BioWorld International Correspondent

LONDON - Cyclacel Ltd. has beaten its larger brethren to in-license CYC682, an orally available nucleoside analogue that has completed two U.S. Phase I trials, from Sankyo Co. Ltd., of Tokyo.

Spiro Rombotis, CEO, told BioWorld International: "The molecule was on open offer, so why select us? The three main reasons are our cancer cell-cycle expertise, our biomarker know-how and the potential synergy of CYC682 with our CDK [cyclin-dependent kinase] inhibitor, CYC202. I think they realized we had more reasons to do a good job than anyone else."

Dundee-based Cyclacel made an undisclosed up-front payment and will pay milestones and royalties. In return, it has exclusive worldwide rights, apart from Sankyo retaining a right of first negotiation to market the compound in Japan.

Rombotis said Cyclacel would begin a Phase I/II dose-ranging monotherapy study of CYC682 in 2004.

CYC202, its lead drug, acts mainly on the G1/S part of the cell cycle, inducing apoptosis in cancer cells, while CYC682 appears to act by delaying cell-cycle progression in the S phase and inducing arrest at the G2 phase. Rombotis said the potential therefore exists for CYC682/CYC202 combinations that would kill more cancer cells than either drug alone.

"We will complete the Phase II monotherapy trial [of CYC682] and then decide whether to go ahead with a combination trial," he said.

In-house preclinical data suggested a synergistic effect between CYC202 and gemcitabine, which is the leading marketed nucleoside analogue, and the combination is currently in a Phase IIa trial in non-small-cell lung cancer.

CYC682 could have advantages over gemcitabine, as it is orally available and has greater activity. Phase I data in 88 patients with a variety of cancers showed CYC682 is well tolerated, and stable disease was observed in 17 patients.