[ * ] = 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 24B-2 OF THE SECURITIES EXCHANGE ACT OF 1934, AS
AMENDED.

EXHIBIT 10.23

AMENDMENT

          AMENDMENT dated December 15, 1997 (this “Amendment”), to the Amended
and Restated Research, Development and Marketing Collaboration Agreement between
Onyx Pharmaceuticals, Inc., a California corporation (“Onyx”) and Warner-Lambert
Company, a Delaware corporation (“Warner”), which Amended and Restated Agreement
(the “Agreement”) was executed during July 1997.

W I T N E S S E T H:

          WHEREAS, Onyx and Warner desire, among other things to modify the
field of their cell cycle control collaboration under the Agreement, extend the
term of the Agreement and modify their mutual rights under the Agreement to
Japan,

          NOW, THEREFORE, the parties hereby agree as follows:

          1.     Definitions. (a) Capitalized terms used but not defined in this
Amendment will have the meanings ascribed thereto in the Agreement.

               (b) The following definitions are hereby added to Article 1 of
the Agreement:

    “Generation 1 Collaboration Compounds” shall mean Collaboration Compounds
that are initially identified under the Collaboration as having activity against
any of the following targets: [*].       “Generation 2 Collaboration Compounds”
shall mean Collaboration Compounds that are initially identified under the
Collaboration as having activity against any targets in the Field other than
those set forth in the definition of Generation 1 Collaboration Compounds.

          2.     Field. The definition of “Field” found in Article 1 of the
Agreement is hereby amended by deleting the third and all later paragraphs
thereof in their entirety and replacing the same by the following:

    Field

1.

--------------------------------------------------------------------------------

 

    The Field will consist of [*]. The field shall also include [*] The Field
will also include the [*] as well as targets that control the activity of [*]  
    Exclusions       Notwithstanding the general description of the Field
provided above, the Field will exclude:

  (a)   All molecular entities that are part of or that regulate [*] This
includes but is not restricted to [*] This also includes molecules that directly
or indirectly regulate the aforementioned molecules, [*] This also includes [*]
This exception shall not include (by way of example and not limitation) [*]

3.     Term of Research Collaboration. Section 2.3 of the Agreement is hereby
deleted in its entirety and replaced by the following:

            2.3      Research Term. Work under the Research Plan will commence
as of May 2, 1995 and, unless terminated earlier by either party pursuant to the
terms of this Agreement or extended by mutual agreement of the parties, will
terminate on the sixth anniversary thereafter (as terminated, expired or
extended, the “Term of the Research Collaboration”). At least thirty (30) days
prior to the five-year anniversary of the Effective Date, Onyx will provide
Warner a written research proposal for continuation of the research project
beyond such initial six-year Term of the Research Collaboration. Promptly after
Onyx provides such proposal, the Research Management Committee will conduct a
formal review of such proposal and of the status and success of the parties’
work on the Research Plan. By the five-year anniversary of the Effective Date
(the “Evaluation Date”), Warner shall decide in its sole discretion whether to
extend the collaborative research under the research proposal beyond the initial
six-year term for at least one additional year, or not to extend the
collaborative research beyond such initial term, in which case the Agreement
shall terminate at the end of such initial six-year Term of the Research
Collaboration. If Warner does not elect in writing to extend the Term of the
Research Collaboration beyond such initial six-year term, then commencing on or
promptly after the Evaluation Date, the work conducted by Onyx and Warner will
be wound down and ended in an orderly twelve-month phase-out period, ending on
the first anniversary of the Evaluation Date, with Onyx continuing the research
efforts using [*] FTEs over such period. During such phase-out period, Warner
will be obligated to pay Onyx a total of [*] to support Onyx’s research efforts
using [*] FTEs over such phase-out period, which amounts shall be paid in four
equal installments in advance over such year, commencing on the Evaluation Date,
in lieu of the last four research funding payments as specified in Section 9.1.
Furthermore, during the phase-out period, Warner may modify or eliminate its FTE
and other commitments under Section 2.2 in its sole discretion. In the event of
a phase-out during the

2.

--------------------------------------------------------------------------------

 

    final year of the Term of the Research Collaboration, the terms of this
Section 2.3 will supersede those of Section 2.2.

          4.     Research Funding. Section 9.1 of the Agreement is hereby
amended by the addition of the following funding commitments:

         
May 2, 1998
  $ 562,500  
August 2, 1998
    562,500  
November 2, 1998
    562,500  
February 2, 1999
    843,750  
May 2, 1999
    843,750  
August 2, 1999
    843,750  
November 2, 1999
    843,750  
February 2, 2000
    843,750  
May 2, 2000
    843,750  
August 2, 2000
    843,750  
November 2, 2000
    843,750  
February 2, 2001
    843,750  
 
   

--------------------------------------------------------------------------------

 
 
  $ 9,281,250  

          5.     Generation 1 Milestones. The phrase “Collaboration Product”
found throughout Section 9.2(a) and Section 9.2(b) of the Agreement is hereby
deleted in each instance and replaced by the phrase “Generation 1 Collaboration
Product.” The parenthetical “(provided that each such Generation 1 Collaboration
Product is a different chemical entity)” is hereby added immediately after the
two places where the word “approved” is found in Section 9.2(b) of the
Agreement.

          6.     Generation 2 Milestones. The following is hereby added as a new
Section 9.3 of the Agreement:

    9.3   Generation 2 Collaboration Products. (a) Warner will pay Onyx the
following amounts with respect to the first Generation 2 Collaboration Product
to achieve each stated milestone:

         
Commencement of Phase I clinical trials by or on behalf of Warner anywhere in
the world
  [*]    
Commencement of Phase II clinical trials by or on behalf of Warner anywhere in
the world
  [*]    
Commencement of Phase III clinical trials by or on behalf of Warner anywhere in
the world
  [*]    
The FDA’s acceptance for filing of an NDA
  [*]    
Acceptance for filing of an MAA applicable to any of the following countries:
(i) United Kingdom, (ii)
       

3.

