Ligand Pre-Clinical Study Results for Targretin Published in ``Journal of the National Cancer Institute''.

SAN DIEGO--(BW HealthWire)--Dec. 15, 1999--

Suggests Targretin(R) May be Useful for Breast

Cancer Patients Who Have Failed Tamoxifen Therapy

Ligand Pharmaceuticals Incorporated (Nasdaq:LGND) published in the "Journal of the National Cancer Institute" results of its third pre-clinical study of Targretin in breast cancer, showing that Targretin(R) (bexarotene), when added to tamoxifen therapy, caused complete or partial regression in 94 percent of animals with tamoxifen-resistant primary breast tumors.

As a result of the positive indications from multiple pre-clinical studies, Ligand launched a human 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 are now expected in the first half of 2000 from this ongoing clinical trial.

"Our previous studies, published in 'Cancer Research' in December 1996 and February 1998, have shown the efficacy of Targretin in pre-clinical models for breast cancer prevention and for the treatment of well-established breast tumors," said William W. Lamph, Ph.D., Ligand Associate Director, Nuclear Receptor Discovery. "This pre-clinical study showed that a combination of Targretin and tamoxifen was more effective than treatment with either agent alone, suggesting that Targretin may also be a useful therapeutic for breast cancer patients who have failed tamoxifen therapy."

The data published yesterday demonstrated that Targretin, when added to tamoxifen treatment, caused complete or partial regression in 94 percent of primary breast tumors in animals that had stopped responding to and hence failed initial tamoxifen therapy. In contrast, only 33 percent of primary breast tumors that remained on high-dose tamoxifen therapy but did not receive Targretin exhibited a complete or partial regression. The majority of tumors that remained on high-dose tamoxifen therapy alone continued to show progressive growth, consistent with previous studies showing emergence of tamoxifen resistance. The combination of Targretin and tamoxifen showed a significant decrease of 38% in the total number of mammary tumors per animal compared to only a 6% decrease in total number of tumors per animal for those animals that remained on tamoxifen therapy alone. The combination regimen of Targretin and tamoxifen not only reduced the total number of tumors per animal, but also significantly decreased primary tumor burden by 68%. In contrast, primary tumor burden increased by 15% for animals that remained on tamoxifen alone, consistent with their tamoxifen-resistant characteristics. The data published yesterday also demonstrated that 51 percent of mammary tumors that had failed to respond to tamoxifen therapy exhibited a complete or partial regression when Targretin therapy was initiated in the absence of additional tamoxifen administration.

"The current data clearly demonstrate that Targretin can overcome tamoxifen failure in this pre-clinical model and may provide a rationale for combining Targretin with tamoxifen after mammary tumors have failed initial tamoxifen therapy," said Dr. Lamph.

Ligand has filed a New Drug Application (NDA) with the U.S. Food and Drug Administration (FDA) for Targretin capsules to treat patients with cutaneous T-cell lymphoma (CTCL) and is conducting Phase II studies in breast cancer. Ligand met with the FDA's Oncologic Drugs Advisory Committee on December 13 to review the NDA submission of Targretin capsules to treat patients with CTCL, and the FDA is expected to complete its review of the NDA in December 1999.

The results of the pre-clinical study were presented previously at the American Association for Cancer Research (AACR) 90th Annual meeting in Philadelphia, and more recently the initial analysis of this data was presented at the National Surgical Adjuvant Breast and Bowel Project (NSABP) annual conference in Washington, D.C.

Additional data presented earlier this year at both the AACR meeting in Philadelphia and at the 81st Annual meeting of the Endocrine Society in San Diego by Veena Agarwal, Ph.D., a Ligand research scientist, demonstrated that, in this pre-clinical model, Targretin administration altered cellular differentiation within the tumor and that this altered differentiation correlated with mammary tumor regression.

Targretin, also known as LGD1069 (bexarotene), a synthetic retinoid analogue discovered by Ligand scientists, selectively activates a subclass of retinoid receptors called Retinoid X Receptors (RXR), which play an important role in the control of cellular functions.

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 -- Panretin(R) gel and ONTAK(R) -- were approved for marketing in the U.S. in early 1999 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(R) capsules, Targretin(R) gel, Panretin(R) 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 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 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 final results will be supportive of regulatory approvals required to market products, that regulatory filings will be made in a timely manner, that regulatory approvals will be received in a timely manner or at all, or that patient and physician acceptance of these products will be achieved. 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 via our website at http://www.ligand.com. Ligand disclaims any intent or obligation to update these forward-looking statements beyond the date of this release.

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.

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