Sareum Regulatory News (SAR)

2 Oct 2007 07:01

Sareum Holdings PLC02 October 2007 For Immediate Release 2 October 2007 SAREUM HOLDINGS PLC ("Sareum" or the "Company") Research Update: Oncology Portfolio Sareum Holdings plc (Sareum) (AIM: SAR), the specialist structure-based drugdiscovery company, is pleased to announce progress with two additional oncologyresearch programs established to discover novel small molecule compounds thatare effective against important cancer drug discovery targets. The first of the discovery programmes targets Polo-Like Kinase 1 (PLK1). PLK1 isa key regulator of cell division and increased levels of PLK1 are present inmany cancer types. Reduction of PLK1 activity has been shown to lead todecreased tumour size. Sareum's innovative Template Screening platform has successfully identifiednumerous novel chemical series that inhibit the enzyme activity of PLK1.Importantly, x-ray protein structure analysis has shown precisely how thesecompounds interact with PLK1, which will greatly assist rapid medicinalchemistry advancement to clinical candidates. The second program targets the B-raf gene. Abnormally high B-raf activity hasbeen associated with increased tumour aggressiveness and decreased survival inmany types of cancer, particularly skin cancer as well as cancers of the colonand thyroid. Reducing B-raf activity has been shown to prevent tumour cellsurvival. Sareum's expertise in protein structure analysis has enabled the successfuldetermination of high resolution structural information which will be invaluablein identifying small molecule leads and progressing them to drug candidates. These programmes are currently wholly owned by Sareum and form part of a robustand expanding internal oncology portfolio, which also includes the CHK1, Auroraand FLT Kinase programmes which were announced in February and May 2007. Commenting on the announcement, Sareum's Chief Executive Officer, Dr TimMitchell, said: "These discoveries represent a significant development inSareum's internal drug candidate portfolio with key assets identified againstimportant cancer drug discovery targets. We are actively seeking licencingpartners for these programmes to assist the advancement of novel chemical seriesthrough to clinical candidate nomination." For Further Information: Sareum Holdings plc 01223 497700Tim Mitchell, Chief Executive Officer Buchanan Communications 020 7466 5000Tim Anderson, Mary-Jane Johnson Grant Thornton Corporate Finance 020 7383 5100Philip Secrett, Colin Aaronson Notes for editors: About PLK1 PLK1 is a protein kinase and higher levels of this enzyme have been shown to bepresent in many types of cancer including non-small-cell lung cancer, head andneck cancer, esophageal cancer, gastric cancer, melanomas, breast cancer,ovarian cancer, endometrial cancer, colorectal cancer, gliomas, and thyroidcancer. These higher PLK1 levels have also been linked to patients with a poordisease prognosis. In addition, reducing PLK1 enzyme activity or protein levels has been shown toinduce tumour cell death in a variety of biological model systems. The normalcellular role of PLK1 is as a critical regulator of cell division during mitosisand interfering with this process has been shown to lead to the programmed celldeath (apoptosis) of tumour cells. Therapeutically a PLK1 inhibitor would be used as an anti-mitotic agent incancer therapy. One current class of highly effective anti-mitotic agents in theclinic are the Taxanes, which disrupt microtubule function and prevent mitoticprogression. Both dose-limiting toxicity and more importantly multiple types ofdrug resistance to this class have prevented these drugs from becoming moreuniversal anti-cancer agents. For these reasons there is an opportunity todevelop alternative anti-mitotic agents such as PLK1 inhibitors into neweffective cancer treatments. About B-raf Many cancers have been shown to have mutations in the B-RAF gene which cause alarge increase in the enzyme activity of the B-raf protein kinase. Thesemutations have been observed in over 60% of malignant melanoma (a form of skincancer) as well as colorectal, thyroid, cholangiocarcinoma, lung adenocarcinomaand glioblastoma. Introduction of these mutant forms of B-raf into experimentalmodels have reproduced and sustained tumourigenesis. In addition, reducing thelevels of mutant B-raf or its enzyme activity in cells has been shown to preventtumour cell survival. In pre-clinical studies, Small molecule B-raf inhibitorshave been shown to reduce tumour size and slow tumour progression withoutevident side effects. Melanoma is the most fatal form of skin cancer and has shown a dramatic increasein disease incidence in developed countries due to changes in life style (15fold increase in the last 40 years in the US). There are 7000 new patientsdiagnosed with melanoma each year in just the UK alone with 1500 deaths per yearreported from the disease (1 in 100 cancer deaths). The survival rates formetastatic melanoma are extremely poor at less than 5% after 5 years with noeffective therapies currently available. 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's unique approach aims to halve the time ittakes 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 'lock-in' to the proteinwith the aim of reversing or arresting a disease's progression. Knowledge of thestructure of the potential drugs and how they 'lock-in' to their target proteinassists greatly in the development of high-quality drug candidates. Determiningstructure is a complex task and requires leading-edge equipment and experiencedstaff. Sareum's approach to structure determination utilises its proprietaryprotein expression platform in order to produce multiple recombinant proteinsthat accelerate structure determination using x-ray crystallography. Once the structure is determined, the Company's innovative fragment screeningplatform is used to identify novel chemical templates designed to interact withthe target protein. Sareum then uses its high-throughput medicinal chemistryplatform to rapidly optimise these molecules and develop the most promising intopotential 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 This information is provided by RNS The company news service from the London Stock Exchange