EXHIBIT 10.41
PORTIONS OF THIS DOCUMENT HAVE BEEN OMITTED (DESIGNATED BY AN
ASTERISK (*) AND WHITE SPACE) AND FILED SEPARATELY WITH THE
SECURITIES AND EXCHANGE COMMISSION PURSUANT TO A REQUEST FOR
CONFIDENTIAL TREATMENT
DATED January 14, 1998; FILE NO. 0-15609
AMENDMENT TO AGOURON-ROCHE COLLABORATION
This Amendment to the Agouron-Roche Collaboration, dated for reference
purposes only this 1st day of December, 1997, is between Agouron
Pharmaceuticals, Inc., a corporation duly organized and existing under the laws
of the State of California, having a principal place of business at 10350 North
Torrey Pines Road, La Jolla, California, United States of America (hereinafter
referred to as "Agouron," the first party), and F. Hoffmann-La Roche Ltd, a
corporation duly organized and existing under the laws of Switzerland, having a
principal place of business at CH-4070-Basel, Switzerland, and Hoffmann-La Roche
Inc., a corporation duly organized and existing under the laws of the State of
New Jersey, having a principal place of business at 340 Kingsland Street,
Nutley, New Jersey, United States of America (hereinafter collectively referred
to as "Roche," the second party). Agouron and Roche are sometimes hereinafter
each referred to as a party (collectively "parties"). The parties hereby agree
as follows:
ARTICLE I - BACKGROUND
1.01 Defined terms used herein and not expressly defined (i.e., terms
with initial capitalization) shall have the meanings given to them in the
applicable agreements referred to below.
1.02 On June 19, 1996, Agouron and Roche entered into a Letter of
Intent ("LOI") to confirm the parties' formation of a collaboration (sometimes
referred to herein as the "Collaboration") on terms substantially in accordance
with those contained in Exhibit A to the LOI ("Exhibit A"). The components of
such Collaboration include programs for the development and commercialization of
the chemical compounds known as THYMITAQ(TM) (sometimes referred to herein as
AG337) and AG3340 and in certain circumstances substituted or additional backup
compounds, the Cell Cycle Control Research Program, and in certain circumstances
Agouron's right to commercialize a Roche Cancer Product. While Exhibit A
contains the basic terms of the understanding between the parties, the parties
agreed that the terms of the Collaboration would be subject to further
negotiation and preparation of further agreements that contain the full terms of
the Collaboration between the parties.
1.03 On June 11, 1997, the parties entered into the THYMITAQ
Development and License Agreement and the AG3340 Development and License
Agreement, which set forth the full terms of the Collaboration between the
parties with respect to the AG337 and AG3340 chemical compounds (and certain
substituted or additional backup compounds).
1.04 The parties have not entered into further agreements which set
forth the definitive terms under which the parties shall collaborate in the Cell
Cycle Control Research Program or Agouron's right to commercialize a Roche
Cancer Product.
1.05 Pursuant to the terms of the LOI and the THYMITAQ Development and
License Agreement ("THYMITAQ Agreement"), the parties are conducting the
THYMITAQ Development Program.
1.06 Pursuant to the terms of the LOI and the AG3340 Development and
License Agreement ("AG3340 Agreement"), the parties are conducting the AG3340
Development Program and a Backup MMP Inhibitor Research Program.
1.07 Pursuant to the terms of the LOI, the parties are conducting the
Cell Cycle Control Research Program.
1.08 The LOI and Sections 2.04 and 6.02(a) of the THYMITAQ Agreement
and Sections 2.04 and 6.02(a) of the AG3340 Agreement permit Roche to cancel the
development programs being conducted pursuant to such agreements.
1.09 Roche has informed Agouron that it has undertaken a review of its
internal and external research and development programs, and has determined to
refocus certain of its research and development efforts. As part of such
refocusing efforts, Roche has decided to terminate the THYMITAQ and AG3340
Development Programs and its rights to elect to develop and commercialize
substituted or additional backup compounds. Additionally, the parties have
decided to terminate the Cell Cycle Control Research Program and Agouron's right
to commercialize a Roche Cancer Product.
1.10 To effect the preceding and clarify the parties' rights and
obligations under the Collaboration, the parties wish to amend the Collaboration
as noted below.
