CONFIDENTIAL TREATMENT REQUESTED. CONFIDENTIAL PORTIONS OF THIS DOCUMENT HAVE
BEEN REDACTED AND HAVE BEEN FILED SEPARATELY WITH THE U.S. SECURITIES AND
EXCHANGE COMMISSION
Exhibit 10.122
AGREEMENT
by and between
J. URIACH & CIA., S.A.
And
INTERNEURON PHARMACEUTICALS, INC.
September 28, 2001
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THIS AGREEMENT effective as of September 28, 2001 ("Effective Date"), by and
between J. Uriach & Cia., S.A., a Spanish corporation having a principal office
at Xxxx Xxxx, 00, Xxxxxxxxx 00000, Xxxxx ("URIACH") and Interneuron
Pharmaceuticals, Inc., a corporation organized and existing under the laws of
the State of Delaware and having its principal office at 00 Xxxxxx Xxxxxx, Xxxxx
000, Xxxxxxxxx, Xxxxxxxxxxxxx 00000, Xxxxxx Xxxxxx ("INTERNEURON").
WITNESSETH:
WHEREAS, URIACH is the owner of the Patent Assets and the URIACH Know-How, as
defined herein;
WHEREAS, INTERNEURON desires to obtain exclusive license rights, with a right to
grant sublicenses, under the Patent Assets and the URIACH Know-How, and URIACH
desires to grant such license to INTERNEURON, upon the terms and conditions set
forth herein; and
NOW, THEREFORE, in consideration of the foregoing premises and the mutual
covenants herein contained, and for other good and valuable consideration, the
receipt and sufficiency of which are hereby acknowledged, the Parties hereby
agree as follows:
ARTICLE I
DEFINITIONS
Unless specifically set forth to the contrary herein or unless the context
otherwise requires, the following terms, shall have the respective meanings set
forth below, it being understood that (a) words in the singular include the
plural and vice versa and (b) any reference to any Party includes its
Affiliates, successors in title and permitted assigns.
1.1. "Affiliate" shall mean (i) any corporation or business entity of which
more than fifty percent (50%) of the securities or other ownership
interests representing the equity, the voting stock or general
partnership interest are owned, controlled or held, directly or
indirectly, by a Party or by any entity mentioned in (ii) hereinafter;
(ii) any corporation or business entity which, directly or indirectly,
owns, controls or holds more than fifty percent (50%) (or the maximum
ownership interest permitted by law) of the securities or other ownership
interests representing the equity, voting stock or general partnership
interest of a Party or (iii) any corporation or business entity of which
a Party has the right to acquire, directly or indirectly, at least fifty
percent (50%) of the securities or other ownership interests representing
the equity, voting stock or general partnership interest thereof.
1.2. "Business Day(s)" means any day that is not a Saturday or a Sunday or a
day on which the New York Stock Exchange is closed or a day on which
URIACH is not open for business in Barcelona (Spain) as per URIACH's
working calendar which days shall be
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furnished in writing to INTERNEURON by URIACH at the beginning of each Calendar
Year.
1.3. "Calendar Quarter" shall mean the respective periods of three (3)
consecutive calendar months ending on March 31, June 30, September 30 and
December 31.
1.4. "Calendar Year" shall mean each successive period of twelve (12) months
commencing on January 1 and ending on December 31.
1.5. "CA/SA Option" shall mean URIACH's option to obtain from INTERNEURON an
exclusive sublicense to market the Compound and Product in the Central
and South American Countries, as defined in, and subject to the terms and
conditions of, Section 2.4 of this Agreement.
1.6. "cGMP" shall mean current applicable good manufacturing practices as
defined in regulations promulgated by the FDA under the United States
Federal Food Drug and Cosmetic Act of 1934and corresponding applicable
laws and regulations of Spain relating to the formulation, manufacture,
testing prior to delivery, storage and delivery of the Product.
1.7. "Central and South American Countries" shall mean Argentina, Belize,
Bolivia, Brazil, Chile, Colombia, Costa Rica, Ecuador, El Salvador,
Guatemala, Guyana, French Guyana, Honduras, Panama, Paraguay, Peru,
Surinam, Uruguay and Venezuela.
1.8. "Centralized Procedure" shall mean the European Community Centralized
Procedure for marketing authorization in accordance with Council
Regulation EEC (2309-93) or any successor regulations.
1.9. "CFR" shall mean the United States Code of Federal Regulations.
1.10. "Compound" shall mean UR-12746 (including UR-12715) and UR-12746(S), and
any derivative, homolog or analog of any of the foregoing or any isomer,
salt, hydrate, solvate, amide, ester, metabolite, or prodrug of any of
the foregoing, and any pharmaceutical composition containing any of the
foregoing in any pharmaceutically acceptable form.
1.11. "Development Program" shall mean those activities to be undertaken by
INTERNEURON or its designee with respect to Compound or Product which are
devoted to the evaluation of a potential pharmaceutical product in
clinical trials, and/or the conduct of any other activities or studies
directed toward obtaining Regulatory Approval of Compound or Product in
the United States of America, in Europe and in Japan, as more detailed in
Schedule 1.11. to this Agreement.
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1.12. "Effective Date" shall mean the date first above written.
1.13. "Europe" shall mean Spain, the United Kingdom, France, Germany, and
Italy.
1.14. "FDA" shall mean the United States Food and Drug Administration and any
successor agency having substantially the same functions, and any
corresponding or successor regulatory authority in Europe or having
jurisdiction over the Centralized Procedure if the context so indicates.
1.15. "First Commercial Sale" shall mean the first sale of Product by
INTERNEURON or any Sublicensee, for the purpose of placing such Product
in the market for end use or consumption, after Regulatory Approval has
been granted authorizing such sale in the country where it takes place.
1.16. "GAAP" means generally accepted accounting principles in the United
States.
1.17. "Generic Drug(s)" shall mean any product that is defined in a particular
country in the Territory as a generic drug by applicable legal texts or
regulatory authorities in such country, and for which an entity other
than INTERNEURON or any of its Sublicensees has obtained regulatory
approval in such country following an abbreviated procedure relying on
data for any Product previously submitted to the regulatory authority by
INTERNEURON or its Sublicensee.
1.18. "Improvement" shall mean any and all improvements and enhancements,
patentable or otherwise, related to the Compound or Product including,
without limitation, in the manufacture, formulation, ingredients,
preparation, presentation, means of delivery or administration, dosage,
indication, use or packaging of Compound or Product.
1.19. "IND" shall mean an investigational new drug application and any
amendments thereto relating to the use of Compound or Product in the
United States or the equivalent application in any other regulatory
jurisdiction in the Territory, the filing of which is necessary to
commence clinical testing of pharmaceutical products in humans.
1.20. "INTERNEURON Know-How" shall mean all information and materials,
including but not limited to, discoveries, information, Improvements,
processes, formulas, data, inventions, know-how and trade secrets,
patentable or otherwise, which
(a) relate to Compound or Product; and
(b) are owned by INTERNEURON or are in INTERNEURON's possession or
control and as to which INTERNEURON has the right to license or
sublicense to Third Parties.
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Such know-how shall include, without limitation, all chemical,
pharmaceutical, toxicological, preclinical, clinical, assay control,
regulatory, and any other information used or useful for the
development, manufacturing and/or regulatory approval of Compound or
Product, including any data included in or generated as a result of or
under an IND.
1.21. "NDA" shall mean a new drug application filed with the FDA for
marketing authorization of a Product in the United States, or a
corresponding submission in Europe or under the Centralized Procedure
or with the Japanese Ministry of Health and Welfare, if the context so
indicates, and any amendments and supplements thereto.
1.22. "Net Sales" shall mean the actual gross amount invoiced by INTERNEURON,
its Affiliates or Sublicensees, for the commercial sale of Product in
the Territory commencing upon the date of First Commercial Sale, after
deducting, in accordance with GAAP, insofar as the actual gross amount
invoiced (or a credit invoice) includes or reflects a deduction for,
the following:
(i) normal and customary trade, cash and quantity discounts or
rebates or chargebacks or retroactive price reductions (all of
them, collectivelly referred to as "Reductions") actually made.
Without prejudice of INTERNEURON's unrestricted right to
determine any applicable Reductions, any actual gross amount
invoiced shall be reduced by actual Reductions only up to a [*];
provided, however, that if INTERNEURON grants any Reductions at a
[*], they may request that URIACH agree that such excess may
also be deducted from Net Sales; and URIACH shall not deny such
agreement if it is demonstrated by objective evidence that
Reductions at the specified higher rate are consistent with
market practices in the country where such Reductions have been
granted;
(ii) recalls, credits and allowances actually given on account of
returned or rejected Product, including allowance for breakage or
spoilage;
(iii) sales or excise taxes, VAT or other similar taxes related to the
sale of the Product, and transportation and insurance charges and
additional special transportation, custom duties, and other
governmental charges; all of them if identified in invoices;
(iv) rebates or similar payments paid in connection with sales of
Product to any governmental or regulatory authority in respect of
any state or federal Medicare, Medicaid or similar programs in
any country of the Territory; and
(v) write-offs for bad debts in accordance with GAAP.
* Confidential Treatment Requested
Page 6 of 46
Sales or other transfers between INTERNEURON and its Affiliates or
Sublicensees shall be excluded from the computation of Net Sales and no
payments will be payable on such sales or transfers, but Net Sales
shall include the subsequent sales to Third Parties by such Affiliates.
For the purposes of determining Net Sales, the Product shall be deemed
to be sold as determined in accordance with GAAP.
1.23. "Party" shall mean URIACH or INTERNEURON.
1.24. "Patent Assets" shall mean United States and foreign patents and patent
applications (which shall be deemed to include certificates of
invention and applications for certificates of invention) which as of
the Effective Date or at any time during the term of this Agreement
(a) are owned by URIACH or which URIACH through license or otherwise
has or acquires rights, and
(b) relate to Compound, Product or any Improvement, including but not
limited to methods of their manufacture, methods of their use, or
otherwise relate to URIACH Know-How, including all certificates
of invention, divisions, continuations, continuations-in-part,
reissues, supplementary protection certificates or the like of
any such patents and current and future patent applications,
including but not limited to the patents and patent applications
listed on Schedule 1.24 hereto, and any counterparts thereof
which have been or may be filed in other countries.
1.25. "Phase 2 Clinical Trial" shall mean the first clinical trial of Product
in patients with ulcerative colitis that is designed to show safety and
efficacy of Product for its intended use.
1.26. "Phase 3 Clinical Trial" means a trial on a sufficient number of
patients that is designed to establish that a pharmaceutical product is
safe and efficacious for its intended use, and to define warnings,
precautions and adverse reactions that are associated with the
pharmaceutical product in the dosage range to be prescribed, and
supporting marketing authorization of such pharmaceutical product or
label expansion of such pharmaceutical product.
