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EXHIBIT 10.70
COLLABORATIVE RESEARCH AND LICENSE AGREEMENT
BETWEEN
COMBICHEM, INC.
AND
ICOS CORPORATION
MAY 7, 1999
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COLLABORATIVE RESEARCH AND LICENSE AGREEMENT
THIS COLLABORATIVE RESEARCH AND LICENSE AGREEMENT (the "Agreement") is
entered into and made effective as of May 7, 1999 (the "Effective Date"), by and
between COMBICHEM, INC., a Delaware corporation having its principal offices at
0000 Xxxxxx Xxxxx Xx, Xxx Xxxxx, Xxxxxxxxxx 00000 ("CombiChem") and ICOS
CORPORATION, a Delaware corporation having its principal offices located at
00000 00xx Xxxxxx X.X., Xxxxxxx, Xxxxxxxxxx 00000 ("ICOS").
WHEREAS, CombiChem has developed, licensed and/or owns certain drug
discovery technology and intellectual property rights, including chemical
library design software, multi-parallel synthesis and purification methods,
chemical libraries suitable for high throughput biological screening assays and
medicinal chemistry (collectively, "CombiChem Technology");
WHEREAS, as of the Effective Date, ICOS and its Affiliates have
developed and own certain drug discovery and intellectual property rights,
including certain assays, methods and know how regarding the Initial Target,
among other things (collectively "ICOS Technology");
WHEREAS, ICOS desires to utilize CombiChem Technology for its drug
discovery activities under ICOS know-how concerning the identification and
characterization of novel small molecule inhibitors for development as
therapeutics for treatment of diseases in humans;
WHEREAS, the parties wish to collaborate in a chemical lead and drug
discovery program, commencing on the Effective Date against a Collaboration
Target ("Collaboration"); and
WHEREAS, during the Collaboration, the Parties intend to focus on the
Initial Target.
NOW, THEREFORE, the Parties agree as follows:
1. DEFINITIONS
1.1 "Active Compound(s)" means a compound (or compounds) or its
Derivatives which
(a) (i) is selected by the RMC under the Research Program from
Collaboration Compounds under Section 4.2, or
(ii) is a Derivative of a Collaboration Compound which has
been so selected by the RMC to be an Active Compound;
and
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(b) shows In Vitro Activity satisfactory to the requirements of the
Research Plan.
1.2 "Affiliate" of a Party means any corporation or other business
entity controlled by, controlling or under common control with, such Party. For
this purpose "control" shall mean direct or indirect beneficial ownership of
more than fifty percent (50%) of the voting securities or income interest in
such corporation or other business, or if not meeting the preceding
requirements, any company owned or controlled by or owning or controlling such
Party at the maximum control or ownership right permitted in the country where
such company exists.
1.3 "Collaboration" has the meaning set forth in the preamble.
1.4 "Collaboration Compound(s)" means a compound (or compounds)
which (a) is synthesized following the Effective Date for screening against a
Collaboration Target under the Research Program, (b) is a pre-existing or
hereafter acquired CombiChem compound which CombiChem desires to designate as a
Collaboration Compound, or (iii) is a pre-existing or hereafter acquired ICOS
compound which ICOS desires to designate as a Collaboration Compound.
1.5 "Collaboration Patent" means a Patent to which CombiChem has
made an inventive contribution arising out of the Collaboration, as determined
under U.S. Patent law.
1.6 "Collaboration Target" means (a) the Initial Target beginning on
the Effective Date or (b) any other target by mutual written agreement of the
Parties.
1.7 "CombiChem Compound" means a chemical compound that is
proprietary to CombiChem, or whose use or manufacture is proprietary to
CombiChem.
1.8 "CombiChem Technology" has the meaning set forth in the
preamble.
1.9 "Confidential Information" includes, but is not limited to,
(a) all information and materials received by either Party from the
other Party pursuant to this Agreement which is confidential under
Article 11 hereof,
(b) all information and materials by either Party arising out of the
Collaboration during the Research Period including, without
limitation, information directly and specifically deduced from
Confidential Information such as information regarding compounds
that were not active against the Targets in the screening or
secondary selective assays; and
(c) the terms and conditions of this Agreement.
1.10 "CPI" means the Consumer Price Index, All Urban Consumers, as
published by the U.S. Bureau of Labor Statistics.
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1.11 "Daughter Libraries" shall mean the compound libraries which
are designed and synthesized as a part of the Collaboration either by CombiChem
or under the direction of the RMC.
1.12 "Derivative" shall mean a compound (or compounds) which has
resulted
(a) (i) from chemical synthesis, during the Exclusivity Period, to
generate an Active Compound or Development Compound in support of
the Research Program or (ii) from chemical synthesis on an Active
Compound or Development Compound in support of the Research Program;
and
(b) is covered under claims of any Collaboration Patent.
1.13 "Development Compound(s)" means a Collaboration Compound (or
compounds) which
(a) (i) is an Active Compound or (ii) is a Derivative of an Active
Compound; and
(b) is determined by ICOS to be appropriate for the purpose of IND
filing by ICOS either before preclinical studies or from the results
of preclinical studies to determine without limitation, data on
efficacy, potency, toxicity, bioavailability and other
pharmacokinetics related parameters.
1.14 "Due Diligence" means the use of by a Party of its resources in
the Collaboration in a manner which is consistent with the exercise of
reasonable and prudent scientific and business judgment as applied to other
programs of ICOS or CombiChem, as the case may be, targeting products aimed at
markets or patient groups of similar sizes and of similar scientific and
commercial potential. With respect to any Development Compound, "Due Diligence"
shall also require ICOS or its Affiliates, partners or licensees to use
commercially reasonable efforts to conduct all necessary preclinical studies and
to file an IND for such Development Compound within a commercially reasonable
period from the date upon which ICOS has designated such Development Compound
from any Active Compound or its Derivatives. For purposes of this Agreement,
failure to exercise Due Diligence by any Party may be alleged by written notice
to such Party describing such failure with specificity and describing the
actions necessary to cure such failure with specificity (the "Due Diligence
Notice"). Sixty (60) days after delivery of a Due Diligence Notice, if the Party
receiving such Due Diligence Notice has not completed the actions necessary to
cure such failure as specified in such Due Diligence Notice to the reasonable
satisfaction of the other Party, the Parties shall immediately be subject to the
dispute resolution provisions set forth in Article 15 hereof starting at the
discussions between the Parties' Chief Executive Officers described in Section
15.1 hereof.
