Selected RNAi Therapeutics, Core
JCV Patents, and Blocking RNAi Technology

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	 	•	 	Alnylam: Alnylam Technology (other than Core JCV Patents) and Broad RNAi Technology
Collaboration IP

	•	 	Recoveries are allocated between the parties in accordance with Section 6.4.4 of the Biogen
Idec Agreement.

	•	 	Biogen Idec has the right to defend any third party infringement claim, except that Alnylam
may defend any such claim relating to Blocking RNAi Technology or Broad RNAi Technology.

	•	 	Biogen Idec may determine which patent to extend to protect the commercial value for each
selected RNAi Therapeutic.

	•	 	Alnylam may not encumber the rights granted to Biogen Idec under the Alnylam Patent Rights.

Definitions

“Alnylam Collaboration IP” means (a) any improvement, discovery or Know-How, patentable or
otherwise, first identified, discovered or developed solely by employees of Alnylam or its
Affiliates, or other persons not employed by Biogen Idec acting on behalf of Alnylam, under the
Collaboration, and (b) any Patent Rights in the Territory which claim, cover or relate to such
improvements, discoveries or Know-How and are Controlled by Alnylam at any time during the
Collaboration Term. Alnylam Collaboration IP excludes Alnylam’s interest in Joint Collaboration
IP.

“Alnylam Know-How” means Know-How that is either (a) Controlled by Alnylam on the Effective
Date, or (b) comes within Alnylam’s Control during the Term (other than Alnylam’s rights in Joint
Collaboration IP and Alnylam Collaboration IP).

“Alnylam Patent Rights” means Patent Rights that (a) claim (i) Alnylam Know-How, or (ii)
the identification, characterization, optimization, construction, expression, use or production of
an RNAi Therapeutic, and which are useful or necessary to Discover, Develop, Commercialize and/or
Manufacture a Selected RNAi Therapeutic in the Field in the Territory, and (b) are Controlled by
Alnylam at any time during the Collaboration Term.

“Alnylam Technology” means, collectively, Alnylam Know-How, Alnylam Patent Rights, Alnylam
Collaboration IP and Alnylam’s interest in Joint Collaboration IP.

“Biogen Idec Collaboration IP” means (a) any improvement, discovery or Know-How, patentable
or otherwise, first identified, discovered or developed solely by employees of Biogen Idec or its
Affiliates or other persons not employed by Alnylam acting on behalf of Biogen Idec, under the
Collaboration, and (b) any Patent Rights in the Territory which claim, cover or relate to such
improvements, discoveries or Know-How and are Controlled by Biogen Idec at any time during the
Collaboration Term. Biogen Idec Collaboration IP excludes Biogen Idec’s interest in Joint
Collaboration IP.

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“Blocking RNAi Technology” means Biogen Idec Collaboration IP comprising Broad RNAi
Technology which would, in the absence of a license from Biogen Idec, be infringed by the practice
of any invention claimed in a Valid Claim of the Alnylam Patent Rights existing at the end of the
Discovery Term.

“Broad RNAi Technology” means any and all Know-How, whether or not patentable, that (a) is
useful for the identification, characterization, optimization, construction, expression, use or
production of an RNAi Therapeutic, (b) arises from or is necessary for the performance of the
Collaboration and (c) which relates to structural features, properties, motifs, synthesis,
analysis, modifications, delivery and/or uses of siRNAs that has broader utility beyond the
specific embodiments represented by an RNAi Therapeutic directed to JCV and/or particular uses of
such RNAi Therapeutic.

“Core JCV Patents” means Patent Rights Controlled by Alnylam, the claims of which are
specifically directed to (a) RNAi Therapeutics in the Field, or (b) the manufacture or use of RNAi
Therapeutics in the Field.

“Field” means the prophylaxis and/or treatment of progressive multifocal
leukoencephalopathy (PML).

“JCV” means the human polyomavirus known as JC virus.

“Joint Collaboration IP” means, collectively, (a) any improvement, discovery or Know-How,
patentable or otherwise, first identified, discovered or developed jointly by the Parties or their
Affiliates or others acting on behalf of Biogen Idec and Alnylam under the Collaboration, and (b)
any Patent Rights in the Territory which claim, cover or relate to such improvements, discoveries
or Know-How.

“RNAi Therapeutic” means a therapeutic product containing, comprised of or based on one or
more siRNAs or siRNA derivatives or other moieties effective in gene function modulation and
designed to modulate the function of particular genes or gene products through RNA interference.

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

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ROCHE

	14.	 	License and Collaboration Agreement dated July 8, 2007, by and among Alnylam Pharmaceuticals,
Inc., F. Hoffmann-La Roche Ltd (“Roche Basel”) and Hoffmann-La Roche Inc. (together
with Roche Basel, “Roche”) (“Roche Agreement”), effective on August 9, 2007
(“Effective Date”)

Brief Description of Technology Covered by License

	•	 	Alnylam granted Roche and its Affiliates a non-exclusive, worldwide license under Alnylam’s
rights to Architecture and Chemistry IP and Delivery IP as it existed at the effective time of
the Agreement, to develop and commercialize RNAi Products for treatment/prophylaxis of
indications in at least the fields of cancer, certain liver diseases, metabolic disease and
pulmonary disease. Roche has the option to enter additional therapeutic fields and, prior to
granting exclusive licenses in the other Fields, Alnylam must give Roche a right of first
negotiation.

Limitations on Scope of License

Any license granted by Alnylam to a Third Party under Architecture and Chemistry IP or Delivery IP
would be subject to the following limitations:

	•	 	License Grant to Roche. Roche and its Affiliates have a non-exclusive, worldwide license
to develop and commercialize RNAi Products for the treatment/prophylaxis of indications in at
least the primary fields of cancer, certain liver diseases, metabolic disease and pulmonary
disease) and any additional fields (which are listed in a schedule to the Roche
Agreement) to which Roche acquires non-exclusive rights (collectively, “Field”).

	•	 	Designated Targets. If Roche selects a Target which is not a Blocked Target and such
Target is cleared through the Novartis ROFO mechanism, Roche has non-exclusive rights within
the scope of its basic license grant to develop and commercialize RNAi Products directed to
such “Designated Target” in the Field.

	•	 	Alnylam/Roche Discovery Collaboration. Roche and Alnylam have agreed to collaborate on a
specified number of targets during the term of the agreement.

	•	 	ROFN. If Alnylam intends to grant to any Third Party an exclusive license to any
particular additional field which has not yet been acquired by Roche, Alnylam must first offer
Roche the right to extend its non-exclusive licenses into such additional field upon payment
of a specified field option fee.

	•	 	Extension into Additional Fields. Roche may extend its development and commercialization
activities directed to a Target into any additional field, provided that Roche notify Alnylam
of such extension and pay certain milestone payments.

Prosecution and Enforcement

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	•	 	Alnylam is obligated to take reasonable measures to protect and, to the extent Alnylam has
such a right, to enforce the IP being licensed to Roche under the Roche Agreement.

	•	 	Alnylam is also obligated to assume control of the defense of any aspects of any third
party infringement claim that involves the validity, scope and/or enforceability of such
licensed IP. Roche has the right to control the defense of any other third party infringement
claim or aspect thereof related to a Licensed Product. Alnylam must keep Roche advised of
status and consider Roche’s recommendations.

Definitions

	•	 	“Architecture and Chemistry Intellectual Property” refers, generally, to Know-How
and Patent Rights listed on Schedule C to the Roche Agreement, in each case Controlled
by Alnylam as of the Effective Date, and covering (a) the general structure, architecture, or
design of double-stranded oligonucleotide molecules which engage RNAi mechanisms in a cell;
(b) chemical modifications of double-stranded oligonucleotides (including any modification to
the base, sugar or internucleoside linkage, nucleotide mimetics, and any end modifications)
which do not abolish the RNAi activity of the double-stranded oligonucleotides in (a); (c)
manufacturing techniques for the double-stranded oligonucleotide molecules or chemical
modifications of (a) and (b); or (d) all uses or applications of double-stranded
oligonucleotide molecules or chemical modifications in (a) or (b); but
excluding (i) IP to the extent specifically related to Blocked Targets, and (ii)
Delivery IP. Includes future Patent Rights that claim priority to or common priority with any
of the aforementioned Patent Rights.

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

	•	 	“Delivery Intellectual Property” refers, generally, to Know-How and Patent Rights
listed on Schedule C to the Roche Agreement, in each case Controlled by Alnylam as of
the Effective Date, and covering (a) delivery technologies necessary or useful for delivery of
double-stranded oligonucleotide molecules; or (b) manufacturing techniques for such delivery
technologies of (a); but excluding Patent Rights which relate specifically to
Blocked Targets. Includes future Patent Rights that claim priority to or common priority with
any of the aforementioned Patent Rights.

	•	 	“RNAi Compound” means any compound that, in vitro or otherwise, functions through
the mechanism of RNAi and consists of or encodes double-stranded oligonucleotides, and which
double-stranded oligonucelotides optionally may be chemically modified to contain modified
nucleotide bases or non-RNA nucleotides, and optionally may be administered in conjunction
with a delivery vehicle or vector.

	•	 	“RNAi Product” means any product that contains one or more RNAi Compounds as an
active ingredient.

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

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MERCK

	15.	 	Termination Agreement between Merck & Co., Inc. (“Merck”) and Alnylam
Pharmaceuticals, Inc., dated September 18, 2007

Brief Summary of Technology Covered by License

As part of the termination of the Amended and Restated Research Collaboration and License
Agreement, effective as of July 3, 2006, between Merck and Alnylam (the “A-R Agreement”),
Alnylam granted Merck a non-exclusive license under certain Alnylam RNAi technology (excluding
patent rights licensed by Alnylam or its Affiliates under [**]) for the limited purpose of target
identification and/or target validation research relating to drug discovery and/or development
activities of Merck and/or its Affiliates.

Limitations on Scope of License (Section 4)

Any license granted by Alnylam to a Third Party under Alnylam Target Identification and Target
Validation RNAi Patent Rights, Alnylam Technology Collaboration Inventions and Alnylam RNAi
Technology, in each case Controlled by Alnylam or its Affiliates during the Technology
Collaboration Term, and Alnylam-Assigned Therapeutic Collaboration Inventions, but excluding Patent
Rights licensed by Alnylam or its Affiliates under [**], would be subject to the following:

	•	 	A non-exclusive license to Merck, with the right to sublicense to its Affiliates, for the
sole purpose of in vitro and/or in vivo target identification and/or target validation
research relating to drug discovery and/or development activities of Merck and/or its
Affiliates, including in collaborations with Third Parties in which Merck and/or its
Affiliates has any rights to discoveries made.

	•	 	The non-exclusive grant to Merck under Alnylam-Assigned Therapeutic Collaboration
Inventions shall be perpetual.

Definitions

“Alnylam-Assigned Therapeutic Collaboration Inventions” means, generally, any discovery,
improvement, or Invention made by Merck, solely or jointly with Alnylam, with respect to a [**]
Target after receiving the Opt-In Information for such [**]Target.

“Alnylam RNAi Technology” means, generally, Know-How which is Controlled by Alnylam or its
Affiliates and is necessary or useful to Merck for in-vitro and/or in vivo target identification
and/or target validation and/or for the Development, Manufacture or Commercialization of RNAi
Therapeutic Products within the Therapeutic Collaboration, including, but not limited to, knowledge
related to (i) RNAi pathway and mechanism of action in mammalian cells, (ii) informatics approaches
to optimal siRNA design for targeting specific genes and minimizing off-target effects, (iii)
optimal RNA chemistry for siRNA in vivo stability and delivery, (iv) bio-analytical methods for
measurement of pharmacokinetics and biodistribution of siRNAs, and (v) RNAi delivery methods.

Page 83 of 93, Schedule B

 

“Alnylam Target Identification and Target Validation RNAi Patent Rights” means, generally,
any Patent Rights which are Controlled by Alnylam or its Affiliates and are necessary or useful to
Merck for in vitro and/or in vivo target identification and/or target validation.

“Alnylam Technology Collaboration Inventions” means, generally, any Know-How arising from
the Technology Collaboration and developed solely by Alnylam or its Affiliates during the
Technology Collaboration Term.

"[**]” means, generally, [**].

“Technology Collaboration” means the research activities undertaken by the Parties during
the Technology Collaboration Term pursuant to Article 2 of the Research Collaboration and License
Agreement effective September 8, 2003, as amended by Amendment dated September 30, 2004 (which was
superseded by the A-R Agreement), but excluding the [**] Program.

“Technology Collaboration Term” means the period from September 8, 2003 until July 3, 2006.

“Therapeutic Collaboration” means, generally, the Development, Manufacture and
Commercialization activities undertaken by the Parties under the A-R Agreement with respect to
certain products.

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BENITEC

	16.	 	Alnylam/Benitec License Agreement between Benitec Australia, Ltd., and its Affiliates
(collectively, “Benitec”) and Alnylam Pharmaceuticals, Inc. and its Affiliates
(collectively, “Alnylam”), effective April 8, 2005 (“Benitec Agreement”)

Brief Description of Technology Covered by License

	•	 	Alnylam granted Benitec options for licenses under certain patent rights relating to RNAi
interference and methods of inhibition of expression of certain genes to be selected at a
future date, to develop and commercialize certain ddRNAi and siRNA prophylactic or therapeutic
products for the prevention or treatment of human diseases (the “Field”).

Scope of License (Section 2)

	•	 	Alnylam granted Benitec options to the following worldwide licenses:

	 	•	 	non-exclusive license under Alnylam Licensed Patents to research, develop, gain
regulatory approval for, make, have made, use, market, have marketed, sell, have sold,
distribute, have distributed, export, have exported, import or have imported ddRNAi
Licensed Products in the Field. If such license includes a sub-license to CRT Patent
Rights, the Parties will execute an addendum which grants such a sub-license to Benitec.
	 
	 	•	 	exclusive license under Interferx Licensed Patents and Isis Licensed Patents for up to
a specified number of target genes to be named in the future to research, develop, gain
regulatory approval for, make, have made, use, market, have marketed, sell, have sold,
distribute, have distributed, export, have exported, import or have imported siRNA
Licensed Products in the Field. If such license includes a sub-license to CRT Patent
Rights, the Parties will execute an addendum which grants such a sub-license to Benitec.
Alnylam in its sole discretion may grant or deny a license for the specified target. The
license would become effective upon execution of a separate license agreement which
specifies the target gene and addresses other terms as necessary, which terms shall
include the financial terms set forth in either Exhibit D or D.1 of the Benitec Agreement.

Reporting (Section 4)

	•	 	Following option exercise, each Party shall be obligated to advise the other Party of any
regulatory action of which it is aware that may, in such Party’s reasonable judgment, have a
material effect upon the ability to receive approval to market an Option Licensed Product in
any country in the world.

Prosecution and Enforcement (Section 6)

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	•	 	Alnylam is solely responsible for prosecuting, and has the exclusive right (but not the
obligation) to enforce, Alnylam Licensed Patents and Interferx Licensed Patents. The Parties
may, however, agree to proceed against a Party suspected of infringing a Licensed Patent.
Such an agreement shall be in writing and signed by both Parties.

