Document:

Exhibit 10.12

 

AMENDMENT TO AGREEMENT

 

This is an Amendment to the Research
Collaboration and License Agreement between MERCK & CO., INC., a
corporation organized and existing under the laws of New Jersey (“MERCK”) and
ARRIS PHARMACEUTICAL CORPORATION, a corporation organized and existing under
the laws of Delaware, now known as Axys Pharmaceuticals, Inc. (“Axys”)
made as of November 6, 1996 (the “Agreement”).

 

1.             Section 2.8 of
the Agreement is hereby amended to read in its entirety:  “Research Program Term.  Except as otherwise provided herein, the term
of the Research Program shall commence on the Effective Date and continue for a
period of two years (or for three or more years if extended as provided below
in this Section 2.8) (the “Research Program Term”),
except that MERCK may terminate the Research Program and this Agreement in
accordance with Section 8.2.  The
parties by mutual written agreement executed by authorized representatives may
extend the Research Program Term for one or more additional years.  Upon extension of the Research Program Term,
if applicable, Attachment 2.1 setting forth the Research Program shall be
amended in writing by mutual agreement.”

 

2.             Section 5.2 of
the Agreement is hereby amended by adding a new subsection (d) as follows:  “(d) For Each Other
Additional Year of the Research Program Term:  If the Research Program Term is extended for
a Fourth or more additional Years as set forth in Section 2.8 above,
payments for the Fourth Year and for each other additional year shall equal
[***] per required FTE.”

 

3.             All references in the
Agreement to ARRIS or to Arris shall be deemed references to Axys.  All references in the Agreement to Arris
Pharmaceutical Corporation shall be deemed references to Axys Pharmaceuticals, Inc.

 

4.             Section 9.7 of
the Agreement is hereby amended to substitute the following new address of Axys
for the former address of Arris:

 

Axys Pharmaceuticals, Inc.

180 Kimball Way

South San Francisco, California  94080

Attention:  President, Chief Operating
Officer

Telecopier No.:  650/829-1001

 

5.             Capitalized terms
used and not otherwise defined herein shall have the respective meanings set
forth in the Agreement.  The Agreement,
together with this Amendment, contain the entire understanding of the parties
with respect to their subject matter. 
All express or implied agreements and understandings, either oral or
written, heretofore made are expressly merged in and made a part of the
Agreement.  This Agreement may be
amended, or any term thereof modified, only by a written instrument duly
executed by both parties hereto.

 

IN WITNESS WHEREOF,
the parties have executed this Amendment as of February 9, 1998.

 

	
  MERCK & CO., INC.

  	
   

  	
  AXYS PHARMACEUTICAL, INC.

  	
   

  
	
   

  	
   

  	
   

  	
   

  
	
  By:

  	
  /s/ Bennett M. Shapiro

  	
   

  	
  By:

  	
  /s/ Daniel H. Petree

  	
   

  
	
   

  	
  Bennett M. Shapiro

  	
   

  	
   

  	
  Daniel H. Petree

  	
   

  
	
   

  	
  Executive Vice President

  	
   

  	
   

  	
  President &

  	
   

  
	
   

  	
  Worldwide Basic Research

  	
   

  	
   

  	
  Chief Operating Officer

  	
   

  

 

 

[***] indicates material that
has been omitted pursuant to a request for confidential treatment. The omitted
material has been filed separately with the Securities and Exchange Commission.Exhibit 10.13

 

SECOND AMENDMENT TO AGREEMENT

 

This is the
second amendment to the Research Collaboration and License Agreement between
MERCK & CO., INC., a corporation organized and existing under the laws
of New Jersey (“MERCK”) and ARRIS PHARMACEUTICAL CORPORATION, a corporation
organized and existing under the laws of Delaware, now known as Axys
Pharmaceuticals, Inc. (“Axys”) made as of November 6, 1996 (the “Agreement”).
 The purpose of this second amendment is
to extend the Research Program Term in accordance with Section 2.8 of the
Agreement, and to amend Section 1.23(a)(iv) of the Agreement.

