Cyclacel Reports CYC682 Phase I Data at 2005 ASCO.

DUNDEE, Scotland -- Cyclacel Group plc ("Cyclacel"), the cell cycle-based biopharmaceutical company, reported initial data from a Phase I trial of CYC682, its novel, orally available nucleoside analogue, at the 2005 American Society of Clinical Oncology (ASCO) Annual Meeting in Orlando, Florida. The trial is being conducted in the United States at the Cancer Therapy and Research Center in San Antonio, Texas and Fox Chase Cancer Center in Philadelphia, Pennsylvania.

The interim results suggested that CYC682 has an acceptable toxicity profile and that the drug may be active in Non-Small Cell Lung Cancer (NSCLC).

Specifically, 18 patients with advanced solid tumors received by mouth CYC682 monotherapy twice a day for 14 consecutive days followed by seven days of rest. The dose-limiting toxicity was myelosuppression which was reversible after interruption of drug dosing. Non-hematological toxicities were mostly mild to moderate. The best response to treatment was stable disease in six patients, one with ovarian cancer, one with unknown primary-peritoneal carcinomatosis and four with NSCLC. One of the patients with NSCLC, who experienced stable disease, had tumor shrinkage as evidenced by radiological examination.

Dr. Judy Chiao, Cyclacel's VP Clinical Development and Regulatory Affairs, said, "CYC682 is a novel nucleoside analogue that acts by a unique mechanism of inhibiting DNA synthesis and triggering cell checkpoint machinery to arrest cell cycle progression. All four patients with NSCLC treated with CYC682 as monotherapy experienced stable disease including a patient whose CT scan showed tumor shrinkage. The data corroborate clinical evidence of stable disease in NSCLC in an earlier CYC682 Phase I study conducted at The Johns Hopkins Oncology Center. These initial clinical results suggest that CYC682 may have single agent activity against NSCLC and warrant further evaluation in a Phase II setting."

Spiro Rombotis, Cyclacel's Chief Executive Officer, said: "We are encouraged by the recent CYC682 Phase I data. Nucleoside analogues, such as gemcitabine and ara-C, are effective treatments of solid and hematological cancers. Gemcitabine is an intravenously administered drug in wide use for the treatment of breast, NSCLC and other cancers with annual sales in excess of $1 billion. CYC682 may have clinical utility in a broad range of cancers and its oral administration may represent a major advantage for patients."

CYC682 is the second of two clinical stage drugs in development by Cyclacel. Interim data from a Phase IIa clinical trial with the company's lead candidate, seliciclib, in NSCLC, will be presented at the 2005 ASCO meeting on May 15.

About Cyclacel (www.cyclacel.com)

Cyclacel is a biopharmaceutical company dedicated to the discovery, development and commercialization of novel, mechanism-targeted drugs to treat human cancers and other serious disorders. The company is currently evaluating seliciclib (CYC202), an orally-available Cyclin Dependent Kinase inhibitor, in Phase II clinical trials for the treatment of Non-Small Cell Lung Cancer and B-cell hematological malignancies. CYC682 is an orally-available, cell cycle modulating nucleoside analog in Phase I clinical trials for the treatment of cancer. Cyclacel has eight additional programs at preclinical stages.

Notes to Editors:

CYC682 (1-(2-C-cyano-2-deoxy-Beta-D-arabino-pentofuranosyl)-N4-palmitoyl cytosine) 1

CYC682 (or CS-682) is an oral prodrug and a novel derivative of 2'-deoxycytidine analogue CNDAC (1-(2-C-cyano-2-deoxy-Beta-D-arabino-pentofuranosyl)-cytosine). CYC682's availability by mouth is a feature of few new anticancer drugs increasingly favored by patients. Knowledge of CYC682's metabolic pathway and its effects on tumor growth offer the possibility of patient-specific therapy. Studying appropriate biomarkers affected by CYC682 could aid selection of optimal dose and schedule and could eventually predict treatment outcome. Data from to previous Phase I studies in eighty-eight (88) patients with a variety of cancers suggest that CYC682 is well tolerated in man with myelosuppression as dose limiting toxicity. Stable disease was observed in seventeen (17) patients after CYC682 treatment, including one patient with ovarian cancer who experienced a minor response and one patient with a gastrointestinal stromal sarcoma tumor (GIST) who remains on study for 3 years with stable disease after failing multiple therapies.

2005 American Society of Clinical Oncology Annual Meeting, Orlando, Florida, 13-17 May 2005.

Abstract No. 2026: Phase I and pharmacokinetic trial of oral administration of CYC682, a novel 2' deoxycytidine type anti-metabolite pro-drug, in patients with advanced solid tumors or lymphoma. Presenter: Anthony W. Tolcher, MD. (Level 3, 314A, Saturday, May 14, 2005, 8:00 - 11:00am).

(C) 2005 - Cyclacel Group plc All Rights Reserved. Cyclacel(R) is a registered trademark.

(1)SELECTED ADDITIONAL REFERENCES (in chronological order):

Hanaoka, K., et al, Int. J. Cancer, 1999:82:226-236.

Donehower R, et al, Proc Am Soc Clin Oncol, 2000: abstract 764.

Burch, PA, et al, Proc Am Soc Clin Oncol, 2001: abstract 364.