AS FILED WITH THE 

As filed with the Securities and Exchange Commission on May 20, 2009

Registration No. 333-            

UNITED STATES

SECURITIES AND EXCHANGE COMMISSION ON JULY 25, 2003

Washington, D.C. 20549

Form S-3

REGISTRATION STATEMENT NO. 33-___________ ================================================================================ SECURITIES AND EXCHANGE COMMISSION WASHINGTON, D.C. 20549 ------------------------------------ FORM S-3 REGISTRATION STATEMENT

UNDER

THE SECURITIES ACT OF 1933 ------------------------------------

LIGAND PHARMACEUTICALS INCORPORATED (Exact Name

(Exact name of Registrantregistrant as Specifiedspecified in its Charter) DELAWARE (State or Other Jurisdiction of Incorporation or Organization) 77-0160744 (I.R.S. Employer Identification Number) ------------------------------------ charter)

Delaware77-0160744
(State or other jurisdiction of incorporation or organization)(I.R.S. Employer Identification Number)

10275 Science Center Drive

San Diego, California 92121-1117

(858) 550-7500 (Address, Including Zip Code,

(Address, including zip code, and Telephone Number, Including Area Code,telephone number, including area code, of Registrant's Principal Executive Offices) ------------------------------------ David E. Robinson registrant’s principal executive offices)

John L. Higgins

President and Chief Executive Officer LIGAND PHARMACEUTICALS INCORPORATED

Ligand Pharmaceuticals Incorporated

10275 Science Center Drive

San Diego, California 92121-1117

(858) 550-7500 (Name, Address, Including Zip Code,

(Name, address, including zip code, and Telephone Number, Including Area Code,telephone number, including area code, of Agentagent for Service) ------------------------------------ service)

Copies to: Faye H. Russell,To:

Scott N. Wolfe, Esq. CLIFFORD CHANCE US

Latham & Watkins LLP 3811 Valley Centre

12636 High Bluff Drive, Suite 200 400

San Diego, California 92130

(858) 720-3500 ------------------------------------ 523-5400

Approximate date of commencement of proposed sale to the public:  From time to time after the effective date of this registration statement.

If the only securities being registered on this form are being offered pursuant to dividend or interest reinvestment plans, please check the following box: [ ] box.  ¨

If any of the securities being registered on this form are to be offered on a delayed or continuous basis pursuant to Rule 415 under the Securities Act of 1933, as amended, other than securities offered only in connection with dividend or interest reinvestment plans, check the following box: [x] box.  þ

If this form is filed to register additional securities for an offering pursuant to Rule 462(b) under the Securities Act, check the following box and list the Securities Act registration statement number of the earlier effective registration statement for the same offering: [ ] offering.  ¨

If this form is a post-effective amendment filed pursuant to Rule 462(c) under the Securities Act, check the following box and list the Securities Act registration statement number of the earlier effective registration statement for the same offering: [ ] offering.  ¨

If delivery ofthis form is a registration statement pursuant to General Instruction I.D. or a post-effective amendment thereto that shall become effective upon filing with the prospectus is expected to be madeSecurities and Exchange Commission pursuant to Rule 434, please462(e) under the Securities Act, check the following box: [ ] box.  ¨

If this form is a post-effective amendment to a registration statement filed pursuant to General Instruction I.D. filed to register additional securities or additional classes of securities pursuant to Rule 413(b) under the Securities Act, check the following box.  ¨

Indicate by check mark whether the registrant is a large accelerated filer, an accelerated filer, a non-accelerated filer, or a smaller reporting company. See the definitions of “large accelerated filer,” “accelerated filer” and “smaller reporting company” in Rule 12b-2 of the Exchange Act. (Check one):

Large accelerated filer  ¨Accelerated filer  x
Non-accelerated filer  ¨ (Do not check if a smaller reporting company)Smaller reporting company  ¨

CALCULATION OF REGISTRATION FEE

 
Title of Each Class of Securities to be Registered Amount to be
Registered(1)
 Proposed
Maximum
Offering Price
Per Share
 Proposed
Maximum
Aggregate
Offering Price
 Amount of
Registration Fee

Common stock, par value $0.001 per share

 867,637 shares $8.59(2) $7,453,002(2) $415.88

Common stock, par value $0.001 per share

 5,062 shares $8.91(3) $45,102(3) $2.51

Total

     $7,498,104 $418.39
 
 
====================================== =============== ====================== ========================== ================= PROPOSED MAXIMUM TITLE OF SHARES AMOUNT TO BE AGGREGATE OFFERING PROPOSED MAXIMUM AMOUNT OF TO BE REGISTERED REGISTERED
(1) PRICE PER SHARE Pursuant to Rule 416(a), this Registration Statement shall also cover any additional shares of the registrant’s common stock that become issuable by reason of any stock dividend, stock split, recapitalization or other similar transaction effected without receipt of consideration.
(2) AGGREGATE OFFERING REGISTRATION FEE PRICE(2) - -------------------------------------- --------------- ---------------------- -------------------------- ----------------- CommonEstimated solely for purposes of calculating the registration fee in accordance with Rule 457(g). The price per share and aggregate offering price are calculated on the basis of the exercise price of $8.59 for 867,637 shares subject to outstanding warrants.
(3)Estimated solely for purposes of calculating the registration fee in accordance with Rule 457(h). The price per share and aggregate offering price are calculated on the basis of the weighted average exercise price of $8.91 for 5,062 shares subject to outstanding stock options granted under the Pharmacopeia, Inc. Amended and Restated 2004 Stock Incentive Plan and the Pharmacopeia, Inc. 2000 Stock Option Plan.
(4)Each share of common includes a right to purchase one one-thousandth of a share of Series A Junior Participating Preferred Stock, par value $.001$0.001 per 5,835,771 $14.78 $86,252,695.38 $6,977.84 share ====================================== =============== ====================== ========================== ================= share.
(1) This

The registrant hereby amends this registration statement on such date or dates as may be necessary to delay its effective date until the registrant shall file a further amendment which specifically states that this registration statement shall also cover any additional shares of common stock whichthereafter become issuableeffective in connectionaccordance with the shares registered for sale hereby as a result of any stock dividend, stock split, recapitalization or other similar transaction effected without the receipt of consideration which results in an increase in the numberSection 8(a) of the Registrant's outstanding sharesSecurities Act of common stock. (2) Estimated solely for1933 or until this registration statement shall become effective on such date as the purpose of determining the registration fee and computedSEC, acting pursuant to Rule 457(c) based on the average of the high and low sales prices per share of the common stock on July 24, 2003 as reported on The Nasdaq Stock Market. THE REGISTRANT HEREBY AMENDS THIS REGISTRATION STATEMENT ON SUCH DATE OR DATES AS MAY BE NECESSARY TO DELAY ITS EFFECTIVE DATE UNTIL THE REGISTRANT SHALL FILE A FURTHER AMENDMENT WHICH SPECIFICALLY STATES THAT THIS REGISTRATION STATEMENT SHALL THEREAFTER BECOME EFFECTIVE IN ACCORDANCE WITH SECTION 8(A) OF THE SECURITIES ACT OF 1933, AS AMENDED, OR UNTIL THE REGISTRATION STATEMENT SHALL BECOME EFFECTIVE ON SUCH DATE AS THE SEC, ACTING PURSUANT TO SAID SECTION 8(A)said Section 8(a), MAY DETERMINE. ================================================================================ SUBJECT TO COMPLETION, DATED JULY 25, 2003 PRELIMINARY PROSPECTUS LIGAND PHARMACEUTICALS INCORPORATED 5,835,771 SHARES OF COMMON STOCK may determine.


The information in this prospectus is not complete and may be changed. WeLigand Pharmaceuticals Incorporated may not sell these securities until the registration statement filed with the Securities and Exchange Commission, of which this prospectus is a part, is effective. The preliminaryThis prospectus isdoes not constitute an offer to sell, these securities and is not solicitingor a solicitation of an offer to buy thesepurchase, the securities described in this prospectus, or the solicitation of a proxy, in any state where thejurisdiction to or from any person to whom or from whom it is unlawful to make such offer, solicitation of an offer or sale is not permitted.proxy solicitation in such jurisdiction.

Subject to completion, dated May 20, 2009

PROSPECTUS

Ligand Pharmaceuticals Incorporated

872,699 Shares of Common Stock Issuable Upon

Exercise of Warrants and Options

This prospectus relates to an aggregate of:

the resale of up to 867,637 shares of common stock, par value $0.001 per share, issued upon the exercise of certain warrants; and

the issuance of up to 5,062 shares of common stock, par value $0.001 per share, upon the exercise of certain options.

In connection with a merger transaction between Ligand Pharmaceuticals Incorporated, or Ligand, and Pharmacopeia, Inc., or Pharmacopeia, certain warrants to purchase 1,449,696 shares of common stock of Pharmacopeia, were assumed by Ligand and became exercisable to purchase 867,637 shares of Ligand common stock. Also in connection with the merger, certain options to purchase 8,473 shares of common stock of Pharmacopeia, granted under the Pharmacopeia, Inc. Amended and Restated 2004 Stock Incentive Plan, or the 2004 Plan and the Pharmacopeia, Inc. 2000 Stock Option Plan, or the 2000 Plan were assumed by Ligand and became exercisable to purchase 5,062 shares of Ligand common stock. This prospectus relates to the public offering, whichresale by certain selling security holders, from time to time, of up to 867,637 shares of Ligand common stock issuable upon the exercise of the assumed Pharmacopeia warrants and to the offer and sale by Ligand of up to 5,062 shares of common stock issuable upon the exercise of the assumed Pharmacopeia options, and the resale of such shares of common stock.

Our common stock is not being underwritten,listed for trading on the Nasdaq Global Market under the symbol “LGND.” On May 13, 2009, the closing price of 5,835,771our common stock on the Nasdaq Global Market was $2.57 per share.

The selling security holders described in the section entitled “Selling Security Holders” beginning on page 6 of this prospectus or their transferees may offer from time to time up to an aggregate of 872,699 shares of our common stock which is held by some(including 867,637 shares issuable upon exercise of our current stockholders. These stockholders acquired the assumed Pharmacopiea warrants and 5,062 shares issuable upon exercise of the assumed Pharmacopeia options.

We will not receive any proceeds from an affiliatethe sale of Elan Corporation, plc in private transactions completed in July 2003. Ourshares of common stock is traded on The Nasdaq Stock Market under the symbol "LGND." On July 24, 2003, the averageissuable upon exercise of the highassumed Pharmacopeia warrants and low sales prices forassumed Pharmacopeia options by the selling security holders. We will receive proceeds from the exercise of the warrants and options as follows:

Warrants

   Total(1)  Per Share

Price

  $7,451,385.43  $8.59

Underwriter’s Discounts and Commissions

  $—     —  

Net Proceeds

  $7,451,385.43  $8.59

 

Options

 

Price

  $43,466.63   (2)

Underwriter’s Discounts and Commissions

  $—     —  

Net Proceeds

  $43,446.63   (2)

(1)These amounts presume that all warrants and options, as applicable, are exercised.
(2)The exercise price of each option varies from $6.28 to $12.05 depending on the date of grant of such option.

For information on the possible methods of sale that may be used by the selling security holders, see “Plan of Distribution” beginning on page 8 of this prospectus.

Investing in our common stock was $14.78. ---------------------------------- THE COMMON STOCK OFFERED INVOLVES A HIGH DEGREE OF RISK. SEE "RISK FACTORS" COMMENCING ON PAGE 6 FOR A DISCUSSION OF SOME IMPORTANT RISKS YOU SHOULD CONSIDER BEFORE BUYING ANY OF OUR COMMON STOCK. ---------------------------------- NEITHER THE SECURITIES AND EXCHANGE COMMISSION NOR ANY STATE SECURITIES COMMISSION HAS APPROVED OR DISAPPROVED THESE SECURITIES, OR PASSED UPON THE ACCURACY OR ADEQUACY OF THIS PROSPECTUS. ANY REPRESENTATION TO THE CONTRARY IS A CRIMINAL OFFENSE. ---------------------------------- The datesecurities involves risks. See “Risk Factors” on page 2.