1.27. "Product" shall mean any and all products in final form for commercial
sale by prescription, over-the-counter, or by any other method (or,
where the context so indicates, the product being tested in clinical
trials), which contain Compound as at least one of the
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therapeutically active ingredients in all dosage forms and package
configurations for any indication.
1.28. "Proprietary Information" shall mean any and all scientific, clinical,
regulatory, marketing, financial and commercial information or data,
whether communicated in writing, orally or by any other means, which is
owned and under the protection of one Party and is being provided by
that Party to the other Party in connection with this Agreement.
1.29. "Regulatory Approval" means all approvals (including pricing and
reimbursement approvals required for marketing authorization), product
and/or establishment licenses, registrations or authorizations of all
regional, federal, state or local regulatory agency, department, bureau
or other governmental entity, necessary for the manufacture, use,
storage, import, export, transport and sale of Product in a regulatory
jurisdiction.
1.30. "Royalty Year" shall mean each successive twelve (12) month period
commencing with the first day of the first month in which occurs the
First Commercial Sale.
1.31. "Spain Option" shall mean URIACH's option to obtain from INTERNEURON a
sub-license to co-market or market the Compound or Product in Spain, as
defined in, and subject to the terms and conditions of, Section 2.4 of
this Agreement.
1.32. "Specifications" shall mean the written methods, formulae, procedures,
specifications, tests (and testing protocols) and standards pertaining
to the manufacture of the Compound or Product and as such specifications
may be modified in accordance with the applicable NDA from time to time
in writing. All Specifications and any subsequent changes thereto, as
agreed upon by the Parties from time to time and in accordance with the
applicable NDA, shall be in writing, dated and signed by the Parties,
and identified as "Exhibit 1.32."
------------
1.33. "Sublicensee" shall mean any Affiliate of INTERNEURON or any Third Party
to which INTERNEURON grants a sublicense under the terms of this
Agreement.
1.34. "Territory" shall mean all of the countries in the world.
1.35. "Third Party" shall mean a person or entity who or which is neither a
Party nor an Affiliate of a Party.
1.36. "URIACH Know-How" shall mean all information and materials, including
but not limited to, discoveries, information, Improvements, processes,
formulas, data, inventions, know-how and trade secrets, patentable or
otherwise, which
Page 8 of 46
(a) relate to Compound or Product; and
(b) are owned by URIACH or are in URIACH's possession or control and as
to which URIACH has the right to license or sublicense to Third
Parties.
Such know-how shall include, without limitation, all chemical,
pharmaceutical, toxicological, preclinical, clinical, assay control,
regulatory, and any other information used or useful for the
development, manufacturing and/or regulatory approval of Compound or
Product, including any data included in or generated as a result of or
under an IND.
1.37. "URIACH Intellectual Property" shall mean the Patent Assets and URIACH
Know-How.
1.38. "URIACH Options" shall mean the Spain Option and the CA/SA Option.
ARTICLE II
LICENSE; SUBLICENSEES; URIACH OPTIONS
2.1. License Grant. Subject to the URIACH Options, URIACH hereby grants to
INTERNEURON an exclusive (even as to URIACH) license under the Patent
Assets and the URIACH Know-How, including the right to grant
sublicenses, to develop, make, have made, use, import, offer for sale,
promote, market, commercialize, distribute and sell Product in the
Territory, and insofar as necessary for the purposes of exercising such
rights, to develop, make, have made, use, import, offer for sale,
commercialize, distribute and sell Compound.
2.2. Improvements by INTERNEURON. Title to any Improvement developed or
discovered by INTERNEURON in connection with the license granted under
Section 2.1 above shall be vested solely in INTERNEURON. URIACH shall
have the right to exploit such Improvements as set forth in this
Agreement.
2.3. Sublicensees. Subject to the Spain Option set forth in Section 2.4
below, INTERNEURON shall have the right to grant sublicenses to
Sublicensees under any or all of the rights granted to INTERNEURON under
Section 2.1 above. In the event of a sublicense by INTERNEURON to a
Third Party, the provisions of Section 5.3.2 of this Agreement shall be
applicable. Sublicenses may be granted by INTERNEURON subject, in the
case of sublicenses to a Third Party, to URIACH's prior written consent,
which consent shall not be unreasonably withheld and shall be given
within ten (10) Business Days of INTERNEURON's providing URIACH with a
written summary of the material terms of the sublicense. It is also
agreed that URIACH's prior written consent shall be required if
INTERNEURON intends to grant a sublicense including rights to market
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Product in any country (including Spain or not) in favor of a Third
Party having its domicile or its main business activities located in
Spain.
2.4. URIACH Options.
(a) Spain Option. INTERNEURON hereby grants URIACH an option (the
"Spain Option") to obtain from INTERNEURON a sublicense to co-market, together
with INTERNEURON or a Sublicensee, the Product in Spain, subject to the terms
and conditions specified below:
(i) INTERNEURON shall give written notice to URIACH (the "Spain Option
Commencement Notice") upon the earlier to occur of (A) the achievement
of the milestone set forth in Section 5.2 (a) of this Agreement or (B)
at least sixty (60) days' prior to anticipated consummation by
INTERNEURON of a sublicense with a Third Party under Section 2.3 of this
Agreement if such sublicense includes rights to market Product in Spain.
(ii) URIACH shall have the right to exercise its Spain Option by
delivery to INTERNEURON of a written notice of exercise ("URIACH Spain
Notice") within thirty (30) days after the date on which URIACH has
received the Spain Option Commencement Notice.
(iii) In the event that INTERNEURON has not received the URIACH Spain
Notice within thirty (30) days after the date of receipt of the Spain
Option Commencement Notice by URIACH, then INTERNEURON shall send URIACH
a written notice indicating that the Spain Option shall expire unless
URIACH delivers to INTERNEURON the URIACH Spain Notice within a period
of fifteen (15) days from the date of this second notice by INTERNEURON.
(iv) If URIACH exercises the Spain Option:
(A) INTERNEURON (or INTERNEURON's Sublicensee) and URIACH shall
negotiate in good faith to enter into a Co-marketing and Supply
Agreement, which agreement shall (1) set forth the rights,
responsibilities, and obligations of each party to such agreement
with respect to the co-marketing by URIACH of Product in Spain
including, but not limited to provisions addressing regulatory
approvals, adverse events, purchase of product, forecasts and
orders, supply price, specifications, sales and promotion
activities and trademark issues, and such other commercially
reasonable terms consistent with similar types of co-marketing
arrangements as may be negotiated in good faith by the Parties it
being understood that such provisions shall no less favorable to
URIACH than the terms of any other agreement between INTERNEURON
and any INTERNEURON Affiliate or
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Third Party relating to co-marketing of Product in Spain; (2)
provide for URIACH to pay INTERNEURON a royalty equal to [*] of
URIACH's Net Sales in Spain (with Net Sales to be defined
identically to Net Sales in this Agreement) and (3) subject to the
provisions of Section 3.7. of this Agreement, provide that if
INTERNEURON supplies URIACH with Product, such supply shall be
made at a price equal to INTERNEURON's cost plus [*], in
accordance with the terms of such agreement and containing such
other commercially reasonable terms applicable to similar types of
supply arrangements as may be negotiated in good faith by the
Parties; and
(B) the provisions of Section 5.2.(d) shall apply and the
milestone payment referred to in such Section shall be thus
reduced by [*].
(v) In the event INTERNEURON proposes to sublicense rights to market
Product in Spain, which sublicense does not include rights to market
Product in any other country, then the Spain Option shall be deemed an
option by URIACH to sublicense rights to market Product (rather than
co-market Product) from INTERNEURON in Spain on an exclusive basis,
exercisable on the same terms and conditions set forth in (i) through
(iv) above. In this event, INTERNEURON'S sublicense to URIACH shall
include the right to use any of the trademarks owned by INTERNEURON, as
mentioned in Section 3.6. below, for the purposes of marketing the
Product in Spain.
(b) CA/SA Option. INTERNEURON hereby agrees to grant URIACH an option
(the "CA/SA Option") to obtain from INTERNEURON an exclusive sublicense to
market the Product in the Central and South American Countries, on and subject
to the terms and conditions specified below:
(i) INTERNEURON shall grant URIACH the CA/SA Option on the first
anniversary of Regulatory Approval in the United States (the "CA/SA
Option Commencement Date"), unless prior to or on such CA/SA Option
Commencement Date INTERNEURON has granted to a Third Party or Third
Parties license(s) or sublicense(s) to market Product that specifically
include rights to market Product in the Central and South American
Countries. If INTERNEURON so decides, INTERNEURON may grant URIACH the
CA/SA Option prior to the CA/SA Option Commencement Date.
(ii) The CA/SA Option shall be granted through written notice to URIACH
(the "CA/SA Option Commencement Notice").
(iii) URIACH shall have the right to exercise its CA/SA Option by
delivery to INTERNEURON of a written notice of exercise ("URIACH CA/SA
Notice") within thirty (30) days after the date on which URIACH has
received the CA/SA Option Commencement Notice.
*Confidential Treatment Requested
Page 11 of 46
(iv) In the event that INTERNEURON has not received the URIACH CA/SA
Notice within thirty (30) days after the date of receipt of the CA/SA
Option Commencement Notice by URIACH, then INTERNEURON shall send URIACH
a written notice indicating that the CA/SA Option shall expire unless
URIACH delivers to INTERNEURON the URIACH CA/SA Notice within a period
of fifteen (15) days from the date of this second notice by INTERNEURON.
(v) If URIACH exercises the CA/SA Option, INTERNEURON and URIACH shall
negotiate in good faith to enter into a Sublicense and Supply Agreement,
which agreement shall be along the lines set forth in subparagraph (A)
of paragraph (iv) of Section 2.4.(a) above, except that such agreement
shall contain such other commercially reasonable terms consistent with
similar types of sublicense and supply arrangements as may be negotiated
in good faith by the Parties. Such agreement shall also include a
sublicense by INTERNEURON to URIACH of the right to use any of the
trademarks owned by INTERNEURON, as mentioned in Section 3.6. below, for
the purposes of marketing the Product in Central and South American
Countries.
(vi) In the event that INTERNEURON sublicenses rights to market Product
in Central and South American Countries to a Third Party prior to the
CA/SA Option Commencement Date, its agreement to grant URIACH the CA/SA
Option shall terminate.
(c) It is understood and agreed that URIACH may exercise the Spain
Option and/or the CA/SA Option through any of its Affiliates. It is also agreed
that URIACH may sublicense or assign any rights acquired through the exercise of
the URIACH Options to any of its Affiliates for the purposes of marketing the
Product in Spain or to any Affiliates or Third Parties which URIACH may wish to
designate for the purposes of marketing the Product in any or all of the Central
and South American Countries.
