Rhythm has two clinical-stage candidates for obesity and diabetes.

Rhythm obtained $25 million through a Series B financing round. Rhythm will use the proceeds to continue advancing its small-peptide therapeutics for metabolic diseases through Phase II trials. RM-131 is a ghrelin agonist, currently in Phase II, for the treatment of diabetic gastroparesis. RM-493, an agonist of the melanocortin 4 receptor (MC4R), is currently in Phase I trials for the treatment of obesity and diabetes.

“We have made great progress since we started both development programs in 2010, and this could only have been achieved with a strong and dedicated investor syndicate,” states Bart Henderson, founder and president of Rhythm. “These programs have great potential for addressing major unmet needs in diabetes, obesity, and gastrointestinal functional disorders, and this financing supports a broad and thorough Phase II development program for both drugs.”

All existing investors participated in the round—MPM Capital, New Enterprise Associates, and Third Rock Ventures—as well as new investor, Ipsen. This latest round brings the total capital raised by Rhythm to $65 million.

“Ipsen is impressed with the early results for the ghrelin and MC4 programs as well as Rhythm’s track record in executing a precision development program,” says Marc de Garidel, chairman and CEO of Ipsen. Rhythm Pharmaceuticals licensed melanocyte-stimulating hormone (MSH) and ghrelin hormone peptide analogue programs from Ipsen in March 2010, at which time both programs were at the preclinical stage.

As part of the deal Ipsen took a 17% equity stake in Rhythm and could earn another $80 million in development and commercial milestones as well as sales royalties. Rhythm will also tap into Ipsen’s formulation capabilities and expertise to develop delivery systems for the peptides.

RM-131 and RM-493 both leverage advances in peptide engineering, synthesis, and formulation to enable the design of therapeutics that retain the inherent selectivity and specificity of the human hormones from which they are derived, improve on their potency, and reduce the risk of off-target adverse effects compared with small molecule drugs, according to Rhythm.

RM-131 was derived from the natural ghrelin sequence and optimized to stimulate GI motility, weight gain, and anti-inflammatory activity, with enhanced stability and pharmacokinetics. The compound is suited for GI motility disorders as it reverses both surgical and opiate-induced ileus in animal models due to a direct prokinetic effect, the company notes. RM-131 reverses body weight loss in cachexia models, Rhythm adds.

Development of RM-493 is based on the rationale that a common pathway responsible for suppression of feeding and regulation of energy homeostasis is mediated by the melanocortin type 4 receptor (MC4R). Additionally, in humans, mutations of MC4R are associated with obesity and are estimated to be responsible for 4–6% of all severe obesity. In preclinical studies, when stimulated, MC4R induces a reduction in food intake, body weight, and insulin resistance, according to Rhythm.

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