Exhibit No.
10.7(g)


 


Millennium/Aventis


Third Amendment to Collaboration
and License Agreement


Execution
Version


 


Confidential
Materials omitted and filed separately with the 

Securities and Exchange Commission. Asterisks denote omissions.


 


THIRD
AMENDMENT TO COLLABORATION AND LICENSE AGREEMENT


 


This Third Amendment to Collaboration and License
Agreement (this “Third Amendment”) effective as of October 31, 2005 (the “Third
Amendment Date”) is by and between Millennium Pharmaceuticals, Inc., a
corporation organized and existing under the laws of the State of Delaware and
having its principal office at 75 Sidney Street, Cambridge, Massachusetts 02139
(“Millennium”) and Aventis Pharmaceuticals Inc., a member of the sanofi-aventis
Group and a corporation organized and existing under the laws of the State of
Delaware and having its principal office at Route 202-206, P.O. Box 6800,
Bridgewater, New Jersey 08807 (“Aventis”). All capitalized terms used in this
Third Amendment and not otherwise defined in this Third Amendment have the
meanings assigned them in the Collaboration Agreement (as that term is defined
in the first recital paragraph, below).


 


RECITALS


 


WHEREAS, Millennium and Aventis entered into a
Collaboration and License Agreement dated as of June 22, 2000 (as previously
amended, the “Collaboration Agreement”);


 


WHEREAS, in general, the Research Program Term under
the Collaboration Agreement expired on July 21, 2005, but the Parties entered
into a letter agreement dated July 20, 2005 
extending certain aspects of the Research Program for a limited time to
permit the Parties to discuss further collaborative activities (the “Extension
Letter”); and


 


WHEREAS, Millennium and Aventis have agreed to the
following changes to the Collaboration Agreement to facilitate the Parties’
continued work together.


 


AGREEMENT


 


NOW, THEREFORE, Millennium and Aventis hereby agree as
follows:


 


1.                                       End
of Research Program Term. Effective as of the Third Amendment Date, the
Research Program and the Research Program Term have expired for all matters for
which the Research Program Term was extended under the Extension Letter. The
Parties acknowledge the Research Program Term expired on July 21, 2005 for all
other matters.


 


2.                                       Interim
Research Period. After the expiration of the Research Program Term, the
Parties will continue to conduct Pre-EDC Research Evaluation solely on the
Program Compounds identified in this Section 2 and for the specific period (the
“Interim Research Period”) applicable to that Program Compound. The sole
purpose of this continued Pre-EDC Research Evaluation will be to determine
whether one or more of the listed compounds qualifies


 


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as an EDC pursuant to the terms of the Collaboration
Agreement as amended by this Third Amendment. For this purpose, the Parties
will apply the same EDC qualification criteria, governing structures and
decision-making processes as if the Research Program Term had not expired and
the Parties will have the same “opt-in” and “opt-out” rights for any resulting
EDCs as for EDCs identified prior to the expiration of the Research Program
Term. The research licenses granted by each Party to the other Party pursuant
to Sections 7.1.1(a) and 7.2.1(a) of the Collaboration Agreement will be
extended during the applicable Interim Research Period solely to permit the
work contemplated under this Section 2.


 


a.                                       [**]
and [**]. The Parties acknowledge that the only data remaining to determine
whether the Program Compounds known as [**] and/or [**], both of which are
aimed at the Program Target known as [**], meet the requirements to be
classified as an EDC is data for each compound [**] at Aventis as of the date
of signature of this Third Amendment. The Interim Research Period will end as
to each of [**] and [**] upon the earliest to occur of (a) a determination that
such Program Compound meets the requirements for EDC, (b) a determination that
such Program Compound does not meet the requirements for EDC, or (c) 30 days or
the next meeting of the Joint Development Committee, whichever is later, after
receipt of the [**] Program
Compound.