ARTICLE III
DEVELOPMENT AND COMMERCIALIZATION
3.1. Exchange of Information. Within ten (10) days after execution of this
Agreement, URIACH shall disclose to INTERNEURON in writing (to the
extent possible, in English) all URIACH Intellectual Property not
previously available or made available to INTERNEURON in electronic
format, where available, and hard copies. Throughout the term of this
Agreement, and in addition to the other communications required under
this Agreement, URIACH shall also promptly disclose to INTERNEURON in
writing (to the extent possible, in English), on an ongoing basis all
URIACH Intellectual Property, and any and all additions or revisions
thereto. INTERNEURON shall promptly disclose to URIACH (in English) any
INTERNEURON Know-How which may be necessary or
Page 12 of 46
useful in connection with the exercise of URIACH's rights under this
Agreement, including but not limited to the exercise of the URIACH
Options, and those rights which may derive from the exercise of such
URIACH Options. The rights granted by this Section 3.1 shall have no
effect on the rights of ownership of any patent rights or inventions
which shall be governed by applicable patent laws and applicable
provisions of this Agreement, including Article VII hereof.
3.2. Development Program. INTERNEURON shall be responsible for conducting and
funding the Development Program. URIACH is entering into this Agreement
under the assumption that INTERNEURON shall use commercially reasonable
efforts to develop the Product in accordance with the Development
Program. However, URIACH also understands that, taking into account
issues of safety and efficacy, product profile, the competitiveness of
the marketplace, the proprietary position of the Compound or Product,
the regulatory and reimbursement structure involved, the profitability
of the applicable products, and other relevant factors, INTERNEURON may
decide to abandon the development of the Product. If INTERNEURON decides
to do so, INTERNEURON shall give written notice to URIACH under Section
8.2 of this Agreement and if this Agreement then terminates, the
provisions of Section 8.4 shall apply.
3.3. Reporting and Meetings.
(i) INTERNEURON shall provide URIACH with a written report on a
semi-annual basis summarizing the status of INTERNEURON's clinical
development and regulatory activities with respect to Compound and
Product, with the delivery to URIACH of the summary of the annual report
to an IND submitted by INTERNEURON to the FDA in connection with a
clinical trial of Product to be in satisfaction of the foregoing
requirement for one of such reports each year. URIACH shall designate an
appropriate representative of URIACH to receive such clinical
development and regulatory communications and to coordinate further
correspondence between the Parties, which representative shall have the
right to attend meetings between INTERNEURON and the FDA or other
agencies responsible for the grant of any Regulatory Approval relating
to development of Product. URIACH's initial designee shall be notified
to INTERNEURON in writing.
(ii) In addition, prior to receiving the first Regulatory Approval, the
URIACH representative shall have the right to attend an annual
Development Program meeting at INTERNEURON, at which time the Parties
shall discuss the progress and results of the Development Program and
URIACH may provide input to INTERNEURON on the Development Program.
However, subject to the terms and conditions of this Agreement,
INTERNEURON shall retain full control and ultimately shall have the
right to make all decisions related to the Development Program. Such
meetings may not necessarily be
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face-to-face meetings, but upon the agreement of both parties, can be
via other methods of communication, such as teleconferences and/or
videoconferences.
(iii) Any disclosures of such progress and results in any of the
foregoing reports or meetings shall be deemed Proprietary Information
of INTERNEURON.
(iv) INTERNEURON shall promptly notify URIACH upon the receipt of
Regulatory Approvals and of the date of First Commercial Sale.
3.4. Regulatory Matters.
(a) Subject to the provisions of Section 2.4, to the extent
applicable, INTERNEURON or any of its Sublicensees shall own, control
and retain primary legal responsibility for the preparation, filing and
prosecution of all filings and regulatory applications required to
obtain Regulatory Approvals. To the extent required in Spain if URIACH
exercises the Spain Option to obtain co-marketing rights and in the
Central and South American Countries if URIACH exercises the CA/SA
Option, URIACH or any of its Sublicensees shall own, control and retain
primary legal responsibility for the preparation, filing and
prosecution of all additional filings and regulatory applications
required to obtain Regulatory Approval for URIACH to market Product in
such countries. In connection with the exercise by URIACH of the URIACH
Options, INTERNEURON shall allow (and shall cause its Sublicensees, as
the case may be, to allow) URIACH to cross reference or have access to
any Regulatory Approval owned or controlled by INTERNEURON or its
Sublicensees or to which INTERNEURON or its Sublicensees has access and
the legal right to disclose, to the extent required to enable URIACH to
obtain Regulatory Approvals in accordance with the preceding sentence.
Furthermore, upon URIACH's request, INTERNEURON shall consult and
cooperate with URIACH in connection with obtaining Regulatory Approval
of Product.
(b) URIACH shall transfer to INTERNEURON as soon as practicable
after the Effective Date any IND or other regulatory filings relating
to Compound or Product owned or controlled by URIACH, and URIACH shall
allow INTERNEURON to cross reference any other IND, Drug Master File or
other regulatory filing relating to Compound or Product. Upon
INTERNEURON's request, URIACH shall consult and cooperate with
INTERNEURON in connection with obtaining Regulatory Approval of
Product.
3.5. Commercialization. URIACH is entering into this Agreement under the
assumption that INTERNEURON shall use commercially reasonable efforts
to market the Product in the Territory in accordance with its business,
legal, medical and scientific judgment. INTERNEURON agrees to secure
that commercial sales of the Product in the United States, Europe and
Japan begin not later than [*] after Regulatory Approval has been
*Confidential Treatment Requested
Page 14 of 46
obtained in such countries. If this obligation is not met, URIACH may
terminate this Agreement with respect to the country in which the
obligation was not met by notice to INTERNEURON in accordance with the
terms of this Agreement and the provisions contained in Section 8.4.
shall apply regarding said country.
3.6 Trademark. Subject to the provisions of Section 2.4 of this Agreement,
INTERNEURON shall have the right to select, own and maintain trademarks
for Product in the Territory. During the term of this Agreement and
subject to any regulatory or other legal restrictions, a legend such as
"the Compound is an original molecule of URIACH, Spain", or some other
similar one shall be used by INTENEURON and its Sublicensees (i) in
packaging materials for Product and (ii) to the further extent
consistent with industry practice, in other marketing materials
(leaflets, advertisements and sales promotion literature) for the
Product, in all cases as may be mutually acceptable to URIACH and
INTERNEURON or its Sublicensee. A sample of each unit of Product shall
be provided by INTERNEURON or its Sublicensees to URIACH upon request.
3.7 URIACH Manufacturing.
(a) URIACH hereby agrees to manufacture and supply Product
containing up to [*] of UR 12746 (S) for preclinical and
clinical purposes, at URIACH's cost, in compliance with cGMP
and all other applicable laws and regulations, through the end
of Phase 2 clinical trials. Such manufacture and supply shall
be in accordance with the terms of this Agreement, including
the requirements set forth on Appendix 3.7 and such other
terms to be mutually agreed upon between the Parties. Appendix
3.7 shall be updated by mutual agreement of both Parties on a
semi-annual basis. The Parties understand and agree that
Appendix 3.7 is an estimate of INTERNEURON's requirements
based on certain assumptions as of the date of this Agreement
and the actual requirements of Compound and Product may vary.
URIACH agrees to use its commercially reasonable efforts to
meet INTERNEURON's requirements for Compound or Product in
excess of the amounts set forth on Appendix 3.7.
(b) (i) Prior to the end of the Phase 2 clinical trials,
INTERNEURON shall request that URIACH advise INTERNEURON in
writing whether URIACH is willing to be considered as a
manufacturer and supplier of Compound and/or Product for
additional clinical trials beyond the Phase 2 clinical trials
and of Compound and/or Product for commercial use by
INTERNEURON in accordance with INTERNEURON's and regulatory
requirements (the "Primary Commercial Supplier") and providing
a summary of the proposed terms of such supply.
(ii) In the event that URIACH elects to be considered as
the Primary Commercial Supplier, then (A) if INTERNEURON does
not sublicense
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manufacturing rights to a Sublicensee, INTERNEURON and URIACH
shall negotiate in good faith to enter into a supply agreement
between the Parties containing commercially reasonable terms
applicable to similar types of supply arrangements, including
the right of URIACH to be the Primary Commercial Supplier for a
term of five years, subject to provision for a second source
supplier under certain conditions; and (B) if INTERNEURON does
sublicense manufacturing rights to a Sublicensee, such
sublicense shall provide for URIACH to have a right of first
refusal to be the Primary Commercial Supplier to the Sublicensee
in the event such Sublicensee proposes to contract out such
manufacturing to any entity not affiliated with the Sublicensee,
on the same terms and conditions of the proposal between the
Sublicensee and such non-affiliated entity.
(iii) With the exception of Compound or Product supplied in
accordance with Section 3.7(a) above URIACH shall not be
obligated to supply any additional Compound or Product to
INTERNEURON except under the terms and conditions of a supply
agreement which is entered into in connection with this Section
3.7 (b).
(c) It is understood and agreed that, provided there is no
regulatory obstacle, URIACH may entrust any of its Affiliates or any
Third Party designated by URIACH and consented to by INTERNEURON or its
Sublicensee, with such consent not to be unreasonably withheld and to
be applicable only to Third Parties, with any or all of the tasks
contemplated in this Section 3.7., it being understood that such
Affiliates or Third Parties shall at all times be bound by the relevant
provisions of this Agreement and its Appendices and any supply
agreement entered into in accordance with this Section 3.7.
3.8 Adverse Events. Each Party shall promptly (within 48 hours if the event
is serious, as defined by regulatory agencies, and otherwise within 30
days) furnish to the other Party all information concerning safety or
utility of Compound or Product, such as adverse or unexpected side
effects, injury or other events associated with uses, studies,
investigations or tests of Compound or Product, in conformity with any
applicable laws, regulations or guidelines and whether or not such
Party is required to report such information to any regulatory
authority and whether or not such event is determined to be
attributable to Compound or Product, provided, however, that unless and
until URIACH has exercised either the Spain Option or the CA/SA Option
INTERNEURON may satisfy its obligations to URIACH under this Section
3.8 by delivering to URIACH a copy of the adverse event reports
submitted to the FDA.
ARTICLE IV
CONFIDENTIALITY AND PUBLICITY
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4.1. Non-Disclosure and Non-Use Obligations. All Proprietary Information
disclosed by one Party to the other Party hereunder shall be maintained
in confidence and shall not be disclosed to any Third Party or used for
any purpose except as expressly permitted herein without the prior
written consent of the Party that disclosed the Proprietary Information
to the other Party during the term of this Agreement and thereafter for
a period of seven years. The foregoing non-disclosure and non-use
obligations shall not apply to the extent that such Proprietary
Information:
(a) is known by the receiving Party at the time of its receipt, and
not through a prior disclosure by the disclosing Party, as
documented by business records;
(b) is or becomes properly in the public domain or knowledge;
(c) is subsequently disclosed to a receiving Party by a Third Party
who may lawfully do so and is not under an obligation of
confidentiality to the disclosing Party; or
(d) is developed by the receiving Party independently of Proprietary
Information received from the other Party, as documented by
research and development records.
