Exhibit 10.40
Confidential Materials omitted and filed separately with the
Securities and Exchange Commission. Asterisk denote omissions.
FIRST AMENDMENT TO
LICENSE AND COLLABORATION AGREEMENT
     This First Amendment to License and Collaboration Agreement (this
“Amendment”) is entered into as of November 2, 2009 (the “Amendment Effective
Date”), by and between Alnylam Pharmaceuticals, Inc., a corporation organized
and existing under the laws of the State of Delaware and having its principal
office at 300 Third Street, Cambridge, Massachusetts 02142 (“Alnylam”), and
Cubist Pharmaceuticals, Inc., a corporation organized and existing under the
laws of the State of Delaware and having its principal office at 65 Hayden
Avenue, Lexington, Massachusetts 02421 (“Cubist”). Capitalized terms used, but
not defined herein, shall have the meanings ascribed to such terms in the
License and Collaboration Agreement (the “Agreement”) entered into as of the 9th
day of January, 2009 (the “Agreement Effective Date”), by and between Alnylam
and Cubist.
INTRODUCTION
     WHEREAS, on the Agreement Effective Date, Alnylam and Cubist entered into
the Agreement pursuant to which, inter alia, the Parties agreed to collaborate
in the Development of RNAi Products targeting RSV, including the candidate RNAi
Product known as ALN-RSV01;
     WHEREAS, the JSC has designated a second candidate RNAi Product as
ALN-RSV02 and the Parties have completed certain Development activities with
respect to ALN-RSV01 and ALN-RSV02;
     WHEREAS, the Parties now desire to focus their collaborative Development
efforts on ALN-RSV02;
     WHEREAS, Alnylam desires to continue the Development of ALN-RSV01 as an
RNAi Product targeting RSV in adult lung transplant patients; and
     WHEREAS, Cubist desires to grant Alnylam certain rights to continue the
Development of ALN-RSV01 on the terms and conditions set forth in this
Amendment.
     NOW, THEREFORE, in consideration of the foregoing premises and the mutual
covenants herein contained, the Parties hereby agree as follows:
     1. (a) New Definitions. Article I of the Agreement is amended by adding the
following section as Section 1.113 thereto:
     “Section 1.113 Amendment Definitions. As used in this Agreement, each of
the following additional terms shall have the meanings set forth below:
     “Adult Transplant Field”. Adult Transplant Field means the treatment or
prophylaxis of RSV infection in human transplant patients eighteen (18) years
old or greater.
     “ALN-RSV01 Development Costs”. ALN-RSV01 Development Costs means
Development Costs [**] Development of ALN-RSV01 in the Adult Transplant Field
and shall

 