Neither the Securities and Exchange Commission nor any state securities commission has approved or disapproved of these securities or determined if this prospectus is July 25, 2003 PROSPECTUS SUMMARY THE FOLLOWING IS A SUMMARY HIGHLIGHTING SELECTED INFORMATION APPEARING ELSEWHERE IN THIS PROSPECTUS AND MAY NOT CONTAIN ALL OF THE INFORMATION THAT IS IMPORTANT TO YOU. THIS PROSPECTUS INCLUDES INFORMATION ABOUT THE SECURITIES WE ARE OFFERING, AS WELL AS INFORMATION REGARDING OUR BUSINESS AND DETAILED FINANCIAL DATA. WE ENCOURAGE YOU TO READ THIS PROSPECTUS IN ITS ENTIRETY, INCLUDING THE DOCUMENTS INCORPORATED BY REFERENCE. OUR COMPANY We are a biopharmaceutical company involved in the discovery, development and commercialization of new drugs that address critical unmet medical needs in the areas of cancer, pain, men's and women's healthtruthful or hormone related health issues, skin diseases, osteoporosis and metabolic, cardiovascular and inflammatory diseases. Our marketed products and products in development are designed to be safer, more effective, more convenient (taken orally or topically administered) and more cost efficient than existing therapies. We currently market five products and are developing, either exclusively or with our collaboration partners, 24 selected additional products in development for multiple therapeutic indications, as summarized in the table below. Our five marketed products are Avinza(R), ONTAK(R), Targretin(R) capsules, Targretin(R) gel and Panretin(R) gel. Our efforts are directed toward building a profitable biopharmaceutical company that generates income from biopharmaceutical products that we develop and market, and from research, milestone and royalty revenues from our collaborations with large pharmaceutical partners. PRODUCT SUMMARY BY THERAPEUTIC AREA (LIGAND AND COLLABORATIVE PARTNERS)
MARKETED PRODUCTS CLINICAL PROGRAMS PRE-CLINICAL PROGRAMS - ---------------------------------------------------------------------------------------------------------------------- (5 PRODUCTS) (4 PHASE III/7 PHASE II/6 PHASE I PRODUCTS IN (7 PRODUCTS IN DEVELOPMENT) DEVELOPMENT) Cancer Cancer Aging and frailty Moderate/Severe Pain Hormone replacement therapy Autoimmune diseases Osteoporosis Dermatology Dermatology Diabetes Diabetes Hormone replacement therapy Inflammation Inflammatory diseases Thrombocytopenia Sexual dysfunction Dyslipidemia OUR MARKETED PRODUCTS PRODUCT US APPROVED INDICATION EUROPEAN STATUS - ---------------------------------------------------------------------------------------------------------------------- Avinza....................... Once-daily treatment of chronic moderate-to-severe Not applicable pain ONTAK........................ Cutaneous T-cell lymphoma MAA withdrawn Targretin capsules........... Cutaneous T-cell lymphoma MA issued Targretin gel................ Cutaneous T-cell lymphoma MAA withdrawn Panretin gel................. Kaposi's sarcoma MA issued
AVINZA. Avinza is marketed for the once-daily treatment of chronic moderate-to-severe pain to patients who require continuous, around-the-clock opioid therapy. We launched US sales and marketing of Avinza with distribution in June 2002 and national promotion in July 2002 following receipt of FDA approval in March 2002. We licensed exclusive rights to Avinza in the United States and Canada from Elan in 1998. Avinza is an oral once-daily morphine product and has a more rapid onset and more stable pharmocokinetic profile with less peak-to-trough fluctuation than other competing sustained release products. The sustained-release opioid market was estimated at $2.3 billion in the United States in 2001. ONTAK. ONTAK is marketed for the treatment of patients with persistent or recurrent cutaneous T-cell lymphoma, or CTCL. ONTAK was approved by the FDA and launched in the United States in February 1999 as our first product for the treatment of patients with CTCL. ONTAK was the first treatment to be approved for CTCL in nearly 10 years. ONTAK is currently in three Phase II clinical trials for the treatment of patients with B-cell Non-Hodgkin's lymphoma. Clinical trials using ONTAK for the treatment of patients with psoriasis, rheumatoid arthritis and chronic lymphocytic leukemia, or CLL, have also been conducted, and further trials are being considered. There are physician-sponsored Phase II trials ongoing in CLL, peripheral T-cell lymphoma and graft versus host disease. We believe that these indications provide significantly larger market opportunities than CTCL. A European MAA for CTCL was filed in December 2001. In April 2003, we withdrew our MAA in Europe for our first generation product. It was our assessment that the cost of the additional clinical and technical information requested by the European Agency for the Evaluation of Medicinal Products for the first generation product would be better spent on acceleration of the second generation ONTAK development. We expect to resubmit the MAA in Europe with the second generation product in 2004 or early 2005. TARGRETIN CAPSULES. Targretin capsules are marketed for the treatment of patients with CTCL. We launched US sales and marketing of Targretin capsules in January 2000 following receipt of FDA approval in December 1999. Targretin capsules offer the convenience of a daily oral dose administered by the patient at home. We are developing Targretin capsules for a variety of larger market opportunities, including non-small cell lung cancer and moderate-to-severe plaque psoriasis. In March 2001, the European Commission granted marketing authorization for Targretin capsules in Europe for the treatment of patients with CTCL, and our network of distributors began marketing the drug in Europe in the fourth quarter of 2001. TARGRETIN GEL. Targretin gel is marketed for the treatment of patients with CTCL. We launched US sales and marketing of Targretin gel in September 2000 following receipt of FDA approval in June 2000. Targretin gel offers patients with refractory, early-stage CTCL a novel, non-invasive, self-administered treatment topically applied onlycomplete. Any representation to the affected areas of the skin. Preliminary data presented at the American Academy of Dermatology meeting in March 2001 showed that Targretin gel produced an overall response rate of 75% in patients with untreated, early-stage CTCL. Targretin gelcontrary is currently in clinical development for hand dermatitis, and we released interim Phase I/II data from a 55-patient trial in September 2002. PANRETIN GEL. Panretin gel is marketed for the treatment of patients with AIDS-related Kaposi's sarcoma, or KS. Panretin gel was approved by the FDA and launched in February 1999 as the first FDA-approved patient-applied topical treatment for AIDS-related Kaposi's sarcoma. Panretin gel represents a non-invasive option to the traditional management of this disease. Most approved therapies require the time and expense of periodic visits to a healthcare facility, where treatment is administered by a doctor or nurse. AIDS-related KS adversely affects the quality of life of thousands of people in the United States and Europe. Panretin gel was approved in Europe for the treatment of patients with KS in October 2000, and was launched through our distributor network in the fourth quarter of 2001 in Europe. 2 SALES AND MARKETING As of December 2002, our marketing and selling organization consisted of approximately 120 people. Since 1998, we had assembled a 35-person sales force for the United States focused on specialty cancer sales and selling ONTAK, Targretin capsules, Avinza, Targretin gel and Panretin gel. We have also formed a separate sales force of approximately 70 representatives to market only Avinza by targeting pain specialists and general pain centers not currently served by our specialty cancer representatives. Since a relatively small number of physicians are responsible for writing a majority of prescriptions in our target markets, we believe that the size of our sales force is appropriate to reach our target physicians. In addition, in February 2003 we entered into an agreement with Organon Pharmaceuticals USA Inc., a business unit of Akzo Nobel N.V., under which we co-promote Avinza with Organon's primary care, hospital (anesthesiology) and specialty (pain centers) sales forces, which together consist of more than 700 sales representatives. COLLABORATIVE RESEARCH AND DEVELOPMENT PROGRAMS We are currently involved in the research phase of research and development collaborations with Eli Lilly and TAP Pharmaceuticals. Collaborations in the development phase are being pursued by Abbott Laboratories, Allergan, GlaxoSmithKline, Organon (AKZO-Nobel), Pfizer and Wyeth (formerly American Home Products). Currently, our corporate partners have 10 Ligand products in human development, four products moving toward regulatory filings for human clinical trials and numerous compounds in research and pre-clinical stages. These products are being studied for the treatment of health problems in large markets such as osteoporosis, diabetes, contraception and cardiovascular disease. Three of these partner products are being tested in three separate pivotal Phase III clinical trial programs: lasofoxifene, which is being developed by Pfizer for osteoporosis; and bazedoxifene (formerly TSE-424), which is being developed by Wyeth both as monotherapy for osteoporosis and in combination with Wyeth's Premarin as hormone replacement therapy, or HRT. PROPRIETARY TECHNOLOGY PLATFORM Internal and collaborative research and development programs are built around our proprietary science technology, which is based on our leadership position in gene transcription technology, a technology for regulating how genes control cellular activity. Our proprietary technologies involve two natural mechanisms that regulate gene activity: hormone-activated intracellular receptors, or IRs, a type of sensor or switch inside cells that turns genes on and off and alters the production of proteins in response to hormones, and Signal Transducers and Activators of Transcription, or STATs, another type of protein production switch. Targretin capsules, Targretin gel, Panretin gel and all but one of our corporate partner products currently on human development track were discovered using our IR technology. PRODUCT PIPELINE SUMMARY We are developing several proprietary products for which we have worldwide rights for a variety of cancers, skin diseases and other indications, as summarized in the table below. Many of the indications being pursued may present larger market opportunities for our currently marketed products. Our clinical development programs are primarily based on products discovered through our IR technology, with the exception of ONTAK, which was developed using Seragen's fusion protein technology, and Avinza, which was developed by Elan. Five of the products in our proprietary product development programs are retinoids, discovered and developed using our proprietary IR technology. Our research is based on both our IR and STAT technologies. In addition to our proprietary product pipeline, our collaborative partners have multiple products in human development, as well as numerous compounds in research and pre-clinical stages. 3 PRODUCT PIPELINE SUMMARY (CONTINUED)
PRODUCT CLINICAL INDICATION DEVELOPMENT COMMERCIALIZATION RIGHTS STATUS - ---------------------------------------------------------------------------------------------------------------------- OUR MARKETED PRODUCTS AND DEVELOPMENT PROGRAMS Avinza..................... Chronic pain (moderate-to-severe) Marketed United States and Canada ONTAK...................... Cutaneous T-cell lymphoma Marketed Worldwide Peripheral T-cell lymphoma Phase II Chronic lymphocytic leukemia Phase II B-cell Non-Hodgkin's lymphoma Phase II Psoriasis (severe) Phase II Targretin capsules......... Cutaneous T-cell lymphoma Marketed Worldwide Non-small cell lung cancer Phase III (combination and monotherapy) Psoriasis (moderate to severe) Phase II Advanced breast cancer Phase II Renal cell cancer Phase II Targretin gel.............. Cutaneous T-cell lymphoma Marketed Worldwide Hand dermatitis Phase II Psoriasis Phase II Panretin gel............... Kaposi's sarcoma Marketed Worldwide Panretin capsules.......... Kaposi's sarcoma, bronchial metaplasia Phase II Worldwide LGD 1550................... Advanced cancers Phase II Worldwide Acne, psoriasis Pre-clinical LGD 1331................... Acne, prostate cancer, androgenetic Pre-clinical Worldwide alopecia, hirsutism Glucocorticoid agonist..... Inflammation, cancer Pre-clinical Worldwide Mineralocorticoid receptor modulators.............. Congestive heart failure, hypertension Research Worldwide OUR COLLABORATIVE RESEARCH AND DEVELOPMENT PROGRAMS Lasofoxifene............... Osteoporosis and breast cancer prevention Phase III Pfizer Bazedoxifene (TSE424)...... Osteoporosis Phase III Wyeth Bazedoxifene Premarin...... Hormone replacement therapy Phase III Wyeth ERA 923.................... Breast cancer Phase II Wyeth NSP 989.................... Contraception, hormone replacement therapy Phase I Wyeth NSP 989 combo.............. Contraception Phase I Wyeth GW 516 (501516)............ Dyslipidemia Phase I GlaxoSmithKline LY 929..................... Type II diabetes, dyslipidemia Phase I Lilly LY 818..................... Type II diabetes Phase II Lilly SB-497115.................. Thrombocytopenia Phase I GlaxoSmithKline LY 674..................... Dyslipidemia Phase I Lilly LGD 2226/back-ups.......... Sexual dysfunction--hypogonadism IND Track TAP LY YYY..................... Type II diabetes, dyslipidemia IND Track Lilly LY WWW..................... Dyslipidemia IND Track Lilly - ------------------------------------------------------------------------------------------------------------------------
4 criminal offense.

Our principal executive offices are located at 10275 Science Center Drive, San Diego, California, 92121, and our92121. Our telephone number is (858) 550-7500. Our website

The date of this prospectus is                     located at WWW.LIGAND.COM., 2009


TABLE OF CONTENTS

Page

ABOUT THIS PROSPECTUS

1

RISK FACTORS

2

FORWARD-LOOKING STATEMENTS

2

USE OF PROCEEDS

2

DETERMINATION OF WARRANT AND OPTION EXERCISE PRICES

3

DESCRIPTION OF CAPITAL STOCK

4

SELLING SECURITY HOLDERS

8

PLAN OF DISTRIBUTION

12

LEGAL MATTERS

15

EXPERTS

15

DISCLOSURE OF COMMISSION POSITION ON INDEMNIFICATION FOR SECURITIES ACT LIABILITIES

15

WHERE YOU CAN FIND MORE INFORMATION

15

INCORPORATION BY REFERENCE

16

ABOUT THIS PROSPECTUS

You should rely only on the information contained in this prospectus. Neither we nor the selling stockholders have authorized anyone to provide you with information different from that contained in this prospectus or additional information. We are not making an offer of these securities in any state where the offer is not permitted. The information on our websitecontained in this prospectus is not a partaccurate only as of the date of this prospectus. Our trademarks, trade names and service marks referenced in this document include Ligand(R), Avinza(R), ONTAK(R), Panretin(R) and Targretin(R). Each other trademark, trade name or service mark appearing in this document belongs to its holder. Reference to Ligand Pharmaceuticals Incorporated, "Ligand," the "Company," "we" or "our" include Ligand's wholly owned subsidiaries, Glycomed Incorporated, Ligand Pharmaceuticals (Canada) Incorporated, Ligand Pharmaceuticals International, Inc., and Seragen, Inc. RECENT DEVELOPMENTS EXTENSION OF R&D COLLABORATION WITH ELI LILLY AND COMPANY On May 8, 2003, we announced the second extension, until November 2004, of our research collaboration with Eli Lilly and Company focused on discovering novel drugs for type II diabetes and cardiovascular disorders. The Lilly-Ligand collaboration, which began in 1997, already has advanced three peroxisome proliferation activated receptor, or PPAR, modulators into clinical studies. PPARs are a subfamily of intracellular receptors that regulate glucose and lipid homeostasis. They play a key role in enhancing cellular responses to insulin, and in fat tissue stores and metabolism. ORGANIZATIONAL CHANGES On May 15, 2003, we announced the following organizational changes: >> Andres Negro-Vilar, M.D., P.h.D. was promoted to Executive Vice President for Research and Development and Chief Scientific Officer. Dr. Negro-Vilar was previously our Senior Vice President for Research and Development; >> Tod Mertes was promoted to Vice President and Controller. Mr. Mertes was previously our Director of Finance; >> Tom Silberg left to pursue other opportunities. Mr. Silberg was formerly our Executive Vice President and Chief Operating Officer; and >> Gian Aliprandi was promoted to Senior Vice President for Technical, Supply and International Operations. Mr. Aliprandi was previously our Vice President, Senior Corporate Controller and Treasurer. MILESTONE PAYMENT AS GLAXOSMITHKLINE ADVANCES DEVELOPMENT OF 501516 On June 4, 2003, we announced that we had earned a $1.0 million milestone payment from GlaxoSmithKline as a result of GlaxoSmithKline's decision to continue Phase I development of 501516, a novel PPAR modulator for the treatment of dyslipidemias. Under the recently amended terms of our research and development agreement with GlaxoSmithKline, GlaxoSmithKline is responsible for the development and registration of 501516, and may pay us milestone payments of up to $14 million as the product moves through the development process. GlaxoSmithKline has exclusive worldwide marketing rights to 501516, and will pay us up to double-digit royalties on potential product sales. If GlaxoSmithKline decides not to proceed with development of 501516, we will retain the right to develop and commercialize the product. 5 RISK FACTORS IN ADDITION TO THE OTHER INFORMATION IN THIS PROSPECTUS, YOU SHOULD CAREFULLY CONSIDER THE FOLLOWING RISKS AND UNCERTAINTIES BEFORE PURCHASING OUR SECURITIES. EACH OF THESE RISKS AND UNCERTAINTIES COULD ADVERSELY AFFECT OUR BUSINESS, OPERATING RESULTS AND FINANCIAL CONDITION, AS WELL AS THE VALUE OF AN INVESTMENT IN OUR SECURITIES. RISKS RELATED TO US AND OUR BUSINESS OUR PRODUCT DEVELOPMENT AND COMMERCIALIZATION INVOLVES A NUMBER OF UNCERTAINTIES, AND WE MAY NEVER GENERATE SUFFICIENT REVENUES FROM THE SALE OF PRODUCTS TO BECOME PROFITABLE. We were founded in 1987. We have incurred significant losses since our inception. At March 31, 2003, our accumulated deficit was approximately $639 million. To date, we have received the majority of our revenues from our collaborative arrangements and only began receiving revenues from the sale of pharmaceutical products in 1999. To become profitable, we must successfully develop, clinically test, market and sell our products. Even if we achieve profitability, we cannot predict the level of that profitability or whether we will be able to sustain profitability. We expect that our operating results will fluctuate from period to period as a result of differences in when we incur expenses and receive revenues from product sales, collaborative arrangements and other sources. Some of these fluctuations may be significant. Most of our products in development will require extensive additional development, including preclinical testing and human studies, as well as regulatory approvals, before we can market them. We cannot predict if or when anyprospectus, regardless of the products we are developingtime of delivery of this prospectus or those being co-developed with our partners will be approved for marketing. There are many reasons that we or our collaborative partners may fail in our efforts to develop our other potential products, including the possibility that: >> preclinical testing or human studies may show that our potential products are ineffective or cause harmful side effects; >> the products may fail to receive necessary regulatory approvals from the FDA or foreign authorities in a timely manner, or at all; >> the products, if approved, may not be produced in commercial quantities or at reasonable costs; >> the products, once approved, may not achieve commercial acceptance; >> regulatory or governmental authorities may apply restrictions to our products, which could adversely affect their commercial success; or >> the proprietary rights of other parties may prevent us or our partners from marketing the products. WE ARE BUILDING MARKETING AND SALES CAPABILITIES IN THE UNITED STATES AND EUROPE WHICH IS AN EXPENSIVE AND TIME-CONSUMING PROCESS AND MAY INCREASE OUR OPERATING LOSSES. Developing the sales force to market and sell products is a difficult, expensive and time-consuming process. We have developed a US sales force of about 90 people. We also rely on third-party distributors to distribute our products. The distributors are responsible for providing many marketing support services, including customer service, order entry, shipping and billing and customer reimbursement assistance. In Europe, we will rely initially on other companies to distribute and market our products. We have entered into agreements for the marketing and distribution of our products in territories such as the United Kingdom, Germany, France, Spain, Portugal, Greece, Italy and Central and South America and have established a subsidiary, Ligand Pharmaceuticals International, Inc., with a branch in London, England, to coordinate our European marketing and operations. Our reliance on these third parties means our results may suffer if any of them are unsuccessful or fail to perform as expected. We may not be able to continue to expand our sales and marketing capabilities sufficiently to successfully commercialize our products in the territories where they receive marketing approval. With respect to our co-promotion or licensing arrangements, for example our co-promotion agreement for Avinza, any revenues we receive will depend substantially on the marketing and sales efforts of others, which may or may not be successful. 6 OUR SMALL NUMBER OF PRODUCTS MEANS OUR RESULTS ARE VULNERABLE TO SETBACKS WITH RESPECT TO ANY ONE PRODUCT. We currently have only five products approved for marketing and a handful of other products/indications that have made significant progress through development. Because these numbers are small, especially the number of marketed products, any significant setback with respect to any one of them could significantly impair our operating results and/or reduce the market prices for our securities. Setbacks could include problems with shipping, distribution, manufacturing, product safety, marketing, government licenses and approvals, intellectual property rights and physician or patient acceptance of the product. SALES OF OUR SPECIALTY PHARMACEUTICAL PRODUCTS MAY SIGNIFICANTLY FLUCTUATE EACH PERIOD BASED ON THE NATURE OF OUR PRODUCTS, OUR PROMOTIONAL ACTIVITIES AND WHOLESALER PURCHASING AND STOCKING PATTERNS. Excluding Avinza, our products are small-volume specialty pharmaceutical products that address the needs of cancer patients in relatively small niche markets with substantial geographical fluctuations in demand. To ensure patient access to our drugs, we maintain broad distribution capabilities with inventories held at approximately 125 locations throughout the United States. Furthermore, the purchasing and stocking patterns of our wholesaler customers are influenced by a number of factors that vary with each product, including but not limited to overall level of demand, periodic promotions, required minimum shipping quantities and wholesaler competitive initiatives. As a result, the level of product in the distribution channel may average from two to six months' worth of projected inventory usage. If any or all of our major distributors decide to substantially reduce the inventory they carry in a given period, our sales for that period could be substantially lower than historical levels. OUR DRUG DEVELOPMENT PROGRAMS WILL REQUIRE SUBSTANTIAL ADDITIONAL FUTURE FUNDING WHICH COULD HURT OUR OPERATIONAL AND FINANCIAL CONDITION. Our drug development programs require substantial additional capital to successfully complete them, arising from costs to: >> conduct research, preclinical testing and human studies; >> establish pilot scale and commercial scale manufacturing processes and facilities; and >> establish and develop quality control, regulatory, marketing, sales and administrative capabilities to support these programs. Our future operating and capital needs will depend on many factors, including: >> the pace of scientific progress in our research and development programs and the magnitude of these programs; >> the scope and results of preclinical testing and human studies; >> the time and costs involved in obtaining regulatory approvals; >> the time and costs involved in preparing, filing, prosecuting, maintaining and enforcing patent claims, competing technological and market developments; >> our ability to establish additional collaborations; >> changes in our existing collaborations; >> the cost of manufacturing scale-up; and >> the effectiveness of our commercialization activities. We currently estimate our research and development expenditures over the next 3 years to range between $200 million and $275 million. However, we base our outlook regarding the need for funds on many uncertain variables. Such uncertainties include regulatory approvals, the timing of events outside our direct control such as product launches by partners and the success of such product launches, negotiations with potential strategic partners and other factors. Any of these uncertain events can significantly change our cash requirements as they determine such one-time events as the receipt of major milestones and other payments. 7 While we expect to fund our research and development activities from cash generated from internal operations to the extent possible, if we are unable to do so we may need to complete additional equity or debt financings or seek other external means of financing. If additional funds are required to support our operations and we are unable to obtain them on terms favorable to us, we may be required to cease or reduce further development or commercialization of our products, to sell some or all of our technology or assets or to merge with another entity. SOME OF OUR KEY TECHNOLOGIES HAVE NOT BEEN USED TO PRODUCE MARKETED PRODUCTS AND MAY NOT BE CAPABLE OF PRODUCING SUCH PRODUCTS. To date, we have dedicated most of our resources to the research and development of potential drugs based upon our expertise in our IR and STAT technologies. Even though there are marketed drugs that act through IRs, some aspects of our IR technologies have not been used to produce marketed products. In addition, we are not aware of any drugs that have been developed and successfully commercialized that interact directly with STATs. Much remains to be learned about the location and function of IRs and STATs. If we are unable to apply our IR and STAT technologies to the development of our potential products, we will not be successful in developing new products. WE MAY REQUIRE ADDITIONAL MONEY TO RUN OUR BUSINESS AND MAY BE REQUIRED TO RAISE THIS MONEY ON TERMS WHICH ARE NOT FAVORABLE OR WHICH REDUCE OUR STOCK PRICE. We have incurred losses since our inception and may not generate positive cash flow to fund our operations for one or more years. As a result, we may need to complete additional equity or debt financings to fund our operations. Our inability to obtain additional financing could adversely affect our business. Financings may not be available at all or on favorable terms. In addition, these financings, if completed, still may not meet our capital needs and could result in substantial dilution to our stockholders. For instance, in February and March 2002 we issued to Elan 6.3 million shares upon the conversion of zero coupon convertible senior notes held by Elan, and in April 2002 we issued 4.3 million shares of our common stock, in a private placement. These transactions have resulted in the issuance of significant numbers of new shares. In addition, in November 2002 we issued in a private placement $155,250,000 in aggregate principal amount of our 6% convertible subordinated notes due 2007, which could be converted into 25,149,025 sharessale of our common stock. If adequate funds are not available, weOur business, financial condition, results of operations and prospects may have subsequently changed since the date of this prospectus or any prospectus supplement or the date of any document incorporated by reference.

