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Company Press Release

Ligand Presents at ENDO '99: Targretin Causes Complete Regression Of Rat Mammary Tumors by Inducing Fat Cell Differentiation in Tumor Cells

Human Clinical Trials Launched in November 1998

SAN DIEGO--(BW HealthWire)--June 14, 1999-- SAN DIEGO, CA - June 14, 1999 -- Ligand Pharmaceuticals Incorporated (Nasdaq:LGND - news) presented today at the Endocrine Society's annual meeting in San Diego results of a pre-clinical study showing a novel molecular activity of Targretin® (bexarotene), also known as LGD1069, in a rat breast cancer model.

Discovered by scientists at Ligand, Targretin is a synthetic retinoid analogue that selectively activates a subclass of retinoid receptors called retinoid X receptors (RXR). These studies demonstrate that Targretin induces fat cell differentiation and reduces growth of cancer cells, resulting in regression of the tumors.

Veena R. Agarwal, Ph.D., a Ligand Research Scientist, presented the results of a study exploring the molecular activity of Targretin in an animal model of breast cancer. The analysis compared: 1) untreated tumors, 2) Targretin-treated tumors undergoing regression, and 3) progressively growing tumors that have failed Targretin therapy. The data demonstrate that:

``Results from this study indicate that activation of RXR triggers the induction of genes associated with fat-cell differentiation in the cancer cells and a reduction in cancer cell growth,'' said Andres Negro-Vilar, M.D., Ph.D., Ligand Senior Vice President of Research and Chief Scientific Officer. ``This study is the first evidence suggesting that Targretin and other RXR ligands activate a genetic pathway that may provide a novel approach for breast cancer therapy. While this latest data provides important insight into Targretin's mechanism of action in breast cancer, it may not be the only mechanism of action and will continue to be studied by Ligand.''

Previous studies have shown the efficacy of Targretin in preclinial models for breast cancer prevention and for the treatment of well-established breast tumors. Additional preclinical studies have shown that a combined therapy of Targretin and tamoxifen cause complete or partial regression in 94% of tamoxifen-resistant primary breast tumors, as reported by Eric Bischoff, a Ligand Research Scientist, on April 13, 1999, at the annual meeting of the American Association for Cancer Research (AACR). In June 1998, William W. Lamph, Ph.D., Ligand Associate Director, Retinoid Research, presented the initial analysis of this data at the National Surgical Adjuvant Breast and Bowel Project (NSABP) annual conference in Washington, D.C. Both presentations were based on data from pre-clinical studies showing that the activity of Targretin causes complete and partial regression of breast tumors that grew despite tamoxifen therapy. Tamoxifen is currently the most widely prescribed hormonal breast cancer therapy. Ligand scientists have previously reported that Targretin does not alter estrogen, progesterone, or prolactin levels in the scientific model used, and that Targretin can inhibit the undesirable side effects of uterine growth stimulation that occurs with both estrogen and tamoxifen.

As a result of the positive indications from multiple pre-clinical studies, Ligand launched a Phase II clinical trial in November 1998 to assess the effectiveness of Targretin capsules in the treatment of women with advanced breast cancer. Interim results from this ongoing clinical trial are expected in the second half of 1999.

Breast cancer is the second leading cause of cancer death in women. One in eight women in the United States is at risk for developing breast cancer. Current therapies include chemotherapy and hormone therapy, such as the antiestrogen tamoxifen. Although tamoxifen is highly effective, its use is limited by side effects and the fact that the majority of women will eventually fail tamoxifen therapy. Additional novel approaches to the treatment of breast cancer are therefore necessary.

Ligand has also studied Targretin for the treatment of patients with cutaneous T-cell lymphoma, for which Ligand expects to file a new drug application for Targretin capsules in the first half of 1999, as well as for advanced lung cancer, ovarian cancer, head and neck cancer, Kaposi's sarcoma, psoriasis and actinic keratoses.

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. Ligand's first two drugs were approved for marketing in the U.S. in early 1999 -- Panretin® gel and ONTAK(tm) -- and are being marketed through its specialty cancer and HIV-center sales force in the U.S. Four additional oncology-related products are in late-stage development, including Targretin® capsules, Targretin® gel, Panretin® capsules, and Morphelan(tm) (licensed from Elan). 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 statement 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 Targretin, or any product in the Ligand pipeline, will be successfully developed, that regulatory approvals will be granted, that patient and physician acceptance of these products will be achieved, that results of human clinical trials will be consistent with any pre-clinical results, or any results will be supportive of regulatory approvals required to market products. Ligand undertakes no obligation to update the statements contained in this press release after the date hereof.

Note: Public information on Ligand Pharmaceuticals Incorporated, including our financial statements and other filings with the Securities and Exchange Commission, our recent press releases and the package inserts for products approved for sales and distribution in the United States, is available at our website at http://www.ligand.com.

Panretin® and Targretin® are registered trademarks of Ligand Pharmaceuticals Incorporated, and ONTAK(tm) is a trademark of Seragen, Inc., a wholly owned subsidiary of Ligand.

Ligand Pharmaceuticals' releases are available via fax at no charge by calling 888/329-9832 or on the World Wide Web at www.businesswire.com/cnn/lgnd.htm.


Contact:
     Ligand Pharmaceuticals Incorporated
     Paul V. Maier, 858/550-7573



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