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EXHIBIT 10.1
COLLABORATION AGREEMENT
THIS COLLABORATION AGREEMENT (the "Agreement") is made as of August 7,
2000 (the "Effective Date"), by and between Maxim Pharmaceuticals, Inc., a
Delaware corporation having its principal offices at 8899 University Center
Lane, San Diego, California 92122 ("Maxim") and Hoffmann-La Roche, Inc., having
its principal offices at 340 Kingsland Street, Nutley, New Jersey 07110 and F.
Hoffmann-La Roche Ltd, Grenzacherstrasse 124, CH-4070 Basel, Switzerland
(collectively, "Roche").
WHEREAS, Maxim is developing Maxamine (as defined below) in combination
with certain drugs for the treatment of certain diseases, and has rights to
certain intellectual property related thereto;
WHEREAS, Roche is developing Pegasys and Ribavirin (as defined below)
for the treatment of hepatitis C virus and certain cancers; and
WHEREAS, Roche and Maxim wish to undertake clinical trials and related
activities in order to obtain marketing approval of combination therapy with
Maxamine, Pegasys and Ribavirin for the treatment of hepatitis C virus and with
Maxamine and Pegasys for the treatment of certain cancers, subject to and in
accordance with the terms and conditions of this Agreement; and
WHEREAS, Roche and Maxim wish to coordinate sales strategies of
Maxamine, Pegasys and Ribavirin in order to facilitate marketing of the
combination therapy of such products.
NOW THEREFORE, in consideration of the mutual covenants and obligations
set forth herein the parties hereto agree as follows:
1. DEFINITIONS
The following terms as used in this Agreement will have the meanings
set forth in this Section:
1.1 "AFFILIATE" means an individual, trust, business trust, joint venture,
partnership, corporation, association or any other entity which owns, is owned
by or is under common ownership with a party. For the purposes of this
definition, the term "owns" (including, with correlative meanings, the terms
"owned by" and "under common ownership with") as used with respect to any party,
shall mean the possession (directly or indirectly) of 50% or more of the
outstanding voting securities of a corporation or comparable equity interest in
any other type of entity. The term Affiliate of Roche does not include Genentech
Inc., 1 DNA Way, South San Francisco, California 94080-4990, U.S.A., unless
Roche explicitly opts for such inclusion by giving a written notice to Maxim.
1.2 "AGREEMENT PERIOD" means the period referred to in
Section 9.1.
1.3 "ANNUAL BUDGET" has the meaning set forth in
Section 3.1(e).
*** Text Omitted and Filed Separately
Confidential Treatment Requested
Under 17 C.F.R. Sections 200.80(b)(4),
200.83 and 240.24b-2
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1.4 "APPLICABLE LAWS" means all laws, rules, regulations, directives,
ordinances, guidelines, policies and orders applicable to the activities
described hereunder, including, without limitation, the FDCA and all rules and
regulations of the FDA.
1.5 "CGMPS" means current good manufacturing practices as defined from time
to time in regulations promulgated under the FDCA or issued by the European
Union or Japan, or any successor laws or regulations, governing the manufacture
of Maxamine or Pegasys.
1.6 "CLINICAL TRIAL" means pivotal or other human clinical trials of the
Combination Therapy for a specified Indication as described in Exhibit A and B
of this Agreement that are designed to support Regulatory Approval of the
Combination Therapy for treatment of such Indication in the United States, the
European Union, Japan and such other jurisdictions as are determined appropriate
by the JDC. Without limiting the foregoing, a Clinical Trial would be required
to test the Combination Therapy according to a Protocol for the purpose of
establishing that the Combination Therapy is safe and efficacious for its
intended use and to define warnings, precautions and adverse reactions that are
associated with the Combination Therapy in the dosage range to be prescribed.
1.7 "COLLABORATION" means the collaboration established by this Agreement.
1.8 "COLLABORATION PERIOD" means the period that commences on the Effective
Date and continues until all Clinical Trials in the United States and the
European Union have been completed or terminated and all necessary filings
regarding the Combination Therapy with the FDA in the United States and the
European Union have been made.
1.9 "COMBINATION THERAPY" means, as applicable, (a) Maxamine, Pegasys and
Ribavirin used in combination as a treatment for HCV, or (b) Maxamine and
Pegasys used in combination as a treatment for RCC and Other Cancer Indication.
1.10 "CONFIDENTIAL INFORMATION" means discoveries, inventions, proprietary
information, data, know-how, trade secrets, techniques, methods and materials
techniques and data, including, but not limited to, pharmacological,
toxicological and clinical test data, analytical and quality control data,
regulatory submissions, correspondence and communications, marketing, pricing,
distribution, cost, sales, manufacturing, patent and legal data or descriptions,
received by the receiving party from the disclosing party pursuant to this
Agreement; provided that all data and reports derived from the Clinical Trials
will be deemed Confidential Information of both parties. Without limiting the
generality of the foregoing, the Maxim Intellectual Property will be deemed
Confidential Information of Maxim, and the Roche Intellectual Property will be
deemed Confidential Information of Roche.
1.11 "CONTROL" means possession of the ability to grant a license or
sublicense without violating the terms of any agreement with or other
arrangement with any Third Party.
1.12 "FDA" means the United States Food and Drug Administration, the EMEA
or the Japanese Ministry of Health and Welfare, and any successor entity, or any
other applicable Regulatory Authority.
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1.13 "FDCA" means the Federal Food, Drug and Cosmetics Act and all
regulations and rules promulgated thereunder.
1.14 "HCV" means hepatitis C virus.
1.15 "INVENTION" has the meaning set forth in Section 5.1.
1.16 "IND" means the Investigational New Drug application, as defined by
the FDCA and any foreign equivalent, for the Combination Therapy.
1.17 "INDICATION" means (a) HCV or (b) RCC and Other Cancer Indication.
1.18 "JDC" means the joint development committee described in Section 2.1
that oversees the parties' collaborative activities under this Agreement.
1.19 "MAXAMINE" means Maxamine-R-, Maxim's histamine dihydrochloride
product.
1.20 "MAXAMINE MARKETING AGREEMENT" means a marketing or license agreement
granting to a Third Party or Roche the right to market and promote Maxamine
within a Territory. Maxamine Marketing Agreement excludes any distribution,
wholesale or other agreement designed to facilitate the marketing and promotion
of Maxamine within a Territory by Maxim.
1.21 "MAXIM INTELLECTUAL PROPERTY" means all discoveries, inventions,
information, data, know-how, trade secrets, techniques, methods and materials
(whether or not patentable) that are Controlled by, owned by, licensed by, or
assigned to Maxim as of the Effective Date or during the Agreement Period and
that are necessary or useful for the development, manufacture, use or sale of
Maxamine and all Patents or other intellectual property rights Controlled by,
owned by, licensed by, or assigned to Maxim that cover the foregoing.
