Sareum Holdings plc (Sareum) (AIM: SAR), the specialist structure-based drug discovery 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 the effectiveness of traditional cancer therapeutics such as chemotherapy and is the primary target of the joint collaboration. The aim of the programme, first announced in July 2005, is to develop potential cancer treatments with valuable benefits for cancer patients including lower doses of existing therapies, fewer adverse side-effects and efficacy where tumours currently do not respond to chemotherapy. In August 2006 Sareum announced that the collaboration had discovered a novel compound series which showed activity in cancer cell models.

The patent filings are part of an ongoing strategy to secure the intellectual property rights relating to the novel compound series developed from this collaboration, their effectiveness in inhibiting CHK1 function and their use in the treatment of cancer.

Sareum has used its expertise in fragment and structure-based drug discovery to identify novel chemical compounds effective against CHK1. These compound series have been rapidly progressed towards drug candidates utilising Sareum's high throughput medicinal chemistry and structure determination platforms combined with the drug screening, specialist cancer biology and medicinal chemistry expertise at The Cancer Research UK Centre for Cancer Therapeutics at The Institute.

Under the terms of the collaboration agreement, CRT will commercialise the drug candidates developed by the collaboration to secure future clinical development. Payments, milestones and royalties received by CRT will be shared with Sareum and The Institute.

Commenting on the agreement, Sareum's Chief Executive Officer, Dr Tim Mitchell, said: "The progress of these compounds represents an important milestone in Sareum's strategy to generate value through our in-house drug discovery. We are now looking forward to advancing our novel chemical series through to clinical candidate nomination."

Professor Paul Workman, Director of The Cancer Research UK Centre for Cancer Therapeutics 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."

For further information:

Sareum Holdings 01223 497700
Tim Mitchell, Chief Executive Officer

Buchanan Communications 020 7466 5000
Tim Anderson, Mary-Jane Johnson

The Institute of Cancer Research 020 7153 5359
Nadia Ramsey, Science Press Officer

Cancer Research Technology Limited 0207 679 3640
Nick Wells, Marketing and Business Manager

Notes for editors:

About Checkpoint Kinase 1

Many known cancer treatments cause DNA damage by either physically modifying the cell's DNA or disrupting vital cellular processes that can affect the fidelity of DNA replication and cell division, such as DNA metabolism, DNA synthesis, DNA transcription and microtubule spindle formation. Such treatments include for example, radiotherapy, which causes DNA strand breaks, and a variety of chemotherapeutic agents including topoisomerase inhibitors, antimetabolites, DNA-alkylating agents, and platinum-containing cytotoxic drugs. A significant limitation to these genotoxic treatments is drug resistance. One of the most important mechanisms leading to this resistance is attributed to activation of cell cycle checkpoints, giving the tumour cell time to repair damaged DNA. By abrogating a particular cell cycle checkpoint, or inhibiting a particular form of DNA repair, it may therefore be possible to circumvent tumour cell resistance to 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 regulating cell cycle checkpoint signals that are activated in response to DNA damage and errors in DNA caused by defective replication (see, e.g., Bartek and Lukas, 2003). CHK1 transduces these signals through phosphorylation of substrates involved in a number of cellular activities including cell cycle arrest and DNA repair. Two key substrates of CHK1 are the Cdc25A and Cdc25C phosphatases that dephosphorylate CDK1 leading to its activation, which is a requirement for exit from G2 into mitosis (M phase).. Phosphorylation of Cdc25C and the related Cdc25A by CHK1 blocks their ability to activate CDK1, thus preventing the cell from exiting G2 into M phase. The role of CHK1 in the DNA damage-induced G2 cell cycle checkpoint has been demonstrated in a number of studies where CHK1 function has been knocked out.

The reliance of the DNA damage-induced G2 checkpoint upon CHK1 provides one example of a therapeutic strategy for cancer treatment, involving targeted inhibition of CHK1. Upon DNA damage, the p53 tumour suppressor protein is stabilised and activated to give a p53-dependent G1 arrest, leading to apoptosis or DNA repair. Over half of all cancers are functionally defective for p53, which can make them resistant to genotoxic cancer treatments such as ionising radiation (IR) and certain forms of chemotherapy. These p53 deficient cells fail to arrest at the G1 checkpoint or undergo apoptosis or DNA repair, and consequently may be more reliant on the G2 checkpoint for viability and replication fidelity. Abrogation of the G2 checkpoint through inhibition of the CHK1 kinase function has been demonstrated to selectively sensitise p53 deficient cancer cells to genotoxic cancer therapies.

About Sareum Holdings plc

Sareum Holdings plc is a structure-based drug discovery business headquartered in Cambridge, UK. The Company was formed in August 2003 to discover new drugs for the treatment of cancer. Sareum's unique approach aims to halve the time it takes to discover new drug candidates.

A structure-based approach to drug discovery relies on knowledge of the three-dimensional structure of the proteins that cause disease. Once the structure is known, potential drugs are designed to 'lock-in' to the protein with the aim of reversing or arresting a disease's progression. Knowledge of the structure of the potential drugs and how they 'lock-in' to their target protein assists greatly in the development of high-quality drug candidates. Determining structure is a complex task and requires leading-edge equipment and experienced staff. Sareum's approach to structure determination utilises its proprietary protein expression platform in order to produce multiple recombinant proteins that accelerate structure determination using x-ray crystallography.

Once the structure is determined, the Company's innovative fragment screening platform is used to identify novel chemical templates designed to interact with the target protein. Sareum then uses its high-throughput medicinal chemistry platform to rapidly optimise these molecules and develop the most promising into potential drug candidates.

Sareum aims to successfully deliver drug candidates for licensing to larger pharmaceutical companies at the pre-clinical or early clinical trials stage. This is funded by provision of its specialist drug discovery capabilities to partners in the pharmaceutical and biotechnology industries.

Sareum joined the AIM market of the London Stock Exchange in October 2004 and trades under the symbol SAR. For further information, please visit

About The Institute of Cancer Research

The Institute of Cancer Research is Europe's leading cancer research centre with expert scientists working on cutting edge research. It was founded in 1909 to carry out research into the causes of cancer and to develop new strategies for its prevention, diagnosis, treatment and care. For more information please visit

The Institute works in a unique partnership with the Royal Marsden NHS Foundation Trust, forming the largest comprehensive cancer centre in Europe. The Institute is unrivalled in its record in cancer drug discovery and development.

The Institute is a charity that relies on voluntary income. The Institute is a highly 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 and commercialisation company that realises cancer patient benefit from publicly- funded research worldwide. CRT works closely with leading international cancer scientists, their institutes and funding bodies to protect, develop and commercialise oncology-related discoveries. CRT is wholly owned by Cancer Research UK, the largest independent funder of cancer research in the world. Further information about Cancer Research UK can be found at