Exhibit 10.1
SECOND AMENDMENT TO COLLABORATION
AGREEMENT
This Second
Amendment to Collaboration Agreement (this “Second
Amendment”) dated as of January 7, 2005 (the “Second
Amendment Effective Date”), is by and between Regeneron
Pharmaceuticals, Inc., a corporation organized and existing under
the laws of the State of New York and having its principal office
at 777 Old Saw Mill River Road, Tarrytown, New York 10591
(“Regeneron ”) and Aventis Pharmaceuticals Inc., a
corporation organized and existing under the laws of the State of
Delaware and having a principal place of business at 200 Crossing
Blvd., Bridgewater, New Jersey 08807
(“Aventis”).
INTRODUCTION
WHEREAS, Regeneron
and Aventis are Parties to a Collaboration Agreement, having an
Effective Date of September 5, 2003, as amended on
December 31, 2004 (the “Collaboration Agreement”);
and
WHEREAS, Regeneron
and Aventis have determined that it is desirable to amend and
restate certain provisions of the Collaboration Agreement and
document further agreements between them as set forth
herein.
NOW, THEREFORE, in
consideration of the following mutual promises and obligations and
for good and valuable consideration, the receipt and sufficiency of
which are hereby acknowledged, the Parties, intending to be legally
bound, hereby agree as follows:
Capitalized terms used in this
Second Amendment and not defined herein shall have the meanings
ascribed to them in the Collaboration Agreement. The term
“Excluded Ocular VEGF Products” as used in this Second
Amendment shall have the meaning ascribed to it in the amendments
to Sections 1.162 and 1.165 of the Collaboration Agreement set
forth in Section 2 of this Second Amendment.
1. Aventis Rights
Outside of Collaboration. Section 2.4 shall be amended by deleting
subsections (d) and (e) in their entirety and replacing
them with the following new subsections (d) and (e). With
respect to new Section 2.4(d), below, the rights shall be
deemed granted to the Parties retroactively as of the Collaboration
Agreement Effective Date, and each Party hereby waives any rights
it may have had under the deleted Section 2.4(d).
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“ (d) Notwithstanding anything in
Section 2.4 to the contrary, each Party and/or its respective
Affiliates shall be entitled to (i) initiate, sponsor and/or
conduct a clinical trial and/or (ii) participate, directly or
indirectly, whether through the provision of funds, grants or
otherwise, in any clinical trial, initiated, sponsored and/or
conducted by any Third Party; in each of the foregoing cases with
respect to the combination of any Party (or its Affiliate’s)
product, including, but not limited to, in the case of Aventis,
Eloxatin Ò (Oxaliplatin) and Taxotere Ò (Docetaxel), together with any Third Party VEGF
Product that has been granted a Marketing Approval for at least one
indication in the applicable country, including, but not limited to
Avastin Ò (Bevacizumab) (in the United States and any
other country where bevacizumab has been granted a Marketing
Approval), in any oncology indication, unless (A) a VEGF
Product Developed under the Collaboration has been granted a
Marketing Approval in the applicable country for use in combination
with such Party’s (or its Affiliate’s) product in the
same indication(s) as the one to be studied in the intended
clinical trial with the Third Party VEGF Product which is not
approved in such indication or (B) both the Third Party VEGF
Product and a VEGF Product Developed under the Collaboration have
been granted a Marketing Approval in the applicable country for use
in combination with such Party (or its Affiliate’s) product
as the same indication to be studied in the intended clinical trial
with the Third Party VEGF Product and the relevant labeling of both
the Collaboration VEGF Product and the Third Party VEGF Product for
such indication is substantially similar. For any combination study
with a Third Party VEGF Product covered by this Section 2.4(d)
commencing after the Second Amendment Effective Date, the
applicable Party shall notify the other Party prior to initiating
such trial, such notice to include a brief synopsis of the protocol
and a description of the Party’s (or its Affiliate’s)
role(s) and responsibilities in connection with the study. Further,
for any combination study with a Third Party VEGF Product covered
by this Section 2.4(d), each Party shall promptly provide the
other Party with available results of such combination study,
unless such disclosure is prohibited by law or contract. Each Party
and/or its Affiliates shall be entitled to use data from clinical
trials permitted by this Section 2.4 to promote the
combination of such Party product together with such Third Party
VEGF Product, unless a VEGF Product Developed under the
Collaboration has been granted a Marketing Approval in the
applicable country for use in combination with such Party product,
in the same indication. Neither Party nor its respective Affiliates
shall receive any compensation or other payments (either in cash or
in kind) based
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on the
development, promotion, or sale of Third Party VEGF Product.
Neither Party will intentionally delay the commencement, enrollment
or completion of a Clinical Study as a result of any ongoing or
pending clinical trial permitted by this Section 2.4(d). For
the avoidance of doubt, neither Party nor its respective Affiliates
shall use or disclose any Party Information or New Information
subject to the confidentiality provisions of Article 16 in
connection with any of the activities described in this
Section 2.4(d).
(e) Notwithstanding anything in
Section 2.4 to the contrary, each Party may initiate a Party
or its Affiliate’s sponsored pivotal clinical trial in an
indication which combines a Party’s (or its
Affiliate’s) product and a Third Party VEGF Product if, and
only if, such combination trial for Approval of such Party’s
(or its Affiliates) product is required in writing by a Regulatory
Authority, and, prior to the commencement of any such clinical
trial, the applicable Party provides the other Party with a copy of
such written notification, a writing of the commencement of such
clinical trial, and a brief synopsis of the protocol, including the
expected commencement and completion dates.”
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2.