In some cases, the selling stockholders will also be required to delay, reduceprovide a prospectus supplement containing specific information about the scope of or eliminate one or more of our research or drug development programs, or our marketing and sales initiatives. Alternatively, we may be forced to attempt to continue development by entering into arrangements with collaborative partners or others that require us to relinquish some or all of our rights to technologies or drug candidates that we would not otherwise relinquish. OUR PRODUCTS FACE SIGNIFICANT REGULATORY HURDLES PRIOR TO MARKETING WHICH COULD DELAY OR PREVENT SALES. EVEN AFTER APPROVAL, GOVERNMENT REGULATION OF OUR BUSINESS IS EXTENSIVE. Before we obtain the approvals necessary to sell any of our potential products, we must show through preclinical studies and human testing that each product is safe and effective. We and our partners have a number of products moving toward or currently in clinical trials, the most significant of which are our Phase III trials for Targretin capsules in non-small cell lung cancer and three Phase III trials by our partners involving bazedoxifene and lasofoxifene. Failure to show any product's safety and effectiveness would delay or prevent regulatory approval of the product and could adversely affect our business. The clinical trials process is complex and uncertain. The results of preclinical studies and initial clinical trials may not necessarily predict the results from later large-scale clinical trials. In addition, clinical trials may not demonstrate a product's safety and effectiveness to the satisfaction of the regulatory authorities. A number of companies have suffered significant setbacks in advanced clinical trials or in seeking regulatory approvals, despite promising results in earlier trials. The FDA may also require additional clinical trials after regulatory approvals are received, which could be expensive and time-consuming, and failure to successfully conduct those trials could jeopardize continued commercialization. 8 The rate at which we complete our clinical trials depends on many factors, including our ability to obtain adequate supplies of the products to be tested and patient enrollment. Patient enrollment is a function of many factors, including the size of the patient population, the proximity of patients to clinical sitesselling stockholders and the eligibility criteria for the trial. For example, each of our Phase III Targretin clinical trials will involve approximately 600 patients and may require significant time and investment to complete enrollments. Delays in patient enrollment may result in increased costs and longer development times. In addition, our collaborative partners have rights to control product development and clinical programs for products developed under the collaborations. As a result, these collaborators may conduct these programs more slowly or in a different manner than we had expected. Even if clinical trials are completed, we or our collaborative partners still may not apply for FDA approval in a timely manner or the FDA still may not grant approval. In addition, the manufacturing and marketing of approved products is subject to extensive government regulation, including by the FDA, DEA and state and other territorial authorities. The FDA administers processes to assure that marketed products are safe, effective, consistently of uniform, high quality and marketed only for approved indications. For example, while our products are prescribed legally by some physicians for unapproved uses, we may not market our products for such uses. Failure to comply with applicable regulatory requirements can result in sanctions up to the suspension of regulatory approval as well as civil and criminal sanctions. WE FACE SUBSTANTIAL COMPETITION WHICH MAY LIMIT OUR REVENUES. Some of the drugs that we are developing and marketing will compete with existing treatments. In addition, several companies are developing new drugs that target the same diseases that we are targeting and are taking IR-related and STAT-related approaches to drug development. The principal products competing with our products targeted at the cutaneous t-cell lymphoma market are Supergen/Abbott's Nipent and interferon,terms on which is marketed by a number of companies, including Schering-Plough's Intron A. Products that compete with Avinza include Purdue Pharma L.P.'s OxyContin and MS Contin, Janssen Pharmaceutica Products, L.P.'s Duragesic, Elan's Oramorph SR and Faulding's Kadian. Many of our existing or potential competitors, particularly large drug companies, have greater financial, technical and human resources than us and may be better equipped to develop, manufacture and market products. Many of these companies also have extensive experience in preclinical testing and human clinical trials, obtaining FDA and other regulatory approvals and manufacturing and marketing pharmaceutical products. In addition, academic institutions, governmental agencies and other public and private research organizations are developing products that may compete with the products we are developing. These institutions are becoming more aware of the commercial value of their findings and are seeking patent protection and licensing arrangements to collect payments for the use of their technologies. These institutions also may market competitive products on their own or through joint ventures and will compete with us in recruiting highly qualified scientific personnel. THIRD-PARTY REIMBURSEMENT AND HEALTH CARE REFORM POLICIES MAY REDUCE OUR FUTURE SALES. Sales of prescription drugs depend significantly on the availability of reimbursement to the consumer from third party payers, such as government and private insurance plans. These third party payers frequently require drug companies to provide predetermined discounts from list prices, and they are increasingly challenging the prices charged for medical productsoffering and services. Our current and potential products may not be considered cost-effective, and reimbursement to the consumer may not be available or sufficient to allow us to sellselling our products on a competitive basis. For example, we have current and recurring discussions with insurers regarding reimbursement rates for our drugs, including Avinza which was recently approved for marketing. We may not be able to negotiate favorable reimbursement rates for our products or may have to pay significant discounts to obtain favorable rates. Only one of our products, ONTAK, is currently eligible to be reimbursed by Medicare. Proposed changes by Medicare to the hospital outpatient payment reimbursement system may adversely affect reimbursement rates for ONTAK. 9 In addition, the efforts of governments and third-party payers to contain or reduce the cost of health care will continue to affect the business and financial condition of drug companies such as us. A number of legislative and regulatory proposals to change the health care system have been discussed in recent years, including price caps and controls for pharmaceuticals. These proposals could reduce and/or cap the prices for our products or reduce government reimbursement rates for products such as ONTAK. In addition, an increasing emphasis on managed care in the United States has and will continue to increase pressure on drug pricing. We cannot predict whether legislative or regulatory proposals will be adopted or what effect those proposals or managed care efforts may have on our business. The announcement and/or adoption of such proposals or efforts could adversely affect our profit margins and business. WE RELY HEAVILY ON COLLABORATIVE RELATIONSHIPS AND TERMINATION OF ANY OF THESE PROGRAMS COULD REDUCE THE FINANCIAL RESOURCES AVAILABLE TO US, INCLUDING RESEARCH FUNDING AND MILESTONE PAYMENTS. Our strategy for developing and commercializing many of our potential products, including products aimed at larger markets, includes entering into collaborations with corporate partners, licensors, licensees and others. These collaborations provide us with funding and research and development resources for potential products for the treatment or control of metabolic diseases, hematopoiesis, women's health disorders, inflammation, cardiovascular disease, cancer and skin disease, and osteoporosis. These agreements also give our collaborative partners significant discretion when deciding whether or not to pursue any development program. Our collaborations may not continue or be successful. In addition, our collaborators may develop drugs, either alone or with others, that compete with the types of drugs they currently are developing with us. This would result in less support and increased competition for our programs. If products are approved for marketing under our collaborative programs, any revenues we receive will depend on the manufacturing, marketing and sales efforts of our collaborators, who generally retain commercialization rights under the collaborative agreements. Our current collaborators also generally have the right to terminate their collaborations under specified circumstances. If any of our collaborative partners breach or terminate their agreements with us or otherwise fail to conduct their collaborative activities successfully, our product development under these agreements will be delayed or terminated. We may have disputes in the future with our collaborators, including disputes concerning which of us owns the rights to any technology developed. For instance, we were involved in litigation with Pfizer, which we settled in April 1996, concerning our right to milestones and royalties based on the development and commercialization of droloxifene. These and other possible disagreements between us and our collaborators could delay our ability and the ability of our collaborators to achieve milestones or our receipt of other payments. In addition, any disagreements could delay, interrupt or terminate the collaborative research, development and commercialization of certain potential products, or could result in litigation or arbitration. The occurrence of any of these problems could be time-consuming and expensive and could adversely affect our business. Challenges to or failure to secure patents and other proprietary rights may significantly hurt our business. Our success will depend on our ability and the ability of our licensors to obtain and maintain patents and proprietary rights for our potential products and to avoid infringing the proprietary rights of others, both in the United States and in foreign countries. Patents may not be issued from any of these applications currently on file, or, if issued, may not provide sufficient protection. In addition, disputes with licensors under our license agreements may arise which could result in additional financial liability or loss of important technology and potential products and related revenue, if any. Our patent position, like that of many pharmaceutical companies, is uncertain and involves complex legal and technical questions for which important legal principles are unresolved. We may not develop or obtain rights to products or processes that are patentable. Even if we do obtain patents, they may not adequately protect the technology we own or have licensed. In addition, others may challenge, seek to invalidate, infringe or circumvent any patents we own or license, and rights we receive under those patents may not provide competitive advantages to us. Further, the manufacture, use or sale of our products may infringe the patent rights of others. 10 Several drug companies and research and academic institutions have developed technologies, filed patent applications or received patents for technologies that may be related to our business. Others have filed patent applications and received patents that conflict with patents or patent applications we have licensed for our use, either by claiming the same methods or compounds or by claiming methods or compounds that could dominate those licensed to us. In addition, we may not be aware of all patents or patent applications that may impact our ability to make, use or sell any of our potential products. For example, US patent applications may be kept confidential while pending in the Patent and Trademark Office and patent applications filed in foreign countries are often first published six months or more after filing. Any conflicts resulting from the patent rights of others could significantly reduce the coverage of our patents and limit our ability to obtain meaningful patent protection. While we routinely receive communications or have conversations with the owners of other patents, none of these third parties have directly threatened an action or claim against us. If other companies obtain patents with conflicting claims, we may be required to obtain licenses to those patents or to develop or obtain alternative technology. We may not be able to obtain any such licenses on acceptable terms, or at all. Any failure to obtain such licenses could delay or prevent us from pursuing the development or commercialization of our potential products. We have had and will continue to have discussions with our current and potential collaborators regarding the scope and validity of our patents and other proprietary rights. If a collaborator or other party successfully establishes that our patent rights are invalid, we may not be able to continue our existing collaborations beyond their expiration. Any determination that our patent rights are invalid also could encourage our collaborators to terminate their agreements where contractually permitted. Such a determination could also adversely affect our ability to enter into new collaborations.common stock. We may also need to initiate litigation, which could be time-consuming and expensive, to enforce our proprietary rightsadd, update or to determine the scope and validity of others' rights. If litigation results,change in a court may find our patents or those of our licensors invalid or may find that we have infringed on a competitor's rights. Ifprospectus supplement any of our competitors have filed patent applications in the United States which claim technology we also have invented, the Patent and Trademark Office may require us to participate in expensive interference proceedings to determine who has the right to a patent for the technology. We have learned that Hoffmann-La Roche Inc. has received a US patent and has made patent filings in foreign countries that relate to our Panretin capsules and gel products. We filed a patent application with an earlier filing date than Hoffmann-La Roche's patent, which we believe is broader than, but overlaps in part with, Hoffmann-La Roche's patent. We believe we were the first to invent the relevant technology and therefore are entitled to a patent on the application we filed. The Patent and Trademark Office has initiated a proceeding to determine whether we or Hoffmann-La Roche are entitled to a patent. We may not receive a favorable outcome in the proceeding. In addition, the proceeding may delay the Patent and Trademark Office's decision regarding our earlier application. If we do not prevail, the Hoffmann-La Roche patent might block our use of Panretin capsules and gel in specified cancers. We have also learned that Novartis AG has filed an opposition to our European patent that covers the principal active ingredient of our ONTAK drug. We are currently investigating the scope and merits of this opposition. If the opposition is successful, we could lose our ONTAK patent protection in Europe which could substantially reduce our future ONTAK sales in that region. We could also incur substantial costs in asserting our rightsinformation contained in this opposition proceeding, as well as in other interference proceedings in the United States. We also rely on unpatented trade secrets and know-how to protect and maintain our competitive position. We require our employees, consultants, collaborators and others to sign confidentiality agreements when they begin their relationship with us. These agreements may be breached, and we may not have adequate remedies for any breach. In addition, our competitors may independently discover our trade secrets. 11 RELIANCE ON THIRD-PARTY MANUFACTURERS TO SUPPLY OUR PRODUCTS RISKS SUPPLY INTERRUPTION OR CONTAMINATION AND DIFFICULTY CONTROLLING COSTS. We currently have no manufacturing facilities, and we rely on others for clinical or commercial production of our marketed and potential products. In addition, certain raw materials necessary for the commercial manufacturing of our products are custom and must be obtained from a specific sole source. Elan manufactures Avinza for us, Cambrex manufactures ONTAK for us and RP Scherer and Raylo manufacture Targretin capsules for us. To be successful, we will need to ensure continuity of the manufacture of our products, either directly or through others, in commercial quantities, in compliance with regulatory requirements and at acceptable cost. Any extended and unplanned manufacturing shutdowns could be expensive and could result in inventory and product shortages. While we believe that we would be able to develop our own facilities or contract with others for manufacturing services with respect to all of our products, if we are unable to do so our revenues could be adversely affected. In addition, if we are unable to supply products in development, our ability to conduct preclinical testing and human clinical trials will be adversely affected. This in turn could also delay our submission of products for regulatory approval and our initiation of new development programs. In addition, although other companies have manufactured drugs acting through IRs and STATs on a commercial scale, we may not be able to do so at costs or in quantities to make marketable products. The manufacturing process also may be susceptible to contamination, which could cause the affected manufacturing facility to close until the contamination is identified and fixed. In addition, problems with equipment failure or operator error also could cause delays in filling our customers' orders. OUR BUSINESS EXPOSES US TO PRODUCT LIABILITY RISKS OR OUR PRODUCTS MAY NEED TO BE RECALLED, AND WE MAY NOT HAVE SUFFICIENT INSURANCE TO COVER ANY CLAIMS. Our business exposes us to potential product liability risks. Our products also may need to be recalled to address regulatory issues. A successful product liability claim or series of claims brought against us could result in payment of significant amounts of money and divert management's attention from running the business. Some of the compounds we are investigating may be harmful to humans. For example, retinoids as a class are known to contain compounds which can cause birth defects. We may not be able to maintain our insurance on acceptable terms, or our insurance may not provide adequate protection in the case of a product liability claim. To the extent that product liability insurance, if available, does not cover potential claims, we will be required to self-insure the risks associated with such claims. We believe that we carry reasonably adequate insurance for product liability claims. WE USE HAZARDOUS MATERIALS WHICH REQUIRES US TO INCUR SUBSTANTIAL COSTS TO COMPLY WITH ENVIRONMENTAL REGULATIONS. In connection with our research and development activities, we handle hazardous materials, chemicals and various radioactive compounds. To properly dispose of these hazardous materials in compliance with environmental regulations, we are required to contract with third parties at substantial cost to us. Our annual cost of compliance with these regulations is approximately $600,000. We cannot completely eliminate the risk of accidental contamination or injury from the handling and disposing of hazardous materials, whether by us or by our third-party contractors. In the event of any accident, we could be held liable for any damages that result, which could be significant. We believe that we carry reasonably adequate insurance for toxic tort claims. OUR STOCK PRICE MAY BE ADVERSELY AFFECTED BY VOLATILITY IN THE MARKETS. The market prices and trading volumes for our securities, and the securities of emerging companies like us, have historically been highly volatile and have experienced significant fluctuations unrelated to operating performance. For example, in 2002, the intraday sale price of our common stock on the Nasdaq National Market was as high as $20.50 and as low as $4.64. Future announcements concerning us or our competitors as well as other companies in our industry and other public companies may impact the market price of our common stock. These announcements might include: 12 >> the results of research or development testing of ours or our competitors' products; >> technological innovations related to diseases we are studying; >> new commercial products introduced by our competitors; >> government regulation of our industry; >> receipt of regulatory approvals by our competitors; >> our failure to receive regulatory approvals for products under development; >> developments concerning proprietary rights; >> litigation or public concern about the safety of our products; or >> intent to sell or actual sale of our stock held by our corporate partners. AS A NEW INVESTOR, YOU MAY EXPERIENCE IMMEDIATE AND SUBSTANTIAL DILUTION. The offering price of our common stock may be substantially higher than the net tangible book value per share of our common stock. If you purchase common stock in this offering from a selling stockholder for the per-share purchase price of $14.78, which is the average of the high and low sales prices per share of the common stock on July 24, 2003 as reported on The Nasdaq Stock Market, you will incur immediate dilution in tangible net book value of approximately $16.34 per share, based on our tangible net book value of $(1.56) at March 31, 2003. FUTURE SALES OF OUR SECURITIES MAY DEPRESS THE PRICE OF OUR SECURITIES. Sales of substantial amounts of our securities in the public market could seriously harm prevailing market prices for our securities. These sales might make it difficult or impossible for us to sell additional securities when we need to raise capital. YOU MAY NOT RECEIVE A RETURN ON YOUR SECURITIES OTHER THAN THROUGH THE SALE OF YOUR SECURITIES. We have not paid any cash dividends on our common stock to date. We intend to retain any earnings to support the expansion of our business, and we do not anticipate paying cash dividends on any of our securities in the foreseeable future. OUR SHAREHOLDER RIGHTS PLAN AND CHARTER DOCUMENTS MAY HINDER OR PREVENT CHANGE OF CONTROL TRANSACTIONS. Our shareholder rights plan and provisions contained in our certificate of incorporation and bylaws may discourage transactions involving an actual or potential change in our ownership. In addition, our board of directors may issue shares of preferred stock without any further action by you. Such issuances may have the effect of delaying or preventing a change in our ownership. If changes in our ownership are discouraged, delayed or prevented, it would be more difficult for our current board of directors to be removed and replaced, even if you or our other stockholders believe that such actions are in the best interests of us and our stockholders. 13 CAUTIONARY NOTE REGARDING FORWARD-LOOKING STATEMENTS This prospectus may contain forward-looking statements that involve substantial risks and uncertainties regarding future events or our future performance within the meaning of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended. You can identify these statements by forward-looking words such as "may," "will," "expect," "intent," "anticipate," "believe," "estimate" and "continue" or similar words.prospectus. You should read statements that contain these words carefully because they discuss our future expectations, contain projections of our future results of operations or of our financial condition or state other "forward-looking" information. We believe that it is important to communicate our future expectations to our investors. However, there may be events in the future that we are not able to accurately predict or control. The factors listed in the section captioned "Risk Factors,"this prospectus and any accompanying prospectus supplement, as well as any cautionary language included inpost-effective amendments to the registration statement of which this prospectus or incorporated by reference, provide examples of risks, uncertainties and events that may cause our actual results to differ materially fromis a part, together with the expectations we describe in our forward-looking statements. Beforeadditional information described under “Where You Can Find More Information” before you investmake any investment decision.

