Sirtris Pharmaceuticals
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Sirtris Pharmaceuticals, Inc. was a biotechnology company based in
Cambridge, MA Cambridge ( ) is a city in Middlesex County, Massachusetts, United States. As part of the Boston metropolitan area, the cities population of the 2020 U.S. census was 118,403, making it the fourth most populous city in the state, behind Boston, ...
that developed therapies for type 2 diabetes, cancer, and other diseases. Conceived in 2004 by Harvard University biologist David Sinclair and serial entrepreneur
Andrew Perlman Andrew Perlman (born June 19, 1975) is an American entrepreneur who has co-founded nine venture-backed companies in the telecom, high-tech, pharmaceuticals, energy, water, and biotechnology industries. He is currently General Partner of GreatPoin ...
, and founded that year by Sinclair and Perlman, along with
Christoph Westphal Christoph Westphal, M.D., Ph.D., is a biomedical entrepreneur. Background and training Westphal graduated from Columbia College of Columbia University, summa cum laude, in 1990 and finished the MD–PhD program at Harvard University in six y ...
, Richard Aldrich, Richard Pops, and Paul Schimmel, the company was focused on developing Sinclair's research into activators of sirtuins, work that began in the laboratory of
Leonard P. Guarente Leonard Pershing Guarente (born 1952) is an American biologist best known for his research on life span extension in the budding yeast ''Saccharomyces cerevisiae'', roundworms (''Caenorhabditis elegans''), and mice. He is a Novartis Professor o ...
where Sinclair worked as a post-doc before starting his own lab.


Synopsis

The company was specifically focused on
resveratrol Resveratrol (3,5,4′-trihydroxy-''trans''-stilbene) is a stilbenoid, a type of natural phenol, and a phytoalexin produced by several plants in response to injury or when the plant is under attack by pathogens, such as bacteria or fungi. Sourc ...
formulations and derivatives as activators of the
SIRT1 Sirtuin 1, also known as NAD-dependent deacetylase sirtuin-1, is a protein that in humans is encoded by the SIRT1 gene. SIRT1 stands for sirtuin (silent mating type information regulation 2 homolog) 1 ('' S. cerevisiae''), referring to the fact ...
enzyme; Sinclair became known for making statements about resveratrol like: “(It's) as close to a miraculous molecule as you can find.... One hundred years from now, people will maybe be taking these molecules on a daily basis to prevent heart disease, stroke, and cancer.” Most of the anti-aging field was more cautious, especially with regard to what else resveratrol might do in the body and its lack of
bioavailability In pharmacology, bioavailability is a subcategory of absorption and is the fraction (%) of an administered drug that reaches the systemic circulation. By definition, when a medication is administered intravenously, its bioavailability is 100%. Ho ...
. The company's initial product was called SRT501, and was a formulation of resveratrol. Sirtris went public in 2007 and was subsequently purchased and made a subsidiary of
GlaxoSmithKline GSK plc, formerly GlaxoSmithKline plc, is a British multinational pharmaceutical and biotechnology company with global headquarters in London, England. Established in 2000 by a merger of Glaxo Wellcome and SmithKline Beecham. GSK is the tent ...
in 2008 for $720 million. GSK paid $22.50/share, when Sirtris's stock was trading at $12/share, down 45% from its highest price of the previous year. Studies published in 2009 and early 2010 by scientists from
Amgen Amgen Inc. (formerly Applied Molecular Genetics Inc.) is an American multinational biopharmaceutical company headquartered in Thousand Oaks, California. One of the world's largest independent biotechnology companies, Amgen was established in T ...
and
Pfizer Pfizer Inc. ( ) is an American multinational pharmaceutical and biotechnology corporation headquartered on 42nd Street in Manhattan, New York City. The company was established in 1849 in New York by two German entrepreneurs, Charles Pfize ...
cast doubt on whether SIRT1 was directly activated by resveratrol and showed that the apparent activity was actually due to a fluorescent
reagent In chemistry, a reagent ( ) or analytical reagent is a substance or compound added to a system to cause a chemical reaction, or test if one occurs. The terms ''reactant'' and ''reagent'' are often used interchangeably, but reactant specifies a ...
used in the experiments. In August 2010, a nonprofit called the Healthy Lifespan Institute, which had been formed the year before by Westphal and
Michelle Dipp Michelle Dipp is an American scientist, businesswoman, and investor. She is the co-founder and a managing partner at Biospring Partners and serves on the board of Abzena and Kiniciti. Early life and education Michelle Dipp was raised in El Pas ...
, who joined GSK from Sirtris, began selling SRT501 as a
dietary supplement A dietary supplement is a manufactured product intended to supplement one's diet by taking a pill, capsule, tablet, powder, or liquid. A supplement can provide nutrients either extracted from food sources or that are synthetic in order ...
online; when this become public GSK required Westphal and Dipp, who were still GSK employees, to resign from the nonprofit. GSK/Sirtris terminated development of SRT501 in late 2010. GSK said it was terminating SRT501 due to side effects of nausea, vomiting, and diarrhea it caused, and because the compound's activity wasn't specific to SIRT1, at some doses it actually inhibited SIRT1, and the compound itself wasn't patentable. The company said at that time that it was focused on two compounds called
SRT2104 SRT-2104 is an experimental drug that was studied by Sirtris Pharmaceuticals as a small-molecule activator of the sirtuin subtype SIRT1. The compound progressed to Phase II human trials for Type II diabetes before development was discontinued, ...
and SRT2379 that were not resveratrol analogs, had better drug-like qualities, and were more selective SIRT1 activators. In 2013 GSK shut down Sirtris and its development candidates were absorbed into GSK, where research and development continued. At that time, GSK/Sirtris' lead candidate was SRT2104, described as a "first-generation sirtuin-activating compound."


References

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External links


GSK official website
Biotechnology companies of the United States Life sciences industry