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1.15 "Exclusivity Period" means the Research Period plus *** as may
be extended or reduced pursuant to Article 4 hereof.
1.16 "Field" means all therapeutic indications in humans for any
Target against which a Collaboration Compound, Active Compound, Development
Compound or Products may be directed.
1.17 "First Commercial Sale" of a Product shall mean the first sale
for use or consumption of such Product in a country after required marketing and
pricing approval has been granted by the governing health regulatory authority
of such country. Sale to an Affiliate shall not constitute a First Commercial
Sale unless the Affiliate is the end user of the Product.
1.18 "FTE" shall mean a full-time equivalent employee of CombiChem
having the requisite skills to fulfill CombiChem's obligations under this
Agreement. For purposes of this Agreement, the FTEs shall include synthetic and
analytical chemists, compound control scientists and computational scientists.
1.19 "Inactive Compound(s)" means a Collaboration Compound(s) which
is not an Active Compound or an Active Compound that is reclassified as
described in Section 4.2 hereof.
1.20 "ICOS Compound" means a chemical compound that is proprietary
to ICOS or its Affiliates or whose use or manufacture is proprietary to ICOS or
its Affiliates.
1.21 "ICOS-FTE" means a full-time equivalent employee of ICOS having
the requisite skills to fulfill CombiChem's obligations under this Agreement.
For purposes of this Agreement, the ICOS-FTEs shall include synthetic chemists.
1.22 "ICOS Technology" shall have the meaning set forth in the
preamble of this Agreement.
1.23 "In Vitro Activity" shall mean during the Research Tenn, the
observation of *** in assays as described by ICOS in the Research Plan for each
Collaboration Target.
1.24 "Initial Target" shall have the meaning set forth in Section
3.1 hereof.
1.25 "Net Sales" means the gross sales invoiced by ICOS, its
Affiliates or its sublicensees for Products to non-Affiliated Third Parties (and
to Affiliates who are the end users of such Products) less actual deductions or
returns (including withdrawals and recalls), rebates (price reductions,
including formulary or Medicaid and similar types of rebates, e.g. chargebacks),
cash, trade or volume (quantity) discounts, discounts granted at the time of
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invoicing, the cost of transport, insurance, delivery, sales taxes and use,
tariff, excise or other taxes (other than income taxes) directly linked to and
included in the gross sales amount as computed on a product-by-product basis for
the countries concerned, whereby the amount of such sales in foreign currencies
is converted into United States dollars at the exchange rate of the last
business day for each calendar month as reported in The Wall Street Journal.
1.26 "Patent" means (a) valid and enforceable U.S. or non U.S.
Patent, and any non-U.S. equivalent, including any extension (including
Supplemental Protection Certificates), registration, confirmation, reissue,
continuation, divisionals, continuation-in-part, reexamination or renewal
thereof, or (b) pending applications for any of the foregoing, whether filed or
issued before or after the Effective Date.
1.27 "Party" means CombiChem or ICOS, as the case may be, including
their respective Affiliates, permitted successors and assigns.
1.28 "Product(s)" means any product containing an Active Compound or
Development Compound with such compound as the active ingredient or one of the
active ingredients, which is the subject of one or more claims under a
Collaboration Patent and which is granted regulatory approval by the governing
health regulatory authority of the applicable country for marketing in the
Field.
1.29 " *** " shall have the meaning set forth in *** .
1.30 "Research Management Committee" or "RMC" has the meaning set
forth in Article 6 below.
1.31 "Research Period" means that part of the Collaboration
commencing *** , or sooner by mutual written agreement, *** , unless earlier
terminated, and which can be extended in accordance with Section 7.1 below for
the Initial Target.
1.32 "Research Plan" means the research plan to be agreed in writing
between the Parties, which describes in mutually agreed upon detail the research
activities to be performed for each Collaboration Target.
1.33 "Research Program" means the research and activities to be
conducted for the Collaboration during the Research Period including, without
limitation, the activities described in the Research Plan and set forth in
Sections 2.1 and 2.2 of this Agreement.
1.34 "Returned Compound" shall have the meaning set forth in Section
9.2.
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1.35 "Royalty Term" means, in the case of any Product, in any
country in which sales occur, the period of time commencing on the First
Commercial Sale in that country and ending upon the later of (a) *** *** ; or
(b) the expiration of the last-to-expire Patent resulting from the Research
Program filed in the Field during the Exclusivity Period with claims covering
that Product in the relevant country. In the event such *** shall extend beyond
the end of the term or terms of the last to expire Patents resulting from the
Research Program containing a valid claim in such country, the earned royalties
hereunder in such country shall be *** for the remainder of such *** so long as
*** as the Product exists and is sold in competition with the Product.
1.36 "Target" means a biomolecular entity that a Collaboration
Compound is synthesized against wherein the small molecule demonstrates relevant
activity.
1.37 "Target Exclusivity Obligations" shall have that meaning set
forth in subsection 4. 1 (a) hereof.
1.38 "Territory" means *** .
1.39 "Third Party" means an entity other than CombiChem or ICOS or
their respective Affiliates or assigns.
1.40 "UIL" means CombiChem's proprietary Universal Informer
Library(TM).
2. RESEARCH COLLABORATION
2.1 CombiChem Responsibilities. CombiChem shall with Due Diligence
provide the following resources to ICOS and conduct the following activities
under the Research Program and as more fully described in the Research Plan:
(a) Within *** of the Effective Date, CombiChem will deliver to ICOS
its UIL sufficient in quantity for ICOS to screen against the
Initial Target and any Target contained in Appendix B at the time of
such shipment. The Parties hereby agree that the obligations and
responsibilities in this Section 2.1(a) have been fully and finally
completed and performed by the Parties as part of a separate
agreement between the Parties and constitute separate and valuable
consideration between the Parties in respect of this Agreement.
(b) At any time following the Effective Date, CombiChem shall
provide to ICOS data analysis and evaluations for results from the
screening of the UIL against the Initial Target within *** of
CombiChem's receipt of the
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relevant screening data from ICOS. The Parties hereby agree that the
obligations and responsibilities in this Section 2.1(b) have been
fully and finally completed and performed by the Parties as part of
a separate agreement between the Parties and constitute separate and
valuable consideration between the Parties in respect of this
Agreement.