RISK FACTORS

Investment in our common stock youinvolves a high degree of risk. You should be aware thatcarefully consider the occurrencespecific risks described under the heading “Risk Factors” in any applicable prospectus supplement and under the caption “Risk Factors” in any of the events described in the "Risk Factors" section and elsewhere in this prospectus could have a material adverse effect on our business, operating results and financial condition. All subsequent written and oral forward-looking statements attributable to us or persons acting on our behalf are expressly qualified in their entirety by these statements. WHERE YOU CAN FIND MORE INFORMATION We file annual, quarterly and special reports, proxy statements and other information with the SEC. You may read and copy any document we file at the SEC's public reference rooms at 450 Fifth Street, N.W., Washington, D.C. 20549. Please call the SEC at 1-800-SEC-0330 for further information on the public reference rooms. Our SEC filings are also available to the public on the SEC's website at http://www.sec.gov. 14 INFORMATION INCORPORATED BY REFERENCE The SEC allows us to incorporate by reference the information we file with them, which means that we can disclose important information to you by referring you to those documents. The information incorporated by reference is considered to be part of this prospectus, and later information filed with the SEC will update and supersede this information. We incorporate by reference the documents listed below and any future filings we make with the SEC under Sectionpursuant to Sections 13(a), 13(c), 14 or 15(d) of the Securities and Exchange Act of 1934, as amended, or the Exchange Act, which are incorporated herein by reference, before making an investment decision. Each of the risks described in these headings could adversely affect our business, financial condition, results of operations and prospects, and could result in a complete loss of your investment. For more information, see “Where You Can Find More Information.”

FORWARD-LOOKING STATEMENTS

This prospectus and the documents incorporated by reference into this prospectus contain forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995 that involve risks and uncertainties, as well as assumptions, that, if they never materialize or prove incorrect, could cause our results to differ materially from those expressed or implied by such forward-looking statements. Forward-looking statements generally are identified by the words “may,” “will,” “project,” “might,” “expects,” “anticipates,” “believes,” “intends,” “estimates,” “should,” “could,” “would,” “strategy,” “plan,” “continue,” “pursue”, or the negative of these words or other words or expressions of similar meaning. All statements other than statements of historical fact are statements that could be deemed forward-looking statements. For example, forward-looking statements include statements about our future financial and operating results, plans, expectations for potential research and development payments, cash burn rates, timing of achieving positive cash flow, potential revenue and profits of a combined company, costs and expenses, interest rates, outcome of contingencies, financial condition, liquidity, business strategies and cost savings, any statements of the plans, strategies and objectives of management for future operations, any statements concerning our product candidates and product development, any statements regarding future economic conditions or performance, statements of belief and any statement of assumptions underlying any of the foregoing. The risks, uncertainties and assumptions referred to above include other risks and uncertainties that are incorporated by reference into this prospectus.

If any of these risks or uncertainties materializes or any of these assumptions proves incorrect, the our results could differ materially from the dateexpectations in these statements. The forward-looking statements included in this prospectus are made only as of the initial registration statement until the completion of the offering of the securities covered by this prospectus: o Our annual report on Form 10-K for the fiscal year ended December 31, 2002, o Our quarterly report on Form 10-Q for the quarterly period ended March 31, 2003, o Our current reports on Form 8-K filed February 25, 2003, April 2, 2003, April 24, 2003 and May 15, 2003, o The description of our common stock, contained in our registration statement on Form 8-A filed on November 21, 1994, including any amendments or reports filed for the purpose of updating such descriptions, and o The description of our preferred stock purchase rights, contained in our registration statement on Form 8-A filed on September 30, 1996, including any amendments or reports filed for the purpose of updating such descriptions. The reports and other documents that we file after the date of this prospectus, and we are not under any obligation to update our respective forward-looking statements and do not intend to do so.

USE OF PROCEEDS

Any proceeds received by us from the exercise of the assumed Pharmacopeia warrants, representing the exercise price for these warrants, or the exercise of the assumed Pharmacopeia options, representing the exercise price for these options, will update and supersede the information in this prospectus. You may request a copy of these filings, at no cost, by writing or telephoning us at: Ligand Pharmaceuticals Incorporated Attn: Investor Relations 10275 Science Center Road San Diego, California 92121-1117 (858) 550-7500 YOU SHOULD RELY ONLY ON THE INFORMATION PROVIDED OR INCORPORATED BY REFERENCE IN THIS PROSPECTUS OR ANY RELATED PROSPECTUS SUMMARY. WE HAVE NOT AUTHORIZED ANYONE TO PROVIDE YOU WITH DIFFERENT INFORMATION. YOU SHOULD NOT ASSUME THAT THE INFORMATION IN THIS PROSPECTUS OR ANY RELATED PROSPECTUS SUMMARY IS ACCURATE AS OF ANY DATE OTHER THAN THE DATE ON THE FRONT OF THE DOCUMENT. 15 DILUTIONbe used for general corporate purposes. The net tangible book value of Ligand at March 31, 2003 was $(107,839,000), or approximately $(1.56) per share of common stock. Net tangible book value per share represents theactual amount of our tangible assets less total liabilities, divided byproceeds we receive on exercise of the numberassumed Pharmacopeia warrants or the exercise of our outstanding shares of common stock. Net tangible book value dilution per share represents the difference betweenassumed Pharmacopeia options will depend on how many warrants or options are ultimately exercised. However, if all the amount per share paid by purchasers of shares of common stock from selling stockholders in the offering made herebyassumed Pharmacopeia warrants and the pro forma net tangible book value per share of common stock immediately after completion ofassumed Pharmacopeia options were exercised, the offering. Assuming that the sales of 5,835,771 shares of common stock in the offering are made at an offering price of $14.78 per share, which is the average of the high and low sales prices per share of the common stock on July 24, 2003 as reported on The Nasdaq Stock Market, and that we will receive none of the netaggregate proceeds therefrom, the purchasers of common stock from the selling stockholders would experience an immediate dilution in net tangible book value of $16.34 per share, as illustrated in the following table: Assumed public offering price per share.................................. 14.78 Net tangible book value per share as of March 31, 2003 (1).....$(1.56) Pro forma dilution per share to new investors............................$16.34
- ------------------- (1) Because the shares being offered and sold by the selling stockholders are issued and outstanding and we will receive none of the proceeds from the offering of the common stock by the selling stockholders, net tangible book value per share will not change as a result of such offering. USE OF PROCEEDSexceed approximately $7.5 million. We will not receive any of the proceeds from the sale of the shares of ourthe common stock issuable upon exercise of the assumed Pharmacopeia warrants and assumed Pharmacopeia options by the selling stockholders. PLAN

DETERMINATION OF DISTRIBUTION We are registering underWARRANT AND OPTION EXERCISE PRICES

The offering price for the registration statementshares issuable upon exercise of whichthe warrants and options covered by this prospectus is the exercise price of the warrants and options, respectively, which was determined at the time the warrants and options were issued. In accordance with the terms of the merger agreement between us and Pharmacopeia, each Pharmacopeia warrant and option outstanding at the time of the merger was assumed by us and became exercisable for that number of shares of Ligand common stock equal to 0.5985 times the number of shares of Pharmacopeia common stock for which such warrant or option was exercisable before the merger, rounded down to the nearest whole number of shares, plus certain cash consideration, cash in lieu of any fractional share of Ligand common stock and certain contingent value rights. The exercise price per share of each assumed Pharmacopeia warrant and option is equal to the exercise per share of such warrant or option prior to the merger, divided by 0.5985, rounded up to the nearest whole cent. The determination of the exchange ratio of 0.5985 was established through negotiation between the parties to the merger.

DESCRIPTION OF CAPITAL STOCK

The authorized capital stock of Ligand consists of 200,000,000 shares of common stock, $0.001 par value per share, and 5,000,000 shares of preferred stock, $0.001 par value per share. At May 13, 2009, there were 112,978,603 shares of common stock outstanding and no shares of preferred stock outstanding.

The following description of certain matters related to our capital stock is a part 5,835,771summary and is qualified in its entirety by the provisions of our certificate of incorporation and bylaws.

Common Stock

In connection with our acquisition of Pharmacopeia by merger, we agreed to register up to 872,699 shares of our common stock issuable upon exercise of certain warrants and options described above. The holders of common stock are entitled to one vote for each share held of record on behalfall matters submitted to a vote of the selling stockholders. These stockholders acquiredSubject to preferences that may be applicable to any outstanding preferred stock, holders of common stock are entitled to receive ratably such dividends as may be declared by our Board of Directors out of funds legally available. In the shares from an affiliateevent of Elan Corporation, plcour liquidation, dissolution or winding up, holders of common stock are entitled to share ratably in private transactions completed in July 2003. The selling stockholders namedall assets remaining after payment of liabilities and the liquidation preference of any outstanding preferred stock. Holders of common stock have no preemptive rights and no right to cumulate votes in the table belowelection of directors. There are no redemption or pledgees, donees, transferees or other successors in interest sellingsinking fund provisions applicable to the common stock. All outstanding shares receivedof common stock are fully paid and nonassessable.

Warrants

In connection with our acquisition of Pharmacopeia by merger, we agreed to register for resale 867,637 shares of common stock issuable upon the exercise of redeemable common stock purchase warrants, each exercisable into one share of our common stock at $8.59 per share. The warrants may be exercised from a named selling stockholder as a gift, pledge, partnership distribution or other non-sale related transfer after the date of this prospectus may sell the shares from time to time.until October 2011. The selling stockholders will act independently of us in making decisions regarding the timing, manner and size of each sale. The securities being offered by this prospectuswarrants may be sold by the selling stockholders on The Nasdaq Stock Marketexercised in whole or in the over-the-counter market or otherwise, at prices and at terms then prevailing or at prices related to the then-current market price, or in negotiated transactions. The consideration may be cash or another form of consideration negotiated by the parties. The selling stockholders may effect these transactions by selling the shares to or through broker-dealers. The securities may be sold: o in a block trade in which a broker-dealer will attempt to sell the shares as agent but may position and resell a portionpart upon surrender of the block as principal to facilitate the transaction, o in purchases by a broker-dealer as principal and resale by such broker-dealer for its account under this prospectus, o in an exchange distribution in accordance with the rules of the respective exchange, 16 o in ordinary brokerage transactions and transactions in which a broker solicits purchasers, o in an over-the-counter distribution in accordance with the rules of The Nasdaq National Market, o in privately negotiated transactions directly to purchasers, through a specific bidding or auction process or otherwise, o in option transactions, or o through a combination of any such methods of sale. To the extent required, this prospectus may be amended or supplemented from time to time to describe a specific plan of distribution. In effecting sales, broker-dealers engaged by the selling stockholders may arrange for other broker-dealers to participate in the resales. The selling stockholders may enter into hedging transactions with broker-dealers or other financial institutions in connection with distributions of the shares or otherwise. In connection with these transactions, broker dealers or other financial institutions may engage in short sales of the shares in the course of hedging the positions they assume with selling stockholders. The selling stockholders also may sell shares short and redeliver the shares to close out such short positions. The selling stockholders may enter into option or other transactions with broker-dealers which require the delivery to the broker-dealer of the shares. The broker-dealer may then resell or otherwise transfer such shares covered by this prospectus (as supplemented or amended to reflect such transaction). The selling stockholders also may loan or pledge the shares to a broker-dealer or other financial institution. The broker-dealer may sell the shares so loaned, or upon a default the broker-dealer may sell the pledged shares under this prospectus (as supplemented or amended to reflect such transaction). Broker-dealers or agents may receive compensation in the form of commissions, discounts or concessions from selling stockholders. Broker-dealers or agents may also receive compensation from the purchasers of the shares for whom they act as agents or to whom they sell as principals, or both. Compensation as to a particular broker-dealer might be in excess of customary commissions and will be in amounts to be negotiated in connection with the sale. Broker-dealers or agents and any other participating broker-dealers or the selling stockholders may be deemed to be underwriters within the meaning of Section 2(11) of the Securities Act of 1933, as amended (the "Securities Act"), in connection with sales of the shares. Accordingly, any such commission, discount or concession received by them and any profitwarrant certificate on the resale of the shares purchased by them may be deemed to be underwriting discounts or commissions under the Securities Act. Because selling stockholders may be deemed to be underwriters within the meaning of Section 2(11) of the Securities Act, the selling stockholders will be subject to the prospectus delivery requirements of and statutory liabilities under the Securities Act. In addition, any securities covered by this prospectus which qualify for sale in compliance with Rule 144 promulgated under the Securities Act may be sold under Rule 144 rather than under this prospectus. The selling stockholders have advised us that they have not entered into any agreements, understandings or arrangements with any underwriters or broker-dealers regarding the sale of their securities. There is no underwriter or coordinating broker acting in connection with the proposed sale of shares by the selling stockholders. The shares will be sold only through registered or licensed brokers or dealers if required under applicable state securities laws. In addition, in certain states the shares may not be sold unless they have been registered or qualified for sale in the applicable state or an exemption from the registration or qualification requirement is available and is complied with. Under applicable rules and regulations under the Securities Exchange Act of 1934, as amended (the "Exchange Act"), persons engaged in the distribution of the shares may be limited in their ability to engage in market activities with respect to such shares. In addition, each selling stockholder will be subject to applicable PROVISIONS of the Exchange Act and the associated rules and regulations under the Exchange Act, including Regulation M, which provisions may limit the timing of purchases and sales of shares of our common stock by the selling stockholders. We will make copies of this prospectus available to the selling stockholders and have informed them of the need to deliver copies of this prospectus to purchasers at or prior to the timeexpiration date to us or at the office of our warrant agent, completion of the notice of exercise form included as part of the warrant certificate and full payment of the exercise price by wire transfer or immediately available funds for the number of warrants being exercised. The warrants may also be exercised by means of a “cashless exercise” if the volume weighted average share price on the business day immediately preceding the exercise date is greater than the exercise price. A “cashless exercise” means that in lieu of paying the aggregate purchase price for the shares being purchased upon exercise of the warrants in cash, the holder will forfeit a number of shares underlying the warrants with a “fair market value” equal to such aggregate exercise price. We will not receive additional proceeds if the warrants are exercised by cashless exercise.

