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 …Next Page »

Comments | Reprints | Share:        

Christoph Westphal, the CEO of biotech firm Sirtris, says that he and several of his colleagues are forming a new nonprofit group in the Boston area called the Healthy Lifespan Institute. The institute is being formed to research non-pharmaceutical measures that people can take to live longer and healthier lives and to educate people about the aging process, Westphal tells Xconomy.

While Sirtris, a Cambridge, MA, subsidiary of drug giant GlaxoSmithKline, is developing drugs to treat diseases of aging such as Type 2 diabetes and cancer, the new nonprofit group will be focused on educating people about the aging process and conducting human clinical studies into whether such interventions as reducing caloric intake or taking supplements like resveratrol will prolong healthy living. While the plant-derived resveratrol could be considered a pharmaceutical, depending on how it’s defined, a key to the potential life-extending measures of interest to the institute is that they are not traditional FDA-regulated therapeutics. The institute, which is due to officially launch within six months, is expected to be a separate entity  from Sirtris. Though the nonprofit group will certainly be tapping the expertise of people affiliated with Sirtris to advance knowledge of the human aging process.

The past decade or so has been rife with discoveries about the biological underpinnings of how cells and organisms age. For example, studies show that animals such as mice and monkeys on low-calorie diets live longer than animals that eat more. Other animal studies indicate that the red wine chemical resveratrol can mimic the effects of calorie restriction to prolong life. Sirtris’ leadership in this field prompted London-based Glaxo to acquire the startup for $720 million in June 2008. Yet the pharmaceutical industry is primarily focused on developing new drugs for diseases. Aging isn’t considered a disease. So there’s a large need for “rigorous controlled studies” that show the effects of non-FDA regulated measures such as calorie restriction and resveratrol in humans, according to Westphal.

“It’s a pretty straightforward mission statement: to increase healthy lifespan,” Westphal said. “I think there are few people who would disagree with that, and I think it’s a very worthy mission.”

Westphal believes it will cost tens of millions of dollars to fund the human clinical studies that the institute plans to conduct, yet he says that the focus of the nonprofit effort right now is to bring together leaders in the science of aging. The other people involved in the Healthy Lifespan Institute include David Sinclair—the Harvard Medical School professor who co-founded Sirtris with Westphal and others—MIT biology professor and Sirtris scientific adviser …Next Page »

Comments (3) | Reprints | Share:        

Apparently, there were still some people who hadn’t heard of Sirtris and its widely publicized anti-aging pills, because Sunday evening’s 60 Minutes story on the Cambridge, MA, biotech firm sparked a surge in Web searches on the company as well as requests for its experimental drugs.

The 60 Minutes story on CBS was a recap of the well-chronicled story of Sirtris, about how former venture capitalist and current Sirtris CEO Christoph Westphal and Harvard scientist David Sinclair formed the company to commercialize Sinclair’s discovery that activating certain genes can slow down the process of aging, at least in yeast.

The TV story didn’t break any news about Sirtris, but the 12-minute segment was apparently news to the droves of people who e-mailed us at Xconomy and commented on our recent posts on the company, primarily to glean more information about the firm’s drugs and, for some people, to find how they could score a supply. (Sirtris was initially developing a proprietary formulation of resveratrol, a natural anti-aging chemical found in the skins of grapes, but last year the firm announced that it would focus primarily on developing compounds 1,000-times more potent than resveratrol for diseases of aging such as diabetes.)

Indeed, we received a note on Monday from one viewer who wanted to know about Sirtris’ more potent compounds, asking: “Where can I purchase the ultra pure 250mg resveratrol made by Sirtris as seen on 60 Minutes?” And we’ve received e-mails from viewers looking to obtain Sirtris’ experimental drugs as well. (Please see the editor’s note below about such requests.)

I caught up with Sirtris’ Westphal yesterday to get his take on the TV story and the wave of interest in the company. “We got hundreds of telephone calls and e-mails,” Westphal told me. “Our Web site usually has 500 unique hits a day, which is actually fair amount for a small company, but today we’ll get 15,000 to 20,000—so it’s a huge a amount of general public interest in what we’re doing.”

London-based drug giant GlaxoSmithKline, which acquired Sirtris last spring for a tidy $720 million, stands to profit handsomely if Sirtris’ drugs succeed as well in clinical trials as they do in piquing peoples’ hunger for ways to stay young and healthy.

