Ligand Presents Data on Novel RXR Homodimer Antagonist Compound with Potential Utility in Diabetes and Obesity.

Business Editors/Health and Medical Writers

BIOWIRE2K

SAN DIEGO--(BW HealthWire)--Feb. 18, 2000

Ligand Pharmaceuticals Incorporated (Nasdaq:LGND) presented today results of a study describing the compound LG100754, an RXR homodimer antagonist that acts as a selective RXR:PPAR agonist, at the Keystone Symposium: Molecular Control of Adipogenesis and Obesity in Taos, New Mexico.

The results of the study suggest that LG100754 represents a novel class of rexinoid with insulin-sensitizing ability that may have a favorable profile of activity in the treatment of diabetes and obesity compared to first-generation rexinoids.

&uot;Compounds such as the one described today represent significant progress in our quest to develop exciting new therapies for the treatment of individuals with Type II diabetes,&uot; said Andres Negro-Vilar, M.D., Ph.D., Ligand Senior Vice President of Research and Development and Chief Scientific Officer.

Ligand has been a pioneer in the discovery of compounds that act as ligands for the nuclear receptor RXR with distinct selectivity and has termed these novel compounds &uot;rexinoids.&uot; Ligand researchers have now shown that the compound LG100754 represents a novel rexinoid with potential application as an insulin sensitizer in diabetes and obesity. The unique selectivity profile of LG100754 may provide advantages over first-generation rexinoids.

The RXR:PPAR(gamma) (peroxisome proliferator-activated receptor gamma) heterodimer plays an important role in controlling cellular events such as lipid homeostasis and adipocyte (fat cell) differentiation. In addition, it is the presumed target for a class of insulin sensitizers known as thiazolidinediones such as Rezulin(R) (troglitazone), Actos(R) (pioglitazone hydrochloride) and Avandia(R) (rosiglitazone maleate), which bind directly to PPAR(gamma).

Previously, Ligand scientists have shown that compounds capable of activating the RXR homodimer (such as the RXR agonist LG100268) also serve as insulin sensitizers by activating the RXR:PPAR(gamma) heterodimer by binding to RXR. However, LG100268 is non-selective in that it also activates a number of other RXR-containing heterodimers.

The current data show that the rexinoid LG100754 possesses selectivity for RXR:PPAR heterodimers and does not activate many of the other RXR-containing heterodimers. The data thus suggest that LG100754 represent a novel class of rexinoid with insulin-sensitizing ability with potential for an improved profile compared to first-generation rexinoids by selectively activating the desired target genes. Rights to these discoveries fall within the Lilly/Ligand collaborative alliance for the diabetes and obesity fields.

Presented today at the Keystone Symposium: Molecular Control of Adipogenesis and Obesity, the abstract was titled &uot;RXR Homodimer Antagonists Act as RXR:PPAR Selective Agnoists and Modulate Insulin Receptor Phosphorylation&uot; and was authored by Rosemary M. Cesario, M.S., Haleh Razzaghi, M.S., and Deepak S. Lala, Ph.D., Department of Nuclear Receptor Discovery, Ligand Pharmaceuticals, San Diego, California.

Ligand Pharmaceuticals Incorporated

Ligand Pharmaceuticals Incorporated discovers, develops and markets new drugs that address critical unmet medical needs of patients in the areas of cancer, skin diseases, and men's and women's hormone-related diseases, as well as osteoporosis, metabolic disorders and cardiovascular and inflammatory diseases. In addition to the recently approved Targretin(R) capsules, Ligand had two drugs approved during 1999 for marketing in the U.S. -- ONTAK(R) and Panretin(R) gel -- that are being marketed through its specialty cancer and HIV-center sales force in the U.S. Targretin(R) gel is currently under review by the FDA for marketing approval in the U.S., and two additional oncology-related products -- Morphelan(TM) (licensed from Elan) and Panretin(R) capsules -- are in late-stage development. Ligand's proprietary drug discovery and development programs are based on its leadership position in gene transcription technology, primarily related to Intracellular Receptors (IR) and Signal Transducers and Activators of Transcription (STATs).

This news release may contain certain forward-looking statements by Ligand and actual results could differ materially from those described as a result of factors including but not limited to the following. There can be no assurance that LG100754 or any development candidate identified as a result of the Lilly / Ligand collaboration or any compound or product in the Ligand or Seragen pipeline, will be successfully developed, that results from more advanced clinical trials will be consistent with earlier results, that drug candidates will show efficacy in all indications currently being studied, that any products under development by Ligand or any of its collaborative partners will receive approval from the FDA or other authorities to market any of these products, or that if successfully developed and thereafter approved, there will be a market for the drugs.

Additional information concerning these and other factors affecting Ligand's business can be found in press releases as well as in Ligand's public periodic filings with the Securities and Exchange Commission, available on our web site at www.ligand.com. Ligand disclaims any intent or obligation to update these forward-looking statements beyond the date of this release.

Note: Panretin(R) and Targretin(R) are registered trademarks of Ligand Pharmaceuticals Incorporated, and ONTAK(R) is a registered trademark of Seragen, Inc., a wholly owned subsidiary of Ligand. Full prescribing information for ONTAK and Panretin gel may be obtained from Ligand Professional Services by calling toll-free 1-800-964-5836.

Rezulin(R) is a registered trademark of Warner Lambert Company. Actos(R) is a registered trademark of Takeda Chemical Industries, Ltd. Avandia(R) is a registered trademark of SmithKline Beecham PLC.

Ligand Pharmaceuticals' releases are available on the World Wide Web at www.businesswire.com/cnn/lgnd.htm.