With 2010 almost in the books—and a lot of people grounded by the Northeast blizzard—it seems like a good time to take a break and look back at some of Xconomy Boston’s top stories of the year.

These are not necessarily the ones that generated the most traffic (although in some cases they did). Instead, they are stories that best exemplify what we try to deliver to our readers day in and day out—the stories behind the companies, ideas, and people that are helping to create the future of innovation in our network of cities.

Our Boston editor’s picks span a wide range of subjects, from young startups (Baydin, Krush, Energesis) to established public companies (Genzyme, Vertex, Unica, Progress Software), from software and information technology to life sciences, biotech, and energy. They range from unique breaking news stories (Resveratrol) to in-depth features (TripAdvisor), Q&As (John Glaser, Arif Padaria), and commentary/analysis (entrepreneurial Walk of Fame).

Without further ado, here are our top 20 stories of 2010, sorted by sector:

Top 10 Tech Stories

Krush Founder Gina Ashe, Survivor of Horrific Car Crash, Has New Lease on Startup Life

Q&A on Startups and Investing Strategy with Massachusetts Clean Energy Center’s “State Angel” Arif Padaria

Why Rich Levandov Invested Early in Zynga, and Why It Took Off—Lessons Every Entrepreneur Should Consider

Twitter Plea Helps Baydin Get Seed Money from Angel Investor Dave McClure; Startup Moving to the Valley Next Month

Kendall Square Wants an Entrepreneurial Walk of Fame—and So Should Every Innovation Hub

The Unica Story: Yuchun Lee’s Journey from MIT Blackjack Team to IBM Acquisition

Is Boston Becoming a Hub for Female Tech Entrepreneurs? Maybe, and Here’s Why

Tim Berners-Lee and Group of Boston Web Gurus Leading New MIT Class to Get Linked Data to Market

Reinventing Progress Software—Boston’s Next Billion-Dollar Company?

TripAdvisor: The Travel Company That’s Really All About Data

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Top 10 Life Sciences Stories

Avila Therapeutics Pursuing Rival to Lung Cancer Drug in Dana-Farber Lawsuit

Energesis Pharmaceuticals, Co-Founded by Sirtris Vet, Seeks to Tap Power of “Good Fat” in Fighting Obesity and Diabetes

Genzyme Boss Henri Termeer Not Ready to Sell to Sanofi, Ride Into the Sunset, Sources Say

Former Sirtris Execs’ Nonprofit Starts Selling Resveratrol with Potential Anti-Aging Effects Online

John Glaser, Boston’s Top Hospital Geek, Talks About Obama’s Health IT Plan and Getting Booted from Catholic School

Vertex, Worth $7.5B, Eagerly Awaits Final Proof that Hepatitis C Drug Works

Cooking with the Genzyme Recipe: New Players Funding Rare Disease Drugs in Boston

The Genetics Institute Alumni: Where Are They Now?

Prominent Flatley Family Launches Boston Nonprofit for Cystic Fibrosis Drug Research

Chairman Bill Young: Next Biogen Idec CEO May Be a Scientist

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This week we took an in-depth look at several New England area biotechs, and saw some interesting developments from bigger drugmakers.

—I checked in with Holden, MA-based Hygeia Therapeutics, a startup developing topically delivered synthetic hormone treatments, using technology licensed from Yale University. The biotech has gathered pre-clinical data on a synthetic estrogen product for the treatment of age-related skin thinning.

—Ryan profiled Selventa, a Cambridge, MA-based startup formerly named Genstruct that is developing software to help pair the right patients with the right experimental treatments—before expensive clinical research trials are done. The firm, which has kept pretty quiet about its technology since starting in 2002, is now making a push to publicize its research and technology.

—Cambridge-based Aileron Therapeutics inked a deal for exclusive rights to “click” chemistry technology from The Scripps Research Institute in La Jolla, CA.

—Antibody technology developer Adimab, of Lebanon, NH, brought in a $4 million Series E funding round. The startup, which was founded in 2007 and is working on yeast-based human antibody discovery technology, raised the financing at a pre-money valuation of $520 million, which is double the value of the company when it raised its last round in October 2009.

—Cambridge-based Aveo Pharmaceuticals (NASDAQ:AVEO) said it will bring in $25 million in two equal payments from OSI Pharmaceuticals, which has exercised its option to Aveo’s technology for research in cancer and patient biomarker selection. Aveo’s platform allows researchers to engineer animal models with genetic mutations that are present in human forms of cancer.