 


b.                                      [**].
Millennium will conduct additional Pre-EDC Research Evaluation of the Program
Compound known as [**], which is aimed at the Program Target known as [**], to
determine whether [**] meets the requirements to be classified as an EDC. Aventis
will reimburse Millennium [**]percent ([**]%) of the FTE Costs and other costs
incurred by Millennium in the course of conducting this Pre-EDC Research
Evaluation during the extended Research Program Term and the Interim Research
Period for [**] up to a maximum of $[**] U.S. The Interim Research Period will
end as to [**] upon the earliest to occur of (a) a determination that [**]
meets the requirements for EDC, or (b) a determination that [**] does not meet
the requirements for EDC. If [**] does not meet the requirements to become an
EDC, [**] will be distributed to Millennium as a Millennium Single-Party
Research Target, effective as of the end of the Interim Research Period for [**].
If [**] is so distributed, then Millennium will have the same rights and
obligations with regard to [**] and the Small Molecules related to [**] as if
[**] was a Pre-EDC Exempt Target distributed to Millennium upon expiration of
the Research Program through the selection process described in Section
2.7.5(c)(ii) of the Collaboration Agreement. For clarity, and subject to the
exclusivity period regarding SPRT Compounds specified in Section 2.7.3(b) of
the Collaboration Agreement, Aventis retains the right at any time to use [**]
for further validation and drug discovery activities, [**]. For further
clarity, this Section 2(b) provides the final disposition of [**] made during
the Research Program Term and such research assets shall not be further subject
to Section 2.7.5 of the Collaboration Agreement.


 


c.                                       [**].
Aventis will, at its sole cost, conduct additional Pre-EDC Research Evaluation
of the Program Compound known as [**], which is aimed at the Program Target
known as [**], to determine whether [**] meets the requirements to be
classified as an EDC. The Interim Research Period will end as to [**] upon the
earliest to occur of (a) a determination that [**] meets the requirements for EDC,
or (b) a determination that


 


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[**] does not meet the requirements for EDC. If [**]
does not meet the requirements to become an EDC, [**] will be distributed to
Aventis as an Aventis Single-Party Research Target, effective as of the end of
the Interim Research Period for [**]. If [**] is so distributed, then Aventis
will have the same rights and obligations with regard to [**] related to [**]
as if [**] was a Pre-EDC Exempt Target distributed to Aventis upon expiration
of the Research Program through the selection process described in Section
2.7.5(c)(ii) of the Collaboration Agreement. For clarity, and subject to the
exclusivity period regarding SPRT Compounds specified in Section 2.7.3(b) of
the Collaboration Agreement, Millennium retains the right at any time to use
[**] for further validation and drug discovery activities, [**]. For further
clarity, this Section 2(c) provides the final disposition of [**] made during
the Research Program Term and such research assets shall not be further subject
to Section 2.7.5 of the Collaboration Agreement.


 


3.                                       [**].
Effective as of the Third Amendment Date, the Program Target known as [**] will
become an Aventis Single-Party Research Target. Aventis will have the same
rights and obligations with regard to [**] related to [**] as if [**] was a
Pre-EDC Exempt Target distributed to Aventis upon expiration of the Research
Program through the selection process described in Section 2.7.5(c)(ii) of the
Collaboration Agreement. For clarity, and subject to the exclusivity period
regarding SPRT Compounds specified in Section 2.7.3(b) of the Collaboration
Agreement, Millennium retains the right at any time to use [**] for further
validation and drug discovery activities, [**]. For further clarity, this
Section 3 provides the final disposition of [**] made during the Research
Program Term and such research assets shall not be further subject to Section
2.7.5 of the Collaboration Agreement.


 


4.                                       Additional
Indications for Current JDCs. The Parties agree to cooperate in
investigating additional indications, [**], for all JDCs in the interest of
maximizing the value of those assets. Decisions regarding new indications will
be made jointly by the Parties in accordance with the procedures in the
Collaboration Agreement as amended by this Third Amendment, including, but not
limited to, the governing structures, decision-making processes, cost sharing
and profit sharing provisions.


 


5.                                       “Second
Generation” Programs for [**]. A new Section 3.13 is added to the
Collaboration Agreement to read as follows:


 


3.13                           “Second
Generation” Programs


 


3.13.1                  Programs.
Aventis may , at its sole cost but in its discretion, make efforts to identify,
test and qualify Small Molecules to serve as back-up or follow-on compounds for
any EDCs approved by the Parties aimed at [**].


