**Exhibit No.10.7(g)**

** **

*Millennium/Aventis*

*Third Amendment to Collaborationand License Agreement*

***ExecutionVersion***

 

**ConfidentialMaterials omitted and filed separately with the Securities and Exchange Commission. Asterisks denote omissions.**

 

**THIRDAMENDMENT TO COLLABORATION AND LICENSE AGREEMENT**

 

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

 

RECITALS

 

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

 

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

 

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

 

AGREEMENT

 

NOW, THEREFORE, Millennium and Aventis hereby agree asfollows:

 

1.                                       Endof Research Program Term. Effective as of the Third Amendment Date, theResearch Program and the Research Program Term have expired for all matters forwhich the Research Program Term was extended under the Extension Letter. TheParties acknowledge the Research Program Term expired on July 21, 2005 for allother matters.

 

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

 

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

 

a.                                       [**]and [**]. The Parties acknowledge that the only data remaining to determinewhether the Program Compounds known as [**] and/or [**], both of which areaimed at the Program Target known as [**], meet the requirements to beclassified as an EDC is data for each compound [**] at Aventis as of the dateof signature of this Third Amendment. The Interim Research Period will end asto each of [**] and [**] upon the earliest to occur of (a) a determination thatsuch Program Compound meets the requirements for EDC, (b) a determination thatsuch Program Compound does not meet the requirements for EDC, or (c) 30 days orthe next meeting of the Joint Development Committee, whichever is later, afterreceipt of the [**] ProgramCompound.

 

b.                                      [**].Millennium will conduct additional Pre-EDC Research Evaluation of the ProgramCompound known as [**], which is aimed at the Program Target known as [**], todetermine whether [**] meets the requirements to be classified as an EDC. Aventiswill reimburse Millennium [**]percent ([**]%) of the FTE Costs and other costsincurred by Millennium in the course of conducting this Pre-EDC ResearchEvaluation during the extended Research Program Term and the Interim ResearchPeriod for [**] up to a maximum of $[**] U.S. The Interim Research Period willend as to [**] upon the earliest to occur of (a) a determination that [**]meets the requirements for EDC, or (b) a determination that [**] does not meetthe requirements for EDC. If [**] does not meet the requirements to become anEDC, [**] will be distributed to Millennium as a Millennium Single-PartyResearch Target, effective as of the end of the Interim Research Period for [**].If [**] is so distributed, then Millennium will have the same rights andobligations with regard to [**] and the Small Molecules related to [**] as if[**] was a Pre-EDC Exempt Target distributed to Millennium upon expiration ofthe Research Program through the selection process described in Section2.7.5(c)(ii) of the Collaboration Agreement. For clarity, and subject to theexclusivity period regarding SPRT Compounds specified in Section 2.7.3(b) ofthe Collaboration Agreement, Aventis retains the right at any time to use [**]for further validation and drug discovery activities, [**]. For furtherclarity, this Section 2(b) provides the final disposition of [**] made duringthe Research Program Term and such research assets shall not be further subjectto Section 2.7.5 of the Collaboration Agreement.

 

c.                                       [**].Aventis will, at its sole cost, conduct additional Pre-EDC Research Evaluationof the Program Compound known as [**], which is aimed at the Program Targetknown as [**], to determine whether [**] meets the requirements to beclassified as an EDC. The Interim Research Period will end as to [**] upon theearliest 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 toAventis as an Aventis Single-Party Research Target, effective as of the end ofthe Interim Research Period for [**]. If [**] is so distributed, then Aventiswill have the same rights and obligations with regard to [**] related to [**]as if [**] was a Pre-EDC Exempt Target distributed to Aventis upon expirationof the Research Program through the selection process described in Section2.7.5(c)(ii) of the Collaboration Agreement. For clarity, and subject to theexclusivity period regarding SPRT Compounds specified in Section 2.7.3(b) ofthe Collaboration Agreement, Millennium retains the right at any time to use[**] for further validation and drug discovery activities, [**]. For furtherclarity, this Section 2(c) provides the final disposition of [**] made duringthe Research Program Term and such research assets shall not be further subjectto Section 2.7.5 of the Collaboration Agreement.

