Failure isn’t just a possibility in biotech—it’s a probability. Plan accordingly, and don’t let your ego get in the way when you do. It doesn’t matter so much “how” a drug works, as long as it does. And when the inevitable fork in the road comes, don’t be afraid to take the more difficult path—as long as enough of your investors are behind you.
These were just a few of the lessons the speakers at our latest biotech event, “Boston’s Life Science Disruptors,” imparted to a packed house at the Novartis Institutes for Biomedical Research this past week. Attendees got an informal, close-up look at the stories of three Boston startups—Zafgen (NASDAQ: [[ticker:ZFGN]]), Epizyme (NASDAQ: [[ticker:EPZM]]), and Sage Therapeutics (NASDAQ: [[ticker:SAGE]])—and how they navigated the difficult road from a concept to a successful debut on the Nasdaq.
Big thanks to our speakers: Atlas Venture partners Peter Barrett and Bruce Booth; Zafgen CEO Tom Hughes; Bay City Capital managing director Carl Goldfischer and Epizyme CEO Robert Gould; and Third Rock Ventures partner Kevin Starr and Sage Therapeutics CEO Jeffrey Jonas.
Also a special thanks to our event host, Novartis, and our sponsors: BDO, Cubist Pharmaceuticals, Health Advances, Icon, Johnson & Johnson Innovation, and Mintz Levin Cohn Ferris Glovsky and Popeo.
Thanks as well to Tyler Trahan for the photos (more of those to come via a slideshow later this week).
With that, here are a half-dozen highlights from a fun night in Boston:
1. “I remember looking at it and thinking…[it] was probably one of the worst ideas I’ve ever heard in my life.” That was Tom Hughes’s reaction when first approached by the backers of Zafgen. Then in charge of Novartis Institutes for Biomedical Research’s discovery group in cardiovascular and metabolic disease, Hughes got a call from Zafgen’s venture backers in 2006 with this pitch, based on a published paper in Nature: if stopping new blood vessels from forming (angiogenesis) with a drug could shrink tumors, the same approach might work for fat tissue.
Hughes thought it was a terrible idea, but Zafgen over the next few years was able to put together “one of the most compelling datasets I’d ever seen in mice” to back it up. That swayed Hughes to leave Novartis. He later determined the drug’s effect had nothing to do with angiogenesis— it changed the way the body metabolized fat by inhibiting the production of an enzyme called methionine aminopeptidase 2 (MetAP2).
“Whether you dressed it up as an angiogenesis mechanism or not, we were wrong to call it that, but the data were what they were,” said Atlas partner Bruce Booth.
2. A small study, as far away from the FDA as possible. Researchers in the past had tried to develop inhibitors of MetAP2 as an alternative to vascular endothelial growth factor (VEGF) blockers, like bevacizumab (Avastin), for cancer. While those drugs never showed any efficacy, the fact that they’d been tested in humans gave Zafgen a possible development shortcut. But Hughes said that some of the early steps for manufacturing Zafgen’s drug weren’t up to speed; it only had the drug in an IV formulation (rather than a pill); and the underlying paperwork for filing an investigational new drug application with the FDA wasn’t ready. So rather than spending a bunch of money reworking the formulation and getting all the FDA documents ready before getting to the clinic, Zafgen started a very small proof-of-concept study of its IV drug in Australia, which “had a process to allow that to occur,” Hughes said.
The study was a success, and Zafgen parlayed it into more venture financing, sending the startup down the path towards becoming a public company—all while saving some cash and development time.
“This is a great example of the power and impact of being nimble,” Hughes said. “Some things [here] we never would’ve done if we were a big company.”
3. Epizyme: Robert Gould’s chance for redemption. Gould, a longtime Merck executive, was working at the Broad Institute of MIT and Harvard when he got a call from former Merck colleague (and Kleiner Perkins Caulfield Byers partner) Beth Seidenberg about a new company she was helping to put together based around epigenetics—switching genes on or off without affecting the underlying DNA. The idea resonated with Gould. He’d spent decades in drug discovery, but stayed away from kinase inhibitors—which have become fertile ground for cancer drugs.
“One of the great regrets in my life is I personally sort of totally missed the entire kinase inhibitor world,” he said. “How could you ever interfere in something as fundamental as cell signaling safely and effectively? [I] just missed the boat on that totally.”
Epizyme, he said, constituted
