Rhythm is a biopharmaceutical company focused on developing and commercializing peptide therapeutics for the treatment of rare genetic deficiencies that result in life-threatening metabolic disorders.
Our lead peptide product candidate, setmelanotide, is a potent, first-in-class melanocortin-4 receptor (MC4R) agonist for the treatment of rare genetic disorders of obesity. We believe that setmelanotide, for which we have exclusive worldwide rights, has the potential to serve as replacement therapy for the treatment of MC4 pathway deficiencies. MC4 pathway deficiencies result in the disruption of satiety signals and energy homeostasis in the body, which, in turn, leads to intense feelings of hunger and to obesity. We believe that the MC4 pathway is a compelling target for treating these genetic disorders because of its critical role in regulating appetite and weight, and that peptide therapeutics are uniquely suited to activating this target.
Our setmelanotide development efforts are initially focused on six genetic disorders of obesity—Pro-opiomelanocortin (POMC) deficiency obesity, leptin receptor (LepR) deficiency obesity, Bardet-Biedl syndrome, Alström syndrome, POMC heterozygous deficiency obesity, and POMC epigenetic disorders—for which there are currently no effective or approved treatments.
We have demonstrated proof of concept in Phase 2 clinical trials in POMC deficiency obesity, LepR deficiency obesity, and Bardet-Biedl syndrome—three genetic disorders of extreme and unrelenting appetite and obesity—in which setmelanotide dramatically reduced both weight and hunger. The U.S. Food and Drug Administration (FDA), has acknowledged the importance of this preliminary clinical evidence by granting setmelanotide breakthrough therapy designation for the treatment of obesity associated with genetic defects upstream of the MC4 receptor in the leptin-melanocortin pathway, which includes both POMC deficiency obesity and LepR deficiency obesity, enabling an expedited path to approval of setmelanotide for these two indications. In addition, the FDA has granted orphan drug designation for setmelanotide for the treatment of POMC deficiency obesity.
To validate the scientific and clinical importance of our Phase 2 findings, the results of this trial were published on July 21, 2016 in The New England Journal of Medicine, and the accompanying editorial described the trial as demonstrating impressive hunger reduction and weight loss as well as improved insulin sensitivity.
Obesity is epidemic in the U.S., and current treatment approaches have demonstrated limited long-term success for most obese patients. We are taking a different approach to obesity drug development by leveraging new understanding of the genetic causes of severe obesity to develop innovative therapies that we believe have the potential for compelling efficacy. Setmelanotide’s unique mechanism of action at MC4R enables a targeted approach to treating very severe obesity in patients with specific, monogenic defects in the MC4 signaling pathway. By restoring impaired function in this pathway, setmelanotide can serve as replacement therapy for genetic deficiencies, with the potential for dramatic improvements in weight and appetite.
We believe we are at the forefront of improving treatment outcomes in subtypes of severe obesity that are caused by genetically defined defects in the MC4 pathway.