Termination for Convenience (Section 7.4)

	•	 	If Benitec exercises its option for an exclusive license with respect to a specified target
gene, the definitive license agreement will include a provision that such agreement may be
terminated at any time by Benitec upon at least 60 days written notice to Alnylam.

Definitions

“Alnylam Licensed Patents” means patent rights claiming ddRNAi Technology, which is claimed
in or covered by any Valid Claim in the patents and patent applications filed by, issued to or
licensed to Alnylam as set forth in an exhibit to the agreement, including all continuing
applications, divisionals, substitutions and continuation-in-part applications and any patents
issuing on said applications including reissues and any corresponding counterparts.

“CRT Patent Rights” means the patent rights licensed to Alnylam under the License Agreement
between Cancer Research Technology Limited and Alnylam dated 18 July 2003.

“ddRNAi Licensed Product” means any prophylactic or therapeutic product containing,
comprised of or based on ddRNAi Technology.

“ddRNAi Technology” means an RNA composition designed to act primarily through an RNA
interference mechanism where the RNA composition consists of one or more nucleic acid sequences
transcribed from a transcription template within a cell in an organism.

“Interferx Technology” means the siRNA Technology that falls within the scope of a Valid
Claim of an Interferx Licensed Patent licensed by Alnylam to Benitec should the Parties reach
agreement under the terms of Section 2.2 herein. The intellectual property encompassing Interferx
Technology (“Interferx Licensed Patents”) shall be listed in a separate Exhibit and added to the
Benitec Agreement upon execution of a separate writing between the Parties.

“Isis Licensed Patents” shall mean patent rights licensed to Alnylam by Isis
Pharmaceuticals, Inc., (“Isis”) pursuant to a Strategic Collaboration and License Agreement between
Alnylam and Isis dated March 11, 2004.

Page 86 of 93, Schedule B

 

“siRNA Licensed Product” means any prophylactic or therapeutic product containing,
comprised of or based on siRNA Technology.

“siRNA Technology” means a double-stranded ribonucleic acid (RNA) composition designed to
act primarily through an RNA interference mechanism that comprises of either (a) two separate
oligomers of native or chemically-modified RNA that are hybridized to one another along a
substantial portion of their lengths, or (b) a single oligomer of native or chemically-modified RNA
that is hybridized to itself by self-complimentary base-pairing along a substantial portion of its
length to form a hairpin.

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CALANDO

	17.	 	License and Option Agreement between Calando Pharmaceuticals Inc. (“Calando”) and
Alnylam Pharmaceuticals, Inc., dated August 18, 2006, as supplemented by letter agreement
dated August 18, 2006 and Amendment No. 1 dated August 5, 2007

Brief Description of Technology Covered by License

Alnylam granted Calando a license to research, and an option to obtain licenses to develop and
commercialize, certain RNAi products directed to a specified target (the “Target”), under certain
patent rights relating to RNAi interference and methods of inhibition of expression of certain
genes.

Scope of Rights (Section 4)

	 	•	 	Alnylam granted Calando a co-exclusive worldwide license under the Alnylam Patent
Rights, subject to the terms and conditions of any in-license(s) governing the Alnylam
Patent Rights, for the sole and exclusive purpose of Research in the Field with respect to
the Target.

	 	•	 	Alnylam granted Calando an option to obtain a worldwide license under the Alnylam
Patent Rights for purposes of Developing and Commercializing RNAi Products in the Field
directed to the Target. Upon Calando’s exercising the option, Alnylam will grant Calando:

	 	•	 	a co-exclusive (with a potential third party) license under the Alnylam Patent
Rights for the sole and exclusive purposes of Developing and Commercializing in the
Field Licensed RNAi Products directed to the Target.
	 
	 	•	 	an exclusive license under the Alnylam Patent Rights for purposes of Developing and
Commercializing Licensed RNAi Products in the Field directed to the Target that
incorporate Calando Delivery Technology.

	 	•	 	Alnylam granted Calando an option to obtain a (i) co-exclusive, non-royalty bearing
license under the Alnylam Patent Rights for the purpose of Research in the Field with
respect to one target in addition to the Target, and (ii) co-exclusive, royalty bearing
license under the Alnylam Patent Rights for the purpose of Developing and Commercializing
Licensed RNAi Products in the Field for such additional target.

Definitions

“Alnylam Patent Rights” means Patent Rights that are from time to time owned, licensed or
otherwise controlled by Alnylam to the extent Alnylam has the right to grant licenses to, as set
forth in Exhibit A of this Agreement, and as can be supplemented from time to time pursuant to
Section 4.1(d).

Page 88 of 93, Schedule B

 

“Broad RNAi Technology” means RNAi technology arising from or necessary for the performance
of the Research Plan, which relates to structural features, properties, and/or motifs of siRNAs
that has broader utility beyond the specific embodiments represented by a RNAi Product and/or
particular uses of such RNAi Product.

“Calando Delivery Technology” means polymer-based technology useful for the delivery of
siRNA molecules which technology is covered by Calando Intellectual Property as identified on
Exhibit B.

“Field” means all therapeutic treatments in humans.

“Licensed RNAi Product” means an RNAi Product, the identification, characterization,
validation, synthesis, development, use, formulation, manufacture, production or sale of which
would infringe a Valid Claim issuing under any of the Alnylam Patent Rights but for the grant of
the licenses set forth in this Agreement.

“RNAi Product” means a therapeutic product containing, comprised or based on siRNAs or
siRNA derivatives or other moieties effective in gene function modulation and designed to modulate
the function of particular genes or gene products through RNA interference.

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GENECARE

	18.	 	License and Option Agreement between GeneCare Research Institute Co., Ltd.
(“GeneCare”) and Alnylam Pharmaceuticals, Inc., dated January 6, 2005, extended by
letters dated October 26, 2007 and November 16, 2007

Brief Description of Technology Covered by License

	•	 	Alnylam granted GeneCare a license to research, and an option to obtain licenses to develop
and commercialize, certain RNAi products directed to a specified target (the
“Target”), under certain patent rights relating to RNAi interference and methods of
inhibition of expression of certain genes.

Scope of Rights (Sections 3 and 4)

	•	 	Alnylam granted GeneCare an exclusive worldwide license under the Alnylam Patent Rights for
the sole and exclusive purpose of Research in the Field with respect to the Target.

	•	 	Alnylam granted GeneCare an option to obtain an exclusive worldwide license under the
Alnylam Patent Rights for purposes of Developing and Commercializing RNAi Products in the
Field directed to the Target. If Alnylam exercises its right to co-promote the RNAi Product
in North America, such license shall be a co-exclusive license to Develop and Commercialize
such RNAi Product in North America.

Prosecution and Enforcement (Section 6)

	 	•	 	Alnylam has the right to prosecute Alnylam Patent Rights and the first right and
responsibility to prosecute jointly made Patent Rights. GeneCare has the step-in-right to
prosecute Alnylam Patent Rights and jointly made Patent Rights.
	 
	 	•	 	Alnylam has the sole and exclusive right to enforce Alnylam Patent Rights and jointly
made Patent Rights. If Alnylam does not initiate an enforcement action with respect to
jointly made Patent Rights, GeneCare has a step-in-right to enforce such jointly made
Patent Rights.
	 
	 	•	 	Alnylam and GeneCare each has the sole and exclusive responsibility to defend any third
party infringement claim brought against Alnylam or GeneCare, respectively, arising out of
the development, use, manufacture, distribution or sale of RNAi Products.

Definitions

“Alnylam Know-How” means all Know-How that is within the control of Alnylam other than that
licensed to Alnylam by GeneCare pursuant to Section 4.2 of this Agreement.

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“Alnylam Patent Rights” means the Patent rights that are identified on the attached Exhibit
A. Exhibit A shall be completed and agreed by the Parties within thirty (30) days after the
Effective Date.

“Field” means treatment of human disease.

“RNAi Product” means a therapeutic product directed to a Target containing, comprise or
based on siRNAs or siRNA derivatives or other moieties effective in gene function modulation and
designed to modulate the function of particular genes or gene products through RNA interference,
and as the context applies, that is covered by the right and license applicable to RNAi Product(s)
for which an RNAi Product Option has been exercised.

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NASTECH

	19.	 	License and Option Agreement between Nastech Pharmaceutical Company Inc. (“Nastech”)
and Alnylam Pharmaceuticals, Inc., dated July 20, 2005

Brief Description of Technology Covered by License

	•	 	Alnylam granted Nastech a license to research, and an option to obtain licenses to
develop and commercialize, certain RNAi products directed to a specified target (the
“Target”), under certain patent rights relating to RNAi interference and methods
of inhibition of expression of certain genes.

Scope of Rights (Sections 3 and 4)

	•	 	Alnylam granted Nastech an exclusive worldwide license under the Alnylam Core Patent
Rights for the sole and exclusive purpose of Research in the Field with respect to the
Target.
	 
	•	 	Alnylam granted Nastech options to obtain (a) an exclusive license under Alnylam’s
rights in the Alnylam In-Licensed Chemistry Patent Rights for the sole and exclusive
purpose of Researching, and, if applicable, Developing and Commercializing RNAi Products
in the Field directed to the Target, and (b) an exclusive worldwide license under the
Alnylam Core Patent Rights for purposes of Developing and Commercializing RNAi Products in
the Field directed to the Target.
	 
	•	 	The licenses granted do not include licenses to Patent Rights licensed by Alnylam and
its Affiliates under either (a) the agreement between The Board of Trustees of The Leland
Stanford Junior University and Alnylam dated September 17, 2003 (“Stanford Agreement”) or
(b) the License Agreement between Cancer Research Technologies Limited and Alnylam dated
July 18, 2003 (the “CRT Agreement”). Notwithstanding the foregoing, if:

	 	•	 	any Patent Rights under the CRT Agreement and the Stanford Agreement
in-licensed by Alnylam are issued, or
	 
	 	•	 	Alnylam obtains control of any other Patent Rights (excluding Patent
Rights that claim specific siRNA sequences or that claim delivery technologies),

	 	 	and in either case such Patent Rights are determined to cover an RNAi Product in the Field
directed towards the Target, then Nastech will have the option of expanding its licenses
under this Agreement to include the relevant Patent Rights.

Definitions

“Alnylam Core Patent Rights” means Patent Rights that are from time to time within the
control of Alnylam, including without limitation the Patent rights listed in Exhibit A-1 as

Page 92 of 93, Schedule B

 

supplemented from time to time pursuant to Section 4.1(d), but not including the Alnylam
In-Licensed Chemistry Patent Rights.

“Alnylam In-Licensed Chemistry Patent Rights” means Patent Rights licensed to Alnylam under
the third party agreement listed on Exhibit A-2.

“Alnylam Patent Rights” means both Alnylam Core Patent Rights and Alnylam In-Licensed
Chemistry Patent Rights.

“Field” means treatment of human disease.

“RNAi Product” means a therapeutic product containing, comprised, or based on siRNAs or
siRNA derivatives or other moieties effective in gene function modulation and designed to modulate
the function of particular genes or gene products through RNA interference.

Page 93 of 93, Schedule B

 

SCHEDULE C

ASIAN PHARMACEUTICAL COMPANIES

[**]

 

SCHEDULE D

Profit-Sharing Agreement Terms

All capitalized terms used but not otherwise defined in this Schedule D will have the meanings
ascribed to them in the License and Collaboration Agreement (the “LCA”).

	1.	 	Product and Indications: Shared Product for all Indications for which such Shared Product is
Developed and/or Commercialized in the U.S. The Parties will focus their Development and
Commercialization efforts with respect to the Shared Product on particular Indication(s) as
set forth in the Joint Development Plan and Joint Commercialization Plan. In case such Shared
Product is pursued for an Indication in an Additional Field under a Joint Development Plan or
Joint Commercialization Plan, any payment under Section 3.8 of the LCA relating to such Shared
Product shall be reduced by [**] percent ([**]%) and, in furtherance of Section 7.5(b) of the
LCA, shall also be creditable in full and without regard to such [**] percent ([**]%)
reduction against any Field Option Fee under Section 7.4 of the LCA relating to such
Additional Field.
	 
	2.	 	Territory: U.S.
	 
	3.	 	Term: Profit-Share Term, unless earlier terminated in accordance with the LCA.
	 
	4.	 	Conduct of the Collaboration: The Parties shall jointly Develop and Commercialize the Shared
Product in the U.S. (the “Collaboration”), in accordance the Joint Development Plan
and Joint Commercialization Plan.
	 
	5.	 	Joint Development and Joint Commercialization Plans:
	 
	 	 	a. Joint Development Plan. The initial joint Development plan (the “Joint
Development Plan”) and the budget contained therein shall be the Development plan and
budget most recently provided by Takeda to Alnylam pursuant to Section 4.2(b) of the LCA. From
time to time as may be reasonably necessary, Takeda shall have the right, in its sole
reasonable discretion, to modify a Joint Development Plan after consultation with Alnylam and
giving good faith consideration to any reasonable comments or suggestions proposed by Alnylam,
including as to the allocation of responsibilities of the Parties as set forth in Section 7
below. Any material changes to the timeline or budget for the Development of a Shared Product
as such are set forth in the initial or any subsequently agreed Joint Development Plan which
(i) are reasonably likely to delay the filing of the NDA for the applicable Shared Product by
more than [**] or (ii) will increase the applicable Development budget by more than [**]
percent ([**]%) of the most recent applicable Development budget for such Shared Product shall
require the mutual agreement of the Parties: provided, however, that if Takeda
pays the

 

 

	 	 	amount that exceeds [**] percent ([**]%) of the Development budget, such requirement of item
(ii) above (mutual agreement) will not apply.

b. Joint Commercialization Plan. The initial joint Commercialization plan (“Joint
Commercialization Plan”) and the budget contained therein shall be the Commercialization
plan and budget most recently provided by Takeda to Alnylam pursuant to Section 4.2(b). From
time to time as may be reasonably necessary, Takeda shall have the right, in its sole
reasonable discretion, to modify a Joint Commercialization Plan after consultation with Alnylam
and giving good faith consideration to any reasonable comments or suggestions by Alnylam,
including as to the allocation of responsibilities of the Parties as set forth in Section 7
below. Any material changes to the timeline or budget for the Commercialization of a Shared
Product as such are set forth in the initial or any subsequently agreed Joint Commercialization
Plan which (i) are reasonably likely to delay the commercial launch of the Shared Product by
more than [**] or (ii) will increase the applicable Commercialization budget by more than [**]
percent ([**]%) of the most recent applicable Commercialization budget for such Shared Product
shall require the mutual agreement of the Parties: provided, however, that if
Takeda pays the amount that exceeds [**] percent ([**]%) of the Commercialization budget, such
requirement of item (ii) above (mutual agreement) will not apply.

i. Joint Commercialization Plan Details. The Joint Commercialization Plan shall
encompass the planned Commercialization strategy in the U.S. for the applicable Shared
Product and the corresponding budgeted Commercialization Costs. The initial Joint
Commercialization Plan shall include the budgeted Commercialization Costs for pre-launch
Commercialization activities in the U.S. and for Commercialization activities through at
least [**] after the First Commercial Sale of the Shared Product in the U.S. The Joint
Commercialization Plan shall contain, solely in regards to the U.S., the following at a
minimum, unless agreed to otherwise by the Parties:

[**].

