Cell Pathways Initiates Phase II Clinical Study of CP461 in Crohn's Disease.

Business Editors/Health & Medical Writers

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HORSHAM, Pa.--(BW HealthWire)--July 22, 2002

Cell Pathways, Inc. (Nasdaq:CLPA) today announced the initiation of a pilot Phase II study of its investigational drug CP461 as a potential treatment for Crohn's disease. The open-label, multi-center trial will enroll 30 patients with moderate to severely active Crohn's disease (Crohn's Disease Activity Index (CDAI) of greater than 220 but less than 400) under the direction of principal investigator Stephen B. Hanauer, M.D. of the University of Chicago Medical Center.

Patients participating in the study will receive 200 mg of oral CP461 twice daily for eight weeks. The primary endpoint of the study will be the efficacy of CP461 in inducing a clinical response, defined as a reduction in the patient's CDAI of 70 points or more. The ability of CP461 to induce a clinical remission, defined as attaining a CDAI level of less than 150, will be a secondary endpoint for the study. Patients will be monitored over time for safety and assessed for clinical response at weeks four and eight. The investigators will also assess the patients' quality of life using a standard inflammatory bowel disease questionnaire.

"Crohn's disease is a chronic inflammatory condition of the bowel for which current treatments are limited in their effectiveness and/or marked by significant toxicities," said Rifat Pamukcu, M.D., chief scientific officer of Cell Pathways, Inc. "Based on positive preclinical results for CP461 in dogs with an inflammatory bowel disease (IBD) similar to Crohn's disease in humans, we are pleased to initiate this study in a disease where improved therapies are greatly needed." He noted that this clinical study also marked the expansion of clinical investigations with CP461 outside of the field of cancer, to the treatment of certain inflammatory diseases.

Preclinical Results with CP461 in Inflammatory Bowel Disease

As reported at the American Gastroenterology Association (AGA) meeting in May 2002, seven dogs with a history of chronic and refractory IBD that had failed to respond to conventional therapies received treatment with CP461. The clinical signs of IBD started to resolve in all animals by day 10 of treatment, and 86% of the dogs were free of disease symptoms by day 30. There was a recurrence of symptomatic disease following cessation of treatment. Subsequently, four of the dogs were retreated, with three of those animals responding to therapy and remaining symptomatically normal throughout their treatment period.

CP461 Drug Target Demonstrated in Both Cancer and IBD

CP461 and Cell Pathways' other selective apoptotic antineoplastic drugs (SAANDs) inhibit cyclic GMP (cGMP) phosphodiesterases 2 and 5, resulting in the activation of protein kinase G and the triggering of downstream cellular pathways leading to apoptosis (programmed cell death). Cell Pathways scientists and collaborators have previously demonstrated high levels of these SAANDs targets in a wide variety of cancerous cell types, but not normal cells. At AGA, Cell Pathways reported that intestinal biopsies from the dogs and individuals with confirmed IBD contained activated macrophages in the intestinal tissue expressing high levels of PDE 2 and 5. Such macrophages are known to release tumor necrosis factor-alpha (TNF-alpha), an immune modulatory chemical that plays a central role in IBD. The researchers demonstrated the ability of CP461 to induce apoptosis and inhibit TNF-alpha in cell culture, further supporting the hypothesis that CP461 might provide a novel approach to the treatment of IBD.

About Crohn's disease

Crohn's disease is an inflammatory disease of the gastrointestinal tract, which can affect any part of that organ. According to the National Institute of Health, the incidence of Crohn's disease in the United States is 7 people per 100,000 and, overall, 300,000 to 500,000 people suffer from this condition. Crohn's disease is characterized by an abnormal immune response that causes uncontrolled inflammation, leading to abdominal cramping, diarrhea and other gastrointestinal symptoms. This disease is associated with excessive infiltration of inflammatory and immune cells that are resistant to apoptosis. These cells produce cytokines such as TNF-alpha that contribute to the chronic intestinal inflammation and tissue damage.

