Document:

EX-10.1

 

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, EloxatinÒ (Oxaliplatin) and
TaxotereÒ (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 AvastinÒ
(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.”

	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

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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).
	 
	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

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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.
	 
	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 Second Amendment or the Collaboration
Agreement shall entitle Aventis or its Affiliates to any consideration, royalties, fees or
payments based on the manufacture, development or commercialization of any Excluded Ocular
VEGF Products.
	 
	7.  	Purified Bulk Drug Substance. Regeneron shall be entitled to use in the Excluded Field, free
of charge, up to two kilograms of purified bulk drug substance manufactured prior to the
Second Amendment Effective Date for use in the manufacture of Formulated Bulk VEGF Product
(“Purified Bulk Drug Substance”). In addition, Regeneron shall be entitled to use in the
Excluded Field, free of charge, up to two and one-half percent (2.5%) of Purified Bulk Drug
Substance manufactured by Regeneron after the Second Amendment Effective Date. Upon at least
twelve (12) months’ prior notice, Regeneron shall be entitled to purchase at Manufacturing
Cost two and one-half percent (2.5%) of Purified Bulk Drug Substance manufactured after the
Second Amendment Effective Date by Aventis (or its Affiliates or Third Party contractors) for
use in the Excluded Field.
	 
	8.  	Limitation on Aventis’ Rights to Develop or Commercialize Excluded Ocular VEGF Products.
During the Term, except as specifically set forth in Section 7 of this Second Amendment,
neither Aventis nor its Affiliates, either alone or through any Third Party, shall develop,
manufacture for use in the Territory, promote or sell an Excluded Ocular VEGF Product. In the
event that during the Term (i) Aventis or one of its Affiliates acquires, directly or
indirectly, Control (as such term is defined below) of a Third Party, and (ii) the Third Party
or one of its

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	   	Affiliates is the owner of or is holding license rights to Patents relating to
an Excluded Ocular VEGF Product, and (iii) such an Excluded Ocular VEGF Product, at the moment
of acquiring Control, is in pre-clinical or clinical development or accounts for more than
10% of such Third Party’s pharmaceutical sales, then Aventis shall divest or cease the
development or the commercialization of the Excluded Ocular VEGF Product within twelve (12)
months. For the purpose of this paragraph, the term “Control” shall mean the ownership of
more than fifty (50) percent of the voting stock or similar interest.
	 
	9.  	Post-Amendment License. Regeneron shall have a fully paid-up and royalty free, worldwide,
exclusive license (which shall include the right to grant sublicenses) from Aventis and its
Affiliates under Aventis Patent Rights and Aventis Know-How solely in connection with the
development, manufacture, use and sale of Excluded Ocular VEGF Products, in each case, either
(i) existing as of the time of the Second Amendment Effective Date (together with and all
substitutions, divisions, continuations, continuations-in-part, reissues, reexaminations and
extensions thereof and all counterparts thereof in any country which arise on or after the
Second Amendment Effective Date), or (ii) discovered, created or reduced to practice in
connection with Collaboration activities.
	 
	10.  	VEGF Product Labeling. Regeneron and Aventis shall use Commercially Reasonable Efforts to
include language in approved labeling for VEGF Products Commercialized as part of the
Collaboration stating that the product is not intended for local administration to the eye.
Regeneron shall use Commercially Reasonable Efforts to include language in approved labeling
for Excluded Ocular VEGF Products stating that the product is not intended for systemic
administration.

	11.  	Regulatory Coordination. Regeneron and its Affiliates and licensees shall have, and Aventis
and its Affiliates hereby grant to Regeneron and its Affiliates and licensees, the right to
reference the BLA(s), IND(s), and any Registration Filings and/or Approvals requested by
Regeneron to support Regeneron’s (and its Affiliates’ and licensees’, as applicable) IND, BLA,
Registration Filings and/or Approvals for Excluded Ocular VEGF Products anywhere in the world.
Promptly upon the request of Regeneron, Aventis or its Affiliate shall submit a letter of
authorization to FDA or the applicable Regulatory Authority (and take such actions or make
such other filings) in order to permit any VEGF Product IND, BLA, Registration Filing and/or
Approval to be incorporated by reference in such Excluded Ocular VEGF Product regulatory
filings. Both Parties will cooperate with each other to develop and follow specific
procedures to be agreed upon to coordinate the exchange of necessary safety/pharmacovigilance
information from VEGF Products Developed and Commercialized as part of the Collaboration and
Excluded Ocular VEGF Products developed and commercialized by Regeneron

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	   	and its licensees to
ensure prompt communication of such notifications and compliance with reporting obligations to
Regulatory Authorities.
	 
