LETTER OF INTENT
THIS LETTER OF INTENT is made on the 11th day of June 1998, by and 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
00000 Xxxxx Xxxxxx Xxxxx Xxxx, Xx Xxxxx, Xxxxxxxxxx 00000 (hereinafter called
"Agouron"), and The Immune Response Corporation, a corporation duly organized
and existing under the laws of the state of Delaware, having a principal place
of business at 0000 Xxxxxx Xxxxx, Xxxxxxxx, Xxxxxxxxxx 00000 (hereinafter called
"Immune Response"). Agouron and Immune Response are sometimes hereinafter
referred to as a party (collectively "parties") to this Agreement.
BACKGROUND
In accordance with the terms of this Letter of Intent, Immune Response has
agreed to license to Agouron the exclusive rights necessary or useful for the
registration and/or commercialization of the product known as REMUNE, a non-
infectious intact Human Immunodeficiency Virus ("HIV") devoid of outer envelope
proteins. This Letter of Intent, which shall be binding on the parties, sets
forth the basic license terms upon which the parties have agreed. The full
terms of the license will be set forth in a definitive agreement to be prepared
as described below.
NOW, THEREFORE, the parties agree as follows:
1. TERMS. The parties hereby enter into this Letter of Intent to confirm
their entering into a license agreement on terms substantially in accordance
with those contained in Exhibit A hereto. The parties acknowledge that
Exhibit A states the basic terms of the understanding between the parties and
anticipate the further negotiation and preparation of an agreement containing
the full terms of the license between the parties ("Definitive Agreement").
Each party agrees to act in good faith in an effort to negotiate, execute and
deliver the Definitive Agreement on or before September 1, 1998. If the
Definitive Agreement is not executed by September 1, 1998, the provisions of
this Letter of Intent shall continue in effect until the Definitive Agreement
is executed, and the parties will continue to negotiate in good faith in an
effort to execute and deliver the Definitive Agreement as soon as possible.
2. DISCLOSURE. The parties shall jointly prepare and release a statement
about the existence of this Letter of Intent and of the license between Agouron
and Immune Response. Except as agreed to by the parties, neither Agouron nor
Immune Response shall 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 Letter of Intent, or of the license, or of results of clinical
trials of REMUNE, without the prior written consent of the other, which consent
shall not unreasonably be withheld. This prohibition includes, but is not
limited to, press releases, educational and scientific conferences, promotional
materials and discussions with the media. If a party determines that it is
required by law to release information to any third party regarding such
matters, it shall notify the other party of this fact prior to releasing the
information. The notice to the other party shall include the text of the
information proposed for release. The
* * * - Confidential treatment requested. Sections of text which have been
omitted and for which confidential treatment is requested are noted with "***".
An unredacted version of this document has been filed separately with the
Securities and Exchange Commission.
1
other party shall have the right to confer with the notifying party regarding
the necessity for the disclosure and the text of the information proposed for
release.
3. MISCELLANEOUS. This Letter of Intent contains the entire agreement between
the parties as of the date hereinabove written on the matters set forth herein
and shall be governed by and construed in accordance with the laws of the State
of California. Exhibit A describes the parties' understanding with respect to
the registration and commercialization of the "Product" as defined therein. This
Letter of Intent, including Exhibit A, shall not be amended, supplemented or
otherwise modified, except by an instrument in writing signed by duly authorized
officers of both parties. Each party shall bear all of the expenses incurred by
it in connection with the negotiation and preparation of this Letter of Intent
and the Definitive Agreement. Each party represents and warrants that it is not
presently bound by any agreement with any third party which limits its
performance of any of the obligations or activities provided for under this
Letter of Intent or contemplated by the Definitive Agreement. Immune Response
represents and warrants that it is not aware of any patents, patent applications
and/or know-how that it does not have the right to license to Agouron which is
necessary or useful for commercialization of Product by Agouron. Immune
Response further represents and warrants that it will not enter into any
agreements which limit Immune Response's performance of any of the obligations
or activities provided for under this Letter of Intent or contemplated by the
Definitive Agreement. Immune Response, at its expense, shall obtain any
government approval(s) not related to drug product registration, which are
required to enable this Agreement to become effective. At any time after
October 15, 1998, Agouron may elect to immediately terminate, in their entirety,
all of its rights and obligations under this Letter of Intent and the Definitive
Agreement, except that Agouron may exercise this right to terminate only on the
basis of its concerns related to the safety, efficacy, competitiveness, or
commercial feasibility of Product.