4.2. Permitted Disclosure of Proprietary Information. Notwithstanding
Section 4.1, a Party receiving Proprietary Information of another Party
may disclose such Proprietary Information:
(a) to governmental or other regulatory agencies in order to obtain
patents pursuant to this Agreement, or to gain approval to
conduct clinical trials or to market Product, but such
disclosure may be only to the extent reasonably necessary to
obtain such patents or authorizations;
(b) by each of INTERNEURON or URIACH to its respective agents,
consultants, Affiliates, INTERNEURON's sublicensees and/or other
Third Parties for the research and development, manufacturing
and/or marketing of the Compound and/or Product (or for such
parties to determine their interests in performing such
activities) on the condition that such Third Parties agree to be
bound by the confidentiality obligations consistent with this
Agreement; or
(c) if required to be disclosed by law or court order, provided that
notice is promptly delivered to the non-disclosing Party in
order to provide an opportunity to challenge or limit the
disclosure obligations; provided, however, without limiting any
of the foregoing, it is understood that INTERNEURON or its
Affiliates may make disclosure of this Agreement and the terms
hereof in any filings required by the Securities and Exchange
Commission ("SEC"), may file this Agreement as an
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exhibit to any filing with the SEC and may distribute any such
filing in the ordinary course of its business.
(d) Upon execution of this Agreement, INTERNEURON may issue a press
release in the form to be attached as Appendix 4.2. URIACH shall
prepare a press release for local Spanish media, consistent with
the terms of this Agreement, which shall be sent to INTERNEURON
for comments prior to its release by URIACH.
4.3. Publication. In the event any Party, or consultant to any Party wishes
to make a scientific publication relating to Compound or Product which
contains potentially patentable information, it shall deliver to the
other Party a copy of the proposed publication or an outline of the
oral disclosure at least fifteen (15) Business Days prior to submission
or presentation, such that any issue of patent protection can be
resolved in accordance with the terms of this Agreement. Any
submissions of proposed publications shall be in the English language.
ARTICLE V
PAYMENTS, ROYALTIES AND REPORTS
5.1. License Fee. In consideration of the rights granted by URIACH
hereunder, INTERNEURON shall pay URIACH [*], payable within ten (10)
days after the Effective Date.
5.2. Milestone Payments. Subject to the terms and conditions contained in
this Agreement, and in further consideration of the rights granted by
URIACH hereunder, INTERNEURON shall pay URIACH the following milestone
payments, contingent upon occurrence of the specified event, with each
milestone payment to be made no more than once with respect to the
achievement of such milestone (but payable the first time such
milestone is achieved) for Compound or Product by INTERNEURON, any of
its Affiliates or any Sublicensee, as applicable:
(a) [*] upon the commencement (enrollment of the first patient) of a
Phase 3 Clinical Trial;
(b) [*] upon the filing of an NDA with the FDA;
(c) [*] upon receipt of written Regulatory Approval by the FDA;
(d) [*] upon receipt of written Regulatory Approval in Europe,
provided that (i) such amount shall be [*] if the Spain Option
is exercised and (ii) in the event the approval is granted in
less than all of the countries listed in the definition of
"Europe", INTERNEURON shall pay an amount equal to [*]
multiplied by the
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Page 18 of 46
number of countries in Europe in which such approval is
granted (excluding Spain if the Spain Option is exercised);
(e) [*] upon receipt of written Regulatory Approval by the
Ministry of Health and Welfare (or any successor agency having
substantially the same functions) in Japan; and
(f) [*] upon the achievement of cumulative Net Sales of [*],
cumulative meaning the aggregate of Net Sales made by
INTERNEURON and any of its Sublicensees (URIACH included in
the event that URIACH exercises any of the URIACH Options).
INTERNEURON shall notify URIACH in writing within thirty (30) days
after the achievement of each milestone (ninety (90) days for milestone
(f)), and such notice shall be accompanied by payment of the
appropriate milestone payment. Milestone payments made under Section
5.2 (c), (d) and/or (e) shall be creditable against payments required
under Section 5.3.1 or 5.3.2 of this Agreement.
5.3. Royalties and Other Payments.
5.3.1. Royalties Payable By INTERNEURON.
(i) Subject to the terms and conditions of this Agreement,
and in further consideration of the rights granted by
URIACH hereunder, INTERNEURON shall pay to URIACH
royalties in an amount equal to [*] of Net Sales in
each Royalty Year by INTERNEURON or its Affiliates in
the United States of America during the period
mentioned in subparagraph (iii) below.
(ii) Subject to the terms and conditions of this Agreement,
and in further consideration of the rights granted by
URIACH hereunder, INTERNEURON shall pay to URIACH
royalties equal to [*] of Net Sales in each Royalty
Year by INTERNEURON or its Affiliates in each country
in the Territory other than the United States of
America during the period mentioned in subparagraph
(iii) below.
(iii) Royalties on Net Sales at the rates set forth in (i)
and (ii) above shall accrue as of the date of First
Commercial Sale of Product in the applicable country
and shall continue and accrue on Net Sales on a
country-by-country basis until the later of (a) the
expiration of the last to expire patent included in
the Patent Assets in such country or (b) ten (10)
years from the
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date of First Commercial Sale in such country. Thereafter,
INTERNEURON shall be relieved of any royalty payment under this
Section 5.3.
(iv) Notwithstanding the provisions of Subsections (i),(ii) and (iii)
above, no royalties shall be payable in respect of Net Sales of
any given Product in any given country of the Territory as of and
after the date on which a Generic Drug of such Product is sold in
the applicable country in the Territory.
(v) The payment of royalties set forth above shall be subject to the
following conditions:
(A) only one payment shall be due with respect to the same unit
of Product;
(B) no royalties shall accrue on the disposition of Product by
INTERNEURON, Affiliates or sublicensees as samples
(promotion or otherwise) or as donations (for example, to
non-profit institutions or government agencies) or to
clinical trials; and
(C) URIACH shall be responsible for payment of any royalties or
other obligations owed by URIACH to any Third Party.
5.3.2. Payments in the Event of Sublicense.
(i) In the event INTERNEURON enters into a sublicense with a Third
Party or Third Parties under Section 2.3 of this Agreement, then
in lieu of INTERNEURON paying URIACH the royalty payments set
forth in Section 5.3.1 above, INTERNEURON shall pay URIACH [*] of
royalty payments received by INTERNEURON ("INTERNEURON
Royalties") which shall at all times be based on net sales of
Product by Sublicensee(s) (such net sales to be defined in any
sublicense agreement in terms materially consistent with the
definition of Net Sales contained in this Agreement). If
INTERNEURON enters into a sublicense with a Third Party under
Section 2.3 of this Agreement for the United States prior to
completion of the Phase 2 Clinical Trial, INTERNEURON shall pay
URIACH [*] of INTERNEURON Royalties received from such
Sublicensee. Payments shall be required under this Section
5.3.2(i) for so long as INTERNEURON is receiving INTERNEURON
Royalties.
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(ii) INTERNEURON shall exercise commercially reasonable efforts to
collect INTERNEURON Royalties, shall not waive any right to
receive such INTERNEURON Royalties, and shall not assign such
right or otherwise dispose of it without first having obtained
URIACH's written consent, except in accordance with the terms of
or as contemplated by this Agreement.
(iii) INTERNEURON shall also pay URIACH [*] of Sales Based Milestone
Payments (as defined in the next sentence). Sales Based
Milestone Payments shall mean those payments received by
INTERNEURON from a Sublicensee that are contingent upon the
Sublicensee's achievement of specifed levels of net sales of
Product; provided, however, that any amounts payable to URIACH
under this Section 5.3.2 (iii) shall be reduced by the [*]
milestone payment payable by INTERNEURON to URIACH under Section
5.2 (f). Payment under this Section 5.3.2 (iii) shall be made by
INTERNEURON not later than thirty (30) days after having
received the Sales Based Milestone Payment from its Sublicensee.
5.3.3. Compulsory Licenses. If a compulsory license is granted to a Third Party
with respect to Product in any country in the Territory with a royalty
rate lower than the royalty rate provided by Section 5.3.1, then the
royalty rate to be paid by INTERNEURON on Net Sales in that country
under Section 5.3.1 shall be reduced to the rate paid by the compulsory
Third Party licensee.
5.3.4. Third Party Licenses. If INTERNEURON is prevented from developing,
making, having made, using, selling or importing any Compound included
in the Patent Assets in any country of the Territory on the grounds that
by doing so INTERNEURON or any Sublicensee would infringe patent rights
held by a Third Party in said country, and if INTERNEURON wishes to
obtain a license from such Third Party, then [*] of any royalties paid
under such Third Party patent licenses by INTERNEURON in such country
for such Calendar Quarter shall be creditable against the royalty
payable to URIACH by INTERNEURON in consideration for Net Sales of said
Product in such country; provided, however that this provision shall not
apply if (i) the Third Party License is to be otained in any country
which is not listed under the heading "Country" in Schedule 1.24 and/or
(ii) the priority date of the patent rights which are claimed to be
infringed is any date after the Effective Date.
5.4. Reports, Payment of Royalty. During the term of the Agreement for so
long as royalty payments are due, INTERNEURON shall furnish to URIACH a
quarterly written report for the Calendar Quarter showing the sales of
all Products subject to royalty payments sold by INTERNEURON and its
Sublicensees during the reporting period and the royalties payable under
this Agreement. Reports shall be due on the seventy-fifth (75/th/)
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day following the close of each Calendar Quarter. Royalties shown to have
accrued by each royalty report, if any, shall be due and payable on the
date such royalty report is due. INTERNEURON shall keep complete and
accurate records in sufficient detail to enable the royalties hereunder
to be determined.
5.5. Audits. Upon the written request of URIACH and not more than once in each
Calendar Year, INTERNEURON shall permit an independent certified public
accounting firm selected by URIACH and reasonably acceptable to
INTERNEURON to have access during normal business hours, upon ten-days
notice to INTERNEURON, to such of the records of INTERNEURON as may be
reasonably necessary to verify the accuracy of the royalty reports
hereunder for any Royalty Year ending not more than thirty-six (36)
months prior to the date of such request. The accounting firm shall
disclose to URIACH only whether the royalty reports are correct or
incorrect and the specific details concerning any discrepancies.
5.5.1. If such accounting firm concludes that additional royalties were
owed during such period, INTERNEURON shall pay the additional
royalties within sixty (60) days of the date URIACH delivers to
INTERNEURON such accounting firm's written report so concluding;
provided however, that, in the event that INTERNEURON shall not
be in agreement with the conclusion of such report (a)
INTERNEURON shall not be required to pay such additional
royalties and (b) such matter shall be resolved pursuant to the
provisions of Section 10.5 herein. In the event such accounting
firm concludes that amounts were overpaid by INTERNEURON during
such period, INTERNEURON shall have a credit against future
royalties payable to URIACH in the amount of such overpayment.