	12.  	Miscellaneous Amendments to Collaboration Agreement. The following Sections in the
Collaboration Agreement shall be amended as follows: (a) Section 3.2(a) of the Collaboration
Agreement is hereby amended by deleting the second sentence thereof and replacing it with the
following sentence, “The exact number of representatives of each party shall be as determined
by such Party, but shall include at least three (3) senior representatives from each Party.”
(b) Section 19.3 of the Collaboration Agreement is hereby amended by adding the words “, the
First Amendment to the Collaboration Agreement entered into between the Parties as of December
31, 2004 or the Second Amendment to the Collaboration Agreement entered into between the
Parties as of January 7, 2005” following each reference to the words “this Agreement” therein.
	 
	13.  	Continuing Effect. Except as specifically modified by this Second Amendment, all of the
provisions of the Collaboration Agreement are hereby ratified and confirmed to be in full
force and effect, and shall remain in full force and effect.
	 
	14.  	Entire Agreement; Successors and Assigns. The Collaboration Agreement, this Second
Amendment, and any written agreements executed by both Parties pertaining to the subject
matter therein, constitute the entire agreement between the Parties hereto with respect to
subject matter hereof and thereof. Said documents supersede all other agreements and
understandings between the Parties with respect to the subject matter hereof and thereof,
whether written or oral. This Second Amendment shall be binding upon and shall inure to the
benefit of the Parties and their respective heirs, administrators, executors, Affiliates,
successors and permitted assigns.
	 
	15.  	Headings. The section headings contained in this Second Amendment are for reference purposes
only and shall not affect in any way the meaning or interpretation of the Second Amendment.
	 
	16.  	Counterparts. This Second Amendment may be executed in one or more counterparts, all of
which shall be considered one and the same agreement, and shall become a binding agreement
when one or more counterparts have been signed by each Party and delivered to the other Party.
	 
	17.  	Miscellaneous. This Second Amendment shall be governed by the laws of the State of New York,
without regard to its principles of conflicts of laws. Each Party hereby irrevocably and
unconditionally consents to the exclusive jurisdiction of the courts of the State of New York,
and the United States District Court for the Southern District of New York for any action,
suit or proceeding arising out of or relating to this Second Amendment, waives any objections
to such jurisdiction and venue and agrees not to commence any action, suit or proceeding
relating to this Second Amendment except in such courts. This Second Amendment

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	   	supersedes all
prior understandings and agreements, whether written or oral, among the Parties hereto
relating to the essence of this Second Amendment. If there is a direct conflict between the
provisions of the Collaboration Agreement and this Second Amendment, this Second Amendment shall govern. This Second Amendment may
be amended only by a written instrument executed by each of the Parties.
	 
	18.  	Press Release. Regeneron shall have the right to file or register this Second Amendment and
a notification thereof with the United States Securities and Exchange Commission. In
addition, the Parties will issue a joint press release on or promptly after the Second
Amendment Effective Date substantially in the form attached hereto as Exhibit A.

[Signatures appear on following page]

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     IN WITNESS WHEREOF, each of the Parties has caused this Second Amendment to be executed as of
the date hereof by a duly authorized corporate officer.

	 	 	 
	 

	 	AVENTIS PHARMACEUTICALS INC.
	 
	 	 
	

	 	By: /s/ Juergen Lasowski
	 
	 	 
	

	 	Name: Juergen Lasowski
	 
	 	 
	

	 	Title: Vice President, Business Development

& Strategy
	 
	 	 
	

	 	Date: January 7, 2005
	 
	 	 
	

	 	By:  /s/ Pascal Soriot
	 
	 	 
	

	 	Name: Pascal Soriot

	 
	 	 
	

	 	Title: Chief Operating Officer & Head, U.S.
Pharmaceutical Operations
	 
	 	 
	

	 	Date:  January 7, 2005
	 
	 	 
	

	 	REGENERON PHARMACEUTICALS, INC.
	 
	 	 
	

	 	By: /s/ Murray Goldberg
	 
	 	 
	

	 	Name: Murray Goldberg

	 
	 	 
	

	 	Title: Senior Vice President, Finance &

Administration and Chief Financial Officer
	 
	 	 
	

	 	Date: January 7, 2005

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EXHIBIT A

FOR IMMEDIATE RELEASE

SANOFI-AVENTIS REAFFIRMS COMMITMENT TO ALLIANCE

WITH REGENERON PHARMACEUTICALS

Partners Approve Broad-based Cancer Development Program

for the VEGF Trap

Regeneron To Receive $25 million Clinical Development Milestone Payment

Plus Additional $25 Million Payment

Tarrytown, NY – January 10, 2005 – Sanofi-aventis (EURONEXT: SAN and NYSE: SNY) announced today
that, following a review of the Vascular Endothelial Growth Factor (VEGF) Trap program, they have
reaffirmed their commitment to develop the VEGF Trap in oncology in collaboration with Regeneron
Pharmaceuticals Inc. (Nasdaq: REGN). The companies will evaluate the VEGF Trap in a variety of cancer types, both in single-agent
studies and in combination with chemotherapy. Sanofi-aventis also announced that Regeneron has
earned a $25 million clinical development milestone payment.