—GlaxoSmithKline axed a mid-stage clinical trial of SRT501, a drug it picked up as part of its 2008 acquisition of Cambridge-based Sirtris Pharmaceuticals that is a formulation of the “red wine” chemical resveratrol. Glaxo chose to … Next Page »

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London-based GlaxoSmithKline has terminated a mid-stage clinical trial of SRT501 in patients with advanced multiple myeloma, the company said in a statement e-mailed to Xconomy today. The firm acquired the drug, a formulation of resveratrol, in its $720 million buyout of Cambridge, MA-based Sirtris Pharmaceuticals in 2008.

Sirtris has captured wide media attention because of the potential anti-aging benefits of the naturally occurring chemical resveratrol, which can be found in the skin of red grapes and in red wine.

Glaxo decided to end the trial after a review of data from the study found that the formulation of resveratrol “may only offer minimal efficacy while having a potential to indirectly” cause kidney complications that often occur in myeloma patients, according to the company’s statement. The Myeloma Beacon first reported the news about the recent decision to terminate the trial yesterday. Multiple myeloma is a type of cancer found in plasma cells.

The Phase IIa clinical trial tested the use of SRT501 with and without the approved cancer treatment bortezomib (Velcade), according to the government’s clinical trials website.

Glaxo had suspended enrollment of the study in April of this year after cases of acute kidney failure were found in five study patients, according to the company. In the company’s analysis of these cases, it “concluded that these renal failure cases were most likely due to the underlying disease, as kidney complications related to myeloma occur in up to 50 [percent] of cases. However, the formulation of SRT501 was not well tolerated, and side effects of nausea/vomiting/diarrhea may have indirectly led to dehydration, which exacerbated the development of the acute renal failure,” the company said.

Glaxo, which continues to operate Sirtris as its subsidiary in Cambridge, said that it is now focusing on “selective SIRT1 activator compounds that have no chemical relationship to SRT501 and more favorable drug-like properties.” Those selective activators include compounds known as SRT2104 and SRT2379.

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News of funding and partnerships for area biotechs, plus an in-depth interview with a state life sciences administrator, made it a busy news week for us.

—Last week Ryan broke the news that former executives of Sirtris Pharmaceuticals, the biotech known for developing drugs based on the red wine chemical resveratrol, were selling a dietary supplement form of the chemical via their nonprofit, the Healthy Lifespan Institute. GlaxoSmithKline, which acquired Sirtris more than two years ago for about $720 million, ordered Christoph Westphal and Michelle Dipp to stop online sales of the dietary supplement, which is believed to activate anti-aging genes that boost metabolic functions in cells. (The supplements are made in the same synthetic process as the resveratrol drug SRT501; the Healthy Lifespan Institute says that the drug was tested in liquid form in capsules of 5 grams and the supplements are provided in powder form in 250-milligram capsules). Glaxo told Westphal and Dipp to resign from the board of the nonprofit that was selling resveratrol supplements. Glaxo claimed it was unaware resveratrol was being sold via the nonprofit.

—Watertown, MA-based Selecta Biosciences, a biotech company developing nanoparticle-based vaccines, added a new chief executive, Werner Cautreels. He previously worked as CEO at Belgium-based Solvay Pharmaceuticals, until shortly after Abbott Laboratories (NYSE: ABT) bought the company for $6.6 billion. Selecta also attracted a $3 million grant from the National Institutes of Health to research a nicotine vaccine for those addicted to cigarettes.

—Ryan sat down with Susan Windham-Bannister, head of the Massachusetts Life Sciences Center, which is in charge of running the state’s plan to invest $1 billion in the life sciences sector over 10 years. The two-part story on their inerview spotlights Windham-Bannister’s take on topics like Sanofi-Aventis’ potential takeover of Genzyme, the role of activist investor Carl Icahn, and the influence political change could have on the state’s plans for advancing the life sciences industry.

—Shape Up The Nation, a maker of Web-based software and services for employer wellness programs, pulled in a $5 million Series A funding round. Company management, Cue Ball Capital, and Excel Venture Management participated in the financing for Providence, RI-based Shape Up The Nation.

