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Start-up Sirtris Pharmaceuticals Inc. raised $13 million in a Series A round to strengthen what the company called its position as the leader in the field of Class III histone deacetylases, enzymes known to be implicated in a variety of diseases.

Christoph Westphal, CEO of Boston-based Sirtris, acknowledged that the HDAC field is hot, but said "my sense is that there is no other company exclusively focused on these seven enzymes" in Class III.

"There are somewhere between five and eight [drug candidates] addressing Class I and Class II HDACs" in stages of development from Phase I to Phase III, added Westphal, who co-founded Sirtris and is a general partner with Polaris Venture Partners in Waltham, Mass.

Sirtris' name is a palindrome derived from "sirtuins," as the Class III HDACs also are known. The firm began operating in 2004 and has 10 employees, with a plan to stay "lean and mean," but eventually building to between 20 and 25 full-time employees, Westphal said.

"We have several patents and a major estate licensed from Harvard University," where David Sinclair, an assistant professor of pathology at Harvard Medical School and a co-founder of Sirtris, did some important work in the HDAC area, Westphal said.

"It took us about six weeks to raise the Series A," he noted, with speed helped by the general understanding of Sinclair's research, which also includes the isolation of resveratrol, an apparent life-extending chemical found in red wine as well as some vegetables. Sinclair has linked calorie restriction to longer life, too - another story much liked by the mainstream press.

Enticing to big pharma, though, are HDACs. This spring, Merck & Co. Inc., of Whitehouse Station, N.J., completed its acquisition of Tarrytown, N.Y.-based Aton Pharma Inc. for undisclosed terms, gaining the latter's lead candidate, suberoylanilide hydroxamic acid, or SAHA, which is in Phase II trials, and another cancer compound, pyroxamide, in Phase I. Both are HDACs. (See BioWorld Today, Feb. 25, 2004.)

Also this spring, Syrrx Inc., of San Diego, and Nutley, N.J.-based Hoffmann-La Roche Inc. entered a deal for cancer and diabetes drugs that could mean up to $178 million for Syrrx. Included are preclinical programs focused on an HDAC inhibitor and on 11-beta hydroxysteroid dehydrogenase-1, a metabolic target that reduces the production of cortisol, which is overexpressed in diabetics. (See BioWorld Today, May 13, 2004.)

The march continues on many other fronts. Cambridge, Mass.-based Gloucester Pharmaceuticals Inc. pulled down $29 million in October to put an HDAC into pivotal trials for cutaneous T-cell lymphoma. (See BioWorld Today, Oct. 15, 2004.)

Gloucester is working in the Class I and Class II areas, said William McCulloch, chief medical officer at Gloucester.

"We say pan-HDAC,' but we really mean Class I and II," he said. "It's not entirely clear what [Class III HDACs] do, but they're probably involved in a number of processes."

McCulloch said "hematological malignancies have been the main targets to this point," along with renal cancer.

"Maybe they can get more solid tumor activity" with Class IIIs, he added. "We're all just reaching at the moment to see."

Many are reaching. Over the summer, Montreal-based MethylGene Inc. and EnVivo Pharmaceuticals Inc., of Watertown, Mass., entered a collaboration to develop the former's HDACs for neurodegenerative diseases. A month earlier, New Haven, Conn.-based CuraGen Corp. in-licensed a promising HDAC compound from the Danish firm TopoTarget A/S. (See BioWorld Today, June 7, 2004, and July 14, 2004.)

And, just last month, researchers from the University of Texas Southwestern Medical Center in Dallas and Baylor College of Medicine in Houston found another potential application for HDACs: regulating bone formation. (See BioWorld Today, Nov. 18, 2004.)

As phosphorylation proved a fruitful zone for drug development, "acetylation is a big deal in the late 1990s and now, and will lead to many more drugs," predicted Westphal, who also founded the RNAi firm Alnylam Pharmaceuticals Inc., of Cambridge, Mass. There's a chance for profit in founding firms and he enjoys it.

"I like to start these and run them for a couple of years," he said. "It takes about three to four months to percolate the idea, from idea to the first seed round." Sirtris' $5 million seed round came in August.

Among others involved in founding the company is Richard Pops, the high-profile chairman and CEO of Alkermes Inc., also of Cambridge.

Sirtris' Series A was led by new investor the Wellcome Trust, of London. Also participating were current investors and co-leads Polaris; Techno Venture Management, of Munich, Germany; Cardinal Partners, of Princeton, N.J.; and Skyline Ventures, of Palo Alto, Calif.

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