The exercise price and number of shares of common stock issuable upon exercise of the warrants may be adjusted in certain circumstances, including in the event of a stock dividend, a capital reorganization or reclassification, a merger or a consolidation. The warrant holders do not have the rights or privileges of holders of common stock and any voting rights until they exercise their warrants and receive shares of common stock. If the holder of a warrant elects to exercise all or any part of a warrant when there is no effective registration statement permitting the sale of the shares. 17 We will file a supplement to this prospectus, if required, to comply with Rule 424(b) under the Securities Act, upon being notified by a selling stockholder that any material arrangements have been entered into with a broker-dealer for the saleunderlying shares of shares through a block trade, special offering, exchange distribution or secondary distribution or a purchase by a broker or dealer. Such supplement will disclose: o the name of each such selling stockholder and of the participating broker-dealer(s), o the number of shares involved, o the price at which such shares were sold, o the commissions paid or discounts or concessions allowed to such broker-dealer(s), where applicable, o that such broker-dealer(s) did not conduct any investigation to verify the information set out or incorporated by reference in this prospectus, and o other facts material to the transaction. Agents, underwriters and brokers-dealers may be entitled under agreements which may be entered into with us to indemnification by us against specified liabilities, including liabilities incurred under the Securities Act, or to contributioncommon stock by us to payments theythe holder, then we may, be required to make in respect ofupon such liabilities. If required, a prospectus supplement will describe the terms and conditions of such indemnification or contribution. Some of the agents, underwriters or dealers or their affiliates may be customers of, engage in transactions with or perform services for us or our subsidiaries in the ordinary course of business. We will bear all costs, expenses and fees in connection with the registration of the shares of the selling stockholders, except for the fees and expenses of counsel or other advisors for the selling stockholders. The selling stockholders will also bear all commissions and discounts, if any, attributable to the sales of their shares. The selling stockholders may agree to indemnify any broker-dealer or agent that participates in transactions involving sales of the shares against various liabilities, including liabilities arising under the Securities Act. We have agreed to indemnify each selling stockholder that received from Elan more than 50,000 shares of our common stock, any underwriter for such stockholder and any officer or director or person that controls such stockholder or underwriter against various liabilities in connection with the offering of the shares, including liabilities arising under the Securities Act. Each such selling stockholder has agreed to indemnify us, our directors, our officers who sign the registration statement of which this prospectus is a part, persons that control us, any underwriter, each other selling stockholder and any person that controls such underwriter or other selling stockholder against various liabilities in connection with the offering of the shares, including liabilities arising under the Securities Act. We have agreed with selling stockholders that received from Elan more than 50,000exercise, issue shares of our common stock to keep the registration statementholder with appropriate legends and subject to resale restrictions.

Pharmacopeia, Inc. 2000 Stock Option Plan and Pharmacopeia, Inc. 2004 Stock Incentive Plan

In connection with our acquisition of Pharmacopeia by merger, we agreed to register shares of common stock issuable upon exercise of stock options, of which 5,062 are outstanding. Ligand has included a copy of the Pharmacopeia, Inc. 2000 Stock Option Plan, or the 2000 Plan, and the Pharmacopeia, Inc. 2004 Stock Incentive

Plan, or the 2004 Plan, and together with the 2000 Plan, the Plans, as exhibits to the Registration Statement of which this prospectus constitutesProspectus forms a part effectivepart. The Plans were assumed by Ligand on December 23, 2008 in connection with our acquisition of Pharmacopeia by merger.

The following summary of certain provisions of the Plans does not purport to be complete and is subject to, and qualified in its entirety by reference to, the provisions of the Plans, including the definitions therein of certain terms. The Plans are not pension, profit-sharing, or stock bonus plans designed to qualify under Section 401(a) of the Internal Revenue Code of 1986, as amended, or the Code, or employee benefit plans subject to any of the provisions of the Employee Retirement Income Security Act of 1974.

General

Ligand common stock will be issued upon exercise of options granted under the Plans. Effective as of the consummation of the acquisition of Pharmacopeia by Ligand, the share reserves under the Plans were reduced so that such reserves are equal to the number of shares of Ligand common stock issuable upon exercise of the assumed Pharmacopeia options. No additional awards will be granted under the Plans.

Administration of the Plans

The Plans are administered by the Compensation Committee, or the Committee, of the Board of Directors. The Committee has the power to interpret the Plans and to prescribe rules and regulations relating thereto. Copies of the Plans and additional information about the Plans and the administrators may be obtained from Ligand Pharmaceuticals Incorporated, Investor Relations, 10275 Science Center Drive, San Diego, California 92121, (858) 550-7500.

Each stock option granted under the Plans is evidenced by a written award agreement between the grantee and us and is subject to the terms and conditions described below.

Terms and Conditions of Options

Types of Options. While the Plans authorize the granting of either incentive stock options or nonqualified stock options, all of the assumed Pharmacopeia options that remain outstanding under the Plans are nonqualified stock options.

Exercise Price. The exercise price of an option to purchase shares of Pharmacopeia common stock granted under the Plans was determined at the time the option was granted. The exercise price was not less than 100% of the fair market value of the company’s common stock on the date the option was granted. Generally, the fair market value was the closing sale price for such stock on the date of determination as quoted on The Nasdaq Stock Market.

The means of payment for shares issued upon exercise of an option is specified in each option agreement and generally may be made by cash, certain other shares of common stock owned by the optionee for at least six months, delivery of an exercise notice together with irrevocable instructions to a broker chosen by the optionee (and reasonably agreeable to the plan administrator) to deliver the exercise price to us from the sale proceeds (a cashless exercise), any combination of the foregoing methods, or any other consideration to the extent permitted under applicable law. Some of the foregoing payment methods may require the consent of the plan administrator.

Term of the Option. Each stock option agreement specifies the type of option, the term of the option, and the date when the option will become exercisable. However, the term of an option granted under the 2004 Plan is no longer than ten years from the date of grant.

Transferability of Options

The Plans provide that stock options granted thereunder are generally not transferable by a participant except by will or by the laws of descent and distribution and are exercisable during the participant’s lifetime only by the Participant. However, the Plans also provide that the plan administrator may permit certain transfers of nonqualified stock options, on a general or specific basis, in its sole discretion.

Amendment and Termination of the Plans

Ligand’s Board of Directors may modify, amend, or terminate the Plans at any time, except that, to the extent then required by the Plans or an applicable law, rule, or regulation, approval of the company’s stockholders will be required. No amendment, modification or termination shall adversely affect the rights of a participant under a grant previously made to a participant without the consent of the participant.

Federal Income Tax Consequences under the Plans

A participant does not recognize any taxable income at the time he or she is granted a nonqualified stock option. Upon exercise, the participant recognizes ordinary taxable income generally measured by the excess of the then fair market value of the shares over the exercise price. Any taxable income recognized in connection with an option exercise by an employee of the company is subject to tax withholding by us. We are entitled to a deduction in the same amount as the ordinary income recognized by the participant. Upon a disposition of such shares by the participant, any difference between the sale price and the participant’s exercise price, to the extent not recognized as taxable income as provided above, is treated as long-term or short-term capital gain or loss, depending on the holding period.

The foregoing is only a summary of the effect of federal income taxation upon award grantees and us with respect to the grant and exercise of non-qualified stock options under the Plans. It does not purport to be complete, and does not discuss the tax consequences of the employee’s death or the provisions of the income tax laws of any municipality, state or foreign country in which the employee or consultant may reside.

Preferred Stock

As of May 13, 2009, we had no shares of preferred stock outstanding.

Under the terms of our amended and restated certificate of incorporation, our board of directors has the authority, without further action by the stockholders and subject to the limits imposed by the Delaware General Corporation Law to issue shares of preferred stock in one or more series and to designate the rights, preferences, privileges and restrictions of each such series. The issuance of preferred stock could have the effect of restricting dividends on the common stock, diluting the voting power for the common stock, impairing the liquidation rights of the common stock or delaying or preventing a change in control without further action by the stockholders. At present, we have no plans to issue any shares of preferred stock.

Stockholder Rights Plan

On October 13, 2006, our board of directors adopted a stockholder rights plan. Our board of directors declared a dividend of one preferred share purchase right for each outstanding share of our common stock at the close of business on October 13, 2006. Each right entitles the registered holder thereof, after the rights become exercisable and until October 13, 2016 (or the earlier redemption, exchange or termination of the rights), to purchase from us one 1/1000th of a share of Series A Participating Preferred Stock, or Series A Preferred, at a price of $100.00, subject to certain anti-dilution adjustments. The rights do not become exercisable until the earlier to occur of:

10 days (or such later date as may be determined by our board of (i) July 25, 2005,directors) following a public announcement that a person or (ii)group of affiliated or associated persons has acquired, or obtained the right to acquire, beneficial ownership of 20% or more of our outstanding common stock (any such person or group is referred to as an acquiring person); or

10 days (or such later date as may be determined by our board of directors) following the commencement or announcement of an intention to make a tender offer or exchange offer the consummation of which would result in the beneficial ownership by a person or group of 20% or more of our outstanding common stock.

Each share of Series A Preferred purchasable upon exercise of the rights will be entitled to an aggregate dividend of 1,000 times the dividend declared per share of common stock. Each share of Series A Preferred will have 1,000 votes, voting together with the shares of common stock. In the event of any merger, consolidation or other transaction in which the shares of common stock are changed or exchanged, each share of Series A Preferred will be entitled to receive 1,000 times the amount received per shares of common stock. These rights are protected by customary anti-dilution provisions.

In the event that, at any time following the date on which there has been public disclosure that a person or group has become an acquiring person, Ligand is acquired in a merger or other business combination transaction, or 50% or more of Ligand’s consolidated assets or earning power are sold (other than in transactions in the ordinary course of business), proper provision shall be made so that each holder of a right which has not been exercised will thereafter have the right to receive, upon exercise, shares of common stock of the acquiring company having a value equal to two times the purchase price.

At any time after the acquisition by an acquiring person of 20% or more of Ligand’s outstanding shares of common stock and prior to the acquisition by such acquiring person of 50% or more of Ligand’s outstanding shares of common stock, our board of directors may exchange the rights (other than rights owned by the acquiring person), in whole or in part, at an exchange ratio of one shares of common stock per right, subject to adjustment.

The rights will expire on October 13, 2016, unless earlier redeemed, exchanged or terminated. Until a right is exercised, the rights do not convey the right to vote, receive dividends or otherwise provide the holder with any rights as a stockholder.

The rights may be redeemed in whole, but not in part, at a price of $0.01 per right at any time prior to the time that an acquiring person has become such. The redemption of the rights may be made effective at such time, on such basis and with such conditions as all shares covered by this prospectus have been sold pursuant to andour board of directors in accordance with the registration statement. 18 its sole discretion may establish.

SELLING STOCKHOLDERS SECURITY HOLDERS

The following table sets forth the name of each selling security holder and the number of shares owned by each of the selling stockholders. These stockholders acquired the shares from an affiliate of Elan Corporation, plc in private transactions completed in July 2003. This registration statement also shall cover any additionalour warrants, options and shares of common stock beneficially owned by each selling security holder as of on or around March 31, 2009 and the percentage of our outstanding warrants, options and shares of common stock beneficially owned by each selling security holder as of March 31, 2009. The actual amount, if any, of warrants or shares of common stock to be offered by each selling security holder and the amount and percentage of warrants and shares of common stock to be owned by such selling security holder following such offering is unknown. For a description of the warrants and options see “Description of Capital Stock.”

The number of warrants, options and shares of common stock beneficially owned by each selling security holder is determined according to the rules of the SEC, and the information is not necessarily indicative of beneficial ownership for any other purpose. Under current rules, beneficial ownership includes any warrants, options or shares as to which become issuablethe individual or entity has sole or shared voting power or investment power. As a consequence, several persons may be deemed to be the “beneficial owners” of the same warrants, options or shares. Unless otherwise noted in connectionthe footnotes to this table, each of the security holders named in this table has sole voting and investment power with respect to the warrants, options or shares of common stock shown as beneficially owned. The percentage ownership of each selling security holder is calculated based on the warrants, options and shares of common stock that would be outstanding assuming that all warrants and other options held by the selling security holders that are exercisable within 60 days from the date of this prospectus have been fully exercised.

We are registering all of the shares registered for sale herebycovered by this prospectus on behalf of the selling security holders in accordance with certain obligations. This prospectus also covers any common stock that becomes issuable by reason of any stock dividend, stock split, recapitalization or other similar transaction effected without the receipt of consideration whichthat results in an increase in the number of our outstanding shares of common stock. Nonestock and to cover the issuance of shares of common stock upon the exercise of the selling stockholders has had a material relationship with us within the past three yearswarrants or options by persons other than as a result of the ownership of the shares or other securities of ours. We do not know when or in what amounts the selling stockholders maysecurity holders. We are registering shares to permit the selling security holders to offer these shares of common stock for sale. The selling stockholders may decide not to sell all or any of the shares that this prospectus covers. The shares offered by this prospectus may be offeredresale from time to time by the selling stockholders named below.time. Because the selling stockholderssecurity holders may offersell all, some or someno part of thetheir respective shares pursuant toof common stock covered by this offering, and because there are currently no agreements, arrangements or understandings with respect to the sale of any of the shares that the selling stockholders will hold after completion of the offering,prospectus, we cannot estimate the number of shares that the selling stockholders will hold after completion of the offering. The percentages of common stock beneficially ownedthat will be held by the selling security holders upon the termination of this offering. For more information, see “Plan of Distribution.”

Warrant Holders

  Common Stock 

Selling Security Holder

 Beneficially
Owned
Before Offering
  Being
Offered(2)
 Beneficially
Owned
After Offering(2)
 

Name(1)

 Number Percent  Number Number Percent 

Biotech Growth Trust PLC(3)

 78,104 *  78,104 —   —   

Federated Kaufmann Fund(4)

 134,662 *  134,662 —   —   

Balyasny Asset Management, LP(5)

 112,218 *  112,218 —   —   

Merlin Nexus II, LLC(6)

 104,737 *  104,737 —   —   

Funds affiliated with BVF Partners, LP(7)

 17,102,783 15.14% 86,782 17,016,001 15.06%

Funds affiliated with OZ Capital Management(8)

 67,331 *  67,331 —   —   

Funds affiliated with AWM Investment Company(9)

 241,643 *  52,368 189,275 * 

Senvest Master Fund LP(10)

 301,504 *  37,406 264,098 * 

Kilkenny Capital Management, LLC(11)

 36,358 *  36,358 —   —   

Highbridge International LLC(12)

 29,925 *  29,925 —   —   

Funds affiliated with Straus Asset Management, LLC(13)

 13,466 *  13,466 —   —   

Otago Partners, LLC(14)

 12,536 *  12,536 —   —   

Advantage Ad Multi Sector Fd I(15)

 4,907 *  4,788 119 * 

Alexandra Investment Management, LLC(16)

 4,488 *  4,488 —   —   

Additional warrant holders(s)(17)

 92,468 *  92,468 —   —   
            

Total

 18,337,130 16.23% 867,637 17,469,493 15.46%
            

*Represents less than 1.0%.

