Firm will use brown fat biology and research in insulin resistance.
Third Rock Ventures has formed Ember Therapeutics with a $34 million Series A financing . Ember will leverage brown fat biology as well as the mechanisms of selective insulin sensitivity to develop treatments for metabolic diseases.
The founders of the company are Bruce Spiegelman, Ph.D., professor of cell biology, Dana Farber Cancer Institute, Harvard Medical School; Patrick Griffin, Ph.D., chairman and professor of the department of molecular therapeutics at The Scripps Research Institute, Scripps Florida; and C. Ronald Kahn, M.D., professor of medicine, Joslin Diabetes Center and Harvard Medical School, along with Third Rock Ventures.
“It is an unfortunate truth that type 2 diabetes and obesity are a worldwide epidemic,” remarks Louis Tartaglia, Ph.D., president and interim CEO of Ember and partner at Third Rock Ventures. “This rising disease prevalence and a critical need for innovation in the pharmaceutical industry’s metabolic disease pipeline means there is a real opportunity for Ember to discover and develop new approaches to these conditions.”
Dr. Spiegelman explains, “Recent scientific discoveries confirm that adults possess brown fat, and research has now shown that augmenting and activating brown fat results in weight loss and has a significant impact on the drivers of metabolic disease. As a result, brown fat targets and therapeutic pathways are key to developing new and effective treatments for metabolic disorders.
“The new company will harness research breakthroughs in brown fat biology to develop a pipeline of large- and small-molecule programs that augment and activate the body’s brown fat, amplifying the natural ability to efficiently burn fuel stores such as glucose and lipids to reduce stored calories in the body.
“What is equally exciting for Ember,” adds Dr. Spiegelman, “is our position at the important crossroads of insulin resistance and diabetes. More than ever before, we have a true understanding of how novel selective insulin sensitizers could produce antidiabetic effects without the toxic side effects associated with currently available therapies. These advances could significantly change and improve the way patients with metabolic disease are treated.”
The antidiabetic effects of currently available insulin sensitizers are believed to be driven by their agonism of a key nuclear hormone receptor, explains Dr. Spiegelman. However, two key studies published in Nature and authored by Ember founders show that it is the inhibition of CDK5 phosphorylation of this nuclear hormone receptor that is the therapeutic driver of the antidiabetic effect, while the receptor agonism is the driver of the adverse events associated with these therapies.
The studies also show that it is possible to create new drugs that are nonagonists yet potently block the CDK5 phosphorylation of the nuclear hormone receptor, according to Dr. Spiegelman. Building on these findings, Ember plans on developing small molecules that retain the full antidiabetic effect but without the toxic side effects of current treatments.