Cambridge, MA-based Constellation Pharmaceuticals is announcing today that it has formed a major partnership with Roche’s Genentech unit, based in South San Francisco, to develop treatments for cancer and other diseases. The deal is worth $95 million to Constellation in the form of an up-front payment and research support over the next three years. Constellation—which was founded in 2008 and backed by Third Rock Ventures and other leading VC groups—may also receive milestone payments and double-digit royalties on any products that come out of the alliance.

This is by far Genentech’s biggest bet to date on epigenetics—the science of understanding and addressing molecular changes in cells that activate or de-activate disease-causing genes—says James Sabry, vice president of Genentech Partnering. “This is a a once-in-a-decade type of deal for us,” Sabry says. And while there are plenty of other startups working in the field, Genentech chose Constellation for the quality of its scientific progress so far, Sabry says. “Epigenetics is a huge evolving area of biology representing hundreds of new targets,” he says. “We actually sat down on the bench with Constellation’s scientists and we felt the quality of their work was akin to ours.”

For Constellation, the deal is a stamp of approval on a broad-based strategy that the company put in place the day it was founded, says CEO Mark Goldsmith. Constellation is pursuing three classes of enzymes that affect chromatin—the combination of DNA and the proteins that the DNA is wound around in the cell’s nucleus. Those enzymes are commonly referred to as “writers,” ”readers,” and “erasers,” because some place chromatin markers that control the epigenetic process, others read those marks, and still others erase them. While several startups have targeted one or another of the classes, Constellation has developed a platform that can uncover drug candidates in all three of them. “From the outset we have emphasized breadth and depth as a differentiating approach,” Goldsmith says.

Genentech's James Sabry

The two companies will collaborate to identify drug targets and lead molecules in a joint steering committee. The initial focus will be oncology, though the companies expect to identify other disease targets as they learn more. A team of Genentech scientists will work closely with Constellation’s researchers, with the common goal of moving as many drug candidates forward as possible, Sabry says. “They will feel like we’re all one company,” he says.

Goldsmith adds that Genentech’s input will be invaluable to furthering the startup’s progress. “The momentum we already established in R&D is now married with the rigorous scientific input of Genentech, which is well known for its ability to translate scientific benefits to patients,” he says.

There are two features of Constellation’s deal with Genentech that make it stand out from other such drug-discovery alliances. First, Constellation will retain exclusive rights to its two most advanced programs, which focus on … Next Page »

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We saw an interesting mix of financings, collaborations, and research news from New England’s drug and medical device developers this week.

—HealthCare Ventures put $15 million in Series A funding into Cambridge, MA-based Tensha Therapeutics, a startup developing small-molecule drugs designed to treat cancer and other diseases by regulating the expression of disease-associated genes.

—Boston’s Brigham and Women’s Hospital said it will use technology from Cambridge-based GNS Healthcare (part of Via Science) to help manage the cost of treating congestive heart failure patients. GNS Healthcare will apply its computer simulation models to predict the likelihood that the hospital patients will experience adverse drug events or readmission.

—Henri Termeer, who was CEO of Cambridge-based Genzyme before its acquisition by Sanofi-Aventis, donated $10 million to Massachusetts General Hospital to establish the new Henri and Belinda Termeer Center for Targeted Therapies. It will focus on developing more personalized cancer drugs, initially for certain genetic forms of breast cancer, lung cancer, and leukemias.

—Natick, MA-based Boston Scientific (NASDAQ: BSX) revealed that it will be bringing in Michael Mahoney as president starting next month and as CEO in November 2012. Current CEO Ray Elliott announced in May that he’d be stepping down; soon-to-be interim CEO Hank Kucheman will have the job until Mahoney, formerly worldwide chairman of Johnson & Johnson’s medical device and diagnostics group, takes the chief executive role.

—GI Dynamics, a Lexington, MA-based medical device developer, went public on the Australian stock exchange to raise the $80 million it needed to get through the next three years, wrote Xconomy New York editor Arlene Weintraub. The company is looking to get regulatory approval for its device to be used as a treatment for obesity and type 2 diabetes.

—NABsys, a Providence, RI-based maker of gene-sequencing tools, took in a $10 million Series C investment from Stata Venture Partners. The Needham, MA-based firm, founded by semiconductor pioneer Ray Stata, also led NABsys’ $7 million Series B funding round. The startup said it will use the new financing for development and commercialization of its solid-state electronic systems for single-molecule DNA sequencing and analysis.  The company is similar to Ion Torrent, a new unit of Carlsbad, CA-based Life Sciences that’s using semiconductor technology in its gene-sequencing machine.

