New Constellation Pharma CEO Gives Expected Timeline for Epigenetics Firm’s Cancer Drug Research

9/1/09

For all of the publicity it’s gotten lately, Constellation Pharmaceuticals has managed to keep a remarkably tight lid on the specifics of its research. So I was enthused when the Cambridge, MA-based firm’s new CEO, Mark Goldsmith, gave me some insights into where the firm stands in advancing potential drugs in the emerging field of epigenetics.

In quick review: epigenetics is the study of the molecular changes in cells that can activate or mute certain genes without changing the underlying DNA code—for example, by affecting the way DNA strands are folded. Constellation is a company to watch in epigenetics, in part because the startup has raised an impressive $32 million in Series A venture capital since launching in April 2008. And Goldsmith, a physician and scientist by training with both research and industry chops, is the latest of a string of impressive biotech veterans to get behind the fledgling company. (Goldsmith also filled me in recently about his early experience taking the reins at Constellation from Mark Levin, the firm’s founding CEO and chairman, who was CEO of biotech powerhouse Millennium before co-founding Boston venture firm Third Rock Ventures in 2007.)

Constellation, which plans to initially develop drugs for cancer, is so early in its research that it hasn’t decided on a compound to test in clinical trials, according to Goldsmith. The CEO told me that he expects the firm to choose one or more drug candidates for pre-clinical testing (which would include animal studies) by the end of next year, meaning that the company is at least a couple of years from its first real-deal human trial. He was mum, however, about which specific types of cancer the firm hopes to treat.

“At this time we’re not disclosing the specifics for a number of reasons,” Goldsmith said. “But I’d say a couple of things that differentiate us include selecting highly specific DNA modifiers as drug targets and within that we are looking at a variety of different enzymes that encompass these genetic modifications.”

There are multiple classes of enzymes that play a role in epigenetics, but Goldsmith declined to say which ones are of interest to Constellation. He did say that the most oft-targeted enzymes in this category, histone deacetylases (HDACs), aren’t a high priority for Constellation. Because the company hasn’t been forthcoming about the details, it’s unclear how its science differs from that of its Cambridge epigenetics rival, EpiZyme. EpiZyme CEO Kazumi Shiosaki told me early this year that the firm planned to focus on cancer drugs that home in on histone methyltransferases (HMTs), and her plan was to identify compounds for specific epigenetic targets by the end of this year. Shiosaki said the firm hoped to develop drugs to treat blood cancers such as leukemia and solid tumors.

Goldsmith did talk to me about what it’s been like to take the helm at Constellation, which has been largely run by members of its founding VC firm, Third Rock, including founding CEO Levin, who is still chairman of the company, and Third Rock partners Neil Exter, Craig Muir, and Robert Tepper. Goldsmith—who came to Constellation after a stint as senior entrepreneur-in-residence at Prospect Venture Partners in Palo Alto, CA—said that after seeing the progress that Constellation has made, he’s become a believer in venture firms supplying both capital and executive manpower to their portfolio companies. Constellation has already built a staff of 32 scientists here and 15 more contract researchers in China, and Goldsmith said he’s impressed with the quality of the staff and the high level of standards in place.

Mark Goldsmith, CEO of Constellation Pharmaceuticals

Mark Goldsmith, CEO of Constellation Pharmaceuticals

“Mark Levin is experienced at transitioning leadership at companies. He did so at Millennium, and I’ve been looking to him for guidance,” Goldsmith said. “I really am motivated to build upon the success of the first year—this is not a company that is in distress and needs to be fixed.”

Goldsmith’s last operational executive role was as CEO of Cogentus Pharmaceuticals, which reportedly filed for bankruptcy in January after raising $83 million in private capital, according to VentureBeat. The Menlo Park, CA-based company, launched in 2006, had been gearing up for a late-stage clinical trial of a blood thinner that was supposed to reduce the gastrointestinal side effects of such treatments. But the company was unable to raise money for the expensive clinical trial during the peak of the financial crisis last fall, Goldsmith told me in an e-mail.

Constellation recently closed on the last $17.2 million of its $32 million first-round financing, and Goldsmith said that the cash should last into the second half of 2010. He noted, however, that the company has no fixed burn rate and that time frame could change. Meanwhile, he said that he expects that over the next year the startup will land a corporate partnership with a pharmaceutical player that could also provide funds to support the company’s operations.

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