Document:

<PAGE>
                                                                  EXHIBIT 10.287

CERTAIN MATERIAL (INDICATED BY AN ASTERISK) HAS BEEN OMITTED FROM THIS DOCUMENT
PURSUANT TO A REQUEST FOR CONFIDENTIAL TREATMENT. THE OMITTED MATERIAL HAS BEEN
FILED SEPARATELY WITH THE SECURITIES AND EXCHANGE COMMISSION.

                              AMENDED AND RESTATED

                   RESEARCH, DEVELOPMENT AND LICENSE AGREEMENT

                                 by and between

            WYETH, acting through its Wyeth Pharmaceuticals division

                                       and

                       LIGAND PHARMACEUTICALS INCORPORATED

                                      dated

                                DECEMBER 1, 2005
<PAGE>
                                TABLE OF CONTENTS
                                -----------------

<TABLE>
<S>                                                                                                     <C>
ARTICLE 1  -    DEFINITIONS............................................................................  3

ARTICLE 2  -    REPRESENTATIONS AND WARRANTIES........................................................  11

ARTICLE 3  -    RESEARCH PROGRAM .....................................................................  12

ARTICLE 4  -    OMITTED ..............................................................................  13

ARTICLE 5  -    DEVELOPMENT PROGRAM ..................................................................  13

ARTICLE 6  -    LICENSES -- RESEARCH, DEVELOPMENT,
                MARKETING AND MANUFACTURING ..........................................................  15

ARTICLE 7  -    WYETH OPTION TO COVERED COMPOUNDS.....................................................  18

ARTICLE 8  -    LIGAND SCREENING RIGHTS AND OBLIGATIONS...............................................  19

ARTICLE 9  -    ROYALTIES AND OTHER PAYMENTS..........................................................  19

ARTICLE 10 -    ROYALTY REPORTS AND ACCOUNTING........................................................  20

ARTICLE 11 -    PAYMENTS..............................................................................  22

ARTICLE 12 -    INFRINGEMENT ACTIONS BY THIRD PARTIES ................................................  23

ARTICLE 13 -    CONFIDENTIALITY.......................................................................  23

ARTICLE 14 -    PUBLICATION ..........................................................................  25

ARTICLE 15 -    PATENTS ..............................................................................  25

ARTICLE 16 -    TERM AND TERMINATION .................................................................  30

ARTICLE 17 -    PREMARIN(R) EVALUATION................................................................  31

ARTICLE 18 -    INDEMNITY ............................................................................  31

ARTICLE 19 -    FORCE MAJEURE.........................................................................  33

ARTICLE 20 -    ASSIGNMENT............................................................................  33

ARTICLE 21 -    NOTIFICATION OF PATENT TERM RESTORATION...............................................  34

ARTICLE 22 -    SEVERABILITY..........................................................................  34

ARTICLE 23 -    MISCELLANEOUS ........................................................................  34

SIGNATURES............................................................................................  36

SCHEDULE A............................................................................................  37

SCHEDULE B............................................................................................  38

Attachment 1.2........................................................................................  40
</TABLE>

                                  CONFIDENTIAL

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<TABLE>
<S>                                                                                                     <C>
Attachment 1.12.......................................................................................  46

Attachment 1.16.......................................................................................  47

Attachment 1.19.......................................................................................  50

Attachment 1.23.......................................................................................  71

Attachment 1.34.......................................................................................  77

Attachment 1.37.......................................................................................  90

Schedule 2............................................................................................  97

Attachment 1.53.......................................................................................  98

Schedule 3............................................................................................  99
</TABLE>

                                  CONFIDENTIAL

                                       2
<PAGE>
        AMENDED AND RESTATED RESEARCH, DEVELOPMENT AND LICENSE AGREEMENT

                  THIS AMENDED AND RESTATED AGREEMENT, effective the first day
of December, 2005 (the "Effective Date") is by and between Wyeth, (formerly
American Home Products Corporation) acting through its Wyeth Pharmaceuticals
Division ("WYETH"), a Delaware corporation, having its principal place of
business at 500 Arcola Road, Collegeville, Pennsylvania, and LIGAND
PHARMACEUTICALS INCORPORATED ("Ligand")(each a "Party", and collectively the
"Parties"), a Delaware corporation, having its principal place of business at
10275 Science Center Drive, San Diego, California.

                                R E C I T A L S

                  WHEREAS, Ligand has developed expertise and acquired
proprietary rights relating to the discovery and development of pharmaceutical
products which act through estrogen and progesterone receptors;

                  WHEREAS, WYETH has expertise in the discovery, development,
marketing and sales of pharmaceutical products;

                  WHEREAS, WYETH and Ligand entered into that certain Research,
Development and License Agreement effective September 2, 1994 as amended January
16, 1996, May 24, 1996, September 2, 1997 and September 9, 1999 (collectively
the "Agreement") pursuant to which Wyeth and Ligand engaged in a joint research
and development effort to discover and/or design small molecule compounds which
act through the estrogen and progesterone receptors and to develop
pharmaceutical products from such compounds;

                  WHEREAS, in conjunction with such joint research and
development, WYETH sponsored certain research and development activities to be
carried out by Ligand and Ligand and WYETH desire that WYETH commercialize
products resulting from the joint research and development; and

                  WHEREAS the Parties wish to enter into an amended and restated
agreement (the "Amended and Restated Agreement") that restates and amends the
responsibilities and rights of the Parties as it relates to the Agreement.

                  NOW, THEREFORE, in consideration of the foregoing premises and
the mutual covenants herein contained, WYETH and Ligand agree as follows:

                                  CONFIDENTIAL

                                       3
<PAGE>
                                    ARTICLE 1

                                   DEFINITIONS

         For the purposes of this Amended and Restated Agreement, the terms
defined in this Article 1 shall have the respective meanings set forth below:

         1.1 "Affiliate" shall mean, with respect to a Party, any other business
entity which directly or indirectly controls, is controlled by, or is under
common control with, such Party. A business entity or Party shall be regarded as
in control of another business entity if it owns, or directly or indirectly
controls, at least fifty percent (50%) of the voting stock or other ownership
interest of the other business entity, or if it directly or indirectly possesses
the power to direct or cause the direction of the management and policies of the
other business entity by any means whatsoever.

         1.2 "Article 8 Compounds" shall mean those twenty-four Wyeth Library
Compounds, and any analogs thereof synthesized by Ligand or any third party
having knowledge of such compounds gained from Ligand, that were selected by
Ligand under Article 8.1 hereof as ligands for the receptors listed in Exhibit B
of the Agreement. A complete listing of the Article 8 Compounds is set forth in
attachment 1.2 hereto.

         1.3 "Combination Research Compound" shall mean a single formulation of
more than one pharmaceutically active ingredient, at least one of which is a
Research Compound. Two types of Combination Research Compounds are possible: a
Covered Compound Combination or a Wyeth Compound Combination. Any Combination
Research Compound that includes a Covered Compound is a Covered Compound
Combination. For the avoidance of doubt, a Combination Research Compound shall
not include a Research Compound packaged with another pharmaceutically active
ingredient and not included as part of a single formulation with such
pharmaceutically active ingredient.

         1.4 "Combination Research Compound Product" shall mean a Combination
Research Compound that is approved for marketing in a Major Market Country, and
would be either a Covered Compound Combination Product or a Wyeth Compound
Combination Product. For the avoidance of doubt, a Combination Research Compound
Product shall not include a Research Compound packaged with another
pharmaceutically active ingredient and not included as part of a single
formulation with such pharmaceutically active ingredient.

                                  CONFIDENTIAL

                                       4
<PAGE>
         1.5 "Competing Product" shall mean, with respect to each specified
Research Compound or Product, any other Research Compound or Product or any
other Combination Research Compound or Combination Research Compound Product
which is in the same category, wherein the category is one of the following: (i)
PR modulators; (ii) ER modulators.

         1.6 "Commencement Date" shall mean September 1, 1994, which was the
date of commencement of the Research Program under the Agreement.

         1.7 "Covered Compound" shall mean ER Modulators, PR Modulators, Wyeth
PR Compounds, Final Wyeth PR Compounds, and Ligand PR Compounds. For the
avoidance of doubt, compounds that do not have both IC50 </= 100nM and in vitro
selectivity >/= 100X the nearest alternate target shall not be "Covered
Compounds". A complete list of Covered Compounds subject to the payment of
applicable milestones and royalties is set forth in Attachments 1.12, 1.23,
1.37, 1.16 and 1.19. Covered Compounds shall exclude Wyeth Compounds.

         1.8 "Covered Compound Combination" shall mean a single formulation of
more than one pharmaceutically active ingredient, at least one of which is a
Covered Compound. For the avoidance of doubt, Tanaproget (NSP-989)[***]
Combination is a Covered Compound Combination.

         1.9 "Designated Receptors" shall mean the estrogen receptor and the
progesterone receptor.

         1.10 "Discovery Board Recommendation" shall mean a recommendation by
the Wyeth Research Division of WYETH Discovery Executive Committee (DEC), or any
successor body, for advancement of a late stage discovery candidate Research
Compound to pre-development stage.

         1.11 "Development Track Approval" shall mean an approval by the Wyeth
Research Division of WYETH Development Council, or any successor body, for
advancement of a pre-development Research Compound to development track.

         1.12 "ER Modulators" shall mean compounds that were identified and
confirmed as modulating the ER receptor as part of the High Throughput Screening
(HTS) effort of the Wyeth Library Compounds or synthesized by WYETH during the
first three (3) years of the Research Program [September 1, 1994 - September 3,
1997].

                                  CONFIDENTIAL
                                        5
*** Certain information on this page has been omitted and filed separately with
the Commission. Confidential treatment has been requested with respect to the
omitted portions.
<PAGE>
For the avoidance of doubt, ER Modulators shall not include Wyeth Compounds. For
the avoidance of doubt, compounds that do not have both IC50 </= 100nM and in
vitro selectivity >/= 100X the nearest alternate target shall not be "ER
Modulators." A complete list of ER Modulators subject to the payment of
applicable milestones and royalties is set forth in Attachment 1.12 hereto.

         1.13 "Exploratory Development" shall mean development and testing,
beyond the Research Program, designed to document the pharmaceutical profile of
a Research Compound to demonstrate whether such Research Compound reasonably may
be expected to be useful in the Field.

         1.14 "FDA" shall mean the United States Food and Drug Administration or
any successor entity thereto.

         1.15 "Field" shall mean the discovery, development and
commercialization of drugs which are ligands (agonists and antagonists) to the
Designated Receptors for use in hormone replacement therapy, anti-cancer
therapy, gynecological diseases, contraception, the treatment of vasomotor
symptoms and CNS disorders associated with menopause and the treatment of
osteoporosis. As used herein, "treatment of osteoporosis" with respect to an
agonist of the estrogen receptor means prevention or treatment of diseases and
conditions involving bone resorption, bone formation, bone repair, bone growth
and calcium metabolism.

         1.16 "Final Wyeth PR Compounds" shall mean compounds of scaffold I,
that were synthesized by Wyeth and confirmed as modulating the PR receptor via
additional chemistry conducted at Wyeth after the term of the Research Program
as extended plus 18 months, but no later than the Effective Date of this Amended
and Restated Agreement (March 4, 2000 - the Effective Date of this Amended and
Restated Agreement):

                                      [***]

                                  CONFIDENTIAL
                                        6
*** Certain information on this page has been omitted and filed separately with
the Commission. Confidential treatment has been requested with respect to the
omitted portions.
<PAGE>
                                      [***]

For purposes of clarity, Final Wyeth PR Compounds shall not be subject to the
provisions of Sections 6.4.1 or 6.4.2 hereof. For the avoidance of doubt,
compounds that do not have both IC50 </= 100nM and in vitro selectivity >/= 100X
the nearest alternate target shall not be "Final Wyeth PR Compounds."
A complete list of Final Wyeth PR Compounds subject to the payment of applicable
milestones and royalties is set forth in Attachment 1.16 hereto.

         1.17 "First Commercial Sale" shall mean, with respect to a Product, the
first sale to an unrelated third party of such Product in a country after any
required marketing and pricing approval has been granted by the governing health
authority of such country.

         1.18 "Full Development" shall mean development and testing of a
Research Compound, or a Product incorporating such Research Compound, beyond
Exploratory Development, designed to obtain approval by the appropriate
regulatory authorities to market such Research Compound or Product.

         1.19 "Ligand PR Compounds" shall mean compounds that were synthesized
by Ligand and confirmed as modulating the PR receptor during the term of the
Research Program as extended [September 1, 1994 to September 2, 1998]. A
complete listing of Ligand PR Compounds is set forth in Attachment 1.19 hereto.

         1.20 "Major Market Country" shall mean any of the United States, Japan,
France, Italy, Germany, and the United Kingdom.

         1.21 "Net Sales" shall mean:

               A.   With respect to a Product containing a Research Compound as
                    its sole pharmaceutically active ingredient, the gross
                    invoiced sales of such Product by a Party, its Affiliates
                    and/or its sublicensees to unrelated third parties less the
                    following deductions:

                                  CONFIDENTIAL
                                        7
*** Certain information on this page has been omitted and filed separately with
the Commission. Confidential treatment has been requested with respect to the
omitted portions.
<PAGE>

                    i.   discounts, credits, rebates, allowances, adjustments,
                         rejections, recalls and returns;

                    ii.  price reductions, retroactive or otherwise, imposed by
                         government authorities;

                    iii. sales, excise, turnover, inventory, value-added and
                         similar taxes; and

                    iv.  transportation, importation, insurance and other
                         handling expenses directly chargeable to such sales.

                         For the avoidance of doubt, if a Product contains a
                         Research Compound which is packaged with another
                         pharmaceutically active ingredient, but the Product is
                         not a single formulation, Net Sales for such Product
                         shall be determined under this subparagraph (A) and not
                         under subparagraph (B) below.

               B.   (i)   In the event that a Combination Research Compound
                          Product is sold in a country, Net Sales for such
                          Combination Research Compound Product will be
                          reduced by multiplying Net Sales of such
                          Combination Research Compound Product by the
                          fraction A/ (A+B) where A is the current wholesale
                          selling price of the Research Compound if sold
                          separately in the country, and B is the current
                          wholesale selling price of all other
                          pharmaceutically active components in the
                          combination, if sold separately in the country.

