Cyclacel Provides Clinical Development Update On CYC202 CDK Inhibitor

DUNDEE - 15 October 2001 - Cyclacel Limited, the UK-based cancer therapeutics company, announced today that CYC202, its lead CDK inhibitor drug candidate, has completed Phase Ia evaluation in man and is entering multicentre Phase Ib clinical trials. Details of the preclinical and clinical results obtained with CYC202 will be reported on Tuesday 30 October 2001 by Cyclacel's Chief Scientific Officer, Professor Sir David Lane, at a keynote lecture to be delivered at the American Association for Cancer Research - National Cancer Institute - European Organization for Research and Treatment of Cancer joint conference in Miami, Florida.

CYC202 (R-roscovitine) is a small molecule inhibitor of Cyclin Dependent Kinase 2 (CDK2), an enzyme target of the body's own anticancer genes, such as the tumour suppressor p21. CYC202 has successfully completed a Phase Ia single dose pharmacokinetic study in patients with different types of cancer at the Royal Marsden Hospital (Sutton, UK) and has advanced to two Phase Ib studies being conducted at four hospitals in France and the UK.

Professor Lane will report in his lecture that CYC202 has met all primary objectives of the first Phase I study. The drug appears to be orally available in man and well tolerated after a single dose with biodistribution that is consistent with preclinical results. After describing the characteristics of CYC202, Professor Lane will explain that high specificity against CDK2 was a primary consideration for its selection from a large analogue set. CYC202 is the pure R optical isomer of roscovitine. Roscovitine is a mixture of R & S isomers used by academic researchers as a reference cell cycle inhibitor. Cyclacel results suggest that CYC202 is a more potent inhibitor of CDK2 than roscovitine.

The objectives of the Phase Ib studies are to determine the safety, maximum tolerated dose and pharmacokinetic profile of multiple and increasing doses of CYC202 capsules administered orally to cancer patients. Dependent upon successful completion of the Phase Ib clinical studies and if results from a large number of existing and ongoing preclinical studies are supportive, Cyclacel plans to move CYC202 to the next stage of development next year.

Athos Gianella-Borradori, MD, Cyclacel's Director of Medical Affairs, said "CYC202's rapid progress is testimony to Cyclacel's determination to bring this new anticancer drug to the clinic and explore its properties in patients suffering from cancer. Our evolving network of international clinical collaborators opens new development opportunities for CYC202 and our other drug candidates".

Professor Lane said, "Cyclacel was founded to exploit insights in the biology of the cell cycle and discover new classes of cancer therapeutics. CYC202 is the first orally active CDK2 inhibitor to be tested in clinical trials and we look forward to interpreting the data from the studies now in progress. This is clearly an important time for the cell cycle field. I am delighted that the citation of the 2001 Nobel Prize in Medicine pays tribute to the importance of CDKs and cyclins and their role in checkpoint control of cancer cells. The award underlines the significance of this area of scientific enquiry in the war against cancer."

Spiro Rombotis, Cyclacel's Chief Executive, said: "Completion of CYC202 Phase Ia clinical trials is an important milestone for our young company. Although it is still early in the programme to speculate on efficacy, results so far suggest that pharmacological inhibition of cell cycle targets, such as CDK2, may be a promising new approach in cancer treatment. This is encouraging as Cyclacel makes progress in building a competitive pipeline in the cell cycle area with additional drug candidates from our CYC400 CDK inhibitor, CYC103 Cyclin Groove Inhibitor and CYC102 PCNA Inhibitor programmes."