IN WITNESS WHEREOF, the parties hereto have executed this Letter of Intent
by their respective officers thereunto duly authorized, as of the date
hereinabove written. This Letter of Intent may be executed in counterparts and
all of such counterparts taken together shall be deemed to constitute one and
the same instrument.
THE IMMUNE RESPONSE CORPORATION AGOURON PHARMACEUTICALS, INC.
By: s/Xxxxxx X. Xxxxx By: s/Xxxxx Xxxxxxx
-------------------- --------------------
Name: Xxxxxx X. Xxxxx Name: Xxxxx Xxxxxxx
-------------------- --------------------
Title: President Title: President
-------------------- --------------------
By: s/Xxxxxxx X. Xxxxxxx By: s/Xxxx Xxxxxxxx
-------------------- --------------------
Name: Xxxxxxx X. Xxxxxxx Name: Xxxx Xxxxxxxx
-------------------- --------------------
Title: Senior VP Title: Secretary
-------------------- --------------------
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EXHIBIT A
Immune Response, under the terms and conditions specified below, hereby
grants Agouron the exclusive right to use, offer for sale, sell and/or
import, in or into the Licensed Territory, the Product under applicable
Immune Response Patent Rights (including claims therein relating to
compositions and methods of use) and using applicable Immune Response
Know-How.
1. Definitions: Except as otherwise set forth herein, items containing an
initial capitalized letter shall have the meaning stated below or in the
Letter of Intent to which this Exhibit A is an attachment ("LOI").
(a) "Product" means a pharmaceutical product comprising a non-infectious
intact HIV devoid of outer envelope proteins whose manufacture, use or
sale infringes (in the absence of the license rights granted under
this Exhibit A) a valid claim (which has not been abandoned,
disclaimed or declared invalid in a non-appealable order) included in
an issued patent within the Immune Response Patent Rights.
(b) "Licensed Territory" means all countries of the world except the
countries listed in Schedule 1.
(c) "Affiliate" means any person, organization or entity which is,
directly or indirectly, controlling, controlled by, or under common
control with Agouron or Immune Response, as the case may be. The term
"control" (including, with correlative meaning, the terms "controlled
by" and "under common control with"), as used with respect to any
person or entity, means the possession, directly or indirectly, of the
power to direct or cause the direction of the management and policies
of such person, organization or entity, whether through the ownership
of voting securities, or by contract, or court order, or otherwise.
The ownership of voting securities of a person, organization or entity
shall not, in and of itself, constitute "control" for purposes of this
definition, unless said ownership is of a majority of the outstanding
securities entitled to vote of such person, organization or entity.
Affiliate shall also mean a limited partnership in which a subsidiary
of Agouron and/or Immune Response is a general partner.
(d) "Immune Response Patent Rights" means (i) the patents and the patent
applications referred to in Schedule 2 of this Exhibit A; (ii) all
patents arising from said applications, and all patents and patent
applications based on, claiming the priority date(s) of, or
corresponding to any of the foregoing; or (iii) any reissues,
extensions (or other governmental actions that provide exclusive
rights to the patent holder in the patented subject matter beyond the
original patent expiration date), substitutions, confirmations,
registrations, revalidations, re-examinations, additions,
continuations, continuations-in-part, or divisions of or to any of the
foregoing.
*** - Confidential treatment requested. Sections of text which have been
omitted and for which confidential treatment is requested are noted with "***".
An unredacted version of this document has been filed separately with the
Securities and Exchange Commission.
A-1
(e) "Immune Response Know-How" means any know-how, trade secret,
experimental data, formula, expert opinion, experimental procedure,
and other confidential and/or proprietary information specifically
concerning the Product that is Controlled by Immune Response and that
is necessary or useful for either: (i) the formulation, manufacture,
use and/or application of the Product; or (ii) obtaining registration
of the Product.
(f) "Control" and "Controlled" mean possession of the ability to grant a
license or sublicense as provided for herein without violating the
terms of any agreement with, or arrangement with, any third party.
(g) The terms "Net Sales," "Pre-Tax Profits," "Allowable Expenses" and
"Manufacturing Transfer Markup" shall be fully defined in the
Definitive Agreement. The terms "Net Sales and "Allowable Expenses"
shall be determined in accordance with generally accepted accounting
principles and the usual and customary practices of the parties.
