Sirtris Inc., which moved like a shot from its formation in 2004 to a $720 million buyout by GlaxoSmithKline (GSK) plc in 2008, is losing its research facility in Cambridge, Mass., but not its name or mission to develop sirtuins, a family of seven enzymes believed to modulate the aging process.

The decision to close the Sirtris discovery performance unit (DPU) in Cambridge and move the work to GSK's Upper Providence R&D site in Collegeville, Pa., raised eyebrows when the big pharma confirmed the relocation Tuesday, after a Sirtris employee tipped an industry publication to the news. GSK had touted the creation of its DPUs in 2008 as the mend for productivity woes and a mechanism to improve return on investment. Sirtris had recently completed its three-year review as one of 38 DPUs. (See BioWorld Today, Feb. 8, 2012.)

"The larger drug discovery organization offers everything from access to platforms to a broad range of expertise across therapy areas," spokeswoman Melinda Stubbee told BioWorld Today. "We're looking at development of treatments for diseases of aging like diabetes and inflammatory diseases. By being co-located with folks who work in those units, there's a broader range of expertise and experience that's not in Boston," she added, including chemistry, biology and pharmacology teams.

Sirtris was co-founded by David Sinclair of Harvard Medical School, Christoph Westphal, then a general partner at Polaris Venture Partners and the start-up's CEO, and Greatpoint Ventures. By the end of 2004, the company had attracted a $13 million Series A; a $27 million Series B followed three months later. (See BioWorld Today, Dec. 2, 2004, and March 8, 2005.)

The company raised $37 million in in 2006 through a combination of venture funding and debt placement. The following year, Sirtris pulled in $60 million in its initial public offering, pricing at $10, the midpoint of its range. (See BioWorld Today, April 21, 2006, and May 24, 2007.)

GSK acquired the biotech a year later in a cash deal, paying $22.50 per share weeks after the Federal Reserve intervened to save the failing investment bank Bear Stearns – an event many analysts cited as the market's last gasp before the U.S. economy plunged into the Great Recession. (See BioWorld Today, April 24, 2008.)

Five years later, the market has recovered, but sirtuins have hardly set the world on fire. Sirtris generated significant buzz around its first program, SRT501, with publications in scientific journals and mentions in the lay press about the formulation of resveratrol, a natural substance found in red wine that's known to target sirtuin SIRT1, which affects caloric intake. At the time of the GSK acquisition, the small-molecule compound – aimed at targeting SIRT1 in a more efficient manner than natural resveratrol and demonstrating early potential in metabolic and neurodegenerative disorders – was in a Phase IIa study in combination with metformin in Type II diabetes and in MELAS syndrome as a second indication. GSK shelved the candidate in 2010 after an open-label, Phase II study of SRT501 alone or in combination with Velcade (bortezomib, Millennium: The Takeda Oncology Co.) in multiple myeloma showed unexpected safety concerns.

Sirtris subsequently moved SRT2104 – a small-molecule new chemical entity that is structurally distinct from resveratrol – into or through Phase II studies in Type II diabetes, psoriasis, ulcerative colitis and vascular disorders.

The decision to move sirtuin research in-house at GSK has nothing to do with improving efficiency or tweaking the technology, the big pharma maintained.

"Research at Sirtris has been very successful," Stubbee said. "They've done some terrific early biology studies. Now, the folks in R&D think the time is right to provide Sirtris with more resources and expertise as part of our broader drug discovery organization."

In short, Sirtris "has reached a point in its evolution where it's time to take it to the next phase," she added, noting GSK hopes to move some Sirtris-developed compounds into late-stage trials in the next three to four years.

The transfer to Upper Providence is expected to occur as quickly as samples, data and equipment can be relocated from Boston. "They're shooting for April/May," Stubbee said, although GSK has not yet determined how many of the five dozen employees will move. Stubbee said the pharma does not plan to disclose costs associated with the consolidation.

Ironically, GSK's decision came one week after the journal Science published a paper by Harvard's Sinclair and colleagues suggesting that natural substrates of sirtuin have a hydrophobic amino acid in a specific position, and that activation of SIRT1 by resveratrol or any other activator depends on the presence of that hydrophobic amino acid. Changes in the scientific understanding of how to modulate SIRT1 could affect drug development timetables, according to an analysis of the paper scheduled for the March 18 issue of BioWorld Insight.

Although GSK has no plans to discontinue research programs currently under way at Sirtris, "all of the programs will be reviewed as part of this transition period," Stubbee confirmed.

"It's worth pointing out that we're excited about taking sirtuins to the next level," she added. "Sirtris has gotten a lot of publicity over the years, but this move says a lot about the science."