<PAGE>
                                                                   Exhibit 10.25

[*] CERTAIN CONFIDENTIAL INFORMATION CONTAINED IN THIS DOCUMENT, MARKED BY
    BRACKETS, HAS BEEN OMITTED AND FILED SEPARATELY WITH THE SECURITIES AND
    EXCHANGE COMMISSION PURSUANT TO RULE 406 OF THE SECURITIES EXCHANGE ACT OF
    1933, AS AMENDED.


[CYTOKINETICS LOGO]                        280 East Grand Avenue
                                           South San Francisco, CA 94080
                                           Tel (650) 624-3000 Fax (650) 624-3010


July 28, 2003


Glaxo Group Limited, doing business as GlaxoSmithKline
709 Swedeland Road
King of Prussia, Pennsylvania 19406
Attn: Pradip K. Bhatnagar, Ph.D., Director, Genetic & Discovery Alliances


RE: TRACTABLE COMPOUND CRITERIA UNDER THAT CERTAIN COLLABORATION AND LICENSE
AGREEMENT BY AND BETWEEN GLAXO GROUP LIMITED, A GLAXOSMITHKLINE COMPANY,
("GSK") AND CYTOKINETICS, INC. ("CK") OF EVEN DATE JUNE 20, 2001 (THE
"COLLABORATION AGREEMENT")

Dear Pradip:

Pursuant to this letter amendment to the Collaboration Agreement (the "Tractable
Compound Criteria Letter Amendment"), GSK and CK desire to revise the Tractable
Compound Criteria applicable under the Collaboration Agreement as agreed by the
JRC on April 11, 2003, all on the terms set forth herein.

Now therefore, GSK and CK agree as follows:

     1. All capitalized terms not defined herein shall have the meaning
        ascribed to them in the Collaboration Agreement.

     2. For purposes of the Collaboration Agreement, "Tractable Compound
        Criteria" shall mean, effective as of the Effective Date, those criteria
        set forth in the revised Exhibit 1.65 attached hereto and incorporated
        by reference. For clarity, it is understood that the Tractable Compound
        Criteria may only be modified or amended pursuant in a writing signed by
        both Parties referencing the Collaboration Agreement and expressly
        modifying or amending the Tractable Compound Criteria.

     3. Except as specifically modified or amended hereby, the Collaboration
        Agreement shall remain in full force and effect and, as modified or
        amended, is hereby ratified, confirmed and approved. No provision of
        this Tractable Compound Criteria Letter Amendment may be modified or
        amended except expressly in a writing signed by both Parties nor shall
        any terms be waived except expressly in a writing signed by the Party
        charged therewith. This Tractable Compound Criteria Letter Amendment
        shall be governed in accordance with the laws of the [*], without regard
        to principles of conflicts of laws.

* Certain information on this page has been omitted and filed separately with
  the Commission. Confidential treatment has been requested with respect to the
  omitted portions.







<PAGE>
Pradip K. Bhatnagar, Ph.D.
July 28, 2003
Page Two

Please sign and return two copies of this letter if you agree to the foregoing
terms.

Sincerely,

/s/ Robert I. Blum
------------------
Robert I. Blum
Senior Vice President, Finance and Corporate Development
Chief Financial Officer
Cytokinetics, Inc.

Agreed and accepted:

GLAXO GROUP LIMITED

/s/ Pradip K. Bhatnagar
-------------------------
Name: Pradip K. Bhatnagar
      -------------------
Title: Director
       ------------------

cc: Vice President, Business Development, Glaxo Group Limited, doing business
    as GlaxoSmithKline
    Senior Vice President and Assistant General Counsel-R&D Legal Operations,
    GlaxoSmithKline Corporate Legal Department
    Kenneth A, Clark, Esq., Wilson Sonsini Goodrich & Rosati Professional
    Corporation
<PAGE>
                                  EXHIBIT 1.65
                            [Revised April 11, 2003]

                          Tractable Compound Criteria
                         (effective as of June 20, 2001)

                                      [*]

* Certain information on this page has been omitted and filed separately with
  the Commission. Confidential treatment has been requested with respect to the
  omitted portions.