[Editor's note: Xconomy has no information about Sirtris's drugs beyond what we've written in our stories. You can see a rundown of all our stories mentioning Sirtris here; for additional information we suggest visiting Sirtris's website.]

Comments (5) | Reprints | Share:        

Cambridge-based Sirtris Pharmaceuticals says researchers from the company will be featured Tuesday night in a Barbara Walters ABC television special entitled “Live to Be 150: Can You Do It?” As the narrator in a promo video for the special on YouTube enthuses: “It’s not just red wine or diet. Cutting edge scientists say we’re at the edge of living to 150.” In Boston the show will air at 10:00 p.m. on WHDH, Channel 7.

Comments | Reprints | Share:        

News arriving in my inbox from Cambridge, MA-based Sirtris Pharmaceuticals (NASDAQ: SIRT) this morning caused a double-take: the company known for researching drugs that may treat diabetes and cancer by mimicking the effects of calorie restriction is licensing a portion of its technology to Bayer CropScience AG, the German agricultural biotech giant. For a moment, I wondered how the heck a startup focused on improving human health and lifespan could have any insights into plants.

Then I remembered the red wine connection. Sirtris’s drug pipeline is stocked with a number of different molecules that boost cells’ production of lifespan-extending “sirtuin” proteins (hence the company’s name), and the granddady of these molecules—called resveratrol—was originally isolated from plants, most famously from the grapes used to make red wine. Researchers learned early on that resveratrol is found in greater concentrations in plants that are under stress from fungal infections, suggesting that it’s one of the molecules that provoke cellular defenses such as slowed aging and delayed cell death in plants. It was only recently that researchers began to observe such effects in mammals. So in a way, agricultural applications of sirtuin science actually represent a return to the field’s roots. So to speak.

Which leads back to Sirtris’s announcement. The company said it’s granting Bayer CropScience the exclusive, worldwide rights to agricultural applications of “a certain Sirtris technology that contributes to cellular life span extension and stress resistance.” Bayer intends to pursue the technology as one possible way of increasing crop yields and stress resistance in crops such as canola, cotton, rice, and corn.

“The object of Bayer CropScience’s global research activities is to develop a new generation of stress-tolerant, high-yielding varieties,” says Utz Klages, a Bayer CropScience spokesperson whom I reached in Monheim, Germany. “These crops have to be protected against a wide variety of abiotic and biotic stress factors. As Sirtris is also working in this field, it makes the agreement very attractive for Bayer CropScience.”

But exactly what technologies Sirtris is licensing to Bayer remains a little vague. Sirtris’s U.S. and international patents are very broad, covering the general idea of sirtuin enhancement in human, animal, and plant cells as well as a range of potential applications for same. So you might think that the “certain Sirtris technology” referred to in the announcement is a gene or chemical aimed at boosting sirtuin production in crop plants.

That’s what I thought, anyway. But interestingly, John Lacey, Sirtris’s associate director of corporate communications, says the Bayer agreement is not a license for the company to develop methods that would directly modulate the plant equivalents of sirtuin-encoding genes. “It’s a license that involves the fluctuation of the pathway in plants that influences sirtuin members, but it’s not a license to specific sirtuins,” Lacey says. In theory, Sirtris is still free to license agricultural applications of direct sirtuin modulation to another company. But “those discussion haven’t taken place,” says Lacey.

I tried to pin down Klages on which aspect of Sirtris’s technology seems most promising to crop scientists, but he wouldn’t take the bait. He did say, however, that Sirtris’s technology is just one of many approaches Bayer is testing to the challenge of making crops more adaptable to changing climate conditions. “This is the beginning of a medium-term research agreement that might lead to possible new varieties as early as 2015; it’s too early to confirm the details at the moment,” Klages says. “Let’s see how it works and which technology will be the best to get these varieties.”

Sirtris said in the announcement that it will receive “an initial up-front and future success bound milestone payments” in return for the license. Neither company would discuss the amounts or dates of these payments.

Comments (11) | Reprints | Share:        

Cambridge, MA-based Sirtris Pharmaceuticals (NASDAQ: SIRT) generated a flurry of media coverage, and a moderate stock gain, this week after announcing the first evidence that its formulation of resveratrol, a naturally occurring anti-aging substance found in red wine, helps to control symptoms of diabetes in humans. But it’s unclear that the study results—which were not reported in a peer-reviewed forum—will have much impact on the company’s future.