“This is an exciting time for us as we continue to gather evidence on the potential of the VEGF
Trap to block the formation of blood vessels that fuel the growth of cancerous tumors. All of us
at Regeneron are looking forward to working with sanofi-aventis to accelerate the development of
the VEGF Trap,” noted Leonard S. Schleifer, M.D., Ph.D., Regeneron’s President and Chief Executive
Officer. “Sanofi-aventis is clearly committed to discovery, development, and commercialization of
innovative products. Its expertise in oncology, driven by its commitment to the VEGF Trap, can
provide a great resource for us in moving the program forward.”

Marc Cluzel, M.D., Ph.D., Vice President, International Development, Sciences & Medical Affairs of
sanofi-aventis added “This is an important partnership for sanofi-aventis and we continue to
believe that the blockage of VEGF is one of the most innovative approaches to targeted cancer
therapy.”

In addition, the companies have agreed that the exclusive right to develop and commercialize the
VEGF Trap for eye diseases through local delivery systems reverts today to Regeneron. The
collaboration will not currently pursue systemic delivery for eye disease.

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In connection with this agreement, sanofi-aventis will make a one-time, final payment to Regeneron
of $25 million of which 50% is repayable to sanofi-aventis following commercialization of the VEGF
Trap.

About Regeneron

Regeneron is a biopharmaceutical company that discovers, develops, and intends to commercialize
therapeutic medicines for the treatment of serious medical conditions. Regeneron has therapeutic
candidates in clinical trials for the potential treatment of cancer and eye diseases, rheumatoid
arthritis and other inflammatory conditions, asthma, and obesity and has preclinical programs in
other diseases and disorders. Regeneron corporate headquarters are in Tarrytown, NY. For more
information, please visit www.regn.com.

For Regeneron:

This news release discusses historical information and includes forward-looking statements about
Regeneron and its products, programs, finances, and business, all of which involve a number of
risks and uncertainties, such as risks associated with preclinical and clinical development of
drugs and biologics, determinations by regulatory and administrative governmental authorities,
competitive factors, technological developments, the availability and cost of capital, the costs of
developing, producing, and selling products, the potential for any collaboration agreement to be
canceled or to terminate without any product success, and other material risks. A more complete
description of these risks can be found in Regeneron’s filings with the United States Securities
and Exchange Commission, including its Form 10-K(A) for the year ended December 31, 2003 and Form
10-Q for the quarter ended September 30, 2004. Regeneron does not undertake any obligation to
update publicly any forward-looking statement, whether as a result of new information, future
events, or otherwise unless required by law.

About Sanofi-aventis

Sanofi-aventis is the world’s 3rd largest pharmaceutical company, ranking number 1 in Europe.
Backed by a world-class R&D organization, sanofi-aventis is developing leading positions in seven
major therapeutic areas: cardiovascular disease, thrombosis, oncology, diabetes, central nervous
system, internal medicine, vaccines. Sanofi-aventis is listed in Paris (EURONEXT : SAN) and in New
York (NYSE : SNY).

# # #

	 	 	 
	Contact Information:
	 	 
	Investors:

Charles Poole

Vice President, Investor Relations

(914) 345-7640

charles.poole@regeneron.com

	 	Media:

Lauren Tortorete

 Media Relations

(212) 845-5609

ltortorete@biosector2.com

15

 

Additional information about Regeneron and recent news releases are available on Regeneron’s
Worldwide Web Home Page at www.regeneron.com

16

 

FINAL VERSION SANOFI-AVENTIS

07/01/05

Sanofi-aventis and Regeneron Pharmaceuticals

reaffirm development commitment

Paris, France – January 10, 2005 – Sanofi-aventis (EURONEXT: SAN and NYSE: SNY) announced today
that, following a review of the Vascular Endothelial Growth Factor (VEGF) Trap program, they
have reaffirmed their commitment to develop the VEGF Trap in oncology in collaboration with
Regeneron Pharmaceuticals Inc. (Nasdaq: REGN). The companies will evaluate the VEGF Trap in a
variety of cancer types, both in single-agent studies and in combination with chemotherapy.
Sanofi-aventis also announced that Regeneron has earned a $25 million clinical development
milestone payment.

