HORSHAM, PA (April 3, 2000) -- Exisulind (Aptosyn™) and other selective apoptotic antineoplastic drugs (SAANDs) inhibit the growth of prostate cancer cells in two ways, said researchers from Columbia University and their collaborators at Cell Pathways, Inc. (Nasdaq: CLPA). First, they directly kill cancerous prostate cells by inducing apoptosis. Secondly, they decrease expression of the androgen receptor in the cancerous prostate cells, making them less responsive to the growth-promoting effects of androgens in their environment. The Columbia University scientists and their Cell Pathways' collaborators presented their preclinical findings on Sunday April 2, 2000 at the annual meeting of the American Association for Cancer Research (AACR) in San Francisco.
The researchers also demonstrated in a prostate cancer cell line that exisulind (Aptosyn™) and two other SAANDs, CP461 and CP248, inhibited the cellular expression and secretion of prostate specific antigen (PSA) at the same concentrations that induced apoptosis in the cells.
Dr. Bernard Weinstein, the senior investigator of these studies and director of the Columbia University Comprehensive Cancer Center, emphasized that "because of their dual mechanism of action, these agents are also effective in prostate cancer cells that have become independent of androgens."
"These findings also support the usefulness of PSA assays for measuring the efficacy of SAANDs in clinical trials for prostate cancer therapy or chemoprevention, as they demonstrate that a reduction in PSA levels accurately reflects cell death and not merely a reduction in PSA production when these drugs are used," added Rifat Pamukcu, M.D., chief scientific officer and senior vice president of research at Cell Pathways, Inc.
"This laboratory research complements the findings of our clinical trial of exisulind (Aptosyn™) as a treatment for post-prostatectomy men at risk of prostate cancer recurrence," he continued. "That study showed the ability of exisulind (Aptosyn™) to significantly inhibit the rise in average PSA levels in treated patients compared to those on a placebo." Dr. Pamukcu noted that detailed results of the one-year prostate cancer trial would be presented on Monday May 1 at the annual meeting of the American Urological Association (AUA) in Atlanta.
Study Details
The reported research examined the ability of exisulind (Aptosyn™), CP461, CP248 and sulindac sulfide to inhibit growth and induce apoptosis in prostate cancer cell lines, irrespective of bcl-2 over-expression, androgen-dependence, or cyclooxygenase (COX) expression. The researchers showed that with doses that induced apoptosis, exisulind (Aptosyn™), CP248, and CP461 reduced cellular PSA expression and decreased the secretion of PSA from androgen-dependent LNCaP cells. At the same time, PSA levels of LNCaP cells treated with aspirin remained elevated. In addition, cells treated with exisulind (Aptosyn™) showed a decreased activity and expression of the androgen receptor.
Exisulind (Aptosyn™) is the first product candidate from a novel class of compounds under development by Cell Pathways, called selective apoptotic anti-neoplastic drugs (SAANDs). SAANDs inhibit cyclic GMP phosphodiesterase and selectively induce apoptosis (programmed cell death) in abnormally growing precancerous and cancerous cells. Because SAANDs do not induce apoptosis in normal cells, they do not produce the serious side effects normally associated with traditional chemotherapeutic agents. They also do not inhibit cyclooxygenase (COX I or COX II) and have not exhibited the gastric and renal toxicities reported to be associated with non-steroidal anti-inflammatory drugs (NSAIDs), including the COX II specific inhibitors. A New Drug Application for exisulind (Aptosyn™) as a treatment for patients with familial adenomatous polyposis, a precancerous condition that often leads to colon cancer, is currently under review by the U.S. Food and Drug Agency (FDA). The compound is also undergoing further clinical evaluation in a variety of additional precancer and cancer indications.
Cell Pathways, Inc., headquartered in Horsham, Pennsylvania, 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 website at http://www.cellpathways.com.
Certain statements made herein, and oral statements made in respect hereof, constitute "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995. Such statements are those which express plan, anticipation, intent, contingency or future development and/or otherwise are not statements of historical fact. These statements are subject to risks and uncertainties, known and unknown, which could cause actual results and developments to differ materially from those expressed or implied in such statements. Such risks and uncertainties relate to, among other factors, the absence of approved products; history of operating losses; early stage of development; the costs, delays and uncertainties inherent in basic pharmaceutical research, drug development, clinical trials and the regulatory approval process, with respect to both the Company's current product candidates and its future product candidates, if any; dependence on development of Aptosyn™ exisulind; the limitations on, or absence of, the predictive value of data obtained in laboratory tests, animal models and human clinical trials when planning additional steps in product development; the uncertainty of obtaining regulatory approval, including uncertainty of approval of the New Drug Application submitted for Aptosyn™ (exisulind) for familial adenomatous polyposis (a rare disease that puts those afflicted at high risk of developing colon cancer), whether in connection with the adequacy of the data generated in the clinical trials of Aptosyn™ (exisulind) or otherwise; the timing and scope of any approval which might be received for any compound for any indication in the future; acceptance by providers of healthcare reimbursement; the validity, scope and enforceability of patents; the actions of competitors; dependence upon third parties; product liability; and the need for further financing. These and other risks are detailed in the Company's reports filed from time to time under the Securities Act of 1933 and/or the Securities Exchange Act of 1934, including the sections entitled "Business," "Risk Factors," "Management's Discussion and Analysis of Financial Condition and Results of Operations" and "Other Events" in the Company's reports on Form 10-K for the year ended December 31, 1999, Form 10-Q for each of the first three quarters of 1999, Form 8-K in the month of August 1999, and Form S-3 filed in December 1999. Given these uncertainties, current and prospective investors are cautioned not to place undue reliance on any such forward-looking statements, any of which may turn out to be wrong due to inaccurate assumptions, unknown risks, uncertainties or other factors. The Company undertakes no obligation to update or revise the statements made herein or the factors which may relate thereto.