 

1.               In
accordance with Section 2.8 of the Agreement, the Research Program Term is
extended for one additional year, through November 5, 1999. Reference is
made to Section 5.2(C) of the Agreement.  The parties agree that a [***] FTEs will be
required during the period [***] and that [***] FTEs will be required during
the [***] the Research Program Term, i.e., from [***], the [***].

 

2.               Attachment
2.1 setting forth the Research Program is hereby amended to include the
additional research work set forth on the attachment to this second amendment.

 

3.               Section 1.23(a)(iv) is
hereby amended to read in its entirety as follows:

 

[***]

 

4.               Capitalized
terms used and not otherwise defined herein shall have the respective meanings
set forth in the Agreement.  The
Agreement, together with the first amendment dated February 9, 1998, and
this second amendment, contain entire understanding of the parties with respect
to their subject matter.  All express or
implied agreements and understandings, either oral or written, heretofore made
are expressly merged in and made a part of the Agreement as amended by the
first and second amendments.  The
Agreement and its amendments may be amended, or any term thereof modified, only
by a written instrument duly executed by both parties hereto.

 

IN WITNESS
WHEREOF, the parties have executed this Amendment as of November 5, 1998.

 

	
  MERCK & CO., INC.

  	
   

  	
  AXYS PHARMACEUTICAL, INC.

  
	
   

  	
   

  	
   

  
	
  By:

  	
  /s/ Bennett Shapiro

  	
   

  	
  By:

  	
  /s/Daniel Petree

  
	
   

  	
  Bernard W. Shapiro, M.D.

  	
   

  	
   

  	
  Daniel H. Petree

  
	
   

  	
  Executive Vice President

  	
   

  	
   

  	
  President &

  
	
   

  	
  Merck Research Laboratories

  	
   

  	
   

  	
  Chief Operating Officer

  

 

 

[***] indicates material that
has been omitted pursuant to a request for confidential treatment. The omitted
material has been filed separately with the Securities and Exchange Commission.

 

1

 

ATTACHMENT 2.1

 

RESEARCH PROGRAM

 

	
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  [***]

  
	
   

  	
   

  	
   

  
	
   

  	
   

  	
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  7

  	
   

  	
  [***]

  
	
   

  	
   

  	
   

  
	
  a.

  	
   

  	
  [***]

  
	
   

  	
   

  	
   

  
	
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  [***]

  
	
   

  	
   

  	
   

  
	
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  [***]

  

 

[***] indicates material that
has been omitted pursuant to a request for confidential treatment. The omitted
material has been filed separately with the Securities and Exchange Commission.

 

2

 

APPENDIX A-1

 

[***]

 

[***] indicates material that
has been omitted pursuant to a request for confidential treatment. The omitted
material has been filed separately with the Securities and Exchange Commission.

 

3

 

APPENDIX A-2

 

[***]

 

[***] indicates material that
has been omitted pursuant to a request for confidential treatment. The omitted
material has been filed separately with the Securities and Exchange Commission.

 

4

 

APPENDIX B

 

[***]

 

[***] indicates material that
has been omitted pursuant to a request for confidential treatment. The omitted
material has been filed separately with the Securities and Exchange Commission.

 

5

 

APPENDIX C-1

 

[***]

 

[***] indicates material that
has been omitted pursuant to a request for confidential treatment. The omitted
material has been filed separately with the Securities and Exchange Commission.

 

6

 

APPENDIX C-2

 

[***]

 

[***] indicates material that
has been omitted pursuant to a request for confidential treatment. The omitted
material has been filed separately with the Securities and Exchange Commission.