2. As provided below, Immune Response and Agouron shall collaborate to
complete the current program of clinical trials of the Product, including
those aimed at achieving registration of the Product in the Licensed
Territory, in an expeditious manner. Immune Response and Agouron agree to
the following basic approaches to the registration of Product in the
Licensed Territory and the conduct of a committee to be formed to
coordinate the parties' registration of Product in the Licensed Territory:
(a) Immune Response and Agouron shall use reasonable diligence in the
registration of the Product.
(b) A committee, co-chaired by representatives of Immune Response and
Agouron and comprised of representatives from Immune Response and
Agouron, shall be formed to coordinate the registration of the Product
in the Licensed Territory and such other matters that the parties
mutually agree to assign to it. Decisions of the committee shall be
made by a unanimous vote of the committee, with each party having one
(1) vote, regardless of the number of representatives attending a
meeting. The committee shall meet regularly, at least four times per
year, and shall assign study or other registration activities between
the parties as described in this Paragraph 2.
(c) The committee shall review and discuss the registration plans for any
countries involved, as well as a coordinated general strategy and
priorities for preclinical and clinical registration of Product in the
Licensed Territory. Each party's members of the committee will
reasonably consider the adoption of the other party's suggestions and
will accept as many of such suggestions as are reasonable, based upon
medical rationale, drug supply, and the need to conduct the studies in
an expeditious and cost-efficient manner.
(d) The parties will share responsibility and authority to obtain
regulatory approvals for the Product in the Licensed Territory. If
there is a disagreement among the parties concerning an issue related
to the registration of the Product in the Licensed Territory, the
issue shall be resolved in accordance with the provisions of Paragraph
17.
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(e) Agouron, at its expense (except for the cost of clinical supplies of
Product to be provided to Agouron pursuant to the provisions of
Paragraph 9), shall, using reasonable efforts, initiate and conduct a
200-plus patient viral load study to support registration of the
Product.
(f) In partial consideration for the rights granted to Agouron, Agouron
will make up to six (6) quarterly payments of three million dollars
($3,000,000) each to support clinical and manufacturing development
and scale-up of the Product beginning on October 15, 1998, and every
ninety (90) days thereafter, until the earlier of: (i) January 15,
2000; or (ii) the approval of a Product License Application ("PLA")
for the Product in the United States. The above quarterly payments of
three million dollars ($3,000,000) each to support clinical and
manufacturing development and scale-up of the Product shall only be
due and payable by Agouron if Agouron has not elected to terminate, in
its entirety, all of its rights and obligations under the LOI and the
Definitive Agreement before the last permitted payment date for the
applicable quarterly payment.
(g) Immune Response will complete, at its expense, the current worldwide
program of clinical trials of the Product, including the studies
listed in Schedule 3, and will promptly and fully disclose to Agouron
the results of the interim and final analyses of data from these
clinical trials.
(h) Agouron will provide, at its expense, regulatory staff support for
preparation of registration documents as such support is reasonably
requested by Immune Response.
(i) Agouron, notwithstanding the preceding, will be responsible for
negotiating labeling, pricing and reimbursement for Product with the
applicable regulatory authorities in the Licensed Territory, and after
registration of the Product will have the primary responsibility for
the ongoing correspondence and interaction with the applicable
regulatory authorities. Immune Response will provide reasonable
assistance to Agouron in such interactions, if necessary.
(j) Except as provided above, the committee, in assigning the
responsibility for performing specific tasks or activities related to
a study or registration activity among the parties, shall make such
assignments principally based on: (i) the available resources each of
the parties can commit to the task or activity; (ii) the expertise of
each of the parties in conducting or monitoring the task or activity;
(iii) which party can perform the task or activity in the most
expeditious manner; and (iv) which party can perform the task or
activity in the most cost-efficient manner. A party not responsible
for the performance of a task or activity may provide advisory and
support services to the other party. The committee may establish
interdisciplinary project teams comprised of representatives of both
parties having the specialized skills necessary to oversee the conduct
of specific day-to-day registration
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A-3
activities. The committee shall establish procedures concerning the
scope and conduct of activities (including decision-making procedures)
assigned to such project teams.
