Ligand Announces Positive Preclinical Data on IRAK4 Program at the 2011 American College of Rheumatology Annual Scientific Meeting

Ligand Pharmaceuticals Incorporated (NASDAQ: LGND) today announced that data from preclinical studies on its Interleukin-1 Receptor Associated Kinase-4 (IRAK4) program was featured in an oral presentation today at the 2011 Annual Scientific Meeting of the American College of Rheumatology and the Association of Rheumatology Health Professionals (ACR/ARHP) in Chicago. IRAK4 is a protein kinase involved in immune and inflammatory signaling and has become a high priority novel target for drug development in the areas of oncology and inflammation.

In preclinical studies, Ligand evaluated the activity of novel IRAK4 inhibitor compounds and their potential use in inflammatory diseases. The key findings include:

• Ligand has discovered compounds that bind to IRAK4 and potently inhibit IRAK4 kinase activity in cell-based assays.
• IRAK4 inhibitors are pathway selective for interleukin-1 receptor and toll-like receptor 4 with little or no activity on Tumor Necrosis Factor alpha (TNF-a) and Interferon gamma (INF-?) pathways.
• IRAK4 inhibitors showed substantially reduced off-target kinase activity.
• Oral administration of an IRAK4 inhibitor halted disease progression in a mouse model of rheumatoid arthritis.
• IRAK4 inhibition is a novel approach for the treatment of inflammatory diseases.

"We are excited by the advances of our IRAK4 program in unlocking previously intractable targets. We believe this program has the potential to deliver small molecule, oral medicines that will transform the treatment of a range of serious inflammatory diseases. Inhibition of kinases responsible for inflammatory processes continues to be an area of growing importance scientifically and medically, an example of which is JAK3 where an inhibitor has achieved considerable success in late-stage development for inflammatory diseases. Our early research on IRAK4 suggests that it could be the next frontier of small molecule research,” said Matthew W. Foehr, Chief Operating Officer of Ligand Pharmaceuticals. "Given the broad range of therapeutic applications for a novel IRAK4 inhibitor, this program is ideally suited for a collaborative research partnership with a company who has clinical development expertise in a number of therapeutic areas.”

About Ligand’s IRAK4 Program

IRAK4 is a protein kinase involved in signaling innate immune responses from interleukin-1, interleukin 18, and toll-like receptors. This molecule plays an important role in the innate immune system and may also be important for cross-talk between the innate and adaptive immune systems. IRAK4 is a key signaling component downstream of both toll-like receptors and interleukin-1 receptor suggesting that it may have therapeutic value for a range of autoimmune and inflammatory conditions. Inhibition of IRAK4 activity has been implicated in multiple diseases including rheumatoid arthritis, systemic lupus erythematosus, gout, inflammatory bowel disease, asthma, and allergic rhinitis. Inhibitors of IRAK4 may also be useful for the treatment of certain leukemias and lymphomas.

About Ligand Pharmaceuticals

Ligand is a biopharmaceutical company with a business model that is based upon the concept of developing or acquiring royalty revenue generating assets and coupling them to a lean corporate cost structure. Ligand’s goal is to produce a bottom line that supports a sustainably profitable business. By diversifying the portfolio of assets across numerous technology types, therapeutic areas, drug targets, and industry partners, we offer investors an opportunity to invest in the increasingly complicated and unpredictable pharmaceutical industry. In comparison to its peers, we believe Ligand has assembled one of the largest and most diversified asset portfolios in the industry with the potential to generate revenue in the future. These therapies address the unmet medical needs of patients for a broad spectrum of diseases including hepatitis, muscle wasting, Alzheimer's disease, dyslipidemia, diabetes, anemia, COPD, asthma, rheumatoid arthritis and osteoporosis. Ligand’s Captisol platform technology is a patent protected, chemically modified cyclodextrin with a structure designed to optimize the solubility and stability of drugs. Ligand has established multiple alliances with the world's leading pharmaceutical companies including GlaxoSmithKline, Merck, Pfizer, Baxter International, Bristol-Myers Squibb, Celgene, Onyx Pharmaceuticals, Lundbeck Inc. and The Medicines Company. Please visit www.captisol.com for more information on Captisol. For more information on Ligand, please visit www.ligand.com.

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Caution Regarding Forward-Looking Statements

This news release contains forward-looking statements by Ligand that involve risks and uncertainties and reflect Ligand’s judgment as of the date of this release. These include statements regarding data analysis and evaluation of IRAK4, utility or potential benefits to patients, plans for continued development and further studies of IRAK4. Actual events or results may differ from our expectations. For example, there can be no assurance that other trials or evaluations of IRAK4 will be favorable or that they will confirm results of previous studies, that data evaluation will be completed or demonstrate any hypothesis or endpoint, that IRAK4 will provide utility or benefits to certain patients, that any presentations will be favorably received, that IRAK4 will be useful with other drugs, that marketing applications will be filed or, if filed, approved, or that clinical or commercial development of these drugs will be initiated, completed or successful or that our rights to IRAK4 will not be successfully challenged. Our stock price may suffer as a result of the failure of any trials to be completed or meet their endpoints or if any actual events differ from our expectations. Additional information concerning these and other risk factors affecting Ligand can be found in prior press releases as well as in public periodic filings with the Securities and Exchange Commission, available via www.ligand.com. Ligand disclaims any intent or obligation to update these forward-looking statements beyond the date of this release.