	6.	 	Governance: In accordance with Section 4.2(f) of the LCA, Alnylam and Takeda shall establish
the SPC to oversee the activities of the Parties with respect to Shared Product(s). The SPC
shall operate in accordance with the same procedures as set forth in Sections 2.2 — 2.6,
inclusive, of the LCA; provided that a Takeda representative shall chair the SPC. Alnylam and
Takeda may establish such subcommittees of the SPC as deemed necessary, including a joint
Development committee to oversee Development of Shared Product(s) in the U.S. (the “Joint
Development Committee”) and a joint Commercialization committee to oversee
Commercialization of Shared Product(s) in the U.S. (the “Joint Commercialization
Committee”). Notwithstanding the foregoing, Takeda shall have the final authority in
deciding matters that could have substantial impact on Takeda’s global development and
marketing strategies for such Shared Product; provided that Takeda shall provide Alnylam with
reasonable explanation of such substantial impact and shall consider Alnylam’s

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	 	 	reasonable opinion in good faith before making such final decision; provided,
however, that, if Takeda exercises such final decision-making authority on such matter
contrary to Alnylam’s position on such matter, Takeda shall be solely responsible for all the
Development and Commercialization costs with respect to such matter that exceed [**] percent
([**]%) of the Development or Commercialization budget for such matter set forth in the Joint
Development Plan or Joint Commercialization Plan.

	7.	 	Responsibilities of the Parties Generally: Each Party shall use Commercially Reasonable
Efforts to fulfill all responsibilities assigned to it under the Joint Development Plan and
the Joint Commercialization Plan and shall comply with the Profit-Sharing Agreement, all
applicable Laws and Takeda’s code of conduct (which shall be provided to Alnylam at the time
the Profit-Sharing Option is exercised) for marketing and promoting pharmaceutical products in
the U.S. Neither Party shall be required to undertake specific activities with respect to
the Development and Commercialization of Shared Products unless such assigned activities are
set forth in a Joint Development Plan or Joint Commercialization Plan.

a. Alnylam Responsibilities:

     (i) Alnylam shall undertake the responsibilities allocated to Alnylam in the Joint
Development Plan and the Joint Commercialization Plan under the direction and oversight of the
SPC;

     (ii) Alnylam shall Co-Promote the Shared Product in the U.S. in accordance with the Joint
Commercialization Plan and under the direction and oversight of the SPC;

     (iii) Alnylam shall perform its Co-Promotion responsibilities using (A) an appropriate
management infrastructure to supervise the sales representatives required to oversee Alnylam’s
obligations to perform its Detail Requirements and (B) sales representatives and marketing
staff of sufficient size and adequate experience to establish, maintain and implement the Joint
Commercialization Plan for the Shared Product(s);

     (iv) Alnylam shall cooperate and assist Takeda with preparing for submission, obtaining
and maintaining Regulatory Approval in the U.S. with respect to the Shared Product; and

     (v) Alnylam shall cooperate and assist Takeda with such other Commercialization activities
as Takeda may reasonably request.

(b) Takeda Responsibilities:

     (i) Takeda shall undertake the responsibilities allocated to Takeda in the Joint
Development Plan and the Joint Commercialization Plan under the direction and oversight of the
SPC, with the understanding that Takeda shall be the lead Party and have primary responsibility
for such activities;

     (ii) Takeda shall prepare and submit regulatory applications to Regulatory Authorities in
order to obtain the Regulatory Approvals with respect to the Shared Product and shall own and
maintain all Regulatory Approvals and communicate with Regulatory Authorities with

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respect to Shared Product and share with Alnylam material written communication it
receives from Regulatory Authorities;

     (iii)Takeda shall Co-Promote the Shared Product in the U.S. in accordance with the Joint
Commercialization Plan and under the direction and oversight of the SPC. Takeda shall employ
an appropriate management infrastructure to supervise the sales representatives required to
oversee Takeda’s obligations to perform its Detail Requirements and marketing staff of
sufficient size and adequate experience to establish, maintain and implement the Joint
Commercialization Plan for the Shared Product(s);

     (iv) Takeda shall have the sole right and responsibility to record and collect payment for
sales of Shared Products throughout the U.S. Takeda shall be responsible for distribution,
invoicing and collection with respect to sales of Shared Products in the U.S. and shall book
such sales (it being understood that Takeda shall be solely and exclusively responsible for its
own revenue recognition with respect to Shared Products, and Alnylam shall have no
responsibility therefor);

     (v) Takeda shall use Commercially Reasonable Efforts to build and maintain an appropriate
pharmacovigilence infrastructure, including to maintain a global safety database with respect
to the Shared Product, in connection with which the Parties shall enter into a
pharmacovigilence agreement;

     (vi) Takeda shall have the sole right to Manufacture the Shared Product or contract a
Third Party to Manufacture the Shared Product, in either case, in a commercially reasonable
manner, including, managing raw material supply for Manufacturing the Shared Product,
warehousing and distributing the Shared Product; and

     (vii) Takeda shall have the sole right to select, register, maintain, enforce and defend
the Product Trademark for the Shared Product and own such Product Trademark.

	8.	 	Allocation and Reconciliation of Net Profits/Losses; Patent Enforcement Recoveries:

a. Allocation: Takeda and Alnylam shall each receive (in the case of profits) or pay
(in the case of losses), as applicable, fifty percent (50%) of Net Profit/Losses with respect
to the Shared Product in the U.S., to be calculated and paid in accordance with the
reconciliation and payment provisions of this Section 8. In accordance with Section 7.3(c)(ii)
of the LCA, all royalty, milestone and other payments to a Third Party made by either Party
under Third Party agreements (including, but not limited to, Listed Alnylam Third Party
Agreements) with respect to Shared Products shall be deemed Commercialization Costs incurred by
such Party and deducted in calculating Net Profits/Losses so that Takeda and Alnylam shall
share equally in such Commercialization Costs. If any such Third Party payments are made for
rights that relate both to the Shared Product in the U.S. and to other product(s) and/or
territory(ies), only an equitable allocation of such costs shall be deemed Commercialization
Costs. The allocations and limitations on such sharing set forth in Sections 7.3(c), 7.3(d) or
7.3(e) of the LCA shall not apply to such sharing of costs with respect to Shared Products in
the U.S. Notwithstanding the foregoing, to the extent any royalty, milestone or other payments
relating to a Shared Product in the U.S. are owed to a Third Party as a result of a breach by
Alnylam of any of its representations, warranties or

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obligations under the LCA or any other agreement between Alnylam and Takeda, Alnylam shall be
solely responsible for such royalty, milestone or other payments and such royalty, milestone or
other payments shall not be included in calculating Net Profit/Losses.

b. Reporting Gross Revenues and Shared Expenses: Within [**] after the end of each
[**], Alnylam shall submit to Takeda a true and accurate report providing in reasonable detail
all Development Costs, Cost of Goods and Commercialization Costs, to the extent applicable,
incurred by Alnylam (the “Alnylam Incurred Shared Expenses” and such report the
“Alnylam Incurred Shared Expenses Report”), including a calculation showing as separate
line items each component of Development Costs, Cost of Goods and Commercialization Costs.
Within [**] after the end of each [**], Takeda shall, using the Alnylam Incurred Shared
Expenses Report, prepare a reconciliation report for the Shared Products for such [**] (the
“Reconciliation Report”). The Reconciliation Report shall set forth, in reasonable
detail:

          (i) a statement of all Development Costs, Cost of Goods and Commercialization Costs
incurred by Takeda (the “Takeda Incurred Shared Expenses”), the Alnylam Incurred Shared
Expenses and the total expenses to be shared by the Parties;

          (ii) Recoveries, if any;

          (iii) Net Sales of the Shared Product in the U.S.;

          (iv) a calculation of Net Profits/Losses, as applicable; and

          (v) a statement of any amount (“Reconciliation Payment”) owed by one Party to the
other Party.

          All reports under this Section 8 of this Schedule D shall be considered
Confidential Information of the submitting Party, subject to the terms and conditions of
Article 9 of the LCA.

c. Payment. Within [**] after delivery by Takeda of a Reconciliation Report to
Alnylam, Takeda or Alnylam, as the case may be, shall pay the Reconciliation Payment to the
other Party; provided, however, that if within [**] of receipt of the Reconciliation
Report by Alnylam, the Alnylam financial representative informs the Takeda financial
representative that it disputes the amount of all or a portion of the Reconciliation Payment,
the financial representatives of the Parties shall meet and attempt in good faith to resolve
such dispute; provided, however, that the Party owing the Reconciliation
Payment shall pay such portion of the Reconciliation Payment that is not in dispute. To the
extent the dispute is not resolved by such financial representatives, such matter shall be
presented to the SPC for resolution; provided that if such dispute is not resolved by the SPC,
the Parties shall resolve the dispute in accordance with Section 12.2 of the LCA. The Parties
shall have the audit rights set forth in Section 7.9 of the LCA.

-5-

 

d. Maintenance and Enforcement of Intellectual Property Rights; Recoveries. Alnylam and
Takeda shall [**] the costs of maintaining and enforcing Patents Rights and Know-How covering the
Shared Product in the U.S. in accordance with Section 8.2 of the LCA.

	9.	 	ROW Development and Commercialization Costs. Except as provided below, Takeda shall be [**]
responsible for [**] percent ([**]%) of all Development Costs, Cost of Goods and
Commercialization Costs incurred to support Development and Commercialization of Shared
Product(s) that is not allocated to the U.S.
	 
	 	 	a. If data from a clinical study(ies) conducted in ROW is used as pivotal in a substantive and
material manner to seek Regulatory Approval in the U.S., and such Regulatory Approval is
obtained, then the Parties shall discuss what percentage will be included in Development Costs
by taking into consideration the nature of such study(ies).
	 
	 	 	b. If data from a clinical study(ies) conducted in the U.S. in connection with Shared Product
(where the costs for such study are included in Development Costs) is used by Takeda, its
Affiliates or sublicensees as pivotal in a substantive and material manner to seek Regulatory
Approval in any country or countries outside of the U.S., and Regulatory Approval is obtained
in any such country or countries, then the Parties shall discuss as to whether or not Takeda
will pay to Alnylam any amount by taking into consideration the nature of such study(ies).
	 
	10.	 	Adverse Events; Recall: The Parties shall establish procedures for reporting adverse events
and other Shared Product related safety issues. Unless otherwise agreed by the Parties,
Takeda shall have the right and primary responsibility to make decisions and to take immediate
action with respect to Shared Product safety issues, including recalls, in all cases, after
reasonable consultation with Alnylam; provided, however, that Takeda may make
such decision without consultation with Alnylam to the extent necessary for Takeda to comply
with its regulatory obligations.
	 
	11.	 	Shared Product License: For each Shared Product, Takeda will own all Product Trademarks,
Know-How and Patent Rights that are specifically and solely related to such Shared Product and
that are created solely or jointly by Takeda and/or Alnylam under the Joint Development Plan
and/or Joint Commercialization Plan for such Shared Product. Takeda hereby grants Alnylam and
its Affiliates a non-exclusive, royalty-free, right and license under such Product Trademarks,
Know-How and Patent Rights to perform the activities with respect to such Shared Product that
are assigned to Alnylam in the Joint Development Plan and Joint Commercialization Plan for
such Shared Product, such license to become effective upon Alnylam’s election of the
Profit-Share Option for such Shared Product. The license granted to Alnylam in this Section 11
shall terminate with respect to any Shared Product upon Alnylam’s exercise of the Opt-Out
Option pursuant to Section 4.3(b) of the LCA.

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	12.	 	Co-Promotion.
	 
	 	 	a. Generally. Any joint Commercialization activities conducted by the Parties
shall be conducted in accordance with the Joint Commercialization Plan and as directed by
the SPC. The Parties shall only use promotional materials, advertising materials and
literature approved by the SPC. No Party shall be required to undertake any activity
under the LCA which it believes, in good faith, would violate any applicable Laws. The
SPC shall determine, in accordance with the Joint Commercialization Plan, the targeted
number of total Details and Primary Details to be performed by each Party during each
Fiscal Year, if any, (which Details shall be borne one-half by each Party unless otherwise
mutually agreed) and the Target Audience for such Details (the “Detail
Requirements”) in accordance with the following principles:

(i) The overall number of Details shall be set at a level mutually agreed to
by the Parties;

(ii) Alnylam shall in no event be assigned more than [**] percent ([**]%) of
the Parties’ overall Detailing responsibilities;

(iii) Detailing responsibilities shall be allocated between the Parties in an
equitable manner, taking into consideration the capabilities and experience of
each Party’s sales force, subject to the guiding principle that each Party will
bear half of the Detailing responsibilities unless otherwise mutually agreed;

(iv) Detailing responsibilities shall be carried out in accordance with the
applicable Joint Commercialization Plan and Joint Commercialization Budget; and

(v) Detail costs reimbursement shall be the same on a per-Detail basis for
each Party and shall be mutually agreed by the Parties.

b. Detailing Reports. Each Party shall keep complete and accurate records of all
Details performed by its sales force in Co-Promoting Shared Product in the U.S. Within
[**] following the end of each [**], each Party shall provide the SPC with a report
setting forth, in such detail and form as the SPC shall require (the “Internal
Detailing Report”), based upon each Party’s internal Detailing reporting system, the
total number of Details, Primary Details and Secondary Details actually performed by such
Party, segmented by physician specialty of the Target Audience during the immediately
preceding [**]. The Parties will, if reasonably necessary, cooperate through the SPC to
establish compatible Detail reporting and tracking mechanisms for the Co-Promotion of the
Shared Product to facilitate communication and coordination of the Detailing efforts
between the Parties.

c. Audits Pertaining to Details. The Parties shall have the audit rights set
forth in Section 7.9 of the LCA with respect to detailing records. If Alnylam fails to
perform its Detail Requirement by more than [**] percent ([**]%) but less than [**]
percent ([**]%) (i.e., it performed less than [**] percent ([**]%) but more than [**]
percent ([**]%) of its Detail Requirements), or similar medical or scientific liaison
performance measure as may be appropriate, in each case as set forth in the Joint
Commercialization Plan, for [**] consecutive Fiscal Years, then

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Takeda may increase its Details or similar medical or scientific liaison performance measure to
make up for Alnylam’s shortfall and Alnylam shall reimburse Takeda for such efforts at the rate
then set by the SPC, in addition to bearing [**] of the Commercialization Costs (which shall
also include such additional efforts by Takeda) for such Shared Product. If Alnylam fails to
perform its Detail Requirements by [**] percent or more (i.e. it performed [**] percent ([**]%)
or less of its Detail Requirements), or similar medical or scientific liaison performance
measure as may be appropriate, in each case as set forth in the Joint Commercialization Plan,
for [**] consecutive Fiscal Years, then (i) Takeda may increase its Details or similar medical
or scientific liaison performance measure to make up for Alnylam’s shortfall and Alnylam shall
reimburse Takeda for such efforts at the rate then set by the SPC, in addition to bearing [**]
of the Commercialization Costs (which shall also include such additional efforts by Takeda) for
such Shared Product and (ii) Takeda may terminate Alnylam’s Co-Promotion right upon sixty (60)
days’ advance notice; provided, however, that such termination of Alnylam’s
Co-Promotion right shall apply only to the right of Alnylam to participate in the SPC with
respect to, and to perform, Detailing, promotion and marketing activities for the Shared
Product and shall not affect the rights and obligations of Alnylam under the Net Profit/Loss
sharing mechanism hereunder for such Shared Product.

