Clinical Trial Results - Bivamelagon achieved statistically significant BMI reductions in patients with acquired hypothalamic obesity at 14 weeks[5] - At 14 weeks, the 200mg Bivamelagon group saw a mean BMI reduction of 268%, the 400mg group saw a mean BMI reduction of 769%, and the 600mg group saw a mean BMI reduction of 931%[27] - In the placebo group, there was a mean BMI increase of 218% from baseline at 14 weeks[27] - A significant percentage of patients achieved clinically meaningful BMI reductions: 167% in the 200mg Bivamelagon group, 714% in the 400mg group, and 75% in the 600mg group achieved at least a 5% BMI reduction[33] - Bivamelagon also achieved meaningful reductions in 'most' hunger scores at Week 14[44] Safety and Tolerability - Safety and tolerability results were generally consistent with an MC4R MOA and setmelanotide trials in acquired hypothalamic obesity, with limited instances of localized hyperpigmentation[5] - The most common AEs with >=10% in all BIVA dosing (N=21) were nausea, diarrhea, vomiting, and headache[47] Market Opportunity and Future Development - Rhythm Pharmaceuticals intends to request an End-of-Phase 2 meeting with the FDA with intentions to move forward to Phase 3[5] - The company estimates the U S prevalence of acquired hypothalamic obesity to be 5,000 – 10,000 patients[13] - U S patent protection for bivamelagon and RM-718 extends into the 2040s[13]

Core Insights - Rhythm Pharmaceuticals presented new real-world data demonstrating that setmelanotide leads to significant weight reduction in patients with acquired or congenital hypothalamic obesity [1][3][10] Group 1: Clinical Data Presentation - New data was presented at the first-ever Joint Congress between the European Society for Paediatric Endocrinology and the European Society of Endocrinology, and the 32nd annual European Congress on Obesity, showcasing the effectiveness of setmelanotide [1][2] - The presentations included data from 35 patients treated with setmelanotide for up to nine months, showing consistent improvements in body mass index (BMI), BMI-z, and hunger scores [1][4] Group 2: Patient Outcomes - Among adult patients with acquired hypothalamic obesity, there was a mean BMI reduction of -11.9% at three months, -19.2% at six months, and -23.0% at nine months [5] - Pediatric patients also showed a decrease in BMI z-scores, with a mean reduction of 0.3 at three months and 0.4 at both six and nine months [5][11] Group 3: Safety Profile - Setmelanotide was generally well tolerated, with common adverse events including injection site reactions and skin hyperpigmentation, consistent with its established safety profile [6][10] Group 4: Future Developments - Rhythm Pharmaceuticals plans to submit a supplemental New Drug Application to the FDA and a Type II variation request to the European Medicines Agency for setmelanotide in the third quarter of 2025 [10]