Wednesday, November 28, 2007

Sirtris Strikes Again

In a short paper to appear in tomorrow’s Nature, scientists at Sirtris Pharmaceuticals describe the in vitro and in vivo data supporting the development of their next-generation activators of Sirt1, one of the members of the sirtuin family of proteins. It’s another opportunity for their persistent PR machine to talk up the company’s founding premise: that activating sirtuins, which appear to play a role in the aging process, may be useful in treating a variety of things, including diabetes.

Unlike its first drug, a formulation of resveratrol (a Sirt1 activator found in red wine, which is now in early-stage trials), Sirtris found the molecules analyzed in the Letter to Nature by specifically screening for activity against Sirt1. “From a pharmacological perspective, we’ve proved the mechanism,” Sirtris CEO Christoph Westphal said yesterday in a phone interview.

The next-generation Sirt1 program, along with its development of other sirtuin activators, puts Sirtris firmly in the lead in sirtuin field. So much so that Lenny Guarente, the scientific founder of rival company Elixir Pharmaceuticals (now in registration for an IPO), whose discovery that the sirtuin-expressing gene sir2 is an important regulator of life span in several species, has jumped from Elixir to the Sirtris Scientific Advisory Board.

For years, Guarente and Sirtris co-founder David Sinclair, a former member of the Guarente lab, were estranged. And while some news outlets cast Guarente’s bolting as validation for Sirtris -- and it IS a good story -- it’s at least as much a reflection of Elixir’s affirmative determination several years ago that sirtuin-related drug development was just too early to support a company, leading to the in-license of an oral diabetes drug from the Japanese pharma Kissei in March 2006 and an early-stage growth hormone stimulator (a ghrelin agonist) from Bristol-Myers, both of which Elixir’s S-1 rank ahead of its sirtuin program.

No doubt Elixir abandoned Guarente a long time before he actually split. And the circumstance could have been predicted as far back as 2004, when Vaughn Kailian, ex of Millennium Pharmaceuticals and Cor Therapeutics, became Elixir’s Chairman. Kailian, a general partner at MPM Capital who focuses on late-stage investments (and also – DISCLOSURE, DISCLOSURE -- is a director of Windhover Information, IN VIVO’s publisher), is well known for advocating the rapid build-up of commercial capabilities. Indeed, during his tenure at Millennium, the competing interests of research and commercialization created a duality of cultures: what IN VIVO described at the time as “The Two Millenniums.”

Sirtris continues to build its sirtuin platform and expects to bring the first next-generation Sirt1 activator into the clinic in the first half of 2008. It's also got the benefit of buzz from frequent scientific publications in the evolving sirtuin field -- including their link to cell survival/protection mechanisms, which we discussed in the Science Matters column in START-UP a few months back -- as well as the elucidation of the roles of other anti-aging genes/proteins.

That said, it'll be interesting to see if the momentum lasts as it approaches the challenges of later-stage clinical trials.

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