Sirtris Finds Anti-Cancer Effect, Teams with NIH

2/22/08Follow @wroush

Cambridge’s Sirtris Pharmaceuticals is known mainly for studying compounds like resveratrol that affect how the body uses insulin and may therefore have a role in treating metabolic disorders such as diabetes and obesity. But the company has always maintained that resveratrol-like compounds, which apparently work by boosting the activity of a gene called SIRT1, may also help to fight cancer. And this week the company has two pieces of news on the cancer front.

Firstly, John Lacey, Sirtris’s associate director of corporate communications, says that the company will present data next week in San Francisco showing that pushing SIRT1 to greater-than-normal activation levels can suppress tumor formation in an animal model that researchers use to study colon cancer. The as-yet-unpublished data was collected by David Sinclair, a Harvard Medical School pathologist and the company’s co-founder, and MIT biologist Leonard Guarente, the co-chair (and newest member) of Sirtris’s scientific advisory board.

Lacey, citing the Ingelfinger rule, declined to be more specific about which animal model Sinclair and Guarente studied, which compound they used to boost SIRT1 activation, or how great the anti-tumor effect was. (The Ingelfinger rule, named after Franz Ingelfinger, the editor of the New England Journal of Medicine from 1967 to 1977, says that researchers are disqualified from publishing their research in NEJM if the substance of it has already been reported elsewhere. Many other peer-reviewed journals have adopted the same stance, to the eternal frustration of journalists.)

But Lacey did say that the Sirtris study, which Sinclair will discuss on February 28 in a talk at the Gladstone Insitute at the University of California, San Francisco, is the first in which SIRT1 activation has been shown to deter cancer in vivo, that is, outside of a petri dish. And he said the effect was significant enough that Sirtris plans to launch a Phase Ib oncology trial of its SIRT1-activating compound or compounds in humans in the second half of 2008.

The study also represents the first time Sinclair and Guarente have collaborated since Guarente joined Sirtris’s scientific advisory board. As I recounted last November, the two researchers have a convoluted history together. Sinclair was a doctoral student in Guarente’s lab at MIT in the 1990s. He declined to join his mentor when Guarente launched Elixir Pharmaceuticals in 1999 to pursue drugs that might modulate SIRT1 and similar genes. Sinclair then co-founded Sirtris in 2004 to do the same thing. Elixir has since drifted away from its focus on SIRT1 activation and recently postponed its planned IPO; Guarente left the company and, after the expiration of a year-long non-compete agreement, joined the Sirtris advisory board.

Sirtris’s second piece of news is about an agreement to collaborate with the National Institute of Health’s National Cancer Institute (NCI) to study the anti-cancer effects of SRT501, the company’s proprietary formulation of resveratrol, and other unrelated compounds or “new chemical entities” that are reportedly much more powerful activators of SIRT1. Under a recently signed cooperative research and development agreement (CRADA), Peter Elliott, Sirtris’s senior vice president and head of development, will work with Thomas Sayers, a principal investigator at the NCI, to test Sirtris’s compounds on cell lines commonly used to study tumor development, as well as mouse models.

Under the agreement, NCI will foot the bill for the studies. Lacey says it’s not clear how long it will take for the collaboration to produce results. “The NCI is providing the financial resources for the study and the human resources, and we will be providing the new chemical entities and SRT501 as well as guidance in the study,” Lacey says. “In terms of the length of the study, there is no endpoint at this time. It is a study with multiple variables, so it could take some time.”

Elliott and Sayers have their own history together. A similar CRADA between Sayers’ lab at NCI and Cambridge’s Millennium Pharmaceuticals, where Elliott was vice president of pharmacology and development, led to the development of Velcade, a treatment for multiple myeloma and mantle cell lymphoma that is now Millennium’s premier drug product.

“I am proud to be teaming again with Tom Sayers,” Elliott said in a Sirtris press release announcing the agreement. “Several years ago Tom and I worked successfully together on the development of the anti-cancer drug Velcade, and now we are exploring an exciting new opportunity for targeting cancers using SIRT1 activators.”