(1)Unless otherwise noted, this table is based on information supplied to us by the selling stockholders and certain records of Pharmacopeia.
(2)We do not know when or in what amounts a selling stockholder may offer shares for sale. The selling stockholders might not sell any or all of the shares offered by this prospectus. Because the selling stockholders may offer all or some of the shares pursuant to this offering and because there are currently no agreements, arrangements or understandings with respect to the sale of any of the shares, we cannot estimate the number of the shares that will be held by the selling stockholders after completion of the offering. However, for purposes of this table, we have assumed that, after completion of the offering, none of the shares covered by this prospectus will be held by the selling stockholders.
(3)Includes warrants to purchase 78,104 shares of common stock. Orbimed Capital LLC is the Investment Manager of Biotech Growth Trust PLC. Samuel D. Islay, a principal owner of Orbimed Capital LLC, has voting and investment control of the securities held by Biotech Growth Trust PLC.
(4)Includes warrants to purchase 134,662 shares of common stock.
(5)Includes warrants to purchase 112,218 shares of common stock.
(6)Includes warrants to purchase 104,737 shares of common stock.
(7)Includes warrants to purchase approximately 18,673 shares of common stock and 3,826,513 shares of common stock held by Biotechnology Value Fund, LP, warrants to purchase 12,867 shares of common stock and 2,648,783 shares of common stock held by Biotechnology Value Fund II, LP, warrants to purchase 5,566 shares of common stock and 1,009,786 shares of common stock held by Investment 10, LLC and warrants to purchase 49,675 shares of common stock and 9,530,919 shares of common stock held by BVF Investments, LLC. Mark Lampert, as President of BVF, Inc., which is the general partner of BVF Partners, LP, which is the general partner of Biotechnology Value Fund, LP and Biotechnology Value Fund II, LP, the manager of BVF Investments, LLC, and the investment manager of Investment 10, LLC, may be deemed to have investment and/or voting control of the securities held by Biotechnology Value Fund, LP, Biotechnology Value Fund II, LP, Investment 10, LLC and BVF Investments, LLC.
(8)Includes warrants to purchase 63,613 shares of common stock held by OZ Master Fund, Ltd., warrants to purchase 1,323 shares of common stock held by Gordel Holdings Limited, warrants to purchase 840 shares of common stock held by GPC LVII, LLC, warrants to purchase 811 shares of common stock held by Goldman Sachs & Co. Profit Sharing Master Trust and warrants to purchase 744 shares of common stock held by OZ Global Special Investments Master Fund, LP. Daniel S. Och, as Chief Executive Officer of Och-Ziff Holding Corporation, which is the general partner of OZ Management LP, which is the investment manager of Oz Master Fund, Ltd., Gordel Holdings Limited, GPC LVII, LLC and Goldman Sachs & Co. Profit Sharing Master Trust, may be deemed to have investment and/or voting control of the shares held by OZ Master Fund, Ltd., Gordel Holdings Limited, GPC LVII, LLC and Goldman Sachs & Co. Profit Sharing Master Trust. Daniel S. Och, as Chief Executive Officer of Och-Ziff Holding Corporation, which is the General Partner of Oz Advisors II, LP, which is the General Partner of OZ Global Special Investments Master Fund, LP, may be deemed to have investment and/or voting control of the securities held by OZ Global Special Investments Master Fund, LP.
(9)Includes warrants to purchase approximately 26,184 shares of common stock and 88,452 shares of common stock held by Special Situations Private Equity Fund, LP and warrants to purchase approximately 26,184 shares of common stock and 100,823 shares of common stock held by Special Situations Life Sciences Fund, LP. AWM Investment Company, Inc. is the investment advisor to Special Situations Private Equity Fund, LP and Special Situations Life Sciences Fund, LP David M Greenhouse and Austin W. Marxe are the principal owners of AWM Investment Company, Inc. and through their control of AWM Investment Company, Inc. share voting and investment control over the securities held by Special Situations Private Equity Fund, LP and Special Situations Life Sciences Fund, LP.
(10)Includes warrants to purchase 37,406 shares of common stock and 264,098 shares of common stock.
(11)Includes warrants to purchase 36,358 shares of common stock.
(12)

Includes warrants to purchase 29,925 shares of common stock. Highbridge Capital Management, LLC is the trading manager of Highbridge International LLC and has voting control and investment discretion over the securities held by Highbridge International LLC. Glenn Dubin and Henry Swieca control Highbridge Capital Management, LLC and have voting control and investment discretion over the

securities held by Highbridge International LLC. Each of Highbridge Capital Management, LLC, Glenn Dubin and Henry Swieca disclaims beneficial ownership of the securities held by Highbridge International LLC.

(13)Includes warrants to purchase 6,703 shares of common stock held by Straus-GEPT Partners, LP and warrants to purchase 6,763 shares of common stock held by Straus Partners, LP. Andrew Marks, as Managing and Principal General Partner of Straus-GEPT Partners, LP and Straus Partners, LP may be deemed to have investment and/or voting control of the securities.
(14)Lindsey Rosenwald, as Managing Member of Straus, and Michael Chill, as Partner and Investment Advisor, may be deemed to have investment and/or voting control of the securities.
(15)Includes warrants to purchase 4,708 shares of common stock and 119 shares of common stock. Eden Capital Management Partners, LP, may be deemed to have investment and/or voting control of the securities.
(16)Includes warrants to purchase 4,488 shares of common stock.
(17)Includes warrants to purchase 92,468 shares of common stock which were sold by certain selling security holders to persons whose identity is currently unknown. We intend to file a prospectus supplement setting forth information relating to such persons as soon as it becomes available and prior to the issuance of any shares of common stock issuable upon exercise of such warrants.

Option Holders

   Common Stock

Selling Security Holder

  Beneficially Owned
Before Offering
  Being
Offered(2)
  Beneficially Owned
After Offering(2)

Name(1)

  Number  Percent  Number  Number  Percent

Laura Angelucci(3)

  53  *  53  —    —  

Nasrin Ansari(4)

  693  *  40  653  *  

Shalini Bansai(5)

  221  *  221  —    —  

Wie Qing Chen(6)

  430  *  430  —    —  

Camelia Chiriac(7)

  209  *  209  —    —  

Amy Hines(8)

  59  *  59  —    —  

Padma Kosunam(9)

  398  *  398  —    —  

Dennis Lyons(10)

  84  *  84  —    —  

John Olson(11)

  381  *  381  —    —  

John Paciotti(12)

  109  *  109  —    —  

Ajay Panyda(13)

  237  *  166  71  *  

Susan Parlato(14)

  99  *  99  —    —  

Peter Prokopiw(15)

  253  *  253  —    —  

Yajing Rong(16)

  159  *  159  —    —  

Safdar Shamsi(17)

  52  *  52  —    —  

Joel Srigiri(18)

  299  *  299  —    —  

Dawit Tadesse(19)

  592  *  592  —    —  

Ming Wang(20)

  261  *  261  —    —  

Zhaoying Zhang(21)

  2,992  *  1,197  1,795  *  
               

Total

  7,581  *  5,062  2,519  *  
               

*Represents less than 1.0%.

(1)Unless otherwise noted, this table is based on information supplied to us by the selling stockholders and certain records of Pharmacopeia.
(2)

We do not know when or in what amounts a selling stockholder may offer shares for sale. The selling stockholders might not sell any or all of the shares offered by this prospectus. Because the selling stockholders may offer all or some of the shares pursuant to this offering and because there are currently

no agreements, arrangements or understandings with respect to the sale of any of the shares, we cannot estimate the number of the shares that will be held by the selling stockholders after completion of the offering. However, for purposes of this table, we have assumed that, after completion of the offering, none of the shares covered by this prospectus will be held by the selling stockholders.

(3)Includes options to purchase 53 shares of common stock.
(4)Includes options to purchase 40 shares of common stock and 653 shares of common stock.
(5)Includes option to purchase 221 shares of common stock.
(6)Includes options to purchase 430 shares of common stock.
(7)Includes options to purchase 209 shares of common stock.
(8)Includes options to purchase 59 shares of common stock.
(9)Includes options to purchase 398 shares of common stock.
(10)Includes options to purchase 84 shares of common stock.
(11)Includes options to purchase 381 shares of common stock.
(12)Includes options to purchase 109 shares of common stock.
(13)Includes options to purchases 166 shares of common stock and 71 shares of common stock.
(14)Includes options to purchase 99 shares of common stock.
(15)Includes options to purchase 253 shares of common stock.
(16)Includes options to purchase 159 shares of common stock.
(17)Includes options to purchase 52 shares of common stock.
(18)Includes options to purchase 299 shares of common stock.
(19)Includes options to purchase 592 shares of common stock.
(20)Includes options to purchase 261 shares of common stock.
(21)Includes options to purchase 1,197 shares of common stock and 1,795 shares of common stock.

PLAN OF DISTRIBUTION

The common stock issuable upon exercise of our warrants and being offeredoptions will be distributed solely to existing warrant or option holders or their permitted transferees. The warrants and options are calculated based on 69,267,262immediately exercisable, and the shares of common stock issued upon exercise of the warrants and outstandingoptions will be freely tradable. We do not know if or when the warrants or options will be exercised. We also do not know whether any of the common stock acquired upon exercise of the warrants or options will be sold pursuant to this prospectus.

The selling security holders, or their pledgees, donees, transferees, or any of their successors in interest selling securities received from a named selling security holder as a gift, partnership distribution or other non-sale-related transfer after the date of April 30, 2003.
SHARES OWNED PRIOR TO THIS OFFERING --------------------------------------- NUMBER OF SHARES OF NAME OF PERCENTAGE OF COMMON COMMON STOCK SELLING STOCKHOLDER NUMBER STOCK OUTSTANDING REGISTERED HEREBY ------------------- ------ --------------------- ----------------- Ardsley Partners Fund II, L.P. 225,000 * 225,000 262 Harbor Drive 4th Floor Stamford, CT 06902 Ardsley Partners Institutional Fund, 115,000 * 115,000 L.P. 262 Harbor Drive 4th Floor Stamford, CT 06902 Ardsley Offshore Fund, Ltd. 260,000 * 260,000 262 Harbor Drive 4th Floor Stamford, CT 06902 Citadel Equity Opportunity Investments 350,000 * 350,000 Ltd. c/o Dundee Leeds Management Services Ltd. 2nd Floor, Waterfront Centre 28 N. Church Street George Town, Grand Cayman Cayman Islands, BWI
19
SHARES OWNED PRIOR TO THIS OFFERING --------------------------------------- NUMBER OF SHARES OF NAME OF PERCENTAGE OF COMMON COMMON STOCK SELLING STOCKHOLDER NUMBER STOCK OUTSTANDING REGISTERED HEREBY ------------------- ------ --------------------- ----------------- Deerfield Partners, L.P. 2,786,991 4.0 333,008 780 Third Avenue 37th Floor New York, NY 10017 Deerfield International Limited 2,572,608 3.7 307,392 780 Third Avenue 37th Floor New York, NY 10017 FrontPoint Healthcare Fund, L.P. 125,000 * 125,000 80 Field Point Road Greenwich, CT 06830 Goldman, Sachs & Co. 804,671 1.2 804,671 1 New York Plaza 50th Floor New York, NY 10004 INVESCO Stock Funds, Inc. - INVESCO 100,000 * 100,000 Small Company Growth Fund 4350 South Monaco Street Denver, CO 80237 Janus Global Life Sciences Fund 3,340,940 4.8 1,500,000 100 Fillmore Street Suite 200 Denver, CO 80206 Maverick Fund USA, Ltd. 185,800 * 185,800 300 Crescent Court 18th Floor Dallas, TX 75201 Maverick Fund II, Ltd. 93,400 * 93,400 P.O. Box 10658 APO 5th Floor, Harbour Place George Town, Grand Cayman, Cayman Islands Maverick Fund, L.D.C. 420,800 * 420,800 P.O. Box 10658 APO 5th Floor, Harbour Place George Town, Grand Cayman, Cayman Islands
20
SHARES OWNED PRIOR TO THIS OFFERING --------------------------------------- NUMBER OF SHARES OF NAME OF PERCENTAGE OF COMMON COMMON STOCK SELLING STOCKHOLDER NUMBER STOCK OUTSTANDING REGISTERED HEREBY ------------------- ------ --------------------- ----------------- Merlin BioMed Offshore Fund, L.P. 88,000 * 88,000 230 Park Avenue Suite 928 New York, NY 10169 Merlin BioMed Long-Term Appreciation 12,000 * 12,000 Fund, L.P. 230 Park Avenue Suite 928 New York, NY 10169 Eaton Vance Variable Trust 6,000 * 6,000 c/o OrbiMed Advisors LLC 767 Third Avenue 30th Floor New York, NY 10017 Eaton Vance Worldwide Health Sciences 800,000 1.2 800,000 Fund c/o OrbiMed Advisors LLC 767 Third Avenue 30th Floor New York, NY 10017 Eaton Vance Emerald Worldwide Health 22,000 * 22,000 Sciences Emerald Fund c/o OrbiMed Advisors LLC 767 Third Avenue 30th Floor New York, NY 10017 T. Rowe Price Health Sciences Fund, 225,000 * 50,000 Inc. c/o T. Rowe Price Associates, Inc. 100 East Pratt Street Baltimore, Maryland 21202 T. Rowe Price Health Sciences 1,210 * 200 Portfolio, Inc. c/o T. Rowe Price Associates, Inc. 100 East Pratt Street Baltimore, Maryland 21202
21
SHARES OWNED PRIOR TO THIS OFFERING --------------------------------------- NUMBER OF SHARES OF NAME OF PERCENTAGE OF COMMON COMMON STOCK SELLING STOCKHOLDER NUMBER STOCK OUTSTANDING REGISTERED HEREBY ------------------- ------ --------------------- ----------------- TD Mutual Funds - TD Health Sciences 69,101 * 13,600 Fund c/o T. Rowe Price Associates, Inc. 100 East Pratt Street Baltimore, Maryland 21202 VALIC Company I - Health Sciences Fund 23,100 * 6,000 c/o T. Rowe Price Associates, Inc. 100 East Pratt Street Baltimore, Maryland 21202 Manufacturers Investment Trust - 31,400 * 8,700 Health Sciences c/o T. Rowe Price Associates, Inc. 100 East Pratt Street Baltimore, Maryland 21202 IDEX Mutual Funds - IDEX - T. Rowe 10,055 * 1,000 Price Health Sciences c/o T. Rowe Price Associates, Inc. 100 East Pratt Street Baltimore, Maryland 21202 Raytheon Company Combined DB/DC Master 10,300 * 4,100 Trust - Health Sciences c/o T. Rowe Price Associates, Inc. 100 East Pratt Street Baltimore, Maryland 21202 Raytheon Master Pension Trust - Health 14,100 * 4,100 Sciences c/o T. Rowe Price Associates, Inc. 100 East Pratt Street Baltimore, Maryland 21202 TOTAL: 12,692,476 5,835,771 ========== =========
* Indicates lessthis prospectus (all of whom may be selling security holders), may sell some, none or all of the securities covered by this prospectus from time to time on any stock exchange or automated inter-dealer quotation system on which the securities are listed, in the over-the-counter market, in privately negotiated transactions or otherwise, at fixed prices that may be changed, at market prices prevailing at the time of sale, at prices related to prevailing market prices or at prices otherwise negotiated. The selling security holders may sell the securities by one or more of the following methods, without limitation:

block trades in which the broker or dealer will attempt to sell the securities as agent but may position and resell a portion of the block as principal to facilitate the transaction;

purchases by a broker or dealer as principal and resale by the broker or dealer for its own account pursuant to this prospectus;

an exchange distribution in accordance with the rules of any stock exchange on which the securities are listed;

ordinary brokerage transactions and transactions in which the broker solicits purchases;

privately negotiated transactions;

short sales, either directly or with a broker-dealer or affiliate thereof;

through the writing of options on the securities, whether or not the options are listed on an options exchange;

through loans or pledges of the securities to a broker-dealer or an affiliate thereof;

by entering into transactions with third parties who may (or may cause others to) issue securities convertible or exchangeable into, or the return of which is derived in whole or in part from the value of, our common stock;

through the distribution of the securities by any selling security holder to its partners, members or security holders;

one or more underwritten offerings on a firm commitment or best efforts basis;

any combination of any of these methods of sale; and

any other method permitted pursuant to applicable law.

In addition to selling their securities covered by this prospectus, the selling security holders may transfer their securities in other ways not involving market makers or established trading markets, including directly by gift, distribution or other transfer; or sell their securities under Rule 144 of the Securities Act rather than 1% 22 under this prospectus, if the transaction meets the requirements of Rule 144. We do not know of any arrangements by the selling security holders for the sale of any of the securities.

For example, the selling security holders may engage brokers and dealers, and any brokers or dealers may arrange for other brokers or dealers to participate in effecting sales of the securities. These brokers, dealers or

underwriters may act as principals, or as an agent of a selling security holder. Broker-dealers may agree with a selling security holder to sell a specified number of the securities at a stipulated price per security. If the broker-dealer is unable to sell securities acting as agent for a selling security holder, it may purchase as principal any unsold securities at the stipulated price. Broker-dealers who acquire securities as principals may thereafter resell the securities from time to time in transactions on any stock exchange or automated inter-dealer quotation system on which the securities are then listed, at prices and on terms then prevailing at the time of sale, at prices related to the then-current market price or in negotiated transactions. Broker-dealers may use block transactions and sales to and through broker-dealers, including transactions of the nature described above.

The selling security holders may authorize agents, underwriters or dealers to solicit offers by certain specified institutions to purchase securities from them at the public offering price set forth in a prospectus supplement under delayed delivery contracts providing for payment and delivery on a specified date in the future. These contracts would be subject only to those conditions set forth in the prospectus supplement, and the prospectus supplement would indicate the commission to be paid to underwriters, dealers and agents soliciting purchases of the securities pursuant to contracts accepted by us.

From time to time, one or more of the selling security holders may pledge, hypothecate or grant a security interest in some or all of the securities owned by them. The pledgees, secured parties or persons to whom the securities have been hypothecated will, upon foreclosure in the event of default, be deemed to be selling security holders. As and when a selling security holder takes such actions, the number of securities offered under this prospectus on behalf of such selling security holder will decrease. The plan of distribution for that selling security holder’s securities will otherwise remain unchanged.

A selling security holder may, from time to time, sell the securities short, and, in those instances, this prospectus may be delivered in connection with the short sales and the securities offered under this prospectus may be used to cover short sales. A selling security holder may enter into hedging transactions with broker-dealers and the broker-dealers may engage in short sales of the securities in the course of hedging the positions they assume with that selling security holder, including, without limitation, in connection with distributions of the securities by those broker-dealers. A selling security holder may enter into option or other transactions with broker-dealers that involve the delivery of the securities offered hereby to the broker-dealers, who may then resell or otherwise transfer those securities. A selling security holder may also loan the securities offered hereby to a broker-dealer and the broker-dealer may sell the loaned securities pursuant to this prospectus.

