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Epizyme Unveils Technology, Targeting Cancer with Epigenetic Drugs

Xconomy Boston — 

Despite being forthcoming about its big-name venture backers—MPM Capital and Kleiner Perkins Caufield & Byers—Cambridge, MA-based Epizyme has been one of several biotech startups in the Boston that are being demure about the details of their technology. So I was intrigued when the company contacted me recently to let me know that it was lifting the curtains on its bold plans to make “epigenetic” drugs to combat blood cancer and tumors. And two founders also filled me in on the genesis of the company, which began during an MPM meeting in South San Francisco nearly two years ago.

Epigenetics involves enzymes and other molecules in the body that turn genes on and off without changing the underlying DNA code. Whitehouse Station, NJ-based drug giant Merck (NYSE:MRK) markets an early FDA-approved epigenetic treatment, the lymphoma drug vorinostat (Zolinza), which works by inhibiting one such type of enzyme, called histone deacetylases. Now Epizyme is embarking on an effort to discover drugs that target a different class of epigenetic enzymes known as histone methyltransferases (HMTs), company CEO Kazumi Shiosaki, who is also a managing director at MPM, tells me.

Epizyme is initially focused on developing drugs that knock out certain ones of these enzymes that are believed to either turn off cancer-fighting genes or activate genes that promote tumor survival. There are an estimated 70 HMTs, Shiosaki says, and among them are also potential targets for treating inflammation, neurological disorders, and other diseases. Yet it’s still early days for the company, which is in the process of selecting chemical compounds that could be developed as drugs to home in on these epigenetic enzymes. And there are several years of work to do before the firm tests the drugs in humans, the CEO adds.

“We have a very good understanding of the fundamental biochemistry that these enzymes operate under,” Shiosaki says, adding that this understanding puts the company in a strong position to identify drugs that target HMT enzymes.

Indeed, Epizyme has licensed technology from the lab of company co-founder Yi Zhang, a professor of biochemistry at the University of North Carolina at Chapel Hill, who has done extensive research on histone methyltransferase enzymes. The company is working on building an estate of patents related to these enzymes, though company officials believe they have competition on this front. Constellation Pharmaceuticals, a fellow epigenetics startup in Cambridge, was co-founded by another scientist who has been studying this enzyme class, Danny Reinberg, a professor of biochemistry at New York University School of Medicine. Constellation’s chief business officer, Neil Exter, didn’t return a phone message last week, though, and it’s still a bit of a mystery whether the startup plans to develop drugs targeting the same enzymes as Epizyme.

At both Epizyme and Constellation, venture capitalists are making a big bet on science that is largely unproven in human clinical trials. But the bet could prove to be well worth the risk because of the tremendous value that could be built in translating cutting-edge science into a new generation of drugs.

Indeed, that was the frame of mind at MPM when the firm held a meeting in the summer of 2007 to discuss exciting investment opportunities in the field of oncology. The room at MPM’s office in South San Francisco was packed with some heavy hitters in the field, recalls Epizyme co-founder and MPM managing director Ashley Dombkowski, including the chair of MPM’s scientific advisory board, H. Robert Horvitz, an MIT biology professor and Nobel Laureate. (MPM last year provided Luke with some insights on that meeting, in which Epizyme was first conceived.)

“We brought together folks from a lot of different areas that we thought would be interesting for starting new companies—and we were thinking big and broad,” Dombkowski says. Along with epigenetics, the MPM meeting focused on other areas of interest such as cancer stem cells.

But epigenetics rose to the top after Zhang, who had been invited to talk about his research at UNC, gave his presentation. “Yi brought the house down,” says Shiosaki, who was also at the meeting. Inspired by Zhang, Horvitz approached the younger scientist and asked him if he wanted to start a company. (Horvitz and Zhang are the scientific co-founders of Epizyme.)

After the meeting, Dombkowski says, she brought the idea for the company to Brook Byers and Beth Seidenberg at well-known venture firm Kleiner Perkins Caufield & Byers in Menlo Park, CA. It turned out that Kleiner Perkins had been looking into making an investment in the epigenetics field and Epizyme fit the bill. MPM and Kleiner Perkins joined forced to raise an undisclosed amount of money in a first-round financing for the startup in early 2008. Seidenberg and Dombkowski are on the board of directors, which includes industry heavyweights such as Richard Pops, chairman of Cambridge, MA-based biotech Alkermes (NASDAQ:ALKS), and Robert Gould, who heads the novel therapeutics program at the Broad Institute of MIT and Harvard.

Last summer and fall, Epizyme added two senior-level scientific executives to its team: chief scientific officer Robert Copeland, a former vice president of the cancer drug discovery group at London-based drug giant GlaxoSmithKline, and Victoria Richon, vice president of biological sciences, who was one of the scientists who discovered Merck’s epigenetic drug vorinostat as a researcher at Memorial Sloan-Kettering Cancer Center.

Today, Shiosaki says, the 12-person company is focused on discovering drugs to target two HMT enzymes. One of the enzymes is believed to play a role in “liquid cancers” like leukemia, and the other in solid tumors. Her goal is to have identified drug candidates for these two epigenetic targets by the end of 2009.