(k) Each party shall keep the other party informed of its progress in the
registration of Product, including making oral presentations of
progress at the committee meetings and/or the preparing of such
written progress reports as are agreed to by the parties summarizing
such party's activities during each reporting period and its planned
activities for the succeeding period. Each of the parties will assign
a representative to facilitate communications between the parties;
each representative shall report to his/her management on the matters
discussed at each of the meetings of the parties.
(l) Immune Response will disclose to Agouron all relevant Immune Response
Know-How, including, but not limited to, data and information which it
possesses from the pre-clinical and clinical studies of Product
(including toxicology, pharmacokinetics and formulation studies) in a
format which will facilitate the preparation for any regulatory
filings or other correspondence to be filed or made by Agouron.
(m) Immune Response will provide assistance to Agouron in accessing
clinical investigators, clinical sites and testing laboratories for
the purposes of data interpretation and/or evaluation and conduct of
registration activities assigned to Agouron.
(n) Immune Response shall use its reasonable efforts to coordinate its
registration activities in any country(s) located outside the Licensed
Territory with the registration activities of the parties in the
Licensed Territory.
(o) If a licensee of Immune Response wishes to use the results of studies
conducted by Agouron in such licensee's registration and
commercialization activities in a country(s) located outside of the
Licensed Territory, the parties shall enter into good-faith
discussions about the sharing of the costs of such studies and/or the
granting to Agouron of equivalent rights to use the results of any
studies conducted by such licensee.
(p) If development of the Product is discontinued in a country located in
the Licensed Territory due to safety, efficacy or regulatory issues or
by mutual agreement of the parties and Agouron is interested in
developing a substitute drug product whose manufacture, use or sale
would infringe (in the absence of the license rights granted under
this Exhibit A) a valid claim (which has not been abandoned,
disclaimed or declared invalid in a non-appealable order) included in
an issued patent within the Immune Response Patent Rights, then Immune
Response and Agouron shall enter into good faith negotiations
regarding the terms of a license between Immune Response and Agouron
for such substitute drug product. During the period that Agouron is
participating in the development and/or commercialization of the
Product and/or another drug product whose manufacture, use or sale
infringes (in the absence of the license rights granted under this
Exhibit A) a valid claim (which has not been
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abandoned, disclaimed or declared invalid in a non-appealable order)
included in an issued patent within the Immune Response Patent Rights,
Immune Response agrees not to commercialize in the Licensed Territory
other drug products whose manufacture, use or sale is covered by a
valid claim (which has not been abandoned, disclaimed or declared
invalid in a non-appealable order) in an issued patent within the
Immune Response Patent Rights, on its own or with a third party, other
than Agouron, its Affiliates or sublicensees.
3. In partial consideration for the rights granted to Agouron, Agouron will
make the following license-fee milestone payments to Immune Response:
Milestones Payment (US Dollars)
---------- -------------------
Within 30 days of execution of the LOI $10,000,000
*** $ ***
*** $ ***
*** $ ***
*** $ ***
-----------
Total Milestone Payments $45,000,000
-----------
-----------
The above license fee milestone payments shall be payable by Agouron one time
only and shall only be due if Agouron has not elected to terminate, in its
entirety, all of its rights and obligations under the LOI and the Definitive
Agreement before the last permitted payment date for the applicable milestone
payment.
4. Prior to approval of the Product in the United States, Agouron will, "***."
5. The right of Agouron to market Product in the Licensed Territory shall be
subject to commercially reasonable marketing efforts by Agouron, on a
country-by-country basis. For purposes of this paragraph,
commercialization efforts undertaken by Agouron's Affiliates and
sublicensees shall be attributed to Agouron. Agouron shall begin
commercial sales of the in a country no later than "***" after the first
registration of Product in such country; provided, however, that such
period shall be extended for as long as commercially reasonable marketing
efforts to begin commercial sales continue. Following commencement of
commercial sales in a country, Agouron shall keep Product reasonably
available to the public; provided, however, that Agouron shall be released
from this obligation if supply of Product is
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A-5
not available for such country and Agouron is not responsible for arranging
for the commercial production and supply of Product for such country.
6. The term of the license rights granted hereunder will extend on a
country-by-country basis from the effective date of the signing of the
LOI until the last-to-expire of any patents within the Immune Response
Patent Rights covering the Product in such country (as extended by any
governmental actions which provide exclusive rights to the patent holder
in the patented subject matter beyond the original patent expiration
date).