	13.	 	Joint Marketing and Sales Meetings: The Parties shall plan and implement periodic joint sales
and marketing meetings, including a national launch meeting, for the each Shared Product.
	 
	14.	 	Miscellaneous:
	 
	 	 	a. Shared Product Milestones. As set forth in Section 7.5(d) of the LCA.
	 
	 	 	b. No Royalties. For clarity, no royalties will be paid by Takeda to Alnylam for any
Net Sales of Shared Product in the U.S.
	 
	 	 	c. Change of Control. As set forth in Section 12.5(c) of the LCA.
	 
	 	 	d. Product Liability and IP Infringement Liability Contribution for Shared Products.
As set forth in Section 12.1(c) of the LCA.
	 
	 	 	e. Other Provisions. The more detailed profit-sharing agreement to be negotiated between the
Parties shall be based on this Schedule D and contain provisions regarding representations and
warranties, indemnifications, intellectual property, termination rights, confidentiality and
other customary provisions.
	 
	15.	 	Definitions:

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          “Cost of Goods” shall mean the direct and identifiable internal and external costs of
Manufacturing and packaging the Shared Product for Commercialization in the U.S., consisting of the
following: (i) with regard to a Party’s internal costs and charges, Cost of Goods shall include
the direct costs and charges, including direct Manufacturing plant overhead charges reasonably
allocable to the Shared Product, related to the Manufacture, packaging and shipment of the Shared
Product, and shall exclude (A) the Manufacture of other products at a Party’s facilities; (B)
amortization of property, plant or equipment not used in Manufacturing of Shared Product for the
U.S. market; and (C) allocation of general corporate overhead not directly or indirectly involved
in the management of Manufacturing, material procurement or product distribution; and (ii) with
regard to a Party’s external costs and charges, Cost of Goods shall include the invoiced costs and
charges of suppliers of goods and services related to the Manufacture, packaging and shipment of
Shared Product for the U.S. market, and any payments to Third Parties relating to the activities of
manufacturing the Shared Product, including upfront, milestone, royalty payment to Third Parties in
relation to intellectual property license from Third Parties.

          “Commercialization Costs” shall mean all costs incurred by a Party with respect to
Commercialization of the Shared Product in the U.S. in accordance with the Joint Commercialization
Plan, including:, but not limited to

	 	(i)	 	Direct out-of-pocket costs and expenses incurred that are attributable to
the Commercialization of the Shared Product, including, but not limited to, costs for
launch, promotion, advertising, distribution, recalls, marketing (including
telemarketing), medical education activities (consumer and professional), advocate
development programs and symposia, sales meetings, samples, product related public
relations, market research, health economics studies, post-marketing studies not
required to obtain or maintain product approvals, relationships with opinion leaders
and professional societies, training (including any product training), market
research, sales and marketing data, marketing communications, adverse events
reporting, product hotlines, providing product to and administering indigent
programs, monitoring the sales and medical affairs of the product, activities related
to obtaining reimbursement from payers and other costs incurred collecting fees for
Shared Products, costs and damages arising from any recall in excess of insurance
proceeds, and costs associated with obtaining and maintaining insurance relating to
any of the foregoing.
	 
	 	(ii)	 	FTE Costs of a Party’s internal sales and marketing, regulatory,
scientific, medical, technical or managerial personnel necessary to conduct, manage
and oversee the activities set forth in the Joint Commercialization Plan and the
preparation and updating of the Joint Commercialization Plan (and the budget
contained therein) and monitoring the implementation of the Joint Commercialization
Plan (and the budget contained therein);
	 
	 	(iii)	 	Detailing cost in accordance with Section 12 of this Schedule D;
	 
	 	(iv)	 	costs for Manufacturing and distributing product samples;

-9-

 

	 	(v)	 	costs for filing, prosecuting and/or maintaining patents covering, and
other intellectual property relating to, the Shared Product in the U.S.;
	 
	 	(vi)	 	costs associated with selecting, filing, prosecuting, maintaining,
defending and enforcing Product Trademarks for the Shared Product in the U.S.;
	 
	 	(vii)	 	costs associated with Product Liability and IP Infringement Liability
Claims with respect to Shared Product in the US, net of insurance proceeds;
	 
	 	(viii)	 	Payments to Third Parties under Third Parties’ licenses covering the sale or
Commercialization of the Shared Product in the U.S., including upfront, milestone,
royalty payment to Third Parties; and
	 
	 	(ix)	 	costs incurred for obtaining insurance coverage relating to the Shared
Product.

Commercialization Costs will specifically exclude the cost of activities that promote either
Party’s business as a whole without being specific to the Shared Product (such as corporate image
advertising).

          “Detail” or “Detailing” shall mean, with respect to a Shared Product, the
communication by a Sales Representative to a member of the Target Audience (a) involving
face-to-face contact, (b) describing in a fair and balanced manner the Regulatory
Authority-approved indicated uses and other relevant characteristics of such Licensed Product, (c)
using promotional materials in an effort to increase the Target Audience prescribing and/or
hospital ordering preferences of a Licensed Product for its Regulatory Authority-approved indicated
uses, and (d) made at the Target Audience member’s office, in a hospital or other place where the
Target Audience member normally issues prescriptions where the principal objective is to place an
emphasis, either primary or secondary, on a Licensed Product and not simply to discuss a Licensed
Product with a member of the Target Audience. For the avoidance of doubt, discussions at
conventions, congresses and meetings of key opinion leaders organized by a Party shall not
constitute “Details” or “Detailing”.

          “Development Costs” shall mean (i) as used for calculating Past Development Costs, the
following costs incurred by Takeda with respect to Development of a Shared Product allocated for
the U.S. market prior to the effective date of Alnylam’s exercise of its Profit-Sharing Option with
respect to such Shared Product, and (ii) for purpose of the Profit-Sharing Agreement, the following
costs incurred by a Party with respect to Development of the Shared Product for the U.S. market in
accordance with the Joint Development Plan:

(i) Direct out-of-pocket costs paid to Third Parties that are attributable to the
Development of the Shared Product for the U.S. market including but not limited to:

1. Clinical studies, including post-marketing commitments and all activities
associated with starting, maintaining, and closing studies;

2. Clinical materials and manufacturing costs;

3. Consultants and temporaries used to obtain, maintain, or expand the Development
of a the Shared Product for market approval;

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4. Regulatory fees;

5. Costs associated with chemical, formulation or process development activities
relating to the Shared Product, including conformance or qualification lots, process
improvements, scale-up and manufacturing facility transfers;

6. Test method development, stability testing, report writing and ongoing quality
assurance/quality control activities;

7. Costs to prepare, submit, or develop data or information for submission to a
Governmental Authority to obtain, maintain, or expand marketing approval of the Shared
Product (pre- or post-launch);

8. Payments to Third Parties under Third Parties’ licenses covering the
Development of the Shared Product in the U.S., including upfront, milestone, royalty
payment to Third Parties; and

9. Other payments to Third Parties for the performance of any development
activities with respect to the development of the Shared Product in accordance with the
Joint Development Plan or otherwise agreed upon by the Parties; and

     (ii) FTE Costs of a Party’s internal scientific, medical, technical, regulatory or
managerial personnel necessary to conduct, managing and overseeing Development activities and
the preparation and updating of the Joint Development Plan (and the budget contained therein)
and monitoring the implementation of the Joint Development Plan (and the budget contained
therein)

          “Net Profits/Losses” shall mean Net Sales of the Shared Product in the U.S., (i) less
Development Costs, Cost of Goods and Commercialization Costs and (ii) plus Recoveries, if any. For
the avoidance of doubt, costs deducted in calculating Net Sales shall not be deducted a second time
in calculating Net Profit/Losses.

          “Primary Detail” shall mean a Detail for a Shared Product in which such Shared Product
receives the predominant portion of emphasis and time (at least [**] percent ([**]%) of the time)
during the Detail (i.e., no other product receives more emphasis or time during the Detail).

          “Product Trademark” shall mean all trademarks, other than a Party’s housemarks, used
or intended for use in connection with a Shared Product in the U.S.

          “Recoveries” shall mean all cash amounts (plus the fair market value of all non-cash
consideration) received by a Party from a Third Party solely in connection with the judgment, award
or settlement of any enforcement of intellectual property Controlled by Takeda, Alnylam or the
Parties jointly Covering the Shared Product against an infringing Product that competes with the
Shared Product in the U.S.

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          “Sales Representative” shall mean a professional pharmaceutical sales representative
employed by either Party to conduct primarily Detailing and other promotional efforts with respect
to the Licensed Products and who has been trained by either Party in accordance with a training
protocol to be agreed upon by the Parties as set forth in this Schedule D. Notwithstanding
the foregoing, a Party may use a contract sales force upon the other Party’s consent, which consent
shall not be unreasonably withheld, delayed or conditioned; provided, however, that
the investigation by the other Party with respect to the capabilities and expertise of such
contract sales force shall not constitute the unreasonable withholding, delay or conditioning of
such consent.

          “Secondary Detail” shall mean a Detail for a Shared Product in which such Shared
Product receives the second most emphasis and time (at least [**] percent ([**]%) of the time)
during the Detail (i.e., at most, only one other product receives greater emphasis and time during
the Detail).

          “Target Audience” shall mean the physicians or other health care professionals with
authority to prescribe a pharmaceutical product or issue hospital orders for a pharmaceutical
product.

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SCHEDULE E

LISTED ALNYLAM THIRD PARTY AGREEMENTS

Copies of the following agreements, some in redacted form, have been, or shall be, made available
to Takeda as of the Effective Date:

	 	1.	 	Co-Exclusive License Agreement between Max Planck Innovation GmbH (formerly Garching
Innovation GmbH) and Alnylam Pharmaceuticals, Inc., dated December 20, 2002, as amended by
Amendment dated July 2, 2003, the Requirements Amendment effective June 15, 2005, and the
Waiver Amendment effective August 9, 2007
	 
	 	2.	 	License Agreement between Cancer Research Technology Ltd. and Alnylam
Pharmaceuticals, Inc., dated July 18, 2003
	 
	 	3.	 	Agreement between the Board of Trustees of the Leland Stanford Junior University and
Alnylam Pharmaceuticals, Inc., dated September 17, 2003
	 
	 	4.	 	Letter Agreement between Isis Pharmaceuticals, Inc. and Alnylam Pharmaceuticals, Inc.
dated March 9, 2004 (as amended by letter agreement dated October 28, 2005) and Strategic
Collaboration and License Agreement between Isis Pharmaceuticals, Inc. and Alnylam
Pharmaceuticals, Inc., dated March 11, 2004, as supplemented or amended by letter
agreements dated October 28, 2005, March 11, 2004, June 10, 2005, January 31, 2008
regarding Isis Excluded Technology and January 31, 2008 regarding the non-exclusive nature
of future licenses
	 
	 	5.	 	Amended and Restated Exclusive Patent License Agreement between Alnylam
Pharmaceuticals, Inc. and Massachusetts Institute of Technology, dated May 9, 2007, as
amended by Amendment dated May 7, 2008
	 
	 	6.	 	License and Collaboration Agreement between Tekmira Pharmaceuticals Corporation
(formerly INEX Pharmaceuticals Corporation) and Alnylam Pharmaceuticals, Inc., dated
January 8, 2007
	 
	 	7.	 	The Sublicense Agreement between Tekmira Pharmaceuticals Corporation (formerly INEX
Pharmaceuticals Corporation) and Alnylam Pharmaceuticals, Inc., dated January 8, 2007
	 
	 	8.	 	Cross-License Agreement between Protiva Biotherapeutics Inc. and Alnylam
Pharmaceuticals, Inc., dated August 14, 2007
	 
	 	9.	 	License and Collaboration Agreement among Alnylam Pharmaceuticals, Inc., Isis
Pharmaceuticals, Inc. and Regulus Therapeutics LLC, dated September 6, 2007, as
supplemented by letter agreement dated September 6, 2007

 

 

SCHEDULE F

PRE-EXISTING ALLIANCE AGREEMENTS

Copies of the following agreements, some in redacted form, have been, or shall be, made available
to Takeda as of the Effective Date:

	 	1.	 	Letter Agreement between Isis Pharmaceuticals, Inc. and Alnylam Pharmaceuticals, Inc.
dated March 9, 2004 (as amended by letter agreement dated October 28, 2005) and Strategic
Collaboration and License Agreement between Isis Pharmaceuticals, Inc. and Alnylam
Pharmaceuticals, Inc., dated March 11, 2004, as supplemented or amended by letter
agreements dated October 28, 2005, March 11, 2004, June 10, 2005, January 31, 2008
regarding Isis Excluded Technology and January 31, 2008 regarding the non-exclusive nature
of future licenses
	 
	 	2.	 	License and Collaboration Agreement between Tekmira Pharmaceuticals Corporation
(formerly INEX Pharmaceuticals Corporation) and Alnylam Pharmaceuticals, Inc., dated
January 8, 2007
	 
	 	3.	 	The Research Collaboration and License Agreement between Novartis Institutes for
BioMedical Research, Inc. and Alnylam Pharmaceuticals, Inc., effective as of October 11,
2005, as amended by the Addendum Re: Influenza Program effective as of December 13, 2005,
Amendment No. 1 to such Addendum effective as of March 14, 2006, and Amendment No. 2 to
such Addendum effective as of May 5, 2006
	 
	 	4.	 	Amended and Restated Collaboration Agreement between Medtronic, Inc. and Alnylam
Pharmaceuticals, Inc., dated July 27, 2007
	 
	 	5.	 	Collaboration and License Agreement between Biogen Idec MA Inc. and Alnylam
Pharmaceuticals, Inc., dated September 20, 2006
	 
	 	6.	 	License and Collaboration Agreement among Alnylam Pharmaceuticals, Inc., F.
Hoffmann-La Roche Ltd and Hoffman-La Roche Inc., dated as of July 8, 2007
	 
	 	7.	 	License and Collaboration Agreement among Alnylam Pharmaceuticals, Inc., Isis
Pharmaceuticals, Inc. and Regulus Therapeutics LLC, dated September 6, 2007, as
supplemented by letter agreement dated September 6, 2007
	 
	 	8.	 	Limited Liability Company Agreement of Regulus Therapeutics LLC among Alnylam
Pharmaceuticals, Inc., Isis Pharmaceuticals, Inc. and Regulus Therapeutics LLC, dated
September 6, 2007
	 
	 	9.	 	Cross-License Agreement between Protiva Biotherapeutics Inc. and Alnylam
Pharmaceuticals, Inc., dated August 14, 2007

 

 

	 	10.	 	Termination Agreement between Merck & Co., Inc. and Alnylam Pharmaceuticals, Inc.,
dated September 18, 2007
	 
	 	11.	 	Alnylam/Benitec License Agreement between Benitec Australia, Ltd. and its Affiliates
(as defined therein) and Alnylam Pharmaceuticals, Inc. and its Affiliates (as defined
therein), effective April 8, 2005
	 
	 	12.	 	License and Option Agreement between Calando Pharmaceuticals Inc. and Alnylam
Pharmaceuticals, Inc., dated August 18, 2006, as supplemented by letter agreement dated
August 18, 2006
	 
	 	13.	 	License and Option Agreement between GeneCare Research Institute Co., Ltd. and
Alnylam Pharmaceuticals, Inc., dated January 6, 2005, extended by letters dated October
26, 2007 and November 16, 2007
	 
	 	14.	 	License and Option Agreement between Nastech Pharmaceutical Company Inc. and Alnylam
Pharmaceuticals, Inc., dated July 20, 2005

2

 

SCHEDULE G

SUPPLEMENTAL THERAPEUTIC AREAS

Autoimmune Disease: [**], including [**] and excluding autoimmune diseases of [**].