--------------------------------------------------------------------------------

 

         
Spain, (iii)Italy, (iv) France and (v) Germany (each a “Major European Country”)
  [*]  
 
  country up to
 
  [*] total
 
   
Approval by the FDA of an NDA
  [*]  
 
   
Approval of an MAA applicable to a Major European Country
  [*]  
 
  country, up to
 
  [*] total

    (b) Warner will pay Onyx [*] upon the approval by the FDA of an NDA for the
second and each subsequent Generation 2 Collaboration Product so approved
(provided that each such Generation 2 Collaboration Product is a different
chemical entity) and [*] upon the approval of an MAA applicable to each Major
European Country, up to [*] for the second and each subsequent Collaboration
Product so approved (provided that each such Generation 2 Collaboration Product
is a different chemical entity).       (c) Warner will pay Onyx [*] upon
certification by the Research Management Committee that the first screening
assay for the Generation 2 Targets has been completed and the hits analyzed.

             7.   Japanese Milestones. The following is hereby added as a new
Section 9.4 of the Agreement:

      Section 9.4 Japanese Milestones. (a) Warner will pay Onyx the following
amounts with respect to the first Collaboration Product to achieve each stated
milestone:

         
Commencement of Phase I clinical trials by or on behalf of Warner in Japan
    [*]  
 
       
Commencement of Phase II clinical trials by or on behalf of Warner in Japan
    [*]  
 
       
Commencement of Phase III clinical trials by or on behalf of Warner in Japan
    [*]  
 
       
Acceptance for filing by the MHW of an MAA in Japan
    [*]  

    (b) Warner will pay Onyx [*] upon approval of each Collaboration Product for
sale in Japan by the MHW, provided each such Collaboration Product is a
different chemical entity.

4.

--------------------------------------------------------------------------------

 

            8.   Japan. The parenthetical “(except for Japan)” found in
Sections 6.1, 6.2, 6.3 and 6.4 of the Agreement is in each instance hereby
deleted. The phrase “other than Japan” found in the antepenultimate sentence of
Section 5.3 of the Agreement is hereby deleted. Sections 11.1, 11.2 and 11.3 of
the Agreement are hereby deleted in their entirety.

            9.   Exclusivity. Section 12.7 of the Agreement is hereby deleted in
its entirety and replaced by the following:

            12.7    Exclusivity.

            "(a)    Except as otherwise provided in subsection (b) below, during
the Term of the Research Collaboration and for one year thereafter (i) neither
party will conduct any research or development in the Field except pursuant to
this Agreement, (ii) neither party will license (or otherwise permit access to)
any of its Patents or Know-How for research or development in the Field to (or
otherwise collaborate on research or development in the Field with) any other
person or entity and (iii) Onyx will not license (or otherwise permit access to)
any assay developed by it pursuant to the Collaboration to any other person or
entity. In respect of (i), above, each party shall have the right to conduct its
own research and development in the Field during the one year following the end
of the Term of the Research Collaboration, provided that all results of such
work discovered during such period (including without limitation compounds and
assays), and analogs and derivatives of compounds identified during such period
whenever identified, are promptly disclosed to the other party and are covered
by the licenses granted under Sections 1.4, 5.1 and 5.2, as applicable.      
        "(b)    If Warner elects at the Evaluation Date, as provided in Section
2.3, not to extend the Term of the Research Collaboration beyond the end of the
initial six year Term of the Research Collaboration, then as of the Evaluation
Date the provisions of subsection (a) above will be modified as follows: (i) the
phrase “during the Term of the Research Collaboration and for one year
thereafter” in the first sentence of subsection (a) shall be modified to read
“during the Term of the Research Collaboration and for six months thereafter;”
(ii) for any new targets in the Field (the “New Targets”) that Onyx proposed to
Warner, in the written research proposal submitted by Onyx to Warner under
Section 2.3, to be the subject of the Research Collaboration (i.e., targets
within the Field that are not, as of the Evaluation Date, the subject of
collaborative research under the Research Collaboration) then commencing at the
end of the Term of the Research Collaboration and thereafter, the restrictions
in subsections 12.7(b)(i) and 12.7(b)(ii) shall not apply to all such New
Targets; and (iii) the last sentence of subsection (a) shall only apply for six
months after the end of the Term of the Research Collaboration, and shall not
apply to any work conducted by a party after the end of the Term of the Research
Collaboration with respect to New Targets, or to any results of such work
(including without limitation compounds and assays, and analogs and derivatives
of compounds identified).”

5.

--------------------------------------------------------------------------------

 

            IN WITNESS WHEREOF, the parties have caused this Amendment to be
executed by their duly authorized officers as of the date first written above.

      ONYX PHARMACEUTICALS, INC.   WARNER-LAMBERT COMPANY
      By:  /s/ Hollings C. Renton

--------------------------------------------------------------------------------

  By:  /s/ Wendell Wieranga, Ph.D.

--------------------------------------------------------------------------------

      Name:    Hollings C. Renton   Name:    Wendell Wieranga, Ph.D.      
Title:      President and CEO   Title:    Senior Vice President, Worldwide

Preclinical Research, Development and Technologies
Parke-Davis Pharmaceutical Research

[ * ] = 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 24B-2 OF THE SECURITIES EXCHANGE ACT OF 1934, AS
AMENDED.

6.