 


(a)                                  The
Joint Research Committee will meet no less frequently than [**] to discuss
Aventis’s activities and progress in identifying, testing and qualifying such
Small Molecules or, if the Parties agree in a particular instance, Aventis may
provide to


 


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Millennium a written report of its activities and
progress in lieu of a meeting.


 


(b)                                 Millennium
will cooperate reasonably with Aventis in transferring any Program Technology
or Program Materials necessary for Aventis to fulfill its obligations under
this Section 3.13.1.


 


(c)                                  Any
decision whether any Small Molecule identified by Aventis in accordance with
this Section 3.13.1 qualifies as an EDC will be made jointly by the Parties
using the same EDC qualification criteria, governing structures and
decision-making processes as if the Research Program Term had not expired and
the Parties will have the same “opt-in” and “opt-out” rights for any resulting
EDCs as for EDCs identified prior to the expiration of the Research Program
Term.


 


(d)                                 In
addition to the above, Aventis will provide to Millennium a research plan
describing the activities that Aventis intends to undertake to identify, test
and qualify such Small Molecules aimed at [**] within [**] days after signature
of the Third Amendment to this Agreement. If at any time Aventis fails to
pursue the activities described in the research plan for a consecutive [**]
period, Aventis will, at Millennium’s request, transfer the program back to
Millennium at no cost to Millennium, and Millennium will have the right, in its
discretion, to continue to identify, test and qualify such Small Molecules. If
Millennium decides to continue to identify, test and qualify such Small
Molecules, then the provisions of Section 3.13.1(c) shall apply to any Small
Molecules identified by Millennium.


 


3.13.2                  Royalty
and Profit-Sharing Adjustments.


 


(a)                                  If
any Small Molecule directed to [**] identified by Aventis under Section 3.13.1
becomes a Joint Development Product or a Unilateral Development Product, all
applicable royalties due Millennium will be [**] percent ([**]%) from what is
provided in Section 8 of this Agreement.


 


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(b)                                 If
(i) a Small Molecule directed to [**]identified by Aventis under Section 3.13.1
becomes a Joint Development Product or a Unilateral Development Product and
(ii) such Joint Development Product or Unilateral Development Product is not based on or derived from [**], then:


 


1.                                       In the case of a Joint Development
Product, Aventis will receive [**] percent ([**]%) and Millennium will receive
[**] percent ([**]%) of the resulting
Pre-tax Profit or Loss; and


 


2.                                       In
the case of a Joint Development Product or a Unilateral Development Product,
all applicable royalties due Millennium will be [**] percent ([**]%) from what
is provided in Section 8 of this Agreement.


 


(c)                                  If
(i) a Small Molecule directed to [**] identified by Aventis under Section
3.13.1 becomes a Joint Development Product or a Unilateral Development Product
and (ii) such Joint Development Product or Unilateral Development Product is not based on or derived from [**], then:


 


1.                                       In the case of a Joint Development
Product, Aventis will receive [**] percent ([**]%) and Millennium will receive
[**]e percent ([**]%) of the resulting
Pre-tax Profit or Loss; and


 


2.                                       In the case of a Joint Development Product or
a Unilateral Development Product, all applicable royalties due Millennium will
be [**] percent ([**]%) from what is provided in Section 8 of this Agreement.


 


(d)                                 Except
as expressly set forth in this Section 3.13.2, all other sharing of Pre-tax
Profit or Loss or payment of royalties will be in accordance with Section 8 of
this Agreement.


 


3.13.3                  Designation
of EDC Family Compounds.


 


(a)                                  All
compounds first synthesized by either Party after [**] pursuant to Section
3.13.1 directed to [**]


 


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that are based on or are made through the use of
Program Technology or Program Materials shall be deemed members of the EDC
Family for [**] and [**] (even if such compounds number more than [**]).


 


(b)                                 All
compounds directed to [**] first synthesized by Aventis pursuant to Section
3.13.1 or by Millennium that are (i) based on or made through the use of
Program Technology or Program Materials; and either (ii) based on or derived
from [**]; or (iii) not based on or derived from [**] but first synthesized
prior to [**],  shall be deemed members
of the EDC Family for [**] (even if such compounds number more than [**]) if
[**] is declared an EDC. If [**] is not declared an EDC, then the last 4
sentences of Section 2.b of this Third Amendment shall apply.


