EXHIBIT 10.15
AMENDMENT TO DEVELOPMENT, LICENSE AND
MARKETING AGREEMENT ENTERED INTO AS OF
JUNE 26, 1995, AND MADE BY AND BETWEEN
ASTRA AB AND CENTAUR PHARMACEUTICALS, INC.
This Amendment, entered into July 8, 1997, is made by /1/ and between Astra AB,
a corporation organized and existing under the laws of Sweden, X-000 00
Xxxxxxxxxx, Xxxxxx ("Astra") and Centaur Pharmaceuticals, Inc. a corporation
organized and existing under the laws of the State of Delaware, 000 Xxxxxxx
Xxxxxxx, Xxxxxxxxx, XX 00000, XXX ("Centaur").
WHEREAS, the parties wish to clarify and amend certain aspects of the above
mentioned agreement (referred to herein as the "Agreement");
NOW THEREFORE, in consideration of the promises and mutual covenants herein
contained, the parties agree as follows:
I. ADDITIONAL DEFINITIONS/2/
1. CENTAUR LIBRARY. As used herein "Centaur Library" shall mean all chemical
structures contained in Centaur's NRT(TM) Technology substance library as
of June 26, 1995 and additional chemical structures obtained by Centaur
during the period of time Astra is funding at a rate of not less than U.S.
$4
_____________________________
/1/
/2/An initial capitalized term appearing in Section I through III, if not
defined in this Section I, shall have the same meaning as in the Development,
License and Marketing Agreement.
million per year Centaur Research Work and/or Development work under the
Agreement.
2. STRUCTURE INFORMATION. As used herein "Structure Information" shall mean any
and all Confidential Information on the chemical structures of compounds
included in the Centaur Library including, but not limited to, compound
descriptors, such as Mass, NMR, IR and UV spectra, melting point, and
chirality.
3. SCREENING CRITERIA. As used herein "Screening Criteria" shall mean compound
properties specified by the Joint Project Team and approved by the Steering
Committee as prerequisites for selection of Hits (as defined below).
4. CD NOMINATION CRITERIA. As used herein " CD Nomination Criteria" shall mean
the criteria proposed by the Joint Project Team and approved by the Steering
Committee for selection of Potential CDs and CDs in the respective Project.
5. HITS. As used herein "Hits" shall mean each compound that is identified to
meet any Screening Criteria in screens performed in a Project during initial
screening of the Centaur Library.
6. LEAD COMPOUND. As used herein "Lead Compound" shall mean a compound
identified among the Hits as a compound suitable for Lead Optimization, with
the aim to identify Potential CDs (as defined below) meeting the CD
Nomination Criteria.
7. LEAD OPTIMIZATION. As used herein "Lead Optimization" shall mean design
and/or synthesis of new chemical entities based on a Lead Compound using
Centaur's SAR program or other technologies for drug discovery and drug
design in order to find compounds meeting CD Nomination Criteria.
8. PRIMARY PHARMACOLOGY TESTING. As used herein "Primary Pharmacology Testing"
shall mean the testing of Lead Compound(s) and/or compounds synthesized
during Lead Optimization for properties regarding potency and selectivity in
in vitro and in vivo tests related to the cellular and molecular drug
target(s) and/or in models of the target disease in a Project.
9. SECONDARY TESTING. As used herein "Secondary Testing" shall mean the testing
of Lead Compound(s) and/or compounds synthesized during Lead Optimization
for properties regarding safety pharmacology, drug metabolism and
pharmacokinetics, and toxicity in a Project.
10. POTENTIAL CD(S). As used herein "Potential CD(s)" shall mean such Lead
Compound(s) and/or compounds synthesized during Lead Optimization that after
Primary Pharmacology Testing and Secondary Testing are identified by the
Joint Project Team and approved by the Steering Committee to meet the CD
Nomination Criteria in the relevant Project. Each potential CD, as well as
each CD, shall include all of such CD's salts, esters which are easily
cleaved biologically or chemically, complexes, chelates, hydrates,
stereoisomers, crystalline and amorphous
forms, prodrugs, metabolites and metabolic precursors.
11. IDENTIFICATION. As used herein "Identification" means the process in each
Project leading up to and including selection by the Joint Project Team and
the Steering Committee of Potential CDs and CDs. Identification includes
the following phases: 1) initial screening of the Centaur Library for Hits,
2) identification and selection of Lead Compounds among the Hits, 3) Lead
Optimization, 4) Primary Pharmacology Testing, 5) Secondary Testing and 6)
selection of Potential CDs and CDs. In a Project where Identification has
been completed and the desired number of Potential CDs have been selected,
Identification may be resumed, in full or in part, should the Potential CDs
selected later prove inadequate.
