Rhythm Pharmaceuticals, Inc. · NASDAQ:RYTM
Rhythm Pharmaceuticals — 64th Annual Meeting of the European Society for Paediatric Endocrinology (ESPE) 2026
16 slides from Rhythm Pharmaceuticals's conference presentation, September 2026
Slide 1: Efficacy and safety of setmelanotide in paediatric patients with acquired hypothalamic obesity: Final phase 3 results
Oral presentation number: OC8.6 Efficacy and safety of setmelanotide in paediatric patients with acquired hypothalamic obesity: Final phase 3 trial results Scan here for a copy of this presentation Christian L. Roth,1 Jennifer L. Miller,2 Susan A. Phillips,3 Jill Hamilton,4 Shana E. McCormack,5 Mega
Slide 2: Presenting Author Disclosures
Presenting Author Disclosures • Christian L. Roth is supported by grants from the National Institutes of Health (award numbers R21HD115119, R01DK135125, and R01DK135211; unrelated to this study) and was an advisory board member for Rhythm Pharmaceuticals, Inc. • Funding: This study was funded by Rhy
Slide 3: α-MSH Drives MC4R Pathway Signalling to Regulate Energy Balance and Body Weight
α-MSH Drives MC4R Pathway Signalling to Regulate Energy Balance and Body Weight1-3 Hypothalamus1-6 Paraventricular Paraventricular nucleus nucleus α-MSH activates MC4R α-MSH MC4Rs MC4R Hypothalamus neuron MC4R α-MSH production α-MSH & MC4R activation MC4R signalling within the brainstem and spinal c
Slide 4: Loss of α-MSH Production Due to Hypothalamic Damage May Impair MC4R Signalling
Loss of α-MSH Production Due to Hypothalamic Damage May Impair MC4R Pathway Signalling and Lead to Acquired Hypothalamic Obesity1-3 Hypothalamus4-8 Paraventricular Paraventricular nucleus nucleus MC4R Hypothalamus MC4R MC4R α-MSH activation by neuron Hypothalamic DYSREGULATION of DOWNSTREAM α-MSH MC
Slide 5: Setmelanotide Replaces Deficient α-MSH, Restoring MC4R Pathway Signalling
Setmelanotide Replaces Deficient α-MSH, Restoring MC4R Pathway Signalling to Reduce Body Weight1-7 Hypothalamus1-3 Paraventricular nucleus Paraventricular nucleus Hypothalamus MC4R MC4R neuron Setmelanotide, an MC4R activation8,9 MC4R α-MSH analogue, activates MC4Rs Brainstem Arcuate AgRP nucleus MC
Slide 6: TRANSCEND study design
TRANSCEND study design1 Eligibility criteria Dose titration Treatment arms Double-blind, placebo-controlled treatment Participants aged Setmelanotide, SC, QD ≥4 years with R Open-label LTE or Screening documented obesity 2:1 safety follow-up Placebo, SC, QD Study time point, week 0–8 16 20 28 36 44
Slide 7: Introduction – Setmelanotide in aHO
Introduction – Setmelanotide in aHO • Results from the pivotal cohort of 120 participants with aHO in the Phase 3 TRANSCEND trial (NCT05774756) showed statistically significant and clinically meaningful weight and hunger reductions following treatment with the MC4R agonist setmelanotide1 • Inclusion
Slide 8: Disposition
Disposition ALL PATIENT COHORT N=142 (setmelanotide, n=94, placebo, n=48) DISCONTINUED TREATMENT PAEDIATRIC PARTICIPANTS Setmelanotide Placebo N=76 (setmelanotide, n=49, placebo, n=27) (n=4) (n=4) Adverse events (setmelanotide 3*; placebo 2†) COMPLETED 52 WEEKS Withdrawal by participant/guardian on
Slide 9: Baseline participant demographics
Baseline participant demographics Setmelanotide Placebo Setmelanotide Placebo (n=49) (n=27) (n=49) (n=27) Age, mean ± SD (range), y 11.6 ±4.0 (4, 17) 11.7 ± 3.7 (4, 17) Weight, mean (SD), kg 77.0 (33.5) 74.8 (26.9) Sex, n (%) BMI, mean (SD), kg/m2 32.6 (7.4) 32.8 (6.5) Female 22 (44.9) 19 (70.4) BMI
Slide 10: Baseline patient demographics (cont)
Baseline patient demographics (cont) Setmelanotide Placebo Setmelanotide Placebo (n=49) (n=27) (n=49) (n=27) Tumor/damage type, n (%) Endocrine disorders, n (%) 49 (100) 25 (92.6) Craniopharyngioma 37 (75.5) 17 (63.0) Arginine vasopressin deficiency 44 (89.8) 18 (66.7) Glioma 3 (6.1) 4 (14.8) Centra
Slide 11: Significant reduction in BMI and BMI percent of the 95th percentile with setmelanotide at week 52
Significant reduction in BMI and BMI percent of the 95 th percentile with setmelanotide at week 52 (participants aged <18 years) 52-Week Change in BMI Percent 52-Week Change in BMI of the 95th Percentile Setmelanotide Placebo Setmelanotide Placebo 10 n= 49 n=27 10 n= 49 n=27 Percent change in %BMI95
Slide 12: Significant reduction in BMI z-score (WHO) with setmelanotide at week 52
Significant reduction in BMI z-score (WHO) with setmelanotide at week 52 (participants aged <18 years) Change in BMI z-score Over Time 52-Week BMI z-score* Reduction 0.5 ◼ Setmelanotide ◼ Placebo 0.04 0.03 n=46 n=27 BMI z-core change, LSM 0 0.03 -0.07 0 -0.09 0.0 -0.11 Mean change in BMI -0.28 (95%
Slide 13: Change in most hunger score with setmelanotide vs placebo
Change in most hunger score with setmelanotide vs placebo (participants aged ≥12 to <18 years) Reduction in Most Hunger Score* Over Time 52-Week Most Hunger Score† ◼ Setmelanotide ◼ Placebo Reduction Change in maximal daily hunger 0.0 n=25 n=14 0.0 daily hunger score (95% CI) -0.5 score, LSM (95% CI
Slide 14: Safety
Safety Setmelanotide Placebo Overall • One serious AE was considered (n=49) (n=27) (N=76) related to setmelanotide: AEs 49 (100.0) 25 (92.6) 74 (97.4) hypernatremia (sodium levels 150- AE leading to treatment or study discontinuation 2 (4.1) 2 (7.4) 4 (5.3) 158mmol/L [normal upper limit Serious AEs
Slide 15: Conclusions
Conclusions In this paediatric dataset from the final results from the TRANSCEND trial in aHO, setmelanotide was associated with significant reductions in BMI measures The safety profile of setmelanotide was generally consistent with previous trials in participants with aHO and other rare MC4R pathw
Slide 16: 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 16