                    (ii)  If the other pharmaceutically active component or
                          components in the Combination Research Compound
                          Product are not sold separately in the country,
                          Net Sales for the purpose of determining royalties
                          on the Combination Research Compound Product will
                          be reduced by multiplying Net Sales of such
                          Combination Research Compound Product by the
                          fraction A/C where A is the current wholesale
                          selling price of the Research Compound if sold
                          separately in the country and C is the current
                          wholesale selling price of the combination
                          product.

                                  CONFIDENTIAL
                                        8
<PAGE>
                    (iii) If on a country-by-country basis neither the
                          Research Compound nor the other pharmaceutically
                          active component in the Combination Research
                          Compound Product is sold separately in said
                          country, Net Sales for purposes of determining
                          royalties on the Combination Research Compound
                          Product will be reduced by the fraction D/E where
                          D is the standard factory cost of the Research
                          Compound and E is the standard factory cost of all
                          other pharmaceutically active components,
                          including the Research Compound, in the
                          Combination Research Compound Product.

                    (iv)  The fractions used in any of (i) - (iii) may not be
                          less than 0.75 if none of the other pharmaceutically
                          active components is patented or less than 0.5 if one
                          or more other pharmaceutically active components is
                          patented.

         1.22 "Patent Rights" shall mean (a) all patent applications heretofore
or hereafter filed in any country within the Territory owned by or licensed to
Ligand or WYETH, or to which Ligand or WYETH otherwise acquires rights, having
claims which read upon a Product or a Research Compound or the process of
manufacture or use of a Product or a Research Compound, together with any and
all patents that have issued or in the future issue therefrom and (b) all
divisionals, continuations, continuations-in-part, reexaminations, reissues,
renewals, extensions or additions to any such patents and patent applications
and patents issuing thereon; all to the extent and only to the extent that (i)
Ligand or WYETH now has or hereafter will have the right to grant licenses or
other rights thereunder and (ii) the granting of such licenses or rights
thereunder is necessary for either Party to practice the rights and discharge
the obligations it has by reason of this Amended and Restated Agreement.

     1.23 "PR Modulators" shall mean compounds (other than Ligand PR Compounds)
that were identified and confirmed as modulating the PR receptor as part of the
HTS effort of the Wyeth Library Compounds or synthesized by Wyeth during the
first three (3) years of the Research Program [September 1, 1994 - September 3,
1997]. For the avoidance of doubt, PR Modulators shall not include Wyeth
Compounds. For the avoidance of doubt, compounds that do not have both
IC50 </= 100nM and in vitro selectivity >/= 100X the nearest alternate target
shall not be "PR Modulators". A complete list of

                                  CONFIDENTIAL
                                        9
<PAGE>
PR Modulators subject to the payment of applicable milestones and royalties is
set forth in Attachment 1.23 hereto.

         1.24 "Primary Screening" shall mean conducting any assay, screen or
other test on a compound under the Research Program to determine initially
whether such compound functions as an agonist or antagonist of activity mediated
through a Designated Receptor.

         1.25 "Product" shall mean a Research Compound that has been approved
for marketing in a Major Market Country. "Product" shall include Combination
Research Compound Products.

         1.26 "Research Compound" shall mean a Covered Compound or a Wyeth
Compound.

For purposes of clarity, [***]shall be considered to be "Research Compounds" for
all purposes under this Agreement.

For the avoidance of doubt, any compounds confirmed as modulating the ER
Receptor or the PR Receptor synthesized or obtained by Wyeth or Ligand within
the Field after the Effective Date of this Amended and Restated Agreement shall
fall outside this Amended and Restated Agreement, shall not be considered to be
Research Compounds and are not subject to any milestone or royalty payments to
the other party. For the further avoidance of doubt, "Research Compounds" and
all its subsidiary compound definitions each excludes any Series B or Series C
compounds as defined in Schedule A attached hereto. Wyeth shall have no rights
to such Series B or Series C compounds.

The Parties agree that Premarin(R) and its components, reference standards,
comparators, or other known progestins or estrogens shall not be considered to
be Research Compounds, provided that this requirement shall not prevent a
compound from being a Research Compound if it is listed on one of the Covered
Compound or Wyeth Compound attachments (i.e., Attachments 1.12, 1.23, 1.37,
1.16, 1.19 and 1.34).

         1.27 "Research Program" shall mean the three (3) year program of
research and testing in which Ligand and WYETH participated and which is
described generally in the research work plan set forth in Exhibit A of the
Agreement, as revised from time to time as provided in the Agreement, and any
extension thereof pursuant to exercise by WYETH of its option under Section 3.3
or by mutual agreement of the Parties.

                                  CONFIDENTIAL
                                       10
 *** Certain information on this page has been omitted and filed separately with
the Commission. Confidential treatment has been requested with respect to the
omitted portions.
<PAGE>
         1.28 "Research Program Term" shall mean the three (3) year period of
the Research Program measured from the Commencement Date and any extensions
thereof. For the avoidance of doubt, the Research Program Term, including the
extension, was September 1, 1994 to September 2, 1998.

         1.29 "Royalty Term" shall mean, with respect to each Product in each
country, the period of time equal to the longer of (a) ten (10) years from the
date of the First Commercial Sale of a Product in such country or (b) if the use
or sale of a Product in such country falls within the scope of a valid claim
within the Patent Rights covering the Product or the Research Compound therein
per se or a use of the Product (provided that the application for the patent on
use of the Product or Research Compound therein is based on an invention of a
utility in a research and/or development effort arising from or initiated as a
result of Primary and/or Secondary Screening done under the Research Program
which invention is made on or before the fifth (5th) anniversary of the
expiration or termination of the Research Program) the expiration of the last to
expire applicable patent in such country. As used herein, a "valid" claim is a
claim in a pending application or a claim in an unexpired patent which has not
been held to be invalid in a judgment from which no appeal is or can be taken.
The provisions of this Section shall apply to payment of royalties by both
Parties.

         1.30 "Secondary Screening" shall mean conducting any assay, screen or
other test using intracellular receptors or other in vitro cell systems or
reagents involved in other signal transduction pathways on a Research Compound
after the Primary Screening of such Research Compound for the purpose of
confirming the results of the Primary Screening or to test the Research Compound
for cross-reactivity with other than the Designated Receptors.

         1.31 "Series A, B and C Compounds" shall mean the compounds as defined
in Exhibit A attached hereto.

         1.32 "Territory" shall mean the entire world.

         1.33 "WYETH" shall, for the purposes of this Amended and Restated
Agreement, not include Genetics Institute.

         1.34 "WYETH Compounds" shall mean compounds which WYETH has identified
to be ligands of the estrogen receptor possessing potential utility in the
treatment of osteoporosis and other uses within the Field, and which are
specifically defined in Schedule B,

                                  CONFIDENTIAL
                                       11
<PAGE>
which is attached to this Agreement. For the avoidance of doubt, compounds that
do not have both IC50 </= 100nM and in vitro selectivity >/= 100X the nearest
alternate target shall not be "Wyeth Compounds." A complete list of Wyeth
Compounds subject to payment of applicable milestones and royalties is attached
hereto as Attachment 1.34. For the avoidance of doubt, Wyeth shall retain all
rights to applications of Wyeth Compounds within and outside the Field and
Ligand shall have no right to develop Wyeth Compounds outside the Field.
Accordingly, Wyeth Compounds are not subject to Ligand rights as defined in
Article 6 of this Amended and Restated Agreement nor to Ligand rights as defined
in Article 8 of this Amended and Restated Agreement. For the avoidance of doubt,
Wyeth Compounds include, but are not limited to TSE-424 (bazedoxifene) and
ERA-923 (pipendoxifene).

         1.35 "Wyeth Library Compounds" shall mean those compounds from the
Wyeth compound library (formerly the WARD compound library) that were provided
to Ligand and screened during the Research Program Term.

         1.36 "Wyeth Compound Combination" shall mean a single formulation of
more than one pharmaceutically active ingredient, at least one of which is a
Wyeth Compound. For the avoidance of doubt, WAY-140424 (TSE-424)/Conjugated
Estrogen (CE), also known as bazedoxifene/CE is a Wyeth Compound Combination.

         1.37 "Wyeth PR Compounds" shall mean compounds that were synthesized by
Wyeth and confirmed as modulating the PR receptor via additional chemistry
conducted by Wyeth after the first three years of the Research Program and
during the term of the Research Program extension, plus 18 months [September 4,
1997 to March 3, 2000]. For the avoidance of doubt, compounds that do not have
both IC50 </= 100nM and in vitro selectivity >/= 100X the nearest alternate
target shall not be "Wyeth PR Compounds." A complete list of Wyeth PR Compounds
subject to the payment of applicable milestones and royalties is set forth in
Attachment 1.37.

                                    ARTICLE 2

                         REPRESENTATIONS AND WARRANTIES

         Each Party hereby represents and warrants to the other Party as
follows:

         2.1 Corporate Existence and Power. Such Party (a) is a corporation duly
organized, validly existing and in good standing

                                  CONFIDENTIAL
                                       12
<PAGE>
under the laws of the state in which it is incorporated, (b) has the corporate
power and authority and the legal right to own and operate its property and
assets, to lease the property and assets it operates under lease, and to carry
on its business as it is now being conducted, and (c) is in compliance with all
requirements of applicable law, except to the extent that any noncompliance
would not have a material adverse effect on the properties, business, financial
or other condition of such Party and would not materially adversely affect such
Party's ability to perform its obligations under this Agreement.

         2.2 Authorization and Enforcement of Obligations. Such Party (a) has
the corporate power and authority and the legal right to enter into this Amended
and Restated Agreement and to perform its obligations hereunder, and (b) has
taken all necessary corporate action on its part to authorize the execution and
delivery of this Amended and Restated Agreement and the performance of its
obligations hereunder. This Amended and Restated Agreement has been duly
executed and delivered on behalf of such Party, and constitutes a legal, valid,
binding obligation, enforceable against such Party in accordance with its terms.

         2.3 Consents. All necessary consents, approvals and authorizations of
all governmental authorities and other persons required to be obtained by such
Party in connection with the execution, delivery and performance of this Amended
and Restated Agreement have been and shall be obtained.

         2.4 No Conflict. Notwithstanding anything to the contrary in this
Agreement, the execution and delivery of this Amended and Restated Agreement and
the performance of such Party's obligations hereunder (a) do not conflict with
or violate any requirement of applicable laws or regulations and (b) do not and
shall not conflict with, violate or breach or constitute a default or require
any consent under, any contractual obligation of such Party, including with
respect to Ligand, any obligations or duties arising under the Agreement of May
1, 1991 and the Supplementary Agreement of October 1, 1993 with Pfizer Inc and
any settlement of suit.

         2.5 Intellectual Property. Such Party (a) owns or is the licensee in
good standing of all Patent Rights, trade secrets and other intellectual
property to be used by it in connection with the Research Program, except to the
extent that such use is to be based upon patents, trademarks and other
intellectual property furnished by the other Party; (b) has received no notice
of infringement or misappropriation of any alleged rights asserted by any third
party in relation to any technology to be used by it in connection with

                                  CONFIDENTIAL
                                       13
<PAGE>
the Research Program; (c) is not in default with respect to any license
agreement related to the Research Program; and (d) is not aware of any patent,
trade secret or other right of any third party which could materially adversely
affect its ability to carry out its responsibilities under the Research Program
or the other Party's ability to exercise or exploit any license granted to it
under this Amended and Restated Agreement. Such Party agrees to immediately
notify the other Party in writing in the event such Party hereafter receives a
notice of the type referred to in (b) above, becomes in default under any
license agreement referred to in (c) above, or becomes aware of any patent,
trade secret or other right of the nature referred to in (d) above.

         2.6 Disclosure of Research Compounds. Such Party has fully disclosed to
the other Party all Research Compounds in its possession or known to it. For the
avoidance of doubt, the right to exploit any compounds that do not fall within
the definition of "Research Compound" under this Amended and Restated Agreement
is outside the scope of this Amended and Restated Agreement.

         2.7 DISCLAIMER OF WARRANTIES. NOTHING IN THIS AMENDED AND RESTATED
AGREEMENT SHALL BE CONSTRUED AS A REPRESENTATION MADE, OR WARRANTY GIVEN, BY
LIGAND OR WYETH (A) THAT ANY PATENT WILL ISSUE BASED UPON ANY PENDING PATENT
APPLICATION WITHIN THE PATENT RIGHTS, (B) THAT ANY PATENT WITHIN THE PATENT
RIGHTS WHICH ISSUES WILL BE VALID, OR (C) THAT, EXCEPT FOR THE PROVISIONS OF
SECTION 2.5 HEREIN WHICH SHALL NOT BE AFFECTED BY THIS SECTION 2.7, THE USE OF
ANY LICENSE GRANTED HEREUNDER OR THE USE OF ANY PATENT RIGHTS WILL NOT INFRINGE
THE PATENT OR PROPRIETARY RIGHTS OF ANY OTHER PERSON. FURTHERMORE, NEITHER
LIGAND NOR WYETH MAKES ANY REPRESENTATIONS OR WARRANTIES, EXPRESS OR IMPLIED,
WITH RESPECT TO THE PATENT RIGHTS EXCEPT AS PROVIDED IN SECTION 2.5.

                                    ARTICLE 3

                                RESEARCH PROGRAM

         3.1 Records.

             3.1.1 Records. Ligand and WYETH each shall maintain records, in
sufficient detail and in good scientific manner appropriate for patent purposes,
which shall be complete and accurate and shall fully and properly reflect all
work done and results achieved in the performance of the Research Program
(including all data in the form required under all applicable laws and
regulations). Such records shall include books, records, reports, research
notes, charts, graphs, comments, computations,

                                  CONFIDENTIAL
                                       14
<PAGE>
analyses, recordings, photographs, computer programs and documentation thereof,
computer information storage means, samples of materials and other graphic or
written data generated in connection with the Research Program including any
data required to be maintained pursuant to all requirements of applicable laws
and regulations.