Sirtris reported at a JPMorgan health care conference in San Francisco yesterday that a preliminary “Phase 1b” safety trial, conducted on 98 Type 2 diabetes sufferers in India who had taken no previous drugs for diabetes, demonstrated that the company’s drug, called SRT501, had no serious side effects. After four weeks, the company said, patients who received the drug had an increased tolerance for glucose (that is, their bodies controlled glucose levels more effectively than before).

Phase 1 trials are not typically designed, however, to test how well a drug works. They’re usually conducted on healthy volunteers, and are merely intended to assess whether a drug is safe and well-tolerated at various doses, whether it accumulates in the bloodstream, and the like. Sirtris’s trial was somewhat unusual in that the participants were actual diabetes patients, but evidence of the drug’s effectiveness, at this stage, would have little effect on the drug’s chances for eventual regulatory approval—assuming that Sirtris intends to carry SRT501 through to commercialization, which it may not.

Sirtris designed SRT501 to be absorbed by the body more readily than pure resveratrol (which doesn’t show up at therapeutic levels in red wine, by the way, no matter how much you might attempt to drink). But as we reported in November, resveratrol derivatives are rapidly being overshadowed inside Sirtris by unrelated compounds with more power to activate SIRT1, the key gene that’s thought to be involved in the metabolic pathways that regulate aging and that seem to be out of whack in people with aging-related diseases such as diabetes and obesity. In a November Nature paper, Sirtris reported that three such compounds, called SRT1460, SRT1720, and SRT2183, are up to 1000 times as effective at activating SIRT1 as SRT501. CEO Christoph Westphal says the company plans to begin safety studies of the new compounds in the first half of this year.

Sirtris’s stock was hovering around $14.10 on the NASDAQ this morning, up roughly 7 percent over Monday’s price.

UPDATE 3:20 pm, 1/8/08: I spoke this afternoon with a Sirtris representative who emphasized that the company has never said that it will push aside testing and commercialization of SRT501. In fact, the company sees the compound as a potential treatment for MELAS (a rare mitochondrial disorder; the acronym stands for “mitochondrial myopathy, encephalopathy, lactic acidosis, stroke-like episodes”) and for Type 2 diabetes when used in combination with metformin, a popular anti-diabetes drug. The company plans to publish the results of the recent Phase Ib trial in a peer-reviewed publication this spring.

Comments (7) | Reprints | Share:        

When I visited Cambridge-based Sirtris Pharmaceuticals a few weeks ago, CEO Christoph Westphal told me that the company would soon be publishing data on a new drug candidate that’s 1000 times as effective as the company’s lead compound—a diabetes drug—at activating a key gene called SIRT1. Those data are now out in this week’s issue of Nature. It turns out there are actually three new compounds, and Westphal says they “could unlock a new approach to treating Type 2 diabetes.”

Co-founded by David Sinclair, a pathologist at Harvard, Sirtris has staked its future on the idea that compounds that enhance the activity of a family of enzymes including SIRT1 make powerful drugs against diseases of aging such a diabetes and cancer. Sinclair’s research showed that resveratrol—a chemical found in red wine—is a SIRT1 activator that increases stamina and lifespan when fed to mice. Sirtris is currently testing a proprietary formulation of resveratrol in Phase 1B clinical trials, with results due out around the beginning of the new year, Westphal says.

The company has no plans to abandon resveratrol, according to Westphal, but the new compounds—which Sirtris found after screening thousands of small molecules—could prove to be much more potent. The Nature study showed they improved insulin sensitivity in obese mice, and even restored blood-glucose levels to near normal in mice that were fed high-fat diets. Sirtris plans to begin studies in the first half of 2008 to find the most effective doses of the new compounds in humans, according to Westphal.

Comments (4) | Reprints | Share:        

The MIT biologist who co-founded Elixir Pharmaceuticals in 1999 in a bid to turn his research on a gene called Sir2 into drugs that might extend lifespans has defected to Elixir’s primary rival, Sirtris Pharmaceuticals (NASDAQ: SIRT). Both companies are developing drugs against aging-related diseases such as cancer and diabetes, and both are based in Cambridge.

