Innovation: Tech Pioneers

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Jennie Mather left biotech company Genentech also out of frustration when, she says, her bosses wouldn't accept her approach to fighting cancer. She argued that what really counts in a target protein--that is, a protein that causes a disease and that a drug would aim to disable--is the protein's surface. Because a body's natural antibodies do their work entirely on the cell's exterior, she reasoned, drugs should work the same way. Such thinking was heresy to Genentech, whose scientists, she says, generally analyze a target's entire genetic structure. "They were just interested in genomics," she says. "There are 500 to 1,000 genes in a disease--the problem is, it takes a long time to understand what 1,000 genes do."

Genentech says it pioneered the use of antibodies that target the surface protein of cancer, and its popular drugs work on that principle. Nevertheless, Mather saw a way to carve several years out of drug development and left to found Raven Biotechnologies, a drug-discovery company based in South San Francisco. She created a process to keep cells alive outside the body, so she could test her theory in the lab. Her efforts paid off. In December the U.S. Food and Drug Administration approved one of her drugs for human testing. The drug, called RAV 12, is a protein that in the dish destroys another protein found in 90% of all gastrointestinal cancers and in 50% of all breast, lung and prostate cancers.

Similarly, Harren Jhoti left pharmaceutical giant Glaxo Wellcome (now GSK) in 1999 when he realized that his unconventional idea of how to find new drugs to attack disease-causing proteins might never be realized unless he pursued it himself. He founded Astex, based in Cambridge, England, so he could develop his own flexible approach to molecular research. He calls it "fragment based," because rather than throwing an entire proposed drug molecule at the target protein, he throws just pieces at a time.

Jhoti and four of his scientists hit the pub when they had their eureka moment. In October 2002 their advanced X-ray and crystal technique revealed that a chemical was binding to a protein that is a possible cause of Alzheimer's disease. The chemical was a fragment of what could eventually become an Alzheimer's-conquering drug. "I first thought the team had played a trick on me," says Jhoti. Drug giant AstraZeneca, which had been searching for such a chemical for years, enlisted Astex's help. In 2003 the company signed a contract to pay Astex $40 million if Astex hits milestone breakthroughs and to make royalty payments once AstraZeneca sells drugs based on Astex's technology. "AstraZeneca worked on it for four years. We delivered an early candidate within a year of signing with them," says Jhoti. He also hopes to win regulatory approval to begin testing a general anticancer drug in the first half of 2005.