Cyclacel Reports Interim CYC202 Phase I Data In Patients With Advanced Cancer

Clinical benefit observed in several Phase I patients with well-tolerated Cyclin Dependent Kinase inhibitor CYC202

Boston, Massachusetts - 20 November 2003 - Cyclacel Limited, the UK-based biopharmaceutical company, announced today interim results from a Phase I clinical trial of its experimental small molecule CDK inhibitor, CYC202, carried out by investigators at two French hospitals. Clinical benefit in terms of stable disease or tumour regression was reported in several patients with advanced tumours who previously failed several lines of chemotherapy. Separately, German researchers presented preclinical data on the use of CYC202 in combination with docetaxel. Further details will be reported this week in a scientific communication during the American Association for Cancer Research - National Cancer Institute - European Organization for Research and Treatment of Cancer (AACR-NCI-EORTC) joint conference taking place here.

Dr Athos Gianella-Borradori, Medical Director of Cyclacel said, “The results obtained in the Phase I trial in a group of patients with varied tumour types which had been unsuccessfully treated with standard chemotherapeutic agents are a promising baseline from which to extend our clinical trials with this compound. CYC202 did not cause toxicities associated with classical chemotherapy, such as myelosuppression. The investigators observed clinical benefit in nine patients who failed other treatments. In addition, the preclinical results showing synergy provide validation for our Phase II strategy of moving quickly into combination trials with selected chemotherapies.” CYC202 is currently undergoing Phase II clinical trials in combination with standard chemotherapy regimens in advanced breast and lung cancer patients.

The Phase I study carried out by investigators at Institut Gustave Roussy and Institut Curie in Paris, France was designed to identify dose limiting toxicities and maximum tolerated dose along with examining the pharmacokinetic properties of CYC202. The trial enrolled 49 patients who received treatment with CYC202 at various escalating doses as monotherapy after exhausting other treatment options. The patients received CYC202 capsules taken by mouth twice daily for 5 consecutive days every 3 weeks or for 3 consecutive days every 2 weeks.

The investigators reported that CYC202 was well tolerated at doses up to 2000 mg/day for 5 consecutive days every 3 weeks. The Maximum Tolerated Dose was reached at 3200 mg/day and Grade 3-4 vomiting was observed as Dose Limiting Toxicity. The investigators recommended a dose of 2500 mg/day for Phase II trials. In the alternative biweekly schedule the Maximum Tolerated Dose was reached at a dose of 3600 mg/day and Grade 3 hypokalemia and asthenia were observed as Dose Limiting Toxicities. A dose of 3200 mg/day was recommended for Phase II trials in this schedule while a 10-day and a fixed-dosing schedule were not tolerated.

Clinical benefit was observed in 9 of 49 patients (18%) who experienced stable disease for more than four months. One patient with stable disease was reclassified as a partial response after tumour shrinkage of over 30% was observed in a previously progressing hepatocellular carcinoma. A second patient with non-small cell lung cancer remains on trial with stable disease following 13 months of treatment, as is a third with adenocarcinoma of unknown primary following 6.5 months of treatment. The other patients showing clinical benefit suffered from different types of cancer such as colon, colorectal, neuroendocrine, parotid cylindroma, suprarenoma and thymoma.

Patients entering Phase I trials have generally received several rounds of unsuccessful chemotherapy prior to entering a clinical trial and present with a wide variety of tumour types. The fact that the drug is administered as a capsule is also of benefit to patients who do not require hospitalisation during treatment. CYC202 is presently being tested in two international, multicentre Phase IIa clinical trials for the treatment of breast and lung cancer in combination with standard chemotherapy.

In a second report to be presented at the same meeting by Cyclacel collaborators from Germany, preclinical data indicated that CYC202 given in combination with docetaxel exhibited marked synergy over either treatment given alone. The data showed that tumour growth in model systems was slowed very significantly when docetaxel was administered prior to a course of CYC202 in comparison to treatment with docetaxel alone. In the combination treatment final tumour volume was only 3% of that seen in the untreated control group. This data suggests that combination therapy where a Cyclin Dependent Kinase inhibitor is used along with selected standard chemotherapies may provide a new therapeutic option in the treatment of cancer.

Professor Sir David Lane, CSO of Cyclacel said, “The preclinical combination data confirm our observations in cell culture systems and are consistent with our theory of how the cell cycle is being controlled. These results along with the Phase I clinical data support our continued investigation of the clinical benefits of CYC202.”

About Cyclacel ( www.cyclacel.com )
Cyclacel is a biopharmaceutical company that designs and develops small molecule drugs that act on cell cycle regulators to stop uncontrolled cell division in cancer and other diseases involving abnormal cell proliferation. Cyclacel discovery integrates cell cycle biology with a library of gene-based targets, RNAi functional genomics, chemogenomics and clinical biomarker technologies to rapidly deliver new drugs. The most advanced of Cyclacel’s 8 research and development programs is CYC202, a Cyclin Dependent Kinase Inhibitor (CDKI), in Phase IIa trials for breast and lung cancer. CYC202 is also being explored for use in glomerulonephritis, an inflammatory disease associated with kidney cell proliferation. CYC400, 2nd generation CDKIs, and CYC381, clotrimazole analogues, acting on the cancer cell cycle are in preclinical development. Cyclacel has entered into corporate alliances with AstraZeneca, CV Therapeutics, Lorus Therapeutics and a top 5 pharmaceutical major all in the oncology field.