 


(c)                                  All
compounds directed to [**] first synthesized by Aventis pursuant to Section
3.13.1 or by Millennium that are (i) based on or made through the use of
Program Technology or Program Materials; and either (ii) based on or derived
from [**]; or (iii) not based on or derived from [**] but first synthesized
prior to [**],  shall be deemed members
of the EDC Family for [**] (even if such compounds number more than [**]) if
[**] is declared an EDC. If [**] is not declared an EDC then the last 4
sentences of Section 2.c of this Third Amendment shall apply.


 


(d)                                 The
provisions of this Section 3.13.3 will only apply as long as the Parties wish
to continue working together on Small Molecules aimed at the relevant Program
Target, either because the Parties are working together on a JDC or JDP
directed at the relevant Program Target or, in the absence of a JDC or JDP, the
Parties are continuing to work together to qualify EDCs aimed at the relevant
Program Target.


 


6.                                       Development
Program Governance. The following new Section 3.3.3 is added to the
Collaboration Agreement:


 


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3.3.3                        Identification
of Development Lead Party.


 


(a)                                  In
addition to the allocation of Development activities provided under Section
3.3.2, the Global Development Plan for each JDC will designate one Party or the
other as the lead Party for the implementation of the Development Plan of the applicable
JDC through the Proof of Concept Study (the “Pre-POC Development Lead”). For
the purposes of this Section 3.3.3, “Proof of Concept Study” means the first clinical study in the target
patient population for the applicable indication where the JDC is shown to be
active as defined by the agreed-upon clinical endpoints or validated surrogate
endpoints or such other endpoints as the Joint Development Committee agrees
demonstrate proof of concept, thereby validating the mechanism of action of the
JDC.


 


(i)                                     The
Pre-POC Development Lead will be permitted to execute against the approved plan
and within the budget approved by the Joint Steering Committee, plus the
allowable variance from that budget approved by the Joint  Steering Committee at the time of budget
approval, for the activities for which the Party has been designated as Pre-POC
Development Lead. As long as activities are within that range, the “non-lead”
Party would have input, but the Pre-POC Development Lead would have final
decision authority. This right would include, but not be limited to, the right
to subcontract activities without the consent of the “non-lead” Party as long
as the activities were within the range of expenditures permitted under the
approved budget and the arrangements otherwise met the requirements of Section
3.11. Any activities that would result in expenditures outside of the permitted
range would have to be approved by the Joint Development Committee and the
Joint Steering Committee. For avoidance of doubt, as part of the approval of
the plan,  “non-lead” Party will have the
right to approve the key elements of the design of all clinical trials
contemplated in the plan and the right to approve any material alterations to
those elements.


 


(ii)                                  Without
limiting the generality of the foregoing, the Parties agree that (a) Millennium
will be the Pre-POC Development Lead for the JDCs known as [**]; and (b)
Aventis will be the Pre-POC Development Lead should any of those Program
Compounds become EDCs for [**] and any Program Compounds aimed at [**]
developed under Section 3.13.1.


 


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(iii)                               Notwithstanding
anything to the contrary in Section 5.2.1, except in extraordinary
circumstances as determined by the Joint Development Committee, the Pre-POC
Development Lead for a particular JDC in a particular indication will also be
the global Regulatory Lead for all activities relating to that JDC in that
indication.


 


(b)                                 If
a JDC progresses beyond Proof of Concept, the Global Development Plan for such
JDC will designate one Party or the other as the lead Party for the Development
of the applicable JDC for each post-Proof of Concept clinical study (the “Post-POC
Development Lead”).


 


(i)                                     Responsibilities
for Post-POC Development Lead will be assigned according to the following
principles:


 


(1)                                  Aventis
will be the Post-POC Development Lead for all trials in [**].