 

7Exhibit 10.14

 

THIRD AMENDMENT TO AGREEMENT

 

This is the third amendment to the Research
Collaboration and License Agreement between MERCK & CO., INC., a
corporation organized and existing under the laws of New Jersey (“MERCK”) and
ARRIS PHARMACEUTICAL CORPORATION, a corporation organized and existing under
the laws of Delaware, now known as Axys Pharmaceuticals, Inc. (“Axys”)
made as of November 6, 1996 (the “Agreement”).  The purpose of this third amendment is to
extend the Research Program Term through November 5, 2000, and to [***].

 

1.     In accordance with the provisions of Section 2.8
and Section 5.2(d) of the Agreement and subject to MERCK’s right to
terminate the Research Program and the Agreement in accordance with Section 8.2,
the Research Program Term is extended through November 5, 2000, and the
parties agree that [***] FTEs will be required during the period [***].  The FTEs for the period [***] shall be payable
at an annual rate of [***] per FTE. The FTEs for the period [***] shall be
payable at an annual rate of [***] per FTE.

 

2.     Attachment 2.1 setting forth the Research
Program is hereby amended to include the additional research work set forth on
the attachment to this third amendment.

 

3.     Capitalized terms used and not otherwise
defined herein shall have the respective meanings set forth in the Agreement.  The Agreement, together with the first
amendment dated February 9, 1998, the second amendment dated November 5,
1998 and this third amendment contain the entire understanding of the parties with
respect to their subject matter.  All
express or implied agreements and understandings, either oral or written,
heretofore made are expressly merged in and made a part of the Agreement as
amended by the first, second and third amendments.  All other terms and conditions of the
Agreement, as amended, continue in full force and effect.  The Agreement and its amendments may be
amended, or any term thereof modified, only by a written instrument duly
executed by both parties hereto.

 

IN WITNESS WHEREOF, the parties have entered
into this Amendment as of 18 November, 1999.

 

	
  MERCK & CO., INC.

  	
   

  	
  AXYS PHARMACEUTICAL, INC.

  
	
   

  	
   

  	
   

  
	
  By:

  	
  /s/ Roger M. Perlmutter, M.D., Ph.D

  	
   

  	
  By:

  	
  /s/ John P. Walker

  
	
   

  	
  Roger M. Perlmutter, M.D., Ph.D.

  	
   

  	
   

  	
  John P. Walker

  
	
   

  	
  Executive Vice President

  	
   

  	
   

  	
  Chairman

  
	
   

  	
  Worldwide Basic Research

  	
   

  	
   

  	
  Chief Executive Officer

  
	
   

  	
  And Preclinical Development

  	
   

  	
   

  	
   

  

 

[***] indicates material that
has been omitted pursuant to a request for confidential treatment. The omitted
material has been filed separately with the Securities and Exchange Commission.

 

1

 

Attachment
2.1

Research Program

 

ATTACHMENT 2.1

 

RESEARCH  PROGRAM

 

The work outlined below,
initiated [***], will be completed by [***].

 

	
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  d.

  	
   

  	
  [***]

  

 

[***] indicates material that has been omitted
pursuant to a request for confidential treatment. The omitted material has been
filed separately with the Securities and Exchange Commission.

 

2

 

APPENDIX A

 

[***]

 

[***] indicates material that has been
omitted pursuant to a request for confidential treatment. The omitted material
has been filed separately with the Securities and Exchange Commission.

 

3

 

APPENDIX B

 

[***]

 

[***] indicates material that has been
omitted pursuant to a request for confidential treatment. The omitted material
has been filed separately with the Securities and Exchange Commission.

 

4

 

APPENDIX C

 

[***]

 

[***] indicates material that has been
omitted pursuant to a request for confidential treatment. The omitted material
has been filed separately with the Securities and Exchange Commission.

 

5

 

APPENDIX D

 

[***]

 

[***] indicates material that has been
omitted pursuant to a request for confidential treatment. The omitted material
has been filed separately with the Securities and Exchange Commission.

 

6

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