“This is an exciting time for us as we continue to gather evidence on the potential of the VEGF
Trap to block the formation of blood vessels that fuel the growth of cancerous tumors. All of
us at Regeneron are looking forward to working with sanofi-aventis to accelerate the development
of the VEGF Trap,” noted Leonard S. Schleifer, M.D., Ph.D., Regeneron’s President and Chief
Executive Officer. “Sanofi-aventis is clearly committed to discovery, development, and
commercialization of innovative products. Its expertise in oncology, driven by its commitment
to the VEGF Trap, can provide a great resource for us in moving the program forward.”

Marc Cluzel, M.D., Ph.D., Vice President, International Development, Sciences & Medical Affairs
of sanofi-aventis added : “this is an important partnership for sanofi-aventis and we continue
to believe that the blockage of VEGF is one of the most innovative approaches to targeted cancer
therapy.”

In addition, the companies have agreed that the exclusive right to develop and commercialize the
VEGF Trap for eye diseases through local delivery systems reverts today to Regeneron. The
collaboration will not currently pursue systemic delivery for eye disease.

In connection with this agreement, sanofi-aventis will make a one-time payment to Regeneron of
$25 million, of which 50% is repayable to sanofi-aventis following commercialization of the VEGF
Trap.

17

 

About Sanofi-aventis

Sanofi-aventis is the world’s 3rd largest pharmaceutical company, ranking number 1 in
Europe. Backed by a world-class R&D organization, Sanofi-aventis is developing leading positions
in seven major therapeutic areas: cardiovascular disease, thrombosis, oncology, diabetes,
central nervous system, internal medicine, vaccines. Sanofi-aventis is listed in Paris (EURONEXT
: SAN) and in New York (NYSE : SNY).

For Sanofi-aventis :

This press release contains forward-looking statements as defined in the Private Securities
Litigation Reform Act of 1995. Forward-looking statements are statements that are not
historical facts. These statements include financial projections and estimates and their
underlying assumptions, statements regarding plans, objectives and expectations with respect to
future operations, products and services, and statements regarding future performance.
Forward-looking statements are generally identified by the words “expect,” “anticipates,”
“believes,” “intends,” “estimates,” “plans” and similar expressions. Although sanofi-aventis’
management believes that the expectations reflected in such forward-looking statements are
reasonable, investors are cautioned that forward-looking information and statements are subject
to various risks and uncertainties, many of which are difficult to predict and generally beyond
the control of sanofi-aventis, that could cause actual results and developments to differ
materially from those expressed in, or implied or projected by, the forward-looking information
and statements. These risks and uncertainties include those discussed or identified in the
public filings with the SEC and the AMF made by Sanofi-aventis and Aventis, including those
listed under “Forward-Looking Statements” and “Risk Factors” in sanofi-aventis’s annual report
on Form 20-F for the year ended December 31, 2003 and those listed under “Cautionary Statement
Regarding Forward-Looking Statements” and “Risk Factors” in Aventis’s annual report on Form 20-F
for the year ended December 31, 2003. Other than as required by applicable law, sanofi-aventis
does not undertake any obligation to update or revise any forward-looking information or
statements.

About Regeneron

Regeneron is a biopharmaceutical company that discovers, develops, and intends to commercialize
therapeutic medicines for the treatment of serious medical conditions. Regeneron has therapeutic
candidates in clinical trials for the potential treatment of cancer and eye diseases, rheumatoid
arthritis and other inflammatory conditions, asthma, and obesity and has preclinical programs in
other diseases and disorders. Regeneron corporate headquarters are in Tarrytown, NY. For more
information, please visit www.regn.com.

18<PAGE>

                                                                    EXHIBIT 10.1

                              EMPLOYMENT AGREEMENT

      THIS EMPLOYMENT AGREEMENT (this "Agreement") is made and entered into as
of January 10, 2005 (the "Effective Date"), by and between SCOLR Pharma, Inc., a
Delaware corporation ("the Company"), and Alan M. Mitchel ("Employee").

      The parties agree as follows:

      1. Employment.

            1.1 Title and Duties. Company hereby employs Employee as Senior Vice
President of Business and Legal Affairs and Chief Legal Officer, and Employee
hereby accepts such employment, on the terms and conditions set forth herein.
Employee shall perform such duties as are customary for the position of Senior
Vice President Business and Legal Affairs and any additional such duties that
the Company's Chief Executive Officer or Board of Directors ("Board") may assign
from time to time.

            1.2 Full-time and Best Efforts. Employee will expend Employee's best
efforts on behalf of the Company, and will abide by all policies and decisions
made by the Company, as well as all applicable federal, state and local laws,
regulations or ordinances. Employee will act in the best interests of the
Company at all times and will devote Employee's full business time and efforts
to the performance of Employee's assigned duties to the Company.

