Conventional treatment of patients with premalignant lesions ofteninvolves surgery, the use of non-steroidal anti-inflammatory drugs ora wait-and-see approach, which translates into no treatment at all.

Cell Pathways Inc., of West Conshohocken, Pa., is developingtherapeutics, that, according to President Robert Towarnicki, havethe potential to arrest or reverse carcinogenesis by selectivelyaugmenting the rate of apoptosis in premalignant cells.

"We have identified previously unidentified pathways of apoptosis,"said Towarnicki, "but we can't disclose them until the patents arefiled."

New on board at Cell Pathways, Towarnicki was previously founder,president and CEO of MediRel Inc., a drug delivery firm.

Towarnicki said the company is conducting Phase II trials with itsfirst investigational drug, FGN-1, in patients with adenomatouspolyposis coli (APC). Victims of APC inherit the condition; theygrow large numbers of precancerous colonic polyps and face a highrisk of developing colon cancer.

FGN-1, Towarnicki said, restores normal growth patterns topremalignant lesions by increasing the rate of apoptosis, withoutaffecting the rate of cell proliferation. In doing so, FGN-1 restoresthe normal balance of cell growth and death.

Research by Cell Pathways has demonstrated the ability of FGN-1 toaugment apoptosis and inhibit the growth of colon and breast tumorsin both humans and rats, Towarnicki told BioWorld Today.

Gary Piazza, director of cell biology at Cell Pathways, said thesulfide metabolite of sulindac and FGN-1 appears to induce apoptosisin tumor cells by a mechanism separate and fundamentally differentfrom the cell cycle pathways targeted by conventionalchemotherapeutic drugs.

Most apoptosis research has focused on p53 and other cell cyclegenes that monitor cells for DNA damage. When damage to cellularDNA is beyond repair, these genes trigger the cell's death byapoptosis, thus helping to prevent cancer.

Conventional chemotherapy and radiation treat cancer by damagingDNA and halting the cell cycle. By disrupting DNA synthesis, thesetreatments kill both tumor cells and rapidly proliferating normal cells,which leads to a variety of toxic side effects.

Piazza said the sulindac sulfide and FGN-1 increased apoptosis in aHT-29 colon tumor cell line without altering the cells' expression ofp53. This treatment would be particularly attractive for the treatmentand prevention of premalignant lesions where the patient is at highrisk of developing cancer, but is otherwise healthy.

"Phase II is ending successfully," said Towarnicki, "and we haveidentified the dosage regimen. The FDA has granted us an orphandrug status and we hope move to Phase III in 1997 andcommercialize in 1999."

With a burn rate of approximately $400,000 a month, the companyanticipates moving to $800,000 a month in 1997 with the initiation ofPhase III trials.

"We are currently in the process of seeking financing," saidTowarnicki, who listed Northwood Ventures, Technology Partners,Quest Ventures, Jackson Partners and Vulcan Northwest among thecompany's current venture capital investors. To date, Cell Pathwayshas raised a total of $14.5 million, from the venture capital investorsand private investors, including the company's founders.

"We hope to raise another $10 million and would like to position thecompany for public offering in 1997 or 1998," Towarnicki said.

"We currently have no corporate alliances, but are in discussion withseveral major pharmaceutical firms," he added. "We anticipate alicensing with one of these companies some time next year."

Longer term, said Towarnicki, Cell Pathways expects to developFGN-1 and related compounds for the treatment of a variety ofprecancerous conditions. Preclinical studies suggest that FGN-1offers a safety profile that is suitable for long-term, chronic use.

"We plan to extend clinical investigations of FGN-1 beyond APC tothe treatment of sporadic colon polyps, precancerous breast lesionsand cervical dysplasia," he said. n

-- Frances Bishopp

(c) 1997 American Health Consultants. All rights reserved.

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