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not include any costs shared by the Parties under the Development Plan. For
purposes of clarity, costs up to a limit of $[**] associated with [**], to the
extent incurred under the direction of the JSC, shall be costs shared by the
Parties under the Development Plan and shall not be ALN-RSV01 Development Costs
for purposes hereof.
     “ALN-RSV01 Failure”. ALN-RSV01 Failure means the earlier to occur of: (i)
[**].
     “ALN-RSV01 Phase IIb Clinical Study”. ALN-RSV01 Phase IIb Clinical Study
means a Phase II Clinical Study of ALN-RSV01 conducted by Alnylam, as described
in Exhibit J.
     “Amendment Effective Date”. Amendment Effective Date means November 2,
2009.
     “Interim Period”. Interim Period means the period beginning on the
Amendment Effective Date and continuing until the earliest of (a) Cubist’s
exercise of its Opt-in Right pursuant to Section 4A.2(a), (b) the end of the
Opt-in Period after Cubist’s receipt of a Study Completion Package, or (c) an
ALN-RSV01 Failure.”
     “Opt-in Fee”. Opt-in Fee means, subject to the terms of Section 4A.2(a),
the following: If Alnylam has met the Success Criteria specified under clause
(a) of Part B of Exhibit K, but not the Success Criteria specified under clause
(b) of Part B of Exhibit K, the Opt-in Fee will mean [**] percent ([**]%) of the
ALN-RSV01 Development Costs incurred by Alnylam, payable in accordance with
Section 4A.2(a), for the Development of ALN-RSV01 in the Adult Transplant Field
during the Interim Period. If Alnylam has met the Success Criteria specified
under clause (b) of Part B of Exhibit K, the Opt-in Fee will mean [**] percent
([**]%) of the ALN-RSV01 Development Costs incurred by Alnylam, payable in
accordance with Section 4A.2(a), for the Development of ALN-RSV01 in the Adult
Transplant Field during the Interim Period.
     “Opt-in Right”. Opt-in Right shall have the meaning set forth in
Section 4A.2(a) of this Agreement.
     “Opt-in Period”. Opt-in Period shall have the meaning set forth in
Section 4A.2(a) of this Agreement.
     “Study Completion Package”. Study Completion Package means a data package
meeting the requirements set forth in Part A of Exhibit K.
     “Success Criteria” shall have the meaning set forth in Part B of Exhibit K.
     “Success Statement” means a written statement by Alnylam that the Success
Criteria have been met.””
     (b) Definition of RSV01 Product. Section 1.101 is amended in its entirety
to be and read as follows:

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     “Section 1.101 “RSV01 Product.” RSV01 Product means any product containing
as its sole active ingredient Alnylam’s proprietary composition known as
ALN-RSV01. ALN-RSV01 is described on Exhibit B.”
     2. Development of ALN-RSV01 by Alnylam; Cubist Opt-In Right. The following
provisions are added as new Article IVA of the Agreement, immediately prior to
Article 5 of the Agreement:
“ARTICLE IVA
DEVELOPMENT OF ALN-RSV01 BY ALNYLAM; CUBIST OPT-IN RIGHT
     Section 4A.1 Interim Period Activities. The Parties agree that,
notwithstanding anything to the contrary in the Agreement, the following rights
and obligations shall apply during the Interim Period:
          (a) Cubist shall not conduct Development of ALN-RSV01.
          (b) Subject to paragraph (c), the JSC shall have no authority with
respect to ALN-RSV01, and Alnylam’s Development of ALN-RSV01 shall not be
subject to the Development Plan or any related budget.
          (c) Alnylam may conduct, and shall have sole decision-making authority
with respect to, any Development activities with respect to ALN-RSV01, in
Alnylam’s discretion and at Alnylam’s sole expense, without input from the JSC
or Cubist; provided, however, that:
          (i) Alnylam’s rights to Develop ALN-RSV01 will be limited to the Adult
Transplant Field;
          (ii) Alnylam shall provide to the JSC copies of draft and final
protocols for any clinical study to be conducted with ALN-RSV01, including, but
not limited to, the protocol for the ALN-RSV01 Phase IIb Clinical Study. Alnylam
will provide drafts of such protocols at least [**] days prior to initiation of
the applicable clinical trial, and shall consider in good faith the JSC’s
comments, [**];
          (iii) Alnylam will provide the JSC with updates at quarterly JSC
meetings regarding Alnylam’s Development activities with respect to ALN-RSV01;
          (iv) Alnylam shall share with the JSC all data and know-how related to
the Development of ALN-RSV01 as if such activities had been conducted under the
Development Plan; and
          (v) Alnylam will not Develop ALN-RSV01 in such a way [**]; provided,
however, that nothing contained in the concept sheet attached hereto as
Exhibit J [**] Cubist’s Development or potential Commercialization of ALN-RSV02;

