RM-493: A First-in-Class, Phase 2-Ready MC4 Agonist
A new drug class for the treatment of obesity and diabetes

RM-493 is a potent, first-in-class, Phase 2-ready MC4 agonist, which modulates a key pathway in humans that regulates energy, homeostasis, and food intake. The critical role of MC4 in weight regulation was validated with the discovery that a mutation of the MC4 receptor gene resulted in early onset obesity and severe obesity. RM-493 targets the receptor for MC4. The first generation of MC4 agonists were small molecules that failed primarily due to safety issues, particularly increases in blood pressure. In contrast, RM-493 is a peptide that retains the specificity and functionality of the naturally occurring hormone that activates MC4 and has not been shown to adversely affect blood pressure in our Phase 1 and Phase 2 clinical trials.

Development Stage:
As part of our clinical program, we have treated approximately 190 subjects and patients with RM-493, which is administered by subcutaneous injection. We have completed a Phase 1b proof-of-concept clinical trial with RM-493 in obese patients, including one cohort of patients with mutations in one of the MC4 receptor genes. This clinical trial demonstrated promising weight loss in these patients with a four-week treatment. We are preparing to initiate two Phase 2a clinical trials by the end of 2014, each for the treatment of obesity caused by a specific genetic deficiency in the MC4 pathway. The first clinical trial is a personalized medicine approach for treating obesity in people with a mutation of the MC4 receptor gene to assess weight loss and safety. Our second RM-493 Phase 2a clinical trial is in PWS patients; recent scientific evidence supports a role for genetic defects in the MC4 pathway in PWS. We intend to use the results of our Phase 2a clinical trials of RM-493 in these indications potentially as the foundation for planning pivotal registration clinical trials. It is our intention to work with the FDA on a focused clinical program for each indication.