ARTICLE II - AMENDMENT
2.01 Roche hereby irrevocably elects to terminate the THYMITAQ
Development Program effective December 8, 1997 pursuant to the provisions of
Sections 2.04 and 6.02(a) of the THYMITAQ Agreement. Effective December 1, 1997
Roche hereby irrevocably releases and terminates its rights under the provisions
of Sections 2.01(l) and (m) and 2.02 of the THYMITAQ Agreement to develop and
commercialize AG337, the free base form of AG337 and/or another salt thereof.
Roche further elects to terminate its rights under the THYMITAQ Trademark
License including its right to use the THYMITAQ Trademark.
2.02 Roche hereby irrevocably elects to terminate the AG3340
Development Program effective May 20, 1998 pursuant to the provisions of
Sections 2.04 and 6.02(a) of the AG3340 Agreement. Effective December 1, 1997,
Roche hereby irrevocably releases and terminates its rights under the provisions
of Sections 2.01(l) and (m) and 2.02 of the AG3340 Agreement to develop and
commercialize AG3340 and Backup MMP Inhibitors including the compounds listed on
Schedule 2 to the AG3340 Agreement.
2
2.03 Roche shall continue to be obligated for its share of the
Development Costs for the THYMITAQ Development Program until the effective
termination date of the THYMITAQ Development Program (December 8, 1997) and
shall fund and reimburse such obligation as described in Attachment 1 of the
applicable agreement. The parties further agree that no further license issuance
fees payments (other than the initial US$5 million fee) shall be due Agouron
pursuant to the provisions of Section 5.01(a) of the THYMITAQ Agreement.
2.04 Roche shall pay Agouron on or before December 15, 1997 *
in full satisfaction and
settlement of its share of the Development Costs for the AG3340 Development
Program for the period from October 1, 1997 until the effective termination date
of the AG3340 Development Program (May 20, 1998); provided, however, that Roche
shall be entitled to receive a credit against the amount due Agouron equal to
Roche's pre-payment of AG3340 Development Program Development Costs for the
calendar quarter ending December 31, 1997. Agouron shall have no obligation to
account to Roche for any Development Costs which Agouron incurs on or after
October 1, 1997 and shall be entitled to retain and use such * payment from
Roche for any purposes it sees fit, including uses unrelated to the AG3340
Development Program. Agouron shall reimburse Roche for any Development Costs
which Roche incurs after October 1, 1997 in performing development tasks
assigned to it by Agouron or agreed to by the parties including, but not limited
to, Development Costs incurred by Roche in performing the activities described
in Paragraphs 2.16, 2.17, 2.18 and 2.19 of this Amendment; Roche shall invoice
Agouron for such Development Costs in accordance with the provisions described
in Attachment 1 of the AG3340 Agreement. The parties further agree that no
further license issuance fees payments (other than the initial US$10 million
fee) shall be due Agouron pursuant to the provisions of Section 5.01(a) of the
AG3340 Agreement.
2.05 Roche agrees to cooperate with and provide reasonable assistance
to Agouron to effect an orderly transition of Roche's development and
Registration responsibilities for the THYMITAQ and AG3340 Development Programs
to Agouron. Agouron shall lead implementation of the AG3340 Development Program
during such transition. The parties will use reasonable efforts to transition to
Agouron by December 31, 1997 Roche's clinical, regulatory and project management
responsibilities for the AG3340 Development Program. The parties will use
reasonable efforts to complete substantially all of the transition on or before
the effective termination date of the applicable development programs. To the
extent that Roche's reasonable costs of conducting the transition activities
assigned to it by Agouron do not otherwise qualify as Development Costs, such
transition costs shall nevertheless be deemed to be Development Costs if Agouron
pre-approves of a budget for each of Roche's requested transition activites
detailing the basis of the calculation of such costs for each transition
activity and the maximun amount of costs which Roche may incur for each
transition activity; Roche shall be reimbursed for such pre-approved budgeted
transition costs in accordance with the provisions described in Attachment 1 of
the AG3340 Agreement. Roche does not warrant that it will be
3
able to complete any specific transition activity requested by Agouron within
the pre-approved maximun budgeted amount. If Roche determines that an additional
amount will be required to complete such transition activity, it will notify
Agouron of such fact before incurring any costs in excess of the pre-approved
maximun budgeted amount and will receive Agouron's approval for such additional
amount; if Agouron does not reasonably approve such additional amount, Roche
shall be relieved of its obligation to complete such transition activity.