             3.1.2 Inspection of Records. Ligand and WYETH each shall have the
right, during normal business hours and upon reasonable notice, to inspect and
copy all such records of the other Party to the extent reasonably required for
the performance of its obligations under this Amended and Restated Agreement
(with the Party owning the records determining what is reasonably required).
Each Party shall maintain such records and the information of the other Party
contained therein in confidence in accordance with Section 13.1 below and shall
not use such records or information except to the extent otherwise permitted by
this Amended and Restated Agreement.

         3.3 Ligand-in-Licensed Compounds. Ligand retains the right to
in-license from third parties and develop and commercialize on its own behalf
and through third parties, including Affiliates and sublicensees, compounds
which are agonists or antagonists of the Designed Receptors; provided, however,
that until expiration of the Research Program Term, such in-licensed compounds
are, if they act through the progesterone receptor, at least development stage
compounds, but including more advanced compounds up to and including compounds
approved for marketing. As used in this Section 3.3 a "development stage"
compound is a compound requiring only process and scale-up development and
preclinical toxicology and pharmacology investigation to complete IND
requirements.

                               ARTICLE 4 - OMITTED

                                    ARTICLE 5

                               DEVELOPMENT PROGRAM

         5.1 Exploratory Development. Ligand and/or WYETH from time to time
shall make recommendations of Research Compounds for Exploratory Development by
WYETH. WYETH shall have the right in its sole discretion, but without the
obligation, to select Research Compounds for Exploratory Development and shall
give prompt written notice to Ligand of each such selection. WYETH shall conduct
such Exploratory Development of each such selected Research Compound as WYETH
desires and shall inform Ligand of the progress and results thereof. WYETH, at
its sole expense, shall fund the costs of

                                  CONFIDENTIAL
                                       15
<PAGE>
Exploratory Development of any such selected Research Compound.

         5.2 Full Development. Ligand and/or WYETH from time to time shall make
recommendations of those Research Compounds that have completed Exploratory
Development for Full Development by WYETH. WYETH shall have the right in its
sole discretion, but without the obligation, to select Research Compounds for
Full Development and shall give prompt notice to Ligand of each such selection.
WYETH shall use its good faith efforts to conduct such preclinical and human
clinical trials as WYETH determines are necessary or desirable to obtain
regulatory approvals to manufacture and market such Products in the Territory as
WYETH desires and diligently to develop, seek necessary approval to market,
commence marketing and market such Products for such purpose in the Territory
subject to the last sentence of this Section 5.2. WYETH, at its sole expense,
shall fund the costs of Full Development of Research Compounds and Products.
Notwithstanding anything else in this Amended and Restated Agreement, but
subject to Ligand's rights under Section 6.4, WYETH shall have the sole
discretion to determine which Products to develop or market, or to continue to
develop or market, those for which regulatory approval to market will be sought,
and when and where and how and on what terms and conditions, to market such
Products in the Territory.

         5.3 Development Information. Each Party agrees to keep the other
informed of its activities under this Amended and Restated Agreement. WYETH
shall keep Ligand informed as to the progress of the Exploratory Development and
Full Development of all Research Compounds and Products under this Amended and
Restated Agreement and the filing and obtaining of the approvals necessary for
marketing. Within thirty (30) days after the end of each six (6) month period
following the commencement of Exploratory Development by WYETH of the first
Research Compound, WYETH shall provide to Ligand a reasonably detailed written
report which shall describe the progress of the Exploratory Development and/or
Full Development of Research Compounds and Products under this Amended and
Restated Agreement in the form of the template attached hereto as Attachment 5.3
for each Research Compound and Product. Such update would additionally include
the latest copy of an Investigational Drug Brochure (IDB) and any updated
versions thereof. Such update would additionally include a list of all Wyeth
solely owned Patent Rights, other than Patent Rights with claims which read upon
a Wyeth Compound Product or a Wyeth Compound or the process of manufacture or
use of a Wyeth Compound Product or Wyeth Compound. Additionally, Ligand would be
informed, in a timely fashion, of any serious adverse events that might occur
with a Research Compound or Product and, subject to the provisions of Article 14
hereof, of any

                                  CONFIDENTIAL
                                       16
<PAGE>
publications or presentations (including investor presentations) made that refer
to a Research Compound or Product. Notwithstanding the foregoing, Wyeth's
obligations under this Section 5.3 to provide the latest copy of an
Investigational Drug Brochure (IDB) and any updated versions thereof and the
list of all Wyeth solely owned Patent Rights as described above shall no longer
apply in the event of Ligand's transfer or sale of all or substantially all of
its business, or in the event of Ligand's merger or consolidation or change in
control or similar transaction. For the avoidance of doubt, in all events,
Wyeth's obligations to provide information and reports under this Section 5.3,
other than Wyeth's obligation to provide the latest copy of an Investigational
Drug Brochure (IDB) and any updated versions thereof and the list of all Wyeth
solely owned Patent Rights as described above, shall continue.

         5.4 Excused Performance. In addition to the provisions of Article 19
hereof, the obligations of WYETH with respect to any Product under this Amended
and Restated Agreement are expressly conditioned upon the continuing absence of
any adverse condition as determined solely by WYETH relating to the safety or
efficacy or commercial feasibility of that Product, and such obligations shall
be delayed or suspended so long as any such condition or event exists. If any
such delay or suspension with respect to any Product exceeds eighteen (18)
months in duration, such Product shall be subject to Ligand's rights under
Section 6.4 below in the circumstance where WYETH is not seeking to develop and
has not developed any Competing Product and where WYETH's conduct manifests
abandonment of further development or marketing of such Product within the
meaning of 6.4.3.

                                    ARTICLE 6

                       LICENSES -- RESEARCH, DEVELOPMENT,
                           MARKETING AND MANUFACTURING

         6.1 License Grant to WYETH. Subject to the provisions hereof, Ligand
hereby grants to WYETH and directly to its Affiliates an exclusive license,
which license shall be exclusive even as to Ligand, under Ligand's Patent Rights
and trade secrets with respect thereto throughout the Territory, including
Ligand's rights in any jointly owned Patent Rights, to make, have made, use and
sell Products in the Field but subject to Ligand's license granted in Section
6.2. Subject to the provisions of this Amended and Restated Agreement, WYETH may
grant sublicenses to any third party under the license granted by this Section
6.1. WYETH shall deliver a copy of each sublicense to Ligand promptly after
granting such sublicense. Each sublicense shall contain terms and conditions

                                  CONFIDENTIAL
                                       17
<PAGE>
substantially similar to this Amended and Restated Agreement, but no sublicense
shall relieve WYETH of any obligations under this Amended and Restated
Agreement. WYETH will guarantee the performance of any Affiliate or sublicensee
licensed pursuant to this Section 6.1.

         6.2 License Grant to Ligand. Subject to the provisions hereof, WYETH
hereby grants to Ligand and directly to its Affiliates an exclusive license,
which license shall be exclusive even as to WYETH, for Products and their use in
all fields under WYETH's Patent Rights and trade secrets with respect thereto
throughout the Territory, including WYETH's rights in any jointly owned Patent
Rights, which would be infringed but for such license, to make, have made, use
and sell Products. This license shall apply only to Products for which Ligand
acquires rights under Section 6.4.1. In the exercise of the license provided
under this Section 6.2, Ligand shall be required to pay a royalty of six percent
(6%) of the Net Sales thereof and to remit and report such royalties in the
manner required by Articles 9, 10 and 11 and report royalties to AHP in the same
manner as AHP under Articles 10 and 11. Subject to the provisions of this
Amended and Restated Agreement, Ligand may grant sublicenses under such license
to any third party. Ligand shall deliver a copy of each sublicense to WYETH
promptly after granting such sublicense. Each sublicense shall contain terms and
conditions substantially similar to this Amended and Restated Agreement, but no
sublicense shall relieve Ligand of any obligations under this Amended and
Restated Agreement. Ligand shall guarantee the performance of any Affiliate or
sublicensee licensed pursuant to this Section 6.2.

         6.3 Additional Applications of Compounds. Except as provided in this
section 6.3 and Section 7.2 hereof, this Agreement shall not constitute a
restriction on WYETH'S right to develop, make, have made, use and/or sell a
Research Compound or Product for use outside the Field. If at any time a
compound evaluated under the Research Program is determined to have activity
outside the Field, if WYETH so requests and except to the extent that to do so
would violate Ligand's obligation to third parties, Ligand will grant AHP an
exclusive license under the Patent Rights and its trade secrets relating thereto
to make, have made, use and sell the compound for the additional activity and
subject to the milestone payments of Section 9.1 and the royalties of Section
9.2.

             6.3.1 If WYETH so requests, and to the extent Ligand is legally and
contractually permitted to do so, Ligand shall also negotiate in good faith with
WYETH, but with no obligation to negotiate exclusively with WYETH, mutually
acceptable terms and

                                  CONFIDENTIAL
                                       18
<PAGE>
conditions under which Ligand would be willing to collaborate with WYETH
regarding the research, development and commercialization of applications of
Research Compounds or Products outside the Field.

         6.4  Other Ligand Rights.

             6.4.1. At any time after the date eighteen (18) months after the
expiration or earlier termination of the Research Program, Ligand shall have the
right in its sole discretion at its sole expense, for its own benefit or
together with an Affiliate or third party, to develop and commercialize in the
Territory and in the Field (a) those Covered Compounds other than Final Wyeth PR
Compounds which WYETH abandons or elects not to develop in the Field, and (b)
those Products (other than Combination Research Compound Products) based on
Covered Compounds other than Final Wyeth PR Compounds for which WYETH delays or
suspends the development or marketing for more than eighteen (18) months as
described in Section 5.4 above, in each case provided that WYETH, or any of its
Affiliates or sublicensees is not (i) diligently developing or commercializing
such Covered Compound for any other pharmaceutical purpose not in derogation of
Ligand's rights under Section 6.2 or (ii) not diligently conducting Exploratory
Development or Full Development with respect to, or diligently marketing, a
Competing Product.

             6.4.2 Additionally, at any time after the date eighteen (18) months
after the expiration or earlier termination of the Research Program, if WYETH
abandons or elects not to develop a Product containing a Covered Compound other
than a Final Wyeth PR Compound in any Major Market Country, Ligand shall have
the right in its sole discretion at its sole expense, for its own benefit or
together with an Affiliate or third party, to develop and commercialize such
Product in the Field but only in those Major Market Countries in which WYETH
abandons or elects not to develop such Product. Ligand's right to develop and
commercialize shall not come into effect if WYETH, an Affiliate or sublicensee
is diligently conducting Exploratory Development or Full Development of a
Competing Product in the affected Major Market Country or diligently marketing a
Competing Product in that country. For purposes of this Section 6.4.2, by way of
example but without limitation, WYETH shall not be deemed to have abandoned or
elected not to develop a Product in a country if (i) WYETH has received the
necessary regulatory approval to market such Product in the country in question,
and (ii) WYETH has not commenced or has ceased marketing such Product in the
country in question substantially due to adverse business or financial
conditions caused by the

                                  CONFIDENTIAL
                                       19
<PAGE>
regulatory authorities or other government authorities of such country which
would cause marketing such Product in such country by WYETH to be contrary to
the financial best interests of Ligand and WYETH (including not commencing
marketing in a Major Market Country where regulatory authorities or other
government authorities have price approval authority and the price approved or
proposed by the regulatory authorities or other government authorities is
unacceptable to WYETH); provided, however, that WYETH shall commence or resume
marketing such Product in such country as soon as reasonably practical after
such adverse business or financial conditions cease to exist. WYETH shall also
not be deemed to have abandoned or elected not to develop a Product in a country
(or countries) if WYETH has commenced Exploratory Development or Full
Development with respect to such Product in one or more of the Major Market
Countries and has a reasonable intention to commence Exploratory Development or
Full Development with respect to such Product in the remaining Major Market
Countries as soon as reasonably practicable.

             6.4.3 In order to determine whether WYETH has abandoned or elected
not to develop or commercialize a Covered Compound other than a Final Wyeth PR
Compound or Product containing a Covered Compound other than a Final Wyeth PR
Compound for purposes of Sections 5.4, 6.4.1 and 6.4.2 above, upon written
notice from Ligand, WYETH promptly shall inform Ligand in writing whether it has
abandoned or elected not to commercialize such Covered Compound or Product and,
if so requested, shall provide a reasonable explanation of its efforts to
develop or commercialize such Covered Compound or Product. If WYETH has
abandoned or elected not to develop or commercialize such Covered Compound or
Product, then WYETH additionally shall inform Ligand in writing whether it is
diligently conducting Exploratory Development or Full Development with respect
to, or diligently marketing, a Competing Product, and if so requested, shall
provide a reasonable explanation of its efforts with respect to such Competing
Product. If the Parties disagree on the status of any such Covered Compound or
Product for purposes of this Section 6.4, the Parties shall confer and in good
faith attempt to resolve the disagreement between themselves.

6.4.4 If Ligand exercises its rights under this Section 6.4 with respect to any
Covered Compound other than a Final Wyeth PR Compound owned by or licensed to
WYETH, subject to rights of third parties who are not Affiliates, WYETH (a)
shall grant to Ligand an exclusive license (with the exclusive right to
sublicense) in the Territory (or in the case of Section 6.4.2, in the countries
permitted under Section 6.4.2) to make, have made, use and sell Products in the
Field, (b) shall provide Ligand with

                                  CONFIDENTIAL
                                       20

<PAGE>

all such information and data which WYETH, its Affiliates or sublicensees
reasonably has available in such country, for example access to drug master
file, clinical and QA data and the like, and shall execute such instruments as
Ligand reasonably requests, to enable Ligand to obtain the appropriate
regulatory approvals to market such Products in such country and for any other
lawful purpose related to development and commercialization of such Products in
such country, and (c) thereafter shall have no further rights under this Amended
and Restated Agreement with respect to such Covered Compound or Product in the
Territory (or in the case of Section 6.4.2, in the countries permitted under
Section 6.4.2) except as expressly provided in this Amended and Restated
Agreement.