      2. Compensation.

            2.1 Base Salary. As compensation for Employee's performance of
Employee's duties hereunder, the Company shall pay Employee an initial base
salary ("Base Salary") of Two Hundred Forty Five Thousand Dollars ($245,000) per
year, payable in accordance with the normal payroll practices of the Company,
less any amounts that the Company is required by applicable federal, state or
local law to withhold therefrom on account of employment, income or other taxes.
Employee's Base Salary shall be reviewed annually by the Compensation Committee
of the Board and may be increased (but not decreased) and such increased amount
shall hereafter be his "Base Salary". The Compensation Committee shall
periodically review the performance of Employee on not less than an annual
basis.

            2.2 Bonus. Employee shall be eligible to receive a performance-based
annual cash bonus in a targeted amount of up to 50% of Base Salary (as adjusted
from time to time) based on the achievement of certain objectives approved by
the Board of Directors in its sole discretion; provided that there is a minimum
gain in the Company's market capitalization of 20% for the year under
consideration for payment of a bonus. The terms and amount of such bonus shall
be determined by the Compensation Committee of the Board in its sole discretion,
based on performance factors and objectives that are established no later than
ninety (90) days after the first day of the fiscal year. The bonus payment shall
be determined by the Board and paid not later than thirty (30) days after
release of the Company's audited financial statements. In the event Employee's
employment is terminated as a result of Employee's death or disability, Employee
will receive an amount equal to the prior year's Bonus prorated for the portion
of the year of termination and paid within sixty days of such termination. In
addition, Employee shall

<PAGE>

receive a one-time signing bonus of Fifty Thousand Dollars ($50,000), subject to
withholding, upon execution of this Agreement; provided, however that $25,000 of
the signing bonus shall be credited against the first bonus awarded to Employee
by the Compensation Committee. In the event that no annual bonus is awarded,
Employee shall be entitled to retain the $25,000.

            2.3 Stock Options. The Company shall grant to Employee options to
purchase 200,000 shares of the Company's Common Stock under the Company's 2004
Equity Incentive Plan (the "Plan") at an exercise price equal to the fair market
value of that stock on the date of grant, which shall be on or as soon as
administratively feasible after January 10, 2005. Such options shall vest
monthly in 36 equal installments commencing on January 10, 2005. Except as
provided in this Agreement, the option will be subject to the terms and
conditions of the Plan and standard form of stock option agreement, which
Employee will be required to sign as a condition of receiving the options.
Notwithstanding anything to the contrary contained in the Plan, Employee (and
his heirs) shall have one year from the date of termination of employment to
exercise any vested stock options.

      3. Benefits.

            3.1 Fringe Benefits. Employee will be eligible for all customary and
usual fringe benefits generally available to employees of the Company, subject
to the terms and conditions of the Company's plan documents. Company reserves
the right to change or eliminate its fringe benefit programs on a prospective
basis, at any time, effective upon notice to Employee.

            3.2 Vacation. Employee will be entitled to accrue vacation of four
(4) weeks per year in accordance with the Company's vacation policy. Vacation
may be carried over from year to year up to a maximum of eight (8) weeks.

      4. Business Expenses. Company will reimburse Employee for all reasonable
out-of-pocket expenses, including professional dues and related expenses,
incurred in the performance of Employee's duties on behalf of the Company in
accordance with the Company's policies.

      5. Term. The employment relationship formed pursuant to this Agreement
shall continue indefinitely commencing on the Effective Date (the "Term") until
terminated in accordance with the other provisions of this Agreement.

      6. Termination of Employee's Employment.

            6.1 Termination for Cause by the Company. The Company may terminate
Employee's employment immediately at any time for Cause. For purposes of this
Agreement, "Cause" is defined as: (a) Employee's indictment for, or conviction
(or plea of nolo contendere) of fraud, embezzlement, misappropriation, or any
felony or any other act of moral turpitude; (b) acts or omissions constituting
gross negligence, recklessness or willful misconduct on the part of the Employee
with respect to Employee's obligations to the Company or otherwise relating to
the business of the Company that materially harms the Company; (c) Employee's
failure or inability to perform the essential functions of the position, with or
without reasonable accommodation, due to a mental or physical disability, where
such inability continues for a period or periods aggregating ninety (90)
calendar days in any 12-month period; (e) Employee's

                                       2
<PAGE>

death; (f) Employee's material breach of this Agreement, the Company's Code of
Conduct or the Company's Proprietary Information and Invention Agreement,
following written notice and a 30-day opportunity to cure, or (g) any similar or
related act or failure to act which is materially adversely injurious to the
Company. In the event that Employee's employment is terminated in accordance
with this subsection 6.1, Employee shall be entitled to receive only the Base
Salary then in effect, prorated to the date of termination and any benefits and
expense reimbursements to which Employee is entitled by virtue of his prior
employment by Company (collectively, the "Standard Entitlements"). All other
Company obligations to Employee pursuant to this Agreement will become
automatically terminated and completely extinguished except that Employee's
Bonus shall be prorated in the event of termination due to death or disability
in accordance with Section 2.2 above. Employee will not be entitled to receive
the Severance Package described in Section 6.2 below or any part thereof.