7. Agouron shall have the right to sublicense its rights in the Product in one
or more countries of the Licensed Territory. In the event that Immune
Response or its Affiliates shall in the future obtain Control of one or
more additional patent rights and/or know-how necessary or useful for the
commercialization of the Product in the Licensed Territory, then Immune
Response shall grant to Agouron an exclusive license consistent with the
terms of this Exhibit A which adds such patent rights and know-how to the
scope of the applicable Immune Response Patent Rights and Immune Response
Know-How, without any additional obligations due from Agouron to Immune
Response. To the extent that Immune Response grants rights in the Product
to a third party and such third party invents or discovers inventions
and/or know-how necessary or useful for the commercialization of the
Product in the Licensed Territory, then Immune Response shall use its
reasonable efforts to secure rights for Agouron to use such inventions and
know-how.
8. Immune Response hereby grants to Agouron, its Affiliates and sublicensees a
perpetual paid-up, royalty-free, worldwide, exclusive right to use Immune
Response's trademark REMUNE-TM- in the marketing of the Product in the
Licensed Territory.
9. Immune Response shall supply Agouron, and Agouron shall purchase from
Immune Response, sufficient commercial supplies of Product to support and
sustain the launch and subsequent patient demand for Product in the
Licensed Territory. Immune Response hereby agrees to use its commercially
reasonable efforts to have sufficient manufacturing capacity at its
facilities to supply Agouron with commercial quantities of Product which
are necessary for the launch of such Product in the Licensed Territory and
agrees to have at least a monthly manufacturing capacity for the Licensed
Territory of "***" unit doses/month of such Product at the time of launch
of such Product. Immune Response agrees, at its expense, to maintain
commercially reasonable inventory and safety stock of Product for the
Licensed Territory. Immune Response further agrees to discuss with
Agouron, in good faith, Immune Response's acquisition of additional
manufacturing capacity required to meet the projected patient demand for
the Product for the Licensed Territory. Immune Response shall use
diligence in its manufacturing activities and shall provide Agouron such
technical support for the Product as it may reasonably requested.
Commercial supplies of Product shall be supplied to Agouron at Immune
Response's "***."
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10. Immune Response agrees not to enter into any contractual arrangement with
its licensees outside the Licensed Territory which would limit Immune
Response's ability to fully fulfill Agouron's product requirements for the
Licensed Territory, or which would require Immune Response to allocate its
manufacturing capacity among such licensees and Agouron. If supply
shortages of Product are expected to occur during a calendar quarterly
period, and Immune Response's available supply of drug product is required
to be allocated among Immune Response's licensees, Immune Response shall
allocate the available supply of drug product among Immune Response's
licensees during such calendar quarterly period on a pro-rata basis, based
upon: (i) the relative utilization of such Product in each licensee's
respective territories during the twelve (12) month period ending on the
first day of such calendar quarterly period (based on historical sales data
during such twelve (12) month, to the extent such data is available); and
(ii) the projected sales of such Product in each licensee's respective
territories during the twelve (12) month period commencing with the first
day of such calendar quarterly period.
11. If Immune Response is unable to provide Agouron with its requirements of
Product in a timely and cost-efficient manner, Immune Response agrees to
assist Agouron in the identification of alternative low-cost manufacturing
sources for the Product, including but not limited to, access to current
suppliers of starting materials, intermediates, bulk material and/or
finished Product. Immune Response in such circumstances will grant Agouron
the non-exclusive worldwide right to make and have made Product under
applicable Immune Response Patent Rights and Immune Response Know-How
relating to processes, intermediates and materials for manufacturing
Product, and will provide to Agouron without charge, to the extent
available, technical and manufacturing assistance and use of its technology
and proprietary information for the Product, including information on its
analytical methods, validation reports and manufacturing processes.
12. Pre-Tax Profits generated from aggregate Net Sales and royalties from
Products in the Licensed Territory on a country-by-country basis shall be
shared equally by Immune Response and Agouron on a fifty-fifty basis.
"***."