      6.4.5 If Ligand, its Affiliate or sublicensee is not diligently developing
or commercializing any such Covered Compound or Product licensed from WYETH
under Section 6.2 and this Section 6.4 eighteen (18) months after the effective
date of such license, then such license shall terminate, and all rights in and
to such Covered Compound or Product shall revert to WYETH subject to the
provisions of this Amended and Restated Agreement, except the provisions of
Section 6.2 and this Section 6.4. In determining Ligand diligence, Sections 5.4,
and 6.4.1-6.4.3 shall apply to Ligand mutatis mutandis.

      6.4.6 For the avoidance of doubt, the provisions of Section 6.2 and this
Section 6.4 shall not apply to Combination Research Compounds or Combination
Research Compound Products other than [***] but only to those Covered Compounds
other than Final Wyeth PR Compounds that are contained in such combination
Research Compounds or Combination Research Compound Products.

                                    ARTICLE 7
                        WYETH OPTION TO COVERED COMPOUNDS

      7.1 Compounds which meet the requirements of Section 1.26 shall be deemed
to be Research Compounds arising from the Development Program and subject to the
Development Program as defined in Article 5 of this Amended and Restated
Agreement and to the License provisions of Article 6.1 of this Amended and
Restated Agreement. Any Research Compounds which Wyeth elects to develop shall
be subject to the payment of milestones and royalties as provided in Article 9
in the Field and for permitted applications outside the Field for which
provision is made in this Article 7.

                                  CONFIDENTIAL
                                       21

*** Certain information on this page has been omitted and filed separately with
the Commission. Confidential treatment has been requested with respect to the
omitted portions.

<PAGE>

      7.2 Ligand retains all rights to applications of Covered Compounds outside
the Field and Wyeth shall have no right to develop Covered Compounds outside the
Field; provided, however, that Wyeth may develop, make, have made, use and sell
Covered Compounds for applications outside the Field which are (i) first
synthesized by Wyeth and (ii) which Covered Compounds are not covered by a claim
in Ligand's solely owned Patent Rights. Wyeth's rights under this paragraph are
subject to the payment of milestones and royalties as provided in Article 9.

      7.3 In the case of a Covered Compound first synthesized by Wyeth that is
made the subject of development by Wyeth outside this Agreement as provided in
Section 7.2, then at Wyeth's request and unless prohibited by agreements with
third parties, Ligand shall grant Wyeth an exclusive license under any Patent
Rights and trade secrets relating thereto it may have covering or relating to
such Covered Compound and its use outside the Field except in the circumstance
where the same compound is under development or being marketed by Ligand when
Wyeth's request is made.

                                    ARTICLE 8
                     LIGAND SCREENING RIGHTS AND OBLIGATIONS

      8.1 Wyeth Library Compound Disposition. All Wyeth Library Compounds
screened at Ligand under the Research Program shall be and shall remain the sole
property of Wyeth. Ligand represents and warrants (i) that it has destroyed or
(ii) will return any Wyeth Library Compounds it may have in its possession as of
the Effective Date of this Amended and Restated Agreement. Ligand further
represents and warrants that any Wyeth Library Compounds (a) made by Ligand and
covered by joint patent filings and/or (b) received from Wyeth or derived
therefrom, are not included in the Ligand compound library and have not been
used for any other purpose outside of the Agreement and/or this Amended and
Restated Agreement, including Ligand's rights under this Article 8.

      8.2 Article 8 Compounds-Ownership. Ligand hereby returns all rights in and
to the Article 8 Compounds to Wyeth.

                                    ARTICLE 9
                          ROYALTIES AND OTHER PAYMENTS

9.1 Milestone Payments. As additional consideration for the technology and
know-how provided by Ligand to the Research Program and Ligand's participation
in the Research Program and for the

                                  CONFIDENTIAL
                                       22

<PAGE>

licenses granted to Wyeth herein:

(i) within thirty (30) days of the occurrence of each event listed in Schedule
2, Wyeth will pay to Ligand the sums presented in Schedule 2 for each Research
Compound (including a Covered Compound, Wyeth Compound and Combination Research
Compound) or Product (including a Covered Compound Product, Wyeth Compound
Product and Combination Research Compound Product), as the case may be, that
Wyeth, in its sole discretion, chooses to advance into development or to
commercialize; and

(ii) within five (5) days of the Effective Date of this Amended and Restated
Agreement, WYETH will reconcile the Research Event payments for all Research
Compounds versus those amounts previously paid and pay to Ligand the amount due
for such reconciliation. This payment will be $1,840,000. Ligand and Wyeth
acknowledge and agree that such payment constitutes the full payment of all
amounts in dispute between the Parties under the Agreement.

      9.2 Royalties Payable by WYETH. In consideration for the technology and
know-how provided by Ligand and for the licenses and other rights granted to
WYETH herein, during the Royalty Term, WYETH shall pay to Ligand royalties equal
to the following percentages of annual Net Sales calculated each year on a
Product-by-Product basis, including sales for applications other than in the
Field, by WYETH, its Affiliates and sublicensees in the Territory:

<TABLE>
<CAPTION>
                                                                                                Wyeth Product or
                                         Covered Product or Combination                         Wyeth Compound
                                         Covered Compound Product on a                          Combination Product
Annual Net Sales                         Per Product Basis                                      on a Per Product Basis
---------------------------              -------------------------------                        -----------------------
<S>                                      <C>                                                    <C>
For the first
$400,000,000 in Annual
Net Sales                                              [***]                                              [***]
For the next
$600,000,000 in Annual
Net Sales                                              [***]                                              [***]
For Annual Net Sales above
$1,000,000,000                                         [***]                                              [***]
</TABLE>

                                  CONFIDENTIAL
                                       23
*** Certain information on this page has been omitted and filed separately with
the Commission. Confidential treatment has been requested with respect to the
omitted portions.

<PAGE>

The royalties payable under this Section 9.2 will be reduced on a country by
country basis by one third (1/3) during any period when a royalty is owed and
the Product is not covered by a valid claim in an issued patent that has not
expired. As used in this Section 9.2, a valid claim is a claim that has not been
held invalid in a judgment from which no appeal has or can be taken.

As consideration for the modification of the Agreement by the first amendment
dated as of January 16, 1996, WYETH paid Ligand the sum of $1,500,000 for
certain research and development expenses incurred by Ligand with respect to the
Covered Compounds. In the event that no Series A Compound for which an IND
filing is made results in a marketed Product, the $1,500,000 shall be a credit
against twenty-five percent (25%) of future Product royalties due under this
Amended and Restated Agreement until the said $1,500,000 is exhausted.

                                   ARTICLE 10

                         ROYALTY REPORTS AND ACCOUNTING

      10.1 Reports, Exchange Rates. During the term of this Amended and Restated
Agreement following the First Commercial Sale of a Product, WYETH shall furnish
to Ligand a quarterly written report showing in reasonably specific detail, on a
country by country basis, (a) the gross sales of all Products sold by WYETH, its
Affiliates and its sublicensees in the Territory during the reporting period and
the calculation of Net Sales from such gross sales; (b) the royalties payable in
U.S. dollars, if any, which shall have accrued hereunder based upon Net Sales of
Products; (c) withholding taxes, if any, required by law to be deducted in
respect of such sales; (d) the dates of the First Commercial Sales of any
Products in any country in the Territory during the reporting period; and (e)
the exchange rates used in determining the amount of U.S. dollars. With respect
to sales of Products invoiced in U.S. dollars, the gross sales, Net Sales, and
royalties payable shall be expressed in U.S. dollars. With respect to sales of
Products invoiced in a currency other than U.S. dollars, the gross sales, Net
Sales and royalties payable shall be expressed in the domestic currency of the
Party making the sale together with the U.S. dollar equivalent of the royalty
payable, calculated using the average closing buying rate for such currency
quoted in the continental terms method of quoting exchange rates (local currency
per U.S. $1) by Bank of America NOT&SA in London, England, or, in the absence of
quoted exchange rates from Bank of America NOT&SA in London, a comparable bank
or financial institution, on each of the last business day of each month in the
quarter prior to the date of

                                  CONFIDENTIAL
                                       24

<PAGE>

payment. Reports shall be due on the sixtieth (60th) day following the close of
each quarter. WYETH shall keep complete and accurate records in sufficient
detail to properly reflect all gross sales and Net Sales and to enable the
royalties payable hereunder to be determined.

      10.2 Audits.

      10.2.1 Upon the written request of Ligand and not more than once in each
calendar year, WYETH shall permit an independent certified public accounting
firm of nationally recognized standing, selected by Ligand and reasonably
acceptable to WYETH, at Ligand's expense, to have access during normal business
hours to such of the records of WYETH as may be reasonably necessary to verify
the accuracy of the royalty reports hereunder for any year ending not more than
thirty-six (36) months prior to the date of such request. The accounting firm
shall disclose to Ligand only whether the records are correct or not and the
specific details concerning any discrepancies. No other information shall be
shared.

      10.2.2 If such accounting firm concludes that additional royalties were
owed during such period, WYETH shall pay the additional royalties within thirty
(30) days of the date Ligand delivers to WYETH such accounting firm's written
report so concluding. The fees charged by such accounting firm shall be paid by
Ligand; provided, however, if the audit discloses that the royalties payable by
WYETH for the audited period are more than one hundred ten percent (110%) of the
royalties actually paid for such period, then WYETH shall pay the reasonable
fees and expenses charged by such accounting firm.

      10.2.3 WYETH shall include in each permitted sublicense granted by it
pursuant to this Amended and Restated Agreement a provision requiring the
sublicensee to make reports to WYETH, to keep and maintain records of sales made
pursuant to such sublicense and to grant access to such records by Ligand's
accounting firm to the same extent required of WYETH under this Amended and
Restated Agreement. Upon the expiration of thirty-six (36) months following the
end of any year, the calculation of royalties payable with respect to such year
shall be binding and conclusive upon Ligand, WYETH and its sublicensees, and
such sublicensees shall be released from any liability or accountability with
respect to royalties for such year.

      10.3 Confidential Financial Information. Ligand shall treat all financial
information subject to review under this Article 10 or under any sublicense
agreement as confidential, and shall cause

                                  CONFIDENTIAL
                                       25

<PAGE>

its accounting firm to retain all such financial information in confidence.

                                   ARTICLE 11

                                    PAYMENTS

      11.1 Payment Terms. Royalties shown to have accrued by each royalty report
provided for under Article 10 of this Amended and Restated Agreement shall be
due and payable on the date such royalty report is due. Payment of royalties in
whole or in part may be made in advance of such due date.

      11.2 Payment Method. Except as otherwise agreed between the Parties, all
royalties and other payments due hereunder shall be paid in U.S. dollars. All
royalties and other payments by WYETH to Ligand under this Amended and Restated
Agreement shall be originated from a United States bank located in the United
States and shall be made by bank wire transfer in immediately available funds to
such account as Ligand shall designate before such payment is due. If at any
time legal restrictions in any country in the Territory prevent the prompt
remittance in the manner set forth in this Section 11.2 of part or all royalties
owing with respect to Product sales in such country, then the Parties shall meet
and mutually determine a lawful manner of remitting the restricted part of such
royalty payments so long as such legal restrictions exist.

      11.3 Withholding Taxes. All amounts owing from WYETH to Ligand under this
Amended and Restated Agreement are net amounts, and shall be paid without
deduction to account for any withholding taxes, value-added taxes or other
taxes, levies or charges with respect to such amounts payable on behalf of
WYETH, its Affiliates or sublicensees and any taxes required to be withheld on
behalf of WYETH, its Affiliates or sublicensees in any country within the
Territory; provided, however, that WYETH may deduct the amount of any income
taxes required to be withheld on behalf of Ligand by WYETH, its Affiliates or
sublicensees under the laws of any jurisdiction on amounts owing from WYETH to
Ligand hereunder to the extent WYETH, its Affiliates or sublicensees pay to the
appropriate governmental authority on behalf of Ligand such income taxes. WYETH
shall use reasonable efforts to minimize any income taxes required to be
withheld on behalf of Ligand by WYETH, its Affiliates or sublicensees, and
promptly shall deliver to Ligand proof of payment of such income taxes together
with copies of all communications from or with such governmental authority with
respect thereto.

                                  CONFIDENTIAL
                                       26

<PAGE>

      11.4 Late Payments. Unless otherwise provided in this Amended and Restated
Agreement, WYETH shall pay interest to Ligand on the aggregate amount of any
payments by WYETH that are not paid on or before the date such payments are due
under this Amended and Restated Agreement at a rate per annum equal to the
lesser of the prime rate of interest as reported by Bank of America NOT&SA in
San Francisco, California, from time to time, plus two percent (2%), or the
highest rate permitted by applicable law, calculated on the number of days such
payment is delinquent.

                                   ARTICLE 12

                      INFRINGEMENT ACTIONS BY THIRD PARTIES
      If a Party, or to its knowledge, any of its Affiliates, sublicensees or
customers shall be sued by a third party for infringement of a patent because of
the development, manufacture, use or sale of Research Compounds or Products,
such Party shall promptly notify the other in writing of the institution of such
suit. The Party sued shall have the right, in its sole discretion, to control
the defense of such suit at its own expense, in which event the other Party
shall cooperate fully in the defense of such suit and furnish to the Party sued
all evidence and assistance in its control. Any judgments, settlements or
damages payable with respect to legal proceedings covered by this Article 12
shall be paid by the Party which controls the litigation, subject to any claims
against the other Party for breach of or indemnification under this Amended and
Restated Agreement or otherwise available at law or in equity. Any third party
royalty payments required to be paid as the result of a judgment or settlement
under this Article 12 shall be paid by the Party controlling the suit subject to
any claims against the other Party for breach of or indemnification under this
Amended and Restated Agreement or otherwise available at law or in equity;
provided, however, in the case of a Product sold by WYETH, if such third party
royalty payments arise from the infringement of a patent having a claim or
claims which cover the screening activities of Ligand under the Research
Program, the third party royalty payments shall be creditable against royalties
owed Ligand under this Amended and Restated Agreement in the circumstance where
WYETH permits Ligand to defend the suit; provided, further, that in the event
WYETH defends the suit the credit taken for any third party royalties shall not
be in excess of fifty percent (50%) of the royalty due Ligand under this Amended
and Restated Agreement for Product sales which caused such third party royalty
payments, subject to any claims for breach of or indemnification under this
Amended and Restated Agreement or otherwise available at law or in equity.