 

3.                                       [**].Effective as of the Third Amendment Date, the Program Target known as [**] willbecome an Aventis Single-Party Research Target. Aventis will have the samerights and obligations with regard to [**] related to [**] as if [**] was aPre-EDC Exempt Target distributed to Aventis upon expiration of the ResearchProgram through the selection process described in Section 2.7.5(c)(ii) of theCollaboration Agreement. For clarity, and subject to the exclusivity periodregarding SPRT Compounds specified in Section 2.7.3(b) of the CollaborationAgreement, Millennium retains the right at any time to use [**] for furthervalidation and drug discovery activities, [**]. For further clarity, thisSection 3 provides the final disposition of [**] made during the ResearchProgram Term and such research assets shall not be further subject to Section2.7.5 of the Collaboration Agreement.

 

4.                                       AdditionalIndications for Current JDCs. The Parties agree to cooperate ininvestigating additional indications, [**], for all JDCs in the interest ofmaximizing the value of those assets. Decisions regarding new indications willbe made jointly by the Parties in accordance with the procedures in theCollaboration Agreement as amended by this Third Amendment, including, but notlimited to, the governing structures, decision-making processes, cost sharingand profit sharing provisions.

 

5.                                       “SecondGeneration” Programs for [**]. A new Section 3.13 is added to theCollaboration Agreement to read as follows:

 

3.13                           “SecondGeneration” 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 forany EDCs approved by the Parties aimed at [**].

 

(a)                                  TheJoint Research Committee will meet no less frequently than [**] to discussAventis’s activities and progress in identifying, testing and qualifying suchSmall Molecules or, if the Parties agree in a particular instance, Aventis mayprovide to

 

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Millennium a written report of its activities andprogress in lieu of a meeting.

 

(b)                                 Millenniumwill cooperate reasonably with Aventis in transferring any Program Technologyor Program Materials necessary for Aventis to fulfill its obligations underthis Section 3.13.1.

 

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

 

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

 

3.13.2                  Royaltyand Profit-Sharing Adjustments.

 

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

 

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(b)                                 If(i) a Small Molecule directed to [**]identified by Aventis under Section 3.13.1becomes 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 DevelopmentProduct, Aventis will receive [**] percent ([**]%) and Millennium will receive[**]****percent ([**]%) of the resultingPre-tax Profit or Loss; and

 

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

 

(c)                                  If(i) a Small Molecule directed to [**] identified by Aventis under Section3.13.1 becomes a Joint Development Product or a Unilateral Development Productand (ii) such Joint Development Product or Unilateral Development Product is **not** based on or derived from [**], then:

 

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

 

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

 

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

 

3.13.3                  Designationof EDC Family Compounds.

 

(a)                                  Allcompounds first synthesized by either Party after [**] pursuant to Section3.13.1 directed to [**]

 

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

 

(b)                                 Allcompounds directed to [**] first synthesized by Aventis pursuant to Section3.13.1 or by Millennium that are (i) based on or made through the use ofProgram Technology or Program Materials; and either (ii) based on or derivedfrom [**]; or (iii) not based on or derived from [**] but first synthesizedprior to [**],  shall be deemed membersof 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 4sentences of Section 2.b of this Third Amendment shall apply.

 

(c)                                  Allcompounds directed to [**] first synthesized by Aventis pursuant to Section3.13.1 or by Millennium that are (i) based on or made through the use ofProgram Technology or Program Materials; and either (ii) based on or derivedfrom [**]; or (iii) not based on or derived from [**] but first synthesizedprior to [**],  shall be deemed membersof 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 4sentences of Section 2.c of this Third Amendment shall apply.

 

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

 

6.                                       DevelopmentProgram Governance. The following new Section 3.3.3 is added to theCollaboration Agreement:

 

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3.3.3                        Identificationof Development Lead Party.

 

(a)                                  Inaddition to the allocation of Development activities provided under Section3.3.2, the Global Development Plan for each JDC will designate one Party or theother as the lead Party for the implementation of the Development Plan of the applicableJDC through the Proof of Concept Study (the “Pre-POC Development Lead”). Forthe purposes of this Section 3.3.3, “Proof of Concept Study” means the first clinical study in the targetpatient population for the applicable indication where the JDC is shown to beactive as defined by the agreed-upon clinical endpoints or validated surrogateendpoints or such other endpoints as the Joint Development Committee agreesdemonstrate proof of concept, thereby validating the mechanism of action of theJDC.

