Sareum Holdings plc (Sareum) (AIM: SAR), the specialist structure-based drug discovery company, is pleased to announce progress with two additional oncology research programs established to discover novel small molecule compounds that are effective against important cancer drug discovery targets.

The first of the discovery programmes targets Polo-Like Kinase 1 (PLK1). PLK1 is a key regulator of cell division and increased levels of PLK1 are present in many cancer types. Reduction of PLK1 activity has been shown to lead to decreased tumour size.

Sareum’s innovative Template Screening platform has successfully identified numerous novel chemical series that inhibit the enzyme activity of PLK1.  Importantly, x-ray protein structure analysis has shown precisely how these compounds interact with PLK1, which will greatly assist rapid medicinal chemistry advancement to clinical candidates.

The second program targets the B-raf gene. Abnormally high B-raf activity has been associated with increased tumour aggressiveness and decreased survival in many types of cancer, particularly skin cancer as well as cancers of the colon and thyroid. Reducing B-raf activity has been shown to prevent tumour cell survival.

Sareum’s expertise in protein structure analysis has enabled the successful determination of high resolution structural information which will be invaluable in identifying small molecule leads and progressing them to drug candidates.

These programmes are currently wholly owned by Sareum and form part of a robust and expanding internal oncology portfolio, which also includes the CHK1, Aurora and FLT Kinase programmes which were announced in February and May 2007.

Commenting on the announcement, Sareum’s Chief Executive Officer, Dr Tim Mitchell, said: “These discoveries represent a significant development in Sareum’s internal drug candidate portfolio with key assets identified against important cancer drug discovery targets.  We are actively seeking licencing partners for these programmes to assist the advancement of novel chemical series through to clinical candidate nomination.”

 

For Further Information:

Sareum Holdings plc

01223 497700

Tim Mitchell, Chief Executive Officer

 

Buchanan Communications

020 7466 5000

Tim Anderson, Mary-Jane Johnson

 

Grant Thornton Corporate Finance

020 7383 5100

Philip Secrett, Colin Aaronson

 

 

Notes for editors:

About PLK1

PLK1 is a protein kinase and higher levels of this enzyme have been shown to be present in many types of cancer including non-small-cell lung cancer, head and neck cancer, esophageal cancer, gastric cancer, melanomas, breast cancer, ovarian cancer, endometrial cancer, colorectal cancer, gliomas, and thyroid cancer. These higher PLK1 levels have also been linked to patients with a poor disease prognosis.

In addition, reducing PLK1 enzyme activity or protein levels has been shown to induce tumour cell death in a variety of biological model systems. The normal cellular role of PLK1 is as a critical regulator of cell division during mitosis and interfering with this process has been shown to lead to the programmed cell death (apoptosis) of tumour cells.

Therapeutically a PLK1 inhibitor would be used as an anti-mitotic agent in cancer therapy.  One current class of highly effective anti-mitotic agents in the clinic are the Taxanes, which disrupt microtubule function and prevent mitotic progression.  Both dose-limiting toxicity and more importantly multiple types of drug resistance to this class have prevented these drugs from becoming more universal anti-cancer agents.  For these reasons there is an opportunity to develop alternative anti-mitotic agents such as PLK1 inhibitors into new effective cancer treatments.

About B-raf

Many cancers have been shown to have mutations in the B-RAF gene which cause a large increase in the enzyme activity of the B-raf protein kinase. These mutations have been observed in over 60% of malignant melanoma (a form of skin cancer) as well as colorectal, thyroid, cholangiocarcinoma, lung adenocarcinoma and glioblastoma.  Introduction of these mutant forms of B-raf into experimental models have reproduced and sustained tumourigenesis.  In addition, reducing the levels of mutant B-raf or its enzyme activity in cells has been shown to prevent tumour cell survival. In pre-clinical studies, Small molecule B-raf inhibitors have been shown to reduce tumour size and slow tumour progression without evident side effects.

Melanoma is the most fatal form of skin cancer and has shown a dramatic increase in disease incidence in developed countries due to changes in life style (15 fold increase in the last 40 years in the US). There are 7000 new patients diagnosed with melanoma each year in just the UK alone with 1500 deaths per year reported from the disease (1 in 100 cancer deaths).  The survival rates for metastatic melanoma are extremely poor at less than 5% after 5 years with no effective therapies currently available.

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