Sareum Regulatory News (SAR)

6 Feb 2007 07:02

Sareum Holdings PLC06 February 2007 For immediate release 6 February 2007 SAREUM HOLDINGS PLC, THE INSTITUTE OF CANCER RESEARCH AND CANCER RESEARCH TECHNOLOGY LTD Progression of Checkpoint Kinase 1 Drug Discovery Programme Sareum Holdings plc (Sareum) (AIM: SAR), the specialist structure-based drugdiscovery business, The Institute of Cancer Research (The Institute), Europe's leading cancer research centre, and Cancer Research Technology Limited (CRT), the oncology focused development and commercialisation company, are pleased to announce that novel small molecule compounds, the subject of a series of patent filings, show activity in targeting Checkpoint Kinase 1 (CHK1). CHK1 is a key component of a biochemical pathway responsible for preventing theeffectiveness of traditional cancer therapeutics such as chemotherapy and is theprimary target of the joint collaboration. The aim of the programme, firstannounced in July 2005, is to develop potential cancer treatments with valuablebenefits for cancer patients including lower doses of existing therapies, feweradverse side-effects and efficacy where tumours currently do not respond tochemotherapy. In August 2006 Sareum announced that the collaboration haddiscovered a novel compound series which showed activity in cancer cell models. The patent filings are part of an ongoing strategy to secure the intellectualproperty rights relating to the novel compound series developed from thiscollaboration, their effectiveness in inhibiting CHK1 function and their use inthe treatment of cancer. Sareum has used its expertise in fragment and structure-based drug discovery toidentify novel chemical compounds effective against CHK1. These compound serieshave been rapidly progressed towards drug candidates utilising Sareum[?c=8217]shigh throughput medicinal chemistry and structure determination platformscombined with the drug screening, specialist cancer biology and medicinalchemistry expertise at The Cancer Research UK Centre for Cancer Therapeutics atThe Institute. Under the terms of the collaboration agreement, CRT will commercialise the drugcandidates developed by the collaboration to secure future clinical development.Payments, milestones and royalties received by CRT will be shared with Sareumand The Institute. Commenting on the announcement, Sareum[?c=8217]s Chief Executive Officer, Dr TimMitchell, said: [?c=8220]The progress of these compounds represents an importantmilestone in Sareum[?c=8217]s strategy to generate value through our in-housedrug discovery. We are now looking forward to advancing our novel chemicalseries through to clinical candidate nomination.[?c=8221] Professor Paul Workman, Director of The Cancer Research UK Centre for CancerTherapeutics at The Institute of Cancer Research, said: "We are very pleased with the progress that has been made so far with this project. By utilising the complementary expertise of each organisation we can speed up the drug development process and bring new treatments to patients as soon as possible." Sareum Holdings plc 01223 497700 Tim Mitchell, Chief Executive Officer Buchanan Communications 020 7466 5000 Tim Anderson, Mary-Jane Johnson The Institute of Cancer Research 020 7153 5359Nadia Ramsey, Press Officer Cancer Research Technology Limited 0207 269 3640Nick Wells, Head of Marketing Notes for editors: About Checkpoint Kinase 1 Many known cancer treatments cause DNA damage by either physically modifying thecell[?c=8217]s DNA or disrupting vital cellular processes that can affect thefidelity of DNA replication and cell division, such as DNA metabolism, DNAsynthesis, DNA transcription and microtubule spindle formation. Such treatmentsinclude for example, radiotherapy, which causes DNA strand breaks, and a varietyof chemotherapeutic agents including topoisomerase inhibitors, antimetabolites,DNA-alkylating agents, and platinum-containing cytotoxic drugs. A significantlimitation to these genotoxic treatments is drug resistance. One of the mostimportant mechanisms leading to this resistance is attributed to activation ofcell cycle checkpoints, giving the tumour cell time to repair damaged DNA. Byabrogating a particular cell cycle checkpoint, or inhibiting a particular formof DNA repair, it may therefore be possible to circumvent tumour cell resistanceto the genotoxic agents and augment tumour cell death induced by DNA damage,thus increasing the therapeutic index of these cancer treatments. Checkpoint Kinase 1 (CHK1) is a serine/threonine kinase involved in regulatingcell cycle checkpoint signals that are activated in response to DNA damage anderrors in DNA caused by defective replication (see, e.g., Bartek and Lukas,2003). CHK1 transduces these signals through phosphorylation of substratesinvolved