                                  CONFIDENTIAL
                                       27

<PAGE>

                                   ARTICLE 13

                                 CONFIDENTIALITY

      13.1 Nondisclosure Obligations. Except as otherwise provided in this
Article 13 and subject to Article 12 hereof, during the term of this Amended and
Restated Agreement and for a period of five (5) years thereafter, (a) both
Parties shall maintain in confidence information and data resulting from or
related to the Research Program or the development of Research Compounds or
Products; and (b) both Parties shall also maintain in confidence and use only
for purposes of this Amended and Restated Agreement all information and data
supplied by the other Party under this Amended and Restated Agreement, which if
disclosed in writing is marked "Confidential," or if disclosed orally is
promptly thereafter confirmed in writing to be confidential.

      13.2 Permitted Disclosures. For purposes of this Article 13, information
and data described in clause (a) or (b) above shall be referred to as
"Information." To the extent it is reasonably necessary or appropriate to
fulfill its obligations or exercise its rights under this Amended and Restated
Agreement, (w) a Party may disclose Information it is otherwise obligated under
this Article 11 not to disclose to its Affiliates, sublicensees, potential
sublicensees, consultants, outside contractors and clinical investigators, on a
need-to-know basis on condition that such persons or entities agree to keep the
Information confidential for the same time periods and to the same extent as
such Party is required to keep the Information confidential; (x) a Party or its
Affiliates or sublicensees may disclose such Information to government or other
regulatory authorities to the extent that such disclosure is reasonably
necessary to obtain patents or authorizations to conduct clinical trials with,
and to commercially market the Product, provided that the disclosing Party shall
request confidential treatment thereof; (y) a Party may disclose Information as
required by applicable law, regulation or judicial process, provided that such
Party shall give the other Party prior written notice thereof and adequate
opportunity to object to any such disclosure or to request confidential
treatment thereof; and (z) a Party may disclose Information as permitted under
Section 13.1.

      The obligation not to disclose or use Information shall not apply to any
part of such Information that (i) is or becomes patented, published or otherwise
part of the public domain other than by acts of the Party obligated not to
disclose such Information or its Affiliates or sublicensees in contravention of

                                  CONFIDENTIAL
                                       28

<PAGE>

this Amended and Restated Agreement; or (ii) is disclosed to the receiving Party
or its Affiliates or sublicensees by a third party, provided such Information
was not obtained by such third party directly or indirectly from the other Party
under this Amended and Restated Agreement on a confidential basis; or (iii)
prior to disclosure under this Amended and Restated Agreement, was already in
the possession of the receiving Party or any of its Affiliates or sublicensees,
provided such Information was not obtained directly or indirectly from the other
Party under this Amended and Restated Agreement; or (iv) is disclosed in a press
release agreed to by both Parties under Section 13.3 below.

      13.3 Publicity Review.

      13.3.1 Publicity Review. Without the prior written consent of the other
Party, neither Party shall make any statement to the public regarding the
execution and the subject matter of this Amended and Restated Agreement between
WYETH and Ligand, the work under the Research Program or any other aspect of
this Amended and Restated Agreement, provided however, that Wyeth may make
public statements and announcements concerning Wyeth's development, manufacture
or commercialization activities with respect to Research Compounds or Products
without the prior consent of Ligand, provided further however, that the content
of such public statements and announcements will be provided in writing to
Ligand no later than promptly following the public statement or announcement in
question. Notwithstanding the foregoing, any of such statements may be made by
Ligand to a third party to whom Ligand is seeking to sell an equity interest,
e.g., common or preferred stock or an instrument convertible into common or
preferred stock, or from whom Ligand is seeking a loan provided that such third
party is bound under obligations of confidentiality similar to those of this
Article 13; provided, however, that statements made by Ligand to a third party
pharmaceutical company shall not include non-public information about this
Amended and Restated Agreement. Ligand and WYETH shall not disclose any terms or
conditions of this Amended and Restated Agreement to any third party without the
prior consent of the other Party, except as set forth above in this Section 13.3
or as required by applicable law.

                                   ARTICLE 14

                                   PUBLICATION

      14.1 Notice of Publication. During the term of this Amended and Restated
Agreement, Ligand and WYETH each acknowledge the other Party's interest in
publishing certain of its results to obtain

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<PAGE>

recognition within the scientific community and to advance the state of
scientific knowledge. Each Party also recognizes the mutual interest in
obtaining valid patent protection and protecting business interests.
Consequently, either Party, its employees or consultants wishing to make a
publication (including any oral disclosure made without obligation of
confidentiality) relating to work performed by such Party as part of the
Research Program (the "Publishing Party") shall transmit to the other Party (the
"Reviewing Party") a copy of the proposed written publication or an outline of
such oral disclosure at least sixty (60) days prior to submission for
publication or oral disclosure. The Reviewing Party shall have the right (a) to
propose modifications to the publication for patent, trade secret or commercial
reasons and (b) to request a reasonable delay in or avoidance of publication in
order to protect patentable information and trade secrets, the disclosure of
which would materially affect the interests of the Reviewing Party under this
Amended and Restated Agreement. A Party shall have the right in its own
discretion to seek patents on inventions made solely by its own employees.

      14.2 Timing of Publication. If the Reviewing Party requests such a delay
or avoidance, the Publishing Party shall delay submission or presentation of the
publication for a period of ninety (90) days to enable modification as provided
in Section 14.1 or patent applications protecting each Party's rights in such
information to be filed in accordance with Article 15 below. Upon the expiry of
sixty (60) days from transmission to the Reviewing Party, the Publishing Party
shall be free to proceed with the written publication or the presentation,
respectively, unless the Reviewing Party has requested the delay or avoidance
described above.

                                   ARTICLE 15

                                     PATENTS

      15.1 Ownership of Inventions, Applications for Patent and Patents. Subject
to such rights as are granted under this Amended and Restated Agreement, the
entire right, title and interest in all inventions, discoveries, improvements or
other technology directed at a Research Compound or Product and all processes or
uses relating thereto, whether or not patentable (collectively, the
"Inventions"), together with all patent applications or patents based thereon,
made during and as a result of the Research Program (a) by employees or others
acting solely on behalf of Ligand shall be owned solely by Ligand (the "Ligand
Inventions"), (b) by employees or others acting solely on behalf of WYETH shall
be owned

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<PAGE>

solely by WYETH (the "WYETH Inventions"), and (c) by employees or others acting
jointly on behalf of Ligand and WYETH shall be owned jointly by Ligand and WYETH
(the "Joint Inventions"). Any dispute regarding the inventorship of an Invention
or Joint Invention made under the Research Program shall be resolved by the
decision of independent patent counsel, mutually acceptable to the Parties,
after consideration of all evidence submitted by the Parties, except to the
extent such decision is inconsistent with the subsequent determination of the
appropriate patent or judicial authorities. Each Party shall promptly disclose
to the other Party the conception or reduction to practice under the Research
Program of Inventions by employees or others acting on behalf of such Party.
Each Party hereby represents and agrees that all employees and other persons
acting on its behalf in performing its obligations under this Amended and
Restated Agreement shall be obligated under a binding written agreement or
applicable law to assign to such Party or its Affiliate all Inventions made or
developed by such employee or other Person.

      15.2 Patent Applications.

      15.2.1 Priority Filings. When an Invention or Joint Invention has been
made under the Research Program which may reasonably be considered to be
patentable, a priority patent application shall be filed as soon as reasonably
possible. If a Joint Invention has been made under the Research Program, the
parties shall designate mutually acceptable independent patent counsel which
shall file such application which shall be in the name of both Parties. The
Party filing the application with respect to an Invention or Joint Invention
made under the Research Program shall give the other Party an opportunity to
review the text of the application before filing, and in good faith shall
consider and incorporate the reasonable requests of the other Party. The Party
filing the application with respect to any Invention or Joint Invention made
under the Research Program shall supply the other Party with a copy of the
application as filed, together with notice of its filing date and serial number.

      15.2.2 Foreign Filing Decisions. No later than nine (9) months following
the filing date of a priority patent application with respect to an Invention or
Joint Invention made under the Research Program filed according to Section
15.2.1 above, the Parties shall consult together to determine whether such
priority application with respect to such Invention or Joint Invention should be
abandoned without replacement; abandoned and refiled; proceeded within the
country of filing only; or used as the basis for a claim of priority under the
Paris Convention for

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<PAGE>

corresponding applications in or designating other countries. The Parties shall
consult together to ensure that so far as practicable the texts filed in the
United States and in other countries contain the same information and claim the
same scope of protection.

      15.2.3 Prosecution and Maintenance. Ligand and WYETH, as applicable, shall
have the right, using commercially reasonable practices, to control the
prosecution, grant and maintenance of its Patent Rights with respect to each
Invention or Joint Invention made under the Research Program, and to select all
patent counsel or other professionals to advise, represent or act for it in all
matters relating to such Patent Rights. All costs incurred in connection
therewith shall be borne by the Party taking action with respect to such Patent
Rights. In the case of Joint Inventions made under the Research Program, the PMC
shall designate the Party which shall control the prosecution, grant and
maintenance of joint Patent Rights. The Party controlling the prosecution, grant
and maintenance of such joint Patent Rights shall consider all reasonable
requests of the other Party with respect thereto. All costs incurred in
connection with the prosecution, grant and maintenance of such joint Patent
Rights shall be paid in equal parts by the Parties. Each Party shall inform the
other Party at regular intervals, or on request, about the status of all patent
applications or patents for which it is responsible with respect to Inventions
or Joint Inventions made under the Research Program.

      In the event that Ligand or WYETH elects not to file a patent application
on an Invention or Joint Invention made under the Research Program in any
country, or decides to abandon any pending application or granted patent on an
Invention or Joint Invention made under the Research Program in any country, it
shall provide adequate notice to the other Party and give the other Party the
opportunity to file or maintain such application or patent at its own expense.

      15.2.4 Following the Effective Date of this Amended and Restated
Agreement, either Party may elect to discontinue paying its 50% share of the
costs associated with the prosecution, grant and maintenance of Joint Patent
Rights on a country-by-country basis by providing written notice to the other
Party. Upon receipt of such written notice, the other Party may elect to
maintain patent protection in that country, at its own expense. The Party
electing to discontinue paying its 50% share shall assign all rights in and to
the subject Joint Patent Right to the other Party and shall have no rights under
Section 15.5 hereof. For the avoidance of doubt (i) no such discontinuation or
assignment of any Joint Patent Right shall shorten any royalty term or reduce
any

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<PAGE>

royalties or milestones otherwise payable to Ligand hereunder, and (ii) neither
Party shall be required to assign rights to Joint Patent Rights to the other
Party on the basis of a decision to discontinue payment that was made before the
effective date of this Amended and Restated Agreement.

      15.2.5 Promptly following the Effective Date of this Amended and Restated
Agreement, Ligand will assign to Wyeth Ligand's interest in and to all Patent
Rights included in the following eight (8) patent families, worldwide:

                                      [***]

For the avoidance of doubt, the assignment of Ligand's rights in the
above-referenced patent families in and of itself will not shorten any royalty
term or reduce any royalties or milestones otherwise payable to Ligand
hereunder.

      15.2.6 List of Current Patents and Applications. As of the Effective Date
of this Amended and Restated Agreement, the parties agree that Schedule 3 hereto
is a complete list of all jointly owned Patent Rights, other than Patent Rights
with claims which read upon a Wyeth Compound Product or a Wyeth Compound or the
process of manufacture or use of a Wyeth Compound Product or a Wyeth Compound.

      15.3 Cooperation. Each Party shall make available to the other Party or
its authorized attorneys, agents or representatives, its employees, agents or
consultants necessary or appropriate to enable the appropriate Party to file,
prosecute and maintain patent applications and resulting patents with respect to
all Inventions or Joint Inventions made under the Research Program, as set forth
in Section 15.2 above, for a period of time sufficient for such Party to obtain
the assistance it needs from such personnel. Where appropriate, each Party shall
sign or cause to have signed all documents relating to said patent applications
or patents at no charge to the other.

      15.4 No Other Technology Rights. Except as otherwise

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                                       33
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the Commission. Confidential treatment has been requested with respect to the
omitted portions.

<PAGE>

provided in this Amended and Restated Agreement, under no circumstances shall a
Party hereto, as a result of this Amended and Restated Agreement, obtain any
ownership interest or other right in any technology, trade secrets, patents,
pending patent applications, products, vaccines, antibodies, cell lines or
cultures, or animals of the other Party, including items owned, controlled or
developed by the other, or transferred by the other to such Party at any time
pursuant to this Amended and Restated Agreement. It is understood and agreed by
the Parties that this Amended and Restated Agreement does not grant to either
Party any license or other right in basic technology of the other Party except
to the extent necessary to enable the Parties to carry out their part of the
Research Program, Exploratory Development, Full Development, marketing and sales
of Research Compounds and Products.

