TRAGEN PHARMACEUTICALS BEGINS PHASE II CLINICAL TRIAL OF ITS LEAD PRODUCT (ISF154) FOR TREATMENT OF CHRONIC LYMPHOCYTIC LEUKEMIA

TRAGEN PHARMACEUTICALS BEGINS PHASE II CLINICAL TRIAL OF ITS LEAD PRODUCT (ISF154) FOR TREATMENT OF CHRONIC LYMPHOCYTIC LEUKEMIA

Contact:    Charles E. Prussak, Ph.D.            
   President and CEO, Tragen Pharmaceuticals            
858 623-2754 x 228 cprussak@tragenpharm.com                     

Media:   Linda Seaton/Navjot Rai, Mentus, Inc.   
858 455-5500 ext. 133/ext. 106   
lcs@mentusonline.com/
nrai@mentusonline.com   

TRAGEN PHARMACEUTICALS BEGINS PHASE II CLINICAL TRIAL OF ITS LEAD PRODUCT (ISF154) FOR TREATMENT OF CHRONIC LYMPHOCYTIC LEUKEMIA

Chronic Lymphocytic Leukemia is the Most Common Form of Leukemia in the Western Hemisphere

SAN DIEGO, CA -- April 30th, 2002- Tragen Pharmaceuticals, a biopharmaceutical company focused on activating cancer-specific immune responses, today announced the initiation of a Phase II clinical trial to further investigate its lead product, ISF154, in the treatment of patients with Chronic Lymphocytic Leukemia (CLL). ISF154 is designed to activate dormant leukemia B-cells and rally T-cells to selectively attack blood- and tissue-based leukemia cells, according to Charles Prussak, Ph.D., President and CEO of Tragen Pharmaceuticals.

In the single-dose Phase I clinical trial, ISF154 showed its potential as a first-line therapy or as a therapeutic agent that augments the efficacy and safety of therapeutics currently used in the treatment of CLL," Dr. Prussak said. The Phase II clinical trial will evaluate the efficacy of ISF154 as a mono-therapy to eliminate leukemic cells in the blood and lymph nodes, while rebuilding the patients natural immune system. If response rates obtained in the Phase I trial are achieved in this Phase II trial, it will be directly rolled into an expanded pivotal registration trial."

A multi-center clinical trial will be conducted at the University of California, San Diego and by researchers affiliated with Dana Farber/Partners CancerCare, a collaboration of Dana-Farber Cancer Institute, Brigham and Women's Hospital and Massachusetts General Hospital in Boston. Investigators will administer ISF154 as a mono-therapy to 40 patients in two treatment cohorts. In the first cohort, 20 patients who have failed chemotherapy will receive up to 10 doses of ISF154 over a 20-week period. In the second cohort, 20 patients with advanced disease who have declined chemotherapy will receive up to 10 doses of ISF154 as front-line therapy.

ISF154 is based on technology developed at UCSD in the laboratory of Thomas Kipps, M.D., Ph.D., professor of medicine and deputy director for research of the Rebecca and John Moores UCSD Cancer Center.

CLL is a chronic disease in which B-lymphocytes, immune cells in the body, accumulate because they do not undergo apoptosis -- programmed cell death. The increase in abnormally functioning B-lymphocytes is associated with a number of clinical features, including an enlarged liver, spleen and lymph nodes, and abnormalities in the immune system. B-cells normally make proteins such as antibodies. In patients with CLL there is a defect in the function of the normal immune system, which renders the patient susceptible to infections and other immune system-related disorders.

Currently, the cause of CLL is unknown. Many cases are detected by routine blood tests in people with no symptoms. An increased incidence of CLL has been noted in people with certain autoimmune diseases. The incidence increases with age, to 15 people out of 100,000 by 70 years of age.

TRAGENS PRODUCT PIPELINE
ISF154
Tragens lead product, ISF154, is a novel and clinically active immune-based therapy targeting leukemias and lymphomas. In a Phase I clinical trial in patients with chronic lymphocytic leukemia (CLL), a single injection of ISF154 treatment caused rapid destruction of leukemia cells in the blood and lymph nodes of treated patients. ISF154 destroyed the malignant leukemic cells by inducing them to awaken from their inactive state. Upon awakening, these activated leukemic cells functioned like a vaccine to induce an immune response against the leukemia cells. In addition, the activated leukemia cells underwent apoptosis, or programmed-cell death. To expand upon the Phase I results, Tragen has initiated an ISF154 multi-dose Phase II clinical trial in patients with CLL.

ISF154 and Monoclonal Antibody Therapy
The malignant B-cells in CLL express specific B-cell proteins, such as CD20, which can be targeted by monoclonal antibodies. Pre-clinical studies suggest that combination therapy with ISF154 and monoclonal antibodies may prove to be highly effective in treating patients with this disease. Tragen will initiate a Phase I clinical safety trial combining ISF154 with a monoclonal antibody by the 4th quarter of 2002. By combining these complementary biologic therapies, Tragen is seeking to develop a synergistic attack against the leukemic cells, while avoiding the toxicities associated with standard chemotherapies.

Other Hematologic Malignancies
In addition to CLL, ISF154 has potent activities in vitro against other B-cell malignancies, such as non-Hodgkins lymphoma, multiple myeloma, and acute lymphocytic leukemia. ISF154 treatment triggers cellular events in the malignant cells of these diseases that are similar to those seen in CLL. As a result, Tragen expects these leukemias and lymphomas to be susceptible in vivo to ISF154 treatment. Clinical trials against these malignancies are planned for the later part of 2002.

In addition to ISF154, Tragen has also rebuilt members of the TNF family to increase their antineoplastic activity while eliminating the toxicity of these potent molecules. Tragen is currently entering these compounds into clinical trials as directly injectable immunotherapeutics for solid tumors.

Tragen is a biopharmaceutical company focused on activating the power of the immune system to combat certain cancers. Its novel therapeutic platform of stabilized TNF-based compounds is designed to activate dormant B-cells and rally T-cells to selectively attack blood- and tissue-based cancers. In Phase I clinical trials, the Companys first drug candidate, ISF154, for the treatment of chronic lymphocytic leukemia (CLL), caused the rapid destruction of leukemic cells and a significant reduction in circulating and lymph node-bound leukemic cells. Tragen is seeking corporate partners for the development of its novel compounds to treat other cancers and certain autoimmune diseases. Tragen is located in San Diego, CA. More information can be found at www.tragenpharm.com