The fees charged by such accounting firm shall be paid by URIACH;
provided, however, that if an error in favor of URIACH of more
than the greater of (i) [*] or (ii) [*] of the royalties due
hereunder for the period being reviewed is discovered, then the
fees and expenses of the accounting firm shall be paid by
INTERNEURON.
5.5.2. Upon the expiration of thirty-six (36) months following the end
of any Royalty Year the calculation of royalties payable with
respect to such year shall be binding and conclusive upon the
Parties , and each Party shall thereafter be released from any
liability or accountability to the other Party with respect to
royalties for such year.
5.5.3. URIACH and INTERNEURON shall treat all financial information
subject to review under this Section 5.5. or under any sublicense
agreement in accordance with the confidentiality provisions of
this Agreement.
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5.6. Payment Exchange Rate. All payments to URIACH under this Agreement shall
be made in United States dollars. In the case of sales outside the United
States, the rate of exchange to be used to convert the amount of currency
into United States dollars shall be the one published in the Wall Street
Journal, Eastern edition, on the last day of the Calendar Quarter where
such sales shall be reported as set forth in Section 5.4. above, and
royalties shall be paid in United States dollars in accordance with such
converted amount.
5.7. Tax Withholding. If laws, rules or regulations require withholding of
income taxes or other taxes imposed upon payments set forth in this
Article V, URIACH shall provide INTERNEURON, prior to any such payment,
annually or more frequently if required, with all forms or documentation
required by any applicable taxation laws, treaties or agreements to such
withholding or as necessary to claim a benefit thereunder (including, but
not limited to Form W-8BEN or any successor forms) and INTERNEURON shall
make such withholding payments as required and subtract such withholding
payments from the payments set forth in this Article V. INTERNEURON will
use commercially reasonable efforts consistent with its usual business
practices and cooperate with URIACH to ensure that any withholding taxes
imposed are reduced as far as possible under the provisions of the
current or any future taxation treaties or agreements between foreign
countries.
5.8. Exchange Controls. Notwithstanding any other provision of this Agreement,
if at any time legal restrictions prevent the prompt remittance of part
or all of the royalties with respect to Net Sales in any country, payment
shall be made through such lawful means or methods as INTERNEURON may
determine. When in any country the law or regulations prohibit both the
transmittal and deposit of royalties on sales in such a country, royalty
payments shall be suspended for as long as such prohibition is in effect
(and such suspended payments shall not accrue interest), and promptly
after such prohibition ceases to be in effect, all royalties that
INTERNEURON or its Affiliates or sublicensees would have been obligated
to transmit or deposit, but for the prohibition, shall be deposited or
transmitted, as the case may be, to the extent allowable (with any
interest earned on such suspended royalties which were placed in an
interest-bearing bank account in that country, less any transactional
costs). If the royalty rate specified in this Agreement should exceed the
permissible rate established in any country, the royalty rate for sales
in such country shall be adjusted to the highest legally permissible or
government-approved rate.
ARTICLE VI
REPRESENTATIONS AND WARRANTIES
6.1. URIACH. Representations and Warranties. URIACH represents and warrants to
INTERNEURON that as of the Effective Date:
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(a) URIACH is unaware of any reason that the presumption of validity would
not apply to the issued patents included in the Patent Assets or that
a court of competent jurisdiction would, upon investigation, find such
patents invalid or unenforceable. It is however agreed that URIACH
does not warrant that the patents included in the Patent Assets will
be granted or upheld if its validity or enforceability is contested.
Except as set forth in this Agreement, this Agreement shall not be
affected by the status of the Patent Assets, and the failure to obtain
any patent or the fact that any Patent Assets may be declared invalid
or unenforceable shall not provide a basis for termination of this
Agreement under Section 8.3 of this Agreement nor shall it entitle any
party to demand a revision or to renegotiate the terms of this
Agreement;
(b) this Agreement has been duly executed and delivered by URIACH and
constitutes legal, valid, and binding obligations enforceable against
URIACH in accordance with its terms;
(c) no approval, authorization, consent, or other order or action of or
filing with any court, administrative agency or other governmental
authority is required for the execution and delivery by URIACH of this
Agreement or the consummation by URIACH of the transactions
contemplated hereby;
(d) URIACH has the full corporate power and authority to enter into and
deliver this Agreement, to perform and to grant the licenses granted
under Article II hereof and to consummate the transactions
contemplated hereby; all corporate acts and other proceedings required
to be taken to authorize such execution, delivery, and consummation
have been duly and properly taken and obtained;
(e) URIACH has not previously assigned, transferred, conveyed or otherwise
encumbered its right, title and interest in the Patent Assets or
URIACH Know-How or entered into any agreement with any Third Party
which is in conflict with the rights granted to INTERNEURON pursuant
to this Agreement;
(f) it is the sole and exclusive owner under the Patent Assets and URIACH
Know-How, all of which are free and clear of any liens, charges and
encumbrances, and no other person, corporate or other private entity,
or governmental or university entity or subdivision thereof has any
claim of ownership with respect to the Patent Assets or URIACH
Know-how, whatsoever;
(g) To the best of URIACH's knowledge, the development, manufacture, use
and sale of Compound and Products do not infringe any patent rights
owned or possessed by any Third Party;
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(h) Schedule 1.24 is a complete and accurate list of all patents and
patent applications in the Territory relating to Compound or Product
owned by URIACH or to which URIACH has the right to license;
(i) there are no claims, judgments or settlements against or owed by
URIACH or pending or, to the best of its knowledge, threatened claims
or litigation relating to the Patent Assets;
(j) URIACH has disclosed to INTERNEURON all relevant information known by
it regarding the Patent Assets and URIACH Know-How reasonably related
to the activities contemplated under this Agreement;
(k) URIACH is not aware of any contract research organization,
corporation, business entity or individual which have been involved in
any studies conducted for the purpose of obtaining regulatory
approvals having been debarred individuals or entities within the
meaning of 21 U.S.C. section 335(a) or (b);
(l) in connection with development of Compound and Product, URIACH has
complied in all material respects with applicable Spanish laws and
regulations;
(m) the Compound and/or Product manufactured by URIACH at the time of
delivery ex-works shall conform to the Specifications and be
manufactured, tested and stored in accordance with the Specifications
and with cGMPs (or if intended for shipment outside the United States,
any equivalent laws, rules or regulations), and other applicable laws
and regulations;
(n) URIACH has manufacturing facilities and equipment necessary to
manufacture Product pursuant to Specifications and otherwise perform
URIACH's supply obligations hereunder, and the URIACH manufacturing
facility, process and equipment validation to be used in the
manufacture of Compound or Product comply with cGMPs and other
applicable laws and regulations; and
(o) AT THE TIME OF DELIVERY EX-WORKS, THE PRODUCT SHALL NOT (I) BE
ADULTERATED OR MISBRANDED WITHIN THE MEANING OF THE FEDERAL FOOD DRUG
AND COSMETIC ACT OF 1934, AND THE RULES AND REGULATIONS PROMULGATED
THEREUNDER, OR ANY SUCCESSOR ACT, AS THE SAME SHALL BE IN EFFECT FROM
TIME TO TIME OR WITHIN THE MEANING OF ANY APPLICABLE LAW, RULES OR
REGULATIONS, OR (II) BE PROHIBITED FROM BEING INTRODUCED INTO
INTERSTATE COMMERCE.
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(p) EXCEPT AS EXPRESSLY SET FORTH IN THIS SECTION 6.1., URIACH HEREBY
DISCLAIMS ANY AND ALL WARRANTIES WITH RESPECT TO THE URIACH
INTELLECTUAL PROPERTY, THE COMPOUND AND THE PRODUCT INCLUDING WITHOUT
LIMITATION ANY IMPLIED WARRANTY OF MERCHANTABILITY OR FITNESS FOR A
PARTICULAR PURPOSE.
Except as otherwise provided in this Agreement and, if URIACH
exercises any of the URIACH Options, the agreements referred to in
Section 2.4, INTERNEURON shall be responsible for all matters
concerning development of the Products and the use, importation,
commercialization, distribution and sale of Products in the Territory,
including compliance with any and all relevant applicable laws, and
any product liability claims.
6.2. INTERNEURON. Representations and Warranties. INTERNEURON represents and
warrants to URIACH that as of the Effective Date:
(a) this Agreement has been duly executed and delivered by it and
constitutes legal, valid, and binding obligations enforceable against
it in accordance with its terms;
(b) it has full corporate power and authority to execute and deliver this
Agreement and to consummate the transactions contemplated hereby. All
corporate acts and other proceedings required to be taken to authorize
such execution, delivery, and consummation have been duly and properly
taken and obtained;
(c) no approval, authorization, consent, or other order or action of or
filing with any court, administrative agency or other governmental
authority is required for the execution and delivery by it of this
Agreement or the consummation by it of the transactions contemplated
hereby.
ARTICLE VII
PATENT MATTERS
7.1. Filing, Prosecution and Maintenance of Patent Applications or Patents.
URIACH shall file and prosecute patent applications included in the Patent
Assets in any country in which the patents included on Schedule 1.24 have
been filed and are being prosecuted until such time as underlying patents
included in the Patent Assets issue. After the issuance of patents included
in the Patent Assets, INTERNEURON shall maintain the Patent Assets in
URIACH's name and, upon INTERNEURON's request, URIACH shall reasonably
cooperate in the maintenance of such patents. URIACH shall be responsible
for the payment of all patent filing and prosecution costs incurred prior
to the date of issuance of any patent and INTERNEURON shall be responsible
for the payment of all
Page 26 of 46
patent maintenance costs incurred after the date of issuance of the
applicable patent except that, (i) in the event URIACH exercises its
Spain Option, URIACH shall be responsible for and shall reimburse
INTERNEURON for 50% of the patent maintenance costs in Spain incurred
by INTERNEURON after the date URIACH exercises the Spain Option; and
(ii) in the event URIACH exercises the CA/SA Option, URIACH shall be
responsible for and shall reimburse INTERNEURON for all patent
maintenance costs incurred by INTERNEURON in the Central and South
American Countries after the date URIACH exercises the CA/SA Option. In
any event, each Party shall be responsible for the payment of legal
fees incurred by it associated with its respective activities under
this Section 7.1. If URIACH elects not to file or prosecute a patent
application included in the Patent Assets in any country in which the
patents included on Schedule 1.24 have been filed and are being
prosecuted, it shall provide INTERNEURON with written advance notice
sufficient to avoid any loss or forfeiture, and INTERNEURON shall have
the right, at its sole expense, to file or prosecute such patent
application in INTERNEURON's name and URIACH shall assign to
INTERNEURON all of URIACH's right, title and interest in and to such
Patent Assets and shall reimburse INTERNEURON for all patent filing and
prosecution costs incurred by INTERNEURON in connection with such
patent application, it being understood that this shall not affect
INTERNEURON's obligations to pay royalties as set forth in this
Agreement. Upon INTERNEURON's request, URIACH shall reasonably
cooperate in the filing and prosecution of such patent application. If
INTERNEURON elects not to maintain a patent included in the Patent
Assets, it shall provide URIACH with written advance notice sufficient
to avoid any loss or forfeiture, and URIACH shall have the right, at
its sole expense, to maintain such patent. Upon URIACH's request,
INTERNEURON shall reasonably cooperate in the maintenance of such
patent. If INTERNEURON's election refers to Patent [*] or its
equivalent in any specific country, then INTERNEURON's rights under
this Agreement shall terminate regarding such country, which shall be
then excluded from the definition of "Territory", if URIACH so wishes.