—Protein biomarker technology developer Avantra Biosciences of Woburn, MA, raised $7 million in a Series A funding round. The company is developing its technology to … Next Page »

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[Updated and clarified. 8/12/10, 7:25 pm Eastern time. See below.] Cambridge, MA-based Sirtris Pharmaceuticals made international headlines over the past few years for developing drugs based on the anti-aging effects of the red wine chemical resveratrol. Now that the company has been part of London-based drug giant GlaxoSmithKline for more than two years, former Sirtris executives have begun selling their own resveratrol supplements online through their Boston nonprofit, the Healthy Lifespan Institute, Xconomy has learned.

Michelle Dipp, a Sirtris-turned-Glaxo executive, confirmed that the nonprofit that she and former Sirtris CEO Christoph Westphal co-founded last year has started online sales of resveratrol. Dipp leads the effort on the off hours when she isn’t doing her main job as senior vice president of Glaxo’s Center of Excellence for External Drug Discovery.

While the group is charging $540 for a one-year supply of resveratrol, Dipp says that the nonprofit is selling the supplements for cost and is not profiting from the sales. The revenues are covering the manufacturing, distribution, and other functions, all of which have been outsourced, she says.

The nonprofit’s supplements are made the same way as the formulation of resveratrol that Sirtris initially developed as a drug called SRT501 for Type 2 diabetes, cancer, and other diseases, Dipp says. While the chemical formula for the supplement is the same as the drug, the group’s resveratrol supplements are being offered as just that: dietary supplements, not drugs for specific diseases. That means the group can sell resveratrol just like any other dietary supplements without doing FDA-sanctioned clinical trials to get permission to begin sales. (Editor’s note: Though the nonprofit’s supplements are made in the same synthetic process as SRT501, the group says that the drug was tested in liquid form in capsules of 5 grams and the supplements are provided in powder form in 250-milligram capsules.)

Numerous outfits have been selling resveratrol supplements for years. Some were even caught illegally using the likenesses of Sirtris founders David Sinclair, a professor at Harvard Medical School, and Westphal, who now heads Glaxo’s venture firm, SR One. Dipp—who formed the Healthy Lifespan Institute with Westphal and others last year—says that their group is the only one she knows of that manufactures resveratrol in a completely synthetic process with the same high standards for sterilization and purity that govern pharmaceutical production.

To be clear, this resveratrol operation is a volunteer effort that Dipp and Westphal do on the side. Both are still employees of Glaxo, and they have also started a Boston venture firm called Longwood Founders Fund with fellow Sirtris co-founder Rich Aldrich.

“Our main business is … Next Page »

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News surrounding Genzyme’s ongoing battle with billionaire investor Carl Icahn cropped up this week, alongside headlines from other big biotechs and in-depth profiles on newer life sciences names in the New England area.

—Luke caught up with the chief scientist and the co-founder of Cambridge, MA-based Proteostasis Therapeutics, which was built around research from the Scripps Research Institute, the Salk Institute for Biological Studies, and Northwestern University. The company, which launched with a massive $45 million venture capital round in 2008, is out to make drugs that alter the protein pathways that break down as people age, contributing to conditions like Alzheimer’s disease and Parkinson’s.

—Ryan took a look at Ligon Discovery, a spinoff of MIT and Harvard’s Broad Institute that develops small-molecule technology that could have applications in identifying potential disease proteins and finding drugs to home in on those targets.

—Link Medicine, a Cambridge developer of drugs to treat neurodegenerative diseases, exceeded its original expectations for its Series C round of funding by $5 million, the company’s CEO told Ryan. A third closing of the Series C, at $20 million, brought the round’s total to $45 million, money that will go to testing Link’s drug for treating mild Alzheimer’s, which went into its first human clinical trial in November 2009.

—Activist investor Carl Icahn continued his campaign for greater influence on the board of Cambridge-based Genzyme (NASDAQ: GENZ), filing a proxy statement with the SEC in which he called the drugmaker’s manufacturing system “broken,” and advised shareholders not to reelect chairman and CEO Henri Termeer to the board. Icahn, who controls 4.9 percent of Genzyme’s common stock, is vying to get himself and three associates on the board, which has 10 seats up for reelection in mid June. On Thursday, the Genzyme board of directors also announced plans for a $2 billion stock repurchase aimed at increasing shareholder value

—I profiled Beverly, MA-based Eliza, a company that employs intelligent speech-recognition technology in a system of automated phone calls that communicate to patients about their healthcare, on behalf of insurers, employers, and prescription benefit managers. The company has made more than 400 million phone calls in ten years, encouraging patients to do everything from lose weight to schedule preventative screenings.

