Cyclacel Announces RNAi Collaboration

With leading pharma company, cancer research technology and the university of Cambridge to develop new disease models

DUNDEE, UK, 31 March 2003 - Cyclacel Limited, the UK-based biopharmaceutical company, has entered into a collaboration with one of the world’s top five pharmaceutical companies, Cancer Research Technology Limited (CRT) and the University of Cambridge to perfect the use of RNA interference (RNAi) technology for target validation and drug discovery. The new collaboration is aimed at improving RNAi technology in mammalian cells to allow the generation of new disease models and systems for analysing mammalian gene expression. Under the terms of the partnership, the parties have combined their intellectual property and skills to jointly develop the use of the RNAi technique as a tool in target validation, drug discovery and development. Financial terms were not disclosed.

The four-way collaboration will draw mainly on the expertise of Professor David Glover, Chief Scientist of Cyclacel’s Polgen division. In 1999, Professor Glover and colleagues first demonstrated RNAi-mediated inhibition of gene activity in mammalian cells. As a result of the collaboration the parties will pursue advances made in the research programme for their own drug discovery projects. In addition CRT will commercially exploit certain technologies discovered by the collaboration and offer them to third parties against payment of royalties to Cyclacel and the undisclosed pharmaceutical company.

“RNA interference is one of the most exciting recent developments in molecular biology allowing for rapid validation of gene-derived drug targets. This functional genomics technology dramatically accelerates the pace of elucidating the function of candidate genes over previous techniques and is applicable to virtually all genes”, said Professor David Glover, Chief Scientist, Polgen Division. “We look forward to working with the talented scientists at our pharmaceutical partner, CRT and the University of Cambridge to realise the potential of RNAi technology in target validation, drug discovery and development.”

The term RNAi refers to the use of double-stranded DNA to silence genes by causing the degradation of messenger RNA (mRNA) for a gene of interest. Professor Glover is a named inventor on a family of patents held by CRT involved in the use of RNAi in mammalian cells. Polgen uses RNAi in the screening of the Drosophila genome to identify genes involved in the mitotic process, which in turn allows the identification of comparable genes in humans. These genes are then investigated as potential druggable targets based on the understanding of cell cycle biology in diseases such as cancer.

“New technologies for gene identification and target validation are key initial elements of our genes-to-drugs approach and feed our state-of-the-art drug design and development capabilities,” commented Spiro Rombotis, Chief Executive of Cyclacel. “Cyclacel was recently awarded £1.2 ($1.9) million in UK government grants supporting our research into mitotic control mechanisms. This newest collaboration, centred on our RNAi technology, provides industrial validation of the quality of our scientists’ work and underpins our commitment to building a renewable drug discovery pipeline through constant innovation.”

Progress with Cyclacel’s RNAi technology was recently reported at several international conferences. Polgen’s Dr J Grabarek presented data at the Keystone Symposia: New Advances in Drug Discovery in Lake Tahoe on 7-12 January 2003. Polgen’s Dr F Scaerou presented a poster at the American Society for Cell Biology Annual Meeting in San Francisco on 14-18 December 2002. Dr G Bell, General Manager, Polgen Division, presented a poster at the “Genomics on Target” conference in Boston sponsored by Cambridge Healthtech Institute on 18-21 November 2002.

About Cyclacel
Cyclacel is a biopharmaceutical company that designs and develops small molecule drugs that act on key cell cycle regulators to stop uncontrolled cell division in cancer and other diseases involving abnormal cell proliferation. The Company’s discovery engines integrate core cell cycle expertise with a large library of proprietary gene-based targets, state-of-the-art molecular biology, RNAi functional genomics and computational chemistry to rapidly deliver new drug candidates. Cyclacel has five research and development programs underway. Most advanced is CYC202, a Cyclin Dependent Kinase (CDK) inhibitor, currently in Phase II trials for cancer. CYC202 has also completed a Phase I trial in healthy volunteers and is being explored for use in glomerulonephritis, a disease of renal cell proliferation. Cyclacel has a corporate alliance with AstraZeneca to develop a specific Cyclin Groove Inhibitor (CGI) for cancer.