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          provided further, however, that Alnylam shall not have any obligation
to conduct any Development activities with respect to ALN-RSV01 and may
discontinue any and all such Development at any time in Alnylam’s sole
discretion.
     In the event the Parties disagree as to whether Alnylam’s Development of
ALN-RSV01 [**], the matter shall be resolved in the manner set forth in
Article XII of this Agreement, and the Parties shall use good faith efforts to
complete such arbitration within [**] days. Alnylam shall not proceed with
further clinical Development of ALN-RSV01 until such matter has been resolved.
          (d) The licenses granted to Cubist under Section 3.1 shall continue to
apply to ALN-RSV01 as a Licensed Product and the Adult Transplant Field as part
of Field, provided, that Cubist shall not exercise any rights under the license
granted to Cubist pursuant to Section 3.1 with respect to RSV01 Products, and
Cubist shall not, during the Interim Period, sublicense any rights thereunder,
nor shall Cubist grant any rights to, or enter any agreement with, any Third
Party for the sale of any RSV01 Product.
          (e) Neither Cubist nor any of its Affiliates shall, directly or
indirectly, [**] or grant rights to a Third Party to do any of the foregoing,
except that Cubist and the Affiliates shall be permitted to [**], and to allow
Third Parties to [**] under this Agreement to the extent that, [**], subject to
the resolution of any disagreement that the Parties may have regarding such
opinion as set forth in the final sentence of this Section 4A.1(e), or, [**],
and further provided that Cubist and its Affiliates do not, during the Interim
Period, [**] or grant a Third Party the right to do so. In the event the Parties
disagree as to whether Cubist’s [**] that the [**], the matter shall be resolved
in the manner set forth in Article XII of this Agreement, and the Parties shall
use good faith efforts to complete such arbitration within [**] days.
          (f) Without limiting the scope of any other limitation under the
Agreement, neither Alnylam nor any of its Affiliates shall, directly or
indirectly, Develop, Manufacture or Commercialize ALN-RSV01 or any RSV01 Product
for use in any indication other than in the Adult Transplant Field anywhere in
the Territory or grant rights to a Third Party to do any of the foregoing.
          (g) The provisions of Sections 4.4 and 4.5 shall remain in effect with
respect to any Development Costs incurred with respect to ALN-RSV01 on or before
the Amendment Effective Date. The provisions of [**] shall not apply to
ALN-RSV01 unless and until [**], then upon such exercise by Cubist of its Opt-in
Right, the Parties shall [**] and the Parties hereby waive any failure to comply
with [**] prior to such time.
          (h) Alnylam shall have the right to incur ALN-RSV01 Development Costs
in its sole discretion (and, notwithstanding the definition of Development
Costs, without any requirement that such costs be incurred in accordance with
the Development Plan or any related budget); provided that, except for any
reimbursement of ALN-RSV01 Development Costs that Alnylam may receive from
Cubist through Cubist’s payment to Alnylam of the Opt-in Fee if Cubist exercises
its Opt-in Right pursuant to Section 4A.2(a), Alnylam shall be solely
responsible for such Development Costs.