Leonard “Lenny” Guarente, a professor in MIT’s department of biology since 1982, is frequently mentioned as a possible future Nobelist for his discovery that lifespan in mice, yeast, worms, and other organisms is regulated by the activity of Sir2—the more active the gene is, the longer the animal lives. But Sirtris, co-founded by Harvard pathologist David Sinclair in 2004, is now the dominant company doing research on potential drug compounds that enhance the activity of Sir2-like genes in humans. Today Sirtris announced that Guarente—who left Elixir in the fall of 2006—has joined the company as co-chair of its scientific advisory board.

Guarente said in a statement that he was “delighted” to join the SAB at Sirtris, which raised $60 million in an initial public offering in May. Guarente lauded Sirtris for being “highly focused” on developing therapies that target sirtuins, the class of enzymes encoded by Sir2.

That focus has been notably waning at Elixir, which hopes to raise $86 million in its own upcoming IPO. Elixir asserts in its IPO registration statement that its researchers “mine the pathways involved in the regulation of aging discovered by our founders”—but the company’s main commercial hopes rest on Glinsuna and Metgluna, diabetes drugs that it has licensed from a Japanese manufacturer and aims to market in the United States, pending FDA approval. In its 179-page IPO registration statement filed with the SEC, the company does not detail its research on drugs aimed at affecting the activity of sirtuins until page 69—and then, it’s in reference to drugs that block Sir2, rather than enhancing it. (The company believes that blocking sirtuins may help in the treatment of cancer.)

Guarente declined to renew his consulting contract with Elixir after it expired last fall. He has had a long and well-reported courtship with Sirtris, and his appointment to the Sirtis advisory board—which also includes such MIT luminaries as Robert Langer and Philip Sharp—would presumably have come sooner if not for a one-year noncompete agreement with Elixir, which has now run out.

“Guarente and Sirtris are both focused on developing drugs to treat diseases of aging by targeting the sirtuins, genes that control the aging process,” Sirtris CEO Christoph Westphal told Xconomy last night. “Guarente is a leader in academic aging research, and Sirtris is the leading sirtuin company, so this is a natural fit for both of us.”

Yet it’s a fit that wouldn’t have seemed natural just a couple of years ago. Sinclair, a protégé of Guarente’s at MIT in the late 1990s, declined an offer to join Guarente at Elixir. Instead, he and Westphal, then a partner at Polaris Venture Partners, went on to found Sirtris after Sinclair’s own discovery that resveratrol, a chemical found in red wine, mimics the lifespan-extending effects of very-low-calorie diets in mice, flies, and fish—seemingly by activating SIRT-1, one of seven Sir2-like genes in humans. Around the same time, Sinclair and Guarente had a well-publicized falling out over the genetic mechanisms by which caloric restriction leads to longer lifespan in yeast cells.

The former competitors have now patched up their differences. In fact, in October Sirtris obtained an exclusive license to commercialize work in Guarente’s lab on the cholesterol-regulating effects of SIRT-1, and Guarente is co-author with Westphal and Sirtris corporate development director Michelle Dipp on a Trends in Biochemical Sciences review paper on the therapeutic applications of sirtuins, published this month. Guarante’s appointment to the Sirtris advisory board “should be a huge sign to the public that David and Lenny are working together,” says Dipp. “Which is really nice to see, because they are really the leaders in the sirtuin field.”

Sirtris is conducting a Phase II clinical trial in India of a proprietary formulation of resveratrol that may help patients with type 2 diabetes control their glucose levels, and Westphal says that the company will soon publish results on a new compound that is 1000 times as potent as resveratrol when it comes to activating SIRT-1. Elixir, meanwhile, is pursuing research on an entirely different class of biological molecules involved in aging and aging-related diseases: ghrelins, which stimulate the release of growth hormones and increase appetite. The company hopes that compounds that block ghrelins might turn out to be treatments for diabetes and obesity.

Elixir’s IPO filing never mentiones Guarente by name, but the company is clearly aware that his ongoing work could lead to competing treatments for diabetes. In the obligatory section on the risk factors facing the company, Elixir states: “While certain of our founders have continued to assist us in various roles, including as scientific consultants, we no longer have an active relationship with several of our other founders. Although bound by confidentiality obligations relating to their work at Elixir, we do not have rights to any of their future discoveries and none of our founders is prohibited from competing against us.”

Comments (2) | Reprints | Share: