10 April 2008

 

SAREUM HOLDINGS PLC

(“Sareum” or the “Company”)

  

Sareum to Present Chk1 Cancer Research Programme

at AACR Annual Meeting 2008

 

Sareum Holdings plc (Sareum) (AIM: SAR), the specialist structure-based drug discovery business, is pleased to announce that it will present the latest results from its joint research collaboration with The Institute of Cancer Research and Cancer Research Technology Ltd. at the American Association for Cancer Research (AACR) annual meeting, to be held on April 12-16 2008 in San Diego, CA.

Dr John Reader, VP of Chemistry at Sareum, will present a poster entitled “Identification and structure-guided optimization of novel inhibitors of Checkpoint kinase 1 (Chk1) through combined biochemical and crystallographic screening” on Sunday April 13.

Chk1, the target of the joint research collaboration, is a key component of a biochemical pathway responsible for preventing the effectiveness of traditional cancer therapeutics such as chemotherapy. The aim of the collaboration, first announced in July 2005, is to develop novel cancer treatments with the potential to have efficacy against tumours that do not respond to chemotherapy and/or fewer adverse side-effects as a result of lower doses of chemotherapy being required. In August 2006 the collaboration announced the discovery of a novel compound series which showed activity in cancer cell models, and in February 2007 it was announced that a series of patent applications had been filed to secure the intellectual property rights related to compounds developed in the collaboration.

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. 

Commenting on the announcement, Sareum’s Chief Executive Officer, Dr Tim Mitchell, said: “We have made excellent progress in this highly successful cancer research collaboration and we are delighted to be making our first public presentations of these advances. These collaborations endorse Sareum’s technology and the experience of our team.”

 

Sareum Holdings plc

01223 497700

Tim Mitchell, Chief Executive Officer

 

 

 

Buchanan Communications

020 7466 5000

Mary-Jane Johnson, Tim Anderson

 

 

 

Grant Thornton Corporate Finance

020 7383 5100

Philip Secrett, Colin Aaronson

 

 

 

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.  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 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 www.sareum.co.uk