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Cambridge, MA-based drug developer Tensha Therapeutics announced today that it has snapped up $15 million in Series A funding from HealthCare Ventures. The funding will go to developing Tensha’s small molecule drug candidates, which are designed to treat cancer and other diseases by regulating the expression of disease-associated genes.

Tensha’s drugs are inhibitors of so-called bromodomains, protein modules that are key players in epigenetics—the process of turning genes on and off without altering the underlying DNA code. Tensha has an exclusive license from Dana-Farber Cancer Institute to technology developed by one of its investigators, James Bradner, who identified and characterized small molecule inhibitors of certain bromodomain proteins that are key to cancer cell growth, according to today’s announcement. Tensha’s lead drug program is in pre-clinical development for treatment of a rare cancer called BRD4-NUT midline carcinoma, acute myeloid leukemias, multiple myeloma, and other diseases.

“There is a compelling biological rationale for bromodomain inhibition in cancer. Our collaborative studies to date have established the feasibility of targeting epigenetic reader proteins. Through Tensha, we have a foundation for developing and translating novel bromodomain inhibitors,” said Bradner in the announcement of the deal.

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Just two months after reporting positive data from a clinical trial of its lead drug candidate in lung cancer, Waltham, MA-based Syndax said today that the same drug performed well in a Phase 2 breast cancer trial. Results from the trial of the drug, called entinostat, will be presented at the American Society of Clinical Oncology (ASCO) Breast Cancer Symposium this week in San Francisco.

The drug was tested in 130 postmenopausal women with a type of the disease known as estrogen receptor-positive breast cancer. The women received either entinostat plus exemestane (Aromasin, made by Pfizer) or exemestane plus placebo. The combination containing Syndax’s drug nearly doubled the amount of time women survived without their disease progressing—from 2.3 months to 4.3 months. Although such “progression-free survival” was the primary endpoint, the study also showed that overall survival increased by nearly seven months, to a total of 26.9 months.

Syndax is pursuing drugs designed around epigenetics—the molecular changes in cells that can activate or de-activate genes without affecting the underlying DNA. Entinostat inhibits certain enzymes that influence specific epigenetic alterations. Those epigenetic alterations are believed to drive cancer growth and drug tolerance, so blocking them should enhance cancer treatment, Syndax’s researchers believe.

The results were a pleasant surprise for Syndax’s CEO, Joanna Horobin, who trained as a physician before joining the drug industry 25 years ago. “The study was not powered around overall survival, but it is still significant to see a seven-month benefit there,” she says. Based on the positive results from the trial, Syndax plans to start a pivotal Phase 3 trial in early 2012.

Syndax has also identified a biomarker that seems to indicate whether patients with breast cancer are responding to entinostat. The trial demonstrated that median progression-free survival rates in women with that biomarker increased to over six months. “Rather than waiting eight weeks to take a scan to see if it’s working, we can take a blood sample before the treatment, then at day one, day eight, and day 15,” Horobin says. “Then we can see if the drug is impacting the target.” Syndax will incorporate biomarker testing into the Phase 3 trials, she says.

If all goes well with the Phase 3 program, Horobin adds, entinostat could become the first epigenetic therapy approved for patients with solid tumors. “There hasn’t been much to improve the therapies available to breast cancer patients,” Horobin says. “I, as a physician, find this opportunity really exciting.”

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Executives from Syndax Pharmaceuticals are spending their post-holiday week in Amsterdam, where they’ll be presenting three sets of data on the company’s lung cancer drug at the International Association for the Study of Lung Cancer conference. The drug, called entinostat, is in Phase 2 clinical testing, the results of which will be critical to advancing Syndax’s plan to move into Phase 3 next year.

Syndax, based in Waltham, MA, is one of several Boston-area companies pursuing drugs designed around epigenetics—the molecular changes in cells that can activate or de-activate genes without affecting the underlying DNA. Entinostat is a selective histone deacetylase inhibitor. It acts against certain enzymes that influence specific epigenetic alterations that drive cancer growth and drug tolerance. Syndax’s strategy is to test the drug in combination with other cancer therapies, so as to boost the receptiveness of a patient’s tumor to drugs to which it might not normally respond.

In previous studies, Syndax showed that in non-small cell lung cancer patients with high levels of a specific protein called e-cadherin, entinostat plus the blockbuster drug erlotinib (Tarceva) produced a survival benefit over entinostat plus placebo. The e-cadherin biomarker is found in about 40 percent of patients with the disease. On July 6 in Amsterdam, researchers for the company will present data further defining the e-cadherin biomarker and showing that some patients with resistance to erlotinib benefitted from the addition of Syndax’s drug.

Syndax CEO Joanna Horobin says the further definition of the e-cadherin biomarker, as described in the data being presented, will allow the company to better design an effective Phase 3 program. “The most important thing is that this gives us a robust way to select patients” who are most likely to benefit from entinostat, she says. “We can identify the right patients to treat and monitor them while they’re being treated.”

