<PAGE>

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 10.31


      SECOND AMENDMENT TO THE AMENDED AND RESTATED RESEARCH, DEVELOPMENT
      AND MARKETING COLLABORATION AGREEMENT BETWEEN ONYX PHARMACEUTICALS,
      INC., A DELAWARE CORPORATION ("ONYX"), AND WARNER-LAMBERT COMPANY,
                      A DELAWARE CORPORATION ("WARNER")

         THIS SECOND AMENDMENT ("Second Amendment") between Onyx and Warner,
which Agreement was amended and restated July 1997, the AMENDED AND RESTATED
RESEARCH, DEVELOPMENT AND MARKETING COLLABORATION AGREEMENT as amended by that
certain Amendment dated December 15, 1997 (as amended, the "Agreement"), dated
as of May 2, 1995, is entered into and made effective March 1, 2000. Onyx and
Warner may be referred to herein individually as "Party," or collectively, as
the "Parties."

                                   RECITALS

         WHEREAS, Onyx and Warner desire to amend the Agreement to modify the
scope, personnel, resources, term, and research funding.

         NOW, THEREFORE, in consideration of the covenants contained in this
Second Amendment, the Parties hereby agree as follows:

          1.      Section 2.1, Undertaking and Scope, is amended to delete only
                  the fourth (4th) sentence, and replace it with the following:

                  Onyx agrees to use its best efforts at its cost [ * ] to
                  supply protein required to run screening assays relating to
                  biochemical targets, which targets were identified and
                  transferred to Warner prior to the Effective Date of this
                  Amendment.

          2.      Section 2.2, Personnel and Resources, is amended to delete
                  only the second (2nd) sentence, and replace it with the
                  following:

                  From the effective date of the Agreement until March 1, 2000,
                  Warner and Onyx will each maintain at their cost an average of
                  [ * ] full-time equivalents ("FTEs") devoted to cooperative
                  work under the Research Plan. Starting March 1, 2000 until the
                  end of the Term of the Research Collaboration, the number of
                  FTEs that Onyx shall devote to the cooperative work shall be
                  reduced to [ * ]. The number of FTEs may, however, be
                  increased up to [ * ] by the Research Management Committee
                  provided there is a concomitant reduction in the number of
                  FTEs that are working on the Research, Development and
                  Marketing Collaboration



                                       1.
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                  Agreement pertaining to Inflammation ("Inflammation
                  Agreement"), having an effective date of July 31, 1997.

          3.      Section 2.3, Term of the Research Collaboration, 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 August 31,
                  2001.

          4.      Section 9.1, Research Funding, is amended to delete the
                  months May 2, 2000 through February 2, 2001 and substitute
                  therefor the following:

                  June 1, 2000                       [ * ]
                  Sept. 1, 2000                      [ * ]
                  Dec. 1, 2000                       [ * ]
                  Mar. 1, 2001                       [ * ]
                  June 1, 2001                       [ * ]

          5.      Except as otherwise specifically set forth herein, all of the
                  terms and conditions of the Agreement shall remain in full
                  force and effect.

         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/ Peter B. Corr
       -----------------------------                --------------------------

Name:   Hollings C. Renton                   Name:   Peter B. Corr, Ph.D.
       -----------------------------                --------------------------

Title:  President & CEO                      Title:  Corporate Vice-President,
       -----------------------------                --------------------------
                                                      Warner-Lambert Company
                                                      President, Parke-Davis
                                                      Pharmaceutical Research
                                                      & Development



[ * ] = 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.


                                       2.