MPM-Backed Rhythm Advances Drug Programs in Diabetes and Obesity

Xconomy Boston — 

When Boston-based Rhythm Pharmaceuticals started up in 2010 with a plan to develop drugs to address diabetes and obesity, the biotech world was littered with companies struggling to make a mark in those disease areas. San Diego based Arena Pharmaceuticals was fighting to produce data for the FDA showing its obesity drug was safe. Phenomix, also based in San Diego, could no longer afford the FDA-mandated trials for its Type 2 diabetes drug and had to shut down. But the folks at MPM Capital, which started Rhythm by leading a $40 million Series A that closed in September 2010, were undeterred. They licensed two compounds from French biotech company Ipsen that had been tested extensively in animals. “The clarity of the efficacy and safety from those studies—the strength and consistency of the data—led us to believe we could clearly be best-in-class,” says Bart Henderson, co-founder and president of Rhythm.

Rhythm, which is also backed by New Enterprise Associates and Third Rock Ventures, is now completing Phase 1 human trials of its lead compound, RM-131, in patients with Type 2 diabetes. The drug is derived from ghrelin, which is commonly called “the hunger hormone.” Ghrelin is produced in the gut and regulates functions such as food consumption, nutrient absorption, and gastrointestinal motility—the movement of food through the digestive tract.

Several drug companies have tried targeting ghrelin to treat diseases that range from growth-hormone deficiency to muscle degeneration, with limited success. Rhythm is instead going after a common but largely untreated complication of both Type 1 and Type 2 diabetes called gastroparesis, a digestive disorder marked by an abnormal emptying of the stomach. Normally, ghrelin receptors in the gut prompt a well-synchronized handoff of food from the stomach to the rest of the digestive tract. “In diabetes, that process seems to be attenuated, so many patients complain of abdominal pain and bloating,” says Elizabeth Stoner, co-founder and chief development officer of Rhythm. “It causes their glucose control to go amiss, because they’re not really emptying the stomach as expected.”

According to figures Rhythm has collected, about a third of the 25.8 million people with diabetes in the U.S. suffer from gastroparesis, costing the economy $3.5 billion a year. The primary treatment, a generic drug called metoclopramide, can only be taken for a short time because of the risk that it could touch off a potentially dangerous muscle disorder.

If all goes well, Rhythm will start a Phase 2 gastroparesis study in early 2012, Stoner says. Henderson adds that because ghrelin is such an essential hormone, RM-131 could someday prove useful in a range of other diseases, including anorexia and cachexia, or wasting syndrome.

Rhythm’s second compound, RM-493, could address an equally broad population: severely obese people who suffer from diabetes or are at risk of developing it. RM-493 targets melanocortin type 4 receptor (MC4R), which when mutated, is estimated … Next Page »

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