A selling security holder may enter into derivative transactions with third parties, or sell securities not covered by this prospectus to third parties in privately negotiated transactions. If the applicable prospectus supplement indicates, in connection with those derivatives, the third parties may sell securities covered by this prospectus and the applicable prospectus supplement, including in short sale transactions. If so, the third-party may use securities pledged by the selling security holder or borrowed from the selling security holder or others to settle those sales or to close out any related open borrowings of stock, and may use securities received from the selling security holder in settlement of those derivatives to close out any related open borrowings of stock. The third-party in such sale transactions will be an underwriter and, if not identified in this prospectus, will be identified in the applicable prospectus supplement (or a post-effective amendment to the registration statement of which this prospectus forms a part).

To the extent required under the Securities Act, the aggregate amount of selling security holders’ securities being offered and the terms of the offering, the names of any agents, brokers, dealers or underwriters and any applicable commission with respect to a particular offer will be set forth in an accompanying prospectus supplement. Any underwriters, dealers, brokers or agents participating in the distribution of the securities may receive compensation in the form of underwriting discounts, concessions, commissions or fees from a selling security holder and/or purchasers of selling security holders’ securities for whom they may act (which compensation as to a particular broker-dealer might be in excess of customary commissions). Agents, underwriters and dealers may be entitled under relevant agreements with us or the selling security holders to

indemnification by us or the selling security holders against certain liabilities, including liabilities under the Securities Act, or to any contribution with respect to payments which such agents, underwriters and dealers may be required to make.

The selling security holders and any underwriters, brokers, dealers or agents that participate in the distribution of the securities may be deemed to be “underwriters” within the meaning of the Securities Act, and any discounts, concessions, commissions or fees received by them and any profit on the resale of the securities sold by them may be deemed to be underwriting discounts and commissions. Selling security holders who are “underwriters” within the meaning of the Securities Act will be subject to the prospectus delivery requirements of the Securities Act. Agents, underwriters and dealers may be customers of, engage in transactions with, or perform services for, us and our subsidiaries in the ordinary course of business.

The selling security holders and other persons participating in the sale or distribution of the securities will be subject to applicable provisions of the Exchange Act and the rules and regulations thereunder, including Regulation M. This regulation may limit the timing of purchases and sales of any of the securities by the selling security holders and any other person. The anti-manipulation rules under the Exchange Act may apply to sales of securities in the market and to the activities of the selling security holders and their affiliates. Furthermore, Regulation M may restrict the ability of any person engaged in the distribution of the securities to engage in market-making activities with respect to the particular securities being distributed for a period of up to five business days before the distribution. These restrictions may affect the marketability of the securities and the ability of any person or entity to engage in market-making activities with respect to the securities. The selling security holders will act independently of us in making decisions with respect to the timing, manner and size of each sale by them. The selling security holders may sell the securities covered by this prospectus on any stock exchange or automated inter-dealer quotation system on which the securities are listed, in the over-the-counter market or in private transactions, at market prices prevailing at the time of sale, at prices relating to the prevailing market prices or at negotiated prices.

In connection with an offering of securities, underwriters may purchase and sell the securities in the open market. These transactions may include over-allotment, syndicate covering transactions and stabilizing transactions. An over-allotment involves syndicate sales of securities in excess of the number of securities to be purchased by the underwriters in the offering, which creates a syndicate short position. Syndicate covering transactions involve purchases of securities in the open market after the distribution has been completed in order to cover syndicate short positions. Stabilizing transactions consist of some bids or purchases of securities made for the purpose of preventing or slowing a decline in the market price of the securities while the offering is in progress. In addition, the underwriters may impose penalty bids. A penalty bid is an arrangement permitting the representatives to reclaim the selling concession otherwise accruing to an underwriter or syndicate member in connection with an offering if the securities originally sold by that underwriter or syndicate member is purchased in a syndicate covering transaction and has therefore not been effectively placed by that underwriter or syndicate member.

Similar to other purchase transactions, these activities may have the effect of raising or maintaining the market price of the securities or preventing or slowing a decline in the market price of the securities. As a result, the price of the securities may be higher than the price that might otherwise exist in the open market. In addition, a penalty bid may discourage the immediate resale of securities sold in an offering of a selling security holder. The selling security holders do not make any representation or prediction as to the direction or magnitude of any effect that the transactions described above may have on the price of the securities. In addition, the selling security holders do not make any representation that the underwriters will engage in these transactions or that these transactions, once commenced, will not be discontinued without notice.

LEGAL MATTERS

The validity of the securities offered herebyby this prospectus will be passed upon for us by Clifford Chance USLatham & Watkins LLP, San Diego, California.

EXPERTS

The consolidated financial statements for the years endedand schedule of Ligand Pharmaceuticals Incorporated as of December 31, 2002, 2001 and 20002007 incorporated in this prospectus by reference from our Annual Report on Form 10-K forin the year ended December 31, 2002Prospectus constituting a part of this S-3 registration statement have been audited by Deloitte & ToucheBDO Seidman, LLP, an independent auditors, as statedregistered public accounting firm, to the extent and for the periods set forth in their report which is incorporated herein by reference, (which report expresses an unqualified opinion and includes an explanatory paragraph referring to a change in accounting principle), and have been so incorporatedare included in reliance upon thesuch report of such firm given upon theirthe authority of said firm as experts in accountingauditing and auditing. WE HAVE NOT AUTHORIZED ANY PERSON TO MAKE A STATEMENT THAT DIFFERS FROM WHAT IS IN THIS PROSPECTUS. IF ANY PERSON DOES MAKE A STATEMENT THAT DIFFERS FROM WHAT IS IN THIS PROSPECTUS, YOU SHOULD NOT RELY ON IT. THIS PROSPECTUS IS NOT AN OFFER TO SELL, NOR IS IT AN OFFER TO BUY, THESE SECURITIES IN ANY STATE IN WHICH THE OFFER OR SALE IS NOT PERMITTED. THE INFORMATION IN THIS PROSPECTUS IS COMPLETE AND ACCURATE AS OF ITS DATE, BUT THE INFORMATION MAY CHANGE AFTER THAT DATE. 23 5,835,771 SHARES LIGAND PHARMACEUTICALS INCORPORATED COMMON STOCK ---------------------------------- Prospectus ---------------------------------- July 25, 2003 PART II INFORMATION NOT REQUIRED IN PROSPECTUS ITEM 14. OTHER EXPENSES OF ISSUANCE AND DISTRIBUTION. The following table sets forth all expenses, other than underwriting discounts and commissions, payable byaccounting.

On April 1, 2008, the registrant in connection with the saleAudit Committee of the common stock being registered. AllBoard of Directors of Ligand dismissed BDO Seidman, LLP as its independent registered public accounting firm, effective immediately. The consolidated financial statements and schedule and management’s report on the amounts shown are estimates, excepteffectiveness of internal control over financial reporting of Ligand Pharmaceuticals Incorporated as of December 31, 2008 incorporated by reference in the Prospectus constituting a part of this S-3 registration statement have been audited by Grant Thornton LLP, an independent registered public accounting firm, to the extent and for the SEC registration fee. SEC registration fee................................. $6,977.84 Printing and engraving expenses...................... 5,000.00 Legal fees and expenses.............................. 15,000.00 Accounting fees and expenses......................... 5,000.00 Transfer agent and registrar fee..................... 30,000.00 Miscellaneous expenses............................... 10,000.00 --------- TOTAL 71,977.84 =========
ITEM 15. period set forth in their reports incorporated herein by reference, and are included in reliance upon such reports given upon the authority of said firm as experts in auditing and accounting.

DISCLOSURE OF COMMISSION POSITION ON

INDEMNIFICATION OF OFFICERS AND DIRECTORS. Under Section 145FOR SECURITIES ACT LIABILITIES

Our certificate of incorporation and bylaws provide that we will indemnify our directors and officers, and may indemnify our employees and other agents, to the fullest extent not prohibited by the Delaware General Corporation Law, we have broad powers to indemnify our officers, directors and third parties acting on our behalf against liabilities they may incur in such capacities, including liabilities under the Securities Act. Our amended and restated certificate of incorporation provides for the indemnification of all of our officers, directors and third parties acting on our behalf to the fullest extent permissible under Delaware law. Our amended and restated by-laws provide for the indemnification of officers, directors and third parties acting on our behalf if such person acted in good faith and in a manner reasonably believed to be in and not opposed to our best interest, and, with respect to any criminal action or proceeding, the indemnified party had no reason to believe his or her conduct was unlawful. We maintain directors and officers insurance providing indemnification for certain of our directors and officers for certain liabilities. We also entered into indemnification agreements between us and our directors and officers, which may be sufficiently broad to permit indemnification of our officers and directors for liabilities arising under the Securities Act.Law. Insofar as indemnification for liabilities arising under the Securities Act of 1933 may be permitted to directors, officers orand controlling persons controlling us pursuant to the foregoing provisions, or otherwise, we have been informedadvised that, in the opinion of the SECSecurities and Exchange Commission, such indemnification is against public policy as expressed in the Securities Act and is therefore unenforceable. ITEM 16. EXHIBITS. (A) EXHIBITS.

WHERE YOU CAN FIND MORE INFORMATION

We file annual, quarterly and current reports, proxy statements and other information with the SEC. You may read and copy any reports, statements or other information that we file at the SEC’s public reference room at 100 F Street, N.E., Washington, D.C. 20549. Please call the SEC at 1-800-SEC-0330 for further information on the public reference room. Our public filings are also available in electronic format to the public from commercial document retrieval services and at the Internet Web site maintained by the SEC athttp://www.sec.gov. You can also review our SEC filings on our web site at http://www.ligand.com. Information included on our web site is not a part of this prospectus.

We have filed a registration statement and related exhibits on Form S-3 with the SEC. You should rely only on the information contained in this prospectus or on information to which we have incorporated by reference into this prospectus. This prospectus is a part of such registration statement. This prospectus does not contain all of the information set forth in the registration statement because certain parts of the registration statement are omitted as provided by the rules and regulations of the SEC. You may inspect and copy the registration statement at the SEC’s reference room or web addresses listed above.

INCORPORATION BY REFERENCE

The SEC allows us to “incorporate by reference” information into this prospectus, which means that we can disclose important information to you by referring you to another document filed separately with the SEC. The information incorporated by reference is deemed to be part of this prospectus, except for any information superseded by information contained directly in this prospectus. This prospectus incorporates by reference the documents described below that we have previously filed with the SEC, as well as the annexes to this prospectus. These documents contain important information about Ligand and its financial condition.

The following documents listed below that we have previously filed with the SEC are incorporated by reference:

the description of our common stock contained in our registration statement on Form 8-A filed on November 21, 1994, and any amendment or report filed for the purpose of updating such description;

the description of our preferred shares purchase rights contained in our registration statement on Form 8-A filed on October 17, 2006, and any amendment or report filed for the purpose of updating such description;

our definitive proxy statement on Schedule 14A filed with the SEC on April 29, 2009;

our annual report on Form 10-K for the fiscal year ended December 31, 2008 filed with the SEC on March 16, 2009;

our quarterly report on Form 10-Q for the fiscal quarter ended March 31, 2009 filed with the SEC on May 11, 2009;

our current reports on Form 8-K filed with the SEC on January 26, 2009, February 6, 2009, February 18, 2009, February 20, 2009, February 25, 2009, March 27, 2009 and April 22, 2009; and

all documents filed by us with the SEC pursuant to Sections 13(a), 13(c), 14 or 15(d) of the Exchange Act after the date of this prospectus and prior to the termination of this offering of securities.

Any statement incorporated herein shall be deemed to be modified or superseded for purposes of this prospectus to the extent that a statement contained herein or in any other subsequently filed document which also is or is deemed to be incorporated by reference herein modifies or supersedes such statement. Any statement so modified or superseded shall not be deemed, except as so modified or superseded, to constitute a part of this prospectus.

You may request a free copy of any of the documents incorporated by reference in this prospectus by writing to us or telephoning us at the address and telephone number set forth below.

Ligand Pharmaceuticals Incorporated

Attention: Investor Relations

10275 Science Center Drive

San Diego, California 92121

Telephone: (858) 550-7500

Ligand Pharmaceuticals Incorporated’s trademarks, trade names and service marks referenced in this prospectus include Ligand. All other trademarks, trade names or service marks are owned by their respective owners.

PART II

INFORMATION NOT REQUIRED IN PROSPECTUS

EXHIBIT NO. DESCRIPTION 4.1 Instruments defining
ITEM 14.Other Expenses of Issuance and Distribution.

The following table sets forth our best estimate as to our anticipated costs and expenses expected to be paid by us in connection with a distribution of securities registered hereby. All amounts are estimates except for the SEC registration fee:

SEC registration fee

  $418.39

Legal fees and expenses

   35,000.00

Accounting fees and expenses

   10,000.00

Miscellaneous

   2,000.00
    

Total

  $47,418.39
    

ITEM 15.Indemnification of Directors and Officers.

As permitted by Section 102 of the Delaware General Corporation Law, we have adopted provisions in our certificate of incorporation and Bylaws that limit or eliminate the personal liability of our directors for a breach of their fiduciary duty of care as a director. The duty of care generally requires that, when acting on behalf of the corporation, directors exercise an informed business judgment based on all material information reasonably available to them. Consequently, a director will not be personally liable to us or our stockholders for monetary damages or breach of fiduciary duty as a director, except for liability for: any breach of the director’s duty of loyalty to us or our stockholders; any act or omission not in good faith or that involves intentional misconduct or a knowing violation of law; any act related to unlawful stock repurchases, redemptions or other distributions or payment of dividends; or any transaction from which the director derived an improper personal benefit.

These limitations of liability do not affect the availability of equitable remedies such as injunctive relief or rescission. As permitted by Section 145 of the Delaware General Corporation Law, the certificates of incorporation and Bylaws provide that we may indemnify our directors, officers, employees and agents to the fullest extent permitted by the Delaware General Corporation Law, subject to limited exceptions; we may advance expenses to our directors and officers in connection with a legal proceeding to the fullest extent permitted by the Delaware General Corporation Law, subject to limited exceptions; and the rights provided in the certificates of incorporation and Bylaws are not exclusive.

In addition, we have entered into separate indemnification agreements with our directors and officers which may be broader than the specific indemnification provisions contained in the Delaware General Corporation Law. These indemnification agreements may require us, among other things, to indemnify our officers and directors against liabilities that may arise by reason of their status or service as directors or officers, other than liabilities arising from willful misconduct. These indemnification agreements also may require us to advance any expenses incurred by the directors or officers as a result of any proceeding against them as to which they could be indemnified. In addition, we have purchased a policy of directors’ and officers’ liability insurance that insures our directors and officers against the cost of defense, settlement or payment of a judgment in some circumstances. These indemnification provisions and the indemnification agreements may be sufficiently broad to permit indemnification of our officers and directors for liabilities, including reimbursement of expenses incurred, arising under the Securities Act.

In addition, Pharmacopeia, a wholly owned subsidiary of ours, maintains and honors all indemnification arrangements in place for all past and present directors, officers, employees and agents of Pharmacopeia, Inc. as of the date of the merger agreement for acts or omissions occurring at or prior to the effective time of the merger of Margaux Acquisition Corp., a wholly owned subsidiary of Ligand, with and into Pharmacopeia, Inc.

II-1


Pharmacopeia will also indemnify and hold harmless such persons to the fullest extent permitted by applicable Delaware law for acts or omissions occurring in connection with the approval of the merger agreement and the consummation of the transactions contemplated thereby. The organizational documents of Pharmacopeia contain provisions with respect to exculpation and indemnification that are at least as favorable to the past and present indemnified directors, officers, employees and agents of Pharmacopeia as those contained in Pharmacopeia’s certificate of incorporation and bylaws as in effect on the date of the merger agreement. Such provisions will not be amended, repealed or otherwise modified for six years from the effective time of the merger of Margaux Acquisition Corp. with and into Pharmacopeia, Inc. in any manner that would adversely affect the rights thereunder of such indemnified persons.

Subject to certain exceptions, Ligand also maintains a directors’ and officers’ insurance and indemnification policy which covers those persons who are covered by Pharmacopeia’s directors’ and officers’ insurance and indemnification policy as of the date of the merger agreement for events occurring prior to the effective time of the merger of Margaux Acquisition Corp. with and into Pharmacopeia on terms no less favorable than those applicable to the current directors and officers of Pharmacopeia for six years; provided that the Pharmacopeia shall not be obligated to make aggregate annual premium payments which exceed 250% of the annual premium payments on Pharmacopeia’s current policy in effect as of the date of the merger agreement.

ITEM 16.Exhibits.

