Sirtris Advancing No. 1 Drug into Mid-Stage Clinical Trials for Type 2 Diabetes

10/14/09

Cambridge, MA, biotech standout Sirtris has been a quieter operation since it became a subsidiary of drug giant GlaxoSmithKline last summer. But the firm’s drugs, heralded for their potential anti-aging effects, appear to be advancing through the clinic without a hitch.

Brian Gallagher, senior director of corporate development at Sirtris, disclosed during a recent meeting at Harvard Medical School that Sirtris has begun to recruit patients for a mid-stage clinical trial of its lead drug candidate, SRT-2104, for Type 2 diabetes. I don’t typically deem the initiation of a Phase II clinical trial all that newsworthy, but this one is interesting, in part because London-based Glaxo paid $720 million for Sirtris before the startup had accumulated very much human clinical data. Data from this sort of trial could provide an indication of whether Glaxo’s bet is likely to pay off.

Sirtris is developing drugs that have the potential to have a huge impact on the treatment of diseases of aging such as diabetes, cancer, and Alzheimer’s. And in the space of about five years, the firm has grown from a startup founded around Harvard professor David Sinclair’s discovery about the anti-aging effects of so-called sirtuin enzymes (which are activated by the red-wine chemical resveratrol) to a subsidiary of a major pharma company with the therapeutic assets and resources to significantly impact human health.

In the new trial, Sirtris will test its SRT-2104 drug candidate in about 200 patients with Type 2 diabetes in the UK and Eastern Europe. Like in most mid-stage clinical trials, the primary aim of the study is to show whether the drug is safe and tolerable in those patients. Yet the secondary goals of the study are to show whether the drug reduces blood sugar levels and to measure the drug’s effect on patients’ insulin levels. The large trial isn’t expected to yield any data before late 2010.

SRT-2104 is designed to boost the production of one particular sirtuin enzyme, SRT1, which is believed to enhance metabolic function in cells and mimic the effects of a low-calorie diet. It is intended to be more specific in its action than resveratrol, which can have multiple biological effects, and it’s about 1,000 times as potent as the red-wine-derived compound. As Sirtris indicated last year, it has ended development of its proprietary formulation of resveratrol, SRT-501, for Type 2 diabetes, in favor of SRT-2104. In mouse studies, SRT-2104 reduced blood sugar levels and boosted the ability of the insulin to control blood sugar. The new clinical trial will provide an opportunity to see if such effects are reproducible in humans.

In addition to the diabetes work, Sirtris has done pre-clinical testing of its sirtuin-activator drugs on certain targets related to inflammation, such as TNF-alpha proteins. In mice, a compound known as SRT-2183 suppressed proteins that are overabundant in patients with inflammatory bowel disease. Still, Sirtris did not say whether it plans to pursue human clinical trials of an IBD treatment (although its preclinical work indicates that is a distinct possibility.)

Sirtris CEO Christoph Westphal said during the Harvard Medical School meeting that there are 15 active clinical trials of drugs that activate sirtuins, at his firm and others around the world, to treat a variety of diseases. “There are going to be a lot of people working on it,” he said. “It’s a huge field.”

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