Clinical Trial Results & Regulatory - Setmelanotide achieved a 19.8% placebo-adjusted difference in BMI reduction from baseline in the Phase 3 acquired hypothalamic obesity (HO) trial (P<0.0001)[33] - In the setmelanotide arm of the Phase 3 trial, patients experienced a -16.5% change in BMI from baseline[32] - A statistically significant reduction in Most Hunger Score was observed with setmelanotide vs placebo in participants aged ≥12 years (P=0.0086)[40] - Setmelanotide was generally well-tolerated in the Phase 3 trial, with most common adverse events including skin hyperpigmentation (55.6%), nausea (50.6%), and headache (38.3%)[45] Market Opportunity & Commercial Strategy - The estimated U S prevalence of acquired HO is approximately 10,000 individuals[48] - The estimated prevalence in Europe is also around 10,000 individuals[48] - The estimated prevalence in Japan is between 5,000 and 8,000 individuals[48] - Rhythm anticipates strong commercial and Medicaid coverage for setmelanotide in HO, similar to or better than coverage for Bardet-Biedl syndrome (BBS)[82] Company Readiness - Rhythm has established a solid global foundation with IMCIVREE available in >25 countries and >350 employees in 15 different countries[23] - The company has an experienced rare disease team in place to support ongoing growth in BBS[72]

Core Insights - Palatin Technologies, Inc. announced strong preclinical results for PL7737, an oral selective melanocortin-4 receptor (MC4R) agonist, demonstrating effectiveness in rodent models of obesity [1][2] - The company plans to initiate a Phase 1 clinical trial for PL7737 in late 2025, with data expected in the first half of 2026 [2][5] Group 1: Preclinical Study Results - The preclinical study evaluated the weight loss effects of PL7737 in a diet-induced obese rat model, showing statistically significant weight loss after 4 days of treatment [2] - PL7737 monotherapy resulted in a 5% weight loss at the middle dose and 10% at the high dose, while the combination with tirzepatide led to an 11% and 15% weight loss, respectively [6] Group 2: Mechanism and Pipeline - MC4R agonists, like PL7737, offer a unique mechanism of action for obesity treatment, differing from incretin-based therapies [2] - Palatin is developing a pipeline of novel MC4R agonists, including both oral and long-acting peptide candidates, targeting general obesity and rare forms of the disease [2][9] Group 3: Regulatory and Market Potential - The FDA granted orphan drug designation to PL7737 for treating leptin receptor deficiency-related obesity, a rare genetic disorder [2] - There are currently no approved pharmacologic treatments specifically indicated for hypothalamic obesity, highlighting a significant unmet medical need [7]