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          (i) Cubist shall not be responsible for ALN-RSV01 Development Costs
incurred by Alnylam during the Interim Period unless Cubist exercises its Opt-in
Right pursuant to Section 4A.2(a), in which case Cubist shall reimburse Alnylam
for a portion of the ALN-RSV01 Development Costs incurred by Alnylam during the
Interim Period through Cubist’s payment to Alnylam of the applicable Opt-in Fee.
          (j) Section 10.11(b) shall be modified to add a clause (iv) to read in
its entirety as follows: “(iv) the Development, Manufacture, Commercialization
or use of ALN-RSV01 or RSV01 Products by Alnylam or any of its Related Parties
during the Interim Period.”
          (k) Section 10.11(c)(ii) shall be modified to add the following after
the word “Asia”: “or of ALN-RSV01 or RSV01 Products during the Interim Period.”
     Section 4A.2 Opt-In Right.
          (a) Following completion of the ALN-RSV01 Phase IIb Clinical Study (if
Alnylam elects to conduct such study), if the results of such study meet the
Success Criteria (as defined in Exhibit K), Alnylam shall promptly prepare and
provide to Cubist the Study Completion Package, including the applicable Success
Statement. Alnylam shall also provide Cubist with the opportunity to discuss the
information contained in the Study Completion Package with Alnylam in a
face-to-face meeting to occur within [**] of the written request of Cubist,
which such request shall be delivered to Alnylam no later than [**] after
receipt of the Study Completion Package. Cubist may elect to resume its
participation in the Development of ALN-RSV01 (the “Opt-in Right”), by
delivering written notice of Cubist’s exercise of such right to Alnylam and
paying to Alnylam the applicable Opt-in Fee (or portion thereof) within [**]
after Cubist’s receipt of the Study Completion Package (the “Opt-in Period”).
Except as otherwise set forth in this paragraph, the payment of the Opt-in Fee
shall be made as follows: (1) an initial payment equal to [**] of the ALN-RSV01
Development Costs incurred by Alnylam for the Development of ALN-RSV01 in the
Adult Transplant Field during the Interim Period and (2) a subsequent payment,
to be made in amount equal to (x) [**] of the ALN-RSV01 Development Costs
incurred by Alnylam for the Development of ALN-RSV01 in the Adult Transplant
Field during the Interim Period, if [**], or (y) [**] of the ALN-RSV01
Development Costs incurred by Alnylam for the Development of ALN-RSV01 in the
Adult Transplant Field during the Interim Period if [**]; provided, however, if
the terms set forth in clauses (x) and (y) are not met, then no subsequent
payment shall be due by Cubist with respect to the Opt-in Fee. In addition,
Cubist may, at its election, exercise its Opt-In Right at any time prior to the
submission of a Study Completion Package by Alnylam. In the event that Cubist
exercises its Opt-in Right prior to receipt of the Study Completion Package, the
Opt-in Fee will be equal to [**] of the ALN-RSV01 Development Costs incurred by
Alnylam for the Development of ALN-RSV01 in the Adult Transplant Field during
the Interim Period; and Cubist will pay an additional Opt-in Fee of [**] of the
ALN-RSV01 Development Costs incurred by Alnylam for the Development of ALN-RSV01
in the Adult Transplant Field during the Interim Period if, [**].
          (b) Following completion of the ALN-RSV01 Phase IIb Clinical Study (if
Alnylam elects to conduct such study), if the results of such study do not meet
the Success