Horobin says the company aims to start a Phase 3 study of entinostat plus erlotinib in the first half of next year. She adds that if the study succeeds, the drug will most likely be able to be marketed with a companion diagnostic to identify patients whose tumors have high levels of e-cadherin.

As the field of epigenetics continues to evolve, the cancer community is starting to explore the potential of combination epigenetic approaches. Towards that end, Syndax and the National Cancer Institute are studying entinostat … Next Page »

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When Xconomy last checked in on Cambridge, MA, epigenetics startup Constellation Pharmaceuticals, in the fall of 2009, CEO Mark Goldsmith declined to disclose details about the company’s pipeline. These days, he’s willing to be a little more forthcoming. On June 6, during the American Society of Clinical Oncology meeting in Chicago, Constellation announced it had added $15 million to its Series B venture financing—bringing the total amount of money raised to an impressive $70 million.

And now the nascent world of epigenetics is getting a glimpse of how Constellation’s strategy and pipeline are evolving. In an interview a few days after the funding announcement, Goldsmith explained to Xconomy that Constellation is focusing on three different classes of drug targets, and he used terminology developed by Rockefeller University epigenetics researcher David Allis to describe them: “writers,” “erasers,” and “readers.”

In general terms, epigenetics is the study of molecular changes in cells that can activate or de-activate genes without affecting the underlying DNA code. Multiple enzymes—those writers, erasers, and readers that Constellation is targeting—are believed to play a role in epigenetic changes that may promote many diseases, including cancer, which is Constellation’s main focus.

Although the science of these enzymes is still not completely understood, they are all factors that modulate chromatin—the combination of DNA and the proteins that the DNA is wound around in the cell’s nucleus—as a means … Next Page »

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Cambridge, MA-based Constellation Pharmaceuticals said today it has raised $15 million in a Series B extension from its existing investors, including Third Rock Ventures, The Column Group, Venrock Associates, SR One, and Altitude Life Science Ventures. Constellation, whose Series B now totals $37 million (after a $32 million A round in 2008-09) is working to develop drugs for treating cancer, inflammatory and immunologic disorders, and other diseases. The company’s technology is based on epigenetics, the study of molecular changes in cells that can turn certain genes on and off without changing the underlying DNA code. Constellation is led by CEO Mark Goldsmith, who spoke with Xconomy back in 2009 after taking over from founding CEO Mark Levin, the former Millennium Pharmaceuticals boss and co-founder of Third Rock.

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Cambridge, MA-based Epizyme has nabbed another pharmaceutical partnership. Two months after announcing a deal worth as much as $650 million with GlaxoSmithKline (NYSE:GSK), the startup says today that it has landed a partnership with the Japanese drugmaker Eisai to develop drugs against an epigenetic enzyme for treating lymphomas and other cancers.

In its latest deal, Epizyme gets $6 million from Eisai at the start and potentially more than $200 million in milestone payments for various research, development, and sales goals tied to drugs against the EZH2 enzyme target. Tokyo-based Eisai, which has been expanding its investment in cancer research in Cambridge of late, has also agreed to finance all R&D expenses for the program through early human studies or “human proof-of-concept.” Epizyme then has an option to share in the profits and commercialization of products through its partnership with Eisai in the U.S.

The companies aim to develop drugs against this epigenetic target along with a genetic test that shows whether a patient’s cancer has the right genetic profile to respond to the treatments, a strategy that is being used more and more after the success other cancer drugs that use similar approaches such as Roche’s trastuzumab (Herceptin) for breast cancer and, most recently, Plexxikon and Roche’s PLX4032 for melanoma. This deal also provides another endorsement of Epizyme’s research, which is focused on a class of epigenetic enzymes called histone methyltransferases that are believed to play roles in cancers and other diseases.

In general, the field of epigenetics explores how certain genes get turned on and off without changing the underlying DNA code. While Epizyme has made cancer the focus of its research, the firm also sees an opportunity for drugs against epigenetic targets to treat inflammation, metabolic disorders, and neurodegenerative diseases. And the startup’s deal with London-based Glaxo covers cancer and other types of diseases.

From left: Jason Rhodes, chief business officer of Epizyme, and Robert Gould, president and CEO of Epizyme.

Eisai is also taking yet another step to increase its stake in Boston-area cancer drug development with its Epizyme deal. Last month, Eisai said it planned to invest $200 million over 10 years in a Cambridge-based venture called H3 Biomedicine, which is collaborating with scientific luminaries in the Boston area to discover drugs that target weak points in tumors. As of last month, Eisai already employed about 300 people at its R&D operation in Andover, MA, where it does some of its oncology research. And the company has had Boston-area research presence since the 1980s.

