Document:

<PAGE>
                                                                   Exhibit 10.21

[*] 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.

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

December 13, 2002

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: DEFINITION OF TOOL COMPOUND AND USE THEREOF 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 "Letter
Amendment"), GSK and CK desire to use certain tool compounds arising under the
Collaboration Agreement, all on the terms set forth herein.

Now therefore, GSK and CK agree, effective as of December 13, 2002 (the
"Letter Amendment Effective Date"), as follows:

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

     2.   A "Tool Compound" shall mean any Compound, including but not limited
          to [*] and [*], not designated nor intended to be designated as a
          Development Compound, and that the JRC has approved for distribution
          to Third Parties for the conduct of studies that may result in the
          subsequent publication of the results of such studies; provided that,
          such results are not to be reportable to the FDA. At the time of such
          approval by the JRC, the composition of matter and method of use of
          such Tool Compound shall be covered by a Patent within the Licensed
          Technology.

     3.   The JRC may amend the definition of Tool Compound at any time, such
          amendments to be reflected in agreed and approved minutes of JRC
          meetings; provided, once a Compound has met the definition of Tool
          Compound it shall remain a Tool Compound, unless and until otherwise
          mutually agreed in writing by the Parties.

* 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.
December 13, 2002
Page Two

      4.    Notwithstanding Sections 1.13, 1.53 and 5.7, and the restrictions
            on use and disclosure set forth in Sections 4.1 and 9.5, of the
            Collaboration Agreement, each Party shall have the right to use
            Tool Compounds, and information relating thereto, outside the
            Research Program for the sole purpose of generating negative control
            information in studies directed to the research, discovery and
            development of compounds based on their activity in directly
            modulating a target other than a Mitotic Kinesin Target, and
            Collaboration Technology and/or Post-Collaboration Technology shall
            not include any inventions and/or results that arise from such use.

      5.   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 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
           Letter Amendment shall be governed in accordance with the laws of the
           [*], without regard to principles of conflicts of laws.

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 Bhatnagar

Name: Pradip Bhatnagar, Ph.D.

Title: Alliance Management, 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

* 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>
                                                                   Exhibit 10.22

[*] 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 11, 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: ASSIGNMENT OF GSK MEDICINAL CHEMISTRY PERSONNEL TO HIT-TO-LEAD ACTIVITIES
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 that certain letter amendment to the Collaboration Agreement of even
date November 5, 2002 (the "Letter Amendment"), GSK and CK agreed to amend the
Collaboration Agreement in order to allow GSK to assign certain medicinal
chemistry personnel within GSK to perform hit-to-lead activities as part of the
Research Program under the Collaboration Agreement without such assignment
accruing toward the [*] ([*]) FTE limit of establishing a [*] Program pursuant
to Section 2.6.2(a) of the Collaboration Agreement.

Pursuant to this letter amendment to the Collaboration Agreement (the "H2L
Letter Amendment"), GSK and CK desire to void such Letter Amendment in its
entirety and replace it with this H2L Letter Amendment, all on the terms set
forth herein.

Now therefore, GSK and CK agree, effective as of November 5, 2002 (the "H2L
Letter Amendment Effective Date"), as follows:

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

     2.   The Letter Amendment shall be void and have no force or effect as
          between the parties, effective November 5, 2002.

     3.   GSK may assign chemistry personnel (other than CK FTEs) within GSK's
          chemistry resource at the rate (i.e., a running rate) of [*] ([*])
          full-time equivalents or more, solely to perform Hit-To-Lead
          activities under the Research Program relating to a particular Mitotic
          Kinesin Target, without such assignment and Hit-To-Lead activities
          accruing toward the [*]([*]) FTE limit of establishing a [*] Program
          pursuant to Section 2.6.2(a).

* 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 11, 2003
Page Two

     4.   Notwithstanding the foregoing, if a Tractable Compound has been
          identified with respect to a particular Mitotic Kinesin Target, the
          assignment by GSK of any chemistry personnel (other than CK FTEs) to
          perform activities relating to such Mitotic Kinesin Target, including
          without limitation any chemistry personnel within GSK's
          high-throughout chemistry resource (the "HTC Resource") and regardless
          of the activities of such personnel, shall accrue towards the [*]([*])
          FTE limit of establishing a [*] Program pursuant to Section 2.6.2(a).

     5.   As used herein, "Hit-To-Lead" shall mean those activities directed to
          the process of synthesizing and identifying active new chemical
          entities up to and including identification of a compound that meets
          the Tractable Compound Criteria. It is understood that activities
          directed to the subsequent synthetic modification and testing of a
          Tractable Compound are not included in Hit-To-Lead.

     6.   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 H2L 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 H2L Letter Amendment shall be governed in accordance with the
          laws of the [*], without regard to principles of conflicts of laws.

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 Bhatnagar
------------------------------------

Name: Pradip Bhatnagar
     -------------------------------

Title: Director, Alliance Management
      ------------------------------

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

*    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.

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