Rhythm Pharmaceuticals, Inc. · NASDAQ:RYTM
Rhythm Pharmaceuticals — 64th Annual Meeting of the European Society for Paediatric Endocrinology (ESPE) 2026
13 slides from Rhythm Pharmaceuticals's conference presentation, September 2026
Slide 1: Impact of setmelanotide on metabolic index scores in paediatric participants with acquired hypothalamic obesity
Oral presentation number: FC10.4 Impact of setmelanotide on metabolic index scores in paediatric participants with acquired hypothalamic obesity – A phase 3 trial post hoc analysis Scan here for a copy of this presentation, a plain language summary and supplementary materials Hanneke M. van Santen1,
Slide 2: Disclosures
Disclosures • HMvS is a local primary investigator of clinical trials funded by Rhythm Pharmaceuticals, Inc.; has received funding from Novo Nordisk, Pfizer, and Rhythm Pharmaceuticals, Inc. for the organisation of the ESPE Science Symposium and 6th Craniopharyngioma Post-graduate Course; has receiv
Slide 3: Acquired hypothalamic obesity (aHO) is a rare complex disease resulting from hypothalamic injury
Acquired hypothalamic obesity (aHO) is a rare complex disease resulting from physical injury or structural abnormality of the hypothalamus 1,2 • A key feature of aHO is disrupted melanocortin-4 receptor (MC4R) pathway signalling which can lead to hyperphagia (pathological, insatiable hunger), decrea
Slide 4: Background
Background • Setmelanotide, an MC4R agonist, is a precision medicine designed to restore disrupted MC4R pathway signalling • In the Phase 3, double-blind TRANSCEND trial patients with aHO (N=120) aged 4–66 years were randomised 2:1 to receive setmelanotide (0.5 mg subcutaneously [SC] once daily [QD]
Slide 5: Background and objective
Background and objective TRANSCEND primary endpoint (N=120) Setmelanotide Placebo • aHO is associated with metabolic complications, including 10 3.3 insulin resistance, dyslipidaemia, and hepatic steatosis1,2 Percent change in BMI, 5 LSM (95% CI) 0 • In the global Phase 3 TRANSCEND trial (NCT0577475
Slide 6: Methods
Methods Routinely available clinical measurements of well-established composite metabolic indices were used Metabolic index component Metabolic High-density Gamma- Systolic blood glutamyl Lower score index BMI Waist Fasting reflects z-score circumference Triglycerides lipoprotein glucose pressure tr
Slide 7: Results: Baseline demographics
Results Baseline demographics (N=71) Setmelanotide (n=48) Placebo (n=23) Age, mean ± SD (range), y 11.6 ± 4.1 (4, 17) 11.3 ± 3.7 (4, 17) Sex, male, n (%) 26 (54.2) 6 (26.1) Race, n (%) White 40 (83.3) 18 (78.3) Black/African American 2 (4.2) 0 Asian 1 (2.1) 0 Other 5 (10.4) 5 (21.7) Weight, mean (SD
Slide 8: Metabolic burden in paediatric patients with aHO was high at baseline
Metabolic burden in paediatric patients with aHO was high at baseline 100 6.7 Proportion of participants (%) 90 80 44.4 48.1 70 48.3 61.3 62.3 High 60 Elevated 50 Moderate 40 33.3 Low 30 44.4 30.0 19.7 29.0 20 10 22.2 18.0 15.0 9.7 7.4 0 MetS-Z-BMI Met-S-Z-BMI LAP TYG-WC VAI FLI (n=54) (n=63) (n=60)
Slide 9: Improvements across all metabolic index scores with setmelanotide
Improvements across all metabolic index scores with setmelanotide Metabolic index Setmelanotide change n=48 Placebo change from n=23 Placebo-adjusted p value from baseline, mean (SD) baseline, mean (SD) treatment difference MetS-Z-BMI1 −0.8 (0.9) 35 −0.2 (0.5) 19 −0.6 0.006 LAP2 −25.6 (41.0) 41 +3.6
Slide 10: Higher proportion of participants in lower MetS-Z-BMI and TYG-WC risk categories with setmelanotide versus placebo
Higher proportion of participants in lower MetS-Z-BMI and TYG-WC risk categories with setmelanotide versus placebo MetS-Z-BMI score1 TYG-WC score2,3 Setmelanotide (n=35) Placebo (n=19) Setmelanotide (n=38) Placebo (n=22) 100% 100 5.3 9.1 90% 90 17.1 18.2 26.3 80% 80 37.1 Proportion of participants (
Slide 11: Higher proportion of participants in lower LAP, VAI and FLI risk categories with setmelanotide versus placebo
Higher proportion of participants in lower LAP, VAI and FLI risk categories with setmelanotide versus placebo LAP score1,2 VAI score3 FLI score4 Setmelanotide Placebo Setmelanotide Placebo Setmelanotide Placebo (n=41) (n=22) (n=40) (n=22) (n=39) (n=22) 100% 100 90% 90 14.6 Proportion of participants
Slide 12: Conclusions
Conclusions Setmelanotide treatment in paediatric patients with aHO was associated with significant improvements in several metabolic indices versus placebo, suggesting treatment-related reductions in metabolic syndrome severity, visceral adiposity, hepatic steatosis, T2D, and overall cardiometaboli
Slide 13: Thank you
THANK YOU We would like to thank the participants and caregivers, without whom this trial could not have been completed Scan here for a copy of this presentation, a plain language summary and supplementary materials 13