In this event, the provisions of Section 8.4.(b) shall apply with
respect to such country.
7.2. Patent Office Proceedings. Each Party shall inform the other Party of
any request for, filing, or declaration of any proceeding before a
patent office seeking to protest, oppose, cancel, reexamine, declare an
interference proceeding, initiate a conflicts proceeding, or analogous
process involving a patent application or patent included in the Patent
Assets. Each Party thereafter shall cooperate fully with the other with
respect to any such patent office proceeding. Each Party will provide
the other with any information or assistance that is reasonable.
7.3. Enforcement and Defense.
(a) Each Party shall promptly give the other Party notice of any
infringement in the Territory of any patent application or
patent included in the Patent Assets that
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comes to such Party's attention. The Parties will thereafter consult
and cooperate fully to determine a course of action, including, without
limitation, the commencement of legal action by any Party. However,
INTERNEURON shall have the first right to initiate and prosecute such
legal action at its own expense and in the name of URIACH and
INTERNEURON, or to control the defense of any declaratory judgment
action relating to Patent Assets. INTERNEURON shall promptly inform
URIACH if INTERNEURON elects not to exercise such first right, and
URIACH thereafter shall have the right either to initiate and prosecute
such action or to control the defense of such declaratory judgment
action in the name of URIACH and, if necessary, INTERNEURON. In no
event shall URIACH be obligated to enforce or defend any of the Patent
Assets.
(b) If INTERNEURON elects not to initiate and prosecute an infringement or
defend a declaratory judgment action in any country in the Territory as
provided in Subsection 7.3(a), and URIACH elects to do so, the cost of
any agreed-upon course of action, including the costs of any legal
action commenced or any declaratory judgment action defended, shall be
borne solely by URIACH.
(c) For any such legal action or defense, in the event that any Party is
unable to initiate, prosecute, or defend such action solely in its own
name, the other Party will join such action voluntarily and will
execute all documents necessary for the Party to prosecute, defend and
maintain such action. In connection with any such action, the Parties
will cooperate fully and will provide each other with any information
or assistance that either reasonably may request.
(d) Any recovery obtained by INTERNEURON or URIACH shall be shared as
follows:
(i) the Party that initiated and prosecuted, or maintained the
defense of, the action shall recoup all of its costs and expenses
(including reasonable attorneys' fees) incurred in connection
with the action, whether the recovery is by settlement or
otherwise;
(ii) the other Party then shall, to the extent possible, recover its
costs and expenses (including reasonable attorneys' fees)
incurred in connection with the action;
(iii) if URIACH initiated and prosecuted, or maintained the defense of,
the action, the amount of any recovery remaining then shall be
retained by URIACH; and
Page 28 of 46
(iv) if INTERNEURON initiated and prosecuted, or maintained
the defense of, the action, the amount of any recovery
remaining shall be retained by INTERNEURON, except
that URIACH shall receive a portion equivalent to the
royalties or other payments it would have received if
such amount were deemed Net Sales.
(e) URIACH shall inform INTERNEURON of any certification regarding
any Patent Assets it has received pursuant to either 21 U.S.C.
355(b)(2)(A)(iv) or (j)(2)(A)(vii)(IV) or under Canada's
Patented Medicines (Notice of Compliance) Regulations Article
5 and shall provide INTERNEURON with a copy of such
certification within five (5) days of receipt. URIACH's and
INTERNEURON's rights with respect to the initiation and
prosecution, or defense, of any legal action as a result of
such certification or any recovery obtained as a result of
such legal action shall be allocated as defined in Subsections
7.3.(d) (i) through (iv); provided, however, that INTERNEURON
shall exercise the first right to initiate and prosecute, or
defend, any action and shall inform URIACH of such decision
within fifteen (15) days of receipt of the certification,
after which time, if INTERNEURON has not advised URIACH of its
intention to initiate and prosecute, or defend, such action,
URIACH shall have the right to initiate and prosecute, or
defend, such action.
7.4. Infringement of Third Party's rights.
(a) URIACH is not aware of any reason why any Third Party could
claim that the performance of any of the operations
contemplated in this Agreement, including but not limited to
the development, manufacture, use and sale of Compound and
Product would infringe any patent rights owned or possessed by
any Third Party. The above notwithstanding URIACH does not
give any warranty in respect of such matters, and both Parties
agree that URIACH shall not be held liable in case that the
performance of any of the operations contemplated in this
Agreement is deemed to infringe any intellectual property
rights of any Third Parties and that if any Third Party files
any claim or takes any other action as a consequence of or
derived from the performance of any of the operations
contemplated in this Agreement, claiming that such operations
infringe such Third Party's patent rights, whether against
URIACH or against INTERNEURON, any of its Affiliates or
Sublicensees, then INTERNEURON shall bear all costs and
economic liabilities resulting from any such Third Party
action and shall indemnify and hold URIACH harmless.
(b) The Party receiving any claim in respect of which an
obligation to indemnify and hold harmless exists under this
clause shall promptly inform the other. The receiving Party
shall be entitled to appoint counsel to defend its own case,
but shall make sure that the other Party is given access to
all the documentation related to the case and
Page 29 of 46
that such other Party is able to participate also in defending the
case. Either Party, as the case may be, shall render to the other
any reasonable assistance requested to it in connection with the
defense of such action.
(c) INTERNEURON agrees that it shall use commercially reasonable
efforts to contest any claim, interim decision, injunction, order,
judgement, etc stating or ruling that its activities under this
Agreement infringe Third Party patent rights. In the event that
INTERNEURON wishes to waive its rights of appeal or settle any
claim, INTERNEURON shall first consult with URIACH, shall allow
URIACH to actively participate in any settlement negotiations but
INTERNEURON shall not, without URIACH'S prior written consent,
which consent shall not be unreasonably withheld or delayed,
settle any such claim or proceeding
7.5. Patent Term Extensions and Supplemental Protection Certificates. The
Parties shall cooperate in obtaining patent term extensions or
supplemental protection certificates or their equivalents in any country
in the Territory where applicable and where desired by INTERNEURON. If
elections with respect to obtaining such extension or supplemental
protection certificates are to be made, INTERNEURON shall have the right
to make the election, provided that it shall need URIACH'S prior written
consent if it does not intend to seek such extension or supplemental
certificates.
ARTICLE VIII
TERM AND TERMINATION
8.1. Term and Expiration. This Agreement shall be effective as of the
Effective Date and unless terminated earlier pursuant to Section 8.2 and
8.3 below, the term of this Agreement shall continue in effect until
expiration of all royalty obligations hereunder.
8.2. Termination by Notice. Notwithstanding anything contained herein to the
contrary, INTERNEURON shall have the right to terminate this Agreement at
any time by giving thirty (30) days advance written notice to URIACH.
Such notice shall explain the reasons for INTERNEURON's decision.
INTERNEURON shall also give URIACH the opportunity to discuss the matter
and shall refrain from taking any specific action until such discussions
have taken place in good faith. If after having heard URIACH's point of
view, INTERNEURON still wants to go ahead with termination, it shall send
an additional notice to URIACH in writing, and in this event (i) the
rights and obligations hereunder, excluding any payment obligation that
has accrued as of the termination date and excluding rights and
obligations relating to confidentiality, shall terminate immediately, and
(ii) the provisions of Section 8.4 shall be applicable.
8.3. Termination for Cause
Page 30 of 46
(a) Either Party may terminate this Agreement by notice to the other
Party at any time during the term of this Agreement if the other
Party is in breach of any material obligation hereunder by causes
and reasons within its control, or has breached, in any material
respect, any representations or warranties set forth in Article VI,
and has not cured such breach within ninety (90) days after notice
requesting cure of the breach, provided, however, that if the breach
is not capable of being cured within ninety (90) days of such
written notice, the Agreement may not be terminated so long as the
breaching Party commences and is taking commercially reasonable
actions to cure such breach as promptly as practicable.
(b) Either Party may terminate this Agreement by notice to the other
Party at any time during the term of this Agreement upon the filing
or institution of bankruptcy, liquidation or receivership
proceedings, or upon an assignment of a substantial portion of the
assets for the benefit of creditors by the other Party; provided,
--------
however, in the case of any involuntary bankruptcy, reorganization,
-------
liquidation, receivership or assignment proceeding such right to
terminate shall only become effective if the Party consents to the
involuntary proceeding or such proceeding is not dismissed within
ninety (90) days after the filing thereof.
(c) URIACH may terminate this Agreement by by giving thirty (30) days
advance written notice to INTERNEURON at any time during the term of
this Agreement if INTERNEURON challenges the validity of any of the
Patent Assets or opposes any grant or registration of any Patent
Assets or in any other manner cooperates with any person or entity
taking any action of this nature.
8.4. Effect of Expiration or Termination.
(a) Expiration or termination of this Agreement shall not relieve the
Parties of any obligation accruing prior to such expiration or
termination. In addition to any other provisions of this Agreement
which by their terms continue after the expiration of this
Agreement, the provisions of Article IV shall survive the expiration
or termination of this Agreement and shall continue in effect during
the term set forth in Section 4.1. In addition, any other provision
required to interpret and enforce the Parties' rights and
obligations under this Agreement shall also survive, but only to the
extent required for the full observation and performance of this
Agreement. Any expiration or early termination of this Agreement
shall be without prejudice to the rights of any Party against the
other accrued or accruing under this Agreement prior to termination,
including but not limited to URIACH's right to the milestone payment
set forth in Section 5.2.(f) if such milestone is achieved after the
expiration of the term of this Agreement. Except as expressly set
forth herein, the rights to terminate as set forth herein shall be
in addition to all
Page 31 of 46
other rights and remedies available under this Agreement, at
law, or in equity, or otherwise.
(b) In the event of termination by INTERNEURON pursuant to Section
8.2., and in the event of termination by URIACH pursuant to any
of Sections 3.5, 7.1., 8.3.(b) and 8.3.(c) in accordance with
the terms of such respective sections, without prejudice to and
subject to compliance with the provisions of any applicable
law, and if requested by URIACH, INTERNEURON shall take and
shall cause its Affiliates and Sublicensees to take, as the
case may be, using reasonable commercial due diligence, any
action necessary to transfer any and all rights to any
INTERNEURON Know-How, to any Regulatory Approval (in the
Territory, if the Agreement is terminated in its entirety, or
in the applicable country in the Territory if the Agreement is
terminated with respect to that country) and to any trademarks
referred to in Section 3.6 to URIACH or URIACH's designee, at
no cost to URIACH or to such designee, it being the intention
of the Parties to secure that in these cases URIACH is put in a
position where URIACH may, if URIACH so wishes, take over all
the rights on the Compound and the Product in the country(ies)
subject to the termination and exploit them as URIACH may deem
convenient.