Bacterial Infection: Bacterial infection [**].

Cardiovascular: Diseases of the heart or of the vascular system, including [**] and excluding
cardiovascular diseases of [**].

Oral: Diseases of the oral cavity, including [**] and excluding oral diseases of [**].

Dermatology: Diseases of the skin, including [**] and excluding dermatologic diseases of [**].

Endocrine: Diseases of the endocrine system, including diseases of the [**] and excluding endocrine
system diseases of [**].

Ex Vivo Therapy: Any part of gene-based ex vivo therapy including [**] including [**].

Gastrointestinal: Diseases of the gastrointestinal system, including [**] and excluding
gastrointestinal diseases of [**].

Genitourinary: Diseases of the genitourinary system, including [**] and excluding genitourinary
diseases of [**].

Hematology: Diseases of the bone marrow or of cells originating in [**] and excluding hematologic
diseases of [**].

Hepatic: Diseases of the [**], including, [**] and excluding hepatic diseases of [**].

Inflammatory Disease: [**], including those [**], including [**] and excluding inflammatory
diseases of [**].

Musculoskeletal Disease: Diseases of the muscles, ligaments or bone, including, [**] and excluding
musculoskeletal diseases of [**].

Neurodegenerative Disease: [**] involving [**], including [**] and excluding neurodegenerative
diseases of [**].

Neurological or Psychiatric Disease: [**], including [**] and excluding neurological or psychiatric
diseases of [**].

 

 

Opthalmic Disease: Diseases of the eye, including [**] and excluding opthalmic diseases of [**].

Parasitic Disease: Parasitic [**].

Pulmonary Disease: Diseases of the pulmonary system, including [**] and excluding pulmonary
diseases of [**].

Renal Disease: Diseases of the kidney, including [**] and excluding renal diseases of [**].

Transplantation Medicine: [**], and excluding [**].

Viral Disease: Viral [**].

 

 

SCHEDULE H

PROHIBITED COLLABORATORS

[**]

 

 

SCHEDULE I

PROHIBITED SUBLICENSEES

Schedule I-1

[**]

Schedule I-2

[**]

 

 

SCHEDULE J

Summary of Technology Transfer Plan

The Technology Transfer Plan described below outlines the transfer of technology under the License
and Collaboration Agreement (the “Agreement”) dated May 27, 2008, between Takeda Pharmaceutical
Company Limited (“Takeda”) and Alnylam Pharmaceuticals, Inc. (“Alnylam”). Capitalized terms used
and not defined herein shall have the meanings set forth in the Agreement. In case of any conflict
between this Summary of Technology Transfer Plan and the Agreement, the terms of the Agreement
shall govern.

Collaboration Management:

The purpose of the technology transfer is to teach and enable Takeda to practice the Alnylam
Intellectual Property. The Technology Transfer Plan will be overseen and managed by the JTTC. The
details of the Technology Transfer Plan will be developed and adjusted over time by the JTTC. The
Parties have created the following Technology Transfer Plan as the basis for these activities and
it is the intent of the Parties to adapt the Technology Transfer Plan in a manner as necessary to
teach and enable Takeda to successfully practice the Alnylam Intellectual Property. The Technology
Transfer Milestones described below are designed such that if each Party uses its diligent efforts,
the Technology Transfer Plan should be successfully completed in accordance with the timeframes set
forth in the Agreement.

Each Party shall use Commercially Reasonable Efforts to complete the tasks assigned to such Party
under the Technology Transfer Plan in a timely manner and in accordance with the Technology
Transfer Plan. Alnylam shall, subject to Takeda satisfying the Takeda obligations as set forth in
the Technology Transfer Plan, be primarily responsible for Technology Milestones I and II and the
Parties shall be jointly responsible for Technology Milestone III within the time frames set forth
in the Technology Transfer Plan. If an assessment by Takeda reveals an insufficiency in any
technology that has already been transferred, upon Takeda’s request, Alnylam shall disclose any new
and/or more detailed documents and SOPs that it may have related to any such insufficiencies, but
nothing contained herein shall require Alnylam to seek or obtain technology which it does not
already possess.

The Technology Transfer Plan

Overview

The technology transfer will be conducted in stages, which may have activities that overlap. During
technology transfer, each stage will have clearly defined deliverables. Additional transfer
activities associated with each stage may be approved by the JTTC.

 

 

Stage 1: Assessment and Documentation 

This stage involves, as necessary and applicable, (i) appointing the JTTC, (ii) forming
subteams with respect to specific aspects of technology transfer, (iii) each Party
establishing contacts with the technology transfer counterparts at the other Party, and
(iv) the transfer by Alnylam of SOPs, presentations, and materials listed in Table 1 below.
The transfer of the items described in Column J of Table 1 below will occur within [**]
days after the Effective Date (the “Stage 1 Period”). Additional documents listed in Table
1 and to be further defined during the Technology Transfer Period will also be provided by
Alnylam as available. Items to be transferred after the Stage 1 Period may include certain
procedures for IND-enabling studies (such as toxicology, PMDK, CMC) which require assessing
and confirming a large amount of content, and extra time is provided in the Technology
Transfer Plan detailed below to accommodate such assessment and confirmation.

Stage 2: Technology Training and Implementation 

The JTTC shall meet within [**] after the end of the Stage 1 Period (i.e. within [**] after
the Effective Date) to define a detailed training plan for Stage 2. This training plan will
identify a specific number of sessions, the length of each session, content, and the
appropriate participants for each session. These sessions may take place at either Alnylam
facilities or Takeda facilities. Example training sessions are described below, but the
actual training plan will be created by the JTTC as described above. Each training session
is expected to last for [**]. Where practical, multiple related topics and areas may be
taught in a single training session as determined by the JTTC by mutual agreement. For
example, the Parties may design a training sessions in which small-scale synthesis and
analytics are taught simultaneously so that participants can immediately analyze the
quality of the product of the synthesis process. Each session will be led by a technology
specialist from Alnylam. The specific session topics will be determined by the JTTC by
mutual agreement as described above, but are expected to include: (1) a session covering
Bioinformatics, Synthesis and Analytics; (2) a session covering Delivery, Chemistry and
Formulations; (3) a session covering Biological Assays and Screening Techniques; and (4) a
session covering mid-scale synthesis, large-scale manufacturing and visits to contract
manufacturing organizations. All of the training sessions will be completed within [**]
months after the Effective Date (the “Stage 2 Period”). During the Stage 2 Period, the JTTC
may organize additional training sessions at any time. Technology Transfer Milestone II is
defined as, and will be deemed completed upon, the completion of all training sessions or
the end of the Stage 2 Period.

Stage 3: Demonstration of Enablement 

During Stage 3, Takeda scientists will perform siRNA research either on (i) screens of [**]
Targets in vitro or (ii) [**] siRNAs administered in vivo. A Target shall be considered
screened in vitro when at least [**] siRNAs directed against said Target

 

 

have been tested in an in vitro cell culture system and at least [**] siRNAs that result in
greater than [**] percent ([**]%) Target reduction assessed by mRNA or protein expression
are identified. Entry of siRNA in vitro into cells for the purposes of screening will be
achieved by standard methodologies recognized in the field (such as transfection or
electroporation) and quantification of Target expression will be conducted by comparison
with cells similarly treated but receiving no siRNA (commonly known as mock transfection or
untransfected cells). An siRNA shall be considered as administered in vivo when the first
siRNA is delivered into an animal.

Technology Milestone III will be defined as, and deemed completed upon, (a) identification
during the Research Collaboration of an appropriate lead compound which can proceed to the
GLP Toxicology Study stage, or (b) in the event that a compound that is appropriate for a
GLP Toxicology Study is not identified by the third (3rd) anniversary of the Effective
Date, the identification of either (i) [**] siRNAs that result in more than [**] percent
([**]%) Target reduction assessed by mRNA or protein expression, or (ii) [**] siRNAs that
result in pharmacological efficacy in an in vivo model.

Each Party will employ Commercially Reasonable Efforts to achieve Milestone III no later
than the third (3rd) anniversary the Effective Date; however, the Parties agree that they
shall continue to work together to achieve Milestone III in the event that it is not
reached by the third (3rd) anniversary of the Effective Date in accordance with the terms
of the Agreement and the decisions of the JTTC.

Optional Activities

RNAi facility design consulting. At Takeda’s request, Alnylam will provide consulting support for
up to [**] during the first [**] following the Effective Date for the following activities: (1)
RNAi platform facility design and (2) RNAi platform laboratory design and installation.

 

 

Details of Initial Technology Transfer Plan

(Note: The following proposed timelines and schedules will be reviewed and revised at the beginning
of Stage 2 by the JTTC as described above.)

#1 Bioinformatics

Alnylam Lead: [**]

Takeda Lead: [**]

[**]

#2 Small-Scale Synthesis

Alnylam Lead: [**]

Takeda Lead: [**]

[**]

#3 Middle Scale Synthesis

Alnylam Lead: [**]

Takeda Lead: [**]

#4 Large Scale Synthesis

Alnylam Lead: [**]

Takeda Lead: [**]

[**].

#5 Conjugation Chemistry

Alnylam Lead: [**]

Takeda Lead: [**]

[**].

#6 Liposomal Formulations (In-House)

Alnylam Lead: [**]

Takeda Lead: [**]

[**].

#7 Liposomal Formulations (Alnylam Collaborator Formulations)

Alnylam Lead: [**]

 

 

Takeda Lead: [**]

[**].

#8 Pulmonary Formulations

Alnylam Lead: [**]

Takeda Lead: [**]

[**].

#9 Bioanalysis

Alnylam Lead: [**]

Takeda Lead: [**]

[**]

#10 Analytical Methods

Alnylam Lead: [**]

Takeda Lead: [**]

[**].

#11 In Vitro Models and Off-Target Analysis

Alnylam Lead: [**]

Takeda Lead: [**]

[**].

#12 In Vitro Immunoassay Screening

Alnylam Lead: [**]

Takeda Lead: [**]

[**].

#13 5’RACE assay

Alnylam Lead: [**]

Takeda Lead: [**]

[**].

 

 

#14 In vivo Efficacy Reporter Models

Alnylam Lead: [**]

Takeda Lead: [**]

[**].

#15 Toxicity

Alnylam Lead: [**]

Takeda Lead: [**]

[**].

#16 Regulatory

Alnylam Lead: [**]

Takeda Lead: [**]

[**].

#17 CMC Drug Substance

Alnylam Lead; [**]

Takeda Lead; [**]

[**].

#18 CMC Drug Product/Formulations

Alnylam Lead: [**]

Takeda Lead: [**]

[**].

#19 Infrastructure/ Facility Design Consulting

Alnylam Lead: [**]

Takeda Lead: [**]

[**].

 

 

#20 ALN-RSV01 IND TABLE OF CONTENTS

Alnylam Lead: [**]

Takeda Lead: [**]

[**].

 

 

Table 1: List of required objects in Technology Transfer Plan

A total of 63 pages have been omitted pursuant to a request for confidential treatment. Astersisk
denote omissions.

[**]

 

 

SCHEDULE K

SUMMARY OF RESEARCH COLLABORATION PLAN

	I.	 	General Parameters:

	 	1.	 	The Research Collaboration Plan described below outlines the Research Collaboration
to be conducted under the License and Collaboration Agreement (the “Agreement”) dated May
27, 2008, between Takeda Pharmaceutical Company Limited (“Takeda”) and Alnylam
Pharmaceuticals, Inc. (“Alnylam”).
	 
	 	2.	 	Capitalized terms used and not defined herein shall have their respective meanings
set forth in the Agreement.
	 
	 	3.	 	In case of any conflict between this Summary of Research Collaboration Plan and the
Agreement, the terms of the Agreement shall govern.
	 
	 	4.	 	The Research Collaboration Plan shall, [**] with respect to [**].
	 
	 	5.	 	During the Research Collaboration Term, Alnylam shall assign [**] to the Research
Collaboration per Fiscal Year.
	 
	 	6.	 	Takeda may, at any time during the Research Collaboration Term, request that the
Parties amend the Research Collaboration Plan to reduce or increase the number of
Alnylam’s FTEs in accordance with the terms of Section 6.1(c) of the Agreement.

	II.	 	Overview of the Parties Initial Roles and Responsibilities Under the Research Collaboration:
	 
	 	 	[**].

3. The Parties will arrange additional activities through the JRCC in accordance with Article II of
the Agreement.

 

 

SCHEDULE L

ALLOCATION

Allocation of the One Hundred Million United States dollars ($100,000,000) payment pursuant to
Section 7.1 due within [**] of the execution of the Agreement shall be as follows:

	 	 	 	 	 	 	 	 	 
	Intellectual Property	 	Percentage	 	Amount
	Broad RNAi Patent Rights and Broad RNAi Know-How
	 	 	[**]	%	 	 	[**]	 
	Alnylam Delivery Intellectual Property (of which
the technology licensed from [**] represents [**]%
or $[**])
	 	 	[**]	%	 	 	[**]	 
	Ancillary intellectual property from Stanford and
CRT
	 	 	[**]	%	 	 	[**]	 

 

 

SCHEDULE M

JOINT PRESS RELEASE

 

 

	 	 	 
	

	 	           
	Contacts:
	 	 
	Alnylam Pharmaceuticals, Inc.

	 	Takeda Pharmaceutical Company Limited
	Cynthia Clayton (Investors)

	 	Tomoyuki Ooue (Investors)
	617-551-8207

	 	+81-3-3278-2301
	 
	 	 
	Kathryn Morris (Media)

	 	Seizo Masuda (Media)
	Yates Public Relations

	 	+81-3-3278-2037
	845-635-9828
	 	 

Alnylam and Takeda Form Strategic Worldwide Platform Alliance in RNAi Therapeutics

— Alnylam Selects Takeda as its Sole Asian Strategic Partner and

Obtains Options for 50-50 Development and Commercialization of Takeda RNAi Therapeutic

Programs in U.S. Market —

— Takeda Gains Access and Enablement to Alnylam’s Leading RNAi Therapeutics Technology

and Intellectual Property in Fields of Oncology and Metabolic Disease —

— Alliance Includes $150 Million in Upfront and Near-Term Technology Transfer Payments, and

Additional Future Research & Development and Commercial Milestones —

CAMBRIDGE, Mass., USA and OSAKA, Japan, May 27, 2008 — Alnylam Pharmaceuticals, Inc. (Nasdaq:
ALNY) and Takeda Pharmaceutical Company Limited (TSE: 4502) today announced that they have formed a
strategic platform alliance in RNAi therapeutics in the fields of oncology and metabolic disease
with the option to expand to additional therapeutic areas. This landmark alliance is the first
major RNAi therapeutics partnership between a Japanese pharmaceutical company and a U.S.
biotechnology company, representing a new frontier in the advancement of RNAi therapeutics to
patients on a global basis.