“Epizyme’s proprietary product platform; leadership in determining the oncogenic role of EZH2 in genetically-defined cancers; and success in discovering novel, potent, and selective small molecule inhibitors of histone methyltransferases, an important epigenetic target class, led us to them as the partner of choice in epigenetic drug discovery,” Takashi Owa, president of Eisai’s oncology product creation unit, said in a press release.

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Waltham, MA-based Syndax Pharmaceuticals is reporting data from a mid-stage clinical trial that indicate its lead compound might improve the effectiveness of an existing lung cancer drug, at least for a subpopulation of patients.

The company, co-founded by members of the Salk Institute for Biological Studies in La Jolla, CA, in 2005, conducted a double-blind, placebo-controlled Phase II clinical trial of its treatment in 132 patients with advanced non-small cell lung cancer. When the researchers looked at all patients in the study together, those treated with a combination treatment of its molecule, entinostat, and the blockbuster lung cancer drug erlotinib (Tarceva) did not have any longer progression-free survival those who received a combination of erlotinib and a placebo, according to the company. But in the 26 patients who had high levels of a protein called E-cadherin, the Syndax combo was associated with median survival of 9.4 months, versus 5.4 months in those patients who were on erlotinib and placebo.

Syndax’s strategy in clinical trials has been to test entinostat in combination with existing cancer drugs. The lead molecule is intended to block so-called epigenetic enzymes, essentially aiming to reprogram a patient’s tumor to be more receptive to other drugs to which the cancer might not otherwise respond. At least in the specific sub-group patients in its mid-stage clinical trial with erlotinib, the strategy appeared to work. Next year Syndax is expected to report data from a 125-patient mid-stage study of how well its drug improves treatment of advanced breast tumors in combination with the hormone therapy exemestane (Aromasin).

While the findings from the lung cancer study will need to be … Next Page »

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The past decade of cancer research and development was mainly about getting targeted. Chemotherapy that kills all kinds of cells—cancerous and healthy—is still a mainstay of treatment, but more targeted cancer drugs like Roche’s bevacizumab (Avastin) and Novartis’ imatinib (Gleevec) finally broke through and fulfilled at least some of their promise. They showed drugs could hit precise molecular targets integral to the growth and spread of cancer cells, and by doing that, they could hold tumors in check and help people live longer.

That’s past, but where are things heading in the future? Will this be the decade that molecular diagnostics come along and catch cancer at its earliest, most treatable stage? Will the era of complete human genomes for $1,000 a pop finally make the vision of personalized medicine a reality? Or will a whole new generation of antibody drugs and targeted small molecules continue to make step-by-by-step progress (and the occasional leap ahead) against specific malignancies?

These are the kind of questions we will explore on October 20 at our next big event in Boston, called “Xconomy Forum: Boston’s War on Cancer.” We’ll hear keynote talks from someone on the leading edge of research in New England (Tyler Jacks of the David H. Koch Institute for Integrative Cancer Research at MIT) and a leading pharmaceutical industry executive (Deborah Dunsire of Millennium:The Takeda Oncology Company).

In between, as we always do at Xconomy, we will highlight some of the most interesting entrepreneurs and startups pursuing creative strategies in the fight against cancer. We’ll hear 20-minute overview presentations from Doug Fambrough, the CEO of Watertown, MA-based Dicerna Pharmaceuticals; Mark Goldsmith, the CEO of Cambridge, MA-based Constellation Pharmaceuticals; and Dave Okrongly, the CEO of Cambridge, MA-based Quanterix. They will offer up their own insights into what’s hot in RNA interference, epigenetics, and molecular diagnostics, respectively.

Deborah Dunsire

We’ll hear some added perspectives from executives who are pursuing equally innovative strategies, but are currently pushing through the long and expensive slog known as the FDA approval process for a new drug. We’ll bring together Tuan Ha-Ngoc, the CEO of Aveo Pharmaceuticals; Adelene Perkins, the CEO of Infinity Pharmaceuticals; Nancy Simonian, the chief medical officer of Millennium:Takeda; and Alexis Borisy, the CEO of Foundation Medicine and a partner with Third Rock Ventures to talk about the challenges and opportunities they see in cancer drug development. Xconomy’s national life sciences columnist, Sylvia Pagan Westphal, will moderate.

I’m excited to fly in for this event to see all these folks who are leaders in New England, but also on the international stage. There are some tickets left for this event, but there is limited seating, so it’s a good idea to register now by clicking here. See you on October 20.

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We were buzzing this week with news from the boardrooms at big pharma companies, introductions to the life sciences personalities presenting at our XSITE innovation forum, and profiles on emerging health IT companies.