 


(2)                                  The
Post-POC Development Lead for all other trials will be determined by the Joint
Development Committee such that the Parties have substantially equal
opportunities, subject to the factors set forth below, to act as the Post-POC
Development Lead within the collaboration. Assignment of such responsibilities
shall, where possible, be on an indication-by-indication basis for each JDC. In
making this determination, the Joint Development Committee may take into
account the capacity and capabilities of the Parties given such factors as the
cost of the trial, the number of patients in the trial, the number of sites in
the trial, the Parties’ relative experience and expertise, the Parties’
relative resources (including whether the work will be conducted internally or
externally), and the existence and timing of either Parties’ development
programs for Small Molecules aimed at the same Program Target taking place
outside the Parties’ collaborative efforts.


 


(ii)                                  Notwithstanding
anything to the contrary in Section 5.2.1, except in extraordinary
circumstances as determined by the Joint Development Committee, the Post-POC
Development Lead for a particular JDC in a particular indication will also be
the global Regulatory Lead for all activities relating to that JDC in that
indication. It is the understanding of the


 


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Parties that the term
Regulatory Lead has the meaning set forth in Article 5 of this Agreement. For
the avoidance of doubt, the final decision making authority for the Post-POC
Development Lead with respect to development matters does not mean that such
Party shall have final decision making authority with respect to regulatory
matters.


 


(iii)                               The
Post-POC Development Lead will be permitted to execute against the approved
plan and within the budget approved by the Joint Steering Committee, plus the
allowable variance from that budget approved by the Joint  Steering Committee at the time of budget
approval, for the activities for which the Party has been designated as
Post-POC Development Lead. As long as activities are within that range, the “non-lead”
Party would have input, but the Post-POC Development Lead would have final
decision authority. This right would include, but not be limited to, the right
to subcontract activities without the consent of the “non-lead” Party as long
as the activities were within the range of expenditures permitted under the
approved budget and the arrangements otherwise met the requirements of Section
3.11. Activities that would result in expenditures outside of the permitted
range would have to be approved by the Joint Development Committee and the
Joint Steering Committee. For avoidance of doubt, as part of the approval of
the plan, “non-lead” Party will have the right to approve the key elements of
the design of all clinical trials contemplated in the plan and the right to
approve any material alterations to those elements.


 


(c)                                  Notwithstanding
anything to the contrary in Article 12, if the Joint Development Committee is
unable to agree on which Party will be the Post-POC Development Lead for any
set of activities, the dispute will be immediately referred to the Joint
Steering Committee for resolution. If the Joint Steering Committee is unable to
resolve the dispute within ten (10) working days after such referral, then the
chairs of the Joint Steering Committee shall each choose an arbitrator which
arbitrators shall then agree on a third arbitrator which will form an
arbitration panel of three for arbitration on the sole question of which Party
should be the Post-POC Development Lead for the applicable set of activities. The
arbitrators will be required to render a decision within three (3) months after
submission of the question for decision. In rendering a decision, the
arbitrators will only be empowered to select the proposal of one Party or the
other in its entirety on the issue(s) submitted for decision (i.e., “baseball
style”  arbitration) based on


 


9

















 


the criteria in Section
3.3.3(b)(i)(3). The arbitrators’ decision (majority rule) will be final and
binding on both Parties. The Parties agree to discuss and agree upon the
process for selection of the arbitrator and the procedures to be followed in
the arbitration within six (6) months
after the execution of the Third Amendment to this Agreement.


 


7.                                       CMC
Lead. Section 4.1 of the Collaboration Agreement is deleted in its entirety
and replaced with the following:


 


4.1                                 Clinical Supply. As part of the first Global Development
Plan for each Joint Development Compound, the Joint Development Committee shall
specify which Party shall be responsible for manufacturing quantities of such
compound for use in pre-clinical and clinical trials (the “CMC Lead”). It is
expected that only one Party shall be responsible for manufacturing all
quantities of a Joint Development Compound and the related Joint Development
Product necessary for pre-clinical and clinical studies throughout the
Territory. The CMC Lead will be permitted to execute against the approved plan
and within the budget approved by the Joint Steering Committee, plus the
allowable variance from that budget approved by the Joint  Steering Committee at the time of budget
approval, for the activities for which the Party has been designated as CMC
Lead. As long as activities are within that range, the “non-lead” Party would
have input, but the  CMC Lead would have
final decision authority. This right would include, but not be limited to, the
right to subcontract activities without the consent of the “non-lead” Party as
long as the activities were within the range of expenditures permitted under
the approved budget and the arrangements otherwise met the requirements of
Section 4.4. Any activities that would result in expenditures outside of the
permitted range would have to be approved by the Joint Development Committee
and the Joint Steering Committee. The Parties agree that (a) Millennium will be
the CMC Lead for [**]; and (b) Aventis will be the CMC Lead for all other JDCs.