            6.2 Termination Without Cause by Company/Severance. The Company may
terminate Employee's employment under this Agreement without Cause at any time
upon written notice to Employee. In the event of such termination, Employee will
receive the Standard Entitlements (as defined in Section 6.1 hereof), and a
"Severance Package" consisting of (a) a lump sum cash payment equal to 87.5% of
one year of Employee's Base Salary in effect on the date of termination, (b) a
prorated Bonus payment of 50% of Employee's Base Salary for the portion of the
year of termination; provided that there has been a minimum gain in the
Company's market capitalization of 20% during the applicable portion of such
year, together with (c) full accelerated vesting of any and all unvested stock
options held by Employee, and (d) continued medical coverage at the Company's
expense pursuant to COBRA at existing levels as of the date of termination for
up to one year. The payment of the Severance Package is contingent upon
Employee's compliance with the surviving provisions of this Agreement and
execution of a full and general release, releasing all claims, known or unknown,
that Employee may have against Company arising out of or related to Employee's
employment or termination of employment with the Company. All other Company
obligations to Employee pursuant to this Agreement will be automatically
terminated and completely extinguished.

            6.2(a) The parties intend that any severance or other compensation
under this Agreement be paid in compliance with Internal Revenue Code Section
409A such that there are no adverse tax consequences, interest, or penalties as
a result of the payments. The parties agree to modify this Agreement and/or the
timing (but not the gross amount) of the severance payment if necessary to
comply with I.R.C. 409A.

            6.3 Voluntary Resignation by Employee Without Reason. Employee may
voluntarily resign Employee's position with Company for any reason or no reason
on sixty (60) days' advance written notice to the Company. In the event of
Employee's resignation under such circumstances, Employee will be entitled to
receive the Standard Entitlements, including salary and benefits for the sixty
(60) day notice period, but no other salary or benefits for the remaining months
of the current term, if any. All other Company obligations to Employee pursuant
to this Agreement will become automatically terminated and completely
extinguished. In addition, Employee will not be entitled to receive the
Severance Package described in subsection 6.2 above.

                                       3
<PAGE>

            6.4 Resignation For Good Reason.

                  (a) Severance Package. If Employee resigns for Good Reason (as
defined below), Employee shall be entitled to receive the Severance Package
described in subsection 6.2 above, provided Employee complies with all the
conditions described in subsection 6.2 above.

                  (b) Section 280G. If, due to the benefits provided under
subsection 6.4(a) above, Employee is subject to any excise tax due to
characterization of any amounts payable under subsection 6.4(a) as excess
parachute payments pursuant to Section 4999 of the Internal Revenue Code of
1986, as amended (the "Code"), Employee may elect, in Employee's sole
discretion, to reduce the amounts payable under subsection 6.4(a) in order to
avoid any "excess parachute payment" under Section 280G(b)(1) of the Code.

                  (c) Good Reason. "Good Reason" shall mean the occurrence of
one of the following without Employee's express written consent: (i) a material
reduction in the level of Employee's responsibilities for the Company; (ii) the
assignment to Employee of any duties inconsistent with Employee's position as
Senior Vice President and Chief Legal Officer; (iii) a material reduction in the
overall level of employee compensation, benefits or perquisites available to
Employee or Employee's right to participate therein, unless such reduction is
nondiscriminatory as to Employee; or (iv) the Company's requiring Employee to be
based anywhere more than fifty (50) miles from its current business location. No
event shall constitute "Good Reason" unless the Employee shall have notified the
Company of the conduct allegedly constituting "Good Reason" and the Company
shall have failed to correct such conduct within thirty days of the date of its
receipt of such notice. The appointment of a non-executive Chairman of the Board
of Directors shall not constitute "Good Reason" under this Agreement.

      7. No Conflict of Interest. During the term of Employee's employment with
Company, Employee must not engage in any work, paid or unpaid, that creates an
actual or potential conflict of interest with Company. Such work shall include,
but is not limited to, directly or indirectly competing with Company in any way,
or acting as an officer, director, employee, consultant, stockholder, volunteer,
lender, or agent of any business enterprise of the same nature as, or which is
in direct competition with, the business in which Company is now engaged or in
which Company becomes engaged during the term of Employee's employment with
Company, as may be determined by the Board in its sole discretion.

      8. Proprietary Information. Employee agrees to sign, and abide by the
Company's Proprietary Information and Invention Agreement, which is provided
with this Agreement and incorporated herein by reference.

