Fanning the 'Embers' in metabolic research

BOSTON—A new company joined the industry this week as ThirdRock Ventures, LLC, announced the formation of Ember Therapeutics. Emberlaunched with a $34 million Series A financing, and will have a specializedfocus in the area of metabolic diseases, specifically brown fat biology. Thecompany's founders are Bruce Spiegelman, Ph.D., a professor of biology at theDana-Farber Cancer Institute at Harvard Medical School; Patrick Griffin, Ph.D.,chairman and professor of the department of molecular therapeutics at theScripps Research Institute at Scripps Florida; and C. Ronald Kahn, M.D.,professor of medicine at Joslin Diabetes Center and Harvard Medical School,along with Third Rock Ventures. Ember is a private company, and was formerlyknown as Adipothermics.

"It is an unfortunate truth that Type 2 diabetes and obesityare a worldwide epidemic. This rising disease prevalence and a critical needfor innovation in the pharmaceutical industry's metabolic disease pipelinemeans there is a real opportunity for Ember to discover and develop newapproaches to these conditions," Louis Tartaglia, Ph.D., president and interimchief executive officer of Ember and partner at Third Rock Ventures, said in apress release. "Ember's team of world-leading scientists, our proprietaryprograms in brown fat biology and selective insulin sensitization and ourexclusive licenses to key intellectual property and technology uniquelyposition us to address this growing medical challenge and dramatically impactthe lives of patients."

Of the two types of fat in the human body, white fat storesenergy and brown fat burns off caloric energy. Humans are born with largeamounts of the latter, but humans lose most of their stores of brown fat inorder to maximize metabolic efficiency and enable them to survive if there is alack of food. In present times when food is far from scarce, that metabolicefficiency has actually become a key contributor to metabolic diseases such asobesity and type 2 diabetes. Currently, roughly a third of U.S. adults areobese, with another third clinically overweight. One in 10 U.S. adults areaffected by diabetes, and the Centers for Disease Control says that couldincrease to one in three adults by 2050. The combined direct annual medicalcosts associated with obesity and type 2 diabetes are more $265 billion just inthe United States.

"Recent scientific discoveries confirm that adults possessbrown fat, and research has now shown that augmenting and activating brown fatresults in weight loss and has a significant impact on the drivers of metabolicdisease. As a result, brown fat targets and therapeutic pathways are key todeveloping new and effective treatments for metabolic disorders," saidSpiegelman. "What is equally exciting for Ember is our position at theimportant crossroads of insulin resistance and diabetes. More than ever before,we have a true understanding of how novel selective insulin sensitizers couldproduce anti-diabetic effects without the toxic side effects associated withcurrently available therapies. These advances could significantly change andimprove the way patients with metabolic disease are treated."

Ember will study brown fat biology breakthroughs to developa pipeline of small and large molecule programs that will activate and augmentbrown fat in the body, thereby enhancing the body's natural ability to burnfuel stores such as glucose and lipids to reduce stored calories. The companywill also work to develop next-generation, highly selective insulin sensitizerswithout the side effects and safety concerns associated with existing insulinsensitizers.

Existing insulin sensitizers have potent anti-diabetic effects,which are believed to be driven by their agonism of a nuclear hormone receptor.A pair of studies has shown that the inhibition of CDK5 phosphorylation of akey nuclear hormone receptor is the therapeutic driver of the anti-diabeticeffect of insulin sensitizers, and that receptor agonism is actually the driverof associated adverse events. The studies also showed that there is apossibility to create non-agonistic drugs that potently block CDK5phosphorylation of the nuclear hormone receptor, and Ember is aiming to developproprietary small molecules along this line.

SOURCE: Ember Therapeutics press release