1.22 "NDA" means the New Drug Application or Biologics License Application,
as defined by the FDCA, or any foreign equivalent, for the Combination Therapy.
1.23 "OTHER CANCER INDICATION" means a cancer indication other than RCC
selected by the JDC for testing in a Clinical Trial.
1.24 "PATENTS" means (a) unexpired letters patent (including inventor's
certificates) which have not been held invalid or unenforceable by a court of
competent jurisdiction from which no appeal can be taken or has been taken
within the required time period, including without limitation any substitution,
extension, registration, confirmation, reissue, re-examination, renewal or any
like filing thereof and (b) pending applications for letters patent, including
without limitation any continuation, continuation-in-part or division thereof
and any provisional applications.
1.25 "PEGASYS" means Pegasys-R-, Roche's pegylated interferon-alfa 2a
product.
1.26 "PROTOCOL" means, with respect to a Clinical Trial, the protocol for
the Clinical Trial as approved by the JDC.
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1.27 "RCC" means renal cell carcinoma.
1.28 "REGULATORY APPROVAL" means any approvals (including pricing and
reimbursement approvals), licenses, registrations or authorizations of any
Regulatory Authority necessary for the manufacture, distribution, use or sale of
Maxamine and Pegasys, or Maxamine, Pegasys and Ribavirin, as a Combination
Therapy in the applicable jurisdiction.
1.29 "REGULATORY AUTHORITY" means any national, supra-national, regional,
state or local regulatory agency, department, bureau, commission, council or
other governmental entity, with jurisdiction over the manufacture, distribution,
use or sale of Maxamine and Pegasys as a Combination Therapy.
1.30 "RIBAVIRIN" means Roche's branded version of ribavirin product.
1.31 "ROCHE INTELLECTUAL PROPERTY" means all discoveries, inventions,
information, data, know-how, trade secrets, techniques, methods and materials
(whether or not patentable) that are Controlled by, owned by, licensed by, or
assigned to Roche as of the Effective Date or during the Agreement Period and
that are necessary or useful for the development, manufacture, use or sale of
Pegasys or Ribavirin and all Patents or other intellectual property rights
Controlled by, owned by, licensed by, or assigned to Roche that cover the
foregoing.
1.32 "TERRITORY" means any country or group of countries, excluding
Australia, New Zealand, Israel, the West Bank and the Gaza-Palestine Autonomous
Authority.
1.33 "THIRD PARTY" means any person or entity other than Maxim or Roche or
an Affiliate of Maxim or Roche.
1.34 "THIRD PARTY COSTS" means (a) the actual costs incurred by Roche in
excess of $200,000 for non-clinical and clinical pharmacology work performed by
Third Parties necessary to support any filing with respect to the Clinical
Trials with the FDA, and (b) the actual Third Party clinical trial site,
clinical investigator, patient, nursing, investigator meeting, non-drug clinical
supply, and related costs incurred by Roche or Maxim in connection with the
Clinical Trials, as documented in reasonable detail; provided that Third Party
Costs for a given calendar year will not exceed the amount budgeted by the JDC
for Third Party Costs in the Annual Budget for that calendar year.
1.35 "TRIAL DESIGN" means the design for a Clinical Trial, as agreed to by
the parties and attached hereto as Exhibit A or Exhibit B, as applicable.
2. JOINT DEVELOPMENT COMMITTEE
2.1 ESTABLISHMENT OF JDC. The parties will establish the JDC to oversee and
coordinate the development of the Combination Therapy. The JDC will have only
such powers as are specifically delegated to it hereunder and will have no power
to amend this Agreement. The general purpose of the JDC is to (i) establish the
strategy for the clinical development and Regulatory Approval of the Combination
Therapy on a worldwide basis; (ii) oversee the Clinical Trials; and (iii)
coordinate the parties' activities under the Collaboration, all based on the
principles of prompt and diligent development of the Combination Therapy
consistent with good
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pharmaceutical practices. In addition to its overall responsibility for the
Collaboration, the JDC will, in particular, (1) review, modify (if appropriate)
and approve Protocols for the Clinical Trials in accordance with the Trial
Designs; (2) review, modify (if appropriate) and approve IND and NDA filings for
the Clinical Trials; and (3) review, modify (if appropriate) and approve the
Annual Budget.
2.2 COMPOSITION. The JDC will be composed of an equal number of
representatives from each party, selected from the ranks of senior scientists
and senior clinical development management of each party, and will initially
consist of a total of six members. The parties may agree to change the total
number of JDC members from time to time. Within 10 days after the Effective
Date, the parties will designate their representatives on the JDC and will
thereafter notify one another in writing of any change in the membership of the
JDC. With the approval of the JDC, other representatives of each party or of
Third Parties involved in the development, manufacture or commercialization of
Maxamine or Pegasys may attend meetings of the JDC as nonvoting observers. Each
Party shall be responsible for all of its own expenses of participating in the
JDC.
2.3 MEETINGS. The JDC will hold meetings at such times and places as will
be determined by the JDC (it being expected that meetings will alternate between
the offices of each party) but in no event will such meetings be held in person
less frequently than once every quarter. Meetings may be conducted in person or
by audio or video teleconference, provided that two meetings per year will be
conducted in person. The JDC may form and subsequently disband subcommittees
with appropriate representation from each party and may otherwise amend or
expand upon the foregoing procedures for its internal operation.
2.4 VOTING. Meetings of the JDC will be effective only if at least one
representative of each party on the JDC is present or participating. In taking
actions by the JDC, each party will have one vote. All actions by the JDC will
require unanimous approval. If the JDC fails to reach unanimity on a matter
before it for decision, the matter will be referred for resolution to the Chief
Executive Officer of Maxim and the Head of Global Development and/or Head of
Strategic Marketing of Roche (or its appointed designee) for their consideration
and agreement. If they are unable to agree after negotiation in good faith,
either party may request resolution of the matter pursuant to Section 10, except
that adoption of any initial or amended Trial Design or any Annual Budget or
determination of whether Maxim should be the filing party for an IND or NDA must
be by agreement of the parties and may not be determined by dispute resolution
in accordance with Section 10
2.5 CO-CHAIRPERSONS. One representative of Maxim and one representative of
Roche on the JDC will be selected as co-chairpersons of the JDC. The
co-chairpersons of the JDC will have alternating responsibility for preparing
and circulating an agenda in advance of each meeting and preparing and issuing
minutes of each meeting within 30 days thereafter, which minutes will report in
reasonable detail the actions taken by the JDC, the status of any ongoing
development programs, issues requiring resolution and resolutions of previously
reported issues. Final minutes of JDC meetings are to be signed by both of the
JDC co-chairpersons.