Current "first line" therapies for Crohn's disease include aminosalicylates and/or antibiotics. However, most patients have recurrent disease and require corticosteroid therapy or treatment with other immunomodulatory agents. These therapies have limited effectiveness and/or demonstrate toxicity. Recently, a monoclonal antibody that targets TNF-alpha was approved for treatment of moderate to severe Crohn's disease. However, patients treated with this therapy require frequent intravenous infusions that can be associated with hypersensitivity reactions or reactivation of tuberculosis.

About Cell Pathways

Cell Pathways, Inc., headquartered in Horsham, Pa., is a development stage pharmaceutical company focused on the research and development of novel and unique medications to treat and prevent cancer and to treat certain inflammatory diseases. The company additionally markets and sells oncology-related products manufactured by others. The company's initial drug candidates in clinical development are Aptosyn(R) (exisulind) and CP461. For additional information on Cell Pathways, Inc., visit the Company's web site at http://www.cellpathways.com.

Certain statements 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. Statements of historic fact must also be understood in the context of, and subject to, these risks. Such risks and uncertainties relate to, among other factors: early stage of development; absence of approved products; the costs, delays and uncertainties inherent in scientific research, basic pharmaceutical research, drug development, clinical trials and the regulatory approval process, with respect to both our current product candidates and our future product candidates, if any; history of operating losses and the need for further financing; dependence on the development, regulatory approval and market acceptance of one or more of our product candidates for one or more significant disease indications; the risk that CP461 will not exhibit safety and efficacy in Crohn's disease or any other inflammatory disease indication; the risks that accrual of our Phase III trial of Aptosyn(R) and Taxotere(R) is not completed by year-end and that safety and efficacy are not demonstrated by this combination therapy in this trial; 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; uncertainty that additional studies, if any, may not be positive; uncertainty of obtaining regulatory approval of any compound for any disease indication whether due to adequacy of the development program, changing regulatory requirements or otherwise; the risk that the Company does not conduct the clinical studies it may have planned to conduct or does not pursue development plans it may have planned to pursue; the risk that the U.S. Food and Drug Administration may stop or delay any clinical study for reasons of safety or otherwise; the risk that a registration strategy for CP461 in cancer is not fully developed by year-end, whether due to the nature or timing of further clinical results or otherwise; the risk that clinical studies do not result in the safety and efficacy necessary to obtain regulatory approvals; the risks of conducting clinical trials, including the risk of conducting clinical trials of our drugs in combination with other drug therapies; the commercial risk and risk of liability in marketing and selling Gelclair(TM) Concentrated Oral Gel, including the risk that the prescribers do not prescribe the product and sales do not materialize, the risk that the Company does not achieve an arrangement for distribution of Gelclair(TM) into the dental market, the risk that the market opportunity available to Gelclair(TM) is smaller than estimated, due to inaccurate assumptions, competition or other factors, the risks associated with the product launch, manufacturing and marketing risks, and the risk that the Company's sales of Gelclair(TM) are less than the Company's minimum purchase obligations; the commercial risk and risk of liability in providing marketing services promoting Nilandron(R) (nilutamide) manufactured by Aventis Pharmaceuticals, Inc.; the risk that the Company may enter into, or may fail to enter into, licensing, partnership or collaborative arrangements or strategic alliances which accord to other companies rights with respect to one or more Company compounds, technologies or programs or in which the Company acquires rights and obligations; the volatility of the market price of our Common Stock; our ability to sell securities registered under the shelf registration statement or otherwise; the risk of dilution through further financings or strategic alliances; acceptance of any product candidates by physicians and providers of healthcare reimbursement; the actions of competitors; the pace of technological changes in the biopharmaceutical industry; dependence upon third parties; the validity, scope and enforceability of patents; the risk of pending or future class action securities litigation; potential product liability claims; and availability and adequacy of insurance. 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