RNAi is an entirely new approach for the discovery of breakthrough medicines that utilizes a
natural mechanism found within the body to inhibit expression of certain genes. Harnessing the
activity of RNAi creates a direct opportunity to develop specific and potent new medicines for the
treatment of a broad range of diseases, including those that are difficult to treat with today’s
drug approaches. The discovery of RNAi was awarded the 2006 Nobel Prize and the advancement of
RNAi is recognized as one of the most important advances in biomedical sciences in decades.

Page 1 of 4

 

“We are very pleased and honored to have a strategic platform partnership with Takeda, one of the
world’s leading pharmaceutical companies. As the first RNAi technology partnership with a
pharmaceutical company located in Asia, this new alliance expands the advancement of RNAi
therapeutics to patients on a global basis,” said John Maraganore, Ph.D., Chief Executive Officer
of Alnylam. “Across multiple dimensions, this new partnership is a major event in Alnylam’s
efforts to build a leading biopharmaceutical company. A particularly important element in this new
platform alliance is Alnylam’s opportunity to co-develop and co-commercialize Takeda RNAi
therapeutic products with Takeda in the U.S. market.”

“We are excited to work with Alnylam, as the leading worldwide company in the field of RNAi
therapeutics with a strong commitment to scientific excellence and an unparalleled intellectual
property position,” said Yasuchika Hasegawa, President of Takeda. “We believe this alliance will
accelerate our initiatives to establish the foundation for RNAi drug discovery supported by
Alnylam’s platform technologies and know-how. We expect that our product portfolio will be enhanced
by the addition of RNAi therapeutics to our current small molecule and anti-body research
platforms.”

This collaboration provides Takeda with broad, worldwide, non-exclusive access to and enablement
with Alnylam’s RNAi therapeutics platform technology and intellectual property in the fields of
oncology and metabolic disease, with the right to expand the number of therapeutic fields in the
future. The agreement also includes the transfer of platform technology from Alnylam to Takeda, a
collaboration and cross-license of delivery technologies between the two companies, and a drug
discovery collaboration on certain RNAi therapeutic targets, subject to certain Alnylam third party
obligations.

Takeda becomes Alnylam’s strategic partner for RNAi therapeutics over a five-year period and the
only Asian company to obtain a right of first negotiation to develop and commercialize Alnylam RNAi
therapeutic development programs for the Asian market, excluding Alnylam’s ALN-RSV01 program. In
addition, Alnylam obtains opt-in options to co-develop and co-commercialize Takeda RNAi therapeutic
programs in the U.S. market on a 50-50 basis.

The partnership includes $100 million in upfront payments and $50 million in near-term technology
transfer payments for a non-exclusive license in two therapeutic fields and is valued at
potentially over $1 billion in future research and development and commercial milestones, upon
successful commercialization of multiple products. At Takeda’s option, the scope of the
partnership can be expanded to include additional fields with a $50 million per field expansion
payment. Alnylam is also eligible to receive research and development funding related to the drug
discovery collaboration. In addition, Alnylam is eligible to receive up to $171 million in
development and commercial milestone payments and significant royalties per product. Alnylam plans
to update financial guidance when it announces its second quarter 2008 financial results.

# # #

Page 2 of 4

 

About RNA Interference (RNAi)

RNAi (RNA interference) is a revolution in biology, representing a breakthrough in understanding
how genes are turned on and off in cells, and a completely new approach to drug discovery and
development. Its discovery has been heralded as “a major scientific breakthrough that happens once
every decade or so,” and represents one of the most promising and rapidly advancing frontiers in
biology and drug discovery today which was awarded the 2006 Nobel Prize for Physiology or Medicine.
RNAi is a natural process of gene silencing that occurs in organisms ranging from plants to
mammals. By harnessing the natural biological process of RNAi occurring in our cells, the creation
of a major new class of medicines, known as RNAi therapeutics, is on the horizon. RNAi
therapeutics target the cause of diseases by potently silencing specific messenger RNAs (mRNAs),
thereby preventing disease-causing proteins from being made. RNAi therapeutics have the potential
to treat disease and help patients in a fundamentally new way.

About Alnylam Pharmaceuticals

Alnylam is a biopharmaceutical company developing novel therapeutics based on RNA interference, or
RNAi. The company is applying its therapeutic expertise in RNAi to address significant medical
needs, many of which cannot effectively be addressed with small molecules or antibodies, the
current major classes of drugs. Alnylam is leading the translation of RNAi as a new class of
innovative medicines with peer-reviewed research efforts published in the world’s top scientific
journals including Nature, Nature Medicine, and Cell. The company is leveraging these capabilities
to build a broad pipeline of RNAi therapeutics; its most advanced program is in Phase II human
clinical trials for the treatment of respiratory syncytial virus (RSV) infection. In addition, the
company is developing RNAi therapeutics for the treatment of a wide range of disease areas,
including hypercholesterolemia, liver cancers, and Huntington’s disease. The company’s leadership
position in fundamental patents, technology, and know-how relating to RNAi has enabled it to form
major alliances with leading companies including Medtronic, Novartis, Biogen Idec, Roche, and
Takeda. To reflect its outlook for key scientific, clinical, and business initiatives, Alnylam has
established “RNAi 2010” which includes the company’s plan to significantly expand the scope of
delivery solutions for RNAi therapeutics, have four or more programs in clinical development, and
to form four or more new major business collaborations, all by the end of 2010. Alnylam is a joint
owner of Regulus Therapeutics LLC, a joint venture focused on the discovery, development, and
commercialization of microRNA therapeutics. Founded in 2002, Alnylam maintains headquarters in
Cambridge, Massachusetts. For more information, visit www.alnylam.com.

About Takeda

Founded in 1781 and located in Osaka, Japan, Takeda is a research-based global company with its
main focus on pharmaceuticals. As the largest pharmaceutical company in Japan and one of the
global leaders of the industry, Takeda is committed to striving toward better health for
individuals and progress in medicine by developing superior pharmaceutical products.

Additional information about Takeda is available through its corporate website, www.takeda.com.

Page 3 of 4

 

Alnylam Forward-Looking Statements

Various statements in this release concerning Alnylam’s future expectations, plans and prospects,
constitute forward-looking statements for the purposes of the safe harbor provisions under The
Private Securities Litigation Reform Act of 1995. Actual results may differ materially from those
indicated by these forward-looking statements as a result of various important factors, including
risks related to: Alnylam’s approach to discover and develop novel drugs, which is unproven and may
never lead to marketable products; obtaining, maintaining and protecting intellectual property;
Alnylam’s ability to enforce its patents against infringers and to defend its patent portfolio
against challenges from third parties; Alnylam’s ability to obtain additional funding to support
its business activities; Alnylam’s ability to realize future milestones and royalties as well as
co-development and co-commercialization opportunities; Alnylam’s dependence on third parties for
development, manufacture, marketing, sales and distribution of products; obtaining regulatory
approval for products; competition from others using technology similar to Alnylam’s and others
developing products for similar uses; Alnylam’s dependence on collaborators; and Alnylam’s short
operating history; as well as those risks more fully discussed in the “Risk Factors” section of its
most recent quarterly report on Form 10-Q on file with the Securities and Exchange Commission. In
addition, any forward-looking statements represent Alnylam’s views only as of today and should not
be relied upon as representing its views as of any subsequent date. Alnylam does not assume any
obligation to update any forward-looking statements.

Takeda Forward-Looking Statements

This press release contains forward-looking statements regarding the Company’s plans, outlook,
strategies and results for the future. All forward-looking statements are based on judgments
derived from the information available to the Company at this time.
Certain risks and uncertainties could cause the Company’s actual results to differ materially from
any projections presented in this press release. These risks and uncertainties include, but are
not limited to, the economic circumstances surrounding the Company’s business; competitive
pressure; relative laws and regulations; product development programs; and changes in exchange
rates.

We assume no obligation to update or reverse any forward-looking statements or other information
contained in this press release, whether as a result of new information, future events, or
otherwise.

# # #

Page 4 of 4

 

SCHEDULE N

PROHIBITED PARTNERS

[**]exv10w41

Exhibit 10.41

CONFIDENTIAL TREATMENT REQUESTED: Certain portions of this document have been omitted
pursuant to a request for confidential treatment and, where applicable, have been marked
with an asterisk (“[****]”) to denote where omissions have been made. The confidential material
has been filed separately with the Securities and Exchange Commission.

 

SUPPLY AGREEMENT

EVERGREEN SOLAR, INC.

and

DC CHEMICAL CO., LTD.

Dated as of January 30, 2008

 

 

 

Table of Contents

	 	 	 	 	 
	 	 	Page	 
	ARTICLE I SUPPLY OF PRODUCT
	 	 	1	 
	 
	Section 1.1 Quantity and Price of Product
	 	 	1	 
	Section 1.2 Delivery Start Date; Monthly Quantity
	 	 	1	 
	Section 1.3 Quantity Variance
	 	 	2	 
	Section 1.4 Disposition of Product Sold
	 	 	2	 
	Section 1.5 Delivery Schedule
	 	 	2	 
	 
	 	 	 	 
	ARTICLE II PRICE ADJUSTMENT AND ADVANCE PAYMENT
	 	 	3	 
	 
	Section 2.1 Price Adjustment
	 	 	3	 
	Section 2.2 Threshold
	 	 	4	 
	Section 2.3 Non-Refundable Advance Payment
	 	 	4	 
	Section 2.4 Refund of Advance Payment
	 	 	4	 
	 
	 	 	 	 
	ARTICLE III DELIVERY AND SHIPPING
	 	 	5	 
	 
	Section 3.1 Delivery
	 	 	5	 
	 
	 	 	 	 
	ARTICLE IV PAYMENTS
	 	 	5	 
	 
	Section 4.1 Payments
	 	 	5	 
	Section 4.2 Taxes
	 	 	6	 
	Section 4.3 Payment Terms in the Event of Non-Payment
	 	 	6	 
	 
	 	 	 	 
	ARTICLE V SPECIFICATIONS; INSPECTION OF PRODUCT; PLANT
	 	 	6	 
	 
	Section 5.1 Specifications
	 	 	6	 
	Section 5.2 Inspection of Product
	 	 	6	 
	Section 5.3 Plant
	 	 	6	 
	 
	 	 	 	 
	ARTICLE VI CONFIDENTIAL INFORMATION
	 	 	7	 
	 
	Section 6.1 Confidential Information
	 	 	7	 
	Section 6.2 Restrictions On Use and Disclosure
	 	 	7	 
	Section 6.3 Exclusions
	 	 	7	 
	Section 6.4 Compelled Disclosure
	 	 	7	 
	Section 6.5 Press Releases
	 	 	8	 
	Section 6.6 Confidentiality of Agreement
	 	 	8	 
	 
	 	 	 	 
	ARTICLE VII WARRANTIES; DISCLAIMER; REMEDIES
	 	 	8	 
	 
	Section 7.1 Disclaimer of Warranties
	 	 	8	 
	Section 7.2 Title
	 	 	8	 
	Section 7.3 Damaged or Defective Product
	 	 	8	 
	Section 7.4 Failure to Purchase by Buyer
	 	 	9	 
	Section 7.5 Failure to Supply by DCC
	 	 	9	 

 i 

 

 

Table of Contents

(continued)

	 	 	 	 	 
	 	 	Page	 
	Section 7.6 Limitation of Liability
	 	 	9	 
	Section 7.7 Indemnity
	 	 	9	 
	 
	 	 	 	 
	ARTICLE VIII TERM AND TERMINATION
	 	 	10	 
	 
	Section 8.1 Term
	 	 	10	 
	Section 8.2 Termination
	 	 	10	 
	Section 8.3 Effect of Termination
	 	 	11	 
	 
	 	 	 	 
	ARTICLE IX MISCELLANEOUS
	 	 	11	 
	 
	Section 9.1 Force Majeure
	 	 	11	 
	Section 9.2 Governmental Approvals
	 	 	11	 
	Section 9.3 Hierarchy among this Agreement and Purchase Orders
	 	 	11	 
	Section 9.4 Independent Contractors
	 	 	12	 
	Section 9.5 Notice
	 	 	12	 
	Section 9.6 Amendment; No Waiver
	 	 	12	 
	Section 9.7 Governing Law; Jurisdiction
	 	 	12	 
	Section 9.8 Entire Agreement
	 	 	13	 
	Section 9.9 Assignment
	 	 	13	 
	Section 9.10 Non-Exclusive Agreement
	 	 	13	 
	Section 9.11 Successors
	 	 	14	 
	Section 9.12 Headings
	 	 	14	 
	Section 9.13 Word Meanings
	 	 	14	 
	Section 9.14 Language
	 	 	14	 
	Section 9.15 Counterparts
	 	 	14	 

 ii 

 

 

SUPPLY AGREEMENT

     THIS SUPPLY AGREEMENT (this “Agreement”) is entered into as of January 302008, (the
“Effective Date”), by and between DC Chemical Co., Ltd., a corporation organized under the
laws of Korea, having its registered office at Oriental Chemical Building, 50, Sogong-Dong,
Jung-Gu, Seoul, 100-718, Korea (“DCC”), and Evergreen Solar, Inc., a company organized
under the laws of Delaware, having its principal place of business at 138 Bartlett Street,
Marlboro, Massachusetts 01752, U.S.A.(“Buyer”). Each of DCC and Buyer is referred to
herein individually as a “Party” and collectively as the “Parties.”

RECITALS

     WHEREAS, DCC will build and operate a production facility (“Plant”) for the
manufacture of poly-crystalline silicon made from the decomposition of chlorosilane in reactors
(the “Product”);

     WHEREAS, Buyer manufactures poly-crystalline wafers for use in the production of solar
modules; and

     WHEREAS, DCC desires to sell, and Buyer desires to purchase, Products pursuant to the terms
and conditions of this Agreement.

     NOW, THEREFORE, the Parties agree as follows:

ARTICLE I

SUPPLY OF PRODUCT

     Section 1.1 Quantity and Price of Product. Subject to adjustments pursuant to
Sections 1.2, 1.3 and Article II, DCC hereby agrees to sell and Deliver to Buyer, and Buyer hereby
agrees to purchase and receive from DCC, the following quantities of Product for each of the
periods (with respect to each calendar year, the quantity indicated below for such calendar year,
the “Original Annual Quantity”) and at the respective prices (as may be adjusted pursuant
to Sections 2.1 and 2.2) set forth below:

	 	 	 	 	 
	Calendar Year	 	Quantity	 	Price
	2009

	 	[****] kgs
	 	US$[****]/kg
	2010
	 	[****] kgs
	 	US$[****]/kg
	2011
	 	[****] kgs
	 	US$[****]/kg
	2012
	 	[****] kgs
	 	US$[****]/kg
	2013
	 	[****] kgs
	 	US$[****]/kg
	2014
	 	[****] kgs
	 	US$[****]/kg
	2015
	 	[****] kgs
	 	US$[****]/kg
	Total
	 	[****] kgs
	 	US$ [****]

     Section 1.2 Delivery Start Date; Monthly Quantity. Subject to adjustment in
accordance with Section 1.3, for each calendar year set forth in Section 1.1, DCC shall sell and
Deliver, and Buyer shall receive and purchase, the Original Annual Quantity (or, if the

1

 

Original Annual Quantity has been adjusted pursuant to Section 1.3 below, the Adjusted Annual
Quantity (as defined below)) for such calendar year in accordance with the delivery schedule agreed
to by the Parties pursuant to Section 1.5. The monthly quantities to be Delivered, before giving
effect to any adjustments pursuant to Section 1.3, shall herein be referred to as “Original
Monthly Quantity” or “Original Monthly Quantities,” as the context shall require.

