Exhibit 10.57  CONFIDENTIAL TREATMENT  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:  
 *Confidential
Treatment Requested.  Omitted portions
filed with the Securities and Exchange Commission (the Commission).


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 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.  
 *Confidential Treatment Requested.  Omitted portions filed with the Commission.  2


(b)           Definition of RSV01 Product.  Section 1.101 is amended in its entirety
to be and read as follows:  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  
 *Confidential
Treatment Requested.  Omitted portions
filed with the Commission.  3


(v) Alnylam will not
Develop ALN-RSV01in 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;  providedfurther, 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 whetherAlnylam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 []*
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, neitherAlnylam 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 theAmendment
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  
 *Confidential Treatment Requested.  Omitted portions filed with the Commission.  4


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.  (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  
 *Confidential Treatment Requested.  Omitted portions filed with the Commission.  5


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
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.3Effect 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  
 *Confidential Treatment Requested.  Omitted portions filed with the Commission.  6


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.  Section 4A.4Failure 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, if []*, 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)           NeitherAlnylam 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 []*  
 *Confidential Treatment Requested.  Omitted portions filed with the Commission.  7


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 or any of its Affiliates grants rightsshall 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 JSCto 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-RSV01in 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  
 *Confidential Treatment Requested.  Omitted portions filed with the Commission.  8


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.  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:  
 *Confidential Treatment Requested.  Omitted portions filed with the Commission.  9


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 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 afully 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]  
 *Confidential Treatment Requested.  Omitted portions filed with the Commission.  10


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 MaraganoreTitle:
  Chief
  Executive OfficerDate:
  November 2,
  2009CUBIST PHARMACEUTICALS, INC.By:
  /s/
  Steven GilmanTitle:
  Chief
  Scientific Officer, Senior Vice President, Discovery and Non-Clinical
  DevelopmentDate:
  November 2,
  2009  
 *Confidential Treatment Requested.  Omitted portions filed with the Commission.  11


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 infectionProtocol
  Number:
  
  ALN-RSV01-109Phase
  of Development:
  
  Phase
  2bDesign:
  
  []*Study
  Sites:
  
  []*Investigational
  Drug:
  
  ALN-RSV01Dosage,
  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:
  
  []*  
 *Confidential
Treatment Requested.  Omitted portions
filed with the Commission.


GRAPHIC
  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:
  
  []*  23
  September 2009
  Confidential  
 *Confidential
Treatment Requested.  Omitted portions
filed with the Commission.


GRAPHIC
  ALN-RSV01
  ALN-RSV01-109  []*  23
  September 2009
  Confidential  
 *Confidential
Treatment Requested.  Omitted portions
filed with the Commission.


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
  Confidential  
 *Confidential
Treatment Requested.  Omitted portions
filed with the Commission.