BioWorld International Correspondent
LONDON - Astex Technology Ltd., a pioneer of high-throughput X-ray crystallography, raised £22.7 million (US$32.6 million) in the largest first-round venture funding to date by a UK start-up company.
Tim Haines, CEO of Astex, told BioWorld International the financing pulled in "more money than we originally planned, and we had to turn some away. We had more people chasing, and the pie wasn't big enough to satisfy all requests."
Haines said interest was high because of the recognition of the value of protein structure in drug discovery, since the sequencing of the human genome.
"Sequencing the genome means there is no shortage of targets," he said. "The real limiting factor is converting targets into new chemical entities. While there are far more targets, there is significantly less information about them. This is leading to higher attrition rates. One analysis showed there are four times as many targets going through, causing attrition rates to rise, from one in 10, to one in 14."
Astex, based in Cambridge, said it has industrialized X-ray crystallography. It has developed techniques for producing proteins and crystallizing them, along with a system for going from crystals to structure automatically - thus cutting the data analysis and interpretation time from weeks to minutes.
The company also disclosed a research collaboration with London-based AstraZeneca plc, focused on elucidating the structure of P450 cytochromes. These are the most important group of enzymes involved in drug metabolism. Since this link was established in the 1970s, many drugs have been withdrawn from the market, or have failed clinical trials, due to adverse side effects caused by interaction with these enzymes.
Once Astex has solved the structures, AstraZeneca will be able to check how its compounds interact with the enzymes and tweak them accordingly. AstraZeneca is the first partner for the P450 program, but Haines expects to sign other large pharmaceutical partners.
"The beauty of this program is that it is pre-competitive," Haines said. Pharma companies will send us their compounds, and we will tell them how they bind to P450."
As well as helping in drug discovery, Haines said the technique could be used to rescue compounds that failed because of side effects. Astex has recruited Jos Cosme and Pamela Williams, who were involved in solving the first crystal structure of a mammalian P450 cytochrome, to lead the P450 program.
To date, Astex has produced crystals of two of the enzymes, and expects to solve the structures by the end of this year. "There is a race to solve and patent protein structures," Haines said. "We believe our technology gives us a significant lead over other companies."
Astex was established in 1999 with £800,000 seed funding, and subsequently raised £3.3 million in the form of a loan. The new investors are Advent International, of Boston; Alta Partners, of San Francisco; and GIMV, of Antwerp, Belgium.
The company was founded by Harren Jhoti, a former head of structural biology and bioinformatics at London-based-GlaxoWellcome plc (recently merged with SmithKline Beecham), who is CSO, and Tom Blundell, head of biochemistry at Cambridge University, and an expert on protein structure and function and structure-based drug design.
X-ray crystallography, because it was previously a slow, manual process, which required experts to interpret the X-ray images, was used only in lead optimization, when there was already a good lead compound. Astex claims it has made the technique so fast and easy to use that it now can be used earlier in the lead-optimization process, and can be applied to lead discovery.
Haines said much of the new money would be devoted to recruiting staff, with the aim of growing the company to 150 by the end of 2001. It also will buy two more X-ray crystallography machines at around US$500,000 each, doubling the current capacity.
Astex also will build an internal drug discovery capability, concentrating on five targets it has discovered, he said. "We can go from gene to crystal, and then use that to come up with [new chemical entities], at which point we will partner," said Haines.
The money raised in this first round will last two to three years, by which time the company should be self-financing. Haines said he hopes to be in a position to do an initial public offering at that time.