Targretin Capsules in Combination Therapy May Prolong Survival in Patients with Non-Small Cell Lung Cancer; Data from Phase I-II Trials Published in The Journal of Clinical Oncology.

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SAN DIEGO--(BW HealthWire)--May 15, 2001

Ligand Pharmaceuticals Incorporated (Nasdaq: LGND) announced today the publication of results of Phase I-II clinical studies suggesting that Targretin(R) (bexarotene) capsules administered front-line in combination with chemotherapy may prolong survival in patients with non-small cell lung cancer (NSCLC). These results were presented in a poster session at the annual meeting in San Francisco of the American Society of Clinical Oncology, and published in the May 15, 2001, issue of The Journal of Clinical Oncology.

In the Phase I-II trial, Targretin was administered front-line in combination with cisplatin-based chemotherapy to 43 patients with Stage IIIb pleural effusion and Stage IV NSCLC. In Phase I, Targretin dosage was escalated in cohorts of three to six patients from 150 mg/m2/day through 600 mg/m2/day, starting one week prior to introduction of chemotherapy. Phase II was initiated when the optimal dosage was determined to be 400 mg/m2/day. Eight of 43 patients in the Phase I-II trial had major responses, with 7 of 28 responses occurring at 400 mg/m2/day. At this dose, median survival was 14 months, with 7 of 28 patients still alive after 28 months of monitoring. One-year survival was 61 percent, two-year survival was 28 percent. In contrast, results from a recently reported large-scale, randomized Eastern Cooperative Oncology Group study (ECOG 1594) indicate the median survival of late-stage NSCLC patients treated with any one of four leading combination chemotherapy regimens with two agents is approximately eight months, and only approximately one-third of these patients survive one year.

Adverse events included asthenia, nausea, hyperlipemia, vomiting, headache, exfoliative dermatitis, and anorexia.

"We believe our one-, two- and projected three-year survival are among the best reported in the literature," said Fadlo R. Khuri, M.D., Assistant Professor of Medicine, Assistant Internist, and Director of Educational Programs, Department of Thoracic Head and Neck Medical Oncology at the University of Texas M.D. Anderson Cancer Center, and lead investigator. "While this is a Phase II trial with a limited number of patients, these survival data are clinically important and exciting."

The poster, entitled "Phase I-II Trial of Bexarotene (Targretin(R)) with Chemotherapy for Chemo-Naive Patients with Advanced Non-Small Cell Lung Cancer," was presented today by Dr. Khuri. Other authors include Drs. Rigas (Dartmouth Hitchcock Medical Center), Figlin (UCLA Jonsson Comprehensive Cancer Center), Gralla (Ochsner Clinic), Reich (Ligand Pharmaceuticals Inc.), and Hong (MD Anderson Cancer Center).

Targretin Capsules NSCLC Registration Program

Ligand plans to conduct two randomized Phase III trials of approximately 600 patients each. The positive efficacy results of this Phase I-II trial and the manageable toxicity profile of the combination therapy allow Ligand to proceed directly to a Phase III trial to evaluate the benefits of adding Targretin capsules at 400 mg/m2/day to a chemotherapy regimen of cisplatin and vinorelbine in direct comparison to the chemotherapeutic regimen alone. Ligand expects to begin accruing patients during the second quarter 2001. The second trial of similar design will study Targretin capsules in combination with carboplatin and paclitaxel and is expected to commence by year end.

Non-Small Cell Lung Cancer

Lung cancer is the leading cause of cancer death for both men and women. The American Cancer Society estimates that 164,100 Americans will be diagnosed with lung cancer in 2001; of those, 131,200, or approximately 80 percent, will be diagnosed with NSCLC. Early-stage NSCLC is usually treated with surgery or radiation, sometimes combined with chemotherapy. Late-stage NSCLC is usually treated with radiation and/or combination chemotherapy regimens.

Targretin Capsules

Targretin capsules received U.S. Food and Drug Administration (FDA) approval in December 1999 for the treatment of cutaneous manifestations of cutaneous T-cell lymphoma (CTCL) in patients who are refractory to at least one prior systemic therapy. The European Commission granted marketing authorization for Targretin capsules in April 2001. In the U.S., Ligand currently markets its approved products, Targretin capsules, Targretin gel, ONTAK(R) and Panretin(R) gel, through its specialty oncology and dermatology sales forces. In Europe, Ligand has marketing and distribution agreements with Ferrer Internacional SA, Alfa Wassermann, S.p.A, and Elan Pharma International, Ltd.

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 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 which involve risks and uncertainties and reflect Ligand's judgement as of the date of this release. Actual events or results may differ from Ligand's expectations. There can be no assurance that results of subsequent clinical studies of Targretin or any other therapy for NSCLC will confirm early-stage clinical results; that final results will be supportive of regulatory approvals required to market products; that regulatory filings will be made in a timely manner, or that upon submission they will be accepted for filing; that regulatory approvals, including labeling approvals, will be granted in a timely manner, or at all, and that patient and physician acceptance of these products will be achieved. Additional information concerning these and other risk 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: 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 Ligand's products may be obtained in the U.S. from Ligand Professional Services by calling toll free 800-964-5836 or on Ligand's web site at http://www.ligand.com.

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