 

(i)                                     ThePre-POC Development Lead will be permitted to execute against the approved planand within the budget approved by the Joint Steering Committee, plus theallowable variance from that budget approved by the Joint  Steering Committee at the time of budgetapproval, for the activities for which the Party has been designated as Pre-POCDevelopment Lead. As long as activities are within that range, the “non-lead”Party would have input, but the Pre-POC Development Lead would have finaldecision authority. This right would include, but not be limited to, the rightto subcontract activities without the consent of the “non-lead” Party as longas the activities were within the range of expenditures permitted under theapproved budget and the arrangements otherwise met the requirements of Section3.11. Any activities that would result in expenditures outside of the permittedrange would have to be approved by the Joint Development Committee and theJoint Steering Committee. For avoidance of doubt, as part of the approval ofthe plan,  “non-lead” Party will have theright to approve the key elements of the design of all clinical trialscontemplated in the plan and the right to approve any material alterations tothose elements.

 

(ii)                                  Withoutlimiting the generality of the foregoing, the Parties agree that (a) Millenniumwill 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 ProgramCompounds become EDCs for [**] and any Program Compounds aimed at [**]developed under Section 3.13.1.

 

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(iii)                               Notwithstandinganything to the contrary in Section 5.2.1, except in extraordinarycircumstances as determined by the Joint Development Committee, the Pre-POCDevelopment Lead for a particular JDC in a particular indication will also bethe global Regulatory Lead for all activities relating to that JDC in thatindication.

 

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

 

(i)                                     Responsibilitiesfor Post-POC Development Lead will be assigned according to the followingprinciples:

 

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

 

(2)                                  ThePost-POC Development Lead for all other trials will be determined by the JointDevelopment Committee such that the Parties have substantially equalopportunities, subject to the factors set forth below, to act as the Post-POCDevelopment Lead within the collaboration. Assignment of such responsibilitiesshall, where possible, be on an indication-by-indication basis for each JDC. Inmaking this determination, the Joint Development Committee may take intoaccount the capacity and capabilities of the Parties given such factors as thecost of the trial, the number of patients in the trial, the number of sites inthe trial, the Parties’ relative experience and expertise, the Parties’relative resources (including whether the work will be conducted internally orexternally), and the existence and timing of either Parties’ developmentprograms for Small Molecules aimed at the same Program Target taking placeoutside the Parties’ collaborative efforts.

 

(ii)                                  Notwithstandinganything to the contrary in Section 5.2.1, except in extraordinarycircumstances as determined by the Joint Development Committee, the Post-POCDevelopment Lead for a particular JDC in a particular indication will also bethe global Regulatory Lead for all activities relating to that JDC in thatindication. It is the understanding of the

 

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Parties that the termRegulatory Lead has the meaning set forth in Article 5 of this Agreement. Forthe avoidance of doubt, the final decision making authority for the Post-POCDevelopment Lead with respect to development matters does not mean that suchParty shall have final decision making authority with respect to regulatorymatters.

 

(iii)                               ThePost-POC Development Lead will be permitted to execute against the approvedplan and within the budget approved by the Joint Steering Committee, plus theallowable variance from that budget approved by the Joint  Steering Committee at the time of budgetapproval, for the activities for which the Party has been designated asPost-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 finaldecision authority. This right would include, but not be limited to, the rightto subcontract activities without the consent of the “non-lead” Party as longas the activities were within the range of expenditures permitted under theapproved budget and the arrangements otherwise met the requirements of Section3.11. Activities that would result in expenditures outside of the permittedrange would have to be approved by the Joint Development Committee and theJoint Steering Committee. For avoidance of doubt, as part of the approval ofthe plan, “non-lead” Party will have the right to approve the key elements ofthe design of all clinical trials contemplated in the plan and the right toapprove any material alterations to those elements.

