exv10w23



 



[ * ] = 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.