in a number of cellular activities including cell cycle arrest and DNArepair. Two key substrates of CHK1 are the Cdc25A and Cdc25C phosphatases thatdephosphorylate CDK1 leading to its activation, which is a requirement for exitfrom G2 into mitosis (M phase).. Phosphorylation of Cdc25C and the relatedCdc25A by CHK1 blocks their ability to activate CDK1, thus preventing the cellfrom exiting G2 into M phase. The role of CHK1 in the DNA damage-induced G2cell cycle checkpoint has been demonstrated in a number of studies where CHK1function has been knocked out. The reliance of the DNA damage-induced G2 checkpoint upon CHK1 provides oneexample of a therapeutic strategy for cancer treatment, involving targetedinhibition of CHK1. Upon DNA damage, the p53 tumour suppressor protein isstabilised and activated to give a p53-dependent G1 arrest, leading to apoptosisor DNA repair. Over half of all cancers are functionally defective for p53,which can make them resistant to genotoxic cancer treatments such as ionisingradiation (IR) and certain forms of chemotherapy. These p53 deficient cellsfail to arrest at the G1 checkpoint or undergo apoptosis or DNA repair, andconsequently may be more reliant on the G2 checkpoint for viability andreplication fidelity. Abrogation of the G2 checkpoint through inhibition of theCHK1 kinase function has been demonstrated to selectively sensitise p53deficient cancer cells to genotoxic cancer therapies. About Sareum Holdings plc Sareum Holdings plc is a structure-based drug discovery business headquarteredin Cambridge, UK. The Company was formed in August 2003 to discover new drugsfor the treatment of cancer. Sareum[?c=8217]s unique approach aims to halve thetime it takes to discover new drug candidates. A structure-based approach to drug discovery relies on knowledge of thethree-dimensional structure of the proteins that cause disease. Once thestructure is known, potential drugs are designed to [?c=8216]lock-in[?c=8217] tothe protein with the aim of reversing or arresting a disease[?c=8217]sprogression. Knowledge of the structure of the potential drugs and how they[?c=8216]lock-in[?c=8217] to their target protein assists greatly in thedevelopment of high-quality drug candidates. Determining structure is a complextask and requires leading-edge equipment and experienced staff. Sareum[?c=8217]s approach to structure determination utilises its proprietary proteinexpression platform in order to produce multiple recombinant proteins thataccelerate structure determination using x-ray crystallography. Once the structure is determined, the Company[?c=8217]s innovative fragmentscreening platform is used to identify novel chemical templates designed tointeract with the target protein. Sareum then uses its high-throughputmedicinal chemistry platform to rapidly optimise these molecules and develop themost promising into potential drug candidates. Sareum aims to successfully deliver drug candidates for licensing to largerpharmaceutical companies at the pre-clinical or early clinical trials stage.This is funded by provision of its specialist drug discovery capabilities topartners in the pharmaceutical and biotechnology industries. Sareum joined the AIM market of the London Stock Exchange in October 2004 andtrades under the symbol SAR. For further information, please visitwww.sareum.co.uk About The Institute of Cancer Research The Institute of Cancer Research is Europe's leading cancer research centre withexpert scientists working on cutting edge research. It was founded in 1909 tocarry out research into the causes of cancer and to develop new strategies forits prevention, diagnosis, treatment and care. For more information please visitwww.icr.ac.uk The Institute works in a unique partnership with the Royal Marsden NHSFoundation Trust, forming the largest comprehensive cancer centre in Europe. TheInstitute is unrivalled in its record in cancer drug discovery and development. The Institute is a charity that relies on voluntary income. The Institute is ahighly cost-effective major cancer research organisation with over 90p in every£ directly supporting research. About Cancer Research Technology Limited Cancer Research Technology Limited (CRT) is an oncology-focused development andcommercialisation company that realises cancer patient benefit from publicly-funded research worldwide. CRT works closely with leading international cancerscientists, their institutes and funding bodies to protect, develop andcommercialise oncology-related discoveries. CRT is wholly owned by CancerResearch UK, the largest independent funder of cancer research in the world.Further information about CRT can be found at www.cancertechnology.com. This information is provided by RNS The company news service from the London Stock Exchange