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Criteria (as defined in either clause (a) or clause (b) of Part B of Exhibit K)
and Alnylam is not able to make a Success Statement, then, subject to
Section 4A.5, the Interim Period shall continue and Alnylam shall have the
right, but not the obligation, to conduct additional Development of ALN-RSV01
until such time, if any, as Alnylam is able to provide to Cubist a Study
Completion Package that includes a Success Statement.
     Section 4A.3 Effect of Opt-In. Following Alnylam’s receipt of Cubist’s
notice of exercise of its Opt-in Right pursuant to Section 4A.2(a), the Interim
Period shall expire and the Agreement shall again apply in full to the
Development, Manufacture and Commercialization of ALN-RSV01 and RSV01 Products;
provided, however, that the Parties agree that in such circumstances, the
milestone payments to be paid by Cubist with respect to the Development of
ALN-RSV01 solely in the Adult Transplant Field in accordance with Sections 4.7
and 7.2 will be [**] of those set forth in Section 4.7(a)(vi) or Section 7.2, as
the case may be.
Following such exercise by Cubist of its Opt-in Right, the final sentence of
Section 4.7(a)(vi) shall be deleted and the following shall be inserted in its
place:
“The milestone payments set forth in this Section 4.7(a)(vi) shall be paid only
once, upon the first achievement of the applicable milestone event by the first
Licensed Product to achieve such milestone event; provided that if any such
milestone event is first achieved by an RSV01 Product solely in the Adult
Transplant Field following an exercise by Cubist of its Opt-in Right such that,
in accordance with Section 4A.3, Cubist pays only [**] of the amount set forth
in the table above in connection with the achievement of such milestone, then an
additional [**] of such milestone amount shall be paid by Cubist if such
milestone event is subsequently achieved by (a) an RSV02 Product or an
Additional RSV Product, or (b) an RSV01 Product outside the Adult Transplant
Field. For the avoidance of doubt, following the Amendment Effective Date,
Cubist shall not be required to pay more than an aggregate of [**] of the
applicable amount set forth in the table above with respect to achievement(s) of
the corresponding milestone amount. Notwithstanding the foregoing, the milestone
payment reduction under the first paragraph of Section 4A.3 shall not apply in
the event that the triggering event for such milestone is achieved by an RSV01
Product outside the Adult Transplant Field.”
Following such exercise by Cubist of its Opt-in Right, the final sentence of
Section 7.2 shall be deleted and the following shall be inserted in its place:
“The milestone payments set forth in this Section 7.2 shall be paid only once,
upon the first achievement of the applicable milestone event by the first
Licensed Product to achieve such milestone event; provided that if any such
milestone event is first achieved by an RSV01 Product solely in the Adult
Transplant Field following an exercise by Cubist of its Opt-in Right such that,
in accordance with Section 4A.3, Cubist pays only [**] of the amount set forth
in the table above in connection with the achievement of such milestone, then an
additional [**] of such milestone amount shall be paid by Cubist if such
milestone event is subsequently achieved by (a) an RSV02 Product or an
Additional RSV Product, or (b) an RSV01 Product outside the Adult Transplant
Field. For the avoidance of doubt, following the Amendment Effective Date,
Cubist shall not be required to pay more than an aggregate of [**] of the
applicable amount set forth in the

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table above with respect to achievement(s) of the corresponding milestone
amount. Notwithstanding the foregoing, the milestone payment reduction under the
first paragraph of Section 4A.3 shall not apply in the event that the triggering
event for such milestone is achieved by an RSV01 Product outside the Adult
Transplant Field.”
     Section 4A.4 Failure to Opt-In. If Alnylam provides a complete Study
Completion Package under Section 4A.2(a) and has complied with the terms of this
Article IVA, and Cubist does not exercise its Opt-in Right pursuant to
Section 4A.2(a) within the Opt-in Period, then Cubist’s Opt-in Right pursuant to
Section 4A.2(a) and the Interim Period shall both expire and the Parties’
respective rights and obligations with respect to ALN-RSV01 and RSV01 Products
shall be modified as follows, subject to Section 4A.5:
     (a) RSV01 Products shall cease to be Licensed Products and, for the
avoidance of doubt, Cubist’s licenses pursuant to Section 3.1 shall terminate
with respect to RSV01 Products;
     (b) The definition of “Field” set forth in Section 1.46 shall be amended
and restated in its entirety to read as follows:
     “Section 1.46 “Field”. Field means the treatment or prophylaxis of diseases
in humans, but excluding [**].”
     (c) Neither Cubist nor any of its Affiliates shall, directly or indirectly,
[**] or grant rights to a Third Party to do any of the foregoing, except that
Cubist and the Affiliates shall be permitted to [**], and to allow Third Parties
to [**] under this Agreement to the extent that, [**], subject to the resolution
of any disagreement that the Parties may have regarding such [**] as set forth
in the final sentence of this Section 4A.4(c), or, [**], and further provided
that Cubist and its Affiliates do not, following the failure of Cubist to
exercise its Opt-in Right during the Opt-in Period, [**] or grant a Third Party
the right to do so. In the event the Parties disagree as to whether Cubist’s
[**] that the [**] of a [**], the matter shall be resolved in the manner set
forth in Article XII of this Agreement, and the Parties shall use good faith
efforts to complete such arbitration within [**].
     (d) Neither Alnylam nor its Affiliates shall, directly or indirectly
develop, manufacture, or commercialize ALN-RSV01 or any RSV01 Product in any
other indication other than in the Adult Transplant Field or grant rights to a
Third Party to do any of the foregoing. The limitations under the preceding
sentence shall be deemed to prevent Alnylam or any of its Affiliates from
publishing, presenting or discussing in any context use of ALN-RSV01 or RSV01
Products outside the Adult Transplant Field and from allowing a Third Party to
do any of the foregoing; provided, however, that Alnylam and its Affiliates may
publish the results of clinical trials of ALN-RSV01 in the Adult Transplant
Field without limitation provided that Alnylam provide a draft of such
publication to Cubist for informational purposes at least [**] prior to
dissemination. Cubist and its Affiliates, on the one hand, and Alnylam and its
Affiliates, on the other hand, shall [**].
     (e) RSV01 Products that are made, used, offered for sale, sold or imported
for the Adult Transplant Field by Alnylam or any of its Affiliates or any Third
Party to which Alnylam