II. IDENTIFICATION AND ACCESS TO STRUCTURE INFORMATION.
1. OVERVIEW OF PROCESS. In an effort to speed the Identification for the Field
but at the same time being sensitive to Centaur's need for strictly
controlling Structure Information, a limited number of Astra employees will
actively participate with Centaur personnel in the various phases of the
Identification.
2. SCREENING OF THE CENTAUR LIBRARY. The number of Astra employees
participating in each Project in the initial screening of the Centaur
Library for Hits will be separately agreed by the parties on a
case by case basis but will always include Astra's Project leader and one
or more named specialists in chemistry, in modeling and drug design, and in
QSAR technologies.
The said Astra employees will either alone, or together with the respective
Joint Project Teams, be involved in i.a. preparation of proposals to the
Steering Committee on Screening Criteria, design of the screens, analyzing
results from the screens and identifying Hits from the screens and
identifying Lead Compounds. The Astra employees involved in the initial
screening of the Centaur Library will be given access to all Structure
Information on the Hits but not to Structure Information on other compounds
in the Centaur Library except to the extent that is needed or necessary for
Identification in a Project as judged by the Joint Project Team and the
Steering Committee.
Structure Information on compounds disclosed to Astra employees according
to the preceding paragraph, and/or on compounds synthesized during the
process of Lead Optimization may be disclosed within Astra on a need to
know basis. Astra undertakes to keep all Astra employees with access to
Structure Information aware of its strictly confidential nature and that
the confidentiality obligations undertaken by Astra pursuant to Section 16
of the Agreement applies to such information. Astra further undertakes to
identify to Centaur, on a case to case basis, the names of such Astra
employees.
3. NEW CHEMICAL INVENTIONS. Should one or more Astra employees with access to
Structure Information, solely or jointly with Centaur employees, in the
process of Identification, make an invention of a new chemical entity or
new process directly or indirectly on the basis of such Structure
Information, Astra shall promptly make a written assignment of its rights
to such new invention to Centaur in a fashion as mutually agreed and, at a
minimum, compatible with U.S. patent law, and such new invention shall be
used by Astra and Centaur solely within the context of the Agreement,
provided, however, that Centaur may use such new invention outside the
Field subject to the provisions of Section III hereto. Any Astra employee
who is an inventor as above said shall be named as an inventor in the
patent application, notwithstanding assignment of Astra's rights thereto to
Centaur.
4. DESIGNATION OF A LEAD COMPOUND. The Joint Project Team and the Steering
Committee may designate one or more Hits as Lead Compound(s). In the event
of deadlock in the Steering Committee, neither Astra nor Centaur shall have
the sole right to determine whether a Hit is designated as a Lead Compound.
If the parties disagree on whether the standards for selection are met,
then, notwithstanding the provisions of Section 3.4 of the Agreement,
Article 22 will govern resolution of this dispute. The Steering Committee
may also rescind its designation of a Hit as a Lead Compound at any time.
5. DESIGNATION OF A POTENTIAL CD. The Steering Committee may designate one or
more Lead Compound(s) and/or compounds synthesized during Lead Optimization
as Potential CDs or CDs, if they meet the CD Nomination Criteria. Within
each project, and in the Stroke Project within each indication, the parties
will endeavor to select 3-5 Potential CDs, 1-2 of which will serve as back-
ups for the chosen CD ("Back-ups"). In the event of deadlock in the
Steering Committee, Astra shall have the sole right to finally decide on
all matters regarding selection of CDs and Potential CDs serving as Back-
ups.
III. CERTAIN RESTRICTIONS ON CENTAUR'S ABILITY TO COMMERCIALIZE A COMPOUND
OUTSIDE OF THE FIELD.
