BioWorld International Correspondent

LONDON - Astex Technology Ltd. entered a $40 million collaboration with AstraZeneca plc to discover drugs against a key target in Alzheimer's disease.

Although the companies did not specify, the target is thought to be beta-amyloid precursor protein-cleaving enzyme, which mediates the deposition of amyloid plaque in the brain of Alzheimer's sufferers.

Tim Haines, CEO of Astex, told BioWorld International, "The target is very well known in the field but it is not amenable to high-throughput screening. You need another way to come up with leads."

Cambridge-based Astex already has found some initial leads using its high-throughput X-ray crystallography technology. That allows the company to obtain 3-dimensional structures of the target protein and then select the subset of compounds that are compatible with the shape of the active site. The structure of these compounds is then screened, enabling Astex to pick out low-molecular-weight hits that do not have sufficient affinity to be picked up in high-throughput screens.

"AstraZeneca has been working on the target for at least four years and has not been able to come up with high-affinity compounds," Haines said. "We are able to offer technology that is not otherwise available." The technology has already been validated against a number of other targets and has generated leads with novel binding, the company said.

In addition to the lead series generated in-house, Astex will be working to optimize some of London-based AstraZeneca's earlier compounds.

Under the terms of the agreement, AstraZeneca will pay Astex's costs and the rest of the payments will be in preclinical and clinical milestones, with one significant milestone likely to be triggered this year. "The $40 million value is very good, given we are working on early leads, and the royalty rates are very good, given this is early stage research," Haines said.