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Unfocused Elixir seeks new life

A Cambridge company searching for the secrets to human longevity, Elixir Pharmaceuticals, has suddenly seen its own time horizons shortened. The company's investors, it seems, don't have the patience to keep funding Elixir while it searches for the fountain of youth. They'd settle for a bottle of Evian -- and preferably sooner, rather than later.

The 30-person biotech has been a media darling because of its ambitious goal: to leverage scientific breakthroughs that involved the ways yeast and worms age, all in the hopes of coming up with drugs to fight age-related diseases in humans. Elixir expected its drugs to have a very nifty side effect -- tacking on a couple extra healthy years to your life.

The company had two high-profile founders, Lenny Guarente from MIT and Cynthia Kenyon from the University of California at San Francisco, and it has raked in nearly $55 million in venture capital funding to date. But star scientists, major funding, and big ambitions can sometimes result in a lack of focus. And a merger last year with another Cambridge company interested in longevity, Centagenetix, hasn't clarified things much.

Now, the challenge for Elixir is the same one that faces every young biotech: Can it survive long enough to bring a new drug into the world?

In March, the company's first chief executive, Ed Cannon, departed. He has been replaced temporarily by Vaughn Kailian, formerly the vice chairman of Millennium Pharmaceuticals. Kailian is also serving as the company's chairman but didn't want to permanently assume the chief executive job at Elixir. (A new chief executive will likely be announced soon.) The company is putting on hold several of its internally cultivated drug candidates in favor of a drug developed elsewhere that's perceived to be closer to approval, known as ''in-licensing." That could mean a drug that has been through some kind of clinical trial, or even one that has been approved by the Food and Drug Administration.

Both company execs and Elixir's venture capitalists would prefer to downplay the significance of this year's strategic shift. Kailian likens it to ''clearing away some of the underbrush."

''I wouldn't call it repositioning," says Ansbert Gadicke, founding general partner at MPM Capital in Boston, ''I'd call it forward integration." What on earth is that? Gadicke defines forward integration as bringing in ''assets that are closer to the market, so the company would have a shorter time to get to the market and have sales. Then they could fund their own research from revenues." That is, when you're wandering in the desert hunting for the fountain of youth, finding a bottle of Evian can be a good thing.

But Peter DiStefano, the company's chief scientific officer, says that what's happening at Elixir is ''a massive overhaul in our strategy." While the company's early focus was in assembling a war chest of intellectual property related to the aging process, ''we've morphed away from our 'genetics of aging' roots," DiStefano says. Collecting information about the aging process, which seemed like a good strategy when Elixir and Centagenetix were founded, isn't seen as a smart strategy today.

Still, DiStefano emphasizes that any drug candidate the company licenses from another player would be linked to Elixir's base of knowledge, which relates to two different biological circuits, known as DAF-2 and SIR2, discovered by Kenyon and Guarente. Both circuits are thought to have evolved to enable animals to survive through times when food was scarce, helping them store fat. But for humans living in an era when food is plentiful, that mechanism backfires.

''What we're trying to do is turn that [mechanism] down, so you don't create these massive fat stores and run into insulin resistance and obesity and all the other bad things that happen when you accumulate too much fat," DiStefano says. Such a drug could treat Type 2 diabetes, obesity, or other metabolic diseases. But by preventing the body from stockpiling fat, it could also mimic the effects of a restricted-calorie diet, which many believe is a key to a lengthy life span. (Advocates of caloric restriction consume as few as 1,000 calories a day, suffering from chills and diminished sex drive; a pharmaceutical approach might eliminate those side effects.)

While the venture capitalists who initially funded Elixir (and Centagenetix) were enchanted by science that seemed to point the way to longer life, now they want a drug that will address a known disease in a reasonable time frame.

''I'd rather see the company at break-even in a few years, rather than many years," Gadicke says. He's the one who tried to bring on Kailian as Elixir's chief executive, and he says the person who eventually fills that role will have ''significant commercial experience."

Guarente, one of the company's three founders, understands the necessity of creating cash flow in the near term. ''If you can do that, it helps everything else," he says. But he acknowledges that in-licensing a drug, tinkering with it, and trying to push it through clinical trials could distract from Elixir's own internal drug-discovery programs.

Another distraction was the Centagenetix merger. That company built a database of information and genetic samples from people who had lived past 100, in the hopes of arriving at insights about the aging process. DiStefano concedes that ''we haven't used it extensively," but says the database is a valuable asset. Guarente says it is ''an open debate as to how best to use that." Gadicke implies the company will soon be ready to unveil its plan for wringing revenue from the Centagenetix database.

In a sense, every company must at some point surrender some of its promise as it moves toward a real product. But for Elixir, a company founded to continue the centuries-long quest for an antidote to aging, that transition has been much more pronounced. Kailian says that Elixir will no longer be a ''pure research-driven company." His twin mottoes these days are ''conservation of capital" and ''focus."

What needs to happen next for Elixir: a new chief executive, a new round of investment to support an in-licensing program, and a plan to get some money out of the Centagenetix assets. Two out of three wouldn't be bad. But the company needs to regain some momentum -- soon. It's not getting any younger, and its investors aren't getting any more patient.

Scott Kirsner is a contributing editor at Fast Company. He can be reached at skirsner@verizon.net. 

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