AMSTERDAM, the Netherlands - When he was head of structural biology and bioinformatics at Glaxo Wellcome plc, involved in applying protein structure analysis to drug discovery, Harren Jhoti continually was frustrated by the length of time taken to interpret raw X-ray crystallography data. This frustration led him to found Astex Technology Ltd., a start-up that has developed Internet-hosted software called Autosolve for the rapid and automated generation of protein crystal structures.
"At the moment [X-ray crystallography] data interpretation is a huge bottleneck in the process of getting from hits to leads," Jhoti said. "We have developed a system for going from crystals to structure automatically, cutting the data analysis time from weeks to minutes. Crystallography is the gold standard in terms of getting to 3-D structures but it lacks speed. Astex has industrialized X-ray crystallography."
The company, based in Cambridge, UK, was set up only six months ago, and to date has raised #800,000 (US$1.3 million) in seed funding. But it already has signed its first pharmaceutical client, Janssen Research Foundation, of Beerse, Belgium, a subsidiary of Johnson & Johnson. The deal was announced at the European Life Sciences Conference held here last week.
The co-founder of Astex is Tom Blundell, head of biochemistry at Cambridge University, and a world expert on protein structure and function, and structure-based drug design.
Despite ambitions by the pharmaceutical companies to increase output, the number of new chemical entities has remained constant at about 40 per year, at a time when technologies such as genomics are leading to a huge increases in target discovery. "The industry needs to increase the rate of going from hits to true drug candidates, by accelerating the progress of hits and reducing attrition rates," said Jhoti, vice president of research at Astex.
"The proof of concept for using X-ray crystallography is already there. It allows you to image to a high degree of accuracy the way a small molecule binds to a target, allowing you to redesign the molecule to improve it."
Because it currently is a slow, manual process X-ray crystallography is used only in lead optimization, when there already is a good lead compound. Jhoti said Astex has made the technique so fast and easy to use that it could be applied to screening.
The company also has developed Astex Viewer, an Internet-based molecular viewing system. "This sets new standards for ease of use as no special software is required by the client," he said. "Anyone can use this technology to view molecular structures via the Internet, interacting with the structure by rotating, zooming and so on."
Astex is beginning its first round of funding, aiming to raise #10 million to #15 million by the end of 2000. Jhoti said this would be used on equipment, further development of the software, and to commence work on the in-house development portfolio. Although he would give no details, Jhoti said Astex intends to work on several proprietary targets that have been licensed from Cambridge University.
No figures were disclosed, but the Janssen deal involves a "significant financial commitment" with up-front and milestone payments.