—Cambridge’s Ariad Pharmaceuticals (NASDAQ: ARIA) revised a 2007 agreement with Merck & Co, giving the pharma giant exclusive license to develop, produce, and sell Ariad’s cancer drug, ridaforolimus—activities that Merck (NYSE: MRK) will also cover the costs of. Initially, the two companies were sharing the marketing rights and the responsibilities of funding the development of the drug, which is designed to treat certain soft tissue and bone sarcomas. Ariad nabbed $69 million for the revised deal, which comes on top of … Next Page »

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There’s bad news this week about one of the much-hyped drug candidates based on the red wine chemical called resveratrol. Several news outlets are reporting that safety concerns have prompted GlaxoSmithKline to halt a mid-stage clinical trial of the drug, called SRT501, which the London-based drug giant gained in its $720 million buyout of Sirtris Pharmaceuticals in 2008.

Glaxo put a stop to a Phase II trial of the drug in patients with multiple myeloma, a cancer of the bone marrow and plasma, after some patients in the study developed a condition that can lead to kidney failure, according to the Wall Street Journal. Some of the patients in the trial were also taking bortezomib, an approved cancer drug marked as Velcade. The chemist Derek Lowe broke this news on his blog, “In the Pipeline,” on Monday based on an April 22 update on the trial posted on ClinicalTrials.gov, a U.S.-government-run registry of clinical trials.

Normally, the failure of a mid-stage trial at a big pharmaceutical company wouldn’t generate tons of press coverage, but this study is different—perhaps because we reporters have heaped so much coverage on Sirtris, resveratrol, and related “anti-aging” drugs in the first place. (Resveratrol and drugs candidates like SRT501 that are based on it are believed to activate anti-aging enzymes called sirtuins.)

Despite the concerns in Glaxo’s multiple myeloma trial, Sirtris’s formulation of resveratrol had previously been studied in patients with diabetes and other cancers without the same safety problems. Also, Sirtris, which now operates as a subsidiary of Glaxo, says that it has discovered new compounds that are vastly more potent than resveratrol and SRT501, and one such new compound has become the focus of its efforts to find new ways to treat diabetes. Still, the ill-fated study of SRT501 in multiple myeloma is one reason to remain skeptical of the health benefits of resveratrol until they can be proven in further human studies.

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There were a wide variety of developments in the Boston-area life sciences sector over the past week. Companies in the headlines included big ones like Genzyme and Covidien as well as smaller startups such as Humedica and Tetraphase Pharmaceuticals. Here are some highlights:

—We got an early look at Cambridge, MA-based Humedica’s strategy for developing next-generation clinical analytics systems, as well as some insights into why Bain Capital Ventures, General Catalyst Ventures, North Bridge Venture Partners, and Leerink Swann have pumped $30 million into the young company. Company CEO Michael Weintraub talked about how the firm could become a U.S. Census of sorts for healthcare.

—Genzyme faced more setbacks due to previously tainted bioreactors at its Allston, MA, plant. The Cambridge -based biotech powerhouse (NASDAQ:GENZ) revealed that it’s going to take longer than expected to resume full production of its enzyme-replacement drug agalsidase beta (Fabrazyme) for Fabry disease. Also, the company is anticipating lower sales than previously estimated for both agalsidase beta and imiglucerase (Cerezyme).

—Sirtris CEO Christoph Westphal gave Xconomy the first media interview about a new nonprofit group that he and his colleagues are launching in the Boston area to promote longer healthy lives. Can the red wine chemical resveratrol really help people live longer? Westphal talked about how his new group, the Healthy Lifespan Institute, plans to answer that big question and more.

—After a period of poor stock performance for Cambridge-based biotech Alkermes (NASDAQ:ALKS), company Chairman Richard Pops has jumped back into everyday operations as CEO—a post he left in … Next Page »

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Cambridge, MA-based biotech firm Sirtris has garnered national and international attention for its work to use its formulation of resveratrol, a natural chemical found in red wine, to treat diseases of aging such as Type 2 diabetes and cancer. Now the company, a wholly-owned subsidiary of British drug giant GlaxoSmithKline (NYSE:GSK), plans to increase its focus on developing a more potent molecule to treat diabetes, according to CEO Christoph Westphal.

