Investigators Present Results of New Lung Cancer Research

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with Ligand Therapies at ASCO

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SAN DIEGO--(BUSINESS WIRE)--May 17, 2005--Results of new research into treatments for advanced non-small cell lung cancer (NSCLC) using products from Ligand Pharmaceuticals Incorporated (Nasdaq:LGNDE) are being presented today at the annual meeting of the American Society of Clinical Oncology (ASCO) in Orlando.

Lung cancer posters presented today include:

-- a Phase II trial of Targretin® (bexarotene) capsules in patients with advanced NSCLC who have failed two or more prior systemic therapies,

-- a Phase I trial of Tarceva® (erlotinib) and Targretin as a targeted combination therapy for advanced aerodigestive tract cancers including NSCLC and head and neck cancer, and

-- a Phase II trial of ONTAK® (denileukin diftitox) in previously treated patients with advanced NSCLC.

Phase II multi-center trial of Targretin monotherapy in refractory patients shows correlation between Targretin-induced hypertriglyceridemia and survival

A poster presentation by lead author R. Govindan of Washington University Medical Center in St. Louis covers interim data on a Phase II trial of single-agent Targretin in patients with relapsed/refractory advanced NSCLC (average prior treatments: 3; range: 2 - 7). This is the first study to evaluate Targretin monotherapy in this patient population. The study completed accrual with 153 patients enrolled at 36 sites of which 146 received Targretin treatment. In the interim analysis of data covering the 146 patients, overall median survival was five months and overall one-year survival was 15 percent. The data was also analyzed to evaluate the survival of patients based on the triglyceride response to Targretin treatment, in view of the results reported earlier (May 14th) at this meeting that showed an improved survival in patients who showed high grade triglyceridemia after Targretin administration. With this subanalysis, two populations of patients were identified. Those with high triglyceridemia (grade 1 - 4) had a median survival of seven months (p less than 0.0001) and a projected one-year survival of 23%, compared with those with no hypertriglyceridemia who had a median survival of two months and a projected one-year survival of 5%.

"It's exciting that the data from this study provides new information for Targretin monotherapy on third-line patients and also adds additional support to the subgroup analysis that came out of our SPIRIT trials about a triglyceride biomarker that identifies patients with the potential to benefit from Targretin therapy," said Andres Negro-Vilar, M.D. Ph.D., Ligand's executive vice president for research and development and chief scientific officer. "This is important information that will factor into our evolving plans for further studies, whether conducted on our own, with a partner or with a cooperative group."

Targretin and Tarceva combination therapy

K. H. Dragnev of Norris Cotton Cancer Center and Dartmouth-Hitchcock Medical Center, Lebanon, NH, is the lead author of a poster on a Phase I trial of Tarceva (erlotinib) and Targretin (bexarotene) as a targeted combination therapy for advanced aerodigestive tract cancers. Twenty patients with advanced aerodigestive tract cancers (including a majority with NSCLC and some head and neck cancer) who had failed prior chemotherapy were enrolled in the study.

A median survival of 14.1 months was observed both for the NSCLC cohort and for the entire population when including all tumors. Four responses were seen and eight patients had stable disease. Interestingly, all responders were males and two, which were evaluated for EGFR mutations, were found to lack the mutation that sensitizes the patients to tyrosine kinase inhibitors. The authors conclude that the combination of erlotinib and bexarotene is well tolerated and appears active for the treatment of aerodigestive cancers and add that the addition of bexarotene appears to modulate and broaden the range of activity of erlotinib.

The study was based on preclinical data which was previously presented (Abstract #2279 ASCO, 2004) showing either additivity or synergy between bexarotene (Targretin) and EGFR tyrosine kinase inhibitors to down regulate the expression of EGFR, HER-2 and TGF-alpha and to better suppress NSCLC tumor growth.

ONTAK shows NSCLC activity

Another poster, by lead author M. Gerena-Lewis of the University of Cincinnati, reports on a Phase II, multi-center trial of ONTAK (denileukin diftitox) which enrolled 40 patients with advanced NSCLC whose disease had progressed after at least one prior chemotherapy regimen. The study revealed disease control (partial response and stable disease) in 40 percent of the patients. Response or stable disease was associated with an increase in some subtypes of lymphocytes, suggesting an effect of ONTAK via the immune system. The investigators concluded that ONTAK has interesting activity in the management of previously-treated advanced NSCLC.

Additional Presentations

Other posters being presented today include a multi-center Phase II study of ONTAK in patients with fludarabine-refractory B-cell chronic lymphocytic leukemia (CLL). In that study, by lead author M. Lilly of Loma Linda University of Loma Linda, CA, 16 patients were enrolled with 11 patients being evaluable for response. The authors conclude that ONTAK has moderate activity in CLL with toxicities that can be managed with adequate premedication and close monitoring.

A proof-of-principle trial of Targretin in patients with resectable NSCLC by lead author J. R. Rigas examines Targretin's mechanism of action. In patients receiving Targretin prior to surgery, the data provides important correlation between bexarotene, blood and tissue levels and biomarkers of activity (cyclin D1 and triglycerides).

In addition to the posters presented today and the oral presentations given on Saturday, six other abstracts on Targretin and ONTAK research were accepted for publication in the meeting proceedings.

About Targretin

In December 1999, the FDA approved Targretin capsules for the treatment of cutaneous manifestations of cutaneous t-cell lymphoma in patients who are refractory to at least one prior systemic therapy. The European Commission granted marketing authorization for Targretin capsules in March 2001, and the product is currently marketed in many major European countries, including Germany, the United Kingdom, France, and Italy.

About ONTAK

In February 1999, the U.S. Food and Drug Administration granted Seragen, Inc., a wholly owned subsidiary of Ligand, marketing approval for ONTAK for the treatment of patients with persistent or recurrent cutaneous T-cell lymphoma (CTCL) whose malignant cells express the p55 (CD25) component of the IL2 receptor.

About Ligand

Ligand discovers, develops and markets new drugs that address critical unmet medical needs of patients in the areas of cancer, pain, skin diseases, men's and women's hormone-related diseases, 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. For more information, go to www.ligand.com.

Caution Regarding Forward-Looking Statements

This news release contains forward-looking statements within the meaning of section 21E of the Securities Exchange Act of 1934, as amended, that involve risks and uncertainties and reflect Ligand's judgment as of the date of this release. These include statements regarding data analysis and evaluation of Targretin and ONTAK, potential benefits to patients and plans, continued development and other studies of Targretin and ONTAK. Actual events or results may differ from our expectations. For example, there can be no assurance that other studies or evaluations of Targretin or ONTAK will be favorable or that they will confirm results of previous trials, that data evaluation will be completed or demonstrate any hypothesis or endpoint, that Targretin or ONTAK will provide additional benefits to patients, that any presentations will be favorably received, that either drug will be useful in new indications alone or in combination with other drugs, that marketing applications will be filed or, if filed, approved, nor that further clinical or commercial development of these drugs will be completed or successful. Our stock price may suffer as result of the failure of these trials to meet their endpoints or if any actual events differ from our expectations. Additional information concerning these and other risk factors affecting Ligand can be found in prior press releases as well as in public periodic filings with the Securities and Exchange Commission, available via www.ligand.com. Ligand disclaims any intent or obligation to update these forward-looking statements beyond the date of this release.

Contacts

Ligand Pharmaceuticals Incorporated

Paul V. Maier, 858-550-7573

Abe Wischnia, 858-550-7850