1. PROCEDURES RELATING TO POTENTIAL CDS. Should Centaur itself or through a
third party wish to commercialize a Potential CD serving as Back-up to a
chosen CD outside of the Field, then it will provide Astra sixty (60) days
prior written notice that it intends to do so, thereby giving Astra the
opportunity to declare its with that the Steering Committee designates such
Potential CD a CD. Should Astra wish the Steering Committee to declare such
Potential CD a CD, it shall send written notice prior to the end of that
sixty day period. Should Astra not wish the Steering Committee to declare
such Potential CD a CD, it will either so inform Centaur in writing, or do
nothing, and at which point either on such notice or at the end of the
sixty (60) day period Centaur will remain free to commercialize such
Potential CD outside of the Field without compliance with Section 18.2 of
the Agreement and Astra will no longer be able to prevent Centaur from
commercializing such Potential CD outside of the Field at any time in the
future.
2. RESTRICTIONS RELATING TO CDS. When a Potential CD is designated a CD,
Centaur will not itself or through third party commercialize that CD
outside of the Field. Notwithstanding any provision of the Agreement,
Centaur agrees that it will not itself, or through an Affiliate, license or
exploit a CD for any indication, therapy or use whatsoever inside or
outside of the Field anywhere in the world other than as provided in
Section 8 of the Agreement. This provision will become null and void (a) as
far as applications outside the Field are concerned world-wide, should
Astra inform Centaur in writing that it no longer will conduct or support
research, development, use or sale of such CD in the Field or, (b) with
regard to the relevant country, regarding such CD, if Astra fails to comply
with Sections 6.4(a), 6.4(b) or 6.5 of the Agreement and Centaur notifies
Astra of Centaur's intent to terminate the Astra License with regard to the
relevant country in accordance with Section 6.6 of the Agreement. The
parties acknowledge that CPI-22 (also named NXY-059) has been declared a CD
and thus is subject to these restrictions on commercialization by Centaur
outside of the Field. Should the Steering Committee declare a Potential CD
a CD, then Astra will pay the amounts, if any, called for by Section 7.2 of
the Agreement and have
the concomitant obligations to use best reasonable efforts in pursuing any
required pre-clinical studies necessary for filing an IND and subsequent
human clinical trials of the CD and perform other work related to the
commercial development of the CD as called for in Agreement.
3. LAPSE OF RESTRICTIONS ON CDS. At such time as Astra no longer wishes to
continue developing a CD for commercial exploitation or fails to meet the
standards of performance set out in the Agreement, then Centaur will be
free to commercialize that CD outside of the Field itself or through a
third party. Astra shall exert its best reasonable efforts to keep Centaur
informed of the status of all CDs and the likelihood that Astra may cease
developing any CD for commercial exploitation in the future in order that
Centaur may make advance provisions and plans for CDs whose rights may be
returned to Centaur.
In witness whereof the parties hereto have executed this Amendment in two (2)
copies on the day set forth above.
ASTRA AB CENTAUR PHARMACEUTICALS, INC.
(publ)
/s/ Xxxxx Xxxxxxxxxxx /s/ Xxxxx X. Xxxxxxx
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Xxxxx Xxxxxxxxxxx Xxxxx X. Xxxxxxx
Executive Vice President President & Chief Executive
Officer
/s/ Goran Lerenius
-----------------------
Goran Lerenius
General Counsel
September 18, 1997
Xxxxx X. Xxxxxxx
President and Chief Executive Officer
Centaur Pharmaceuticals, Inc.
000 Xxxxxxx Xxxxxxx
Xxxxxxxxx, XX 00000, XXX
Dear Xx. Xxxxxxx:
I refer to your letter of July 18, 1997, in which you request that we waive our
Right of First Negotiation to applications of Centaur's technology outside the
central nervous system. After having completed our internal reviews triggered by
your request, I can now inform you that we are willing to agree to your request.
Consequently, we propose that in Article 18.2 of the Development, License and
Marketing Agreement between the parties dated June 26, 1995, in lines 6-8 the
words "Astra's strategic research areas and/or such other research areas of
interest to ASTRA as set forth in Appendix 4 hereof, and as the same may be
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modified from time to time by ASTRA in writing" be replaced by "the research
area of the Central Nervous System (CNS)."
Please confirm your acceptance of the above amendment which will enter into
immediate effect by your signing and returning to us of the enclosed copy of
this letter.
Your sincerely,
ASTRA AB
Preclinical Affairs,
Research and Development
We hereby accept and agree to the above
/s/ Xxx X. Xxxxxxxx amendment.
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Xxx X. Xxxxxxxx
Vice President CENTAUR PHARMACEUTICALS, INC.
Date: October 7, 1997
/s/ Xxxxx X. Xxxxxxx
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Xxxxx X. Xxxxxxx
President and CEO
