Sirtris Pharmaceuticals trials of red wine derived agent show impressive results for diabetics in initial trials

Sirtris Pharmaceuticals Inc. (NASDAQ: SIRT) held a webcast yesterday, sponsored by J.P. Morgan Chase & Co. in San Francisco and issued a press release Announcing Positive Results with a Proprietary Version of Resveratrol, SRT501, in a Phase 1b Type 2 Diabetes Clinical Study. SRT501, they claim was found to be safe and well-tolerated, and was found to significantly lower glucose in an oral glucose tolerance test conducted as part of a 28 day Phase 1b clinical study in patients with Type 2 Diabetes in India.(WSJ) (See also "Scientists Locate Revved Up Chemical That Mimics Red Wine " 30/10/07

SIRT1 is the founding member of the human sirtuin family of enzymes which control the aging process. Specifically, SRT501 a proprietary type of resveratrol acts on these enzymes in some way by increasing mitochondrial activity and therefore is targeted to address metabolic diseases, such as Type 2 Diabetes....well that's the theory so far.

The name sirtuin is derived from silent mating type information regulation two, the gene responsible for cellular regulation in yeast.

Normally, sirtuin activity is inhibited by nicotinamide, a component of vitamin B3 (also known as niacin), by binding to a specific receptor site. Drugs that interfere with this binding should increase sirtuin activity. It is known that resveratrol, found in red wine, can inhibit this interaction and is a putative agent for slowing down the aging process. However, the amount of resveratrol found naturally in red wine ( or in the various dietary supplements available) is far too low to activate sirtuin. ...although the incidence of coronary heart disease is relatively low in S.France despite high dietary intake of saturated fats ...attributed to the high intake of red wine and hence resveratrol.

This initial 28-day Phase 1b study was designed to assess the safety, tolerability and pharmacokinetics of once-daily, orally administered doses of either 2.5 g or 5 g of SRT501 in patients with Type 2 Diabetes who were naive to other diabetes drug treatments. Both doses of SRT501 were found to be safe and well-tolerated, and pharmacokinetics, a measure of drug levels in the blood, were identical at days one and 28, suggesting no drug accumulation.

There were no serious adverse events and no dose-related adverse events ( i.e no apparent side effects were reported). Importantly, SRT501 showed a statistically significant improvement in an oral glucose tolerance test on day 28 at two hours and a trend towards lower fasting plasma glucose levels.

"This is the first time that a small molecule targeting sirtuins, the genes which control the aging process, has shown efficacy in a disease of aging," said Peter Elliott, Ph.D., Senior Vice President of Development at Sirtris. ( a professor at Harvard Medical School ) "These Phase 1b study results are an important step forward for Sirtris because they represent significant progress in our clinical development of sirtuin therapeutics. We are very pleased to see the safety profile observed in preclinical studies translate into a well-tolerated drug molecule in patients, and we are very encouraged by the glucose lowering effects measured in the oral glucose test."

David Sinclair at Harvard had found that resveratrol significantly increases the lifespan of yeast and mice.

Sirtris, Cambridge, Mass., is working on commercializing resveratrol and related drugs to fight a number of diseases. Advocates suspect resveratrol may also increase life span, though that hasn't yet been shown.

The company has said 2012 is the earliest it could get to the market with a diabetes drug, which would happen only if further phases of clinical testing in much larger groups of patients (which have been started) are successful.

Elixir Pharmaceuticals is another Cambridge, Mass based company which is hoping to develop products that affect specific genes and enzymes that can slow the aging process, and are developing compounds that stimulate these interactions and will be used to treat a range of diseases of aging, including metabolic disease such as type II diabetes.

Elixir are preparing for an IPO. Credit Suisse Securities (USA) LLC will act as sole book-runner for the offering. Pacific Growth Equities, LLC and Leerink Swann LLC will act as co-managers.

Sirtris Pharmaceuticals Share price - ended up today approx 1.5 %



Other blog posts on the topic.