MerLion and CRT in UK-Asia cancer deal.

MerLion Pharmaceuticals has entered into a large-scale screening programme with Cancer Research Technology (CRT) to identify new anti-cancer drug candidates derived from natural product chemistry.

The two-year collaboration teams the Singapore-based drug discovery company with the UK specialists in oncology drug discovery and commercialisation and represents the partnering of two countries, which are at the forefront of cancer research.

Following the identification of lead compounds, it is anticipated that the medicinal chemistry both at MerLion and CRT will be utilised to perform compound optimisation.

The companies will work in partnership throughout the target selection and screening process. The results of the collaboration will be jointly owned. No financial details of the transaction were disclosed.

Chris Molloy, business development manager for Merlion Pharmaceuticals told DrugResearcher.com: "Single drug molecules derived from natural sources, such as microorganisms and plants have provided the basis for a great range of leading cancer medicines."

"A good example of these are the plant derived taxanes, such as Taxol (trade name Paclitaxel, Bristol Myers Squibb, USA). Such diverse, natural chemistry remains a rich source of molecules that are able to interact with the cellular machinery responsible for cancer," he added.

Molloy also pointed to the recent success in clinical trials of the new epotholone compounds such as Ixabepilone (Bristol Myers Squibb, USA) and also Temsirolimus (Wyeth, USA).

Despite a huge amount of effort, the demand for improved treatment strategies remains. While cancer prevention campaigns have resulted in falling numbers of sufferers, there is still significant room for improvement in survival rates.

Often, the benefits of many existing cancer therapies have to be weighed against serious side effects.

"Cancer research in the UK has a deservedly high profile and this collaboration opens up opportunities to find novel drugs for the new generation of cancer targets being discovered there, said Dr Tony Buss, CEO of MerLion.

This international partnership follows the Joint Statement on Science, Engineering and Technology signed by Prime Ministers Lee Hsien Loong and Tony Blair on 4th July 2005, building on the UK-Singapore Partners in Science initiative.

"Within the collaboration MerLion will screen their natural compound collection against high throughput screens developed by scientists at CRT in order to isolate new therapeutic compounds against validated cancer targets," said Dr Clive Stanway, Director of Technology Development at CRT.

Mr Ian Pearson MP, UK Minister of State for Trade who is currently visiting Singapore expressed his delight that CRT and MerLion Pharma had entered into this collaboration.

"This is the type of collaboration that was envisaged by our Prime Ministers in July when they signed their joint statement on science. There are many more opportunities for a wide range of UK and Singaporean-based businesses and researchers to work together," he said.

The future cancer market is likely to be dominated by two main trends: the introduction of drugs with improved efficacy and better tolerability than existing products, and the increased use of combination therapy, involving drugs or procedures with different modes of action to disrupt parts of the cancer's life cycle.

Current medical practice to treat cancer usually comprises surgery, supported by chemotherapy and radiotherapy to mop up residual cancer cells. This approach is invasive, aggressive and not wholly effective.

Side effects caused by toxic compounds attacking healthy cells can limit treatment to sub-optimal levels.

However, a common strategy for new drug development is to target the treatment to the cancer, avoiding damage to normal cells and tissues.

UK companies have approached this problem in several ways, although a number have harnessed antibodies as their 'magic bullet.'

One such company, Antisoma, has several antibodies in clinical development, some operating alone and others carrying a killing mechanism, such as an enzyme that induces programmed cell death, or a cytokine.

Another, Xenova, is employing a number of different strategies for targeting cancer cells. TransMID, currently in Phase III development, is a modified diphtheria toxin conjugated to transferring receptors, which are particularly prevalent on cancer cells.

Once inside the cancer cell, the diphtheria toxin interferes with protein synthesis and causes cell death. Now in a Phase I clinical study, XR5944 was originally thought to affect the DNA replication process through a mechanism of action that involved the dual inhibition of topoisomerases I and II.

Recent evidence has shown that XR5944 is a novel DNA/RNA targeting agent with a mechanism of action distinct from current cytotoxic agents.

The research highlighted demonstrates a major trend running across drug discovery screening. Large companies are becoming more willing to perform screening-based discovery activities with external partners increasing the focus upon the quality, and type, of compound chemistry that is being accessed.

Thus there is a clear recognition across the industry that a renaissance in interest in natural product derived chemistry is underway.

Many drug discovery companies that reduced their interest in natural products during the 1990s have seen a decline in the novelty of their discoveries, particularly in the cancer and infectious disease areas and in the growing drug target area of protein: protein interactions.

Many are now recognising that multiple approaches are necessary to achieve success and that natural products chemistry remains one of the many important tools required.