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).
5
“ (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
6
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.”
| 2. |
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 |
7
| |
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). |
| |
| 3. |
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. |
| |
| 4. |
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 |
8
| |
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. |
| |
| 5. |
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. |
| |
| 6. |
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 use the Termination Payment for any and all purposes. Except
for the agreement to consider the Termination Payment as a
Development Cost for purposes of determining the Development
Balance, nothing in this Sec |
|