(c) During the Research Period, CombiChem shall (i) review data and
information regarding the Collaboration Target provided by ICOS and
derived from the UIL by CombiChem; (ii) based on such data and
information and using the CombiChem Technology, design Daughter
Libraries; and (iii) supply all lead chemistries and synthesize
compounds as provided in Section 5.4 hereof.
(d) During the Research Period, CombiChem shall keep ICOS informed
of its activities performed in connection with the Collaboration,
including, without limitation, providing ICOS with data and
information (and, upon ICOS's request, reasonable quantities of
samples pursuant to Section 5.4) regarding the status of all
Collaboration Compounds prior to the meetings of the Research
Management Committee.
(e) Subject to Section 2.3, Article 3 and Section 8.3 hereof, and at
all times during the Research Period, CombiChem shall dedicate, in
separate laboratory facilities as to its chemistry efforts, *** , to
conduct all of CombiChem's activities in connection with the
Collaboration at a per annum rate of U.S. *** per FTE to be paid by
ICOS. The ***
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*** unless the RMC recommends otherwise and ICOS and CombiChem
agree in writing to alter the size of *** .
2.2 ICOS Responsibilities. ICOS shall with Due Diligence provide the
following resources to CombiChem and conduct the following activities under the
Research Program as more fully described in the Research Plan:
(a) ICOS shall make payment to CombiChem for the Collaboration as
set forth in Article 8 hereof, provide screening, biological and
structural data and information (including leads and/or screening
hits and any assay methods relating to Collaboration Compounds) to
CombiChem necessary for CombiChem to perform its duties under this
Agreement, and will assume scientific, financial and
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administrative responsibility for screening and biological support
activities, drug development and regulatory filings during and after
the term of the Collaboration on the terms set forth below.
(b) During the Research Period, ICOS shall provide CombiChem with
data and information regarding Collaboration Compounds and the
Collaboration Target assays developed by ICOS under the Research
Program prior to the meetings of the Research Management Committee.
(c) During the Exclusivity Period, ICOS shall screen Collaboration
Compounds for *** Activity and, where ICOS reasonably deems it to be
appropriate, *** activity against the Collaboration Target.
(d) During the Exclusivity Period, with respect to any Collaboration
Target against which an Active Compound has been designated by the
RMC, ICOS shall (i) screen Active Compounds, (ii) determine
Development Compounds, and (iii) endeavor to develop Products. At
any time during the Collaboration, ICOS may apply chemistry effort,
including synthesis, to any Collaboration Compound as agreed and
directed by the RMC.
(e) Following the first IND filing through First Commercial Sale,
ICOS shall provide CombiChem with an annual report similar to that
which would be provided in the usage of the trade or business, by a
licensee to a licensor summarizing ICOS's activities in developing
Development Compounds that shall include, without limitation, all
material information with respect to the following: (i) status of
both regulatory filings and communications with the United States
Food and Drug Administration or any foreign equivalent ("FDA"); (ii)
status of Patents within and outside of the United States; (iii)
status of current and planned clinical trials; (iv) occurrence of
any milestone events; and (v) any permitted sublicensing under this
Agreement.
(f) During the Research Period and in connection with CombiChem
providing the services in Section 2.1(e) hereof, ***
***
*** to support the activities under this Agreement at CombiChem's
San Diego facilities under the Research Program. By mutual written
agreement, such ICOS-FTEs may perform the work requirements
necessary under this Agreement in ICOS's facilities. Such ICOS-FTEs
on the Project Team shall report to the CombiChem project leader.
ICOS shall have sole responsibility for the general salary and
living expenses associated with its visiting chemists, including,
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without limitation, salary, travel, living and other associated
expenses of such chemists.
2.3 Conduct of Research Program. The Parties hereby agree that the
Research Programs shall be carried out in accordance with the Research Plan and
this Agreement, as each may be amended from time to time. The Research
Management Committee shall review the Research Plan on a regular and ongoing
basis and may make written changes to the Research Plan so long as such changes
are mutually agreed to in writing by CombiChem and ICOS.
2.4 Third Party Licenses. Each Party shall be solely responsible for
any Third Party license fees required to perform its obligations under this
Agreement.
3. TARGETS
3.1 Initial Target. ***
3.2 Substitute Target. After the commencement of a Research Program
with respect to the Collaboration Target, the Parties, by mutual written
agreement, may substitute another target for such Collaboration Target.
4. EXCLUSIVITY
4.1 Collaboration Target Exclusivity.
(a) Following the Effective Date, so long as ICOS or its Affiliates
are proceeding with Due Diligence for that Collaboration Target,
CombiChem shall not work on, or provide services, or advise, either
independently, or with any Third Parties (except where CombiChem is
providing its UIL to Third Parties without knowledge of such Third
Parties' target) (the "Target Exclusivity Obligations"), except (a)
as provided for in Section 12.2 hereof with regard to any Public
Statements, (b) with respect to any Third Parties who are
collaborators or proposed collaborators of CombiChem, CombiChem
shall have the right, consistent with its corporate policy (but
without identifying any Collaboration Target), to notify any such
Third Party of its decision and/or inability to work on such
Collaboration Target with that Third Party or (c) if CombiChem's
Target Exclusivity Obligations have terminated pursuant to
subsection 4.1(b) below.
(b) Upon the commencement of the Research Period and following
synthesis of a Daughter Library by CombiChem for the Collaboration
Target, the Target Exclusivity Obligations with respect to such
Collaboration Target shall continue until (1) ICOS has provided
CombiChem with a notice and release of Target
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Exclusivity Obligations, effective in sixty (60) days, that, because
of business and scientific reasons, ICOS has decided to cease
research and/or development activities for the Initial Target, or
(2) ICOS has provided CombiChem with a notice and release of Target
Exclusivity Obligations, effective *** from the date of such notice
and release, that ICOS has decided to cease research and/or
development activities for a specific Collaboration Target except
the Initial Target, or (3) *** after the date of the written notice
provided by ICOS under Section 3.2(b) herein, or (4) (A) ICOS has
failed to exercise Due Diligence with respect to that Collaboration
Target and (B) has not transferred or assigned its control of the
development of its program for that Collaboration Target to a Third
Party with due diligence requirements no less stringent than those
set forth in this Agreement. In the event of such transfer or
assignment to a Third Party, the Target Exclusivity Obligations with
respect to such Collaboration Target shall continue until the
earlier of (a) receipt by CombiChem of a written release from such
Third Party, or (b) the failure of such Third Party to exercise Due
Diligence with respect to that Target. Any notice under this
subsection 4.1(b) shall be provided by ICOS to CombiChem promptly
following the relevant decision under subsections (1), (2) or (3)
above or failure under subsection (4) above.
