Third Rock Looks to Fight Fat in a New Way, With Ember Therapeutics

Xconomy Boston — 

Obesity is one of the biggest public health problems of the 21st century, and now a Boston biotech startup is looking to fight it in an unorthodox way. The bet at Ember Therapeutics is that it can coax the body to burn off some of that unwanted fat.

The company is emerging from stealth mode today with a $34 million Series A financing from Boston-based Third Rock Ventures. The idea is to make drugs that take advantage of some of the new understanding about “brown fat,” a type of tissue that helps mammals to burn off the more familiar “white fat” tissue that stores excess energy. The company has recruited some big name advisors from the brown fat field, including Bruce Spiegelman of the Dana-Farber Cancer Institute, Patrick Griffin of The Scripps Research Institute in Florida, and Ron Kahn of the Joslin Diabetes Center.

Ember (not to be confused with the Boston wireless sensor network firm with that name) is being born during a rough time for the obesity drug business, as public companies like Arena Pharmaceuticals (NASDAQ: ARNA), Orexigen Therapeutics (NASDAQ: OREX), and Vivus (NASDAQ: VVUS) have all failed to win FDA approval for new weight loss drugs. Regulators have often cited underwhelming effectiveness, along with various safety concerns for pills that have potential to be taken by millions of people with a condition that isn’t immediately life-threatening. But obesity does lead to a wide variety of expensive, chronic health problems like diabetes, heart disease, arthritis, and depression. The potential market for an effective new weight loss drug is huge, as an estimated one-third of U.S. adults are obese and another one-third are considered overweight.

Lou Tartaglia

Third Rock’s bet is that it can come up with a more effective alternative through this new biology that seeks to help people burn off excess calories, rather than more traditional approaches that seek to work on the central nervous system by suppressing appetite.

“We can’t wait to get going,” says Third Rock partner Lou Tartaglia, the interim CEO of Ember.

Scientists have long known that newborns have a lot of brown fat, which is loaded with mitochondria that expend energy, and release heat to keep them warm. Most of this tissue disappears as people grow up, and adults begin to accumulate more “white fat” which stores excess energy from food we eat. But recent discoveries using positron emission tomography (PET) scans have shown that adults do retain some small amounts of brown fat tissue (usually along the back) which sends signals to burn excess white fat, Tartaglia says.

What’s interesting from a pharmaceutical perspective is that scientists have now identified biologic pathways that suggest it could be possible to “recruit and augment” the brown fat tissue that’s already operating in the body, Tartaglia says. Ember, which takes its name from the slow-burning embers that you see in a campfire, is looking to use either conventional small-molecule pills or large-molecule injectable biotech drugs to help the body maintain a steady “gentle combustion” of unwanted fat, Tartaglia says. Specifically, Ember is looking to develop drugs to interact with a protein called irisin that is secreted by brown fat, as well as other undisclosed molecular targets, Tartaglia says.

No brown fat-based drug is yet in clinical trials, and as with any experimental drug, lots of safety issues could derail the program at any point along the way. But Tartaglia says the company should be able to get to clinical trials on this large Series A financing.

Competitors have shown interest in the brown fat field, and just yesterday Switzerland-based pharma giant Roche disclosed promising results from a brown fat study in mice that was was covered by Bloomberg News. Cambridge, MA-based Acceleron Pharma has also done research into brown fat, in collaboration with Spiegelman. Ember says its intent is to get the upper hand by rallying enough scientific leaders, intellectual property, and money around its plan, Tartaglia says. “Like all hot areas, there are a number of companies interested. We are seeing a little bit of that now,” he says.

Ember also isn’t the only Third Rock portfolio company seeking to fight obesity. Cambridge, MA-based Zafgen is developing a new drug that works in a different way, through what scientists say is a mechanism that enables the body to burn fat it would otherwise store away.

Like Zafgen, Ember is being built as a virtual company, with a small core team of about a half dozen senior managers who oversee experimental work done by contract organizations. Mike Solomon, previously the chief business officer of Cambridge, MA-based Link Medicine, has signed on as Ember’s chief operating officer. And David White is the company’s new vice president of biology.

Ember will be getting some inside perspective on what pharma wants to see from one of its scientific advisors, John Amatruda, the former senior vice president at Merck and head of its diabetes and obesity franchise. If Ember can hit some of its early scientific goals, then it will likely need to form a partnership with a major pharmaceutical company because of the sheer size of the market.

Given how gun-shy pharma companies have been about obesity in the wake of past safety debacles like Wyeth’s fen-phen combo and Sanofi’s rimonabant (Acomplia), it will be a major feat if Ember can hit goals that entice a pharma company to open up its checkbook, either through a partnership or acquisition.

But Tartaglia says he’s confident the new biologic mechanism, working on brown fat, makes all the difference. “There are tractable approaches to expanding and augmenting brown fat that are realistic from a pharma perspective,” he says.

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