     Section 1.3 Quantity Variance.

     (a) With respect to each Original Annual Quantity, DCC may, at its sole and absolute
discretion, increase or decrease the amount of such Original Annual Quantity by an amount
which is no greater than [****]% of such Original Annual Quantity by providing advanced
written notice (the “Notice of Adjustment”) to Buyer. Any Original Annual Quantity
which has been so adjusted shall become the “Adjusted Annual Quantity”. The Notice
of Adjustment shall become effective on the date which is [****] months after the date of
such Notice of Adjustment. Upon effectiveness of such Notice of Adjustment, that portion of
the Adjusted Annual Quantity remaining to be Delivered as of such effective date shall be
equitably adjusted by mutual agreement of the parties, provided however, in the absence of
mutual agreement, that portion of the Adjusted Annual Quantity then remaining to be
delivered shall be equally divided among the calendar months remaining in such calendar
year. Any Original Monthly Quantity which has been so adjusted shall become the
“Adjusted Monthly Quantity”.

     (b) If the actual quantity of Products Delivered is less than [****]% of the Original
Monthly Quantity or Adjusted Monthly Quantity, as applicable, then remedial measures in
respect of such deficiency shall be discussed between DCC and Buyer pursuant to which DCC
and Buyer shall find an amicable solution to such deficiency, including rolling over the
deficient quantity to one or more subsequent Deliveries. In no event shall such deficiency
be deemed to be a default under this Agreement, provided however, DCC shall have exerted
[****] efforts to Deliver the Original Monthly Quantity or Adjusted Monthly Quantity, as
applicable.

     Section 1.4 Disposition of Product Sold. Buyer shall utilize the Product for the
manufacturing purposes of itself and Buyer shall not re-sell the Product, or become a re-seller or
distributor of the Product sold to Buyer under this Agreement.

     Section 1.5 Delivery Schedule. At least [****] days prior to the beginning of each
calendar year, the Parties shall discuss and consult with each other as to timing and quantities of
Original Monthly Quantities to be Delivered during such calendar year. Absent agreement by the
Parties to the contrary, DCC shall Deliver to Buyer the applicable Original Annual Quantity over
substantially equal batches during each month of such calendar year, pursuant to a monthly purchase
order to be Delivered by Buyer to DCC at least [****] days prior to the beginning of such month,
which purchase order shall specify the agreed Original Monthly Quantity to be Delivered in such
month. The schedule for Deliveries of Adjusted Annual Quantities shall be determined in accordance
with Section 1.3(a).

2

 

ARTICLE II

PRICE ADJUSTMENT AND ADVANCE PAYMENT

     Section 2.1 Price Adjustment. The price per kilogram of Product sold during any
calendar year (the “Relevant Year”) shall be subject to adjustment in accordance with the
following:

     If the absolute value of “(A – B)/B” is equal to or greater than “[****]%”, then the new price
per kilogram of Product for the Relevant Year (the “Adjusted Price”) shall equal C.

     Where:

     A = [****];

     B = [****];

     C = [****];

     [****]

     For the avoidance of doubt, DCC shall calculate and determine whether the price for Products
for a Relevant Year is required to be adjusted in accordance with this Section 2.1 promptly as
practicable, and notify Buyer in writing of any adjustment to the price, if any. In the event that
a determination has been made that an adjustment is required to be made to the price in respect of
any Relevant Year, such adjustment shall apply to any Original Monthly Quantities or Adjusted
Monthly Quantities, as applicable, remaining to be Delivered during such calendar year, but not to
any Original Monthly Quantities or Adjusted Monthly Quantities, as applicable, already Delivered in
respect of such calendar year nor to the Original Annual Quantity of any other calendar year.

     Section 2.2 Threshold. If the Adjusted Price for any of (i) the [****] or
calendar years is less than [****]% or greater than [****]% or (ii) the [****] calendar years is
less than [****]% or greater than [****]%, in each case, of the respective prices for such years
set forth in the table in Section 1.1, then the actual amount of the adjustment to be applied to
determine the Adjusted Price for such calendar year shall be discussed between DCC and Buyer
pursuant to which DCC and Buyer shall agree on a mutually acceptable adjustment amount.

     Section 2.3 Advance Payment. Buyer agrees to make an interest free, and
non-refundable (except as set forth in Section 2.4) advance payment to DCC (paid to an account
designated by DCC) in the aggregate amount of US$36,540,000 (the “Advance Payment”), in
accordance with the schedule set forth below:

	 	 	 
	Date	 	Amount
	Within 1 month after contract date
	 	US$10.962,000
	Within 3 months after the 1st installment
	 	US$[****]
	December 1, 2008
	 	US$[****]
	Total
	 	US$36,540,000

3

 

In respect of each payment from Buyer to DCC, Buyer shall be entitled to an Advance
Payment Credit.

“Advance Payment Credit” in respect of any payment shall mean the number equal to the
product of (i) the Pro Rata Percentage and (ii) the amount of such payment, to the
extent that the Advance Payment Balance at the time of calculation is greater than such
number, and if the Advance Payment Balance is less than such number, the amount of the
Advance Payment Balance.

“Pro Rata Percentage” shall equal the fraction, the numerator of which is equal to the
amount of the Advance Payment and the denominator of which is equal to the aggregate
purchase price for all of the Original Annual Quantities set forth in Section 1.1.

“Advance Payment Balance” as of a certain time, shall mean a number which is equal to
(i) the amount of the Advance Payment less (ii) the aggregate amount of all Advance Payment
Credits prior to such time.

     Section 2.4 Refund of Advance Payment. Upon termination of this Agreement pursuant to
[****] DCC shall refund to Buyer within [****] days of the effective date of such termination the Advance
Payment Balance as of the date of such refund, less any amounts due and payable by Buyer to DCC
which are outstanding as of the date of such refund.

ARTICLE III

DELIVERY AND SHIPPING

     Section 3.1 Delivery. The Product shall be delivered to Buyer [****] (Incoterms
2000); accordingly, the availability of an Original Monthly Quantity or Adjusted Monthly Quantity,
as applicable, for receipt by Buyer at the Plant shall constitute “Delivery” for the
purposes of this Agreement.

ARTICLE IV

PAYMENTS

     Section 4.1 Payments. Contemporaneously with each Delivery under this Agreement, DCC
shall issue an invoice to Buyer for the Products being Delivered. Invoices will reflect the
purchase price for the applicable delivery after having given effect to the adjustment to

4

 

such purchase price pursuant to Section 2.3 and may be sent by any normally reliable means,
including electronically, facsimile, hand delivery or other methods. Buyer shall pay all amounts
due under any invoice submitted by DCC within [****] days from the date of such Delivery. All
payments made to DCC shall be made in cash by wire transfer to an account specified by DCC. All
such payments shall be free and clear of all withholdings, taxes, set-off, encumbrances of any
kind. Late payment interest of [****]%) per annum may be assessed by DCC on payment past due from
the payment due date to the date payment is received.

     This Agreement is a [****] such that Buyer is [****]

     Section 4.2 Taxes. DCC shall be responsible for all sales, use, excise, value-added
or other taxes, tariffs, duties or assessments, including interest and penalties, levied or imposed
at any time by any governmental authority arising from or relating to the supply of Product. Buyer
shall be responsible for all sales, use, excise, value-added or other taxes, tariffs, duties or
assessments, including interest and penalties, levied or imposed at any time by any governmental
authority arising from or relating to purchase or use of the Product.

     Section 4.3 Payment Terms in the Event of Non-Payment. In the event that Buyer does
not pay for Product as required hereunder, in addition to DCC’s other remedies hereunder, including
termination as permitted in Article VIII hereof, DCC shall be entitled, notwithstanding any other
provisions in this Agreement to the contrary, to cease delivery of any further Product until any
arrearages are cured, including applicable late payment charges, and/or require payment of all
future orders and shipments [****]

ARTICLE V

SPECIFICATIONS; INSPECTION OF PRODUCT; PLANT

     Section 5.1 Specifications. All of the Product to be supplied by DCC shall meet the
specifications set forth in Schedule 1, which may be amended from time to time upon mutual
agreement (the “Specifications”).

     Section 5.2 Inspection of Product. Unless Buyer notifies DCC in writing within [****]
days of Delivery that any Product does not conform to the Specification, such shipment shall be
deemed to conform to the Specifications. If Buyer desires to submit a claim that any Product did
not meet the Specifications at the time of Delivery, Buyer shall submit documentary evidence of any
third party inspection at the time of Delivery as evidence of such claim, whereupon DCC shall have
the right to undertake its own inspection, including, of samples of Products at the time of
Delivery. Any disputes as to whether certain Products meet the Specification shall be settled in
accordance with Section 9.7. Buyer’s failure to notify DCC within the time period set forth in the
first sentence of this paragraph with respect to any Products Delivered shall irrevocably release
DCC from any obligations or liabilities for defective Product, including but not limited to any
warranties under Section 7.3, with regard to such Products (including for any latent defects, if
any).

5

 

     Section 5.3. Plant. Until completion of the Plant, Buyer shall have the right to
request periodic visits to the Plant while the Plant is being constructed and DCC and Buyer shall
discuss in good faith the timing and frequency of such visits, it being agreed that such visits
shall take place no sooner than one month from the date of such request, during normal business
hours and not unreasonably disrupt the ordinary course of business and construction of the Plant

ARTICLE VI

CONFIDENTIAL INFORMATION

     Section 6.1 Confidential Information. Any information provided by one Party to the
other Party which is confidential in nature shall be deemed confidential information (the
“Confidential Information”).

     Section 6.2 Restrictions On Use and Disclosure. Once any Confidential Information is
provided by one Party (the “Disclosing Party”) to the other Party (the “Receiving
Party”), the Receiving Party shall, and shall cause its respective directors, officers,
principals, members, employees, consultants, contractors, agents, advisors and representatives
(collectively, “Representatives”) (i) not to deliver, divulge, disclose or
communicate, or permit to be delivered, divulged, disclosed or communicated, to any third party,
directly or indirectly, any Confidential Information, (ii) to disclose or give access to,
or permit to be disclosed or given access to, any such Confidential Information, other than those
of its Representatives that have a need to know such Confidential Information for the purposes of
performing the Receiving Party’s obligations under this Agreement, (iii) to ensure that
such Representatives keep the Confidential Information confidential, and (iv) to take all
other reasonably necessary or advisable actions to preserve the confidentiality and security of the
Confidential Information.

     Section 6.3 Exclusions. The foregoing restrictions contained in Section 6.2 shall not
apply to Confidential Information that (i) is or becomes generally known to the public
through no fault of the Receiving Party or its Representatives including without limitation any
acts or omissions of the Receiving Party or its Representatives in violation of this Agreement,
(ii) is disclosed to the Receiving Party without obligation of confidentiality by a third
person who has a right to make such disclosure and the Receiving Party is able to document the
independent source, (iii) was in the possession of the Receiving Party at or prior to the
time of receipt from the Disclosing Party, as evidenced by contemporaneous, corroborated written
records, without being subject to another obligation of confidentiality or (iv) is independently
developed by the Receiving Party without reference to the Disclosing Party’s Confidential
Information.

     Section 6.4 Compelled Disclosure. If the Receiving Party or its Representatives is
required to disclose any Confidential Information otherwise than in accordance with this Agreement
by government authority or pursuant to any applicable laws, regulations, or

6

 

judicial orders, the Receiving Party shall provide the Disclosing Party with prompt prior
written notice of such request or requirement prior to disclosing the Confidential Information.

     Section 6.5 Press Releases. Except as permitted under this Article VI, neither Party
shall issue any press release or make any public announcement which includes or otherwise uses the
name of the other Party, or relates to this Agreement or to the performance hereunder in any public
statement or document, without the prior review and written approval of the other Party, which
approval shall not be unreasonably withheld or delayed. Any such review shall be completed as soon
as practicable, but in any event within five (5) days of receipt of the proposed statement or
document. Notwithstanding the foregoing, the Parties shall endeavor in good faith to agree upon
and issue a joint press release announcing the relationship between the parties promptly after the
date hereof.

     Section 6.6 Confidentiality of Agreement. The terms and conditions of this Agreement,
shall be treated as Confidential Information and shall not be disclosed by either Party to any
third party, except (i) with the Party’s consent, which consent shall not be unreasonably
withheld or delayed, (ii) as may be required by law or regulation or rules of a nationally
recognized stock exchange, (iii) to legal counsel, accountants, investors, lenders and
financial advisors, (iv) in connection with any action or claim to enforce its rights
hereunder or in any related transaction and (v) as reasonably required in connection with a
bona fide financing or sale transaction in which all or substantially all of a Party’s business,
assets or equity capital is proposed to be sold.

ARTICLE VII

WARRANTIES; DISCLAIMER; REMEDIES

     Section 7.1 Disclaimer of Warranties. EXCEPT AS SET FORTH IN THIS ARTICLE VII, DCC
DISCLAIMS ANY AND ALL WARRANTIES, EXPRESS OR IMPLIED, INCLUDING ANY WARRANTY OF MERCHANTABILITY,
FITNESS FOR A PARTICULAR PURPOSE, NON-INFRINGEMENT AND THOSE ARISING FROM A COURSE OF DEALING OR
USAGE OF TRADE.

     Section 7.2 Title. DCC warrants that it has good title to the Products sold to Buyer
hereunder and the right to sell them to Buyer free of any security interest, lien or any other
encumbrance whatsoever.

     Section 7.3 Damaged or Defective Product. DCC warrants that the Products Delivered
shall conform to the Specifications. In the event of Delivery of defective Products, upon notice
by Buyer to DCC pursuant to Section 5.2 above, DCC and Buyer shall discuss the appropriate method
of curing such defect, pursuant to which DCC and Buyer shall find an amicable solution to such
damage or defect, provided however, in the absence of agreement to the contrary, Buyer agrees [****]

7

 

provided however, DCC shall first allocate Products to Buyer under
option (i) above in a manner so that Buyer is treated no less favorably than if DCC had
allocated all available Products to all of its customers on a pro rata and equitable basis after
also taking into account DCC’s existing contractual obligations to its customers.

     Section 7.4 Failure to Purchase by Buyer. If Buyer fails to take Delivery of or
purchase [****] the Original Annual Quantity or Adjusted Annual Quantity, as applicable, for any
calendar year for any reason whatsoever, DCC shall be entitled to the remedies set forth in Section
4.1, provided that failure by Buyer to purchase [****] such Original Annual Quantity or Adjusted
Annual Quantity, as applicable, made available for Delivery shall not constitute a breach of this
Agreement if DCC shall have received [****] in respect of such applicable Original Annual Quantity
or Adjusted Annual Quantity, as applicable, in accordance with the [****] applicable for such
Original Annual Quantity or Adjusted Annual Quantity, as applicable.