2.06 In recognition of Agouron's continuing commercial interest in
THYMITAQ and AG3340 and the termination of Roche's commercial interest therein,
and notwithstanding any provision contained in the LOI, the THYMITAQ Agreement
and/or the AG3340 Agreement, Roche, its Affiliates, and their employees,
clinical investigators and consultants *
2.07 The parties agree that no New MMP Compound Patent Rights have
arisen from the conduct of the parties' research activities under the
Collaboration, and that effective December 1, 1997, the parties' collaborative
research activities conducted pursuant to the provisions of Section 4.05 of the
AG3340 Agreement shall terminate.
2.08 The parties agree effective December 1, 1997 to terminate the Cell
Cycle Control Research Program, and that the last day of the Cell Cycle Control
Research Term shall be December 1, 1997.
2.09 The parties agree that Agouron shall be deemed to have fully
earned and shall be entitled to retain all research support funding paid to it
by Roche pursuant to the provisions of Section B(2) of Exhibit A to the LOI and
that after November 30, 1997 Agouron shall have no obligation to assign its
scientists to work on the Cell Cycle Control Research Program. Additionally, the
parties agree that Roche shall not be obligated to pay Agouron for the amount of
the research support funding obligation which it would otherwise be
contractually obligated to pay Agouron on the second anniversary of the signing
of the LOI.
2.10 The parties agree that no Program Compounds, as such term is
defined in Section B(1) of Exhibit A to the LOI, shall be deemed to have been
invented by Roche and/or Agouron, separately or jointly, in the Cell Cycle
Control Research Program during the
4
Cell Cycle Control Research Term. *
The parties further acknowledge that Roche and/or Agouron,
separately or jointly, may each in the future file patent application(s) on
compounds invented by its employees during the Cell Cycle Control Research Term,
that such compounds shall be assigned to and owned by the employer(s) of the
employee(s) inventing such compounds and that the owner(s) of such compounds
shall determine the most appropriate manner to prepare, file, prosecute,
maintain and extend patent applications and issued patents to protect its
commercial interests in such compounds.
2.11 The parties agree that no Cell Cycle Control Research Program
Patent Rights have arisen from the conduct of the parties' research activities
under the Cell Cycle Control Research Program.
2.12 During the Research Term of the Cell Cycle Control Research
Program, the parties acknowledge that the parties have made *
2.13 The parties agree that each party shall be free, without any
further obligation to the other, to continue work in pursuit of the objectives
of the Cell Cycle Control Research Program (CDK4) on its own or with any third
party, and to retain, use and disclose to any such third party, information and
materials which have been developed in the Cell Cycle Control
5
Research Program (CDK4), provided that a party shall not disclose to such third
party the confidential and proprietary information of the other party and shall
not use such confidential and proprietary information for purposes other than in
pursuit of the objectives of the Cell Cycle Control Research Program (CDK4).
2.14 Upon written request from a party, the other party shall return to
the requesting party all remaining samples of any materials or compounds
provided to such party during the Collaboration. Each parties shall return all
copies of patent applications received from the other party as a result of the
negotiation and conduct of the Collaboration. *
2.15 Except as is necessary for Agouron's development and
commercialization of AG337 and AG3340 (and other backup compounds) or as
otherwise stated in this Amendment, each party shall have no further obligation
to disclose to the other party information, data or results, patents and/or
patent applications and/or to report or consult on its research, development,
commercialization and/or patent activities under the Collaboration.