Westphal made a presentation of some new data from studies his biotech firm has conducted with the new chemical entities, or NCEs, at the Boston Biotech R&D conference the company hosted at Harvard Medical School yesterday. Sirtris says the new drugs are more than 1,000 times more potent than its formulation of resveratrol, dubbed SRT501. Westphal told me in an interview that his company plans to conduct Phase 2 clinical trials of a new molecule called SRT2104 as a treatment for diabetes next year. Meantime, the earlier form of resveratrol is being scrapped in diabetes, yet Westphal says the company plans to continue developing it to treat colon cancer and a rare metabolic disorder called MELAS.

“I think ultimately, from a pharmaceutical- company perspective, a patented, composition-of-matter compound that is 1,000 times more potent is going to be more attractive than reformulated resveratrol, so definitely our focus is more on the NCEs,” Westphal says.

The new drugs, like resveratrol, are designed to activate genes linked to the production of sirtuins, which have shown in early studies to increase metabolic function and essentially mimic the benefits of consuming fewer calories.

Sirtris presented basic findings from an early human study of the new chemical, revealing only that it was well-tolerated and caused no serious side effects in humans. Sirtris and GSK aren’t saying how well it works in treating diabetes in humans, says Michelle Dipp, Sirtris’ vice president of corporate development. (The company did highlight that the compound about doubled the lifespan of mice in a new study, however.)

In a related development, Westphal revealed publicly for the first time that the company plans to develop its new drugs to treat neurological disorders such as Alzheimer’s, Huntington’s, Parkinson’s disease and chronic obstructive pulmonary disorder. He says his company won’t necessarily get bigger in Cambridge, because GSK can do much of the clinical trials work at other research and development units around the world.

Westphal gave credit to his new pharma parent GSK—which acquired Sirtris in a $720 million buyout earlier this year—for providing his firm the resources to pursue more drug development programs. GSK recently approved a $200 million budget for its Sirtris unit for the next three years, which Westphal says is about twice as much as his company could have afforded to spend as an independent biotech.

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Sirtris is now part of pharmaceutical behemoth GlaxoSmithKline (NYSE:GSK), but the British giant has allowed its acquisition a unique dose of autonomy since it bought the small, Cambridge, MA-based biotech in June for $720 million. For those who still haven’t heard, Sirtris is known around the world for the dazzling potential of its drugs to lengthen healthy human lifespan. Christoph Westphal, CEO of Sirtris, says his company will have some exciting news to share next month about the first human tests of its next-generation drugs—which will likely make it even better-known. Yet, when I caught up with him last week, the news about its trials was just one of several insights Westphal shared about what’s been brewing at Sirtris this summer.

Xconomy: What are the perks of Big Pharma ownership?

Christoph Westphal: There’s actually a lot of perks. I think the most important one is we think it is much more likely we’re going to get a drug to market than it was before. And there are several reasons for that. We have a budget that we’ve just been given for the next three years, which is 30 to 50 percent greater than we could have afforded as an independent company. Secondly, we have an opportunity to leverage global GSK, so there’s a lot of skill sets and abilities and machines and scale-up capabilities. It’s literally dozens and dozens of things that we never could have done on our own that we can now do as part of GSK.

X: What makes Sirtris unique from other biotechs acquired by Big Pharma?

CW: Both GSK and we were interested in keeping Sirtris independent and autonomous, which is why we’ve retained our name, we’ve retained our management structure [no more board of directors anymore, of course], we had a strong incentive to retain our employees, which we’ve done, and really almost all decisions are made almost exactly the same way they were before. That may be a little bit different than some acquisitions, where quickly the company was no longer autonomous. Literally, there’s no one here from GSK, five months after we announced the acquisition. And they’ve been very hands-off in all of our decisions. I think they are very smart and careful and thoughtful. So we pitched them on what our three-year plan is, but they are basically funding us like venture guys would fund us or public market folks would fund us, saying, ‘Day-to-day decisions are totally up to you, but we do expect in the next several years you to generate significant value,’ which I think is fair.

X: How long do you plan to stay with Sirtris?
… Next Page »

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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.

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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.

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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.”

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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.

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