     Section 7.5 Failure to Supply by DCC. If DCC is unable, after exerting commercially
reasonable efforts, to sell or Deliver all or any portion of the first [****] kilograms of the
aggregate amount of the Original Annual Quantities set forth in Section 1.1 (after giving effect to
Section adjustment pursuant to Section 1.3), Buyer’s sole remedy pursuant to this Agreement shall
be to terminate this Agreement.

     Section 7.6 Limitation of Liability. BUYER’S REMEDIES IN RESPECT OF ANY CLAIM
RELATING TO DEFECTIVE PRODUCTS SHALL BE LIMITED BY AND SUBJECT TO SECTION 7.3. IN NO EVENT SHALL
EITHER PARTY BE LIABLE TO THE OTHER PARTY FOR COSTS OF PROCUREMENT OF SUBSTITUTE GOODS, LOSS OF
PROFITS, OR FOR ANY INDIRECT, SPECIAL, CONSEQUENTIAL, INCIDENTAL, EXEMPLARY OR PUNITIVE DAMAGES,
WHETHER ARISING OUT OF CONTRACT, TORT, STRICT LIABILITY OR OTHERWISE RESULTING FROM OR RELATED TO
THIS AGREEMENT (WHETHER OR NOT SUCH PARTY KNEW OR SHOULD HAVE KNOWN OF THE POSSIBILITY OF ANY SUCH
DAMAGES).

     Section 7.7 Indemnity. A Party, (the “Indemnitor”) shall indemnify, defend
and hold the other Party and its officers, directors, employees, consultants, agents and other
representatives (the “Indemnitees”) harmless from and against any and all liability,
damage, loss, cost or expense (including reasonable attorneys’ fees) arising out of third party
claims or lawsuits (a “Claim”) related to or arising out of the Indemnitor’s breach of any
of its covenants, representations or warranties set forth in this Agreement. Upon the assertion of
any such claim or suit, the Indemnitees shall promptly notify the Indemnitor and the Indemnitor
shall appoint counsel reasonably acceptable to the affected Indemnitees to represent such
Indemnitees with respect to any claim or suit for which indemnification is sought. The Indemnitees
may select their own respective counsel, at the Indemnitor’s cost, upon notice to the Indemnitor;
provided, however, that they shall not settle any claim or suit hereunder without the prior written
consent of the Indemnitor.

8

 

ARTICLE VIII

TERM AND TERMINATION

     Section 8.1 Term. This Agreement shall commence upon the Effective Date and shall
remain in full force until December 31, 2015, unless earlier terminated pursuant to Section 8.2
below.

     Section 8.2 Termination.

     (a) Mutual Agreement. This Agreement may be terminated at any time upon mutual
agreement of the Parties.

     (b) Termination For Breach. Except as otherwise set forth herein, the failure
by a Party to comply in any material respect with any of the obligations contained in this
Agreement shall entitle the other Party to give notice to have the default cured. If such
default is material and not cured within sixty (60) days after the receipt of such notice,
or diligent steps have not begun to be taken to cure such default within thirty (30) days or
if by its nature such default is not capable of being cured, the other Party shall be
entitled to immediately terminate this Agreement.

     (c) Bankruptcy/Insolvency. If a Party (or its creditors or any other eligible
party) files for its liquidation, bankruptcy, reorganization, composition, dissolution or
other similar proceedings or arrangement, or if such Party is unable to pay any debts as
they become due, has explicitly or implicitly suspended payment of any debts as they became
due (except debts contested in good faith), or if the creditors of the such Party have taken
over its management, or if the relevant financial institutions have suspended clearing house
privileges with regard to such Party, then the other Party shall be entitled to immediately
terminate this Agreement.

     (d) No Plant. DCC may terminate this Agreement if it reasonably believes,
despite having exerted commercially reasonable efforts, that it will not be able to Deliver
the first [****] kilograms of the aggregate amount of the Original Annual Quantities in
Section 1.1 to Buyer. (after giving effect to Section adjustment pursuant to Section 1.3).
In the event of a termination of the Agreement by DCC under this Section 8.2(d) or Buyer
pursuant to Section 7.5, DCC’s obligations to sell and Deliver, and Buyer’s obligation to
purchase and receive, Products and Original Annual Quantities or Adjusted Annual Quantities,
as applicable, for all calendar years not Delivered prior to such termination shall be
deemed to be discharged in full without recourse and with prejudice.

     (e)
Conflicting Interest. If at any time, Buyer (together with any of
its affiliates) produces, or Buyer (together with any of
its affiliates) has acquired, or has agreed to acquire, a
greater than [****] percent ([****]%) stake in the
equity capital (including options, warrants, convertible/exchangeable
bonds and other similar securities, but excluding non-convertible
debt securities) of an entity that produces, any product which is
similar to or competes with the Products, Buyer shall provide immediate written notice to DCC and DCC may, at its sole discretion, terminate
this Agreement with immediate effect. In the event of termination by this Agreement by DCC
under this Section 8.2(e), DCC’s obligations

9

 

to sell and Deliver, and Buyer’s obligation to purchase and receive, Products and
Original Annual Quantities or Adjusted Annual Quantities, as applicable, for all calendar
years not Delivered prior to such termination shall be deemed to be discharged in full
without recourse.

     Section 8.3 Effect of Termination. Except as specifically set forth in Section
8.2(d), the expiration or termination of this Agreement shall not relieve the Parties of any
obligations accruing prior to such termination, and any such termination shall be without prejudice
to the rights of either Party against the other conferred on it by this Agreement. In addition,
the provisions of Article VI, VII, VIII and IX shall survive expiration or termination of this
Agreement for any reason for as long as necessary to permit their full discharge.

ARTICLE IX

MISCELLANEOUS

     Section 9.1 Force Majeure. Neither Party shall be responsible for suspension of its
performance under this Agreement (other than the obligation of payment) if such suspension is
caused by a shortage of raw materials, fire, flood, epidemics, quarantine restrictions, strikes,
lockouts or other labor disputes, freight embargoes, severe weather, riots, terrorism, acts of war,
acts of God or the public enemy or compliance with applicable laws, rules or regulations of any
governmental authority or by compliance with any order or decisions of any court, board or other
governmental authority or by any cause beyond the reasonable control of such Party, whose effects
are not capable of being overcome without commercially unreasonable expense to such Party
(“Force Majeure”); provided, however, that this Section 9.1 shall not relieve a Party of
its obligation to pay for any Product or other payment required by this Agreement. In addition, if
due to Force Majeure, DCC is unable to produce sufficient Products to meet all demands from
customers, DCC shall (a) inform Buyer of such reduction in production of Product;
(b) undertake commercially reasonable efforts to overcome such situation; and (c)
have the right to allocate production among its customers in a manner no less favorable to Buyer if
DCC had allocated production among its customers on a pro rata and equitable basis, after
consulting with Buyer. Buyer shall have no obligation to pay for Products not Delivered to Buyer
if such failure to Deliver is due to DCC claiming the occurrence of a Force Majeure. If DCC is
unable to meet its obligations hereunder due to a Force Majeure for more than 180 consecutive days,
Buyer shall have the right to terminate this Agreement with written notice to DCC.

     Section 9.2 Governmental Approvals. DCC shall obtain all necessary Korean
governmental approvals required for the export of the Products to Buyer. Buyer shall obtain all
other government approvals for the import of Products by Buyer.

     Section 9.3 Hierarchy among this Agreement and Purchase Orders. If there is a
conflict between or among the terms of this Agreement, its Schedules or a Purchase Order, the
following order of precedence shall apply: this Agreement, Schedules, and the Purchase Order;
provided, however, a specific written agreement to amend this Agreement (which contains a specific
reference to Section 9.6 of this Agreement) signed by the Parties that

10

 

expresses the intent of the Parties to modify this Agreement shall take precedence over this
Agreement.

     Section 9.4 Independent Contractors. The Parties hereto are independent contractors.
Neither Party to this Agreement nor any of its employees, customers or agents, shall be deemed to
be the representative, agent or employee of the other Party for any purpose whatsoever, nor shall
any of them have the right or authority to assume or create an obligation of any kind or nature,
express or implied, on behalf of the other, nor to accept service of any legal claims or notices
addressed to or intended for the other.

     Section 9.5 Notice. For the purpose of this Agreement, notices and all other
communications provided for in the Agreement shall be in writing, shall be deemed to have been duly
given when received and may be sent by personal delivery, facsimile (to the respective facsimile
number set forth below or last given by each Party to the other) or sent by express courier
(prepaid and addressed to the respective addresses set forth below or last given by each Party to
the other). The Parties’ respective initial addresses for purposes of receiving notices pursuant
to this Agreement shall be as follows:

	 	 	 	 	 
	 

	 	If to DCC:
	 	If to Buyer:
	 
	 	 	 	 
	 

	 	DC Chemical Co., Ltd.
	 	Evergreen Solar, Inc.
	 

	 	Oriental Chemical Building
	 	138 Bartlett Street
	 

	 	50, Sogong-Dong, Jung-Gu
	 	Marlboro, MA 01752
	 

	 	Seoul, 100-718
	 	U.S.A.
	 

	 	Korea
	 	Attn: Richarf G. Chleboski
	 

	 	Attn: Andy Kim
	 	Fax: +1-508-229-7722
	 

	 	Fax: +82-2-727-9559	 	 

     Section 9.6 Amendment; No Waiver. This Agreement cannot be amended, changed, modified
or supplemented orally, and no amendment, change, modification or supplement of this Agreement
shall be recognized nor have any effect, unless the writing in which it is set forth is signed by
both Parties, nor shall any waiver of any of the provisions of this Agreement be effective unless
in writing and signed by the Party to be charged therewith. The failure of either Party to
enforce, at any time, or for any period of time, any provision hereof or the failure of either
Party to exercise any option herein shall not be construed as a waiver of such provision or option
and shall in no way affect that Party’s right to enforce such provision or exercise such option.
No waiver of any provision hereof shall be deemed to be, or shall constitute, a waiver of any other
provision, or with respect to any succeeding breach of the same provision.

     Section 9.7 Governing Law; Jurisdiction.

     (a) This Agreement shall be governed by and construed and enforced in accordance with
the laws of Korea, without giving effect to the rules respecting its

11

 

conflicts of law principles. The United Nations Convention on Contracts for the
International Sale of Goods shall not apply.

     (b) The Parties hereby agree that any dispute arising under this Agreement, or in
connection with any breach thereof, shall be finally resolved through binding arbitration
conducted in administered by the ICC (as defined below) accordance with the rules and
procedures of the International Chamber of Commerce (“ICC”) by one (1) arbitrator
appointed in accordance with the applicable rules of the ICC. Any such arbitration shall be
held in Hong Kong. Any written evidence originally in a language other than English shall
be submitted in English translation accompanied by the original or a true copy thereof. The
costs of the arbitration, including administrative and arbitrators’ fees, shall be shared
equally by the Parties, and each Party shall bear its own costs and attorneys’ and witness’
fees incurred in connection with the arbitration. Any award may be entered in a court of
competent jurisdiction for a judicial recognition of the decision and applicable orders of
enforcement. The Parties may apply to any court of competent jurisdiction for a temporary
restraining order, preliminary injunction, or other interim or conservatory relief, as
necessary, without breach of this arbitration requirement and without any abridgment of the
powers of the arbitrator.

     (c) If any portion of this Agreement is held invalid by a court or tribunal of
competent jurisdiction, such portion shall be deemed to be of no force and effect and this
Agreement shall be construed as if such portion had not been included herein, provided
however, if the deletion of such provision materially impairs the commercial value of this
Agreement to either Party, the parties shall attempt to renegotiate such provision in good
faith.

     Section 9.8 Entire Agreement. This Agreement constitutes the entire agreement between
the Parties with respect to the subject matter hereof and supersedes all prior agreements,
understandings and arrangements, oral or written, between the Parties with respect to the subject
matter hereof. No agreement or representations, oral or otherwise, express or implied, with
respect to the subject matter hereof have been made either Party which is not expressly set forth
in this Agreement.

     Section 9.9 Assignment. Either Party may assign or otherwise transfer this Agreement
to its subsidiary, affiliate or other successor in the event of a merger, acquisition or change of
control of such Party or to the purchaser of substantially all of the assets of such Party. Except
as provided in the preceding sentence, neither Party shall have the right to assign or otherwise
transfer this Agreement, or any of its rights or obligations hereunder, without the prior written
consent of the other Party.

     Section 9.10 Non-Exclusive Agreement. This Agreement is a non-exclusive agreement.
DCC expressly reserves the right to contract with others to supply any of its products or services.
Buyer expressly reserves the right to contract with others for any of the products or services it
may require.

12

 

     Section 9.11 Successors. This Agreement shall inure to the benefit of and be binding
upon each of the Parties and their respective permitted successors and assigns.

     Section 9.12 Headings. The headings used in this Agreement are for convenience of
reference only and shall not affect the meaning or construction of this Agreement.

     Section 9.13 Word Meanings. Words such as herein, hereinafter, hereof and hereunder
refer to this Agreement as a whole and not merely to a section or paragraph in which such words
appear, unless the context otherwise requires. The singular shall include the plural, and each
masculine, feminine and neuter references shall include and refer also to the others, unless the
context otherwise requires.

     Section 9.14 Language. The official language of this Agreement is English. All
contract interpretations, notices and dispute resolutions shall be in English. Any attachments or
amendments to this Agreement shall be in English. Translations of any of these documents shall not
be construed as official or original versions of such documents.

     Section 9.15 Counterparts. This Agreement may be executed in counterparts or
duplicate originals, both of which shall be regarded as one and the same instrument, and which
shall be the official and governing version in the interpretation of this Agreement.

[Signature pages follow]

13

 

     IN WITNESS WHEREOF, the Parties hereto have caused this Agreement to be executed by their
respective duly authorized officers as of the Effective Date.

	 	 	 	 	 
	 	DC Chemical Co., Ltd.

 	 
	 	By:  	/s/ Woo Sug Baik
 	 
	 	Name:	Woo Sug Baik 	 
	 	Title:	Chief Executive Officer 	 
	 

[Signature page to Supply Agreement]

 

 

	 	 	 	 	 
	 	Evergreen Solar, Inc.

 	 
	 	By:  	/s/ Richard C. Chleboski
 	 
	 	Name:	Richard G. Chleboski 	 
	 	Title:	Vice President 	 
	 

[Signature page to Supply Agreement]

 

 

Schedule 1

Specifications

TO BE DETERMINED BY MUTUAL AGREEMENT BASED ON TESTS CONDUCTED AT THE PLANT UPON MANUFACTURE OF
PRODUCT THEREIN

PRODUCT SHALL BE OF SOLAR GRADE

UNLESS OTHERWISE AGREED, THE PRODUCT SHALL BE SHIPPED TO BUYER IN [****]

Source: [{"source": "alea-institute/alea-institute/kl3m-data-edgar-agreements/train-00146-of-00352.parquet"}, [{"source": "alea-institute/alea-institute/kl3m-data-edgar-agreements/train-00146-of-00352.parquet"}]]