Document:

Exhibit 10.15

 

FOURTH AMENDMENT TO AGREEMENT

 

This is the fourth 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 fourth amendment is 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 parties agree that [***]
FTE’s will be required during the period [***] payable at an annual rate
of [***] per FTE.

 

2.     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 November 18, 1999, and this fourth 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, third and
fourth 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 March 3, 2000.

 

	
  MERCK & CO., INC.

  	
   

  	
  AXYS PHARMACEUTICAL, INC.

  
	
   

  	
   

  	
   

  
	
  By:

  	
  /s/ Mervyn Turner

  	
   

  	
  By:

  	
  /s/ Michael Venuti 3/15/00

  
					

 

 

[***] 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.

 

1Exhibit 10.16

 

FIFTH AMENDMENT TO AGREEMENT

 

This is the fifth 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 fifth amendment
is to extend the research term of the collaboration through November 5,
2001.

 

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, 2001 and the parties agree that [***] FTEs will
be required during the period [***] payable at an annual rate of [***]  per FTE.

 

2.             Attachment 2.1
setting forth the Research Program is hereby amended to include the additional
work set forth in the attachment to this fifth 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, the third amendment
dated November 18, 1999, the fourth amendment dated March 3, 2000 and
this fifth 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, third, fourth
and fifth 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 November, 2000.

 

	
  MERCK &
  CO., INC.

  	
  AXYS
  PHARMACEUTICALS, INC.

  
	
   

  	
   

  	
   

  
	
  BY:

  	
   

  	
   

  	
  BY:

  	
  /s/MICHAEL
  C. VENUTI 11/6/00

  
	
   

  	
   

  	
  Michael C.
  Venuti, Ph.D.

  
	
   

  	
   

  	
  Sr. VP
  Research, Chief Technical

  
	
   

  	
   

  	
  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.

 

 

ATTACHMENT 2.1

 

RESEARCH PROGRAM

 

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

 

	
  1.

  	
   

  	
  [***]

  
	
   

  	
   

  	
   

  
	
   

  	
   

  	
  [***]

  
	
   

  	
   

  	
   

  
	
  2.

  	
   

  	
  [***]

  
	
   

  	
   

  	
   

  
	
   

  	
   

  	
  [***]

  
	
   

  	
   

  	
   

  
	
  3.

  	
   

  	
  [***]

  
	
   

  	
   

  	
   

  
	
   

  	
   

  	
  [***]

  
	
   

  	
   

  	
   

  
	
  4.

  	
   

  	
  [***]

  
	
   

  	
   

  	
   

  
	
   

  	
   

  	
  [***]

  
	
   

  	
   

  	
   

  
	
  5.

  	
   

  	
  [***]

  
	
   

  	
   

  	
   

  
	
   

  	
   

  	
  [***]

  
	
   

  	
   

  	
   

  
	
  6.

  	
   

  	
  [***]

  
	
   

  	
   

  	
   

  
	
   

  	
   

  	
  [***]

  
	
   

  	
   

  	
   

  
	
  7.

  	
   

  	
  [***]

  
	
   

  	
   

  	
   

  
	
  a.

  	
   

  	
  [***]

  
	
   

  	
   

  	
   

  
	
  b.

  	
   

  	
  [***]

  
	
   

  	
   

  	
   

  
	
  c.

  	
   

  	
  [***]

  
	
   

  	
   

  	
   

  
	
  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.

 

 

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.

 

 

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.

 

 

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.

 

 

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.Exhibit
10.17

 

SIXTH AMENDMENT TO AGREEMENT

 

This is the sixth 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 sixth
amendment is to restructure the Milestone Payments pursuant to Section 5.3
of the Agreement.

 

1.                                       In
accordance with the provisions of Section 9.10 of the Agreement with
regard to an amendment of the Agreement, the parties hereby agree to amend Section 5.3
of the Agreement [***].  Accordingly, the
parties hereby agree that Section 5.3 shall be replaced in its entirety by
the following Section 5.3.

 

5.3                                 Milestone Payments.  Subject to the terms and conditions of this
Agreement, MERCK shall pay to Axys the following milestone payments:

 

(a)                                [***] upon MERCK’s validation, in
its sole reasonable judgment exercised in good faith, that an Active Compound
has met the criteria set forth in Section 1.23(a) of this Agreement,
as amended;

 

(b)                               [***] upon MERCK’s acceptance in its
sole discretion of a Program Compound for Safety Assessment as defined by
MERCK;

 

(c)                                [***] upon MERCK’s initiation of
Phase I human clinical trials using a Program Compound;

 

(d)                               [***] upon MERCK’s initiation
of Phase Ell human clinical trials using a Program Compound;

 

(e)                                [***] upon the
filing of an application with the Food and Drug Administration to
register a Licensed Product for marketing in the United States;

 

(f)                                  [***] upon approval by the
Food and Drug Administration to market a Licensed Product in the United States.

 

MERCK shall notify Axys in writing within 30 days
upon the achievement of each milestone described in (a) through (f) above,
and upon such notice shall pay Axys the appropriate milestone payment.

 

[***] 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

 

The
milestone payments described in (a) and (b) above shall [***].

 

The
milestone payments described in (c) through (f) above shall be [***].  Notwithstanding the foregoing, if [***], and
[***], MERCK shall [***], which shall include [***]. 

 

[***]
percent ([***]%) of each milestone payment made for the achievement of a
milestone described in (e) and (f) as set forth above shall [***]; provided, however,
that [***].

 

Notwithstanding
the foregoing, the parties hereby confirm that [***].

 

2.             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, the third amendment dated November 18, 1999, the fourth amendment
dated March 3, 2,000, and the fifth amendment dated November 10, 2000 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, third, fourth, fifth and sixth 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 the date of
the last party to sign below.

 

	
  MERCK & CO., INC.

  	
   

  	
  AXYS PHARMACEUTICALS, INC.

  
	
   

  	
   

  	
   

  
	
  BY:

  	
   

  	
   

  	
  BY:

  	
  /s/ [illegible]

  
	
  DATE:

  	
   

  	
   

  	
  DATE:

  	
   

  
							

 

[***] 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

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