BioWorld International Correspondent

LONDON - Cyclacel Ltd. said its lead compound, CYC202, the first oral cyclin dependent kinase inhibitor (CDK) designed to initiate apoptosis, entered Phase I trials.

The Phase I trial at the Royal Marsden Hospital in Sutton, Surrey, will evaluate safety and pharmacokinetics in patients with a range of cancers. If the three-month study is successful, another multicenter Phase I trial will take place later this year.

CEO Spiro Rombotis told BioWorld International, "We have not announced the number [of patients] in the Phase I trial because this is commercially sensitive information. The trial will measure the distribution of the drug and look at several different doses."

The second Phase I trial involving dozens of patients will measure dose response and look for early evidence of effect on some biochemical markers. "There may also be some early hints as to efficacy," Rombotis said.

CDK inhibitors act on the same CDK enzyme targets as the body's own tumor suppressor genes such as p53 and p21. The genes stop cancer cells at cell cycle checkpoints, causing them to commit suicide. There are several CDK enzymes, and CYC202, a small molecule, inhibits CDK2. Rombotis said the evidence is that CDK2 inhibition is the essential target for initiating programmed cell death, or apoptosis. The pharmaceutical company Aventis SA has an inhibitor of CDK4 in Phase II clinical trials, but it is administered intravenously.

Rombotis said the start of the trials was an important milestone because the company has met its goal of getting to the clinic within three years.

Cyclacel's second CDK inhibitor, CYC400, will be in clinical trials by early 2002, and several other programs will follow close after.

Cyclacel, based in Dundee, Scotland, was founded in 1996 by David Lane, who discovered the p53 tumor suppressor gene. The company has raised £13 million (US$18.8 million) to date, and is currently in the middle of a private placement.