Rhythm Pharmaceuticals has acquired exclusive, worldwide rights from Takeda to develop and commercialize T-3525770 (now RM-853). 

RM-853 is a potent, orally available ghrelin o-acyltransferase (GOAT) inhibitor currently in preclinical development for Prader-Willi Syndrome (PWS). PWS is a rare genetic disorder that results in hyperphagia and early-onset, life-threatening obesity, for which there are no approved therapeutic options.

Ghrelin is an orexigenic peptide, secreted by the stomach and proximal small intestine in response to a negative energy balance. Ghrelin plays a key physiological role in stimulating appetite and promoting food intake, thereby maintaining overall energy balance. In people living with PWS, levels of active ghrelin are elevated, contributing to an unrelenting hunger, known as hyperphagia, which leads to severe obesity. RM-853 is designed to block GOAT, the key enzyme involved in the production of the active form of ghrelin, with the expected effect of lowering active ghrelin levels. This blockage increases the levels of des-acyl-ghrelin (DAG), a ghrelin precursor. High levels of DAG are believed to have independent beneficial effects on the control of appetite and tissue homeostasis, which might add to the potential efficacy of RM-853 in PWS.

“The in-licensing of RM-853 represents an important milestone for Rhythm, as we execute on our mission of developing therapies for people living with rare genetic disorders of obesity,” said Keith Gottesdiener, M.D., chief executive officer of Rhythm. “While PWS is one of the most prevalent rare genetic disorders of obesity, there are no approved treatments available. With RM-853, we have the opportunity to develop a first-in-class therapy with a likely dual mechanism of action, which may more effectively mediate the hyperphagia and weight gain associated with PWS.  We look forward to broadening our ongoing efforts in PWS and to advancing RM-853 through preclinical studies.”

Under the terms of the agreement, Rhythm will assume sole responsibility for the global product development and commercialization of RM-853. Takeda will receive an upfront payment of $5 million in Rhythm common stock, back-end development milestones, and single-digit royalties on future RM-853 sales.