—IBM declared medicine authentication company Sproxil the winner of its Boston SmartCamp, a day-long competition for companies working in “smart” technology, which uses IT to make things in the physical world more efficient. Somerville, MA-based Sproxil is working with manufacturers to produce scratch-off labels with unique product codes for medicine in developing countries like Nigeria, where the counterfeiting of drugs is a big problem. Consumers text the code to Sproxil, which confirms whether the product they’re about to buy is the real thing or not. (Sproxil will also be presenting at the Xpo segment of XSITE, so be sure to come and check it out.)

—Ryan took a look at Eldersync, a Boston startup developing a Web-based system for coordinating communication between home nursing agencies, doctors, patients, and their families. Healthcare workers can use the Eldersync technology to schedule visits, verify via text if they’ve seen a patient, and file patient notes using home Internet devices.

—We dished a bit about the biotech presence you can expect at the annual Xconomy Summit on Innovation, Technology & Entrepreneurship (XSITE) next week. Luke noted that Alkermes, Ironwood Pharmaceuticals, ImmunoGen, and Mersana Therapeutics are among the successful Boston-area life sciences companies that will be represented at panels and keynote chats throughout the day. Ryan discussed the mobile health panel, which will showcase how organizations from Healthrageous to the MIT Media Lab are innovating at the intersection of healthcare and technology.

—Cambridge, MA-based drugmaker Genzyme (NASDAQ: GENZ) announced its board of directors had nominated Dennis Fenton, who spent 25 years at Thousand Oaks, CA-based Amgen (NASDAQ: AMGN), to a seat on the board. Genzyme’s 10 board members are all up for reelection at the company’s annual meeting on June 16. Later in the week, the company announced it had reached an agreement with Carl Icahn, the investor who has been loudly lobbying to get four spots on the Genzyme board. Genzyme will appoint two of Icahn’s choices in exchange for his support of the company’s 10 nominees, including president and CEO Henri Termeer, whose removal Icahn had previously called for. The additions of … Next Page »

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Women lose a valuable weapon against their breast tumors when the potency of hormone therapy fades. But what if there was a way to “reprogram” breast tumor cells to be receptive to hormone therapy? Waltham, MA-based Syndax Pharmaceuticals might have such a way.

Syndax has shown in a 26-patient clinical trial that its drug, entinostat, could improve the ability of hormone therapies to kill breast cancer. The biotech startup—which was co-founded by scientists from the Salk Institute for Biological Studies in La Jolla, CA in 2005—has embarked on a new human study that will give it a clearer picture than previous studies provided of how well its drug improves breast cancer treatment. Its research has been displayed in recent days at the American Society of Clinical Oncology (ASCO) annual meeting in Chicago.

The company’s new Phase II clinical trial for entinostat for breast cancer patients is a big test of the firm’s technology. The firm has raised $49 million from venture capital firms such as the San Diego venture firms Domain Associates, Avalon Ventures, and Forward Ventures as well as MPM Capital, of Boston and South San Francisco, and Pappas Ventures in Durham, NC. (Eckard Weber, a well-known partner at Domain in San Diego, co-founded and served as an early CEO of Syndax.) Joanna Horobin, the firm’s CEO, said that the startup raised its latest $9 million in venture financing this year to complete its new mid-stage clinical trial, which she hopes will yield evidence of its lead drug’s utility by early next year.

For several years Syndax has been one of the biotechs to watch in the hot field of epigentics, which involves the study chemical changes in cells that impact how genes are expressed or suppressed without changing the underlying DNA code. Epigenetics grabbed the cover of Time magazine in January. For instance, breast tumor cells can undergo epigenetic changes that make them immune to hormone therapies, which are intended to stymie the production of estrogen needed to sustain tumor survival. Syndax’s drug aims to reprogram breast tumor cells in which those detrimental epigenetic switches occur.

“The idea is that you turn off the … Next Page »

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There were fewer life sciences headlines this week than we’ve seen lately, but the news covered an array of biotech companies fighting everything from baldness to skin disease to stubborn bacteria.

—Watertown, MA-based Tetraphase Pharmaceuticals pulled in a $45 million Series C round that was led by new investor Excel Venture Management and also included some of the biotech company’s existing backers. Tetraphase is using proprietary technology to develop tetracycline antibiotics, which can allow for more alterations than traditional antibiotics developed through fermentation, and as a result better combat pathogens that have built resistances to existing treatments.

—SynapDx, a Waltham, MA-based developer of diagnostics for early detection of autism, snagged $9 million in Series A funding, from Bain Capital, General Catalyst Partners, and North Bridge Venture Partners. The quiet startup was founded by Stanley Lapidus, the life sciences entrepreneur known for launching companies such as Helicos BioSciences (NASDAQ: HLCS) and Exact Sciences (NASDAQ: EXAS).

