Cyclacel Group Reports Beneficial Effects of Seliciclib -CYC202- in Models of Kidney Disease.

DUNDEE, Scotland -- Cyclacel Group plc ("Cyclacel"), the UK-based biopharmaceutical company, announced today preclinical data showing activity of its experimental CDK inhibitor drug seliciclib (CYC202 or R-roscovitine) in two models of kidney disease. The results were reported in last week's American Society for Nephrology meeting by two independent Italian and British teams investigating seliciclib in lupus nephritis and crescentic glomerulonephritis.

Investigators from the Mario Negri Institute and Ospedali Riuniti, Bergamo, Italy, presented data showing that seliciclib significantly improved survival of animals with lupus nephritis and at the same time had a protective effect on kidney function. In one arm of the study where the drug was administered as preventive treatment early in disease progression, seliciclib decreased indicators of renal damage and significantly increased the life span of treated over untreated animals (p less than 0.01). In a second study in animals with established disease, seliciclib treatment in combination with a low dose of methylprednisolone, a drug commonly used to treat patients with this disease, markedly improved survival over untreated animals (p less than 0.0001), reduced proteinuria (p less than 0.01) and delayed the onset of renal damage compared with either treatment alone (p less than 0.01). The investigators further reported that in both the preventive and therapeutic studies seliciclib treatment reduced the levels of serum anti-DNA antibodies (p less than 0.01), a biomarker reflecting kidney disease activity.

Investigators from Hammersmith Hospital, London, presented data showing that seliciclib attenuated disease in a mouse model of crescentic glomerulonephritis, an autoimmune disease in which overgrowth of kidney cells caused by inflammation results in irreparable damage to the kidney. In these experiments seliciclib prevented cellular proliferation, crescent formation and renal impairment. Formation of crescents is a marker of overgrowth of kidney cells, leads to blockage of blood filtration and ultimately impaired renal function and kidney failure. The investigators demonstrated that seliciclib decreased crescent formation over controls (p less than 0.05) even when the disease was established prior to any treatment.

Spiro Rombotis, Chief Executive Officer of Cyclacel, said: "Independent investigators continue to validate our belief that CDK inhibitor drugs may be useful in diseases beyond cancer, although cancer remains our main focus. There is a pressing medical need to treat patients suffering from inflammatory kidney diseases and cell cycle inhibitors could make important contributions in this field."

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 also has seven programs in preclinical development.

Notes for Editors:

Crescentic glomerulonephritis (CG)

Crescents are defined as the presence of two or more layers of cells in a kidney compartment called the Bowman space. The presence of crescents in kidney glomeruli is a marker of severe renal injury. CG is initially associated with disruption of the glomerular basement membrane and glomerular capillaries. Circulating cells, inflammatory mediators and plasma proteins pass through capillary walls into the Bowman space. Cells and mediators from the interstitium enter the Bowman space resulting in disruption of the Bowman capsule, which leads to development of crescents. CG is mediated by antibody or cellular immunity and results from deposition of antibodies along the basement membrane and/or glomerular deposition of preformed soluble immune complexes. Its clinical symptoms are cell proliferation and proteinuria.

Lupus nephritis

Lupus nephritis is one of the most serious complications of systemic lupus erythematosus (SLE). It usually manifests within five years of diagnosis. Lupus nephritis occurs histologically in the majority of patients with SLE, even if they are not clinically diagnosed with renal disease. The disease is difficult to diagnose and its symptoms are generally related to hypertension, proteinuria and renal failure.

American Society of Nephrology -- Renal Week 2004 Conference -- October 27-November 1, 2004; St. Louis, Missouri (www.asn-online.org).

1. Poster Board Number: SU-PO707. R-Roscovitine (CYC202), a Cyclin Dependent Kinase (CDK) Inhibitor, Reduces Autoimmune Renal Injury and Prolongs Life in Murine Lupus Nephritis. Authors: Carla Zoja, Sara Conti, Daniela Corna, Daniela Rottoli, Federica Casiraghi, Athos Gianella-Borradori, Giuseppe Remuzzi, Ariela Benigni. Date/Time: Sunday, October 31, 2004 Pathogenic Mechanisms in Glomerulonephritis (10:00 AM - 12:00 PM).

2. Poster Board Number: SU-PO715. Cyclin Dependent Kinase (CDK) Inhibitor CYC202 Ameliorates Experimental Crescentic Glomerulonephritis. Authors: Abdulmunem M. Sheryanna, Jennifer Smith, Anna Barnett, Steven McClue, Terence Cook, Charles D. Pusey. Date/Time: Sunday, October 31, 2004 Basic/Experimental Inflammation: Renal Disease (10:00 AM - 12:00 PM).

Spiro Rombotis, 46, joined Cyclacel in August 1997. He has 21 years of experience with pharmaceutical and biotech companies. He was previously Vice President, International Operations & Business Development, Managing Director, Europe and Director Japanese joint venture, The Liposome Company, Inc.; Vice President, Pharmaceuticals, Central & Eastern Europe and Director International Marketing, Bristol-Myers Squibb Company; Head European Marketing and Sales, Head Corporate Development, Centocor, Inc.; Business Development, Novartis AG. BA, Williams College, USA. He holds an MBA and Master's degree in Hospital Management with honors, Kellogg Graduate School of Management, where he serves on the Advisory Board, Kellogg Center for Biotechnology.

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