 

(c)                                  Notwithstandinganything to the contrary in Article 12, if the Joint Development Committee isunable to agree on which Party will be the Post-POC Development Lead for anyset of activities, the dispute will be immediately referred to the JointSteering Committee for resolution. If the Joint Steering Committee is unable toresolve the dispute within ten (10) working days after such referral, then thechairs of the Joint Steering Committee shall each choose an arbitrator whicharbitrators shall then agree on a third arbitrator which will form anarbitration panel of three for arbitration on the sole question of which Partyshould be the Post-POC Development Lead for the applicable set of activities. Thearbitrators will be required to render a decision within three (3) months aftersubmission of the question for decision. In rendering a decision, thearbitrators will only be empowered to select the proposal of one Party or theother in its entirety on the issue(s) submitted for decision (i.e., “baseballstyle”  arbitration) based on

 

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the criteria in Section3.3.3(b)(i)(3). The arbitrators’ decision (majority rule) will be final andbinding on both Parties. The Parties agree to discuss and agree upon theprocess for selection of the arbitrator and the procedures to be followed inthe arbitration within six (6) monthsafter the execution of the Third Amendment to this Agreement.

 

7.                                       CMCLead. Section 4.1 of the Collaboration Agreement is deleted in its entiretyand replaced with the following:

 

4.1                                 **Clinical Supply**. As part of the first Global DevelopmentPlan for each Joint Development Compound, the Joint Development Committee shallspecify which Party shall be responsible for manufacturing quantities of suchcompound for use in pre-clinical and clinical trials (the “CMC Lead”). It isexpected that only one Party shall be responsible for manufacturing allquantities of a Joint Development Compound and the related Joint DevelopmentProduct necessary for pre-clinical and clinical studies throughout theTerritory. The CMC Lead will be permitted to execute against the approved planand within the budget approved by the Joint Steering Committee, plus theallowable variance from that budget approved by the Joint  Steering Committee at the time of budgetapproval, for the activities for which the Party has been designated as CMCLead. As long as activities are within that range, the “non-lead” Party wouldhave input, but the  CMC Lead would havefinal decision authority. This right would include, but not be limited to, theright to subcontract activities without the consent of the “non-lead” Party aslong as the activities were within the range of expenditures permitted underthe approved budget and the arrangements otherwise met the requirements ofSection 4.4. Any activities that would result in expenditures outside of thepermitted range would have to be approved by the Joint Development Committeeand the Joint Steering Committee. The Parties agree that (a) Millennium will bethe CMC Lead for [**]; and (b) Aventis will be the CMC Lead for all other JDCs.

 

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

 

9.                                       Freezeof FTE Rate. Notwithstanding anything to the contrary in Exhibit B to theCollaboration Agreement, the FTE Rate will remain $[**] U.S. per FTE per yearuntil [**]. Thereafter, the FTE Rate will increase by [**] percent ([**]%) perannum to reflect inflation.

 

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

 

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

 

12.                                 Eliminationof June 3, 2003 Letter Agreement. The Parties acknowledge that (a) theProgram Compound known as [**] (formerly known as [**]) ceased to be part ofthe 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 theterms of the June 3, 2003 letter agreement between the Parties regarding “Additionof Research Rights Relating to Certain Program Compounds” (the “[**] ResearchLetter”) reached EDC status by July 21, 2005 when the Research Program expiredas to those Program Compounds. Therefore, the Parties acknowledge that, exceptfor the obligation to share data from research conducted under the auspices ofthe [**] Research Letter that was commenced prior to June 6, 2005 with regardto****[**] and July 22, 2005 with regard tothe other Designated Compounds, the [**]Research Letter is of no further forceand effect.

 

13.                                 PublicationApproval Process. The reference in the fifth sentence Section 10.4 of theCollaboration 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.                                 Changesto Dispute Resolution Provisions. The Parties agree to discuss possiblechanges in the method of resolving disputes that may arise between the Partiesrelating to JDCs within three (3) months after the execution of this ThirdAmendment.

 

15.                                 ContinuingEffect. Except as otherwise specifically set forth herein, all terms andconditions 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 whichcounterparts, when so executed and delivered, shall be deemed to be anoriginal, and all of which counterparts, taken together, shall constitute oneand the same instrument.

 

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IN WITNESS WHEREOF, each of the Parties has causedthis 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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