Ligand's Targretin May Extend Survival in Lung Cancer Patients; Data Reported at the NCI-EORTC-AACR Meeting.

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SAN DIEGO--(BW HealthWire)--Nov. 8, 2000

Ligand Pharmaceuticals Incorporated (Nasdaq:LGND) today announced that, at the NCI-EORTC-AACR meeting in Amsterdam, Phase I/II clinical trial results were presented demonstrating that Targretin(R) (bexarotene) capsules, in conjunction with chemotherapy, may be an effective treatment for patients with non-small cell lung cancer (NSCLC). These results add to Phase II/III results recently reported by the Company and to a growing body of data that suggests Targretin therapy may delay disease progression and extend survival of patients with some forms of solid tumor cancer.

Researchers found that Targretin capsules plus chemotherapy yielded acceptable response rates, with better-than-expected survival in stage III/IV NSCLC patients.

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

"The results from this multi-center study are most notable in terms of the high survival rate, perhaps the best reported for Phase II trials of NSCLC, while the tumor response rate is comparable to results of other Phase II platinum-based combination trials," said Steven D. Reich, M.D., Ligand's Senior Vice President of Clinical Research. "In the trials of patients with NSCLC reporting two-year survival rates, few have reported two-year survival rates better than 15%. Our experience with Targretin capsules for actual two-year survival was 32%, and the projection for three-year survival is 30%. At the maximum tolerated dose of 400 milligram per meter squared of body surface area (mg/m2) per day, Targretin capsules showed substantial activity in combination with a third-generation NSCLC chemotherapy regimen with a tolerable safety profile."

"The body of evidence is now large enough to begin initiating large-scale Phase III clinical studies to conclusively demonstrate Targretin capsules' benefit in the treatment of patients with NSCLC," said Andres Negro-Vilar, M.D., Senior Vice President of Research and Development and Chief Scientific Officer at Ligand. "After discussions with the FDA, we anticipate launching the Phase III trials in the first half of 2001."

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 Incorporated), and Hong (M.D. Anderson Cancer Center).

Forty-three previously untreated patients with stage IIIb with pleural effusion and stage IV non-small cell lung cancer (Karnofsky Performance Status greater than or equal to 70) were treated in a Phase I/II trial of Targretin capsules in combination with an active chemotherapy regimen of cisplatin (100 mg/m2) along with vinorelbine (alternating doses of 30 mg/m2 and 15 mg/m2). In the Phase I portion of the trial, Targretin capsules dosage was escalated in cohorts of three to six patients from 150 mg/m2 through 600 mg/m2 daily, starting one week prior to cisplatin (P) and vinorelbine (V). Once the maximum tolerated dose (MTD) of Targretin capsules plus PV was determined to be 400 mg/m2 daily, the Phase II portion was initiated.

Response rate was the primary endpoint with median survival and one-year survival as secondary endpoints. Eight of 43 patients in the Phase I/II trial had major responses, with seven of 28 responses (25 percent) occurring in phase II. Median survival in the Phase II trial was 416 days (14 months), with 61 percent surviving one year by life-table analysis and nine of 28 patients (32 percent) surviving 24 or more months. Three-year survival based on Kaplan Meier analysis is projected at 30 percent. Adverse events included asthenia, nausea, hyperlipemia, vomiting, headache, exfoliative dermatitis, and anorexia. Hematologic toxicities were not greater than with PV alone. One death from renal insufficiency occurred during the Phase I trial. Toxicities in the Phase II portion of the trial were consistent with Targretin monotherapy and with what one would expect with combination chemotherapy with cisplatin and vinorelbine.

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 2000; of those, 131,200, or approximately 80 percent, will be diagnosed with NSCLC. The four stages of NSCLC are identified using the Tumor, Nodule, Metastasis (TNM) system, also known as the American Joint Committee of Cancer (AJCC) system. Early-stage NSCLC is usually treated by surgery or radiation, sometimes combined with chemotherapy. Late-stage NSCLC is usually treated with radiation and/or combination chemotherapy regimens.

Targretin(R) Capsules

In December 1999, the U.S. Food and Drug Administration (FDA) approved Targretin capsules for the treatment of all stages of cutaneous T-cell lymphoma (CTCL) refractory to at least one prior systemic therapy. The European Agency for the Evaluation of Medicinal Products (EMEA) is reviewing a Marketing Authorization Application (MAA) submitted by Ligand in November 1999 for Targretin capsules for the treatment of patients with CTCL.

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 judgment as of the date of this release. Actual events or results may differ from Ligand's expectations. There can be no assurance that results from large-scale clinical trials will be consistent with the results seen in these phase I/II trials or that final results will be supportive of regulatory approvals required to market Targretin for treatment of NSCLC. 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.

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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