Research, Development and License Agreement [Amendment No. 2] - American Home Products Corp. and Ligand Pharmaceuticals Inc.
SECOND AMENDMENT TO AGREEMENT
This Second Amendment to Agreement, effective May 24, 1996, is by and
between AMERICAN HOME PRODUCTS CORPORATION ("AHP"), a Delaware corporation, as
represented by its Wyeth-Ayerst Research Division, having its principal place of
business at 533 East Lancaster Pike, St. Davids, Pennsylvania and LIGAND
PHARMACEUTICALS INCORPORATED ("Ligand"), a Delaware corporation having its
principal place of business at 9393 Towne Center Drive, San Diego, California.
WHEREAS, AHP and Ligand have previously entered into a Research,
Development and License Agreement effective September 2, 1994 (the "Agreement")
under which AHP sponsors research at Ligand with the goal of discovering and/or
designing small molecule compounds which act through the estrogen and
progesterone receptors and to develop pharmaceutical products from such
compounds;
WHEREAS, AHP and Ligand have previously amended the Agreement by a first
Amendment (the "First Amendment") effective January 16, 1996, in order to give
effect to mutually agreed upon modifications to the definition of Exhibit
Compounds and to the nature, terms and conditions of the provisions of Article 7
of the Agreement;
WHEREAS, concurrently with the execution of the Agreement, on even date the
parties executed an Option Agreement by which Ligand granted AHP the irrevocable
option (the "Option"), exercisable on or after January 1, 1996, to extend
research at Ligand to include within the Field (as defined in the Agreement) the
discovery, development and commercialization of drugs for the treatment of
osteoporosis which are ligands of the estrogen receptor, which Option
<PAGE>
AHP exercised by a writing on February 12, 1996, accompanied by the payment to
Ligand of the sum of $*** as per Article 3 of the Option Agreement;
WHEREAS, prior to AHP's exercise of the aforementioned Option, AHP
discovered within its own internal research programs series of chemical
compounds (the "AHP Compounds") active at the *** and having potential utility
in the treatment of *** , which compounds have never been subject to screening
by Ligand within the framework of the Research Program of the Agreement and all
of which series undergoing active development at AHP are described in Schedule B
hereto;
WHEREAS, in order to create a broad chemical base of Research Compounds (as
defined in the Agreement) from which can be selected those compounds most
suitable for further evaluation and development, whether such Research Compounds
are *** *** AHP and Ligand have mutually agreed to integrate the AHP Compounds
into the Research Program, whereby the AHP Compounds are deemed to be Research
Compounds suitable for further evaluation and selection for preclinical testing;
WHEREAS, AHP and Ligand wish to make a second amendment of the Agreement to
give effect to the mutually agreed upon integration of the AHP Compounds into
the Research Program;
NOW, THEREFORE, in consideration of the foregoing and of the mutual
covenants hereinafter set forth, it is agreed by AHP and Ligand as follows:
1. Terms not otherwise defined herein shall have the meanings given them in
the Agreement.
2. Present Article 1 of the Agreement is hereby modified by the inclusion
of a new definition for "AHP Compounds":
*** Portions of this page have been omitted pursuant to a request for
Confidential Treatment and filed separately with the Commission.
Page 2 of 7
<PAGE>
1.27. "AHP Compounds" shall mean those compounds which AHP has identified
to be *** possessing potential utility in the treatment of *** and other uses
within the Field, and which are specifically defined in Schedule B, which is
attached to this Second Amendment and is deemed to be an integral part of the
Agreement. This definition shall also mean the analogues, whether or not
patented and whether or not within the scope of the definition of Schedule B,
related to the compounds defined in Schedule B synthesized by Ligand and/or AHP
subsequent to the effective date of this Second Agreement, provided, however,
that the analogues synthesized by Ligand i) before the effective date of this
Second Amendment or ii) after the effective date by Ligand, provided that such
synthesis be demonstrably (by Ligand) done by persons not having knowledge of
the Schedule B compounds or related analogues shall not be AHP Compounds under
the Agreement.
3. Present Section 1.20 is hereby modified to read as follows:
1.20. "Research Compound" shall mean an AHP Compound, or a compound,
including an Existing Compound for which AHP acquires rights under Article 7 of
this Agreement, which is identified and confirmed as acting through or mediating
the activity of a Designated Receptor (a) during the terms of the Research
Program, or (b), except in the case of termination by AHP under 16.3 below, by
AHP, within *** after expiration or earlier termination of the Research Program.
4. The parties agree that AHP Compounds shall be deemed to be Research
Compounds in the Research Program which are suitable for further evaluation and
preclinical testing, and subject to the Development Program as defined in
Article 5 of the Agreement.
*** Portions of this page have been omitted pursuant to a request for
Confidential Treatment and filed separately with the Commission.
Page 3 of 7
<PAGE>
5. The parties further agree that AHP Compounds which AHP elects to develop
shall be subject to the payment of milestones and royalties specifically
provided therefor in Article 9, as hereinafter modified.
6. AHP retains all rights to applications of AHP Compounds within and
outside the Field, and Ligand shall have no right to develop AHP Compounds
outside the Field. Accordingly, AHP Compounds are not subject to Ligand rights
as defined in Article 6 of the Agreement, nor to Ligand rights as defined in
Article 8 of the Agreement.
7. In recognition of the expansion of the chemical base of Research
Compounds by the integrating of AHP Compounds into the Research and Development
Programs, the parties have agreed to provide for a separate category of
milestone and royalty payments in Article 9 of the Agreement to specifically
relate to Research Compounds or Products which are AHP Compounds. Accordingly,
Section 9.1 is modified by the inclusion therein of a third milestone category,
denominated AHP Compounds, with the following payment schedule:
*** ***
*** ***
*** ***
*** ***
***
***
***
*** ***
*** ***
*** ***
*** ***
*** ***
Likewise, Section 9.2 is modified by the inclusion therein of a third royalty
category, denominated AHP Compounds, with the following royalty schedule:
*** Portions of this page have been omitted pursuant to a request for
Confidential Treatment and filed separately with the Commission.
Page 4 of 7
<PAGE>
***
***
***
8. Except as expressly amended or supplemental by this Second Amendment to
the Agreement, all of the terms and conditions of the Agreement and the First
Amendment shall remain in full force and effect in accordance with their terms.
No agreement or understanding bearing on this Second Amendment to Agreement
shall be binding on either party hereto unless it shall be in writing and signed
by the duly authorized officer or representative or each of AHP and Ligand and
shall expressly refer to this Second Amendment to Agreement.
IN WITNESS WHEREOF, the parties have caused the Amendment to be executed by
their duly authorized representatives.
AMERICAN HOME PRODUCTS CORPORATION LIGAND PHARMACEUTICALS INCORPORATED
By: /s/ illegible By: /s/ David E. Robinson
------------------------------ -----------------------------------
(Signature) (Signature)
Title: Vice President Title: President/CEO
--------------------------- ------------------------
*** Portions of this page have been omitted pursuant to a request for
Confidential Treatment and filed separately with the Commission.
Page 5 of 7
<PAGE>
SCHEDULE B
AHP Compounds are compounds defined by the following structural
formulae:
I
***
***
***
*** Portions of this page have been omitted pursuant to a request for
Confidential Treatment and filed separately with the Commission.
Page 6 of 7
<PAGE>
***
***
***
*** Portions of this page have been omitted pursuant to a request for
Confidential Treatment and filed separately with the Commission.
Page 7 of 7