      15.5 Enforcement of Patent Rights. Ligand and WYETH each shall use good
faith efforts to enforce the Patent Rights against infringers, and to consult
with the other Party both prior to and during said enforcement. Upon learning of
significant and continuing infringement of such Patent Rights by a third party
in the Field, Ligand or WYETH, as the case may be, promptly shall provide notice
to the other Party in writing of the fact and shall supply the other Party with
all evidence possessed by the notifying Party pertaining to and establishing
said infringement(s). Ligand may elect to initiate legal action with respect to
a patent owned solely by Ligand against such third party in its sole discretion,
and WYETH shall cooperate fully with Ligand in any such action at its own
out-of-pocket expense, further provided that WYETH shall have the right to join
as a party provided it funds up to one half (1/2) of the costs of such suit.
WYETH shall have the right to be represented by legal counsel of its own
choosing at its sole expense. If Ligand, within six (6) months of receipt of
such notice or such lesser period of time if a further delay would result in
material harm, or the loss of a material right, has not commenced legal action
against an infringer whose infringing product has a market share larger than
thirty percent (30%) of the sales of a competing Product embraced by a valid
claim of said Ligand patent in that country, which patent is licensed to WYETH
hereunder, upon written notice from WYETH, Ligand shall promptly either: (i)
initiate such action; or (ii) authorize WYETH to commence such action. WYETH may
elect to initiate legal action with respect to a patent owned jointly or solely
by WYETH against such third party in its sole discretion, and Ligand shall
cooperate fully with WYETH in any such action at its own out-of-pocket expense,
further provided that Ligand shall have the right to join as a party provided it
funds up to one-half (1/2) of the costs of

                                  CONFIDENTIAL
                                       34

<PAGE>

such suit. Ligand shall have the right to be represented by legal counsel of its
own choosing at its sole expense. If WYETH, within six (6) months of receipt of
such notice or such lesser period of time if a further delay would result in
material harm, or the loss of a material right, has not commenced legal action
against an infringer whose infringing product has a market share larger than
thirty percent (30%) of the sales of a competing Product embraced by a valid
claim of said WYETH patent in that country, upon written notice from Ligand,
WYETH shall promptly either: (i) initiate such action; or (ii) authorize Ligand
to commence such action. Notwithstanding anything to the contrary, any
settlement of such legal action by the initiating Party shall require the
consent of the non-initiating Party, which consent will not be unreasonably
withheld. The Party whose Patent Rights allegedly are being infringed shall not
be obligated to bring or maintain more than one such suit at any time with
respect to claims directed to any one method of manufacture or composition of
matter. All monies recovered upon the final judgment or settlement of any such
suit shall be shared, after reimbursement of expenses, by Ligand and WYETH pro
rata according to the respective percentages of costs borne by each Party in
such suit pursuant to this Section 15.5. Notwithstanding the foregoing, Ligand
and WYETH shall fully cooperate with each other in the planning and execution of
any action to enforce such Patent Rights, and shall join suit if required by law
to do so in order to bring such action.

      15.6 Unauthorized Use of Patent Rights. Neither Ligand nor WYETH shall
willfully take any action which would, directly or indirectly, infringe, or
induce or contribute to the infringement of, one or more claims of any issued
patent of the other Party or its Affiliates, except to the extent such action is
authorized by a license granted under this Amended and Restated Agreement. If
either Ligand or WYETH takes any action, directly or indirectly, to challenge
the validity of any issued patent of the other Party or its Affiliates, then the
other Party shall have the right in its sole discretion to terminate the
Research Program; provided, however, in the circumstance where the challenged
patent is included within the Patent Rights of the other Party, the other Party
additionally shall have the right to terminate the license granted under Article
6 above, to the extent permitted by law, on a country-by-country basis. For the
avoidance of doubt this right to terminate shall not apply to license rights in
the U.S. provided that the licensee is not in breach of any obligation which
would otherwise give rise to a right of termination. A Party shall not be
entitled to withhold any milestone payment or payment of any royalty accruing
during any challenge to the validity of a patent included within the Patent
Rights of the other Party.

                                  CONFIDENTIAL
                                       35

<PAGE>

         15.7 Disposition of Certain Claims of [***]or any national patent or
patent application resulting there from or (ii) in any other patent or patent
application owned or controlled by Ligand, any subject matter that is claimed in
any Ligand-Wyeth jointly-filed patent application. Ligand further represents and
warrants that all compounds falling under [***]and disclosed in [***]were
synthesized after September 2, 1998 and no such compounds meet the Research
Compound selection criteria set forth in Section 1.20 of this Amended and
Restated Agreement, i.e. that a compound have in vitro IC50 =100nM and in vitro
selectivity = 100X the nearest alternate target.

                                   ARTICLE 16

                              TERM AND TERMINATION

         16.1 Expiration. Unless terminated earlier pursuant to Section 16.3
below, this Amended and Restated Agreement shall expire on the expiration of the
last Party's obligations to pay royalties under this Amended and Restated
Agreement.

         16.2 Effect of Expiration or Termination. Expiration or termination of
this Amended and Restated Agreement shall not relieve the Parties of any
obligation accruing prior to such expiration or termination. The provisions of
Article 11, Article 12, Article 13 and Article 18 shall survive the expiration
or termination of this Amended and Restated Agreement.

         16.3 Termination In Case of Bankruptcy. A Party shall have the right to
terminate this Amended and Restated Agreement by delivering sixty (60) days
prior written notice to the other Party in the event of the other Party's
bankruptcy (not to include reorganization) or insolvency, provided that federal
bankruptcy laws shall apply.

                                  CONFIDENTIAL
                                       36
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the Commission. Confidential treatment has been requested with respect to the
omitted portions.

<PAGE>

                                   ARTICLE 17

                             PREMARIN(R) EVALUATION

      17.1 Evaluation of Premarin(R). WYETH provided Ligand with a quantity of
Premarin(R) and its components sufficient to permit Ligand to make an evaluation
thereof as described in Exhibit C of the Agreement using its own resources. The
results of the Premarin(R) evaluation were reported to WYETH. All rights and
interest in and to such results are and shall remain the sole and exclusive
property of Wyeth. Ligand shall have no rights to (i) Premarin(R) or any of its
components or (ii) any data or materials developed as a result of the
Premarin(R) evaluation as described in Exhibit C of the Agreement. If WYETH
should decide, in its sole discretion, to initiate a Research Program with
respect to any data or materials developed during the Premarin(R) evaluation as
described in Exhibit C of the Agreement, then Ligand will only be entitled to
receive royalties and milestone payments as otherwise provided for in this
Amended and Restated Agreement, but will have no other rights whatsoever to any
such data or materials.

                                   ARTICLE 18

                                    INDEMNITY

      18.1 Direct Indemnity. Each Party shall indemnify and hold the other
Party, its Affiliates and sublicensees harmless, and hereby forever releases and
discharges the other Party, its Affiliates and sublicensees, from and against
all claims, demands, liabilities, damages and expenses, including attorneys'
fees and costs (collectively, "Liabilities") arising out of negligence,
recklessness or intentional misconduct of the indemnifying Party, its Affiliates
or sublicensees in connection with the work performed by such Party during the
Research Program, Exploratory Development, Full Development or the marketing or
sale of Research Compounds or Products hereunder; except in each case to the
extent such Liabilities resulted from negligence, recklessness or intentional
misconduct of the other Party.

         18.2 Other Indemnity. Each Party shall indemnify and hold the other
Party, its Affiliates and sublicensees harmless from and against all Liabilities
suffered or incurred in connection with third party claims for personal injuries
or any product recall to the extent caused by: (a) any failure to test for or
provide adequate warnings of adverse side effects to the extent such failure
arises out of negligence, recklessness or intentional

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<PAGE>

misconduct in connection with the indemnifying Party's preclinical or clinical
testing obligations hereunder, (b) any manufacturing defect in any Product or
any other material manufactured by the indemnifying Party, its Affiliates or
permitted sublicensees, or (c) any other act or omission (without regard to
culpable conduct) of the indemnifying Party, its Affiliates or permitted
sublicensees in connection with the activities contemplated under this Amended
and Restated Agreement; except in each case to the extent such Liabilities
resulted from negligence, recklessness or intentional misconduct of the other
Party.

      18.3 Procedure. A Party (the "Indemnitee") that intends to claim
indemnification under this Article 18 shall promptly notify the other Party (the
"Indemnitor") of any Liability or action in respect of which the Indemnitee or
any of its Affiliates or sublicensees intend to claim such indemnification, and
the Indemnitor shall have the right to participate in, and, to the extent the
Indemnitor so desires, jointly with any other Indemnitor similarly noticed, to
assume the defense thereof with counsel selected by the Indemnitor; provided,
however, that an Indemnitee shall have the right to retain its own counsel, with
the fees and expenses of such counsel to be paid by the Indemnitee, if
representation of such Indemnitee by the counsel retained by the Indemnitor
would be inappropriate due to actual or potential differing interests between
such Indemnitee and any other Party represented by such counsel in such
proceedings. The indemnity agreement in this Article 18 shall not apply to
amounts paid in settlement of any loss, claim, damage, liability or action if
such settlement is effected without the consent of the Indemnitor, which consent
shall not be withheld unreasonably. The failure to deliver notice to the
Indemnitor within a reasonable time after the commencement of any such action,
if prejudicial to its ability to defend such action, shall relieve such
Indemnitor of any liability to the Indemnitee under this Article 18, but the
omission so to deliver notice to the Indemnitor will not relieve it of any
liability that it may have to any Indemnitee otherwise than under this Article
18. The Indemnitee under this Article 18, its employees and agents, shall
cooperate fully with the Indemnitor and its legal representatives in the
investigation of any action, claim or liability covered by this indemnification.

      18.4 Insurance. WYETH shall maintain, through self-insurance or otherwise,
product liability insurance with respect to the development, manufacture and
sale of Products in such amount as WYETH customarily maintains with respect to
its other products. WYETH shall maintain such insurance for so long as it
continues to develop, manufacture or sell any Products, and thereafter for so

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<PAGE>

long as WYETH maintains insurance for itself covering such manufacture or sales.
The requirement to maintain insurance shall apply mutatis mutandis to Ligand in
the circumstance where Ligand acquires the right under this Amended and Restated
Agreement to commercialize a Product.

     18.5 Indemnity Exclusion. A Party that relinquishes rights to a Research
Compound or Product to the other Party shall not be obligated to indemnify the
other Party, its Affiliates or sublicensees under Sections 18.1 and 18.2 with
respect to their use of information obtained from the relinquishing Party as a
result of the relinquishing of rights to the Research Compound or Product.

                                   ARTICLE 19

                                  FORCE MAJEURE

      Neither Party shall be held liable or responsible to the other Party nor
be deemed to have defaulted under or breached this Amended and Restated
Agreement for failure or delay in fulfilling or performing any term of this
Amended and Restated Agreement when such failure or delay is caused by or
results from causes beyond the reasonable control of the affected Party
including but not limited to fire, floods, embargoes, war, acts of war (whether
war be declared or not), insurrections, riots, civil commotions, strikes,
lockouts or other labor disturbances, acts of God or acts, omissions or delays
in acting by any governmental authority or the other Party.

                                   ARTICLE 20

                                   ASSIGNMENT

      This Amended and Restated Agreement may not be assigned or otherwise
transferred, nor, except as expressly provided hereunder, may any right or
obligations hereunder be assigned or transferred by either Party without the
consent of the other Party; provided, however, that either Ligand or WYETH may,
without such consent, assign this Amended and Restated Agreement and its rights
and obligations hereunder in connection with the transfer or sale of all or
substantially all of its business pertaining to this Amended and Restated
Agreement, or in the event of its merger or consolidation or change in control
or similar transaction. Any permitted assignee shall assume all obligations of
its assignor under this Amended and Restated Agreement. If Ligand desires to
assign this Amended and Restated Agreement and its rights and obligations
hereunder in connection with the transfer or sale of

                                  CONFIDENTIAL
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<PAGE>

all or substantially all of its business, or in the event of its merger or
consolidation or change in control or similar transaction prior to the fourth
anniversary of the Commencement Date, WYETH shall have the right within thirty
(30) days after receipt of written notice thereof from Ligand to terminate the
Research Program, in which case the Research Program shall terminate upon
receipt by Ligand of written notice of such election to terminate. If WYETH
elects to terminate the Research Program under the immediately preceding
sentence, (a) at the time WYETH delivers such written notice of its election to
terminate, WYETH shall pay to Ligand an amount equal to three-fourths (3/4) of
the Aggregate Annual Research Fee, net of the unused portion, if any, of WYETH's
most recent payment to Ligand under Section 3.2 above; and (b) any compound
which is identified by WYETH, within twenty four (24) months after termination
of the Research Program, as acting through or mediating the activity of one or
more Designated Targets shall be a Research Compound. Nothing in this Article 20
shall prevent a Party from assigning its rights to develop and commercialize a
product for which it acquires rights from the other under this Amended and
Restated Agreement which assignment shall be subject to any rights accorded the
non-assigning Party as a result of this Amended and Restated Agreement.

                                   ARTICLE 21

                     NOTIFICATION OF PATENT TERM RESTORATION

      Ligand or WYETH, as the case may be, shall notify the other Party of (a)
the issuance of each U.S. patent, or foreign patent where extension is possible,
included within the Patent Rights, giving the date of issue and patent number
for each such patent, and (b) each notice pertaining to any patent included
within the Patent Rights which it receives as patent owner pursuant to the Drug
Price Competition and Patent Term Restoration Act of 1984 (hereinafter called
the "Act") or equivalent foreign laws, including notices pursuant to Sections
101 and 103 of the Act from persons who have filed an abbreviated NDA ("ANDA").
Such notices shall be given promptly, but in any event within five (5) calendar
days of each such patent's date of issue or receipt of each such notice pursuant
to the Act, whichever is applicable. Ligand or WYETH, as the case may be, shall
discuss relevant issues and decide upon appropriate action with respect to
patent term restoration under the Act, any allegations of failure to show due
diligence and all awards of patent term restoration (extensions) with respect to
the Patent Rights. Likewise, Ligand or WYETH, as the case may be, shall inform
the other Party of patent extensions and periods of data exclusivity in the rest
of the world regarding any Product.

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<PAGE>

                                   ARTICLE 22

                                  SEVERABILITY

      Each Party hereby agrees that it does not intend to violate any public
policy, statutory or common laws, rules, regulations, treaty or decision of any
government agency or executive body thereof of any country or community or
association of countries. In any term or provision of this Amended and Restated
Agreement is held to be invalid, illegal or unenforceable by a court or other
governmental authority of competent jurisdiction, such invalidity, illegality or
unenforceability shall not affect any other term or provision of this Amended
and Restated Agreement, which shall remain in full force and effect. The holding
of a term or provision to be invalid, illegal or unenforceable in a jurisdiction
shall not have any effect on the application of the term or provision in any
other jurisdiction.

                                   ARTICLE 23

                                  MISCELLANEOUS

      23.1 Notices. Any consent, notice or report required or permitted to be
given or made under this Amended and Restated Agreement by one of the Parties
hereto to the other shall be in writing, delivered personally or by facsimile
transmission effective upon such delivery and, in case of facsimile
transmission, confirmation of receipt by the recipient (and promptly confirmed
by personal delivery, U.S. first class mail or courier), U.S. first class mail
or courier, postage prepaid (where applicable), addressed to such other Party at
its address indicated below, or to such other address as the addressee shall
have last furnished in writing to the addressor and (except as otherwise
provided in this Amended and Restated Agreement) shall be effective upon receipt
by the addressee.

