Call it the 27-year-old startup: ImmunoGen, one of biotech’s oldest companies, has yet to get a drug on the market more than a quarter century after its formation in 1981. This year may mark a long-awaited turning point for the Cambridge, MA-based company, though. If all goes well, compelling efficacy data will emerge from ongoing Phase 2 trials with ImmunoGen’s cancer drugs, paving the way for pivotal trials that could lead to the FDA-approved promised land. When I dropped by ImmunoGen (NASDAQ: IMGN) last week, CEO Mitch Sayare began by acknowledging that “I’m more optimistic than I’ve ever been” since taking the company’s helm in 1986. But he couldn’t resist adding a verbal version of knocking on wood: “My optimism is tempered by experience.”
He might have said bitter experience: Few cancer therapies have looked as good in theory—and have proved as frustrating in practice—as ImmunoGen’s. Spun out of Boston’s Dana-Farber Cancer Institute, the company has pioneered “immunoconjugates”—two-part medicines consisting of monoclonal antibodies, the guided missiles of biology, chemically attached to highly toxic molecules designed to amplify tumor-killing power. Such drugs can target cancer cells with poisons that are far more potent than traditional chemotherapeutics, in principle enabling tiny doses with relatively minor side effects to knock out tumors.
Unfortunately, for years the approach worked just well enough to lure ImmunoGen down a tortuous dead end. The company spent most of its early life trying to demonstrate efficacy with conjugates employing a form of ricin, a toxin derived from castor beans that’s said to be 12,000 times as deadly as rattlesnake venom. Monoclonals studded with ricin-derived molecules duly “killed targeted cells in patients,” says Sayare. “But what defeated us was ricin’s immunogenicity”—after one or two doses, patients developed immune responses to the ricin-ferrying drugs that cleared them from the blood before they could do any good. “You can’t treat cancer with an agent that you can use only once,” he adds, “because even if you can kill 99 percent-plus of cancer cells with the first dose, there will still be billions left.” ImmunoGen shelved its ricin conjugates in the mid-1990s after more than a decade of work on them.
Such key-project failures have been known to kill small biotechs. Indeed, “there were times in the late ’90s when we came very close to the big pit,” recalls Sayare. “We looked down and were able to walk away.” Pulling ImmunoGen back from the brink … Next Page »
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