4.2 Active Compound Exclusivity. Any Active Compound shall be
exclusively available to ICOS for research or application within or outside the
Collaboration, during the Research Period, and CombiChem shall not work on or
provide information regarding such Active Compound to any Third Party, except to
take any steps necessary to protect ICOS's exclusivity hereunder. Following the
expiration of the Research Period, Active Compounds for which a Patent has not
been filed within *** shall be deemed to be Inactive Compounds for all purposes
hereunder; provided, that any Active Compound which is the subject of claim(s)
under a pending Collaboration Patent shall continue to be treated as Active
Compounds until a Collaboration Patent is issued with respect to one or more of
such claims; or until all of such Patent claims have been denied and all appeals
and refiling procedures have been exhausted, at which time the compounds which
are the subject of those claims shall be Inactive Compounds hereunder.
4.3 Inactive and Returned Compounds. Any Inactive Compounds and
Returned Compounds (subject to Section 9.2 hereof) shall be available to
CombiChem (except for any pre-existing ICOS Compound) and ICOS for any purpose.
4.4 Survival. This Article 4 shall survive termination or expiration
of this Agreement.
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5. COLLABORATION COMPOUNDS
5.1 Pre-Existing Compounds or Other Pre-Existing Rights. Neither
Party shall have any rights then existing in the other Party to any pre-existing
compound of the other Party unless and until such compound is designated as a
Collaboration Compound by such Party. Additionally, CombiChem may decline (after
informing ICOS) to synthesize a particular compound or library of compounds by
written notice to ICOS of existing Patents, Patent Applications and/or
contractual obligations with Third Parties restricting CombiChem's performance
of such activities and such notice shall contain a statement of warranty that
such Patents, Patent Applications and/or contractual obligations exist and that
their existence and the obligations of CombiChem predate an ICOS request of
CombiChem to synthesize such compound or library of compounds.
5.2 Intellectual Property Rights, License to ICOS. Subject to
Section 9.2 hereof, and except as set forth in this Section 5.2, ***
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relating to Active Compounds, Development Compounds and Products and the subject
matter contained therein and resulting from the Research Program ***
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*** and the subject matter claimed therein which are necessary for the
development and *** or its designee; provided under no circumstances does ***
*** in any Active Compound, Development Compound or Products are *** to the
extent such Active Compound, Development Compound or Products may be ***
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5.3 Structural Information. Neither Party shall disclose the
structure of the other Party's compound, any Active Compound, Development
Compound or Product to any Third Party without the other Party's written
permission, ***
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5.4 Supply of Collaboration Compounds. Aliquots of *** *** of any
Collaboration Compound that has been synthesized will be prepared and given to
ICOS. CombiChem shall replenish that amount upon ICOS's reasonable request.
CombiChem shall maintain aliquots of any Collaboration Compound that has been
synthesized by CombiChem. CombiChem shall also provide ICOS with additional
requirements of samples at CombiChem's cost. To the extent that Collaboration
Compounds are not available in a timely and sufficient quantity to allow the
earliest start of necessary large scale preclinical or other studies such
unavailability of Collaboration Compounds shall not be cited as a lack of Due
Diligence provided that the Parties have made commercially reasonable attempts,
and continue such attempts, to provide such unavailable Collaboration Compounds
in required quantities in the most expedient manner.
6. RESEARCH MANAGEMENT COMMITTEE
The design, review and conduct of the Research Program will be
coordinated by the Research Management Committee, which will meet regularly on a
mutually-agreeable schedule. Each Party shall bear its own expenses related to
such meetings. The Research Management Committee may establish and amend or
revise the Research Plan as reasonable and necessary to reflect the scientific
progress and work performed under the Research Program, such amendments to be
mutually agreed to in writing by ICOS and CombiChem. The Research Management
Committee will consist of an equal number of members from ICOS and CombiChem and
will include appropriate representatives from ICOS and CombiChem as mutually
agreed in writing. ***
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*** and subsequently may change as each Party determines for its
co-chair. Decisions of the Research Management Committee shall be by consensus.
If a decision is not reached by the RMC with respect to management of the
Research Program, the dispute will be referred to the co-chairs of the RMC. If
the co-chairs of the RMC are unable to resolve the dispute, the dispute will be
referred to the Chief Executive Officer of CombiChem and the Chief Executive
Officer of ICOS for resolution. If those officers are unable to resolve the
dispute, after good faith discussions, the dispute shall be resolved first by a
process of mediation and then in the case of a failure to resolve the dispute,
as determined per Section 15.2 hereof. Any decisions, recommendations,
amendments or performance criteria agreed by consensus of the RMC which could,
or may, materially affect any obligations concerning consideration or ownership
of intellectual property shall be consistent with the terms of this Agreement
and shall be ratified in writing by both CombiChem and ICOS prior to it being
binding on either party and any performance or partial performance of an
unratified agreement shall not be construed as a waiver or acquiescence of the
right of ratification.
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7. RESEARCH PERIOD; TERMINATION OF RESEARCH PROGRAM
7.1 Research Period: Option to Extend the Research Period. The
initial term of the Collaboration shall commence on the Effective Date and
conclude at the end of the Research Period, subject to extension upon mutual
written agreement. ***
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7.2 Termination of Research Program Upon Breach. The Research
Program and/or this Agreement may be terminated by a Party for the material
breach by the other Party as provided by Section 10.2 hereof.
8. CONSIDERATION
8.1 Fees.
(a) As of the Effective Date, ICOS shall be obligated to pay
CombiChem a non-refundable, noncontingent project initiation fee of U.S. *** in
cash, by registered check or wire transfer, to initiate the Research Program for
the Initial Target within fifteen (15) days of the Effective Date.