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13. At any time after October 15, 1998, Agouron may elect to immediately
terminate its development obligations in the Licensed Territory for Product
under the LOI and the Definitive Agreement, except that Agouron may
exercise this right to terminate only on the basis of its concerns related
to the safety, efficacy, competitiveness, or commercial feasibility of
Product. In the event that Agouron elects to terminate its development
obligations for Product under the LOI and the Definitive Agreement, Immune
Response, its Affiliates and sublicensees shall be free, without any
further action by Immune Response or Agouron, to develop and/or
commercialize Product in the Licensed Territory, on their own, or with any
third party, and to retain, use and disclose to any such third party
information and materials that have been developed by Agouron in its
development activites for Product; provided, that Immune Response shall not
disclose to such third party the confidential and proprietary information
of Agouron (other than clinical, regulatory and manufacturing information
and materials specifically relating to Product). In the event of the
termination of Agouron's development obligations in the Licensed Territory
for Product under the LOI and the Definitive Agreement, the licenses
granted to Agouron to use, offer for sale, sell and/or import, in or into
the Licensed Territory, the Product under applicable Immune Response Patent
Rights and using applicable Immune Response Know-How, shall be terminated.
Agouron shall transfer ownership of any dossiers for Product in the
Licensed Territory to Immune Response, and shall cooperate with Immune
Response to effect an orderly transition of Agouron's development
responsibilities in the Licensed Territory to Immune Response.
14. At any time after October 15, 1998, Agouron may elect to immediately
terminate, on a country-by-country basis, its marketing rights for Product
in the Licensed Territory under the LOI and the Definitive Agreement,
except that Agouron may exercise this right to terminate only on the basis
of its concerns related to the safety, efficacy, competitiveness, or
commercial feasibility of Product. In the event that Agouron elects to
terminate its marketing rights for Product in a country: (i) the licenses
granted to Agouron to use, offer for sale, sell and/or import, in or into
such country, the Product under applicable Immune Response Patent Rights
and using applicable Immune Response Know-How, shall be terminated, and
Immune Response and its Affiliates and sublicensees shall be free to market
such Product in such country, on its own, or with any third party; (ii)
Agouron shall transfer ownership to Immune Response of any dossiers for
Product in such country; and (iii) Agouron shall cooperate with to Immune
Response to effect an orderly transition of Agouron's marketing
responsibilities in such country to Immune Response.
15. Immune Response, in accordance with the reasonable directions of Agouron,
shall prepare, file, prosecute, maintain and extend: (i) patent
applications and patents included in the Immune Response Patent Rights; and
(ii) applicable Immune Response trademarks. Immune Response shall own any
Immune Response Patent Rights and Immune Response trademarks and shall be
responsible for all preparation, filing, prosecution, maintenance,
extension and enforcement expenses for such Immune Response Patent Rights
and Immune Response trademarks. Within fourteen (14) days after the
execution of the LOI, Immune Response shall provide Agouron with copies of
the material patent prosecution file histories for the Immune Response
Patent Rights. Immune Response shall be solely responsible for any
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royalties or other payments due to Xxxxx-Xxxxxxx Xxxxx Inc. (including
payments due because of license fees or commercial sales of the Product)
because of their previously contractual arrangement (or the termination
thereof) involving the Product. "***."
16. This Agreement shall be assignable by a party with the prior written
consent of the other party. Any assignment (other than to an Affiliate)
without the prior written consent of the other party shall be void. If
this Agreement is assigned to an Affiliate of a party, the assigning party
shall still be responsible for all of its obligations specified in this
Agreement. Notwithstanding the preceding, the LOI shall be assignable to
the transferee or successor company in the event of: (i) a sale or
transfer of all or substantially all of a party's assets; or (ii) the
merger or consolidation of the party with another company.
17. If the representatives of the parties are unable to reach agreement on a
decision required under the terms of the LOI, the issue shall be submitted
for consideration, in the case of Immune Response, to a designee of its
Chief Executive Officer, and, in the case of Agouron, to a designee of its
Chief Executive Officer. If they are unable to agree, then the Chief
Executive Officers of the parties shall agree upon the appropriate
decision. If the Chief Executive Officers of the parties are unable to
reach agreement on a decision required of them, then the issue shall be
settled by arbitration in San Diego, California in accordance with the
Commercial Arbitration Rules of the American Arbitration Association then
in effect. The decision of the arbitrator(s) shall be final and binding on
all parties. The cost of such arbitration shall be borne by the
non-prevailing party, unless otherwise decided by the arbitrator(s).
18. "***."