—Healthcare products company Covidien said it will buy ev3 (NASDAQ: EVVV), a Plymouth, MN-based medical devices firm, for $22.50 per share, or a total of $2.6 billion in cash. Ev3 is known for products that treat vascular diseases. Mansfield, MA-based Covidien (NYSE: COV) (which is legally incorporated in Ireland) expects the purchase to be finalized by July 31.

—Follica, the stealthy biotech company that has generated plenty of buzz on our site for its work in developing drugs to fight male pattern baldness, hit our radar screen again with $7.5 million in equity-based funding. Company co-founder Daphne Zohar of PureTech Ventures said the financing represents part of Follica’s Series B round. Follica hasn’t said how close its technology, which is designed to stimulate the growth of hair follicles, is to hitting the market.

—Constellation Pharmaceuticals, a Cambridge, MA-based company that’s developing drugs that target diseases by turning DNA on and off, grabbed a $22 million Series B round, led by GlaxoSmithKline’s venture investing arm, SR One. Boston-area life sciences force Christoph Westphal became president and head of Glaxo’s (NYSE: GSK) SR One earlier this spring, and was involved in the financing. Constellation’s technology aims to block enzymes that make it harder for tumor-suppressor genes to do their job. Previous Constellation backers Altitude Life Sciences, The Column Group, Third Rock Ventures, and Venrock Associates also contributed to the second-round funding.

—Ryan took a look at MoMelan Technologies, a stealthy Cambridge startup that’s out to fight the physical effects of skin diseases by developing a device that can stretch skin to cover a larger area than a traditional skin graft could. The science for the company comes from Harvard dermatologist and MoMelan co-founder R. Rox Anderson. It could help treat disease like vitiligo, which causes the irregular formation of white spots on the skin. MoMelan raised more than $1 million in convertible debt funding in March.

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Scientists have been buzzing for years now about new drugs that can turn DNA on or off in ways that affect many diseases. Now more big pharmaceutical dollars are flowing to support this idea at a Cambridge, MA-based biotech that specializes in making drugs based this field of genetics research.

SR One, the venture capital arm of London-based drug giant GlaxoSmithKline, has led a $22 million Series B round of financing for Cambridge, MA-based Constellation Pharmaceuticals. (Christoph Westphal, a well-known biotech entrepreneur based in Boston, became the president and head of SR One in April.) Constellation also drew part of its second-round financing from its previous venture backers: Altitude Life Sciences, The Column Group, Third Rock Ventures, and Venrock Associates.

Constellation, which has now raised $54 million since it was founded in 2008, is searching for new ways to treat cancer with drugs that target so-called epigenetic enzymes. The enzymes can control how spools of DNA strands in our cells express or mute certain genes. The drugs could be useful, say, in blocking the enzymes that prevent tumor-suppressing genes from making natural proteins that kill cancer cells. (More on epigenetics here.) Mark Goldsmith, the company’s CEO, says drugs that target epigenetic enzymes could also be used to treat inflammatory, immune, and diseases other than cancer.

Glaxo (NYSE:[GSK), one of the ten largest drug firms in the world, has made Constellation its latest bet in the field of epigenetics. In October, the drug giant spent $8 million upfront to form a collaboration with the Dublin, CA-based biotech firm SuperGen to develop cancer drugs that home in on epigenetic targets. Also, Glaxo operates an epigenetic research group in the U.K. called EpiNova.

With SR One's investment in Constellation, Westphal is making his leadership at Glaxo's venture arm felt in his hometown. Though SR One is officially headquartered in Conshohocken, PA, Westphal has said he would remain based in the Boston area, where he's co-founded and served as CEO of such high-flying biotech firms as Alnylam Pharmaceuticals (NASDAQ:[[ALNY]]), Momenta Pharmaceuticals (NASDAQ:MNTA), and, perhaps most famously, Sirtris Pharmaceuticals. Glaxo bought Sirtris, a developer of drugs that target anti-aging genes, for $720 million in May 2008. And Westphal had remained CEO of Sirtris until April, when he resigned to take the helm at SR One.

On top of his SR One duties, Westphal is quietly putting together the pieces for a new venture firm in Boston called … Next Page »

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Epizyme, a high-flying startup focused on the hot field of epigenetics, has recruited a new CEO and a new chief dealmaker. Robert Gould started work this week as chief executive of the Cambridge, MA-based biotech, having resigned from a big job at the Broad Institute of MIT and Harvard.

Gould has served on the board of directors at Epizyme since its founding two years ago, as it has grown from one to 20 employees and closed a $40 million Series B financing. (The firm has now raised a total of $54 million from New Enterprise Associates, MPM Capital, Kleiner Perkins Caufield & Byers, Bay City Capital, Astellas Venture Partners, and Amgen Ventures.) He’s replacing founding CEO Kazumi Shiosaki, a managing director at MPM, as part of a transition plan in which she will remain a board member of the company.