 


8.                                       Regulatory
Lead. The phrase “Except as provided in Section 3.3.3(b),” is added to the
beginning of the second sentence of Section 5.2.1.


 


9.                                       Freeze
of FTE Rate. Notwithstanding anything to the contrary in Exhibit B to the
Collaboration Agreement, the FTE Rate will remain $[**] U.S. per FTE per year
until [**]. Thereafter, the FTE Rate will increase by [**] percent ([**]%) per
annum to reflect inflation.


 


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The Parties will, no later than [**], commence good
faith discussions regarding different ways of calculating the FTE Rate after
[**].


 


10.                                 Change
to Roll-In Letter. The phrase “Aventis and Millennium shall each have” at
the beginning of Paragraph 3(iii) of the letter agreement between the Parties
dated July 27, 2001 is amended to read “Millennium shall have.”


 


12.                                 Elimination
of June 3, 2003 Letter Agreement. The Parties acknowledge that (a) the
Program Compound known as [**] (formerly known as [**]) ceased to be part of
the Research Program when it was designated as an EDC on June 6, 2005; and (b)
none of the other Program Compounds that were Designated Compounds under the
terms of the June 3, 2003 letter agreement between the Parties regarding “Addition
of Research Rights Relating to Certain Program Compounds” (the “[**] Research
Letter”) reached EDC status by July 21, 2005 when the Research Program expired
as to those Program Compounds. Therefore, the Parties acknowledge that, except
for the obligation to share data from research conducted under the auspices of
the [**] Research Letter that was commenced prior to June 6, 2005 with regard
to [**] and July 22, 2005 with regard to
the other Designated Compounds, the [**]Research Letter is of no further force
and effect.


 


13.                                 Publication
Approval Process. The reference in the fifth sentence Section 10.4 of the
Collaboration to “sixty (60) days” is amended to read “forty-five (45) days.”
Further, the reference in the sixth sentence of Section 10.4 to “ninety (90)
days” is amended to read “sixty (60) days.”


 


14.                                 Changes
to Dispute Resolution Provisions. The Parties agree to discuss possible
changes in the method of resolving disputes that may arise between the Parties
relating to JDCs within three (3) months after the execution of this Third
Amendment.


 


15.                                 Continuing
Effect. Except as otherwise specifically set forth herein, all terms and
conditions of the Collaboration Agreement remain in full force and effect.


 


16.                                 Counterparts.
This Third Amendment may be executed in one or more counterparts, each of which
counterparts, when so executed and delivered, shall be deemed to be an
original, and all of which counterparts, taken together, shall constitute one
and the same instrument.


 


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IN WITNESS WHEREOF, each of the Parties has caused
this Third Amendment to be executed as of the date first set forth above.


 


	
  Millennium
  Pharmaceuticals, Inc.

  	
   

  	
  Aventis
  Pharmaceuticals Inc.

  
	
   

  	
   

  	
   

  
	
  By:

  	
                 /s/

  	
  A. Protopapas

  	
   

  	
  By:

  	
           /s/

  	
  Larry Bangh

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  Name:

  	
   

  	
  A. Protopapas

  	
   

  	
  Name:

  	
   

  	
  Larry Bangh

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  
	
  Title:

  	
  SVP, Corporate
  Develop.

  	
   

  	
  Title:

  	
   

  	
  Site Director

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
  By:

  	
           /s/

  	
  Mark L. Staudenne

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
  Name:

  	
   

  	
  Mark L. Staudenne

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
  Title:

  	
   

  	
  V.P. Finance

  	
   

  
									



 


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