Sirtris and Harvard Unveil Promising, Novel SIRT1 Activators for Treating Diseases of Aging; Therapeutic Type 2 Diabetes Data Published in the Journal Nature
In November 2006, Sirtris scientists and Sirtris co-founder, Prof. David Sinclair from Harvard Medical School, published consecutive papers in the journals Cell and Nature showing that resveratrol, a SIRT1 activator found in red wine, could reduce the impact of a high fat diet, increase stamina two fold and significantly extend lifespan of mice. Unfortunately, it was estimated that a person would need to drink 1000 bottles of red wine to obtain an equivalent dose of resveratrol. Now, scientists at Sirtris have developed SIRT1 activating molecules that are chemically distinct from resveratrol and are 1000 times more potent.
"The new drug candidates represent a significant milestone because they are the first molecules that have been designed to act on genes that control the aging process. For this reason, we feel they have considerable potential to treat diseases of aging such as Type 2 Diabetes," said Christoph Westphal, M.D., Ph.D., Chief Executive Officer and Vice Chair of Sirtris Pharmaceuticals. "The breakthrough in potency we have achieved with the novel chemical entities (NCEs) means that we can obtain the health benefits of resveratrol in a more specific manner."
The Nature paper from Sirtris shows that in diet-induced obese and genetically obese mice, Sirtris' small molecule NCEs improve insulin sensitivity, lower plasma glucose levels and increase the function of mitochondria (the powerhouses of all cells). In another well-established preclinical model of Type 2 Diabetes and insulin resistance (Zucker fa/fa rats), these SIRT1 activators improved whole-body glucose homeostasis and insulin sensitivity in adipose tissue, skeletal muscle and liver. These rodent models of diabetes are considered highly predictive of efficacy in humans.
The World Health Organization (WHO) indicates that Type 2 Diabetes (formerly called adult-onset diabetes) results from the body's ineffective use of insulin. Type 2 Diabetes accounts for 90% of diabetes around the world, and is largely the result of excess body weight and physical inactivity. WHO estimates that more than 180 million people worldwide have diabetes and this number is likely to more than double by 2030. Furthermore, WHO projects that deaths due to diabetes will increase by more than 50% in the next 10 years. Activating SIRT 1 appears to mimic the beneficial effects of calorie restriction on mitochondrial and metabolic function in mammals in vivo and holds promise for treating diseases of aging, such as Type 2 Diabetes.
"We are very excited about these findings, which expand on the breakthrough data published in 2006 in the journals Nature and Cell, which demonstrated that SIRT1 activators mimic calorie restriction and extend lifespan. For the first time, the article published today shows that the novel drug candidates we have identified are the most potent SIRT1 activators ever to be published -- 1,000 times more potent than resveratrol -- and can potentially unlock a whole new approach to treating Type 2 Diabetes," stated Jill C. Milne, Ph.D., lead author of the Nature study and Senior Director of Biology at Sirtris.
Westphal added, "These NCEs represent the first molecules to be designed to activate SIRT1. Now we have an even more potent and specific way of eliciting the beneficial effects observed in earlier research with resveratrol. The NCEs characterized in this study are significantly more potent than and structurally unrelated to resveratrol. These findings highlight the tremendous potential of our NCE program to treat diseases of aging, and we look forward to advancing one of these promising new compounds into human clinical studies in the first half of 2008."
Sirtuins are a recently-discovered family of enzymes that promote the body's natural defense against disease. There are seven human sirtuins (SIRT1-7). Sirtuins are attractive drug targets because some have a specialized function in mitochondrial activity which may be therapeutically beneficial for metabolic and other diseases of aging. Sirtuin therapeutics offer the potential for a novel class of drugs that can treat diseases of aging in a new way.
Online copies of the article "Small molecule activators of SIRT1 as therapeutics for the treatment of type 2 diabetes" by Jill C. Milne, et al., Nature; November 29, 2007 can be obtained at: http://www.nature.com and a PDF of the paper can be obtained on www.sirtrispharma.com.
About Sirtris Pharmaceuticals
Sirtris Pharmaceuticals is a biopharmaceutical company focused on discovering and developing proprietary, orally available, small molecule drugs with the potential to treat diseases associated with aging, including metabolic diseases such as Type 2 Diabetes. Our drug candidates are designed to mimic certain beneficial health effects of calorie restriction, without requiring a change in eating habits, by activation of sirtuins, a recently discovered class of enzymes that control the aging process. The Company's headquarters are in Cambridge, Massachusetts.
This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Such statements include, but are not limited to, the potential therapeutic effects of SIRT1 activators, including NCEs and SRT501, for diseases of aging, such as Type 2 Diabetes, the progress and potential results of clinical studies of SIRT1 activators including NCEs, and the potential of sirtuin modulators to receive regulatory approval. These forward-looking statements about future expectations, plans and prospects of Sirtris Pharmaceuticals involve significant risks, uncertainties and assumptions, including risks related to the lack of results that would provide a basis for predicting whether any of the Company's product candidates will be safe or effective, or receive regulatory approval, the possibility that results of pre-clinical studies are not necessarily predictive of clinical trial results, the Company's potential inability to initiate and complete pre-clinical studies and clinical trials for its product candidates, the fact that none of the Company's product candidates has received regulatory approvals, the potential inability of the Company to gain market acceptance of the Company's product candidates, and those other risks factors that can be found in the Company's filings with the Securities and Exchange Commission. Actual results may differ materially from those Sirtris Pharmaceuticals contemplated by these forward-looking statements. Sirtris Pharmaceuticals does not undertake to update any of these forward-looking statements to reflect a change in its views or events or circumstances that occur after the date of this release.
Sirtris Pharmaceuticals, Inc.
Michelle Dipp, 617-252-6920
Sheryl Seapy, 949-608-0841
Posted: November 2007