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Ophthalmology Program
. Effective as of Second
Amendment Effective Date, the scope of the Collaboration shall
exclude all local administration of any VEGF Product to the eye,
including, without limitation, by topical, intravitreal,
periorbital, implants, or other means, for the treatment or
diagnosis of any ocular disease or disorder (the “Excluded
Field”) and, except to the extent required by Aventis to
fulfill its obligations under this Second Amendment, all licenses
and rights granted by Regeneron to Aventis and its Affiliates under
the Collaboration Agreement with respect to VEGF Products
(including, without limitation, VEGF Trap Products) in the Excluded
Field shall automatically terminate and revert to Regeneron. In
furtherance thereof, the definitions of “VEGF Products”
in Section 1.162 of the Collaboration Agreement, and
“VEGF Trap Products” in Section 1.165 shall each
be amended by adding the following sentences at the end thereof:
“Notwithstanding anything herein to the contrary, effective
as of January 7, 2005, this definition shall specifically
exclude any molecule delivered via local administration to the eye,
including, without limitation, by topical, intravitreal,
periorbital, implants, or other means, (“Excluded Ocular VEGF
Products”).” Furthermore, the definition of
“Therapeutic Area” in Section 1.159 of the
Collaboration Agreement shall be amended by adding after each
reference to the phrase “diseases of the eye” therein a
reference to the parenthetical phrase “(other than through
local administration to the eye)”. For the avoidance of
doubt, Regeneron and Aventis shall continue to collaborate on the
Development and Commercialization of all VEGF Products in the
Territory outside the Excluded Field under the terms of the
Collaboration Agreement. To further clarify, and by
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way
of example, for the purposes of determining the occurrence of a
milestone event delineated in Schedule 2 , as amended,
Excluded Ocular VEGF Products shall not be considered VEGF
Products, VEGF Trap Products or Regeneron VEGF Products. For the
further avoidance of doubt, after the Second Amendment Effective
Date, neither Aventis nor its Affiliates shall have any right,
title, or interest in Regeneron’s Excluded Ocular VEGF
Products and Regeneron shall have the sole discretion to undertake
any further development or commercialization of any Excluded Ocular
VEGF Products, including, without limitation, any VEGF Trap
Products in the Excluded Field, either on its own or with or
through any Third Party licensee(s).
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3.
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Ocular Development
Payments . In
the event that there is a first commercial sale of an Excluded
Ocular VEGF Product in any Major Market Country that predates the
First Commercial Sale of a VEGF Product in any Major Market
Country, Aventis shall have the right to receive Ocular Development
Payments as part of the Quarterly True-Up until such time as there
is a First Commercial Sale of a VEGF Product in any Major Market
Country. “ Ocular Development Payment ” shall
mean, with respect to the calendar quarter beginning with the first
calendar quarter commencing two years after the first commercial
sale of an Excluded Ocular VEGF Product in any Major Market
Country, unless Regeneron chooses to pay a higher amount in such
calendar quarter, the product of (x) the Ocular Development
Balance, and (y) .05. The “ Ocular Development Balance
” shall mean Seven Million Five-Hundred Thousand US Dollars
($7,500,000.00) less the aggregate amount of Ocular Development
Payments made up to the end of the prior calendar quarter. The
Development Balance shall be reduced in an amount of and to the
extent that any Ocular Development Payments are made by Regeneron
to Aventis.
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4.
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Confidentiality
. Aventis shall promptly
collect and destroy, and cause its Affiliates to collect and
destroy, all documents containing Party Information or New
Information relating solely to the VEGF Products in the Excluded
Field, and shall immediately cease and cause its Affiliates to
cease all further use of any such Party Information or New
Information with respect to VEGF Products in the Excluded Field.
Each of Aventis and Regeneron reaffirm their commitment under
Article 16 to keep confidential all New Information and all
Party Information of the other Party. In accordance therewith, the
rights granted to Aventis under Section 2 of this Second
Amendment do not provide Aventis with any rights to use or disclose
New Information or Regeneron Party Information, unless otherwise
provided under Article 16 of the Collaboration Agreement.
However, notwithstanding anything provided in Section 16.1 to
the contrary, as of the Second Amendment Effective Date, Regeneron
shall have the right to use and disclose, any New Information
and/or Regeneron’s Party Information for use in the
manufacture, development, use, and commercialization of Excluded
Ocular VEGF Products anywhere in the world; provided, however, that
any such disclosure of confidential New Information to a Third
Party (other than a Governmental Authority or as part of a public
disclosure in the interest of patient
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safety)shall be subject to
confidentiality obligations to Regeneron on the part of such Third
Party at least as stringent as those set forth in the Collaboration
Agreement, except that the term of such confidentiality obligation
shall not be less than five (5) years.
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5.
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Initial Co-Development
Plan . The
Parties agree to finalize a Co-Development Plan, which shall
replace the Initial Co-Development Plan, within ninety
(90) days of the Second Amendment Effective Date. Unless
otherwise agreed by both Parties, the Co-Development Plan shall
include the Co-Development Budget and Development activities
approved by the JSC on December 23, 2004.
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6.
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Consideration.
In consideration for
Regeneron’s agreement to enter into this Second Amendment,
Aventis shall pay to Regeneron, on or before January 21, 2005,
a non-refundable, non-creditable termination and restructuring
payment of Twenty Five Million US Dollars ($25,000,000.00) (which
shall not be reduced by any withholding or similar taxes) (the
“Termination Payment”). The Termination Payment shall
be considered a Development Cost solely for purposes of determining
the Development Balance in accordance with the Collaboration
Agreement. Regeneron may
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