Sirtris Pharmaceuticals filed for an initial public offering, seeking to raise $60 million for clinical trials using a substance found in red wine to produce a compound that allows calorie restriction without the hunger pangs.

The 3-year-old company, based in Cambridge, Mass., focuses on human sirtuins, especially SIRT1, that could be targets for treating cancer or metabolic, inflammatory and neurodegenerative disorders. Based on research showing that resveratrol, a natural substance found in red wine, can activate SIRT1, the company has developed SRT501, a formulation of resveratrol that is currently in Phase Ib clinical trials for Type 2 diabetes.

If successful, the company said sirtuin therapeutics could represent a new class of drugs for treating disorders such as Type II diabetes. Sirtris expects the first clinical trials to focus on lowering glucose and reducing weight in Type II diabetics, and to treat neurodegenerative conditions, such as amyotrophic lateral sclerosis, Huntington's disease and certain rare mitochondrial disorders. (See BioWorld Today, April 21, 2006)

The company's lead candidate could compete with San Diego-based Amylin Pharmaceuticals Inc.'s Byetta (exenatide), a twice-a-day injectable that lowers glucose and weight in diabetes patients. Sirtris, however, is focusing on development of orally available products.

Two Phase Ia clinical studies found SRT501 was safe and well tolerated. The 28-day Phase Ib study, launched in October, is studying the oral administration of the drug in 90 Type II diabetes patients who are not on medication. A similar Phase 1b study has been initiated with twice daily dosing. Results are expected in the second half of 2007.

The company also is investigating SRT501 for MELAS syndrome (mitochondrial encephalopathy, lactic acidosis and stroke-like episodes) an inherited disorder caused by a mutation in the DNA of mitochondria. Sirtris is seeking to begin a European Phase 1b trial in MELAS by the end of 2007. It also plans to seek orphan drug status for SRT501 in MELAS in both Europe and the U.S.

The company also is exploring development of orally available, small-molecule NCEs that activate SIRT1. In studies of next-generation activators in a preclinical model of Type 2 diabetes in mice, one was found - administered at one-tenth the dose as SRT501 - to be as effective in reducing glucose levels and improving insulin sensitivity. Pending completion of investigational new drug application and other preclinical studies, the company plans to move at least one of these candidates into clinical studies by mid-2008.

Sirtris' said in its prospectus that it expects to use just more than half the $60 million sought to continue development of SRT501 and advance other preclinical candidates, with the remainder to expand research targeting other sirtuins, and repay existing debt facilities. Last April the company raised $22 million in a Series C round and secured another $15 million through a debt placement. Since its founding, Sirtris has raised $82 million. It reported a loss of $17 million in 2006.

In other IPO news:

• Helicos BioSciences Corp., of Cambridge, Mass., has filed a statement for an initial public offering to raise $100 million to fund development of its first commercial product, the HeliScope. It is designed to enable ultra-high-throughput genetic analysis based on the direct sequencing of single DNA molecules or single copies of RNA. The system is designed to produce a raw throughput of about 25-90 million bases per hour, and may advance to one billion per hour, which it says is a 10,000-fold improvement over current gene sequencing technologies. It plans to launch its product in the fourth quarter of 2007 with a specialized direct sales and service force.