Besides Gould, Epizyme has also brought on Jason Rhodes, a former VP of business development at Cambridge, MA-based Alnylam Pharmaceuticals (NASDAQ:ALNY), to lead deal-making activities as the startup’s chief business officer. Rhodes certainly got exposed to a lot of deals during his stint from 2007 to this year at Alnylam, the RNA interference company; Alnylam has active partnerships with Roche, Novartis, Takeda Pharmaceuticals and other big drug companies.

Both executives spoke of the huge opportunity for Epizyme in the field of epigenetics, which involves turning on and off certain genes without altering the underlying code of DNA. Based on the company’s epigenetics research, Epizyme is in the early stages of pursuing small molecule drugs that block enzymes believed to be involved in cancer, called histone methyltransferases. The startup says its research could also lead to the discovery of drugs for diseases outside of the cancer field, where it will focus its initial efforts. It’s got a local rival in Cambridge’s Constellation Pharmaceuticals, which is also doing epigenetics research to find cancer therapies.

Gould, 55, left the Broad Institute after spending three years in charge of a group that looked for potential medical applications for scientific discoveries made at the renowned genomic research center in Cambridge. He was previously a vice president at Whitehouse Station, NJ-based Merck (NYSE: MRK), where he worked on ushering 20 drugs into clinical trials. In his new post, Gould hopes to eventually begin testing Epizyme’s drugs in cancer patients, but he declined to provide a timetable for when trials will begin or the specific types of cancer the company plans to treat.

Robert Gould, CEO of Epizyme.

When asked why he took the job, Gould said he is “anticipating the exciting possibilities in treating cancer and in epigenetics.” He added, “[It] seemed to me to be a great opportunity to continue building a company.”

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For all of the publicity it’s gotten lately, Constellation Pharmaceuticals has managed to keep a remarkably tight lid on the specifics of its research. So I was enthused when the Cambridge, MA-based firm’s new CEO, Mark Goldsmith, gave me some insights into where the firm stands in advancing potential drugs in the emerging field of epigenetics.

In quick review: epigenetics is the study of the molecular changes in cells that can activate or mute certain genes without changing the underlying DNA code—for example, by affecting the way DNA strands are folded. Constellation is a company to watch in epigenetics, in part because the startup has raised an impressive $32 million in Series A venture capital since launching in April 2008. And Goldsmith, a physician and scientist by training with both research and industry chops, is the latest of a string of impressive biotech veterans to get behind the fledgling company. (Goldsmith also filled me in recently about his early experience taking the reins at Constellation from Mark Levin, the firm’s founding CEO and chairman, who was CEO of biotech powerhouse Millennium before co-founding Boston venture firm Third Rock Ventures in 2007.)

Constellation, which plans to initially develop drugs for cancer, is so early in its research that it hasn’t decided on a compound to test in clinical trials, according to Goldsmith. The CEO told me that he expects the firm to choose one or more drug candidates for pre-clinical testing (which would include animal studies) by the end of next year, meaning that the company is at least a couple of years from its first real-deal human trial. He was mum, however, about which specific types of cancer the firm hopes to treat.

“At this time we’re not disclosing the specifics for a number of reasons,” Goldsmith said. “But I’d say a couple of things that differentiate us include selecting highly specific … Next Page »

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Constellation Pharmaceuticals is on a mission to discover the next generation of cancer drugs by tapping the science of “epigenetics.” The Cambridge, MA-based biotech startup said today that a veteran physician and executive has come aboard to helm the effort, and the firm’s investors have handed over $17.2 million to support the cause.

New Constellation CEO Mark Goldsmith, who spent a decade on the faculty at the School of Medicine of the University of California, San Francisco, comes to the startup after a stint as an executive-in-residence at Prospect Venture Partners, a Palo Alto, CA, venture firm. He’s also been a CEO before, for California drug developer Cogentus Pharmaceuticals. Mark Levin, the venture capitalist and former chief executive of Millennium Pharmaceuticals who served as founding CEO of Constellation, is remaining chairman of the biotech. Levin’s Third Rock Ventures, of Boston, was behind the launch of the company and helped the biotech put together a $32 million Series A financing deal last year; the $17.2 million that Constellation has just collected is the third and final installment of that financing, according to a company spokeswoman.

