**Exhibit 10.29**

 

*****Text Omitted and Filed Separately**

**with the Securities and Exchange Commission.**

**Confidential Treatment Requested**

**Under 17 C.F.R. Sections 200.80(b)(4)**

**and 240.24b-2.**

 

August 29, 2005

 

Metabasis Therapeutics, Inc.

9390 TowneCentre Drive, Suite 300

San Diego, CA 92121

 

**Re:****          ExclusiveLicense and Research Collaboration Agreement dated as of December 23,2003, as amended prior to the date hereof (as so amended. the “CollaborationAgreement”) between Merck & Co., Inc. (“Merck”) and Metabasis Therapeutics,Inc. (“Metabasis”)**

 

Ladies and Gentlemen:

 

This Letter (this ***“Letter”***)will confirm the understanding of Merck and Metabasis regarding certain mattersrelating to the Collaboration Agreement and is intended to be legally bindingon both parties. Capitalized terms used but not otherwise defined in this Letter shall have the meaningsprovided in the Collaboration Agreement. Pursuant to this Letter the Partieshereby agree to amend the Agreement as follows:

 

**1.        **Thedefinition of “Merck HCV Compound” set forth in Section 1.35 of the Agreement,is hereby amended and restated in its entirety as follows: “**“Merck HCV Compound”** shall mean (a) any of the [***] on PartA of ***Schedule I*** to the Research Plan; (b) any of theDesignated Compounds; and/or (c) any [***] and/or any [***] HepDirectTechnology or [***] Technology), [***] of the [***] listed under [***] on PartA of ***Schedule I***.”

 

**2.        **The definition of “Collaboration Compound”set forth in Section 1.5 of the Agreement is hereby amended and restated in itsentirety: **“Collaboration Compound”**shallmean a chemical entity that is synthesized solely by a Party or jointly by theParties prior to or in the course of the Research Program, or prior to the [***]of the expiration or termination of the Research Program Term, that is (a) any [***]that [***] incorporates HepDirect Technology; (b) any [***] of a [***] that [***]incorporates HepDirect Technology; (c) any [***] that does not [***]incorporate HepDirect Technology; and/or (d) any [***]  listed under numbers [***]  on Part A of ***Schedule I*,**whether or not they incorporate HepDirect Technology or [***]  Technology.”

 

**3.         *Schedule I***Part A is hereby amended to list Merck HCV Compound [***]  having the following structural formula:

 

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*****Confidential Treatment Requested**

 

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[***]

 

**[***]**

** **

**4.        **The Research Plan has been modified and isfully set forth in its entirety in its current form in ***Exhibit A*****to this Letter;(provided that ***Schedules II***,***III, IV***and***V***to the Research Plan shall remain in the forms in effect immediately prior tothe effective date of this Letter Agreement;

 

**5.        **Metabasis acknowledges and agrees that Merck’srepresentation and warranty under Section 6.2(c) of the Agreement extends onlyto “Merck HCV Compounds” as defined in the Agreement as it existed on theEffective Date;

 

**6.        **This Letter shallbecome effective as of the date first written above. Except as amended by thisLetter, together with the Schedules and Exhibits attached hereto, the terms andconditions of the Collaboration Agreement shall remain in full force and effectin all other respects, unless further amended by written agreement inaccordance with Section 11.7 of the Collaboration Agreement. On and after theeffectiveness of this Letter, each reference in the Agreement to “thisAgreement”, “hereunder”, “hereof”, “herein” or words of like import referringto the Collaboration Agreement shall mean and be a reference to theCollaboration Agreement as amended by this Letter. The Parties hereby furtheragree that the terms and conditions set forth in Article 11 of theCollaboration Agreement, including without limitation the Assignment and Changeof Control provisions of Section 11.2, the Applicable Law provisions of Section11.5 and the Dispute Resolution provisions of Section 11.6, shall apply to thisLetter as if fully set forth herein; and

 

**7.        **This Letter may be executed (including,without limitation, by facsimile signature) in two counterparts, each of whichshall be deemed an original, but both of which together shall constitute oneand the same instrument.

 

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*****Confidential Treatment Requested**

 

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If the foregoing isacceptable to you, please sign this Letterin the space provided below and return it to me.

 
|       | Sincerely,                 |
|------------|----------------------------|
|       |                       |
| ** ** | **MERCK  & CO., INC.** |
|       |                       |   |
|       |                       |   |
|       | By:                        | /s/ Mervyn J.  Turner |
|       | Name:                      | M.J. Turner,  Ph.D. |
|       | Title:                     | Senior Vice  President |
|       |                       | Worldwide  Licensing and External |
|       |                       | Research |

 

*Agreed toand accepted as of the date first set forth above:*

 

**METABASISTHERAPEUTICS, INC.**

 

 

 
| By:    | /s/ Ed  Baracchini                    |   |
|--------|---------------------------------------|--------|
| Name:  | Ed Baracchini,  Ph.D., MBA            |   |
| Title: | Vice President,  Business Development |   |

 

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**EXHIBIT A**

 

**AmendedResearch Plan**

 

The Research Plan may be revised to [***]subject to mutual agreement by the Parties and subject to availability of FTEswithin the Research Program as described in the Agreement.

 

During the [***]of the Research Program [***]In summary, over [***]. One of the mostinteresting [***] which was found tobe [***]. When the compound was [***] at the same time the [***]. Thus the [***]. A series of [***] was observed. [***] was seen, suggesting a [***].

 

[***] Interestingly, the [***]On the basis of [***] As an additionalcontrol [***].

 

[***]

 

[***]

 

 

After [***]to the Research Program Metabasis [***] HepDirect prodrugs [***].

 

Merck assessed [***]. However, it was determined by [***].

 

[***]

 

During the last [***]the following are the high priorityobjectives for the collaboration:

 

•                  Merck will analyze [***] anddetermine if [***].Metabasis will prepare [***] and the[***]in an attempt [***].

 

•                  Inthe event that a [***] or [***].

 

•                  Merck will supply Metabasis [***].

 

•                  Metabasiswill prepare [***].

 

•                  Assuming [***] Merck will [***].

 

[***]

 

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*****Confidential Treatment Requested**

 

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