Rhythm Metabolic, Inc. is developing setmelanotide (RM-493), a novel peptide MC4 agonist for the treatment of obesity caused by genetic deficiencies in the MC4 pathway. In this round, new investors OrbiMed, Deerfield Management, Wellington Management Company, and an undisclosed public healthcare investment fund joined existing investors MPM Capital, New Enterprise Associates, Third Rock Ventures, Pfizer Ventures, and Ipsen. Associated with the financing, Jonathan Silverstein, JD, Partner and Co-Head of Global Private Equity at OrbiMed, joined the Rhythm Metabolic Board of Directors.

'Rhythm is pioneering targeted therapy for life-threatening obesity caused by MC4 pathway genetic defects,' said Mr. Silverstein. 'This is a unique and exciting approach that has the potential for transformative effects in orphan obesity disorders such as Prader-Willi syndrome and POMC deficiency obesity. We are excited to help make the Rhythm program a success.'

Prader-Willi syndrome (PWS) and POMC-deficiency obesity are rare genetic disorders of obesity associated with defects in the MC4 signaling pathway. A Phase 2a clinical trial is under way in PWS, evaluating the safety and efficacy of setmelanotide on weight and eating. A second Phase 2a clinical trial is evaluating the safety and efficacy of setmelanotide on weight and appetite in patients with POMC deficiency obesity. The company expects to initiate another Phase 2a study in an additional MC4 pathway genetic disorder of obesity, and to invest in clinical, and business infrastructure to support the upcoming clinical trials.

'Setmelanotide is essentially replacement therapy in genetic MC4 pathway defects, so we are now evaluating its impact on the obesity and hyperphagia that is the hallmark of Prader-Willi and POMC deficiency obesity,' said Keith Gottesdiener, MD, CEO of Rhythm. 'We are very excited for this outstanding group of investors to join us in developing a new paradigm for treating rare genetic disorders of obesity.'

About Setmelanotide (RM-493)
Setmelanotide is a potent, first-in-class MC4 agonist in development for the treatment of obesity caused by genetic deficiencies in the MC4 pathway, a key pathway in humans that regulates energy expenditure, homeostasis, and appetite. MC4's critical role in weight regulation was validated with the discovery that a mutation of the MC4 receptor gene results in early-onset and severe obesity, as do other genetic defects in the MC4 pathway. A Phase 2 trial is ongoing for the treatment of Prader Willi syndrome (PWS), a rare genetic disorder that causes life-threatening obesity. Recent scientific evidence implicates defects in the MC4 pathway as the root cause of the weight and appetite abnormalities in PWS. A second Phase 2 trial is ongoing for the treatment of POMC deficiency obesity, a very rare, life-threatening genetic disorder. As in Prader-Willi syndrome, the obesity and appetite abnormalities in POMC deficiency patients is caused by a genetic defect in the MC4 pathway.

About Prader-Willi Syndrome
Prader-Willi Syndrome (PWS) is a rare genetic disease with a prevalence ranging from approximately one in 8,000 to one in 25,000 patients in the U.S. A hallmark of PWS is severe hyperphagia-an overriding physiological drive to eat-leading to severe obesity and other complications. Obesity is one of the greatest health threats to PWS patients, and hyperphagia impairs the ability of PWS patients to live independently, requiring costly and constant supervision to prevent overeating. Without supervision, these patients are likely to die prematurely as a result of choking, stomach rupture, or from complications caused by morbid obesity. Currently, there are no approved treatments for the obesity and hyperphagia associated with PWS.

About POMC Deficiency Obesity
First described as POMC deficiency syndrome, patients with POMC deficiency obesity have homozygous loss-of-function in the pro-opiomelanocortin (POMC) genes, which results in early-onset, severe obesity. This genetic disorder may also be associated with hormonal deficiencies, such as hypoadrenalism, and red hair and fair skin are common. POMC-null obesity is a very rare genetic disorder, and there are no approved treatments for the obesity and hyperphagia associated with this condition.

About Rhythm (www.rhythmtx.com)
Rhythm is a biopharmaceutical company developing peptide therapeutics that address unmet needs in gastrointestinal diseases and obesity. Rhythm's subsidiary, Rhythm Pharmaceuticals, Inc., is developing the ghrelin peptide agonist, relamorelin (RM-131), for the treatment of diabetic gastroparesis and other gastrointestinal functional disorders. Rhythm's subsidiary, Rhythm Metabolic, Inc., is developing the MC4R peptide agonist, setmelanotide (RM-493), for obesity caused by genetic deficiencies in the MC4 pathway. The company is based in Boston, Massachusetts.