8.2 Research Program Funding.
(a) Research Support for Project Team. Beginning on the *** and
continuing throughout the Research Period, ICOS shall make payments to CombiChem
for direct research support for its Project Team, which shall initially consist
of *** of CombiChem, as modified by the RMC pursuant to Section 8.2(b) below.
The total amount payable per FTE shall be U.S. *** per FTE per annum, which
amount shall be upwardly adjusted annually based on cumulative changes in the
CPI, using 1999 as the base year. All payments for direct research support shall
be paid by ICOS to CombiChem, quarterly in advance, and adjusted as necessary in
subsequent quarters, of such amounts as are equal to the product of (i) the
number of CombiChem FTEs allocated to the Research Program by the RMC for the
calendar quarter to which each such payment applies, multiplied by (ii) U.S. ***
(i.e., the quarterly amount per CombiChem FTE on the basis of U.S. *** per
annum).
(b) Expansion or Contraction of Project Team. Notwithstanding
Section 2.1(e) herein, either Party may request that CombiChem expand or
contract its Project Team during the Research Period in order to properly
regulate the work-flow on a Collaboration Target. In such event, the RMC shall
promptly confer as to the appropriate number of *** to be added to the Project
Team, at a cost to ICOS of U.S. *** per FTE, as upwardly adjusted
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annually based upon cumulative changes in the CPI, using 1999 as the base year,
to be paid as specified in Section 8.2(a) hereof and make a recommendation to
such expansion or contraction of the Project Team which recommendation may be
adopted by mutual written agreement of ICOS and CombiChem.
8.3 Milestone Payments. Within thirty (30) days of the occurrence of
a development milestone triggered by the activities of ICOS or its Affiliates as
shown on Appendix A attached hereto, ICOS shall pay CombiChem the related
milestone payment in U.S. dollars as set forth on Appendix A attached hereto.
Such payments shall apply to any milestone reached by an Active Compound,
Development Compound or Product, for a Target within the Collaboration.
8.4 Royalties. During the Royalty Term, ICOS will pay CombiChem an
earned royalty of (i) *** of Net Sales of Products sold by ICOS, its Affiliates
or its sublicensees on the first *** of Net Sales made per calendar year *** ,
and (ii) *** on any Net Sales of Products sold by ICOS, its Affiliates or its
sublicensees over *** made per calendar year in *** (iii) *** of Net Sales of
Products sold by ICOS, its Affiliates or its sublicensees on the first *** of
Net Sales made per calendar year *** , and (iv) *** on any Net Sales of Products
sold by ICOS, its Affiliates or its sublicensees over *** made per calendar year
*** *** . Each payment of royalties shall be accompanied by a report of Net
Sales of Products in sufficient detail to permit confirmation of the accuracy of
the royalty payment made.
(a) ICOS may reduce the percentage amount of earned royalties
payable for a Product under this Agreement by *** the amount in excess of ***
that ICOS decides, in its reasonable business judgment, to pay to third parties
who are not Affiliates or sublicensees of ICOS (not including any royalties
payable to CombiChem hereunder) in order to sell the Product to avoid or settle
a patent infringement action relating to *** *** under a Collaboration Patent;
provided however, that the royalties payable by ICOS to CombiChem for the sale
of Product shall not be reduced to less than *** the amount that ICOS would
otherwise be obligated to pay to CombiChem.
(b) For any Product which is sold in combination with any other
active ingredient which other ingredient is not royalty bearing hereunder (a
"Combination Product"), Net Sales, for purposes of calculating royalties, as
defined in this Section 8.4, on a Combination Product, shall be calculated by
multiplying the net sales with respect to the Combination Product determined in
the same manner as Net Sales for a Product by the fraction A/B where A is the
gross selling price of the Product sold separately (i.e., without the other
active ingredients) and B is the gross selling price of the Combination Product.
In the event that no such separate sales are
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made, net sales value shall be calculated by multiplying net sales of the
Combination Product by the fraction C/(C + D), where C and D shall be negotiated
by the Parties in good faith prior to such sales.
(c) Earned royalty *** shall be paid in the manner provided herein
on a country-by-country basis.
8.5 Manner and Place of Payment. *** and reports for Net Sales of
Products shall be calculated in local currencies and reported for each calendar
quarter. All *** owed under this Agreement shall be made by wire transfer to the
bank account to be designated by CombiChem within sixty (60) days following the
end of each such calendar quarter.
8.6 Records and Audit. During the term of this Agreement and for a
period of three (3) years thereafter, ICOS shall keep complete, and accurate
records pertaining to the sale or other disposition of Products in sufficient
detail to permit CombiChem to confirm the accuracy of all payments due
hereunder. CombiChem shall have the right to cause an independent certified
public accounting firm reasonably acceptable to ICOS to audit such records to
confirm ICOS's Net Sales for the preceding year. Any information obtained during
such audit shall be treated as Confidential Information. Such audits may be
exercised after reasonable notice during normal business hours of ICOS no more
than once each year. ***
***
***
***.
8.7 Taxes. All income and other taxes levied on account of the ***
and *** accruing to CombiChem under this Agreement shall be paid by CombiChem,
including taxes levied thereon as income to CombiChem. If provision is made in
law or regulation for withholding, such tax shall be deducted from the royalty
or other payment made by ICOS to the proper taxing authority and a receipt of
payment of the tax secured and promptly delivered to CombiChem. Each Party
agrees to assist the other Party reasonably in claiming exemption from such
deductions or withholdings under any double taxation or similar agreement or
treaty from time to time in force.
9. LICENSE GRANTS; SUBLICENSE
9.1 CombiChem License Grant to ICOS. In addition to ICOS's
non-exclusive right to use CombiChem Technology as necessary to conduct
activities under the Research Program as described in Section 2.2 hereof,
subject to the terms and conditions of this Agreement, CombiChem hereby grants
to ICOS an exclusive, royalty-free, worldwide license, with the right to
sublicense to use such CombiChem Technology as is necessary to make, have
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Confidential Treatment and filed separately with the Commission.
