Sirtris Pharmaceuticals was a biotechnology company focused on developing treatments for age-related diseases. It aimed to translate cutting-edge scientific discoveries into therapies by targeting proteins believed to influence the aging process, addressing conditions such as type 2 diabetes and other chronic ailments.
The Founding and Mission of Sirtris
Sirtris Pharmaceuticals was founded in 2004 by a team including Harvard University biologist David Sinclair. The company’s vision centered on transforming groundbreaking research in sirtuin biology into new treatments for diseases linked to aging. Sirtris sought to develop orally available, small molecule drugs with the potential to treat metabolic and inflammatory diseases.
The company’s early funding included a $13 million Series A round by the end of 2004, followed by a $27 million Series B three months later. This initial investment, alongside a $37 million raise in 2006, highlighted the scientific community’s excitement about its mission.
The Science Behind Sirtris: Sirtuins and Resveratrol
Sirtris Pharmaceuticals was built upon the study of sirtuins, a family of seven proteins that play a role in various cellular processes, including metabolism and aging. These proteins are nicotinamide adenine dinucleotide (NAD+)-dependent protein deacetylases, meaning they require NAD+ to function. Research suggested that mammalian sirtuins could offer protection against age-related conditions like metabolic and cardiovascular diseases, neurodegeneration, and cancer.
Resveratrol, a compound found in red wine, gained attention for its hypothesized ability to activate sirtuins, specifically SIRT1. Early studies in organisms like yeast, worms, and fruit flies suggested that resveratrol could extend their lifespans. Sirtris focused on developing formulations and derivatives of resveratrol, and later, more potent synthetic sirtuin activators.
The theoretical mechanism involved sirtuin activation mimicking the effects of caloric restriction, a dietary approach known to extend lifespan in some organisms. However, later research raised questions about whether resveratrol directly activated SIRT1, with some studies suggesting the observed activity was due to experimental artifacts involving fluorescent reagents.
Acquisition by GSK and Subsequent Developments
GlaxoSmithKline (GSK) acquired Sirtris Pharmaceuticals in 2008 for approximately $720 million, a substantial sum that underscored the pharmaceutical giant’s interest in the burgeoning field of aging research. The acquisition was driven by GSK’s desire to incorporate Sirtris’s sirtuin-targeting drug pipeline into its broader research efforts.
Following the acquisition, Sirtris’s lead drug candidate, SRT501, a formulation of resveratrol, progressed into human clinical trials. SRT501 was in a Phase IIa study for type 2 diabetes in combination with metformin and a Phase Ib trial for MELAS syndrome. However, development of SRT501 was terminated in late 2010 due to safety concerns, including side effects like nausea, vomiting, and diarrhea, and reports of kidney failure in some patients with multiple myeloma.
Questions also arose regarding SRT501’s specificity for SIRT1, with some studies suggesting it might inhibit SIRT1 at certain doses and was not patentable. GSK shifted its focus to other synthetic sirtuin-activating compounds, such as SRT2104 and SRT2379, which were not resveratrol analogs and possessed more favorable drug-like properties. Ultimately, in 2013, GSK shut down Sirtris as a distinct entity, integrating its remaining development candidates into GSK’s larger research and development operations.
Sirtris’s Impact and Legacy
Despite the eventual discontinuation of its initial drug candidates and the closure of its distinct facility, Sirtris Pharmaceuticals left a lasting impact on both the scientific community and the pharmaceutical industry. The company played a significant role in bringing sirtuin biology and the potential of aging research into the mainstream spotlight. Its high-profile acquisition by GSK validated the field, attracting considerable investment and attention to longevity science.
Sirtris’s journey highlighted the complexities involved in translating basic scientific discoveries into viable clinical treatments. The challenges encountered with SRT501, including questions about its mechanism of action and clinical trial outcomes, provided valuable lessons for drug discovery in complex age-related conditions. The company’s efforts, even with their setbacks, contributed to a deeper understanding of cellular metabolism and the intricate pathways involved in aging, influencing how future research in longevity is approached.