      9. Post-Termination Non-Competition.

            9.1 Consideration For Promise To Refrain From Competing. Employee
agrees that Employee's services are special and unique, that the Company's
disclosure of confidential, proprietary information and specialized training and
knowledge to Employee, and that Employee's compensation and benefits and
severance, as applicable, are partly in consideration of and conditioned upon
Employee not competing with the Company. Employee

                                       4
<PAGE>

acknowledges that such consideration for Employee's services under this
Agreement is adequate consideration for Employee's promises contained within
this Section 9.

            9.2 Promise To Refrain From Competing. In exchange for the
consideration described in subsection 9.1 above, Employee agrees that for the
period of one (1) year following the date Employee ceases to render services to
the Company, Employee will not either directly or indirectly, whether as a
owner, director, officer, manager, consultant, agent or employee: (i) work for a
competitor, which is defined to include any company directly or indirectly
engaged, or known to Employee to be preparing to engage, in the development of
over-the-counter products, prescription drugs or nutraceutrical products
employing extended release formulations, or engaged in any business that is
directly competitive with any business the Company is engaged, or is known to
Employee to be preparing to engage, at the time the Employee's employment with
the Company terminates ("Restricted Business"); or (ii) make or hold any
investment in any Restricted Business, whether such investment be by way of
loan, purchase of stock or otherwise, provided that there shall be excluded from
the foregoing the ownership of not more than 1% of the listed or traded stock of
any publicly held corporation. For purposes of this section 9, the term "the
Company" shall mean and include the Company, any subsidiary or affiliate of the
Company, any successor to the business of the Company (by merger, consolidation,
sale of assets or stock or otherwise) and any other corporation or entity of
which Employee may serve as a director, officer or employee at the request of
the Company or any successor of the Company.

            9.3 Reasonableness of Restrictions. Employee represents and agrees
that the restrictions on competition, as to time, geographic area, and scope of
activity, required by this section 9 are reasonable, do not impose a greater
restraint than is necessary to protect the goodwill and business interests of
the Company, and are not unduly burdensome to Employee. Employee expressly
acknowledges that the Company competes on a nationwide basis and that the
geographical scope of these limitations is reasonable and necessary for the
protection of the Company's trade secrets and other confidential and proprietary
information.

            9.4 Reformation if Necessary. In the event a court of competent
jurisdiction determines that the geographic area, duration, or scope of activity
of any restriction under this section 9 and its subsections is unenforceable,
the restrictions under this section and its subsections shall not be terminated
but shall be reformed and modified to the extent required to render them valid
and enforceable.

      10. Non-Solicitation. Employee agrees that during the term of this
Agreement and for a period of one (1) year after the termination of this
Agreement, Employee will not, either directly or indirectly, separately or in
association with others, interfere with, impair, disrupt or damage the Company's
business by soliciting, encouraging or recruiting any of the Company's employees
or causing others to solicit or encourage or recruit any of the Company's
employees to discontinue their employment with the Company.

      11. Nondisparagement. Upon termination of Employee's employment
relationship hereunder, the Company and Employee agree that, unless otherwise
legally required to do so, they will each at all times thereafter refrain from
discussing the circumstances relating to such termination and from disparaging,
or describing in a derogatory light, the performance,

                                       5
<PAGE>

capabilities, services, business practices, or ethics of the other (or of the
officers, directors or controlling shareholders of the other). This provision
does not apply to statements made by Employee to Employee's immediate family or
attorneys, or to statements made by either party in legal proceedings in
conjunction with legal actions to pursue rights and/or remedies under this
Agreement.

      12. Right To Injunction/Costs Of Enforcement. Employee acknowledges that
the Company will suffer immediate and irreparable harm that will not be
compensable by damages alone in the event Employee repudiates or breaches
Section 7, 8, 9, 10 or 11 or threatens or attempts to do so. In the event of any
such breach or any threatened or attempted breach, Employee agrees that the
Company, in addition to and not in limitation of any other rights, remedies or
damages available to it at law or in equity, shall be entitled to obtain
temporary, preliminary and permanent injunctions to prevent or restrain any such
breach, and the Company shall not be required to post a bond as a condition for
the granting of such relief.

      13. Agreement to Arbitrate. To the fullest extent permitted by law,
Employee and Company agree to arbitrate any controversy, claim or dispute
between them arising out of or in any way related to this Agreement, the
employment relationship between Company and Employee and any disputes upon
termination of employment. Claims for workers' compensation, unemployment
insurance benefits and Company's right to obtain injunctive relief pursuant to
Section 13 above are excluded. The arbitration will be conducted in Seattle,
Washington by a single neutral arbitrator and in accordance with the then
current rules for resolution of employment disputes of the American Arbitration
Association ("AAA"). The parties are entitled to representation by an attorney
or other representative of their choosing. The arbitrator shall have the power
to enter any award that could be entered by a judge of the trial court of the
State of Washington, and only such power, and shall follow the law. In the event
the arbitrator does not follow the law, the arbitrator will have exceeded the
scope of his or her authority and the parties may, at their option, file a
motion to vacate the award in court. The parties agree to abide by and perform
any award rendered by the arbitrator. Judgment on the award may be entered in
any court having jurisdiction thereof. Each party shall bear one half the cost
of the arbitration filing and hearing fees, and the cost of the arbitrator.