NCI is interested in SRT501 and Sirtris’s other compounds because of the dearth of novel treatments for cancer, and because Sirtris’s early studies have shown that activating SIRT1 is a safe and promising approach, according to Lacey. “What we’ve seen from the Phase Ia and Ib studies that we’ve reported is that SRT501 is safe, and that it lowers insulin, which is proof of principle that the benefits of SIRT1 activation seem to be carried over to humans,” Lacey says. “And one of the things about the overexpression of SIRT1 in long-lived mouse models is that you do not see cancer in these animals. So that makes it an interesting potential therapy.”

Wade Roush is a contributing editor at Xconomy. Follow @wroush

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  • Mary Wright

    Resveratrol can help you to lead a long and healthy life so says Dr. Oz.
    Natural resveraatrol has few side effects and can simulate caloric resriction.
    Resveratrol Supplements can help you control your weight naturally
    by increasing energy, reducing cravings, and limiting your appetite.
    According to Wikipedia, Consumer Lab, an independent dietary
    supplement and over the counter products evaluation organization,
    published a report on 13 November 2007 on the popular resveratrol
    supplements. The organization reported that there exists a wide range
    in quality, dose, and price among the 13 resveratrol products
    evaluated. The actual amount of resveratrol contained in the
    different brands range from 2.2mg for Revatrol, which claimed to have
    400mg of “Red Wine Grape Complex”, to 500mg for Biotivia.com Transmax,
    which is consistent with the amount claimed on the product’s label.
    Prices per 100mg of resveratrol ranged from less than $.30 for
    products made by Biotivia.com, jarrow, and country life, to a high of
    $45.27 for the Revatrol brand. None of the products tested were found
    to have significant levels of heavy metals or other contaminants.

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  • Elisabeth Hamilton

    This ingredient, resveratrol, is possible to obtain via supplements at dosages that equal the Dr. Sinclair Harvard study in which mice lived 31% longer. I parallel with the Sirtris studies are a wide range of researchers and universities engaged in the study of resveratrol itself. Transmax, a concentrated lab-grade extract consisting of entirely the trans isomer of resveratrol is being trialed at Woods Hole, Colombia, and several German institutes investigating its anti-cancer, neuroprotective and DNA repair properties. While the Sirtris drug is at least five years away resveratrol can be easily acquired now, without a prescription.

  • http://resveratrol.com Neal Miller

    Sirtris has shown in HUMAN models that resveratrol has a promising future in treating type 2 diabetes. This is just the start. Resveratrol will be used to treat aging in the near future.
    Check out Resveratrol.com for some good insights. Neal Miller

  • Zan Robertson

    Ingelfinger rule? – this does not make sense in the context of what Sirtris is saying. They are not publishing in the NEJM here. Let me translate for you; the compound was resveratrol – SRT501. Sirtris does not want this known. What is their business model if resveratrol, not their “more potent” artificial chemical entities can treat cancer? Greed.

  • Dr. LeClair

    We can all agree that resveratrol has long been accepted as one of many components to living a more health protective quality of life. Cynics can argue forever that an artificial compound produced by a “for profit” corporation is only done so in the measure of greed and profit. The truth remains, however, that isolated compounds from naturally occurring elements of nature still may have biologically active components that “side effect” the body in a way other than scientists intend. The only way to know with 100% certainty that what you are prescribed is going to produce the intended effect is to synthesize it in a lab.
    I wish we could find the natural complement for every drug that my colleagues and I prescribe for our patients- if for nothing more than as a preventative measure from staving off potential disease. But we prescribe these drugs in doses much higher than found in nature. The much higher dose of the unintended other molecules might end up doing more harm than good! Therefore, perhaps you may want to consider the advice that we give to all our patients- Eat a healthy balanced diet and take a standardized multivitamin! Surely, if we start at health prevention, then we wouldn’t be so focused on the cynicism of why a drug company makes a drug! Afterall, there are millions of EASIER ways to make a profit and be greedy than coming up with a new synthetic drug! Thank you.