2.6 SUBCOMMITTEES. Any subcommittee established by the JDC will have
appropriate representation of each party and may include representatives who are
not members
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of the JDC. Any such subcommittee will be given assignments from the JDC, will
be subject to the authority of the JDC and will report its actions to the JDC.
At the request of either party at any time, any such subcommittee will be
dissolved and its powers and functions returned to the JDC. The JDC will retain
the right of final approval before the implementation of any actions by the
subcommittees.
3. DEVELOPMENT OF COMBINATION THERAPY
3.1 CLINICAL TRIALS.
(a) Roche will be responsible for managing and monitoring two Clinical
Trials of the Combination Therapy for the treatment of HCV in humans, including,
without limitation, site recruitment, site monitoring, safety and medical
monitoring, laboratory testing, data management, document control, analysis of
results, regulatory reporting, and provision of information and reports in
accordance with Section 3.4. The initial Trial Design for such Clinical Trials
will be finalized and attached hereto as Exhibit A within 30 days after the
Effective Date and may be amended only by mutual written agreement of the
parties.
(b) Roche will be responsible for managing and monitoring two Clinical
Trials of the Combination Therapy for the treatment of RCC and Other Oncology
Indication in humans, including, without limitation, site recruitment, site
monitoring, safety and medical monitoring, laboratory testing, data management,
document control, analysis of results, regulatory reporting, and provision of
information and reports in accordance with Section 3.4. The initial Trial Design
for such Clinical Trials will be finalized and attached hereto as Exhibit B
within 30 days after the Effective Date and may be amended only by mutual
written agreement of the parties.
(c) The Clinical Trials described in Section 3.1(a) and (b) would be
conducted globally as is determined appropriate by the JDC. Roche, and Maxim,
will prepare the Protocol for each Clinical Trial in accordance with the Trial
Design for such Clinical Trial. Roche will submit the Protocol to the JDC for
review, modification (if appropriate) and approval. Roche and Maxim will make
any modification to the Protocol recommended by the JDC. Roche and Maxim will
perform their obligations with respect to such Clinical Trials in accordance
with the Protocol and Applicable Laws and will ensure that any research
institution or organization and any investigator that participates in any such
Clinical Trial will conduct such Clinical Trial in accordance with the Protocol
and Applicable Laws. Roche and Maxim will be responsible for supervising and
managing research institutions or organizations and investigators that
participate in the Clinical Trials. Maxim will provide personnel experienced in
the use of Maxamine to participate in the training of, and act as a liaison to,
such research institutions or organizations and investigators.
(d) Roche will prepare the IND and NDA filings associated with the
Clinical Trials described in Section 3.1(a) and (b). Maxim will provide to Roche
such assistance and technical support related to Maxamine as is necessary or
appropriate to prepare the IND and NDA filings associated with such Clinical
Trials, including, without limitation, the chemistry, manufacturing and controls
section of the NDA filings. Roche and Maxim will submit the IND and NDA filings
associated with such Clinical Trials to the JDC for review, modification (if
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appropriate) and approval. Roche and Maxim will make any modification to the IND
and NDA filings recommended by the JDC. Once an IND or NDA filing associated
with such Clinical Trials is approved by the JDC, Roche will file the IND or
NDA, unless the JDC determines that Maxim should be the filing party, in which
case Maxim will file the IND or NDA; provided that, if the JDC cannot reach
agreement over whether Maxim should be the filing party, then Roche will be the
filing party. The filing party will be responsible for strategy, as approved by
the JDC, and communications with the FDA with regard to the Clinical Trials
consistent with the Protocol and the IND and NDA filings; provided, however,
that the non-filing party will have the right to participate in all meetings
with the FDA involving such IND or NDA. The filing party will provide the
non-filing party with a copy of all correspondence submitted to or received from
the FDA within one week after its submission or receipt. Each party will provide
to the other party such assistance and technical support related to Maxamine or
to Pegasys or Ribavirin, as applicable, as is necessary or appropriate with
respect to FDA comments or requests with respect to the IND and NDA filings
associated with the Clinical Trials. The filing party will be responsible for
maintaining any registrations for the Combination Therapy in the United States
during the Agreement Period in compliance with Applicable Laws.
(e) Roche and Maxim will prepare an annual budget for all Third Party
Costs to be incurred in the following calendar year (the "Annual Budget"). Roche
and Maxim will submit the Annual Budget to the JDC for review, modification (if
appropriate) and approval at least 60 days prior to the beginning of the
calendar year to which the Annual Budget applies. The JDC will make any
appropriate modification to the Annual Budget and approve the Annual Budget no
later than the first day of the calendar year to which the Annual Budget
applies.
(f) Either party may terminate a Clinical Trial in the event of
identification of any medical risk to subjects in the Clinical Trial,
unsatisfactory results from the Clinical Trial, non-compliance with applicable
requirements of any Regulatory Authority or notice of action by any Regulatory
Authority terminating or suspending the Clinical Trial.
3.2 SUPPLY OF DRUGS FOR CLINICAL TRIALS.
(a) Maxim will have the exclusive right and the obligation to supply,
without charge, to Roche all requirements for Maxamine for use in the Clinical
Trials described in Section 3.1(a) and (b) (including manufacturing, packaging,
labeling and quality assurance). Maxim warrants that the Maxamine supplied by
Maxim will be manufactured in accordance with Applicable Laws, including cGMPs.
(b) Roche will have the exclusive right and the obligation to supply,
without charge, all requirements for Pegasys and ribavirin for use in the
Clinical Trials described in Section 3.1(a) and (b) in accordance with the
Protocol (including manufacturing, packaging, labeling and quality assurance).
Roche warrants that the Pegasys and ribavirin supplied by Roche will be
manufactured in accordance with Applicable Laws, including cGMPs.
(c) EXCEPT AS EXPRESSLY STATED IN THIS SECTION 3.2, MAXIM MAKES NO
OTHER WARRANTIES, EXPRESS OR IMPLIED, WITH RESPECT TO MAXAMINE SUPPLIED
HEREUNDER, AND ROCHE MAKES NO OTHER WARRANTIES, EXPRESS OR IMPLIED, WITH RESPECT
TO PEGASYS OR RIBAVIRIN
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SUPPLIED HEREUNDER. ALL OTHER WARRANTIES, EXPRESS OR IMPLIED, INCLUDING, WITHOUT
LIMITATION, THE IMPLIED WARRANTIES OF MERCHANTABILITY AND FITNESS FOR A
PARTICULAR PURPOSE ARE HEREBY EXPRESSLY DISCLAIMED.
3.3 COSTS OF CLINICAL TRIALS.
(a) Roche and Maxim will share equally all Third Party Costs. On a
quarterly basis, Roche will provide Maxim with a statement showing the Third
Party Costs incurred during the applicable quarter in reasonable detail. Maxim
will reimburse Roche for 50% of the Third Party Costs reflected on such
statement within 30 days after the end of the applicable quarter. Roche shall
maintain, and cause its Affiliates and Third Parties acting for its account to
maintain, books of account and complete and accurate records pertaining to Third
Party Costs in sufficient detail to permit confirmation of the correct
calculation of these Third Party Costs. Upon the request by Maxim, Roche at
Maxim's expense, agrees to instruct its independent accounting firm to perform
such additional auditing and accounting procedures as are necessary to enable
such accounting firm to confirm to Maxim the correct calculation of Third Party
Costs; it being understood that such auditing shall not be requested to be
performed more frequently than once per calendar year nor more frequently than
once with respect to records covering any specific period of time and shall not
commence later than two years following the end of the period requested to be
audited. The failure of Maxim to request verification of any calculation of
Third Party Costs during the period when records have to be retained shall be
considered acceptance of the accuracy of such reporting by Maxim. Roche will
promptly pay to Maxim any amounts that Maxim overpaid as determined by the
independent accounting firm.
(b) Maxim will bear all costs incurred by Maxim in connection with
Maxim's responsibilities under Sections 3.1(d) and 3.2(a).
(c) Roche will bear all costs incurred in connection with the Clinical
Trials, except as specifically provided in Section 3.3(a) and (b). Roche and
Maxim will equally share the cost of maintaining any registrations for the
Combination Therapy during the Agreement Period.
3.4 REPORTS AND ACCESS.
(a) During the course of the Clinical Trials, Roche will provide to
Maxim information, data and reports with regard to the Clinical Trials as
appropriate to enable Maxim to monitor the progress of the Clinical Trials on a
monthly basis. In addition, Roche will provide to Maxim clinical data,
statistical reports and related documentation derived from the Clinical Trials
promptly following the time that such data or reports are available to or
prepared by Roche.
(b) Roche's personnel will make periodic visits to the sites at which
the Clinical Trials are conducted. Roche will provide Maxim with schedules of
the visits relating to such Clinical Trials. Maxim personnel may, upon
reasonable notice, accompany Roche's personnel on such site visits.
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(c) Each party will promptly notify the other party of inspections by
the FDA or any other governmental or regulatory authority relating to the
Clinical Trials of which it becomes aware. Maxim will have the right to be
present at any such inspections, and the parties will cooperate in preparing any
responses which may be required. In connection with any such inspection, Roche
and Maxim will provide representatives of FDA with access to any of its
facilities, personnel, documentation, procedures, equipment, records and
activities involved in the Clinical Trials or otherwise required for Regulatory
Approval.
(d) The party that filed the IND and NDA will hold the IND and NDA but
will give the non-filing party access to all IND, NDA and related filings and
underlying data, reports and information associated with the Combination Therapy
and the Clinical Trials which have been generated during the term of this
agreement. Each party will be entitled to use such data, reports and information
for its own filings, if any; provided that neither party will use such data,
reports and information relating to the Combination Therapy for any filing to
the FDA without the other party's prior written approval, which will not be
unreasonably withheld, or unless required by the FDA.
3.5 EXCLUSIVITY.
(a) During the Collaboration Period, Maxim agrees not to conduct,
or support the conduct, of any clinical trial of Maxamine and any pegylated
interferon (other than Pegasys) used in combination as a treatment for HCV or
for RCC and Other Cancer Indication, provided that such exclusivity agreement
will terminate if (a) Roche does not obtain approval to market Pegasys in the
United States by [...***...]; or (b) worldwide sales of Pegasys do not
represent at least [...***...]% of the global market for pegylated interferon
in HCV by [...***...], and at least [...***...]% of the global market for
pegylated interferon in HCV by [...***...], based on IMS data; or (c) the
objectives regarding IND filing deadlines, Clinical Trial commencement date
deadlines, or NDA filing deadlines detailed in Exhibit C are delayed by more
than three months.
(b) Maxamine must be approved and marketed in the United States by
[...***...] or Roche may terminate this Agreement upon 30-day written notice
to Maxim.
4. MARKETING
4.1 STRATEGIC MARKETING EFFORTS. The parties agree that, with respect to
the Combination Therapy, Maxim will be responsible for the marketing and sales
of Maxamine and Roche will be responsible for the marketing and sales of Pegasys
and Ribavirin. Maxim and Roche agree that they will cooperate in the development
of promotional materials which reference Maxamine and Pegasys and Ribavirin, and
in the training of their respective sales forces in order to maximize the
opportunity to market and sell Maxamine, and Pegasys and Ribavirin,
respectively, as a Combination Therapy. Each party will bear the costs of
training of its own sales force. Each party's respective package insert will
refer to the brand name of the other party's components of the Combination
Therapy.
4.2 RIGHT OF FIRST REFUSAL. Maxim agrees that prior to entering into any
Maxamine Marketing Agreement with any Third Party in any Territory it will offer
to Roche the right of first refusal to enter into an agreement with Maxim under
terms that are substantially equivalent to the terms of the proposed agreement
with such Third Party. Prior to entering into a Maxamine
*Confidential Treatment Requested*
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Marketing Agreement with any Third Party in any Territory, Maxim will
communicate to Roche a copy of the proposed term sheet negotiated under arms'
length conditions for this agreement, and Roche will have 45 days to notify
Maxim in writing if Roche is electing to enter into such Maxamine Marketing
Agreement for that Territory under terms that are substantially equivalent to
the terms which have been negotiated by Maxim with the Third Party. In the event
that Roche makes the aforementioned election on a timely basis, then Maxim and
Roche agree to negotiate and complete a Maxamine Marketing Agreement consistent
with the proposed terms within 30 days of such election.
4.3 COMPLIANCE WITH APPLICABLE LAWS. Roche will comply with all Applicable
Laws with respect to its promotion of Pegasys as part of the Combination
Therapy. Maxim will comply with all Applicable Laws with respect to its
promotion of Maxamine as part of the Combination Therapy. Each party will also
ensure that any Third Parties that are involved in the marketing, sale or
distribution of the Combination Therapy through any contract or arrangement with
such party comply with the material provisions of this Agreement, as well as
with all Applicable Laws with respect to the promotion of the Combination
Therapy.
5. INTELLECTUAL PROPERTY RIGHTS
5.1 OWNERSHIP. Except as otherwise set forth herein, ownership of any
inventions (whether or not patentable) that are conceived of by any employee or
agent of Maxim or Roche and arise from the Clinical Trials or other activities
performed in accordance with this Agreement ("Inventions") shall be determined
in accordance with United States laws of inventorship and any contractual
obligations of the inventors as to the assignment of such inventions,
5.2 MAXIM INTELLECTUAL PROPERTY. Maxim will own all right, title and
interest in and to Maxamine and all Maxim Intellectual Property. All Inventions
arising from the Clinical Trials or other activities performed in accordance
with this Agreement that comprise enhancements or improvements to the Maxim
Intellectual Property, whether made solely by Maxim, solely by Roche or jointly
by Maxim and Roche, will be owned solely by Maxim. Roche hereby irrevocably
assigns to Maxim all of its right, title and interest in and to any such
Inventions and intellectual property rights therein.
5.3 ROCHE INTELLECTUAL PROPERTY. Roche will own all right, title and
interest in and to Pegasys, Ribavirin and all Roche Intellectual Property. All
Inventions arising from the Clinical Trials or other activities performed in
accordance with this Agreement that comprise enhancements or improvements to the
Roche Intellectual Property, whether made solely by Roche, solely by Maxim or
jointly by Roche and Maxim, will be owned solely by Roche. Maxim hereby
irrevocably assigns to Roche all of its right, title and interest in and to any
such Inventions and intellectual property rights therein.
5.4 LICENSE. Each party will retain a royalty-free, fully paid up,
worldwide, perpetual license under any Invention (and any intellectual property
rights covering such Invention) owned by the other party to sell its respective
product (Pegasys and Ribavirin on the part of Roche and Maxamine on the part of
Maxim) as part of a Combination Therapy for the therapeutic indications
developed in the Clinical Trials.
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5.5 ENFORCEMENT. Roche will act in good faith to inform Maxim of any
infringement of which Roche becomes aware by any Third Party of the Maxim
Intellectual Property. Maxim will act in good faith to inform Roche of any
infringement of which Maxim becomes aware of Roche Intellectual Property. Both
parties agree not to infringe or encourage the infringement of the Intellectual
Property of the other party.
6. CONFIDENTIALITY
6.1 TREATMENT OF CONFIDENTIAL INFORMATION. During the Agreement Period and
for five years thereafter, a party receiving or gaining access to Confidential
Information, as defined below, of the other Party will (i) maintain in
confidence such Confidential Information to the same extent the receiving party
maintains its own proprietary information, (ii) not disclose such Confidential
Information to any Third Party without prior written consent of the disclosing
party, and (iii) not use such Confidential Information for any purpose except as
permitted by this Agreement. A party shall have no obligations under this
Section 6 with respect to any portion of such Confidential Information which:
(a) is publicly disclosed by the disclosing party, either before or
after it becomes known to the receiving party; or
(b) was known to the receiving party, without obligation to keep it
confidential, prior to when it was received from the disclosing party; or
(c) is subsequently disclosed to the receiving party by a Third Party
lawfully in possession thereof without obligation to keep it confidential; or
(d) has been independently developed by the receiving party without
the aid, application or use of Confidential Information; or
(e) is required by law to be disclosed, but then only to the limited
extent of such legally required disclosure; and provided that the disclosing
party is notified reasonably in advance of such disclosure and that the
receiving party cooperates fully with the disclosing party in attempting to
obtain confidential treatment of such Confidential Information.
6.2 PUBLICITY. The parties agree that the public announcement of the
execution of this Agreement shall be substantially in the form of the press
release attached as Exhibit D. Any other publication, news release or other
public announcement relating to this Agreement or to the performance hereunder,
shall first be reviewed and approved by both parties, which approval shall not
be unreasonably withheld or delayed; provided, however, that any disclosure
which is required by law as advised by the disclosing party's counsel may be
made without the prior consent of the other party, although the other party
shall be given prompt notice of any such legally required disclosure and to the
extent practicable shall provide the other party an opportunity to comment on
the proposed disclosure. In this regard, the parties recognize that Maxim is a
publicly held biotechnology company, Maxamine is among Maxim's first potential
products and Maxim will need to provide information regarding the status of
Maxamine, its clinical trials, and clinical trial results to the investment
community from time to time.
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6.3 PUBLICATIONS. The parties will cooperate in appropriate publication of
the results of the Clinical Trials, but subject to the predominating interest to
obtain patent protection for any patentable subject matter. To this end, prior
to any public disclosure of such results, the party proposing disclosure will
send the other party a copy of the information to be disclosed, and shall allow
the other party 30 days from the date of receipt in which to determine whether
the information to be disclosed contains subject matter for which patent
protection should be sought prior to disclosure, or otherwise contains
Confidential Information of the reviewing party. The party proposing disclosure
will be free to proceed with the disclosure unless prior to the expiration of
such 30-day period the non-disclosing party notifies the other party that the
disclosure contains subject matter for which patent protection should be sought
or Confidential Information of the non-disclosing party, and the party proposing
publication will then delay public disclosure of the information for an
additional period of up to three months to permit the preparation and filing of
a patent application on the subject matter to be disclosed or for the parties to
determine a mutually acceptable modification to such publication to protect the
Confidential Information of the non-disclosing party adequately. The party
proposing disclosure will thereafter be free to publish or disclose the
information. The determination of authorship for any paper will be in accordance
with accepted scientific practice as determined by the JDC. Both parties shall
have the right to present the Clinical Trial results, with requests for such
presentations to be approved by the JDC.
6.4 TERMS OF THE AGREEMENT. The parties agree that the material terms of
this Agreement will be considered Confidential Information of both parties.
Notwithstanding the foregoing, each party shall have the right to disclose the
material terms of this Agreement in confidence to any bona fide potential
investor, investment banker, acquirer, merger partner or other potential
financial partner, and where reasonably practicable, shall obtain an adequate
agreement of confidentiality consistent with the terms of this Agreement. A
party that makes any disclosure pursuant to the preceding sentence will notify
the other party of such disclosure.
7. REPRESENTATIONS; DISCLAIMERS
7.1 MUTUAL AUTHORITY. Each party represents and warrants to the other party
that (a) it has the authority and right to enter into and perform this
Agreement, and (b) its execution, delivery and performance of this Agreement
does not conflict with the terms of any other agreement to which it is a party
or by which it is bound.
7.2 DISCLAIMER. The parties understands that Maxamine, Pegasys and
ribavirin are the subject of ongoing clinical research and development and that
no assurance can be made with regard to the safety or usefulness of Maxamine,
Pegasys or ribavirin or the Combination Therapy. Except as expressly set forth
in Section 3.2(a) and (b) and Section 7.1, NEITHER PARTY MAKES ANY
REPRESENTATION NOR EXTENDS ANY WARRANTIES OF ANY KIND, EITHER EXPRESS OR
IMPLIED. THERE ARE NO EXPRESS OR IMPLIED WARRANTIES OF MERCHANTABILITY OR
FITNESS FOR A PARTICULAR PURPOSE OR NON-INFRINGEMENT.
7.3 LIMITATION OF LIABILITY. SUBJECT TO THE PARTIES' INDEMNIFICATION
OBLIGATIONS UNDER SECTION 8, NEITHER PARTY WILL BE LIABLE TO THE OTHER FOR ANY
INDIRECT, INCIDENTAL, SPECIAL OR CONSEQUENTIAL
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DAMAGES, INCLUDING LOST PROFITS, REGARDLESS OF WHETHER THE CLAIM IS BASED ON
CONTRACT, TORT, WARRANTY, OR OTHERWISE, EVEN IF THE OTHER PARTY HAS BEEN ADVISED
OF THE POSSIBILITY OF SUCH DAMAGES.
8. INDEMNIFICATION.
8.1 BY MAXIM. Maxim will indemnify, defend and hold Roche, its Affiliates
and their officers, agents and employees harmless from and against any and all
Third Party claims, damages, losses, costs and expenses, including reasonable
attorneys' fees (collectively, "Claims") arising directly or indirectly from (a)
the manufacture, use, handling, storage, transport, distribution, sale or other
disposition of Maxamine by Maxim or its Affiliates, agents or sublicensees, or
(b) any breach of any of Maxim's warranties under Section 3.2(a) or 7.1 hereof,
except to the extent that such Claims result from negligence or willful
misconduct of Roche.
8.2 BY ROCHE. Roche will indemnify, defend and hold Maxim, its Affiliates
and their officers, agents and employees harmless against any Claim arising
directly or indirectly from (a) the manufacture, use, handling, storage,
transport, distribution, sale or other disposition of Pegasys or ribavirin by
Maxim or its Affiliates, agents or sublicensees, , or (b) any breach of any of
Roche's warranties under Section 3.2(b) or 7.1, except to the extent that such
Claims result from negligence or willful misconduct of Maxim.
8.3 PROCEDURE.
(a) In the event that a party receives notice of or becomes aware of a
Claim in respect of which it may seek indemnity hereunder from the other party,
the indemnified party will promptly provide the indemnifying party with notice
of such Claim and of its intention to seek indemnity.
(b) The indemnifying party will have the right at its option and its
own expense, to defend the indemnified party against, negotiate, settle or
otherwise deal with any such Claim, provided that the indemnifying party will
not enter into any settlement or compromise of any such Claim which could lead
to liability or create any financial or other obligation on the part of the
indemnified party without the indemnified party's prior written consent. The
indemnified party may participate in the defense of any Claim with counsel of
its own choice and its own expense. The parties agree to cooperate fully with
each other in connection with the defense negotiation or settlement of any such
Claims.
(c) In the event that the indemnifying party does not undertake the
defense, compromise or settlement of a Claim, the indemnified party will have
the right to control the defense or settlement of such Claim with counsel of its
choosing at the expense of the indemnifying party, provided, however, that the
indemnified party will not settle or compromise any such claim without the
indemnifying party's prior written consent, which consent will not be
unreasonably withheld.
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9. TERM AND TERMINATION
9.1 AGREEMENT PERIOD. The term of this Agreement will commence as of the
Effective Date and will expire five years after completion or termination of the
last Clinical Trials, unless earlier terminated pursuant to Section 3.5(b) or
9.2.
9.2 TERMINATION. This Agreement may be terminated (a) by the parties by
mutual agreement, or (b) by either party upon written notice to the other party
in the event the other party has breached a material term of this Agreement and
has not cured such breach within 60 days after receiving notice of such breach
from the non-breaching party.
9.3 SURVIVAL. All rights and obligations of the parties under this
Agreement will terminate upon termination or expiration of this Agreement,
except that (a) termination or expiration of this Agreement will not relieve
either party of any liability or obligation that accrued hereunder prior to the
effective date of such termination or expiration, and (b) the provisions of
Sections 3.2(c), 3.3 (excluding the first three sentences and only for the
two-year period following the date of such termination or expiration), 3.4(d),
5, 6.1, 7.2, 7.3, 8, 9.3, 9.4, 10 and 11 will survive any termination or
expiration of this Agreement.
9.4 REMEDIES. In the event of any breach of any provision of this
Agreement, in addition to the termination rights set forth herein, each party
shall have all other rights and remedies at law or equity to enforce this
Agreement.
10. DISPUTE RESOLUTION
10.1 DISPUTES. The parties recognize that disputes as to certain matters
may from time to time arise which relate to either party's rights and/or
obligations hereunder. It is the objective of the parties to establish
procedures to facilitate the resolution of such disputes in an expedient manner
by mutual cooperation and without resort to arbitration. To accomplish this
objective, the parties agree to follow the procedures set forth in Section 10.2
if and when such a dispute arises between the parties.
10.2 PROCEDURES. If any dispute arises between the parties relating to the
interpretation, breach or performance of this Agreement or the grounds for the
termination of this Agreement, and the parties cannot resolve the dispute within
30 days of a written request by either party to the other party, the parties
agree to hold a meeting, attended by the Chief Executive Officer of Maxim and
the Head of Global Development and/or the Head of Strategic Marketing of Roche
or their assignees, to attempt in good faith to negotiate a resolution of the
dispute prior to pursuing other available remedies. If, within 60 days after
such written request, the parties have not succeeded in negotiating a resolution
of the dispute, such dispute shall be submitted to final and binding arbitration
under the then current commercial rules and regulations of the American
Arbitration Association ("AAA") relating to voluntary arbitrations. The
arbitration proceedings shall be held in New Jersey. The arbitration shall be
conducted by three arbitrators, who are knowledgeable in the subject matter at
issue in the dispute and who shall be selected by mutual agreement of the
parties or, failing such agreement, shall be selected in accordance with the AAA
rules. Each party shall initially bear its own costs and legal fees associated
with such arbitration. The prevailing party in any such arbitration shall be
entitled to
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<PAGE>
recover from the other party the reasonable attorneys' fees, costs and expenses
incurred by such prevailing party in connection with such arbitration. The
decision of the arbitrator shall be final and binding on the parties. The
arbitrator shall prepare and deliver to the parties a written, reasoned opinion
conferring its decision. Judgment on the award so rendered may be entered in any
court having competent jurisdiction thereof.
11. MISCELLANEOUS
11.1 NO WAIVER. Failure of either party to insist upon strict observance of
or compliance with any of the terms of this Agreement in one or more instances
will not be deemed to be a waiver of its right to insist upon such observance or
compliance with those or other terms of this Agreement with respect to
subsequent breaches of any of the terms of this Agreement.
11.2 NOTICES. All notices and demands required or permitted hereunder will
be in writing and delivered (a) by certified or registered mail, postage
prepaid, (b) by a nationally recognized express mail service, (c) by hand
delivery, or (d) by facsimile, with receipt confirmed, at the following
addresses:
If to Roche: Roche Pharmaceuticals Inc
340 Kingsland Street
Building 85/8th Floor
Nutley, New Jersey 07110
Attn: Frederick C. Kentz, Corporate Secretary
Tel: (+1 973) 235-5000
Fax: (+1 973) 235-3500
F-Hoffmann-La Roche Ltd.