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made, use, have used, sell, have sold, import and export Active Compounds,
Development Compounds and/or Products in the Territory. Such license shall
remain exclusive (including as to CombiChem) in relation to an Active Compound,
Development Compound and/or Product so long as ICOS or its licensee continues to
develop and commercialize such Active Compound, Development Compound and/or
Product against a Collaboration Target with Due Diligence.
9.2 ICOS License Grant to CombiChem. Subject to Article 4 hereof and
following the decision of ICOS or its licensee to not develop and commercialize
with Due Diligence an Active Compound, a Development Compound or Product, as the
case may be (collectively, "Returned Compounds"), ICOS shall grant to CombiChem
a royalty-bearing license, with the right to sublicense, under those
Collaboration Patents and know-how which are resulting from the Research Program
and related exclusively to the Returned Compound, to make, have made, use, have
used, sell, have sold, import and export such Returned Compound in the
Territory. ***
***
***
***.
9.3 ICOS Sublicense. ICOS shall have the right to transfer, assign
or sublicense to a Third Party the Products or Collaboration Patents covering
the Products, subject to CombiChem's right to receive all royalties and
milestone payments as provided in Sections 8.4 and 8.5 hereof. All payments
payable hereunder shall be made to CombiChem by wire transfer to such bank
account designated by CombiChem within five (5) business days after receipt by
ICOS or its Affiliates of such payments from a Third Party. As an express
condition of any such sublicense, any such licensee shall be required to agree
in writing (a) to be bound by due diligence, royalty reporting and recordkeeping
and inspection provisions no less stringent than those contained in this
Agreement and (b) to allow CombiChem to institute or join legal actions against
any ICOS sublicensee who fails to satisfy any obligations provided pursuant to
this Section 9.3. ICOS shall remain responsible to CombiChem for all milestone
and royalty payments actually received by ICOS from its sublicensees. In
addition, CombiChem shall have the right to receive all audit reports relating
to sales of Products of ICOS's sublicensees, and to cause ICOS or its Affiliates
or assigns to have an independent certified public accounting firm (reasonably
acceptable to ICOS) audit such sublicensee's records on the same terms as those
specified in Section 8.6 hereof.
9.4 Rights to Inactive Compounds. Each Party shall be free to screen
Inactive Compounds against any target other than a Collaboration Target. In the
event that either ICOS or CombiChem shall develop, market and/or sell, or enter
into a binding agreement with a Third Party to develop, market and/or sell, any
product containing the Inactive Compound as an active ingredient, then except to
the extent that such Inactive Compound is subject of a valid claim in a
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Patent or Collaboration Patent giving rights to the Party, the other Party
hereto shall not be entitled to any payments, milestones. royalties, fees or
compensation of any kind.
10. TERM AND TERMINATION OF THE AGREEMENT
10.1 Term. The term of this Agreement shall commence upon the
Effective Date and unless earlier terminated as provided in this Agreement,
shall expire at the end of the Research Period.
10.2 Termination by ICOS or CombiChem. If either Party materially
breaches this Agreement and fails to remedy that breach within ninety (90) days
of receiving written notice thereof from the other Party, or enters into any
arrangement of compromise with its creditors or goes into liquidation,
insolvency, bankruptcy, receivership or reorganization proceedings, whether
voluntarily or compulsorily which is not dismissed by a court of competent
jurisdiction within ninety (90) days, then the other Party may at any time, by
notice in writing or by facsimile transmission, terminate this Agreement. Within
ninety (90) days following termination for any Research Program and/or research
related to any Target under this Agreement, the RMC shall prepare a detailed,
final written report to each Party, and provide any remaining supply of
compounds in synthesis to date, for each Target or Research Program being
terminated.
10.3 Termination by ICOS. ICOS may terminate this Agreement
effective at any time after *** from the Effective Date, in its sole discretion,
upon *** *** prior written notice.
10.4 Termination by CombiChem. CombiChem may terminate this
Agreement effective at any *** the Effective Date, in its sole discretion, upon
*** prior written notice. In the event that CombiChem elects to terminate under
this Section 10.4, CombiChem shall not work on or provide services, or advice,
either independently or with any Third Party on any Collaboration Target for a
period of *** from the date that the termination is effective. No termination of
this Agreement pursuant to this Section 10.4 shall extend the Target Exclusivity
Obligations set forth in Section 4.1 hereof.
10.5 After Termination. Any termination of this Agreement or the
Research Program shall be without prejudice to the accrued rights of either
Party prior to the termination. In case of termination of this Agreement or the
Research Program pursuant to Sections 10.2, 10.3 or 10.4 above, all royalty,
milestone, payment and confidentiality obligations set forth in Sections 8.1,
8.4, 8.5, 9.3, 9.4 hereof and Articles 4, 11 and 12 hereof shall survive any
such termination. Moreover, ICOS shall not be entitled to any refund of any
payments made to CombiChem hereunder upon the expiration of the term of this
Agreement or earlier termination pursuant to this Article 10.
*** Portions of this page have been omitted pursuant to a request for
Confidential Treatment and filed separately with the Commission.
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10.6 Effect of Termination on Licensees. In the event of any
termination of this Agreement pursuant to this Article 10 where such termination
shall not have been caused by the action or inaction on the part of any
respective licensee of ICOS or CombiChem, or by any breach by such licensee of
its obligations under its license from ICOS or CombiChem, as appropriate, such
termination of this Agreement shall be without prejudice to the rights of each
non-breaching licensee and such licensee shall be deemed to be a direct licensee
hereunder.
11. CONFIDENTIAL INFORMATION
11.1 Nondisclosure. During the term of this Agreement and for a
period of five (5) years after termination or expiration thereof, each Party
will maintain all Confidential Information in trust and confidence and will not
disclose any Confidential Information to any third party or use any Confidential
Information for any purpose except (i) as expressly authorized by this
Agreement, (ii) as required by law or court order, after as much advance notice
as is practical to the other Party, (iii) to its consultants, subcontractors or
agents who need to know to accomplish the purposes of this Agreement and who are
bound by equivalent written confidentiality obligations. Each Party may use the
other Party's Confidential Information only to the extent required to accomplish
the purposes of this Agreement. Each Party will use at least the same standard
of care as it uses to protect proprietary or confidential information of its own
to ensure that its Affiliates, employees, agents, consultants and other
representatives do not disclose or make any unauthorized use of the Confidential
Information. Each Party will promptly notify the other upon discovery of any
unauthorized use or disclosure of the Confidential Information.
