Sirtris Pharmaceuticals was a high-profile biotechnology startup that emerged in 2004, capturing global attention for its bold focus on the science of aging and life extension. Founded by Harvard biologist David Sinclair and entrepreneur Andrew Perlman, the company quickly positioned itself at the forefront of a controversial but potentially revolutionary field of medicine. The company’s trajectory was marked by rapid growth, intense media scrutiny, and a massive acquisition by the pharmaceutical giant GlaxoSmithKline (GSK). Sirtris aimed to develop novel therapies to treat diseases associated with the aging process, such as metabolic disorders and neurodegeneration. Its short lifespan serves as a prominent case study on the promise and risks of translating cutting-edge academic research into viable drug products.
The Core Scientific Focus
Sirtris Pharmaceuticals centered its research on a family of enzymes known as sirtuins, particularly Sirtuin 1 (SIRT1), which had been hypothesized to regulate cellular health, metabolism, and lifespan in various organisms. These enzymes are nicotinamide adenine dinucleotide (NAD+)-dependent protein deacetylases, meaning they require the coenzyme NAD+ to remove acetyl groups from target proteins, thereby influencing gene expression and cellular function. The scientific theory driving the company was that activating these enzymes could mimic the beneficial effects of caloric restriction—a dietary regimen known to extend the lifespan of many species—without the need for extreme dieting.
The company’s goal was to create small molecule drugs, known as sirtuin-activating compounds (STACs), that could switch on SIRT1 activity to combat age-related decline. Their initial and most publicized compound was SRT501, a proprietary formulation of resveratrol, a natural compound found in the skin of red grapes and red wine. Resveratrol’s initial promise stemmed from laboratory studies suggesting it could activate SIRT1, leading to excitement within the scientific and investment communities regarding its potential to treat conditions like Type 2 Diabetes, cancer, and inflammation.
Sirtris quickly moved beyond the natural product, developing synthetic STACs that were up to a thousand times more potent than resveratrol and possessed favorable drug-like properties. These second-generation molecules, such as SRT1720 and SRT2104, were designed to be more selective and effective in modulating SIRT1, providing a robust foundation for clinical development. The company’s work established the premise that diseases of aging could be addressed by modulating a single biological pathway, a concept that attracted significant capital and attention.
The High Profile Acquisition
The scientific promise and the speed of Sirtris’s development trajectory quickly positioned it as a highly desirable acquisition target for major pharmaceutical companies. Following its founding in 2004 and a successful initial public offering in 2007, the company was acquired by GlaxoSmithKline (GSK) in 2008 for approximately $720 million. This acquisition was a landmark event, representing a significant investment by a major pharmaceutical player into the then-controversial field of aging research.
GSK paid $22.50 per share for Sirtris, which represented a substantial premium over the company’s trading price at the time, underscoring the perceived value of the sirtuin technology. The rationale behind the deal was GSK’s desire to enhance its research pipeline in metabolic, neurology, immunology, and inflammation research by gaining immediate access to the sirtuin field. GSK’s head of research and development described the modulation of the sirtuin family of enzymes as a transformative science that could address multiple age-related diseases.
As part of the acquisition structure, GSK initially allowed Sirtris to operate as a largely autonomous unit, retaining its management team and facilities in Cambridge, Massachusetts. This arrangement was intended to preserve the entrepreneurial and innovative culture of the smaller biotech company while providing the resources of a global pharmaceutical organization. This hybrid approach was a common strategy at the time, designed to integrate promising new science without stifling the creativity of the original team.
Clinical Trials and Company Absorption
Despite the initial hype and massive investment, the translation of Sirtris’s laboratory success into marketable drugs faced significant scientific and clinical hurdles. The company’s lead compound, SRT501, a formulation of resveratrol, was being tested in clinical trials for Type 2 Diabetes and other conditions. However, development was halted in late 2010 due to side effects observed in patients, which included gastrointestinal issues like nausea, vomiting, and diarrhea.
Beyond the safety concerns, the core scientific mechanism of the sirtuin activators came under intense scrutiny from other research groups. Independent studies, including those from Amgen and Pfizer, raised questions about the direct activation of SIRT1 by resveratrol and the synthetic STACs. Researchers suggested the observed activation in early assays was an artifact dependent on the specific fluorescent substrate used, or that the compounds might be acting through off-target mechanisms, such as activating the metabolic sensor AMP-activated protein kinase (AMPK).
Sirtris attempted to pivot by focusing on its next-generation synthetic compounds, such as SRT2104, which progressed into Phase II studies for conditions like Type 2 Diabetes and psoriasis. However, the accumulated challenges and the difficulty of proving efficacy in complex human diseases led to the end of the company. In 2013, GSK shut down the Sirtris facilities in Cambridge and fully absorbed the remaining intellectual property and development candidates into its broader internal R&D structure. The Sirtris brand ceased to exist, marking the conclusion of the company’s operational history, though its scientific legacy continued to influence GSK’s research into age-related diseases.