Law Department
Grenzacherstrasse 123
CH-4070 Basel
Switzerland
Tel: +41 61 688 11 11
If to Maxim: Maxim Pharmaceuticals, Inc.
8899 University Center Lane
San Diego, California 92122
Attn: Chief Executive Officer
Tel: (858) 453-4040
Fax: (858) 453-4005
or to such other address as to which either part may notify the other. Notice
will be deemed to be effective three (3) days after mailing, or upon receipt if
hand delivered or sent by express mail service or by facsimile.
11.3 ASSIGNMENT. Except as expressly provided hereunder, neither this
Agreement nor any rights or obligations hereunder may be assigned by either
party without the prior written consent of the other party (which consent shall
not be unreasonably withheld); PROVIDED,
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HOWEVER, that either party may assign this Agreement and its rights and
obligations hereunder without the other party's consent (a) in connection with
the transfer or sale of all or substantially all of the business of such party
to which this Agreement relates to a Third Party, whether by merger, sale of
stock, sale of assets or otherwise, or (b) to any Affiliate. Notwithstanding the
foregoing, any such assignment to an Affiliate shall not relieve the assigning
party of its responsibilities for performance of its obligations under this
Agreement. The rights and obligations of the parties under this Agreement shall
be binding upon and inure to the benefit of the successors and permitted assigns
of the parties. Any assignment not in accordance with this Section 11.3 shall be
void.
11.4 GOVERNING LAW. This Agreement is governed by the laws of the State of
California as applied to agreements executed and to be performed entirely in the
State of California by residents of the State of New Jersey.
11.5 SEVERABILITY. In the event any one or more of the provisions of this
Agreement should for any reason be held by any court of authority having
jurisdiction over eider the parties or this Agreement to be invalid, illegal or
unenforceable, such provision or provisions will be validly reformed so as to
nearly approximate the intent of the parties as possible or, if such provision
or provisions cannot be validly reformed, will be divisible and deleted in such
jurisdiction; otherwise, this Agreement will continue in full force effect.
11.6 INDEPENDENT CONTRACTORS. Nothing in this Agreement is intended or will
be deemed to constitute a partnership, agency, employer-employee or joint
venture relationship between the parties. All activities by the parties
hereunder will be performed by them as independent contractors. Neither party
will incur any debts or make any commitments for the other party, except the
extent specifically provided herein.
11.7 ENTIRE AGREEMENT; AMENDMENT. This Agreement (including the exhibits
attached hereto) sets forth all of the covenants, promises, agreements,
warranties, representations, conditions and understandings between the parties
hereto with respect to the subject matter hereof and supersedes and terminates
all prior agreements and understandings between the Parties. There are no
covenants, promises, agreements, warranties, representations conditions or
understandings, either oral or written, between the parties other than as set
forth herein. No subsequent alteration, amendment, change or addition to this
Agreement shall be binding upon the parties hereto unless reduced to writing and
signed by the respective authorized officers of the parties.
11.8 FORCE MAJEURE. Neither party shall be held liable or responsible to
the other Party nor be deemed to have defaulted under or breached this Agreement
for failure or delay in fulfilling or performing any term of this Agreement
(other than non-payment) when 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 be 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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11.9 COUNTERPARTS. This Agreement may be executed in multiple counterparts,
each of which shall be deemed an original, but all of which together shall
constitute one and the same instrument.
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IN WITNESS WHEREOF, the parties have caused this Agreement to be
executed by their duly authorized representatives as of the day and year
indicated below.
<TABLE>
<CAPTION>
F. HOFFMANN-LA ROCHE LTD. MAXIM PHARMACEUTICALS, INC.
<S> <C>
By: /s/ BERTRAND LEHUU By: /s/ LARRY G. STAMBAUGH
-------------------------------------- ------------------------------------------
Title: Licensing Manager Title: Chairman and Chief Executive Officer
----------------------------------- ---------------------------------------
Date: August 7, 2000 Date: August 2, 2000
------------------------------------ ----------------------------------------
</TABLE>
By: /s/ PASCAL BUERGIN
--------------------------------------
Title: Legal Counsel
-----------------------------------
Date: August 7, 2000
------------------------------------
HOFFMANN-LA ROCHE INC.
By: /s/ FREDERICK C. KENTZ
--------------------------------------
Title: Vice President & General Counsel
-----------------------------------
Date: August 7, 2000
------------------------------------
<PAGE>
EXHIBIT A
TRIAL DESIGNS - HCV
[The Agreement contemplates that this Exhibit will be agreed upon by the
parties at a future date. As a result, this Exhibit has not been prepared or
agreed upon by the parties as of the date the Agreement was executed and
at the time this Exhibit was filed with the SEC.]
<PAGE>
EXHIBIT B
TRIAL DESIGNS - RCC AND OTHER CANCER INDICATION
[The Agreement contemplates that this Exhibit will be agreed upon by the
parties at a future date. As a result, this Exhibit has not been prepared or
agreed upon by the parties as of the date the Agreement was executed and
at the time this Exhibit was filed with the SEC.]
<PAGE>
EXHIBIT C
TIMELINE OBJECTIVES
<TABLE>
<CAPTION>
Clinical Trial NDA
Indication IND Filing Commencement Filing
---------- ---------- ------------ ------
<S> <C> <C> <C>
1ST HCV CLINICAL TRIAL [...***...] [...***...] [...***...]
(OR INITIAL SAFETY OR DOSE FINDING STUDY LEADING TO IND
ACCEPTANCE)
2ND HCV CLINICAL TRIAL [...***...] [...***...] [...***...]
RCC [...***...] [...***...] [...***...]
(OR INITIAL SAFETY OR DOSE FINDING STUDY LEADING TO IND
ACCEPTANCE)
OTHER CANCER INDICATION [...***...] [...***...] [...***...]
</TABLE>
*Confidential Treatment Requested*
<PAGE>
EXHIBIT D
PRESS RELEASE
[Logo]
Contacts:
Larry G. Stambaugh Ethan Denkensohn (Investors)
Chairman, President and CEO Kathy Jones, Ph.D. (Media)
Dale A. Sander Burns McClellan
Chief Financial Officer (212) 213-0006
(858) 453-4040
MAXIM PHARMACEUTICALS AND HOFFMANN - LA ROCHE
ENTER INTO SIGNIFICANT DEVELOPMENT COLLABORATION
- MAXIM AND ROCHE EXPECT COLLABORATION TO LEAD TO IMPORTANT ADVANCES
IN THE TREATMENT OF CANCER AND HEPATITIS C -
San Diego, CA, August 10, 2000 - Maxim Pharmaceuticals (Nasdaq NM: MAXM, SSE:
MAXM) announced that it has entered into a comprehensive development
collaboration with F. Hoffmann - La Roche Ltd, Switzerland and its US branch
Hoffmann - La Roche, Inc. for the development of Maxim's lead drug MAXAMINE-R-
(histamine dihydrochloride) in combination with the investigational compound
Pegasys-R-, Roche's pegylated interferon-alpha agent. Both parties expect that
the combination of MAXAMINE and Pegasys will lead to important advances in the
treatment of cancer and hepatitis C.