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or any of its Affiliates grants rights shall be deemed not to be Directly
Competitive Products except to the extent that Alnylam and its Affiliates and
such Third Parties fail to be in compliance with paragraph (d) and, for the
avoidance of doubt, the restrictions set forth in Section 10.1 shall not apply
with respect to such RSV01 Products that are made, used, offered for sale, sold
or imported for the Adult Transplant Field except to the extent that Alnylam and
its Affiliates and such Third Parties fail to be in compliance with paragraph
(d).
     (f) [**] ALN-RSV01 or RSV01 Products, provided that:
          (i) Alnylam shall share information and data with respect to worldwide
development, manufacture and commercialization of ALN-RSV01 and RSV01 Products
with Cubist and the JSC to the same extent as [**];
          (ii) Alnylam shall provide to the JSC copies of draft and final
protocols for any clinical study to be conducted with ALN-RSV01, and shall
consider in good faith the JSC’s comments. Alnylam will provide drafts of such
protocols at least [**] prior to initiation of the applicable clinical trial,
and shall consider in good faith the JSC’s comments;
          (iii) Alnylam will provide the JSC with updates at quarterly JSC
meetings regarding Alnylam’s Development, manufacturing and Commercialization
activities with respect to ALN-RSV01; and
          (iv) Alnylam will not Develop ALN-RSV01 in such a way [**] Cubist’s
Development or potential Commercialization of ALN-RSV02; provided, however, that
nothing contained in the protocol attached hereto as Exhibit J [**] Cubist’s
Development or potential Commercialization of ALN-RSV02. In the event the
Parties disagree as to whether Alnylam’s Development of ALN-RSV01 [**] Cubist’s
Development or potential Commercialization of ALN-RSV02, the matter shall be
resolved in the manner set forth in Article XII of this Agreement, and the
Parties shall use good faith efforts to complete such arbitration within [**]
days. Alnylam shall not proceed with further clinical Development of ALN-RSV01
until such matter has been resolved.
     (g) Cubist shall not be responsible for Development Costs incurred by
Alnylam for the Development of ALN-RSV01 or RSV01 Products following the Interim
Period.
     (h) Cubist shall, at Alnylam’s cost, as promptly as practicable, transfer
to Alnylam or Alnylam’s designee: (i) possession and ownership of [**] the
Development or Manufacture of RSV01 Products and (ii) copies of [**] the
Development or Manufacture of RSV01 Products, including all [**] RSV01 Products
[**], in each case as requested by Alnylam and to the extent not originally
obtained by Cubist from Alnylam, and provided Cubist may maintain copies of each
such document transferred to Alnylam under this Section.
     (i) Cubist shall, at Alnylam’s cost, execute all documents and take all
such further actions as may be reasonably requested by Alnylam in order to give
effect to the foregoing clauses (a) through (h) as soon as practicable.

