Epizyme, Riding High on Two Big Pharma Deals, Zeroes in on Personalized Cancer Therapy

Xconomy Boston — 

Big Pharma companies are not exactly known for being nimble, but they have made a couple of quick bam-bam moves in succession to land deals with Cambridge, MA-based Epizyme.

The company made news in January when it pocketed $20 million upfront, and lined up another $630 million in development milestones, through a drug discovery partnership with London-based GlaxoSmithKline (NYSE:GSK). Two months later, Epizyme delivered an encore, with a new partnership worth $6 million upfront and another $200 million in milestones from Japan-based Eisai Pharmaceuticals, to develop cancer drugs against a specific biological target. Suddenly, it was time to look for a new office with double the space.

Those are all pretty encouraging signs of progress for a biotech company that’s barely three years old. It’s also an indication of enthusiasm for epigenetics, an emerging field of science that looks at how certain genes can be turned on or off without altering the underlying DNA. Instead of using chemotherapy that kills all kinds of fast-dividing cells, or a targeted cancer drug that rifles in on one specific mutant protein, Epizyme’s idea is to turn off the activity of a specific enzyme that basically makes it possible for multiple genes and proteins to spin out of control in cancer patients.

“These genes are really part of an orchestra,” says Epizyme’s chief business officer, Jason Rhodes. “We can influence the entire orchestra.”

The proof, like with anything in biotech, will be in the clinical trials, which aren’t here yet. But the Epizyme approach has some obvious appeal in that it’s going after biological targets that have only been well characterized, and clearly implicated in cancer, for a few years. The epigenetic targets are also enzymes, which means that scientists ought to be able to synthesize conventional small-molecule drugs that bind very specifically with these 3-D structures, Rhodes says.

It will still probably be “a couple years” before Epizyme finishes all the work it needs to bring its first drug into clinical trials, CEO Robert Gould says. And, like you’d expect from a scientist, he knows a lot of things can still go wrong: “There’s still a long, rocky road between where we are to the clinic,” he says. Plus, Epizyme isn’t the only company out there in hot pursuit of epigenetic drug targets—Cambridge, MA-based Constellation Pharmaceuticals is one notable competitor.

From left: Jason Rhodes, chief business officer of Epizyme, and Robert Gould, president and CEO of Epizyme.

In some ways, Epizyme represents a “quintessential biotech story,” says Richard Pops, the CEO of Alkermes (NASDAQ: ALKS) and a member of the startup’s board. Epizyme, he says, has all the classic ingredients of exciting science, top-notch people involved, and experienced VCs willing to push a project way out ahead of Big Pharma. While that might be exciting for a while, it doesn’t last, which is partly why the last few months have been important at Epizyme.

“As it came together we saw it as a higher risk/return company than was fashionable at the time,” Pops says. “Now, with the progress and validation of the deals, it is becoming more and more concrete.”

The GlaxoSmithKline deal was particularly important, both to bring in cash and to help the company build out its pipeline to hedge its bets. The Glaxo deal is set up to support research against a certain number of biological targets, which aren’t being disclosed, for the treatment of cancer and other diseases. But Epizyme made sure it didn’t give away the entire store to Glaxo. Epizyme got support for its research, while retaining full ownership of its two most advanced drug development programs.

One of those programs is directed against a target known as DOT1L, and the other is called EZH2. Holding onto EZH2 meant that Epizyme was in position to negotiate a deal with Eisai on that target alone. In that deal, Eisai will pay for all development until a drug candidate against that target generates proof that it works in humans. At that point, Epizyme has the right to opt in to a 50-50 profit sharing deal in the U.S.

The headlines were a nice sign that things are on track. But Gould was also quick to point out yesterday that headlines are fleeting, and now it’s time for the company to execute. Both he and Rhodes say they have had a lot of interest from other prospective partners, but they aren’t interested in doing more deals just for the sake of doing more deals and looking good in the news.

“We’re not following a partnering business model,” Rhodes says. “We’ll be deliberate with the deals we make. It’s easy to get on a treadmill, and do a number of deals, and feel like you’re making progress.”

Cash is the key ingredient here that gives Rhodes and Gould the ability to tell partners “thanks, but no thanks.” Epizyme isn’t saying how far its existing cash reserves will last. But the company raised $54 million combined in 2008 and 2009 from a crew of venture backers that includes New Enterprise Associates, Bay City Capital, MPM Capital, Kleiner Perkins Caufield & Byers, Amgen Ventures, and Astellas Venture Partners. Most of that money remains unspent, Rhodes says, and Epizyme has pulled in $28 million in cash from its partnerships. The company now plans to grow from about 30 employees to some number in the “mid-40s” by year-end, Gould says, to get the organizational bandwidth it needs to really hit its milestones.

Once Epizyme can hit a few of those milestones, and tee up its first program for the clinic, it could deliver some pretty clear answers pretty quickly, Rhodes says.

The vision here is to enroll patients with a certain pathological form of cancer—say, breast cancer—and take blood or biopsy samples that will enable researchers to divide patients into separate groups, one for those who have an overactive form of the given epigenetic enzyme, the other for those who don’t. If the drug works like it’s supposed to—really well for the specific epigenetic population in mind—that would be a huge win. One company that had this kind of personalized strategy—Berkeley, CA-based Plexxikon—was acquired for up to $935 million about six months after publishing some very promising results in a genetic subpopulation of patients with melanoma that had spread through the body. Another closely watched cancer drug in the works, Pfizer’s c-Met and ALK inhibitor, is designed to get after a clearly defined genetic population of cancer patients.

Who knows if Epizyme will ever deliver results like that, but that’s at least the playbook it is following. The plan here isn’t to do what most cancer drug developers do—go after a relatively vaguely defined form of cancer based on its organ of origin, give it to all comers in a clinical trial with the related form of cancer, and hope that 25 or 30 percent will respond to therapy. Epizyme, by looking at how epigenetic profiles of patients differ, hopes to generate a much higher percentage of responses in the initial patients, which ought to be highly predictive of what happens when the drug enters much bigger clinical trials.

“We’re going into defined patient populations. If you think of Pfizer’s ALK inhibitor, or Plexxikon’s B-raf inhibitor, they generated very compelling data relatively early,” Rhodes says. “That’s the kind of path we’re likely to go down as well.”

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