Constellation is focusing on the field of epigenetics, which involves proteins and other molecules that can turn genes on and off without changing the genetic code itself. Epigenetic drugs designed to neutralize specific gene-modifying proteins in cancer cells, for example, could kill the cells by stymieing the genes they need to survive. Epigenetic drugs could also activate certain genes that would otherwise not function properly in a diseased cell. If this sounds familiar, there are other companies in the Boston area such as Cambridge-based Epizyme and Acetylon Pharmaceuticals that are trying to develop new epigenetic drugs as well. Such drugs are believed to have the potential to treat infections, neurological disorders, and a host of other major diseases; Constellation is initially focused on cancer.

“Constellation has made great progress building a powerful product engine and outstanding team,” Levin said in a statement, “and we’re very excited to bring an accomplished physician-scientist with executive leadership experience to the helm at this stage.”

For now, Constellation hasn’t spoken a great deal about the specific types of cancer it plans to treat. We’ll report back on this company after we speak to the new chief executive, Goldsmith, and learn about his plans for the operation.

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Despite being forthcoming about its big-name venture backers—MPM Capital and Kleiner Perkins Caufield & Byers—Cambridge, MA-based Epizyme has been one of several biotech startups in the Boston that are being demure about the details of their technology. So I was intrigued when the company contacted me recently to let me know that it was lifting the curtains on its bold plans to make “epigenetic” drugs to combat blood cancer and tumors. And two founders also filled me in on the genesis of the company, which began during an MPM meeting in South San Francisco nearly two years ago.

Epigenetics involves enzymes and other molecules in the body that turn genes on and off without changing the underlying DNA code. Whitehouse Station, NJ-based drug giant Merck (NYSE:MRK) markets an early FDA-approved epigenetic treatment, the lymphoma drug vorinostat (Zolinza), which works by inhibiting one such type of enzyme, called histone deacetylases. Now Epizyme is embarking on an effort to discover drugs that target a different class of epigenetic enzymes known as histone methyltransferases (HMTs), company CEO Kazumi Shiosaki, who is also a managing director at MPM, tells me.

Epizyme is initially focused on developing drugs that knock out certain ones of these enzymes that are believed to either turn off cancer-fighting genes or activate genes that promote tumor survival. There are an estimated 70 HMTs, Shiosaki says, and among them are also potential targets for treating inflammation, neurological disorders, and other diseases. Yet it’s still early days for the company, which is in the process of selecting chemical compounds that could be developed as drugs to home in on these epigenetic enzymes. And there are several years of work to do before the firm tests the drugs in humans, the CEO adds.

“We have a very good understanding of the fundamental biochemistry that these enzymes operate under,” Shiosaki says, adding that this understanding puts the company in a strong position to identify drugs that target HMT enzymes.

Indeed, Epizyme has licensed technology from the lab of company co-founder Yi Zhang, a professor of biochemistry at the University of North Carolina at Chapel Hill, who has done extensive research on histone methyltransferase enzymes. The company is working on building an estate of patents related to these enzymes, though company officials believe they have competition on this front. Constellation Pharmaceuticals, a fellow epigenetics startup in Cambridge, was co-founded by another scientist who has been studying this enzyme class, Danny Reinberg, a professor of biochemistry at … Next Page »

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MPM Capital and Kleiner Perkins Caufield & Byers see a big idea for medicine emerging from the science of epigenetics. The two venture firms are building a startup, called EpiZyme, to take advantage of research that looks at how genes can be turned on or off without any alteration to the underlying sequence.

I got the inside scoop this week on a visit to MPM Capital’s offices on the 54th floor of the John Hancock Tower in Boston (one of the few places in town where you can look down on the Prudential Tower.)

The company is still mostly in stealth mode, but here’s what I gathered, from EpiZyme’s founding CEO, Kazumi Shiosaki (who’s also a managing director at MPM, and a former senior vice president of scientific development at Millennium Pharmaceuticals): EpiZyme got its start about a year ago after hearing input about the new big things in biology at a retreat of the MPM scientific advisory board, a group that includes Nobel Laureate H. Robert Horvitz of MIT, Stanford University stem cell biologist Irving Weissman, and George Daley, a professor at Harvard Medical School. Since then, EpiZyme has hired a “dynamic duo” of executives from two big drugmakers, Shiosaki says, though the company’s not yet naming names. The company’s scientific advisory board has one Nobel Laureate and a “strong IP foundation” with a license from a leading academic lab, she says.

Yesterday EpiZyme launched its website, www.epizymebio.com, which delivers a flashy introduction to epigenetics, complete with Madison Avenue-style taglines like “DNA and genetics are just the beginning,” and “Identical genes, striking differences: Profound implications for medicine.” But the company isn’t yet disclosing any real details about how its technology is supposed to work, the amount of funding it has raised, what diseases it’s pursuing, or what sets it apart from others in the field, like Cambridge, MA-based Constellation Pharmaceuticals. More of those details will be made public by the end of this year, Shiosaki says.

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