"Roche clearly represents a great development partner for Maxim due to the
success they have had with the clinical development of Pegasys, and the fact
that they share our commitment to advancing the treatment of hepatitis C and
cancer," said Larry G. Stambaugh, Maxim's Chairman and Chief Executive
Officer. "This collaboration not only produces a substantial strategic and
economic benefit to us, it allows us to accelerate and expand the clinical
development of MAXAMINE."
"We are excited about the potential contribution that the combination of
MAXAMINE and Pegasys may make to the treatment of hepatitis C and the targeted
cancers," said Simon Pedder, Ph.D., Pharmaceutical Business Director for
Pegasys. "Hepatitis C in particular is a substantial unmet need. Our hope is
that the addition of MAXAMINE to Pegasys, an agent that has produced promising
clinical data in hepatitis C as a monotherapy, will result in a combination
therapy that represents a further improvement in patient care. In addition, the
data from the Phase III trial of MAXAMINE in advanced malignant melanoma
encouraged us to move aggressively forward with the development of the
Pegasys/MAXAMINE combination treatment in cancer."
Under the agreement, Maxim and Roche will undertake clinical trials and other
activities designed to seek regulatory approval of the combination of MAXAMINE
and Pegasys for the treatment of hepatitis C and certain cancers. Specifically,
the collaboration program will include two Phase III trials of the MAXAMINE and
Pegasys combination for the treatment of hepatitis C, one Phase III trial of
MAXAMINE and Pegasys for the treatment of advanced-stage renal cell carcinoma,
and an additional Phase III trial in another cancer to be selected by the two
companies. Roche will perform the management, monitoring and data management of
the trials
<PAGE>
at its own cost and Roche and Maxim will share equally the third party costs of
the trials. Each company will retain marketing responsibilities and revenues for
their respective drugs, although under the collaboration agreement they will
cooperate in the training of their respective sales forces.
The U.S. Phase III trial of MAXAMINE for the treatment of malignant melanoma was
completed in March 2000 and the related New Drug Application was filed by Maxim
with the U.S. Food and Drug Administration in July 2000. In addition, interim
24-week results from a Phase II dose-ranging hepatitis C study showed that the
combination of the optimal dosing regimen of MAXAMINE and interferon-alpha
achieved a complete viral response in 69 percent of all patients, compared to
the 29 percent or less response that is commonly observed in patients treated
with interferon-alpha alone.
MAXAMINE MODE OF ACTION
Research suggests that a universal mechanism in the human body suppresses the
capacity of the immune system to detect and destroy tumor cells or virally
infected cells in patients with cancer and chronic infectious diseases. MAXAMINE
is designed to reverse this immune suppression, thereby enhancing the
effectiveness of immunotherapy, a class of therapies that employ the body's
immune system to fight these diseases. MAXAMINE protects critical immune cells
and is administered in combination with stimulators of these same immune cells
(cytokines such as interferon-alpha and IL-2). More than 1,200 patients have
been treated in the Maxim's completed and ongoing clinical trials.
In addition to the U.S. Phase III trial for the treatment of malignant melanoma
completed in March 2000, MAXAMINE is currently being tested in two additional
Phase III cancer clinical trials in 12 countries for malignant melanoma and
acute myelogenous leukemia. Phase II trials of MAXAMINE are also underway for
the treatment of hepatitis C and advanced renal cell carcinoma. MAXAMINE is an
investigational drug and safety and efficacy have not been established at this
time. However, clinical trial results to date suggest that MAXAMINE THERAPY, the
administration of MAXAMINE in combination with cytokines, is a safe, at-home
treatment that may improve patient survival.
MAXIM OVERVIEW
Maxim Pharmaceuticals is a late-stage biopharmaceutical company developing
advanced drugs and therapies for cancer, infectious diseases, degenerative
diseases and topical disorders. In addition to MAXAMINE, the Company has also
developed product candidates based on its MAXDERM-TM- technology that are
designed for the treatment of medical conditions for which topical therapy is
appropriate such as oral mucositis, herpes, decubitus ulcers, shingles, burns
and related conditions. Further, Maxim is developing small-molecule inhibitors
and activators of caspases, key enzymes that modulate and carry out the cellular
signaling pathways involved in programmed cell death, also known as apoptosis.
Compounds that can either inhibit caspases or induce caspases may form the basis
for important new drugs for a wide variety of disease targets, such as cancer,
cardiovascular disease and other degenerative diseases.
THIS NEWS RELEASE CONTAINS CERTAIN FORWARD-LOOKING STATEMENTS THAT INVOLVE RISKS
AND UNCERTAINTIES. SUCH FORWARD-LOOKING STATEMENTS INCLUDE STATEMENTS REGARDING
THE EFFICACY AND
<PAGE>
INTENDED UTILIZATION OF MAXAMINE, MAXDERM AND THE CASPASE
MODULATOR COMPOUNDS, AND REGARDING THE COMPANY'S CLINICAL TRIALS. SUCH
STATEMENTS ARE ONLY PREDICTIONS AND THE COMPANY'S ACTUAL RESULTS MAY DIFFER
MATERIALLY FROM THOSE ANTICIPATED IN THESE FORWARD-LOOKING STATEMENTS. FACTORS
THAT MAY CAUSE SUCH DIFFERENCES INCLUDE THE RISK THAT PRODUCTS THAT APPEARED
PROMISING IN EARLY RESEARCH AND CLINICAL TRIALS DO NOT DEMONSTRATE SAFETY OR
EFFICACY IN LARGER-SCALE CLINICAL TRIALS, THE RISK THAT THE COMPANY WILL NOT
OBTAIN APPROVAL TO MARKET ITS PRODUCTS, AND THE RISKS ASSOCIATED WITH THE
DEPENDENCE UPON COLLABORATIVE PARTNERS. THESE FACTORS AND OTHERS ARE MORE FULLY
DISCUSSED IN THE COMPANY'S PERIODIC REPORTS AND OTHER FILINGS WITH THE
SECURITIES AND EXCHANGE COMMISSION.
Note: MAXAMINE-Registered Trademark-, MAXAMINE THERAPY-Trademark-,
MAxDerm-Trademark-, and the Maxim logo are trademarks of the Company.
Editor's Note: This release is also available on the
Internet at: http://www.maxim.com.
