Ligand Receives FDA Marketing Clearance for Targretin Gel; Approval Adds Fourth Product to Ligand's Specialty Oncology Products Business.

Business Editors/Health & Medical Writers

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SAN DIEGO--(BW HealthWire)--June 29, 2000

Ligand Pharmaceuticals Incorporated (Nasdaq:LGND) announced today that the U.S. Food and Drug Administration (FDA) has granted marketing clearance for Targretin(R) (bexarotene) gel 1%, a novel therapy for the topical treatment of cutaneous lesions in patients with early-stage (TNM Stage IA and IB) cutaneous T-cell lymphoma (CTCL) who have refractory or persistent disease after other therapies or who have not tolerated other therapies. Targretin gel is Ligand's fourth product in the U.S. and is the first and only topical therapy approved by the FDA for treating patients with CTCL.

Ligand plans to make this important new treatment available to patients in the coming weeks and to market Targretin gel in the U.S. through its current specialty oncology and dermatology-focused sales force.

Topically-applied, Targretin gel offers patients with CTCL a novel, non-invasive, self-administered treatment that is applied only to the affected areas of the skin. Other currently available but unapproved treatments for early-stage CTCL, including nitrogen mustard and carmustine, may be limited by allergic hypersensitivity reactions, commercial availability, and an increased risk of secondary skin cancers. Unlike Targretin gel, topical nitrogen mustard is generally applied to the skin over the entire body; this can be a time-consuming and difficult task for many patients, especially those who live alone. Many other current therapies for CTCL, such as electron beam treatment, photopheresis, and psoralen plus UV-A light (PUVA), require frequent visits to a clinic, hospital or doctor's office for administration by healthcare professionals.

"The FDA's approval of Targretin gel is another milestone within our overall strategic goals," said David E. Robinson, Ligand Chairman, President and CEO. "Targretin gel is our fourth drug approved for marketing in the U.S. and joins Targretin capsules, ONTAK(R) and Panretin(R) gel, approved in 1999.

"The anticipated launch of Targretin gel, added to the ongoing launch of Targretin capsules, will cause us to further intensify our efforts and coverage of private practice dermatologists in addition to our efforts with private practice oncologists for ONTAK. The focus of Ligand's clinical and commercial operations, until the expected launch next year of Morphelan(TM) (if approved; NDA submitted 5/00), is to penetrate the first indication market and broaden the indications and use of Targretin and ONTAK to build our near-term revenue base."

Basis for Approval

The FDA based its decision for Targretin gel on a multicenter, open-label Phase III clinical trial that was conducted in the U.S., Canada, Europe and Australia involving 50 patients; a Phase I-II clinical program involving 67 patients; and supporting data from 200 patients with CTCL treated with Targretin capsules. Efficacy results in the Phase III trial exceeded the protocol-defined response rate target. Side effects were primarily limited to local skin reactions and included rash, itching, skin disorder, and pain.

"Patients studied in the Phase III clinical trial for Targretin gel failed at least two prior therapies and often had received multiple other treatments," said Steven D. Reich, M.D., Ligand Senior Vice President, Clinical Research. "Targretin gel can provide patients with early-stage CTCL a treatment alternative that is both effective and generally well tolerated in managing the cutaneous manifestations of CTCL, a progressive and symptomatic disease. With Targretin capsules and ONTAK, the introduction of Targretin gel allows us to offer patients and physicians a comprehensive range of therapeutic options for all stages of CTCL."

Marketing Rights

Ligand discovered and developed Targretin gel and has the worldwide rights to the product. Ligand will market and sell Targretin gel in the U.S. and, pending additional approvals, in Canada and selected European markets through its specialty oncology sales and marketing group. If approved in the respective jurisdictions, Targretin gel and other oncology products will be marketed and distributed by Alfa Wassermann in Italy and by Ferrer Internacional, S.A. in Spain, Portugal, Greece, and Central and South America. Ligand expects to add marketing and distribution partners for select European and Asian markets.

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 typically 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.

Targretin Gel, Targretin Capsules, and ONTAK: A Comprehensive Portfolio for Early- to Late-Stage CTCL

With the approval of Targretin gel, Ligand now provides clinicians and patients with a comprehensive portfolio of rigorously studied, effective treatments for the management of CTCL. Ligand can now offer topical (Targretin gel), oral (Targretin capsules), and injectable (ONTAK) treatment options for appropriate patients suffering from CTCL. These three products are the first new agents approved for use in patients with CTCL in the last ten years.

The FDA granted marketing approval in December 1999 for Targretin capsules in the treatment of cutaneous manifestations of early- and advanced-stage CTCL in patients who were refractory to at least one prior systemic therapy. A Marketing Authorization Application (MAA) was submitted in November 1999 to the European Agency for the Evaluation of Medicinal Products (EMEA) for Targretin capsules in the treatment of patients with all clinical stages of CTCL (IA-IVB) in the following categories: patients with early stage CTCL who have not tolerated other therapies, patients with refractory (including resistant) or persistent early stage CTCL, and patients with refractory advanced stage CTCL. Ligand is targeting submission of an MAA with the EMEA for Targretin gel during 2000.

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.

ONTAK was approved by the FDA in February 1999 for the treatment of patients with persistent or recurrent CTCL whose malignant cells express the CD25 component of the IL-2 receptor. ONTAK is the first in a new class of targeted cytotoxic biologics called fusion proteins.

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 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; that Ligand will be able to successfully commercialize Targretin gel or any other product; or that Targretin capsules or any product in the Ligand pipeline will be successfully developed for psoriasis, breast cancer or any other indication; or that for Targretin gel or for any other Ligand product, regulatory filings will be made and regulatory approvals will be granted in a timely manner or at all. 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.

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