Ligand's ONTAK Shows Potential to Treat Chronic Lymphocytic Leukemia, Non-Hodgkin's Lymphoma, and Graft-Versus-Host Disease, Four Abstracts from ASH Meeting Demonstrate.

Business Editors/Health/Medical Writers

American Society of Hematology

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SAN DIEGO--(BUSINESS WIRE)--Dec. 8, 2003

Ligand's (Nasdaq: LGND) ONTAK(R) (denileukin diftitox) may benefit patients with chronic lymphocytic leukemia (CLL), B- and T-cell non-Hodgkin's lymphoma (NHL), and graft-versus-host disease (GVHD) which is steroid resistant or refractory after allogeneic hematopoietic stem cell transplantation, according to four abstracts presented or published at the 45th annual meeting of the American Society of Hematology, underway now in San Diego.

"The positive results observed in heavily pretreated patients with relapsed or refractory B- and T-cell lymphomas, and fludarabine-refractory chronic lymphocytic leukemia (CLL) support an expanding role for ONTAK(R) in the treatment of lymphomas and leukemias," said Andres Negro-Vilar, M.D., Ph.D., Ligand's executive vice president for research and development and chief scientific officer. "Coupled with the very promising studies reported at this meeting on steroid-resistant graft-versus-host-disease (GVHD) these clinical reports add to the growing body of evidence showing significant benefits for patients receiving ONTAK(R) across a spectrum of difficult to treat cancers or with serious compromise of the immune system."

ONTAK Benefits More Than Half of Patients with Relapsed or Refractory NHL

In ASH abstract 4935, scientists from the M.D. Anderson Cancer Center in Houston reported final results from their Phase II study of ONTAK in patients with relapsed or refractory B- and T-cell NHL, most of whom had undergone multiple prior treatments, including autologous stem cell transplants. Many of the patients had depressed bone marrow status.

"Our study showed that ONTAK does have activity in relapsed B- and T-cell lymphoma," said lead author Nam Dang, M.D., Ph.D., assistant professor of medicine at M.D. Anderson Cancer Center. "Perhaps the most important or striking result we observed was among those patients with suppressed bone marrow status, who tolerated treatment well and without further myelosupression."

Fifty-six patients have entered the study, 39 of whom were available for response evaluation. Four patients had a complete response, seven had partial responses, and ten had stable disease, indicating that ONTAK benefited 54% of evaluable study patients overall. For B-cell NHL, 45% of 29 patients responded; for T-cell NHL, 80% of the ten patients responded. ONTAK was well tolerated in the study, with the majority of side effects being mild to moderate and transient. Importantly, no hematological toxicity was observed.

Complete Resolution of GVHD Achieved By 32% of Study Patients; Overall Response Rate of 73%

In ASH abstract 850, researchers from Dana-Farber Cancer Institute, Brigham and Women's Hospital, Harvard Medical School, and Ligand reported results from their Phase II study of ONTAK in patients with steroid-refractory GVHD after allogeneic hematopoietic stem cell transplantation. Twenty-eight patients were treated with ONTAK for grade II, grade III or grade IV GVHD. They had received a mean of two prior treatments of immune suppressive agents, excluding steroids. Twenty-two patients were evaluable for GVHD response.

At day 29 of the study, seven of 22 evaluable patients (32%) treated with ONTAK had complete resolution of GVHD, and nine (41%) had a partial response, for an overall response rate of 73%. Of the nine patients showing a partial response, three additional patients showed a complete response after day 29, without additional GVHD therapy. Ten patients who failed to respond to daclizumab before starting ONTAK, achieved an overall response rate of 80% (1 complete, 7 partial).

ONTAK Active in Steroid-Resistant Acute GVHD

In ASH abstract 2646, physicians from the Texas Transplant Institute, University of Texas Health Science Center, Audie Murphy VA Hospital, and Oncology/Hematology Care (Cincinnati) reported treating 17 patients who had steroid-resistant acute GVHD. Initial response was observed in 15 patients (88%), and at day 36 of the study, 10 patients (59%) had responded; nine with complete response and one with partial response. At day 100, five of 15 evaluable patients (33%) had responded (4 with complete response, 1 with partial response). In a median follow-up of 84 days, 8 patients (47%) are alive. Prior to day 100, complete response was observed in two patients. ONTAK was well tolerated and demonstrated activity in treating steroid resistant aGVHD without an increase in relapse risk or unexpected infections.

ONTAK Demonstrates Significant Activity in Fludarabine-Refractory CLL

In ASH abstract 2493, scientists from Peter MacCallum Cancer Centre (Melbourne) reported results of a study in which seven CLL patients who were fludarabine-refractory were treated with ONTAK. All patients had been extensively pretreated and were considered profoundly chemotherapy- and corticosteroid-resistant. Five of the patients were evaluable for this report. Of the five, two had a partial response, two had minor response. One patient had an overall response that included greater than 30% reduction in nodal size. Six of the seven patients had significant and rapid reduction in peripheral lymphocytosis, including two who otherwise had no significant response.

Adverse effects of varying severity were observed in all patients, including vascular leak syndrome and abnormal liver function. All biochemical abnormalities resolved spontaneously and completely.

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 CTCL whose malignant cells express the p55 (CD25) component of the IL-2 receptor.

Full prescribing information for Ligand's products can be obtained in the United States from Ligand professional services by calling 800-964-5836, or on Ligand's internet site at www.ligand.com.

Full abstracts for the four ONTAK studies discussed in this news release are available on the ASH internet site at www.hematology.org.

About Ligand

Ligand Pharmaceuticals Incorporated discovers, develops and markets new drugs that address critical unmet medical needs of patients in the areas of cancer, 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 (IRs) and Signal Transducers and Activators of Transcription (STATs).

Caution Regarding Forward-Looking Statements

This news release may contain certain forward-looking statements by Ligand that 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 of subsequent studies of ONTAK, alone or in combination with any therapy, will confirm results presented here. 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 internet site at www.ligand.com. Ligand disclaims any intent or obligation to update these forward-looking statements beyond the date of this release. This caution is made under the safe harbor provisions of the Private Securities Litigation Reform Act of 1995.