Antibodies that can zero in on specific diseased cells are some of the biggest-selling and fastest-growing fields in all of biotech. Yet after three decades of R&D, if you talk to people who try to discover these things, they’ll tell you it’s a long and risky slog to get any good candidates for clinical trials. San Francisco-based Ablexis is betting that it has created a more effective way to generate promising antibodies, and revamped its business model to try to generate real cash.
The company made some news earlier this month when it attracted a $12 million financing from Boston’s Third Rock Ventures and New York-based Pfizer Venture Investment. The Third Rock team, which consists of well-known biotech executives like Mark Levin, Bob Tepper and Cary Pfeffer, is doing their usual roll-up-the-sleeves-and-get-involved routine along with CEO Larry Green, a co-inventor of a pioneering antibody discovery technique of years past, the Abgenix Xenomouse. I heard more about the company’s strategy during a chat with Green when I was in San Francisco a couple weeks ago to prepare for the launch of Xconomy San Francisco.
The idea of antibody drugs that can specifically zero in on diseased cells, while mostly sparing healthy ones, has captivated the imagination of scientists and biotech investors since they were first discovered by Georges Kohler and Cesar Milstein in 1975. It took more than two decades for the idea to be translated into real products. But over the last decade, antibodies have become one of the backbone technologies of the life sciences industry. The antibody drug market was expected to generate $30 billion in worldwide sales in 2009, with an annual growth rate of 14 percent through 2012, according to Datamonitor.
But there have always been major technical challenges with these Y-shaped proteins. The earliest engineered antibodies came from mouse DNA. When these drugs were injected into people, the human immune system often identified them as foreign, creating severe side effects. That gave rise to years of effort to “humanize” the antibody drugs, so they wouldn’t provoke a nasty immune reaction. The work of companies like Protein Design Labs, Abgenix, and Medarex who plugged in certain snippets of human DNA to make these drugs more palatable became one of the key enabling technologies underpinning many of today’s successful antibodies, like Roche’s trastuzumab (Herceptin) for certain forms of breast cancer.
But Ablexis, Green says, still sees plenty of room for improvement and a major business opportunity for anyone who can seize it. Many of the prior “humanization” technologies have been acquired by big drugmakers who have made it more difficult for them to be widely used throughout the industry, Green says. And the existing technologies often force highly-skilled molecular biologists to do all sorts of tinkering with the antibodies to make them “humanized,” which can often introduce new characteristics into the antibodies that make them less potent binders against the desired targets. That’s a serious problem, because if a drug isn’t potent enough, its less likely to work at the desired doses.
Green was pretty coy when I pressed him about exactly what Ablexis is doing that’s new and truly innovative. It is clear that Ablexis is creating genetically modified mice that are intended to churn out a wide diversity of fully-human antibodies against a certain target. Instead of creating these antibodies in a lab dish, or even something futuristic like on a computer, the product that Ablexis sells to Big Pharma customers is an actual mouse. These mice, in all the vast complexity of their live immune systems, will be able to offer a better guide to antibody discovery teams as they try to pick
