http://www.biodundee.co.uk/news.asp?nID=85
CYCLACEL INITIATES PHASE II CLINICAL TRIALS FOR CYC202 IN CANCER
MULTI-CENTRE TRIALS TO EVALUATE COMBINATION THERAPY IN LUNG CANCER AND BREAST CANCER
DUNDEE, UK, 20 January 2003 - Cyclacel Limited, the UK-based biopharmaceutical company, announced today the initiation of patient screening and enrolment into two Phase IIa clinical trials for its oral CDK inhibitor CYC202 for the treatment of breast and lung cancer in combination with standard chemotherapy regimens. The opening for enrolment of CYC202 Phase II studies follows an extensive Phase I programme in which CYC202 was given to approximately 78 subjects without the major side effects associated with standard cancer chemotherapy. Full results will be published in the future in a peer-reviewed medical journal. CYC202 is also in clinical trials for the treatment of glomerulonephritis, an inflammatory disease of the kidney.
One trial will explore the use of CYC202 in the treatment of stage IIIB/IV Non-Small Cell Lung Cancer (NSCLC) in combination with gemcitabine and cisplatinum. The other trial will evaluate the use of CYC202 in the treatment of advanced breast cancer in combination with capecitabine, an oral prodrug of 5-fluorouracil. These open-label studies will each recruit up to 30 patients and will be conducted in several hospitals in Belgium, France, Netherlands and the United Kingdom. Both trials will evaluate the safety, pharmacokinetic profile, anti- tumour activity and the effect on biomarkers of the combination of CYC202 and chemotherapy.
Cyclacel’s dedicated Biomarker Team will use blood samples from patients in both studies to identify specific molecular markers that may be used to monitor susceptibility or resistance to the treatment. Biomarker technology is a state-of- the-art approach to understand the molecular mechanism of action of novel drugs such as CYC202 in humans and also provide valuable insights into their pharmacological properties. In the long-term biomarker analysis of tumour tissues may allow selective treatment with CYC202 of those patients identified as likely to benefit from the drug based on the specific profile of their tumour.
Dr Athos Gianella-Borradori, Cyclacel’s Medical Director commented, "In the Phase I programme we established CYC202’s good tolerability profile. In the Phase II programme CYC202 offers the potential of a new cellular mechanism to work together with established chemotherapies against solid tumours. The preclinical and Phase I data provided us with indications of how this can best be achieved in terms of dose, sequence and other parameters. We look forward to confirming these possibilities in the Phase IIa studies with the objective of designing further optimised trials tailored to the properties of this novel cancer treatment.”
CYC202 (R-roscovitine) is a novel cell cycle drug belonging to the Cyclin Dependent Kinase (CDK) inhibitor class (US pat. 6,316,456). CDK inhibition is an important new approach in the quest for drugs that target the same molecular mechanisms as the body’s own cancer stopping genes. Because CDK inhibitors act at a different part of the cell cycle than current chemotherapies, giving these drugs in combination to patients may work synergistically to improve anti- tumour activity compared to standard therapies.
“Initiation of CYC202 Phase II trials in cancer is a very important milestone for our young company and marks the culmination of many months of hard work by Cyclacel and our collaborators,” said Spiro Rombotis, CEO. “We still have a long way to go in the clinic. We are nevertheless excited about the contributions of our talented Biomarker Team and converting our understanding of biological pathways into practical guidelines on appropriate drug use and eventually tailoring patient treatment. We look forward to advancing CYC202 to Phase II in glomerulonephritis, bringing additional drug candidates to Phase I clinical trials and constructing a rich pipeline of products from our genes-to-drugs platform.”
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, computational chemistry and biomarker technology to rapidly deliver new drug candidates. Cyclacel has five research and development programmes 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, an inflammatory disease of kidney cell proliferation. The Company has a corporate alliance with AstraZeneca to develop a specific Cyclin Groove Inhibitor (CGI) for cancer.
- # # # - Notes to editors Cyclin Dependent Kinase (CDK) Inhibitors are a novel class of drugs that act on the same CDK enzyme targets as the body’s own cancer stopping genes. Tumour suppressor genes, such as p53 and p21, stop cancer cells at cell cycle checkpoints and cause them to commit suicide. The goal of cancer treatment with CDK inhibitors is to emulate tumour suppressor gene behaviour and cause cancer cells to die. Although there are several CDK enzymes that appear to be promising targets, scientific publications suggest that inhibition of CDK2 appears to be directly linked with programmed death of cancer cells through apoptosis. The discovery of CDKs and cyclins and their role in checkpoint control of the cancer cell cycle has been honoured with the 2001 Nobel Prize for Medicine and Physiology. Dr Athos Gianella-Borradori, 47, joined October 2000. Previously Director Preclinical Development, Manufacturing, Clinical & Regulatory Affairs, Bavarian Nordic Research Institute GmbH; Vice President Clinical Affairs, CruCell BV; and Head, Oncology & Hematology Clinical R&D, Senior Adviser Genetic Therapy and Stem Cell Technologies, Novartis Pharma Ltd. MD University of Bern; fellow Charing Cross Hospital, London; Children’s Hospital, Los Angeles; University of Glasgow Royal Infirmary; University of Lausanne; University of Zurich. Board certified in Pediatrics Hematology and Oncology. Spiro Rombotis, 44, joined August 1997. Has 20 years of experience with pharmaceutical and biotech companies. 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. MBA and Master's degree in Hospital Management with honours, Kellogg Graduate School of Management, where he serves on the Advisory Board, Kellogg Center for Biotechnology. © 2003 - Cyclacel Limited. Cyclacel®, Fluorescience®, Penetratin® and Polgen® are registered trademarks.
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