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     Section 4A.5 Delays in Development and ALN-RSV01 Failure.
     (a) If (x) Alnylam issues a Success Statement, (y) Cubist has not exercised
its Opt-in Right and (z) Alnylam fails to either (i) [**] or (ii) [**], as
indicated in such Success Statement, then Alnylam shall provide Cubist with
another Study Completion Package [**], and Cubist shall have the right to
exercise its Opt-in Right at such time in accordance with the terms hereof;
provided, however, that Alnylam may have [**]. In the event an ALN-RSV01 Failure
occurs, then, if Cubist has not previously exercised its Opt-In Right, this
Article 4A shall no longer have any force or effect and the Agreement shall
again apply in full to the Development, Manufacture and Commercialization of
ALN-RSV01 and RSV01 Products in the Field as defined on the Effective Date.
     (b) The Parties agree that in the event that there is an ALN-RSV01 Failure
in accordance with Section 4A.5(a), then the milestone payments to be paid by
Cubist with respect to the Development of ALN-RSV01 solely in the Adult
Transplant Field in accordance with Sections 4.7 and 7.2 will be [**] of those
set forth in Section 4.7(a)(vi) or Section 7.2, as the case may be.
Following such exercise by Cubist of its Opt-in Right, the final sentence of
Section 4.7(a)(vi) shall be deleted and the following shall be inserted in its
place:
“The milestone payments set forth in this Section 4.7(a)(vi) shall be paid only
once, upon the first achievement of the applicable milestone event by the first
Licensed Product to achieve such milestone event; provided that if any such
milestone event is first achieved by an RSV01 Product solely in the Adult
Transplant Field such that, in accordance with Section 4A.5(b), Cubist pays only
[**] of the amount set forth in the table above in connection with the
achievement of such milestone, then an additional [**] of such milestone amount
shall be paid by Cubist if such milestone event is subsequently achieved by
(a) an RSV02 Product or an Additional RSV Product, or (b) an RSV01 Product
outside the Adult Transplant Field. For the avoidance of doubt, following the
Amendment Effective Date, Cubist shall not be required to pay more than an
aggregate of [**] of the applicable amount set forth in the table above with
respect to achievement(s) of the corresponding milestone amount. Notwithstanding
the foregoing, the milestone payment reduction under the first paragraph of
Section 4A.3 shall not apply in the event that the triggering event for such
milestone is achieved by an RSV01 Product outside the Adult Transplant Field.”
Following an ALN-RSV01 Failure, as described under Section 4.A.5(a), the final
sentence of Section 7.2 shall be deleted and the following shall be inserted in
its place:
“The milestone payments set forth in this Section 7.2 shall be paid only once,
upon the first achievement of the applicable milestone event by the first
Licensed Product to achieve such milestone event; provided that if any such
milestone event is first achieved by an RSV01 Product solely in the Adult
Transplant Field such that, in accordance with Section 4A.5(b), Cubist pays only
[**] of the amount set forth in the table above in connection with the
achievement of such milestone, then an additional [**] of such milestone amount
shall be paid by Cubist if such milestone event is subsequently