      If to Ligand:     Ligand Pharmaceuticals Incorporated
                        10275 Science Center Drive
                        San Diego, California 92121
                        Attention:  General Counsel

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<PAGE>

      If to WYETH:      Wyeth, acting through its Wyeth
                        Pharmaceuticals division
                        500 Arcola Road
                        Collegeville, PA  19426
                        Attn:  Senior Vice President
                               Corporate Business Development

      With a copy to: Wyeth
                        Five Giralda Farm
                        Madison, NJ  07940
                        Attn:  General Counsel

      23.2 Applicable Law. The Amended and Restated Agreement shall be governed
by and construed in accordance with the laws of the State of California.

      23.3 Entire Agreement. This Amended and Restated Agreement and the
concurrently executed Stock and Note Purchase Agreement and the accompanying
Promissory Notes between Ligand and WYETH to which Ligand and WYETH are parties
contain the entire understanding of the Parties with respect to the subject
matter hereof and shall supersede all express or implied agreements and
understandings, either oral or written, heretofore made. This Amended and
Restated Agreement may be amended, or any term hereof modified, only by a
written instrument duly executed by both Parties hereto.

      23.4 Headings. The captions to the several Articles and Sections hereof
are not a part of this Amended and Restated Agreement, but are merely guides or
labels to assist in locating and reading the several Articles and Sections
hereof.

      23.5 Independent Contractors. It is expressly agreed that Ligand and WYETH
shall be independent contractors and that the relationship between the two
Parties shall not constitute a partnership, joint venture or agency. Neither
Ligand nor WYETH shall have the authority to make any statements,
representations or commitments of any kind, or to take any action, which shall
be binding on the other, without the prior consent of the Party to do so.

      23.6 U.S. Export Laws and Regulations. Each Party warrants and represents
to the other that it does not intend to, nor will it export from the United
States or reexport from any foreign country, or permit a third Party to export
or reexport technology or technical information of the other Party, to a country
where such export or reexport would be in violation of U.S. Export
Administration Regulations.

                                  CONFIDENTIAL
                                       42

<PAGE>

      23.7 Waiver. The waiver by either Party hereto of any right hereunder or
the failure to perform or of a breach by the other Party shall not be deemed a
waiver of any other right hereunder or of any other breach or failure by said
other Party whether of a similar nature or otherwise.

      23.8 Counterparts. This Amended and Restated Agreement may be executed in
two or more counterparts, each of which shall be deemed an original, but all of
which together shall constitute one and the same instrument.

      23.9 Amendment and Restatement. This Amended and Restated Agreement amends
and restates the Agreement in its entirety. Notwithstanding the amendment and
restatement of the Agreement, each Party retains all rights and obligations
under the Agreement which have accrued to it prior to the Effective Date of this
Amended and Restated Agreement.

      IN WITNESS WHEREOF, the Parties have executed this Amended and Restated
Agreement as of the date first set forth above.

WYETH, acting through its          LIGAND PHARMACEUTICALS
Wyeth Pharmaceuticals division     INCORPORATED

By:__________________________               By:__________________________

Title:_______________________               Title:_______________________

                                  CONFIDENTIAL
                                       43

<PAGE>
                                   SCHEDULE A

                                    [***]

                                  CONFIDENTIAL
                                       44
*** Certain information on this page has been omitted and filed separately with
the Commission. Confidential treatment has been requested with respect to the
omitted portions.
<PAGE>
                                   SCHEDULE B

                                    [***]

                                  CONFIDENTIAL
                                      45-46
*** Certain information on this page has been omitted and filed separately with
the Commission. Confidential treatment has been requested with respect to the
omitted portions.
<PAGE>
                                 ATTACHMENT 1.2

                                    [***]

                                  CONFIDENTIAL
                                      47-52
*** Certain information on this page has been omitted and filed separately with
the Commission. Confidential treatment has been requested with respect to the
omitted portions.
<PAGE>
                                 ATTACHMENT 1.12

                                    [***]

                                  CONFIDENTIAL
                                       53
*** Certain information on this page has been omitted and filed separately with
the Commission. Confidential treatment has been requested with respect to the
omitted portions.
<PAGE>
                                 ATTACHMENT 1.16

                                    [***]

                                  CONFIDENTIAL
                                      54-56
  *** Certain information on this page has been omitted and filed separately
 with the Commission. Confidential treatment has been requested with respect
                           to the omitted portions.
<PAGE>
                                 ATTACHMENT 1.19

                                    [***]

                                  CONFIDENTIAL
                                      57-77
*** Certain information on this page has been omitted and filed separately with
the Commission. Confidential treatment has been requested with respect to the
omitted portions.
<PAGE>
                                 ATTACHMENT 1.23

                                    [***]

                                  CONFIDENTIAL
                                      78-83
*** Certain information on this page has been omitted and filed separately with
the Commission. Confidential treatment has been requested with respect to the
omitted portions.
<PAGE>
                                 ATTACHMENT 1.34

                                    [***]

                                  CONFIDENTIAL
                                      84-96
*** Certain information on this page has been omitted and filed separately with
the Commission. Confidential treatment has been requested with respect to the
omitted portions.
<PAGE>
                                 ATTACHMENT 1.37

                                    [***]

                                  CONFIDENTIAL
                                     97-103
*** Certain information on this page has been omitted and filed separately with
the Commission. Confidential treatment has been requested with respect to the
omitted portions.
<PAGE>
                                   SCHEDULE 2
     RESEARCH EVENT PAYMENTS TO LIGAND FOR COVERED PRODUCTS AND COMBINATION
                                    PRODUCTS

<TABLE>
<CAPTION>
        RESEARCH EVENT        COVERED          COVERED     WYETH COMPOUNDS    WYETH COMPOUND
                             COMPOUNDS        COMPOUND                        COMBINATIONS
                                            COMBINATIONS
--------------------------------------------------------------------------------------------
<S>                          <C>            <C>            <C>                <C>
      DISCOVERY BOARD          [***]            [***]          [***]                [***]
      RECOMMENDATION

      DEVELOPMENT TRACK        [***]            [***]          [***]                [***]
      APPROVAL

      IND FILING               [***]            [***]          [***]                [***]

      ICE                      [***]            [***]          [***]                [***]

      INITIATION OF            [***]            [***]          [***]                [***]
      PHASE III

      U.S. NDA FILING          [***]            [***]          [***]                [***]

      EX. U.S. FILING IN       [***]            [***]          [***]                [***]
      A MAJOR MARKET
      COUNTRY

      U.S. NDA APPROVAL        [***]            [***]          [***]                [***]

      EX. US APPROVAL          [***]            [***]          [***]                [***]
      WITH PRICING IN A
      MAJOR MARKET
      COUNTRY

      TOTAL                    [***]            [***]          [***]                [***]
</TABLE>

As used in this Schedule 2, "ICE" means the decision of the Wyeth Development
Council or its equivalent to continue development of a drug candidate based on
an "interim clinical evaluation" of evidence accruing from Phase I/IIa studies.

                                  CONFIDENTIAL
                                       104
*** Certain information on this page has been omitted and filed separately with
the Commission. Confidential treatment has been requested with respect to the
omitted portions.
<PAGE>
                                 ATTACHMENT 5.3

                                                                    CONFIDENTIAL

                                 WYETH RESEARCH
                            Development Status Update

For Ligand Pharmaceuticals

COMPOUND NO.:                             COMPOUND NAME:
THERAPEUTIC AREA:                         TARGET INDICATION:       CONTRACEPTION
MOLECULAR TARGET:                         DEVELOPMENT PHASE:
MECHANISM OF ACTION:                      STATUS:

          ACTUAL and PROJECTED DEVELOPMENT & MILESTONE PAYMENT DATES

<TABLE>
<CAPTION>
   DISCOVERY    DEVELOPMENT                                   INTERIM
     BOARD         TRACK        IND       FIRST   START OF   DECISION   START OF     NDA (OR EQUIV.)      NDA (OR EQUIV.)
RECOMMENDATION    APPROVAL    FILING   HUMAN DOSE  PHASE 2  POINT (POC)  PHASE 3          FILING             APPROVAL
                                                                                      US     EX - US 1     US     EX - US 2
---------------------------------------------------------------------------------------------------------------------------
<S>             <C>           <C>      <C>        <C>       <C>         <C>          <C>     <C>          <C>     <C>
                Dev.                                        POC =
                Track=Start                                 Proof of
                of Phase 0                                  Concept
</TABLE>

EXPLANATION FOR DATE CHANGES SINCE THE LAST REPORT AND PLANS FOR RESOLUTION

TARGETED NEXT KEY DEVELOPMENT DATE, EVENTS, ETC.  (FIM, PHASE II DOSING, ETC.)

PUBLICATIONS:

                                  CONFIDENTIAL
                                       105
<PAGE>
                                   SCHEDULE 3

                                    [***]

 *** Certain information on this page has been omitted and filed separately with
the Commission. Confidential treatment has been requested with respect to the
omitted portions.<PAGE>
                                                                  EXHIBIT 10.289

                       LIGAND PHARMACEUTICALS INCORPORATED

                            STOCK ISSUANCE AGREEMENT

            This STOCK ISSUANCE AGREEMENT is made this _____ day of
______________, 200__ (the "Grant Date"), by and between Ligand Pharmaceuticals
Incorporated, a Delaware corporation, and _________________________, a member of
the Board and a Participant in the Corporation's 2002 Stock Incentive Plan.

            All capitalized terms in this Agreement shall have the meaning
assigned to them in this Agreement or in the attached Appendix.

      A. PURCHASE OF SHARES

            1. PURCHASE. Participant hereby purchases _____________ shares of
Common Stock (the "Purchased Shares") pursuant to the provisions of the Stock
Issuance Program at the purchase price of $______ per share (the "Purchase
Price"). The Purchase Price is equal to the Fair Market Value per share of the
Common Stock on the Grant Date.

            2. PAYMENT. Concurrently with the delivery of this Agreement to the
Corporation, Participant shall pay the Purchase Price for the Purchased Shares
in any form of consideration permitted under the Plan (including by an election
to apply Participant's right to receive all or a portion of his or her annual
fees for calendar year 2006 to the payment of the Purchase Price) and shall
deliver a duly executed blank Assignment Separate from Certificate (in the form
attached hereto as Exhibit I) with respect to the Purchased Shares.

            3. STOCKHOLDER RIGHTS. Until such time as the Purchased Shares are
forfeited pursuant to the Forfeiture Restriction, Participant (or any successor
in interest) shall have all the rights of a stockholder (including voting,
dividend and liquidation rights) with respect to the Purchased Shares, subject,
however, to the transfer restrictions of this Agreement.

            4. ESCROW. The Corporation shall have the right to hold the
Purchased Shares in escrow until those shares have vested in accordance with the
Vesting Schedule.

            5. COMPLIANCE WITH LAW. Under no circumstances shall shares of
Common Stock or other assets be issued or delivered to Participant pursuant to
the provisions of this Agreement unless, in the opinion of counsel for the
Corporation or its successors, there shall have been compliance with all
applicable requirements of applicable securities laws, all applicable listing
requirements of any stock exchange (or the Nasdaq National Market, if
applicable) on which the Common Stock is at the time listed for trading and all
other requirements of law or of any regulatory bodies having jurisdiction over
such issuance and delivery.

<PAGE>

      B. TRANSFER RESTRICTIONS

            1. RESTRICTION ON TRANSFER. Except for any Permitted Transfer,
Participant shall not transfer, assign, encumber or otherwise dispose of any of
the Purchased Shares which are subject to the Forfeiture Restriction.

            2. RESTRICTIVE LEGEND. The stock certificate, if any, for the
Purchased Shares shall be endorsed with the following restrictive legend:

            "THE SHARES REPRESENTED BY THIS CERTIFICATE ARE UNVESTED AND SUBJECT
      TO CERTAIN FORFEITURE RESTRICTIONS AND ACCORDINGLY MAY NOT BE SOLD,
      ASSIGNED, TRANSFERRED, ENCUMBERED, OR IN ANY MANNER DISPOSED OF EXCEPT IN
      CONFORMITY WITH THE TERMS OF A WRITTEN AGREEMENT BETWEEN THE CORPORATION
      AND THE REGISTERED HOLDER OF THE SHARES (OR THE PREDECESSOR IN INTEREST TO
      THE SHARES). A COPY OF SUCH AGREEMENT IS MAINTAINED AT THE CORPORATION'S
      PRINCIPAL CORPORATE OFFICES."

            3. TRANSFEREE OBLIGATIONS. Each person (other than the Corporation)
to whom the Purchased Shares are transferred by means of a Permitted Transfer
must, as a condition precedent to the validity of such transfer, acknowledge in
writing to the Corporation that such person is bound by the provisions of this
Agreement and that the transferred shares are subject to the Forfeiture
Restriction to the same extent such shares would be so subject if retained by
Participant.

      C. FORFEITURE RESTRICTION

            1. GRANT. Subject to the provisions of Paragraph C.2 below, if
Participant ceases for any reason to remain in service as a member of the Board,
all of the Unvested Shares (as defined below) shall thereupon be forfeited
immediately and without any further action by the Corporation (the "Forfeiture
Restriction"). Upon the occurrence of such a forfeiture, the Corporation shall
become the legal and beneficial owner of the Unvested Shares being forfeited and
all rights and interests therein or relating thereto, and the Corporation shall
have the right to retain and transfer to its own name the number of Unvested
Shares being forfeited by Participant. In the event any of the Unvested Shares
are forfeited under this Paragraph C.1., any dividends or other distributions
paid on such Unvested Shares and held by the escrow agent pursuant to Paragraph
A.4 shall be promptly paid by the escrow agent to the Corporation. For purposes
of this Agreement, all of the Purchased Shares in which Participant is not, at
the time of his or her cessation of service as a member of the Board, vested in
accordance with the Vesting Schedule set forth in Paragraph C.2 of this
Agreement or the special vesting acceleration provisions of Paragraph C.4 of
this Agreement are hereinafter referred to as the "Unvested Shares."