      14. General Provisions.

            14.1 Assignment. The rights and obligations of the Company under
this Agreement shall inure to the benefit of, and be binding upon, the
successors and assigns of the Company. Employee shall not be entitled to assign
any of Employee's rights or obligations under this Agreement.

            14.2 Waiver. Either party's failure to enforce any provision of this
Agreement shall not in any way be construed as a waiver of any such provision,
or prevent that party thereafter from enforcing each and every other provision
of this Agreement.

            14.3 Severability. In the event any provision of this Agreement is
found to be unenforceable by an arbitrator or court of competent jurisdiction,
such provision shall be deemed modified to the extent necessary to allow
enforceability of the provision as so limited, it being intended that the
parties shall receive the benefit contemplated herein to the fullest extent

                                       6
<PAGE>

permitted by law. If a deemed modification is not satisfactory in the judgment
of such arbitrator or court, the unenforceable provision shall be deemed
deleted, and the validity and enforceability of the remaining provisions shall
not be affected thereby.

            14.4 Interpretation; Construction. The headings set forth in this
Agreement are for convenience only and shall not be used in interpreting this
Agreement. Legal counsel representing Company has drafted this Agreement and
Employee has been represented by independent counsel. Therefore, the normal rule
of construction to the effect that any ambiguities are to be resolved against
the drafting party shall not be employed in the interpretation of this
Agreement.

            14.5 Governing Law. This Agreement will be governed by and construed
in accordance with the laws of the United States and the State of Washington.
Each party consents to the jurisdiction and venue of the state or federal courts
in Seattle, Washington, if applicable, in any action, suit, or proceeding
arising out of or relating to this Agreement.

            14.6 Attorneys' Fees. The prevailing party in any action to enforce
its rights under this Agreement shall be entitled to recover from the other
party its reasonable attorneys' fees and costs, including any costs incurred on
appeal.

            14.7 Notices. Any notice required or permitted by this Agreement
shall be in writing and shall be delivered as follows with notice deemed given
as indicated: (a) by personal delivery when delivered personally; (b) by
overnight courier upon written verification of receipt; (c) by telecopy or
facsimile transmission upon acknowledgment of receipt of electronic
transmission; or (d) five (5) days following deposit in the U.S. Mail, certified
or registered mail, postage prepaid and return receipt requested. Notice shall
be sent to the addresses set forth below, or such other address as either party
may specify in writing.

      IF TO THE COMPANY, TO:        SCOLR Pharma, Inc.
                                    3625 132nd Avenue NE
                                    Bellevue, WA 98006

      IF TO EMPLOYEE, TO:           Alan M. Mitchel
                                    6839 West Mercer Way
                                    Mercer Island, WA 98040

            14.8 Survival. Sections 7 ("No Conflict of Interest"), 8
("Confidentiality and Proprietary Information"), 9 ("Post-Termination
Non-Competition"), 10 ("Nonsolicitation"), 11 ("Nondisparagement"), 14 ("General
Provisions") and 15 ("Entire Agreement") of this Agreement shall survive
Employee's employment by Company.

      15. Entire Agreement. This Agreement, including the Employee's Proprietary
Information and Invention Agreement incorporated herein by reference and the
Plan and related option documents described in Subsection 2.3, constitutes the
entire agreement between the parties relating to this subject matter and
supersedes all prior or simultaneous representations, discussions, negotiations,
and agreements, whether written or oral. This Agreement may be

                                       7
<PAGE>

amended or modified only with the written consent of Employee and the Board. No
oral waiver, amendment or modification will be effective under any circumstances
whatsoever.

      16. This Agreement may be executed via facsimile and in one or more
counterparts, each of which shall be deemed an original, but all of which
together constitute one and the same instrument, binding on the parties.

THE PARTIES TO THIS AGREEMENT HAVE READ THIS AGREEMENT, AND FULLY UNDERSTAND
EACH AND EVERY PROVISION. WHEREFORE, THE PARTIES HAVE EXECUTED AND MADE THIS
AGREEMENT EFFECTIVE AS OF THE DATE SET FORTH ABOVE.

"The Company"

                               SCOLR Pharma, Inc.

                               By /s/
                                  ----------------------------------------------
                                  Daniel O. Wilds, President and Chief Executive
                                  Officer

"Employee"                     /s/
                               -------------------------------------------------
                               Alan M. Mitchel

                                       8

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