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achieved by (a) an RSV02 Product or an Additional RSV Product, or (b) an RSV01
Product outside the Adult Transplant Field . For the avoidance of doubt,
following the Amendment Effective Date, Cubist shall not be required to pay more
than an aggregate of [**] of the applicable amount set forth in the table above
with respect to achievement(s) of the corresponding milestone amount.
Notwithstanding the foregoing, the milestone payment reduction under the first
paragraph of Section 4A.3 shall not apply in the event that the triggering event
for such milestone is achieved by an RSV01 Product outside the Adult Transplant
Field.”
     4A.6 Cubist shall, at Alnylam’s request, grant to Alnylam a fully paid-up,
non-royalty-bearing, perpetual, worldwide, exclusive right and license, with the
right to grant sublicenses, under the Cubist Collaboration IP, to make, have
made, use, offer for sale, sell and import RSV01 Products in the Adult
Transplant Field. If Alnylam elects to receive such license, (a) Alnylam will
pay to Cubist a royalty on Net Sales of such products (such definition modified
accordingly for this purpose) in the amount of [**] of the royalty rate that
would apply to a product for which Cubist’s termination takes effect after the
First Opt-Out Milestone but prior to the Second Opt-Out Milestone in
Section 11.4(d) (i.e., the first column of the table in Section 11.4(d)), and
(b) the provisions of Sections 11(e) shall apply; provided, however, that the
royalty payable to Cubist in respect of such license shall never be [**] as a
result of the grant of such license to Alnylam and Alnylam’s exercise of the
rights thereunder.
     3. New Exhibits. Exhibit J and Exhibit K attached to this Amendment are
hereby appended to the Agreement immediately following Exhibit I to the
Agreement.
     4. Miscellaneous. The Parties hereby confirm and agree that, as amended
hereby, the Agreement remains in full force and effect and is a binding
obligation of the Parties hereto. This Amendment may be executed in
counterparts, each of which shall be deemed an original, and all of which
together shall constitute one and the same instrument.
[Remainder of page intentionally left blank]

-10-

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     IN WITNESS WHEREOF, Alnylam and Cubist have caused this Agreement to be
duly executed by their authorized representatives under seal, in duplicate on
the dates written herein below.

            ALNYLAM PHARMACEUTICALS, INC.
      By:   /s/ John Maraganore         Title: Chief Executive Officer       
Date: November 2, 2009        CUBIST PHARMACEUTICALS, INC.
      By:   /s/ Steven C. Gilman         Title: Chief Scientific Officer, Senior
Vice President, Discovery and
Non-Clinical Development       Date: November 2, 2009  

-11-

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EXHIBIT J
ALN-RSV01 Phase IIb Clinical Study
ALN-RSV01-109 PROTOCOL SYNOPSIS

     
Protocol Title:
  [**] in lung transplant patients infected with respiratory syncytial virus
(RSV)
 
   
Indication:
  Lung transplant patients with RSV infection
 
   
Protocol Number:
  ALN-RSV01-109
 
   
Phase of Development:
  Phase 2b
 
   
Design:
  [**]
 
   
Study Sites:
  [**]
 
   
Investigational Drug:
  ALN-RSV01
 
   
Dosage, Route of Administration and Duration of Treatment of Investigational
Drug:
  [**]
 
   
Control Drug:
  [**]
 
   
Dosage, Route of Administration and Duration of Treatment of Control Drug:
  [**]
 
   
Time on Study:
  [**]
 
   
Primary Objective:
  [**]
 
   
Secondary Objectives:
  [**]
 
   
Sample Size:
  Up to 76 lung transplant patients infected with RSV.
 
   
Key Inclusion Criteria:
  [**]

 

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(ALNYLAM LOGO) [b78674b7867400.gif]
  ALN-RSV01
ALN-RSV01-109 Protocol Concept Sheet  

 

     
Key Exclusion Criteria:
  [**]
 
   
Safety Assessments:
  [**]
 
   
Efficacy Assessments:
  [**]
 
   
Resistance Monitoring
  [**]
 
   
Committees for BOS Adjudication and Virologic Monitoring
  [**]
 
   
Study Endpoints:
  [**]
 
   
Statistical Methodology:
  [**]
 
   

 

         
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  ALN-RSV01
ALN-RSV01-109 Protocol Concept Sheet  

 
[**]
A total of four pages were omitted pursuant to request for confidential
treatment.
 

         
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(ALNYLAM LOGO) [b78674b7867400.gif]
  ALN-RSV01
ALN-RSV01-109 Protocol Concept Sheet  

 
EXHIBIT K
A. Study Completion Package
     The Study Completion Package shall be comprised of the following: [**].
B. Success Criteria
     The Success Criteria will be deemed to have been met if the results of the
ALN-RSV01 Phase IIb Clinical Trial achieve the following:
     [**].
        .
 

         
23 September 2009
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