Rhythm Pharmaceuticals (Boston, USA), a biopharmaceutical company aimed at developing and commercializing therapies for the treatment of rare genetic disorders of obesity, announced that it has acquired exclusive, worldwide rights from Takeda Pharmaceutical Company 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.
In preclinical research, RM-853 prevented body weight gain and reduced fat mass in high fat-fed mice, with a favorable pharmacokinetic, pharmacodynamic, and safety profile. Rhythm plans to complete preclinical studies of RM-853 and file an investigational new drug application with the U.S. FDA in the first quarter of 2020.