                                       2
<PAGE>

            2. TERMINATION OF THE FORFEITURE RESTRICTION. The Forfeiture
Restriction shall terminate and cease to be applicable with respect to any and
all Purchased Shares in which Participant vests in accordance with the following
Vesting Schedule:

            Participant shall acquire a vested interest in, and the Forfeiture
            Restriction shall lapse with respect to, the Purchased Shares in a
            series of twelve (12) successive equal monthly installments upon
            Participant's completion of each calendar month of service as a
            member of the Board during calendar year 2006, with the first such
            installment to become vested upon Participant's continuation in
            Board service through January 31, 2006.

            In the event any Unvested Shares are released from the Forfeiture
Restriction, any dividends or other distributions paid on such shares and held
by the escrow agent pursuant to Paragraph A.4 shall be promptly paid by the
escrow agent to Participant.

            3. RECAPITALIZATION. Any new, substituted or additional securities
or other property which is by reason of any Recapitalization distributed with
respect to the Purchased Shares shall be immediately subject to the Forfeiture
Restriction and any escrow requirements hereunder, but only to the extent the
Purchased Shares are at the time covered by such Forfeiture Restriction or
escrow requirements. Appropriate adjustments to reflect such distribution shall
be made to the number and/or class of securities subject to this Agreement in
order to reflect the effect of any such Recapitalization upon the Corporation's
capital structure.

            4. CHANGE IN CONTROL OR HOSTILE TAKE-OVER. Immediately prior to the
consummation of any Change in Control or Hostile Take-Over effected during
Participant's period of Board service, the Forfeiture Restriction shall
automatically lapse in its entirety and the Purchased Shares shall vest in full.

            5. DEATH OR DISABILITY. In the event a Participant's period of Board
service terminates as a result of his or her death or Permanent Disability, the
Forfeiture Restriction shall automatically lapse in its entirety and the
Purchased Shares shall vest in full.

                                       3
<PAGE>

      D. TAXES

            Participant has reviewed with Participant's own tax advisors the
federal, state, local and foreign tax consequences of this investment and the
transactions contemplated by this Agreement. Participant is relying solely on
such advisors and not on any statements or representations of the Company or any
of its agents. Participant understands that Participant (and not the
Corporation) shall be responsible for Participant's own tax liability that may
arise as a result of this investment or the transactions contemplated by this
Agreement. Participant understands that Participant will recognize ordinary
income for federal income tax purposes under Section 83 of the Code. In this
context, "restriction" includes the Forfeiture Restriction set forth in Article
C.

      E. GENERAL PROVISIONS

            1. ASSIGNMENT. The Corporation may assign any of its rights under
this Agreement to any person or entity selected by the Board, including (without
limitation) one or more stockholders of the Corporation.

            2. NO RIGHT TO CONTINUED SERVICE. Nothing in this Agreement or in
the Plan shall confer upon Participant any right to continue in service as an
employee, director or consultant to the Company or any Parent or Subsidiary for
any period of specific duration or interfere with or otherwise restrict in any
way the rights of the Corporation (or any Parent or Subsidiary employing or
retaining Participant) or of Participant, which rights are hereby expressly
reserved by each, to terminate Participant's service at any time for any reason,
with or without cause.

            3. NOTICES. Any notice required to be given under this Agreement
shall be in writing and shall be deemed effective upon personal delivery or upon
deposit in the U.S. mail, registered or certified, postage prepaid and properly
addressed to the party entitled to such notice at the address indicated below
such party's signature line on this Agreement or at such other address as such
party may designate by ten (10) days advance written notice under this paragraph
to all other parties to this Agreement.

            4. NO WAIVER. No waiver of any breach or condition of this Agreement
shall be deemed to be a waiver of any other or subsequent breach or condition,
whether of like or different nature.

            5. CANCELLATION OF SHARES. If any Unvested Shares are forfeited to
the Corporation as provided in this Agreement, then from and after the time of
such forfeiture, the person forfeiting such shares shall no longer have any
rights as a holder of such shares. Such shares shall be deemed forfeited in
accordance with the applicable provisions hereof, and the Corporation shall be
deemed the owner and holder of such shares, whether or not the certificates
therefor have been delivered as required by this Agreement.

            6. PARTICIPANT UNDERTAKING. Participant hereby agrees to take
whatever additional action and execute whatever additional documents the
Corporation may deem

                                       4
<PAGE>
necessary or advisable in order to carry out or effect one or more of the
obligations or restrictions imposed on either Participant or the Purchased
Shares pursuant to the provisions of this Agreement.

            7. AGREEMENT IS ENTIRE CONTRACT. This Agreement constitutes the
entire contract between the parties hereto with regard to the subject matter
hereof. This Agreement is made pursuant to the provisions of the Plan and shall
in all respects be construed in conformity with the terms of the Plan.

            8. GOVERNING LAW. This Agreement shall be governed by, and construed
in accordance with, the laws of the State of California without resort to that
State's conflict-of-laws rules.

            9. COUNTERPARTS. This Agreement may be executed in counterparts,
each of which shall be deemed to be an original, but all of which together shall
constitute one and the same instrument.

            10. SUCCESSORS AND ASSIGNS. The provisions of this Agreement shall
inure to the benefit of, and be binding upon, the Corporation and its successors
and assigns and upon Participant, Participant's assigns and the legal
representatives, heirs and legatees of Participant's estate, whether or not any
such person shall have become a party to this Agreement and have agreed in
writing to join herein and be bound by the terms hereof.

                                       5
<PAGE>

            IN WITNESS WHEREOF, the parties have executed this Agreement on the
day and year first indicated above.

                                   LIGAND PHARMACEUTICALS INCORPORATED

                                   By:______________________________________

                                   Title:___________________________________

                                   Address:_________________________________

                                   _________________________________________

                                   PARTICIPANT

                                   _________________________________________
                                   Signature

                                   Address:_________________________________

                                   _________________________________________

                                       6
<PAGE>

                             SPOUSAL ACKNOWLEDGMENT

            The undersigned spouse of Participant has read and hereby approves
the foregoing Stock Issuance Agreement. In consideration of the Corporation's
granting Participant the right to acquire the Purchased Shares in accordance
with the terms of such Agreement, the undersigned hereby agrees to be
irrevocably bound by all the terms of such Agreement, including (without
limitation) the right of the Corporation (or its assigns) to purchase any
Purchased Shares in which Participant is not vested at the time of his or her
termination of service as a member of the Board.

                                   _________________________________________
                                             PARTICIPANT'S SPOUSE

                                   Address:_________________________________

                                   _________________________________________

<PAGE>

                                    EXHIBIT I

                      ASSIGNMENT SEPARATE FROM CERTIFICATE

            FOR VALUE RECEIVED _______________________ hereby sell(s), assign(s)
and transfer(s) unto Ligand Pharmaceuticals Incorporated (the "Corporation"),
_____________________ (________) shares of the Common Stock of the Corporation
standing in his or her name on the books of the Corporation represented by
Certificate No. ______________ herewith and do(es) hereby irrevocably constitute
and appoint ____________________ Attorney to transfer the said stock on the
books of the Corporation with full power of substitution in the premises.

Dated:  _________________, _____.

                                   Signature________________________________

INSTRUCTION: Please do not fill in any blanks other than the signature line.
Please sign exactly as you would like your name to appear on the issued stock
certificate. The purpose of this assignment is to enable the Corporation to
enforce the Forfeiture Restriction without requiring additional signatures on
the part of Participant.

<PAGE>

                                    APPENDIX

            The following definitions shall be in effect under the Agreement:

            A. AGREEMENT shall mean this Stock Issuance Agreement.

            B. BOARD shall mean the Corporation's Board of Directors.

            C. CHANGE IN CONTROL shall mean a change in ownership or control of
the Corporation effected through any of the following transactions:

                  (i) a merger, consolidation or other reorganization approved
            by the Corporation's stockholders, unless securities representing
            more than fifty percent (50%) of the total combined voting power of
            the voting securities of the successor corporation are immediately
            thereafter beneficially owned, directly or indirectly and in
            substantially the same proportion, by the persons who beneficially
            owned the Corporation's outstanding voting securities immediately
            prior to such transaction, or

                  (ii) the sale, transfer or other disposition of all or
            substantially all of the Corporation's assets in complete
            liquidation or dissolution of the Corporation, or

                  (iii) the acquisition, directly or indirectly by any person or
            related group of persons (other than the Corporation or a person
            that directly or indirectly controls, is controlled by, or is under
            common control with, the Corporation), of beneficial ownership
            (within the meaning of Rule 13d-3 of the 1934 Act) of securities
            possessing more than fifty percent (50%) of the total combined
            voting power of the Corporation's outstanding securities pursuant to
            a tender or exchange offer made directly to the Corporation's
            stockholders.

            D. COMMON STOCK shall mean shares of the Corporation's common stock.

            E. CODE shall mean the Internal Revenue Code of 1986, as amended.

            F. CORPORATION shall mean Ligand Pharmaceuticals Incorporated, a
Delaware corporation, and any successor corporation to all or substantially all
of the assets or voting stock of Ligand Pharmaceuticals Incorporated.

            G. FAIR MARKET VALUE per share of Common Stock on any relevant date
shall be determined in accordance with the following provisions:

                  (i) If the Common Stock is at the time traded on the Nasdaq
            National Market, then the Fair Market Value shall be deemed equal to
            the closing selling price per share of Common Stock on the date in
            question, as the price is reported by the National Association of
            Securities Dealers on the Nasdaq National

                                      A-1
<PAGE>

            Market and published in The Wall Street Journal. If there is no
            closing selling price for the Common Stock on the date in question,
            then the Fair Market Value shall be the closing selling price on the
            last preceding date for which such quotation exists, or

                  (ii) If the Common Stock is at the time listed on any Stock
            Exchange, then the Fair Market Value shall be deemed equal to the
            closing selling price per share of Common Stock on the date in
            question on the Stock Exchange determined by the Plan Administrator
            to be the primary market for the Common Stock, as such price is
            officially quoted in the composite tape of transactions on such
            exchange and published in The Wall Street Journal. If there is no
            closing selling price for the Common Stock on the date in question,
            then the Fair Market Value shall be the closing selling price on the
            last preceding date for which such quotation exists.

            H. FORFEITURE RESTRICTION shall mean the right granted to the
Corporation in accordance with Article C.

            I. GRANT DATE shall mean the date of grant as specified in the first
paragraph of this Agreement.

            J. HOSTILE TAKE-OVER shall mean a change in ownership or control of
the Corporation effected through either of the following transactions:

                  (i) a change in the composition of the Board over a period of
            thirty-six (36) consecutive months or less such that a majority of
            the Board members ceases, by reason of one or more contested
            elections for Board membership, to be comprised of individuals who
            either (A) have been Board members continuously since the beginning
            of such period or (B) have been elected or nominated for election as
            Board members during such period by at least a majority of the Board
            members described in clause (A) who were still in office at the time
            the Board approved such election or nomination; or

                  (ii) a Hostile Tender-Offer.

            K. HOSTILE TENDER-OFFER shall mean the acquisition, directly or
indirectly, by any person or related group of persons (other than the
Corporation or a person that directly or indirectly controls, is controlled by,
or is under common control with, the Corporation) of beneficial ownership
(within the meaning of Rule 13d-3 of the 1934 Act) of securities possessing more
than fifty percent (50%) of the total combined voting power of the Corporation's
outstanding securities pursuant to a tender or exchange offer made directly to
the Corporation's stockholders which the Board does not recommend such
stockholders to accept

            L. 1934 ACT shall mean the Securities Exchange Act of 1934, as
amended.

                                      A-2
<PAGE>

            M. OWNER shall mean Participant and all subsequent holders of the
Purchased Shares who derive their chain of ownership through a Permitted
Transfer from Participant.

            N. PARENT shall mean any corporation (other than the Corporation) in
an unbroken chain of corporations ending with the Corporation, provided each
corporation in the unbroken chain (other than the Corporation) owns, at the time
of the determination, stock possessing fifty percent (50%) or more of the total
combined voting power of all classes of stock in one of the other corporations
in such chain.

            O. PARTICIPANT shall mean the person to whom the Purchased Shares
are issued under the Stock Issuance Program.

            P. PERMITTED TRANSFER shall mean (i) a gratuitous transfer of the
Purchased Shares, provided and only if Participant obtains the Corporation's
prior written consent to such transfer, (ii) a transfer of title to the
Purchased Shares effected pursuant to Participant's will or the laws of
inheritance following Participant's death or (iii) a transfer to the Corporation
in pledge as security for any purchase-money indebtedness incurred by
Participant in connection with the acquisition of the Purchased Shares.

            Q. PLAN shall mean the Corporation's 2002 Stock Incentive Plan.

            R. PLAN ADMINISTRATOR shall mean either the Board or a committee of
the Board acting in its administrative capacity under the Plan.

            S. PURCHASE PRICE shall have the meaning assigned to such term in
Paragraph A.1.

            T. PURCHASED SHARES shall have the meaning assigned to such term in
Paragraph A.1.

            U. RECAPITALIZATION shall mean any stock split, stock dividend,
recapitalization, combination of shares, exchange of shares or other change
affecting the Corporation's outstanding Common Stock as a class without the
Corporation's receipt of consideration.

            V. STOCK EXCHANGE shall mean the American Stock Exchange or the New
York Stock Exchange.

            W. STOCK ISSUANCE PROGRAM shall mean the Stock Issuance Program
under the Plan.

            X. SUBSIDIARY shall mean any corporation (other than the
Corporation) in an unbroken chain of corporations beginning with the
Corporation, provided each corporation (other than the last corporation) in the
unbroken chain owns, at the time of the determination, stock possessing fifty
percent (50%) or more of the total combined voting power of all classes of stock
in one of the other corporations in such chain.

                                      A-3
<PAGE>

            Y. VESTING SCHEDULE shall mean the vesting schedule specified in
Paragraph C.3, pursuant to which the Purchased Shares are to vest in a series of
installments over Participant's period of service as a member of the Board.

            Z. UNVESTED SHARES shall have the meaning assigned to such term in
Paragraph C.1.

                                      A-4

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