BioWorld International Correspondent

LONDON - Pharmagene plc made further progress on the road to transforming itself from a drug discovery services provider to a company focused on drug discovery, announcing an extension of its collaboration with Argenta Discovery Ltd. for lead optimization in two of its internal programs and the discovery of potential novel targets in chronic obstructive pulmonary disease.

The terms of the deal with Argenta, of Harlow, UK, were not disclosed, but the companies will work together to optimize a series of leads already identified in each program. In the case of R4 for the treatment of migraine, the leads came from an earlier collaboration with Argenta. In the case of R1 in the treatment of irritable bowel syndrome (IBS), the leads already have been investigated for the treatment of a different indication. Their potential use in IBS was uncovered with Pharmagene's Indication Switch platform, which suggests new indications for existing compounds.

Alastair Riddell, CEO of Pharmagene, said, "Our scientists have worked closely together and the quality of the results is reflected in the decision to extend our original migraine program and also work together [with Argenta] in IBS."

At the same time Pharmagene, of Royston, UK, announced that its collaboration with WITA Proteomics AG, of Berlin, to provide validated targets for licensing has completed a proteomic evaluation of human tissue affected with chronic obstructive pulmonary disease. The study identified a number of differentially regulated proteins, including membrane proteins and enzymes, in WITA's protein database, compared to control tissue.

Riddell said the partners would continue to validate the potential targets. "We expect to create novel and validated drug target programs, which are protected by valuable intellectual property rights. This can only continue to add to our therapeutic programs at Pharmagene."

Both the R1 and R4 programs are based on novel targets that Pharmagene has uncovered using its human tissue-based drug discovery and evaluation platforms. The R1 program is based on the discovery of a novel role for the 5HT2beta receptor in the colon, in that it enhances the contractile response of the colon to nerve stimulation. The R4 program is looking for EP4 receptor antagonists, following the discovery that EP4 is involved in the dilation of the cerebral vasculature, the cause of pain in migraine.

Those programs are in their early stages, but Pharmagene expects its lead compound, R52 for the treatment of cystic fibrosis, to enter the clinic by the end of 2002. It also was discovered in-house, through the Indication Switch platform, which uses human tissues to identify novel therapeutic applications for existing compounds, based on understanding of the molecular target on which the drug acts, and the distribution and functional role of that target throughout the body.

In March, Pharmagene signed its first collaboration in Indication Switch, with Sosei Co. Ltd., of Tokyo, to screen a number of compounds Sosei sourced from Japanese pharmaceutical companies. Those have either stalled in clinical development for reasons other than toxicity, or have been sold in Japan, but not Western markets.