(c) In the event this Agreement is terminated by URIACH pursuant to
Section 8.3. (a), the provisions of Section 8.4. (b) shall also
apply, provided; however, that if INTERNEURON disagrees with
such termination URIACH shall give INTERNEURON the opportunity
to discuss the matter and shall refrain from taking any
specific action until such discussions have taken place in good
faith. If after having heard INTERNEURON'S point of view,
URIACH still wants to go ahead with termination, it shall send
an additional notice to INTERNEURON in writing and the matter
will be subject to the dispute resolution provisions of Section
10.5 of this Agreement; provided, however that if it is finally
determined that such termination by URIACH was justified, then
the provisions of Section 8.4. (b) shall apply.
ARTICLE IX
INDEMNIFICATION
9.1 Indemnification by INTERNEURON. INTERNEURON shall indemnify, defend and
------------------------------
hold URIACH and its officers, directors, shareholders, agents and
employees harmless against any and all claims, liability, damage, loss,
cost or expense (including reasonable attorney's fees) (collectively,
"Losses") arising or resulting from any Third Party claim made or suit
------
brought against URIACH or such persons to the extent any such Losses
arise out of (i) any breach by INTERNEURON of any of its representations
or warranties
Page 32 of 46
in this Agreement; (ii) INTERNEURON's negligence or willful misconduct;
or (iii) the development, manufacture, use, importation, promotion,
marketing commercialization, distribution and sale of the Compound or
Product by INTERNEURON, or its Affiliates, or its Sublicensees,
provided, however, that INTERNEURON shall not be required to indemnify
any indemnified party referred to in this paragraph to the extent it is
determined that the Losses resulted from the negligence or willful
misconduct of such indemnified party or if an indemnified party would
be required to indemnify INTERNEURON under Section 9.2 below.
9.2 Indemnification by URIACH. URIACH shall indemnify, defend and hold
-------------------------
INTERNEURON, and its sublicensees, and their officers, directors,
shareholders, agents and employees harmless against any and all Losses
arising or resulting from any Third Party claim made or suit brought
against INTERNEURON, its sublicensees or such other persons to the
extent any such Losses arise out of (i) any breach by URIACH of any of
its representations or warranties in this Agreement, (ii) URIACH'S
negligence or willful misconduct; (iii) any defect associated with the
Compound and/or the Product which should have been detected by URIACH
when carrying out the development activities performed by URIACH prior
to the Effective Date; or (iv) URIACH's manufacturing of Compound and
Product as set forth in this Agreement and any activity by URIACH, its
Affiliates or its sublicensees as a result of the exercise of any of
the URIACH Options, provided, however, that URIACH shall not be
required to indemnify any indemnified party referred to in this
paragraph to the extent it is determined that the Losses resulted from
the negligence or willful misconduct of such indemnified party or if an
indemnified party would be required to indemnify URIACH under Section
9.1 above. For the avoidance of doubt it is expressly stated that
URIACH shall not be held liable in the event that any Compound or
Product causes any damage as a result of any intrinsic defect provided
that such defect could not have been detected by URIACH at the time
URIACH performed its development and/or manufacturing activities of
Compound or Product.
ARTICLE X
MISCELLANEOUS
10.1. Force Majeure. Neither Party shall be held liable or responsible to the
other Party nor be deemed to have defaulted under or breached the
Agreement for failure or delay in fulfilling or performing any term of
the Agreement during the period of time 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, flood, embargo,
war, acts of war (whether war be declared or not), insurrection, riot,
civil commotion, strike, lockout or other labor disturbance, act of God
or act, omission or delay in acting by any governmental authority or
the other Party. The affected Party shall notify the other Party of
such force majeure circumstances as soon as reasonably practicable and
the affected
Page 33 of 46
Party shall use commercially reasonable efforts to avoid or remove such
causes of non-performance as promptly as practicable and shall continue
performance with the utmost dispatch whenever such causes are removed.
When such circumstances arise, the parties shall discuss what, if any,
modification of the terms of this Agreement may be required in order to
arrive at an equitable solution.
10.2. Assignment. The Agreement may not be assigned or otherwise transferred
without the prior written consent of the other Party, provided,
however, that either Party may assign all or any part of this Agreement
to an Affiliate or in connection with the transfer or sale of its
business or all or substantially all of its assets or in the event of a
merger, consolidation, change in control or similar corporate
transaction. Any permitted assignee shall assume all obligations of its
assignor under this Agreement.
10.3. Severability. In the event that any of the provisions contained in this
Agreement are held invalid, illegal or unenforceable in any respect,
the validity, legality and enforceability of the remaining provisions
contained herein shall not in any way be affected or impaired thereby,
unless the absence of the invalidated provision(s) adversely affect the
substantive rights of the Parties. In such event, the Parties shall
replace the invalid, illegal or unenforceable provision(s) with valid,
legal and enforceable provision(s) which, insofar as practical,
implement the purposes of this Agreement.
10.4. Notices. All notices or other communications which are required or
permitted hereunder shall be in writing and sufficient if delivered
personally, sent by facsimile (and promptly confirmed by personal
delivery, registered or certified mail or overnight courier), sent by
nationally-recognized overnight courier or sent by registered or
certified mail, postage prepaid, return receipt requested, or by
e-mail, addressed as follows:
if to INTERNEURON to:
INTERNEURON PHARMACEUTICALS, INC.
00 Xxxxxx Xxxxxx, Xxxxx 000
Xxxxxxxxx, XX 00000
Attention: President
Fax No.: 000-000-0000
if to URIACH to:
J. URIACH & CIA.
Xxxx Xxxx, 00
00000 Xxxxxxxxx, Xxxxx
Attention: Chief Executive Officer
Fax No.: 93-456.21.03
Page 34 of 46
or to such other address as the Party to whom notice is to be given may
have furnished to the other Parties in writing in accordance herewith.
Any such communication shall be deemed to have been given or received
when delivered if personally delivered or sent by facsimile or e-mail
on a Business Day, upon confirmed delivery by nationally-recognized
overnight courier if so delivered and on the third Business Day
following the date of mailing if sent by registered or certified mail.
10.5. Applicable Law and Dispute Resolution. This Agreement shall be governed
by and construed in accordance with the UNIDROIT principles (1994)
applicable to International Commercial Contracts to the extent
applicable, it being understood and agreed that any agreement between
INTERNEURON and any Sublicensee may be governed by and construed in
accordance with any other laws. The Parties agree to attempt initially
to solve all claims, disputes, or controversies arising under, out of,
or in connection with this Agreement by conducting good faith
negotiations. If the Parties are unable to settle the matter between
themselves within forty-five (45) days, either Party may initiate
mediation upon written notice to the other Party. If the Parties have
not reached a settlement within forty-five (45) days of the initiation
of the mediation, then either Party may initiate binding arbitration
proceedings. Whenever a Party shall decide to institute arbitration
proceedings, it shall give written notice to that effect to the other
Party. The Party giving such notice shall refrain from instituting the
arbitration proceedings for a period of sixty (60) days following such
notice. During such period, the Parties shall continue to make good
faith efforts to amicably resolve the dispute without arbitration. Any
arbitration hereunder shall be conducted under the rules of the
International Chamber of Commerce ("ICC"). Each such arbitration shall
be conducted by a panel of three arbitrators: one arbitrator shall be
appointed by each of INTERNEURON and URIACH and the third shall be
appointed by the other two arbitrators. Any such arbitration shall be
held in London, England. The arbitrators shall have the authority to
grant specific performance. Judgment upon the award so rendered may be
entered in any court having jurisdiction or application may be made to
such court for judicial acceptance of any award and an order of
enforcement, as the case may be. In no event shall a demand for
arbitration be made after the date when institution of a legal or
equitable proceeding based on such claim, dispute or other matter in
question would be barred by the applicable statute of limitations. Each
Party shall bear its own costs and expenses incurred in connection with
any arbitration proceeding and the Parties shall equally share the cost
of the arbitration levied by the ICC.
10.6. Entire Agreement. This Agreement contains the entire understanding of
the Parties with respect to the subject matter hereof. All express or
implied agreements and understandings, either oral or written,
heretofore made are expressly merged in and made a part of this
Agreement. This Agreement may be amended, or any term hereof modified,
only by a written instrument duly executed by all Parties hereto.
Page 35 of 46
10.7. Independent Contractors. It is expressly agreed that the Parties shall
be independent contractors and that the relationship between the
Parties shall not constitute a partnership, joint venture or agency.
Neither Party shall have the authority to make any statements,
representations or commitments of any kind, or to take any action,
which shall be binding on the other Party, without the prior consent of
such other Party.
10.8. Waiver. The waiver by a Party hereto of any right hereunder or the
failure to perform or a breach by another Party shall not be deemed a
waiver of any other right hereunder or of any other breach or failure
by said other Party whether of a similar nature or otherwise.
10.9. Headings. The captions to the several Articles and Sections hereof are
not a part of the Agreement, but are merely guides or labels to assist
in locating and reading the several Articles and Sections hereof.
10.10. Counterparts. The Agreement may be executed in two or more
counterparts, each of which shall be deemed an original, but all of
which together shall constitute one and the same instrument.
10.11. Other duties. The Parties shall perform all other reasonable duties and
acts, execute and deliver all other documents, and provide other
information and assistance, whether or not specifically provided for
herein, as may be reasonably necessary to carry out the intent of the
Parties as stated in this Agreement.
Page 36 of 46
IN WITNESS WHEREOF, the Parties have executed this Agreement as of the date
first set forth above.
J. URIACH & CIA., S.A. INTERNEURON PHARMACEUTICALS, INC.
By: /s/Xxxxxxx Uriach Xxxxxxx By: /s/Xxxxx X. Xxxxxx, M.D.
------------------------- ------------------------
Name: Xxxxxxx Uriach Xxxxxxx Name: Xxxxx X. Xxxxxx, M.D.