2.16 Roche agrees to complete and provide Agouron, in written and/or
electronic format as appropriate, within 10 days after it becomes available to
Roche, the interim and final results, as well as supporting data, for all of its
ongoing toxicology and other pre-clinical studies *
2.17 Except for supplies of AG3340 needed by Roche to complete its
ongoing toxicology and other pre-clinical studies for AG3340, Roche agrees to
ship to Agouron (or its designee)* all existing bulk supply and finished product
of AG3340 which it then currently possesses. If requested by Agouron, Roche
agrees to use its reasonable efforts to complete the in-process *
Additionally, if
requested by Agouron, * Roche will use its reasonable efforts to
complete production of *
Roche agrees to
ship to Agouron (or its designee) as soon as it is available for shipment the *
Product(and copies of applicable batch records, manufacturer's certificates and
certificates of analysis), * and all remaining raw materials and
intermediates which were specifically purchased for AG3340
manufacturing activities that remain in Roche's possession
6
after completion of the manufacture of the above described batches. Agouron
plans to use the AG3340 Product in clinical trials and for other purposes.
2.18 Roche agrees to provide Agouron with all relevant available data
created in the applicable Development Program and samples to facilitate
Agouron's manufacture of AG337, AG3340, and any Backup MMP Inhibitors,
including*
2.19 Prior to May 20, 1998, Roche agrees to make its relevant personnel
available for reasonable consulting to assist in the manufacture of AG3340 and
any Backup MMP Inhibitors and in the transition of the manufacturing process
from Roche.
2.20 The parties shall jointly prepare and release a statement about
the amendment of the Collaboration between Agouron and Roche. Agouron shall be
entitled to release any further information about the THYMITAQ and AG3340
Development Programs which it deems appropriate; provided, however, Agouron
shall not use the Roche name in releases about the THYMITAQ and AG3340
Development Programs without the prior written consent of Roche. Roche shall not
release any further information to any third party who is not under an
obligation of confidentiality with respect thereto about any of the terms of
this Amendment or of the THYMITAQ and AG3340 Development Programs without the
prior written consent of Agouron, which consent may be withheld in Agouron's
sole discretion. This prohibition includes, but is not limited to, press
releases, educational and scientific conferences, promotional materials and
discussions with the media, investors and analysts. If Roche determines that it
is required by law to release information to any third party regarding the
subject matter of the THYMITAQ and AG3340 Development Programs, it shall use
reasonable efforts to notify Agouron of this fact prior to releasing the
information. The notice to Agouron shall include the text of the information
proposed for release. If possible Agouron shall have the right to confer with
Roche regarding the necessity for the disclosure and the text of the information
proposed for release.
2.21 Effective December 1, 1997, Agouron hereby irrevocably elects to
release and terminate its rights under the provisions of Section C(1) of Exhibit
A to the LOI to receive
7
marketing or acquisition rights in a Roche Cancer Product in the United States
and under Section C(2) of Exhibit A to the LOI to receive co-promotion rights in
a CDK2 Inhibitor in North America.
2.22 The parties agree to execute such further documents, instruments,
assignments, confirmations, certificates and assurances which are necessary or
desirable to carry out the purposes of this Amendment and to document, confirm
and certify the transfer of rights and obligations provided for hereunder.
2.23 Except as expressly amended by the terms contained herein, the
provisions of the LOI (including Exhibit A), the THYMITAQ Agreement, and the
AG3340 Agreement (including Section 5.01(c)) shall remain in full force and
effect unless the further application of any specific provision can not
reasonably be construed to remain in full force and effect after a good faith
consideration of the termination of the THYMITAQ and AG3340 Development
Programs, the Cell Cycle Control Research Program and/or Agouron's rights in a
Roche Cancer Product.
8
IN WITNESS WHEREOF, the parties have caused their duly authorized
representatives to enter into this Amendment to the Agouron-Roche Collaboration
effective as of the dates set forth above.
F. HOFFMANN-LA ROCHE LTD AGOURON PHARMACEUTICALS, INC.
By: /s/ R. Schaffner By: /s/ R. Kent Snyder
Name: R. Schaffner Name: R. Kent Snyder
Title: Head of Licensing Title: Sr. Vice President
By: /s/ St. Arnold By: /s/ Gary Friedman
Name: St. Arnold Name: Gary Friedman
Title: ppa Title: Corp. Vice President
HOFFMANN-LA ROCHE INC.
By: /s/ George W. Johnston
Name: George W. Johnston
Title: Vice President
By: /s/ William H. Epstein
Name: William H. Epstein
Title: Assistant Secretary
9