11.2 Exceptions. Confidential Information shall not include any
information which the receiving Party can prove by competent evidence: (a) is
now, or hereafter becomes, through no act or failure to act on the part of the
receiving Party, generally known or available; (b) is known by the receiving
Party at the time of receiving such information, as evidenced by its written
records; (c) is hereafter disclosed to the receiving Party by a Third Party, as
a matter of right and without restriction on disclosure; (d) is independently
developed by the receiving Party without the aid, application or use of
Confidential Information; or (e) is the subject of a written permission to
disclose provided by the disclosing Party.
12. PUBLICATIONS AND PUBLIC STATEMENTS
12.1 Publications. Without affecting obligations under Article 11
above, neither Party shall publish any information with respect to Collaboration
Compounds or Development Compound during the Exclusivity Period without the
prior written permission of the other Party. Such permission shall be approved
or disapproved within thirty (30) days of written request for permission unless
the other Party requests additional time (not to exceed ninety (90) days) for
the purpose of protecting its intellectual property position. Such permission
shall not be unreasonably withheld. The Party proposing to publish such
information shall give the other Party ninety (90) days prior written notice and
an opportunity to review such manuscript in order to determine the patentability
of the information contained therein.
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12.2 Public Statements. Neither Party shall use the name of the
other Party in any public statement, prospectus, annual report or press release
or other public communication (collectively "Public Statements") (except to the
extent that use of the name is required for disclosure by the Securities and
Exchange Commission or other governmental rules or regulations) without the
prior written approval of the other Party, which may not be unreasonably
withheld or delayed; provided, however, that both Parties shall endeavor in good
faith to give the other Party a minimum of two (2) business days to review such
Public Statements; provided, further, that, upon approval of any such Public
Statement, both Parties may disclose to Third Parties the information contained
in such Public Statement without the further approval of the other; and
provided, further, that if a Party does not approve such Public Statement,
either Party may still use the name of the other Party in any Public Statement
without the prior written approval of the other Party, if such Party is advised
by counsel that such disclosure is required to comply with applicable law.
13. INDEMNIFICATION
13.1 EACH PARTY HEREBY AGREES TO SAVE, DEFEND AND HOLD THE OTHER
PARTY AND ITS OFFICERS, DIRECTORS, EMPLOYEES, CONSULTANTS AND AGENTS HARMLESS
FROM AND AGAINST ANY AND ALL SUITS, CLAIMS, ACTIONS, DEMANDS, LIABILITIES,
EXPENSES AND LOSSES, INCLUDING REASONABLE LEGAL EXPENSES AND ATTORNEYS' FEES
("LOSSES") RESULTING DIRECTLY OR INDIRECTLY FROM THE INDEMNIFYING PARTY'S ACTS
OR OMISSIONS IN CONNECTION WITH THE MANUFACTURE, DEVELOPMENT, USE, HANDLING,
STORAGE, SALE OR OTHER DISPOSITION OF CHEMICAL AGENTS, COLLABORATION COMPOUNDS,
ACTIVE COMPOUNDS, DEVELOPMENT COMPOUNDS OR PRODUCTS BY SUCH PARTY, ITS
AFFILIATES OR LICENSEES EXCEPT TO THE EXTENT SUCH LOSSES RESULT FROM THE
NEGLIGENCE (WHETHER ACTIVE, PASSIVE OR IMPUTED), BREACH OF THIS AGREEMENT OR
WILLFUL MISCONDUCT OF THE PARTY CLAIMING A RIGHT OF INDEMNIFICATION UNDER THIS
ARTICLE 13.
13.2 Infringement
(a) Subject to Section 13.2(c) below, ICOS shall hold CombiChem and
its officers, directors, employees, consultants, and agents
harmless from and against any and all losses resulting from the
infringement of any Third Party's Patent issued as of the Effective
Date due to the performance by ICOS or its Affiliates of any
activity contemplated hereunder, including, but not necessarily
limited to, ICOS's responsibilities under Section 2.2 above,
developing Products, and selling Products.
(b) Subject to Section 13.2(c) below, CombiChem shall hold ICOS and
its officers, directors, employees, consultants, and agents
harmless from and against any and all losses resulting from the
infringement of any Third Party's Patent issued as of the Effective
Date due to the performance by CombiChem of any
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activity contemplated hereunder, including, but not necessarily
limited to, CombiChem's responsibilities under Section 2.1 above.
(c) The indemnity provided in Sections 13.2(a) and 13.2(b) above
shall not apply where the loss is due to the breach by the
indemnified Party of a warranty made in Article 19.
13.3 Procedures. If either Party (the "Indemnified Party") seeks
indemnification under this Article 13, it shall inform the other Party (the
"Indemnifying Party") of a claim as soon as reasonably practicable after it
receives notice of the claim, shall permit the Indemnifying Party to assume
direction and control of the defense of the claim (including the right to settle
any claim brought against the Indemnified Party upon prior written consent,
which shall not be unreasonably withheld), and shall give reasonable cooperation
(at the expense of the Indemnifying Party) in the defense of such claim.
14. ASSIGNABILITY
This Agreement may not be assigned by either Party without the
prior written consent of the other Party, not to be unreasonably withheld;
provided, however, that either Party may assign this Agreement, in whole or in
part, to an Affiliate or to a successor of a Party in connection with the
merger, consolidation or sale of all or substantially all of such Party's assets
or that portion of its business pertaining to the subject matter of this
Agreement (and upon doing so will promptly notify the other Party in writing);
provided that the assigning Party remains fully liable as obligated hereunder.
15. DISPUTE RESOLUTION PROCEDURES
15.1 Senior Executives Discussions. If a decision on a matter
regarding the management of the Research Program as provided herein is not
reached by the RMC, the dispute will be resolved as set forth in Article 6
above. If a dispute arises between CombiChem and ICOS with respect to matters
other than the management of the Research Program, either during or after the
Research Period, such dispute will be referred to the appropriate senior
management in the area of the dispute. If such senior management are unable to
resolve such dispute, such dispute will be referred to the Chief Executive
Officer of ICOS and the Chief Executive Officer of CombiChem. If such officers
are unable to reach an agreement within thirty (30) days following the
initiation of discussions between them, such dispute shall be submitted to
mediation and if there is no settlement of the dispute within sixty (60) days
following the commencement of such mediation process, such dispute may, at the
Party's mutual written agreement, be settled by arbitration as described in
Section 15.2 below.
