Cell Pathways' Second-generation Compound, CP461, Induces Apoptosis in Leukemic Cells Isolated From Patients With CLL.

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HORSHAM, Pa.--(BUSINESS WIRE)--Dec. 10, 2001

Compound Subject of Ongoing Phase IIa Clinical Study

Laboratory research, reported today at the American Society for Hematology (ASH) meeting in Orlando, showed CP461 selectively triggered programmed cell death, or apoptosis, in primary leukemic cell samples from patients with chronic lymphocytic leukemia (CLL). At the same time, the drug had marginal pro-apoptotic effect on normal peripheral blood white cells. These data are supportive of the potential of Cell Pathways, Inc. (Nasdaq:CLPA) second-generation selective apoptotic antineoplastic drug (SAAND) as a treatment for CLL. Cell Pathways' collaborators Adam Lerner, M.D. and Eunyi Moon, Ph.D. of Boston University's Boston Medical Center published the research.

In work done in other cell systems, CP461 and other SAAND compounds have been shown to selectively trigger cell death by apoptosis in abnormally growing cancerous and precancerous cells but not in normal cells by inhibiting certain cyclic GMP phosphodiesterase enzymes (cGMP PDEs). Cell Pathways has shown over-expression of these cGMP PDEs in a wide variety of tumor types.

"Treatment with 30 micromolar CP461 induced greater than 50% apoptosis within 24 hours in 10 of 10 primary leukemic cell samples taken from patients with CLL, while the same drug concentration induced only a marginal 14% apoptosis in normal peripheral blood white cells," said Dr. Lerner. "Researchers have made considerable study in the past of the role of cyclic AMP in leukemic white blood cells. This new study suggests that cyclic GMP pathways may also be involved and merit further study."

"These preclinical results, among others, prompted us to initiate the ongoing Phase IIa clinical study of CP461 in patients with previously untreated CLL," remarked Rifat Pamukcu, M.D., chief scientific officer of Cell Pathways, Inc. "The preliminary data from the first 15 patients in that trial, reported on October 9th, revealed reductions of up to 48% from baseline in the absolute lymphocyte counts in some of the patients receiving a 400 mg daily dose of CP461 within two to six weeks of treatment. More recently, we continue to be encouraged in that three of these patients have shown reductions of 50% to 80% in their absolute lymphocyte counts. Another patient has shown durability of a hematological response out to 22 weeks of therapy. In the interim, investigators have initiated testing a higher dose of CP461 in additional patients, to investigate any dose-response relationship of CP461 in the treatment of CLL."

In addition to the direct apoptotic effects of CP461 on the CLL patient isolates, the Boston researchers also observed that the drug blocked cell proliferation in a CLL cell line by inducing G2 arrest in the cycle of cell division. They also noted the disruption of cellular structures called microtubules in the treated leukemic cell line, as well as a change in cell shape.

About CLL

Chronic lymphocytic leukemia (CLL) is a form of cancer characterized by an accumulation of abnormal lymphocytes in the blood, bone marrow and lymph nodes. These lymphocytes function abnormally and interfere with the production of other blood cells, leading to such complications as infections, anemia, coagulation problems and other conditions. According to the CLL Foundation, approximately 7,300 new cases of CLL are diagnosed annually, mostly in people over age 50. CLL is a chronic disease that usually progresses slowly, over years, and for which there is presently no cure. In a subset of patients, the disease can suddenly progress more quickly and behave more aggressively. Early stages of CLL can lack significant symptoms, and treatment generally begins when symptoms of the disease become troublesome. Currently approved treatments, including chemotherapy and a monoclonal antibody-based therapy, may cause the disease to go into remission for periods of time and are associated with significant adverse side effects. Eventually, however, the disease becomes resistant to treatment and achieving subsequent remissions becomes more difficult.

About Cell Pathways' SAANDs

CP461 is the second of a new class of potential anticancer agents discovered and developed by Cell Pathways, called selective apoptotic antineoplastic drugs or SAANDs. SAANDs inhibit cyclic GMP phosphodiesterases (cGMP PDEs) that show unique patterns of expression in tumors, thus selectively inducing apoptosis (programmed cell death) in precancerous and cancerous cells. Preclinical and clinical research to date suggests drugs that target specific cGMP PDEs, as SAANDs do, have the potential to lead to the development of new therapeutics with broad-based activity. Cell Pathways is conducting clinical studies with Aptosyn(TM) (exisulind), its first-generation SAAND, in combination with conventional chemotherapeutic drugs in a variety of clinical indications.

Cell Pathways, Inc., headquartered in Horsham, Pa., is a development stage pharmaceutical company focused on the research, development and commercialization of novel and unique medications to prevent and treat cancer. For additional information on Cell Pathways, Inc., visit the company's web site at www.cellpathways.com.

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