Ligand Receives Approvable Letter from FDA for Targretin Gel; Approval Would Mark Fourth Product Approval for Ligand in Past 18 Months.

Business Editors & Health/Medical Writers

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SAN DIEGO--(BW HealthWire)--June 12, 2000

Ligand Pharmaceuticals Incorporated (Nasdaq:LGND) announced today that the U.S. Food and Drug Administration (FDA) has issued an approvable letter regarding the New Drug Application (NDA) for Targretin(R) (bexarotene) gel 1%, a novel therapy for the topical treatment of cutaneous lesions in patients with early-stage cutaneous T-cell lymphoma (CTCL) who have refractory or persistent disease after other therapies or who have not tolerated other therapies. Final FDA marketing approval of Targretin gel is pending final labeling agreement. Targretin gel, which was granted priority review status by the FDA, would be Ligand's third approved product for CTCL and the first topical therapy approved by the FDA for CTCL.

"We are pleased with the FDA's issuance of an approvable letter for Targretin gel," said David E. Robinson, Ligand Chairman, President and CEO. "We will continue to work closely with the agency to finalize labeling so that we can supply Targretin gel to patients with refractory early-stage CTCL in the U.S. as soon as possible. Targretin gel is expected to further accelerate the sales in our specialty oncology and dermatology business and enhance the development of the Targretin brand franchise."

Topically-applied Targretin gel would offer patients with CTCL a novel, non-invasive, self-administered treatment applied only to the affected areas of the skin. Treatments currently available for early-stage CTCL, such as nitrogen mustard and carmustine, are generally applied daily to the patient's whole body; this can be a time-consuming and difficult task for many patients, especially those who live alone. Other available therapies for CTCL, such as electron beam treatment, photophoresis, and Psoralen plus ultraviolet light (PUVA), require frequent visits to a clinic, hospital or doctor's office for administration by a healthcare professional. For patients with refractory early-stage CTCL, Targretin gel would offer an effective and convenient new therapeutic option. Side effects occurred primarily at the application site and included rash, itching and pain.

Cutaneous T-Cell Lymphoma Background

Affecting an estimated 16,000 people in the U.S., CTCL is a form of non-Hodgkin's lymphoma which results in circulating malignant T-lymphocytes (white blood cells involved in the body's immune system). CTCL ordinarily manifests itself initially in the skin, but over time may progress to involve other organs. CTCL is most commonly a slowly progressing cancer, and many patients live with the complications of CTCL for 10 years or more after diagnosis. Some patients, however, have a much more aggressive form of this disease, and the median survival for advanced-stage patients is less than three years.

Ligand's CTCL Assets: Targretin gel, Targretin(R)capsules and ONTAK(R)

With the approval of Targretin gel, Ligand will be able to offer topical (Targretin gel), oral (Targretin capsules), and injectable (ONTAK) treatment options for appropriate patients suffering from CTCL. ONTAK, approved by the FDA in February 1999 for treatment of patients with persistent or recurrent cutaneous T-cell lymphoma whose malignant cells express the CD25 component of the IL-2 receptor, was the first of these three products approved for CTCL and was the first new agent approved for this disease in the last 10 years.

Ligand is targeting submission of a Marketing Authorization Application (MAA) with the European Agency for the Evaluation of Medicinal Products (EMEA) for Targretin gel during 2000.

The FDA granted marketing approval in December 1999 for Targretin capsules in the treatment of cutaneous manifestations of early- and late-stage CTCL in patients who were refractory to at least one systemic therapy. An MAA was submitted in November 1999 to the EMEA for Targretin capsules in the treatment of patients with all clinical stages of CTCL (IA-IVB).

In Phase II trials, Targretin capsules are being studied in patients with moderate to severe psoriasis and advanced breast cancer. Interim results are expected in the second half of 2000.

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 had three drugs approved during 1999 for marketing in the U.S. -- Targretin(R) (bexarotene) capsules, ONTAK(R) (denileukin diftitox) and Panretin(R) (alitretinoin) gel -- that are being marketed through its specialty cancer and dermatology-focused sales force. An NDA for Morphelan(TM) (licensed from Elan) is currently under review by the FDA. Ligand's proprietary drug discovery and development programs are based on its leadership position in gene transcription technology, primarily related to Intracellular Receptors (IRs) 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 outside of the control of Ligand. There can be no assurance that: Ligand and the FDA will reach timely agreement on final labeling for Targretin gel; Targretin or any product in the Ligand pipeline will be successfully developed for psoriasis, breast cancer or any other indication; regulatory filings will be made and regulatory approvals will be granted in a timely manner or at all; Targretin gel or any other approved Ligand product will be accepted by physicians for prescribing, by patients for use and by insurance companies/agencies for reimbursement. Additional information concerning these and other factors affecting Ligand's business can be found in prior press releases as well as in Ligand's public periodic filings with the Securities and Exchange Commission, available via Ligand's website at http://www.ligand.com. Ligand disclaims any intent or obligation to update these forward-looking statements beyond the date of this release.

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

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