Exhibit
Number

Exhibit Description

  2.1Agreement and Plan of Merger, dated as of September 24, 2008, by and among Ligand Pharmaceuticals Incorporated, Pharmacopeia, Inc., Margaux Acquisition Corp. and Latour Acquisition, LLC (included as Annex A to the rights of stockholders. Reference is made to our Form 8-A registration statementproxy statement/prospectus filed with the SEC on November 21, 199417, 2008).
  4.1Specimen stock certificate for shares of common stock of Ligand Pharmaceuticals Incorporated (incorporated into this registration statement by reference), the Amended and Restated Certificate of Incorporation (incorporated into this registration statement by reference to Exhibit 3.2 to our Form S-44.1 of Ligand Pharmaceuticals Incorporated’s registration statement on Form S-1 (No. 33-47257) filed with the SEC on July 9, 1998), the BylawsApril 16, 1992, as amended).
  4.22006 Preferred Shares Rights Agreement, dated as of October 13, 2006, by and between Ligand Pharmaceuticals Incorporated and Mellon Investor Services LLC (incorporated into this registration statement by reference to Exhibit 3.34.1 of ourLigand Pharmaceuticals Incorporated’s Current Report on Form S-4 registration statement,8-K filed with the SEC on July 9, 1998), the Amended Certificate of Designation of Rights, Preferences and Privileges of Series A Participating PreferredOctober 17, 2006).
      4.3(1)Pharmacopeia, Inc. 2004 Stock Incentive Plan.
      4.4(2)Pharmacopeia, Inc. 2000 Stock Option Plan (incorporated into this registration statement by reference to Exhibit 3.3 to10.323 of our quarterly reportAnnual Report on Form 10-Q10-K for the periodyear ended December 31, 2008, filed with the SEC on March 31, 1999)16, 2009).
      4.5(3)Form of Warrant.
  5.1Opinion of Latham & Watkins LLP regarding the legality of the securities being registered.
23.1Consent of BDO Seidman, LLP, independent registered public accounting firm.
23.2Consent of Grant Thornton LLP, independent registered public accounting firm.
23.3Consent of Latham & Watkins LLP (included in Exhibit 5.1).
24.1Powers of Attorney (included with the signature pages to this registration statement).

(1)Pursuant to resolutions adopted by the board of directors of Pharmacopeia, Inc., effective immediately prior to the effective time of the merger between Ligand and our Form 8-A registration statement filed on September 30, 1996, includingPharmacopeia, the Pharmacopeia, Inc. 2004 Stock Incentive Plan was terminated with respect to the grant of any amendments or reports filedadditional awards thereunder.

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(2)Pursuant to resolutions adopted by the board of directors of Pharmacopeia, Inc., effective immediately prior to the effective time of the merger between Ligand and Pharmacopeia, the Pharmacopeia, Inc. 2000 Stock Option Plan was terminated with respect to the grant of any additional awards thereunder.
(3)Following the effective date of the merger between Ligand and Pharmacopeia, in lieu of shares of Pharmacopeia common stock, upon the payment of the applicable exercise price, each warrant shall instead be exercisable for the purposesapplicable per share merger consideration which would have been received by the holder if the warrant had been exercised immediately prior to the effective date of updating such descriptions. 5.1 Opinion of Clifford Chance US LLP 23.1 Consent of Deloitte & Touche LLP, Independent Auditors 23.2 Consent of Clifford Chance US LLP. Included in the Opinion of Clifford Chance US LLP filed as Exhibit 5.1 24.1 Power of Attorney (See Signature Page on Page II-3). merger.
- ------------------ II-1 ITEM 17. UNDERTAKINGS. The undersigned registrant

ITEM 17.Undertakings.

We hereby undertakes: (1)undertake:

1. To file, during any period in which offers or sales are being made, a post-effective amendment to this registration statement:

(i) to include any prospectus required by Section 10(a)(3) of the Securities Act of 1933; Act;

(ii) to reflect in the prospectus any facts or events arising after the effective date of the registration statement (or the most recent post-effective amendment thereof) which, individually or in the aggregate, represent a fundamental change in the information set forth in the registration statement. Notwithstanding the foregoing, any increase or decrease in the volume of securities offered (if the total dollar value of securities offered would not exceed that which was registered) and any deviation from the low or high end of the estimated maximum offering range may be reflected in the form of prospectus filed with the CommissionSEC pursuant to Rule 424(b) if, in the aggregate, the changes in volume and price represent no more than 20 percent change in the maximum aggregate offering price set forth in the "Calculation“Calculation of Registration Fee"Fee” table in the effective registration statement; and

(iii) to include any material information with respect to the plan of distribution not previously disclosed in the registration statement or any material change to such information in the registration statement; (2)

provided, however,that paragraphs (1)(i), (1)(ii) and (1)(iii) do not apply if the information required to be included in a post-effective amendment by those paragraphs is contained in reports filed with or furnished to the SEC by us pursuant to Section 13 or 15(d) of the Exchange Act that are incorporated by reference in the registration statement, or is contained in a form of prospectus filed pursuant to Rule 424(b) that is part of the registration statement.

2. That, for the purpose of determining any liability under the Securities Act, of 1933, each such post-effective amendment shall be deemed to be a new registration statement relating to the securities offered therein, and the offering of such securities at that time shall be deemed to be the initialbona fideoffering thereof; (3)thereof.

3. To remove from registration by means of a post-effective amendment any of the securities being registered which remain unsold at the termination of the offering. The undersigned registrant

4. That, for the purpose of determining liability under the Securities Act to any purchaser:

(i) each prospectus filed by us pursuant to Rule 424(b)(3) shall be deemed to be part of the registration statement as of the date the filed prospectus was deemed part of and included in the registration statement; and

(ii) each prospectus required to be filed pursuant to Rule 424(b)(2), (b)(5), or (b)(7) as part of a registration statement in reliance on Rule 430B relating to an offering made pursuant to Rule 415(a)(1)(i), (vii) or (x) for the purpose of providing the information required by Section 10(a) of the Securities Act shall be deemed to be part of and included in the registration statement as of the earlier of the date such form of prospectus is first used after effectiveness or the date of the first contract of sale of securities in the offering described in the prospectus. As provided in Rule 430B, for liability

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purposes of the issuer and any person that is at that date an underwriter, such date shall be deemed to be a new effective date of the registration statement relating to the securities in the registration statement to which that prospectus relates, and the offering of such securities at that time shall be deemed to be the initialbona fide offering thereof. Provided, however, that no statement made in a registration statement or a prospectus that is part of the registration statement or made in a document incorporated or deemed incorporated by reference into the registration statement or prospectus that is part of the registration statement will, as to a purchaser with a time of contract of sale prior to such effective date, supersede or modify any statement that was made in the registration statement or prospectus that was part of the registration statement or made in any such document immediately prior to such effective date.

5. That, for the purpose of determining our liability under the Securities Act to any purchaser in the initial distribution of the securities, we undertake that in a primary offering of our securities pursuant to this registration statement, regardless of the underwriting method used to sell the securities to the purchaser, if the securities are offered or sold to such purchaser by means of any of the following communications, we will be a seller to the purchaser and will be considered to offer or sell such securities to such purchaser:

(i) any preliminary prospectus or prospectus of ours relating to the offering required to be filed pursuant to Rule 424;

(ii) any free writing prospectus relating to the offering prepared by or on behalf of us or used or referred to by us;

(iii) the portion of any other free writing prospectus relating to the offering containing material information about us or our securities provided by or on behalf of us; and

(iv) any other communication that is an offer in the offering made by us to the purchaser.

We hereby undertakesundertake that, for purposes of determining any liability under the Securities Act, of 1933, each filing of the registrant'sour annual report pursuant to Section 13(a) or Section 15(d) of the Securities Exchange Act of 1934 (and, where applicable, each filing of an employee benefit plan'splan’s annual report pursuant to Section 15(d) of the Securities Exchange Act of 1934)Act) that is incorporated by reference in the registration statement shall be deemed to be a new registration statement relating to the securities offered therein, and the offering of such securities at that time shall be deemed to be the initialbona fideoffering thereof.

If and when applicable, we hereby undertake to supplement the prospectus, after the expiration of the subscription period, to set forth the results of the subscription offer, the transactions by the underwriters during the subscription period, the amount of unsubscribed securities to be purchased by the underwriters, and the terms of any subsequent reoffering thereof. If any public offering by the underwriters is to be made on terms differing from those set forth on the cover page of the prospectus, a post-effective amendment will be filed to set forth the terms of such offering.

Insofar as indemnification for liabilities arising under the Securities Act of 1933 may be permitted to our directors, officers and controlling persons of the registrant pursuant to the foregoing provisions, or otherwise, the registrant haswe have been advised that in the opinion of the Securities and Exchange CommissionSEC such indemnification is against public policy as expressed in the Securities Act and is, therefore, unenforceable. In the event that a claim for indemnification against such liabilities (other than the payment by the registrantus of expenses incurred or paid by a director, officer,one of our directors, officers or controlling person of the registrantpersons in the successful defense of any action, suit or proceeding) is asserted by such director, officer or controlling person in connection with the securities being registered, the registrantwe will, unless in the opinion of itsour counsel the matter has been settled by controlling precedent, submit to a court of appropriate jurisdiction the question of whether such indemnification by itus is against public policy as expressed in the Securities Act and will be governed by the final adjudication of such issue. II-2 POWER OF ATTORNEY KNOW ALL PERSONS BY THESE PRESENTS, that each individual whose signature appears below constitutes and appoints David E. Robinson and Paul V. Maier, and each of them, his or her true and lawful attorneys-in-fact and agents, with full power of substitution, for him or her and in his or her name, place and stead, in any and all capacities, to sign any and all amendments (including post-effective amendments) to this registration statement, and to sign any registration statement for the same offering covered by this registration statement that is to be effective upon filing pursuant to Rule 462(b) promulgated under the Securities Act of 1933, as amended, and all post-effective amendments thereto, and to file the same, with all exhibits thereto and all documents in connection therewith, with the Securities and Exchange Commission, granting unto said attorneys-in-fact and agents full power and authority to do and perform each and every act and thing requisite and necessary to be done in and about the premises, as fully to all intents and purposes as he or she might or could do in person, hereby ratifying and confirming all that said attorneys-in-fact and agents, or his or their substitute or substitutes, may lawfully do or cause to be done by virtue hereof.

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SIGNATURES

Pursuant to the requirements of the Securities Act, of 1933, the registrantLigand Pharmaceuticals Incorporated certifies that it has reasonable grounds to believe that it meets all of the requirements for filing on Form S-3 and has duly caused this registration statement to be signed on its behalf by the undersigned, thereunto duly authorized, in the Citycity of San Diego, State of California, on July 25, 2003. LIGAND PHARMACEUTICALS INCORPORATED By: /S/DAVID E. ROBINSON ----------------------------- David E. Robinson, President and May 20, 2009.

LIGAND PHARMACEUTICALS INCORPORATED
By:/s/    JOHN L. HIGGINS        
John L. Higgins
Chief Executive Officer, President and Director

POWER OF ATTORNEY

KNOW ALL PERSONS BY THESE PRESENTS, that each person whose signature appears below constitutes and appoints John L. Higgins and Charles S. Berkman and each of them, and any successor or successors to such offices held by each of them, acting individually, as such person’s true and lawful attorneys-in-fact and agents, each with full power of substitution and resubstitution, for such person in his name or her name, place and stead, in any and all capacities, to sign any and all amendments (including post-effective amendments) to this registration statement, and to file the same, with all exhibits thereto and other documents in connection therewith, with the Securities and Exchange Commission, granting unto said attorneys-in-fact and agents, and each of them, full power and authority to do and perform each and every act and thing requisite and necessary to be done in connection therewith, as fully to all intents and purposes as such person might or could do in person, hereby ratifying and confirming all that said attorneys-in-fact and agents, or any of them, or their or his or her substitutes, may do or cause to be done by virtue thereof. This power of attorney may be executed in counterparts.

Pursuant to the requirements of the Securities Act of 1933, this Registration Statementregistration statement has been signed by the following persons in the capacities and on the dates indicated: indicated.

SIGNATURE TITLE DATE --------- ----- ---- /S/DAVID E. ROBINSON July 25, 2003 - ----------------------------------------- David E. Robinson

Signature

Title

Date

/s/    JOHN L. HIGGINS        

John L. Higgins

President, and Chief Executive Officer and Director (Principal Executive Officer) /S/PAUL V. MAIER July 25, 2003 - ----------------------------------------- Paul V. Maier Senior May 20, 2009

/s/    JOHN P. SHARP        

John P. Sharp

Vice President, Finance and Chief Financial Officer (Principal Financial and Accounting Officer) /S/HENRY F. BLISSENBACH July 25, 2003 - ----------------------------------------- Henry F. Blissenbach May 20, 2009

/s/    JASON M. ARYEH        

Jason M. Aryeh

Director /S/ALEXANDER D. CROSS July 25, 2003 - ----------------------------------------- Alexander D. Cross May 20, 2009

/s/    STEVEN J. BURAKOFF        

Steven J. Burakoff

Director /S/JOHN GROOM July 25, 2003 - ----------------------------------------- John Groom May 20, 2009

/s/    TODD C. DAVIS        

Todd C. Davis

Director /S/IRVING S. JOHNSON July 25, 2003 - ----------------------------------------- Irving S. Johnson, Ph.D. May 20, 2009

/s/    DAVID M. KNOTT        

David M. Knott

Director - ----------------------------------------- May 20, 2009

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Signature

Title

Date

/s/    JOHN W. KOZARICH        

John W. Kozarich

Director /S/CARL C. PECK July 25, 2003 - ----------------------------------------- Carl C. Peck Director /S/MICHAELMay 20, 2009

/s/    BRUCE A. ROCCA July 25, 2003 - ----------------------------------------- MichaelPEACOCK        

Bruce A. Rocca Peacock

DirectorMay 20, 2009

/s/    STEPHEN L. SABBA        

Stephen L. Sabba

DirectorMay 20, 2009
II-3 EXHIBIT

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INDEX TO EXHIBITS

EXHIBIT NO. DESCRIPTION 4.1 Instruments defining

Exhibit
Number

Exhibit Description

  2.1Agreement and Plan of Merger, dated as of September 24, 2008, by and among Ligand Pharmaceuticals Incorporated, Pharmacopeia, Inc., Margaux Acquisition Corp. and Latour Acquisition, LLC (included as Annex A to the rights of stockholders. Reference is made to ourproxy statement/prospectus on Form 8-A registration statementS-4 filed with the SEC on November 21, 199417, 2008).
  4.1Specimen stock certificate for shares of common stock of Ligand Pharmaceuticals Incorporated (incorporated into this registration statement by reference), the Amended and Restated Certificate of Incorporation (incorporated into this registration statement by reference to Exhibit 3.2 to our Form S-44.1 of Ligand Pharmaceuticals Incorporated’s registration statement on Form S-1 (No. 33-47257) filed with the SEC on July 9, 1998), the BylawsApril 16, 1992, as amended).
  4.22006 Preferred Shares Rights Agreement, dated as of October 13, 2006, by and between Ligand Pharmaceuticals Incorporated and Mellon Investor Services LLC (incorporated into this registration statement by reference to Exhibit 3.34.1 of ourLigand Pharmaceuticals Incorporated’s Current Report on Form S-4 registration statement,8-K filed with the SEC on July 9, 1998), the Amended Certificate of Designation of Rights, Preferences and Privileges of Series A Participating PreferredOctober 17, 2006).
      4.3(1)Pharmacopeia, Inc. 2004 Stock Incentive Plan.
      4.4(2)Pharmacopeia, Inc. 2000 Stock Option Plan (incorporated into this registration statement by reference to Exhibit 3.3 to10.323 of our quarterly reportAnnual Report on Form 10-Q10-K for the periodyear ended December 31, 2008, filed with the SEC on March 31, 1999)16, 2009).
      4.5(3)Form of Warrant.
  5.1Opinion of Latham & Watkins LLP regarding the legality of the securities being registered.
23.1Consent of BDO Seidman, LLP, independent registered public accounting firm.
23.2Consent of Grant Thornton LLP, independent registered public accounting firm.
23.3Consent of Latham & Watkins LLP (included in Exhibit 5.1).
24.1Powers of Attorney (included with the signature pages to this registration statement).

(1)Pursuant to resolutions adopted by the board of directors of Pharmacopeia, Inc., effective immediately prior to the effective time of the merger between Ligand and our Form 8-A registration statement filed on September 30, 1996, includingPharmacopeia, the Pharmacopeia, Inc. 2004 Stock Incentive Plan was terminated with respect to the grant of any amendments or reports filedadditional awards thereunder.
(2)Pursuant to resolutions adopted by the board of directors of Pharmacopeia, Inc., effective immediately prior to the effective time of the merger between Ligand and Pharmacopeia, the Pharmacopeia, Inc. 2000 Stock Option Plan was terminated with respect to the grant of any additional awards thereunder.
(3)Following the effective date of the merger between Ligand and Pharmacopeia, in lieu of shares of Pharmacopeia common stock, upon the payment of the applicable exercise price, each warrant shall instead be exercisable for the purposesapplicable per share merger consideration which would have been received by the holder if the warrant had been exercised immediately prior to the effective date of updating such descriptions. 5.1 Opinion of Clifford Chance US LLP 23.1 Consent of Deloitte & Touche LLP, Independent Auditors 23.2 Consent of Clifford Chance US LLP. Included in the Opinion of Clifford Chance US LLP filed as Exhibit 5.1 24.1 Power of Attorney (See Signature Page on Page II-3). merger.
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