19. Neither party shall be held liable or responsible to the other party nor be
deemed to have defaulted under or breached the LOI for the failure or delay
in fulfilling or performing any term of the LOI to the extent, and for so
long as, such failure or delay is caused by or results from causes beyond
the reasonable control of the affected party, including but not limited to
fire, floods, embargoes, war, acts of war (whether war is declared or not),
insurrections, riots, civil commotions, strikes, lockouts or other labor
disturbances, acts of God, or acts, omissions or delays in acting by any
governmental authority or the other party.
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20. In partial consideration for the rights granted to Agouron, Agouron will
purchase from Immune Response two million dollars ($2,000,000) of
unregistered Immune Response Common Stock on each of the purchase dates
listed below at the premiums to Fair Market Value ("FMV") set forth
opposite the applicable purchase date:
Purchase Date Premium
--------------------- --------
Execution Date of LOI 50%
10/15/98 ***
1/15/99 ***
4/15/99 ***
7/15/99 ***
10/15/99 ***
1/17/00 ***
FMV shall mean the average closing price of Immune Response Common Stock
for the five trading days immediately preceding the above purchase dates;
provided, however, that if the FMV of Immune Response Common Stock is "***"
on the applicable purchase date, the premium to FMV shall be "***."
Agouron's obligation to purchase Immune Response Common Stock shall
terminate with respect to any purchase obligations whose applicable
purchase dates occur after Agouron has elected to terminate, in its
entirety, all of its rights and obligations under the LOI and the
Definitive Agreement.
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SCHEDULE 1
COUNTRIES NOT INCLUDED IN THE LICENSED TERRITORY
The following countries, subject to the provisions of Paragraph 18 of Exhibit A,
are excluded from the Licensed Territory "***:"
***
***
***
***
***
***
***
***
***
***
***
***
***
***
***
***
***
***
***
***
The following countries, subject to the provisions of Paragraph 18 of Exhibit
A, are excluded from the Licensed Territory "***."
***
***
***
***
***
***
***
***
***
***
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SCHEDULE 2
IMMUNE RESPONSE PATENT RIGHTS
U.S. Patent No. 5,256,767, issued October 26, 1993, from U.S. Patent
Application Serial No. 07/975,899, filed November 10, 1992.
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*** - Confidential treatment requested
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SCHEDULE 3
SUMMARY OF CLINICAL TRIALS OF PRODUCT BEING CONDUCTED BY IMMUNE RESPONSE
1. Trial 806 is a multi-center, double-blind, Phase III clinical end point
study. Patients are HIV positive with CD4 counts between 300 and 549
cells/mul.
2. Trial 816 is a multi-center, double-blind, Phase II study intended to
evaluate the combination of REMUNE-TM- and triple antiviral drug therapy
(AZT, 3TC and Crixivan) on the induction of an HIV-1 specific immune
response. Patients are HIV positive with CD4 counters > 350 cells/ul.
3. Trial 2102 is a multi-center, double-blind, adjuvant-controlled, Phase II
study of REMUNE plus AZT and ddI versus AZT and ddI alone in HIV-infected
subjects. The trial is being conducted in Spain and patients have CD4
counts between 300 and 700 cells/mul.
4. Trial 808 is a Phase I study to evaluate the safety and immunogenicity of
REMUNE in children with HIV-infection.
5. The Switzerland trial is a single center, randomized, open label, Phase II
study combining antiviral therapy (1592U89) plus Nelfinavir plus Saquinavir
or 141W94) alone or antiviral therapy plus immune-based therapy
(subcutaneous interleukin-2 or REMUNE) in antiviral naive HIV-1 infected
subjects with CD-4 + counts > 250 cells/mul.
6. The England trial is a single center, randomized, open labeled Phase I
study of antiviral therapy (two nucleoside analogues and at least one
protease inhibitor) versus antiviral therapy plus IL-2; antiviral therapy
plus IL-2 plus REMUNE; antiviral therapy plus REMUNE. Patients are HIV
positive with CD4 counts > 300 cells/mul.
7. Trial 818 is a Phase II study intended to evaluate the combination of
interferon-alpha (IFN) and REMUNE on HIV-1 specific immunogenicity in HIV-1
infected subjects with CD-4 counts > 300 cells/mul.
8. Trial 2101B is a Phase II, double-blind, randomized, adjuvant controlled
study of REMUNE.
9. Trial 822 is a randomized, double-blind, adjuvant controlled, research
study to evaluate the combination of REMUNE and HAART on the induction of
HIV-1 specific immune responses.
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