15.2 Binding, Arbitration. If the Parties have not been able to
resolve the dispute as provided in Section 15.1 above and the Parties mutually
agree in writing, the dispute shall be finally settled by binding arbitration.
Any arbitration hereunder shall be conducted under rules of the American
Arbitration Association. The arbitration shall be conducted before three
arbitrators chosen according to the following procedure: each of the parties
shall appoint
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one arbitrator and the two so nominated shall choose the third. If the
arbitrators chosen by the parties cannot agree on the choice of the third
arbitrator within a period of thirty (30) days after their appointment, then the
third arbitrator shall be appointed by the Court of Arbitration of the American
Arbitration Association. If CombiChem brings an arbitration action, such
arbitration shall occur in Seattle, Washington. If ICOS brings an arbitration
action, such arbitration shall occur in San Diego, California. The arbitrators
shall have the authority to grant specific performance, and to allocate between
the parties the costs of arbitration in such equitable manner as they determine.
The arbitral award (i) shall be final and binding upon the parties; and (ii) may
be entered in any court of competent jurisdiction.
15.3 Injunctive and Other Relief. Nothing contained in this Article
15 or any other provisions of this Agreement shall be construed to limit or
preclude a Party from bringing any action in any court of competent jurisdiction
for injunctive or other provisional relief to compel the other Party to comply
with its obligations hereunder before or during the pendency of arbitration
proceedings. In the event that the Parties do not mutually agree to enter
binding arbitration as provided in Section 15.2 hereof, the Parties may pursue
all available legal remedies.
16. NOTICES
Any notice required or permitted to be given hereunder shall be
deemed sufficient if sent by facsimile letter or overnight courier, or delivered
by hand to ICOS or CombiChem at the respective addresses and facsimile numbers
as set forth below or at such other address and facsimile number as either Party
hereto may designate. If sent by facsimile letter, notice shall be deemed given
when the transmission is completed if the sender has a confirmed transmission
report. If a confirmed transmission report does not exist, then the notice will
be deemed given when the notice is actually received by the person to whom it is
sent. If delivered by overnight courier, notice shall be deemed given when it
has been signed for. If delivered by hand, notice shall be deemed given when
received.
if to CombiChem, to:
CombiChem, Inc.
0000 Xxxxxx Xxxxx Xx
Xxx Xxxxx, Xxxxxxxxxx 00000
Attention: President
Fax number: (000) 000-0000
with a copy to:
Xxxxxxx, Xxxxxxx & Xxxxxxxx LLP
000 Xxxx X Xxxxxx, Xxxxx 0000
Xxx Xxxxx, Xxxxxxxxxx 00000
Attention: Xxxx X. Xxxxxxx, Esq.
Fax number: (000) 000-0000
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if to ICOS to:
ICOS Corporation
00000 00xx Xxxxxx, X.X.
Xxxxxxx, Xxxxxxxxxx 00000
Attention: Legal Department
Fax number: (000) 000-0000
17. SURVIVAL
The provisions of Sections 2.4, 5.1, 5.2, 5.3, 10.5, 10.6 and Articles
4, 8, 9, 11, 12, 13, 15, and this Article 17 shall survive termination of this
Agreement in addition to those provisions which by their terms survive.
18. ADDITIONAL TERMS
18.1 Entire Agreement. This Agreement constitutes the entire
understanding between the Parties with respect to the subject matter hereto and
supersedes and replaces all previous negotiations, understandings,
representations, writings and contract provisions and rights relating hereof.
18.2 Amendment; No Waiver. No provision of this Agreement may be
amended, revoked or waived except by a writing signed and delivered by an
authorized officer of each Party. Any waiver on the part of either Party of any
breach or any fight or interest hereunder shall not imply the waiver of any
subsequent breach or waiver of any other right or interest.
18.3 Validity. The invalidity or unenforceability of any provision
of this Agreement shall not affect the validity or enforceability of any other
provision of this Agreement, each of which shall remain in full force and
effect.
18.4 Headings. The descriptive headings are inserted for
convenience of reference only and are not intended to be part of or to affect
the meaning of or interpretation of this Agreement.
18.5 Counterparts. This Agreement may be executed in one or more
counterparts, each of which shall be deemed an original, and all of which
together shall be deemed to be one and the same instrument.
18.6 Further Assurances. At any time and from time to time after
the Effective Date, the Parties shall each do, execute, acknowledge and deliver,
and cause to be done, executed, acknowledged or delivered, all such further
acts, transfers, conveyances, or assignments as may be reasonably required to
carry out the transactions contemplated by this Agreement.
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19. REPRESENTATIONS AND WARRANTIES
19.1 Authorization. All action on the part of each of CombiChem,
ICOS and their respective officers, and directors necessary for the
authorization, execution and delivery of this Agreement and the performance of
all obligations of CombiChem, ICOS and ICOS, respectively, hereunder has been
taken.
19.2 Rights to Intellectual Property. Each Party warrants that it
has the power to grant all of the rights granted and make such required
assignments, and to assume all of the obligations required, under this
Agreement. Under no circumstances does CombiChem warrant to ICOS that its rights
in any Active Compound, Development Compound or Products are exclusive to the
extent such Active Compound, Development Compound or Products may be covered
under the patent claims of Third Parties wherein such claims are not the direct
result of a collaboration between the Third Party and CombiChem.
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IN WITNESS WHEREOF, the parties have executed this Agreement to be
effective as of the Effective Date.
COMBICHEM, INC. ICOS CORPORATION
By: /s/ Xxxxxxx Xxxxx, Xx. By: /s/ illegible
----------------------------- --------------------------------------
Its: President & CEO Its: Vice President, Business Development
-------------------------------- -------------------------------------
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Appendix A
Milestones and Payments(1)
--------------------------
(in U.S. Dollars)
Milestone Milestone Payment(2)
--------- --------------------
*** ***
*** ***
*** ***
Total ***
(1) Paid in U.S. Dollars
***
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Confidential Treatment and filed separately with the Commission.
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