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Innovation Economy

One of biotech's brightest players is now a free agent

In September, when Elixir Pharmaceuticals Inc. said it intended to raise $86 million in an initial public offering, one name was conspicuously missing from the company's filing: Lenny Guarente, the Massachusetts Institute of Technology professor who cofounded Elixir in 1999.

Some think that Guarente's scientific work could one day win a Nobel Prize. So it was odd he'd resigned from Elixir exactly a year earlier.

Elixir is one of two Cambridge companies founded to commercialize the science behind the mechanism that makes humans age and doles out diseases like diabetes, cancer, and Parkinson's along with our decrepitude. The other company is Sirtris Pharmaceuticals Inc., which went public last May, raising $60 million.

Not coincidentally, Sirtris is now romancing Guarente. Now that Guarente's one-year noncompete agreement with Elixir has expired, Sirtris chief executive Christoph Westphal has been trying to lure him onto Sirtris's scientific advisory board.

Westphal said the company is interested in Guarente because "everyone who's a leader in the sirtuin space," the area of science both Elixir and Sirtris were founded to explore, is on Sirtris's advisory board. "I think Lenny's going to win the Nobel Prize some day for finding genes related to the aging process," said Westphal, a former venture capitalist who sports a PhD and an MD, but is not a master of understatement.

The rivalry between the two companies has been endlessly explored in the press.

Elixir was founded first, by Guarente and another researcher at the University of California at San Francisco, Cynthia Kenyon. Kenyon was looking at a gene that seemed to extend the lifespan of worms, and Guarente was studying yeast. Guarente honed in on a gene known as Sir2 (its name led to the term "sirtuins," which describes a group of enzymes produced by genes like Sir2) and invited David Sinclair, a researcher he'd mentored, to join the company.

Sinclair passed, but later joined Westphal, Alkermes Inc. chairman Richard Pops, and others to start Sirtris.

Elixir raised a phenomenal amount of private capital in its hunt to find chemicals that would be able to dial in human sirtuin levels, ideally having an impact on age-related diseases. Guarente believes tweaking sirtuin levels may mimic the effects of drastic calorie restriction - without requiring you to eat less - which has been shown to produce older, healthier mice.

No one thought it would be wise to design a Food and Drug Administration trial to prove the company discovered a drug that extended human lifespan; that would take too long. But Guarente and others at Elixir alluded to the possibility of a few extra years as a pleasant potential side effect.

In the company's recent filing with the Securities and Exchange Commission, Elixir said it racked up $82 million in losses since its founding in 1999. Much of that was fronted by Oxford Bioscience Partners and MPM Capital, two Boston-based venture firms.

But over time, Elixir's backers began to get impatient with how long it was taking to discover drugs that might have an impact on sirtuins. (Red wine contains a substance called resveratrol that can activate sirtuins - but in too small a dose to be useful.) So Jonathan Fleming and Ansbert Gadicke, two venture capitalists who served on Elixir's board, decided to bring in a new chairman and CEO who had more experience getting drugs to market quickly.

Vaughn Kaillian, former chairman of Millennium Pharmaceuticals, became Elixir's chairman. And in 2004, William Heiden, a former Schering-Plough executive, became CEO. Slowly, work related to the sirtuins was shifted to the back burner.

Last year, Elixir licensed a diabetes drug already approved in Japan, Glufast, with an intention of getting it blessed in the United States by the FDA. Glufast helps lower the high glucose levels diabetics can experience immediately after eating. Elixir's plan is to build its own sales force to market the drug.

Sirtris, meanwhile, was branding itself as the "leading sirtuin therapeutics company" and hurtling toward an IPO.

But some in the local life sciences industry, including Elixir's backers, grumble that Sirtris went public based on scant clinical data. Sirtris's first drug candidate, dubbed SRT501, is a proprietary formulation of resveratrol - far more concentrated than what you'd get from a couple of cases of red wine. It's currently being tested in India on patients suffering from Type 2 diabetes whose blood sugar levels aren't well-managed by currently available drugs in a trial that should last through the end of 2008.

Sirtris also has no alliances with major drug companies, a normal way for young biotechs to bring in early revenue. But Westphal says that is part of the plan, explaining the company wants to prove it has found drugs that can affect sirtuins, and then establish partnerships when the company has better negotiating leverage.

Coincidentally, Sirtris is headquartered in a building that was once home to Alnylam Pharmaceuticals, a company Westphal helped start while he was at Polaris Venture Partners. Alnylam went public by scooping up many of the researchers and much of their intellectual property related to RNA interference, an approach to blocking the effect of the genes that trigger diseases. This included work done by Craig Mello and Andrew Fire, who shared last year's Nobel Prize in medicine.

"Christoph's playbook is a direct copycat of the Alnylam playbook," says a person close to Elixir. "He can go tell the world that he's got all the important players."

Over the last three years, Guarente had been getting frustrated that Elixir wasn't interested in his latest patents. The company, as he saw it, was getting "very conservative," focusing most of its resources on Glufast.

And, he says, when he'd file a new patent, it was Sirtris, not Elixir, that was licensing it from MIT. But Elixir wouldn't allow Guarente to consult for Sirtris, so he resigned from the company.

"I just really wanted to do something more adventurous," he says. An arrangement with Sirtris hasn't been finalized, and Guarente says there's a chance he might create a new start-up instead.

But just as he was when founding Elixir, Guarente is still convinced that sirtuins have huge potential. And potential, whether grand or mundane, is what fuels the biotech industry.

"What's emerging is that extending life and forestalling diseases are coupled," Guarente says. "If you have a drug that will do the first, it'll also do the second."

Innovation Economy is a weekly column focusing on entrepreneurship, technology, and venture capital in New England. Scott Kirsner can be reached at

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