Title: Chief Executive Officer Title: President and Chief Executive
Officer
Page 37 of 46
SCHEDULE 1.11
Development Program
UR-12746 DEVELOPMENT PROGRAM
Page 1 of 2
1. CMC
---
Active Pharmaceutical Ingredients
---------------------------------
. Physical & clinical characteristics
. Synthesis, isolation & purification
. Packaging & labeling
. Specifications and analytical methods
. Reference standard
. Preparation & certification
. Stability
Drug Product
------------
. Specification & analytical methods
. Description of manufacturing & packaging
. Stability
2. Preclinical
-----------
Toxicology (to be completed by NDA submission)
----------
. Chronic studies in rats & monkeys
. Reproductive studies
. Carcinogenicity studies
. Additional mutagenicity studies
Pharmacology
------------
. Assay validation
Page 38 of 46
Page 2 of 2
3. Clinical
--------
. Phase I multiple dose study (to be completed by [*])
- Tolerance & packaging (tablet evaluation)
. Phase II Trial(s) (to be initiated within [*])
- Evaluate safety vs. placebo
- Evaluate dosing frequency
. Phase III Trials (to be initiated within [*], in any event after [*])
- Efficacy & safety vs. placebo
- Comparative (superiority evidence) v. [*]
4. Clinical Pharmacology (to be completed by [*])
----------------------
. Gastrointestinal studies
. Ophthalmologic, neurologic & cardiac studies
. Renal & hepatic disease studies
. Elderly & pediatric studies
5. NDA Summary (to be completed by [*])
-----------
. [*]
. [*]
6. Phase IV Trial(s) ([*])
-----------------
It is agreed that the Development Program is subject to variations by
INTERNEURON as INTERNEURON may wish to introduce after consultation with URIACH
if INTERNEURON deems convenient. Furthermore, URIACH also understands that the
activities set forth in the Development Program may sometimes not be conducted.
If INTERNEURON determines to conduct supplementary studies not defined in the
Development Program, INTERNEURON shall establish in good faith, after
consultation with URIACH, the studies to be made as soon as it is known to
INTERNEURON. However, the Parties agree that the decisions regarding the
Development Program are within the sole discretion of INTERNEURON.
*Confidential Treatment Requested
Page 39 of 46
SCHEDULE 1.24
PATENT ASSETS
Compound Patent No. Country Filing Date Status
----------------------------------------------------------------------
[*] [*] PCT [*] [*]
[*] Europe [*] [*]
[*] USA [*] [*]
[*] Canada [*] [*]
[*] Japan [*] [*]
[*]
[*] Korea [*] [*]
[*] Mexico [*] [*]
[*]
[*] Norway [*] [*]
[*]
[*] Chile [*] [*]
[*]
[*] Venezuela [*] [*]
[*] [*] PCT [*] [*]
[*] Europe [*] [*]
[*] USA [*] [*]
[*] Canada [*] [*]
[*] Japan [*] [*]
[*]
[*] Korea [*] [*]
[*] Mexico [*] [*]
[*] Norway [*] [*]
[*]
[*] Brazil [*] [*]
[*] Argentina [*] [*]
[*] Chile [*] [*]
[*]
[*] Venezuela [*] [*]
[*] [*] PCT [*] [*]
[*] Argentina [*] [*]
[*] Chile [*] [*]
[*] Venezuela [*] [*]
*Confidential Treatment Requested
Page 40 of 46
Page 1 of 3
EXHIBIT 1.32
SPECIFICATIONS
(Tentative synthesis route. Subject to adjustments and improvements by Uriach)
[*]
*Confidential Treatment Requested
Page 41 of 46
Page 2 of 3
UR-12746 Sodium Salt- Tentative Specifications
[*] [*]
[*] [*]
[*] [*]
[*] [*]
[*] [*]
[*] [*]
[*] [*]
[*] [*]
[*] [*]
[*] [*]
[*] [*]
[*] [*]
[*] [*]
[*] [*]
Note: [*]
*Confidential Treatment Requested
Page 42 of 46
Page 3 of 3
SPECIFICATIONS OF PRODUCT FORMULATION
[*]
The stability of the following prototype is currently under study:
[*][*]
[*][*]
[*][*]
[*][*]
[*]
[*]
All the excipients meet pharmacopoeial monographs and have been extensively used
for oral products; tablets comply with the required quality standards. [*]
[*]
*Confidential Treatment Requested
Page 43 of 46
APPENDIX 3.7
CLINICAL TRIAL PRODUCT REQUIREMENTS
--------------------------------------------------------------------------------
Appendix 3.7
--------------------------------------------------------------------------------
[*] [*] [*]
--------------------------------------------------------------------------------
[*] [*]
--------------------------------------------------------------------------------
[*] [*] [*]
--------------------------------------------------------------------------------
[*] [*] [*]
--------------------------------------------------------------------------------
[*] [*]
--------------------------------------------------------------------------------
[*] [*]
--------------------------------------------------------------------------------
[*] [*] [*]
--------------------------------------------------------------------------------
[*] [*] [*]
--------------------------------------------------------------------------------
[*] [*]
--------------------------------------------------------------------------------
[*] [*] [*]
--------------------------------------------------------------------------------
[*] [*] [*]
--------------------------------------------------------------------------------
[*] [*]
--------------------------------------------------------------------------------
[*] [*] [*]
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[*]
--------------------------------------------------------------------------------
[*]
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[*] [*]
--------------------------------------------------------------------------------
[*] [*] [*] [*]
--------------------------------------------------------------------------------
[*]
[*]
*Confidential Treatment Requested
Page 44 of 46
APPENDIX 4.2
FORM OF PRESS RELEASE
FOR IMMEDIATE RELEASE
Contact:
Xxxxxxx X. Xxxxxx Xxxxxxx X. Xxxx
Executive VP and CFO VP, Corp. Communications
(000) 000-0000 (000) 000-0000
INTERNEURON ACQUIRES WORLDWIDE RIGHTS TO DERSALAZINE
FOR TREATMENT OF INFLAMMATORY BOWEL DISEASE
Compound Has Unique Mechanism of Action Combining the Activities of an
Approved Anti-inflammatory Agent and a Novel Potent PAF and Cytokine Inhibitor
LEXINGTON, MA, October 1, 2001 -- Interneuron Pharmaceuticals, Inc. (NASDAQ:
IPIC) today announced that it has licensed exclusive worldwide rights to
dersalazine, a compound in early clinical development to treat Inflammatory
Bowel Disease (IBD), which includes ulcerative colitis and Crohn's disease, from
J. Uriach & Cia., S.A. of Barcelona, Spain.
In exchange for an up-front licensing payment, development milestones and
royalty payments to Uriach, Interneuron gains worldwide marketing rights to
dersalazine, except in Spain, where Uriach retains an option to co-market the
product. Interneuron will be responsible for the future clinical development,
regulatory activities and commercialization of dersalazine. Interneuron plans to
complete the Phase I clinical program and initiate Phase II trials in ulcerative
colitis by the second half of 2002. Future studies will also explore the utility
of the drug in Crohn's disease.
"Dersalazine is an important addition to Interneuron's pipeline," said Xxxxx X.
Xxxxxx, M.D., president and chief executive officer of Interneuron. "This
compound possesses a unique mechanism of action that combines the known
anti-inflammatory activity of 5-ASA (5-Aminosalicylic Acid) with potent PAF
(platelet activating factor) antagonism and cytokine inhibition. Our new
partner, Uriach, possesses significant expertise in the field of
anti-inflammatory therapeutics, and dersalazine represents the culmination of
years of internal research. Standard effective therapies for ulcerative colitis
are based on the activity of 5-ASA. The addition of PAF antagonism and cytokine
inhibition has the potential to yield a medicine with advantages over currently
available agents.
-more-
Page 45 of 46
-2-
"New treatment options that induce and maintain remissions, minimize side
effects and improve quality of life are needed for these diseases, which are
growing in prevalence particularly in the U.S. and Europe," said Xx. Xxxxxx.
"Strategically, the planned development program for dersalazine is consistent
with Interneuron's objective to acquire compounds with significant pre-clinical
or early clinical data and subsequently to pursue a clear clinical and
regulatory pathway for these products," said Xx. Xxxxxx.
"In line with our R&D strategy, Uriach has been seeking a partner for the
worldwide development of dersalazine," said Xxxxxxx Uriach, chief executive
officer of J. Uriach & Cia. "This compound has the potential for helping in a
significant way the numerous patients who are affected by IBD worldwide. The
potential of the U.S. market, Interneuron's expertise and commitment to the
project, and above all, the synergies between the objectives of both companies,
have been the main factors for reaching an agreement with Interneuron. This
collaboration is one more example of Uriach's goal of forging long-lasting
partnerships with other companies in order to jointly develop potential drug
candidates originated at Uriach's R&D center."
Dersalazine is a new chemical entity that combines a well-known
anti-inflammatory agent, 5-ASA, with a novel potent agent that acts as a PAF
antagonist and an inhibitor of key interleukin cytokines to achieve a
synergistic therapeutic effect when compared to the activities of each component
separately. Chemical cleavage of dersalazine by colonic bacteria releases the
two active compounds for the topical treatment of inflammation in the colon. The
5-ASA molecule contained in dersalazine has known antioxidant properties which
may ameliorate the deleterious inflammatory effects ascribed to the
overproduction of free radicals. The PAF antagonist component in dersalazine
blocks the effects of platelet activating factor, a naturally occurring mediator
with pro-inflammatory effects implicated in the pathogenesis of IBD. In
addition, dersalazine is believed to inhibit multiple cytokine interleukins that
may be involved in the pathogenesis of the disease. An agent with these multiple
anti-inflammatory actions might be expected to have significant advantages over
existing therapies.
In various experimental models of acute and chronic colitis, dersalazine has
ameliorated or prevented the inflammatory response, as measured by tissue damage
and biochemical inflammatory markers. Dersalazine appears to act locally on the
colon without the liability of unwanted systemic absorption. The safety of
single oral doses of dersalazine has been
Page 46 of 46
demonstrated in healthy volunteers, in whom the systemic absorption of the
compound and its two active components was low.
Ulcerative colitis is a chronic disease that primarily affects the colon and
causes inflammation in the upper layers of the large intestine, while Crohn's
disease usually occurs in the small intestine and causes inflammation deeper
within the wall of the intestine. Up to one million patients in the U.S. and two
million worldwide suffer from these diseases. Fifty percent of these are
affected by ulcerative colitis and 50 percent by Crohn's disease.
Uriach is a private Spanish pharmaceutical company, established in 1838, with a
broad commercial presence in Spain and with a world class research and
development center that focuses its efforts in the early stages of drug
development. Uriach's R&D efforts are centered in the cardiovascular and
inflammation areas.
Interneuron Pharmaceuticals is engaged in the development and commercialization
of a portfolio of products and product candidates for panic/anxiety disorders,
overactive bladder, liver disease, prevention of HIV infection, stroke and other
disorders.
Except for the descriptions of historical facts contained herein, this press
release contains forward-looking statements that involve risks and uncertainties
that could cause the Company's actual results and financial condition to differ
materially from those anticipated by the forward looking statements. These risks
and uncertainties are set forth in the Company's filings under the Securities
Act of 1933 and the Securities Exchange Act of 1934 under "Risk Factors" and
elsewhere, and include, but are not limited to: uncertainties relating to
clinical trials and regulatory approvals; need for additional funds and
corporate partners; history of operating losses and expectation of future
losses; risks relating to the Redux-related litigation; product liability;
dependence on third parties for manufacturing and marketing; the early stage of
products under development; government regulation, patent risks and competition.
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