Rhythm Pharmaceuticals, Inc. · NASDAQ:RYTM
Rhythm Pharmaceuticals — ENDO 2026
26 slides from Rhythm Pharmaceuticals's conference presentation, Jun 13, 2026
Slide 1: Positive Interim Six-month Results from Phase 2 Trial Evaluating Setmelanotide in PWS
Rhythm Pharmaceuticals Positive Interim Six-month Results from Phase 2 Trial Evaluating Setmelanotide in Patients with Prader-Willi Syndrome June 13, 2026 ® © Rhythm® Pharmaceuticals, Inc. All rights reserved.
Slide 2: Forward-looking Statements
Forward-looking Statements This presentation and the accompanying oral presentation contain forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. All statements contained in this presentation that do not relate to matters of historical fact should be
Slide 3: On Today's Call
On Today’s Call David Meeker, MD Jennifer Miller, MD Chairman, President & Chief Professor of Pediatric Executive Officer, Endocrinology, University of Rhythm Pharmaceuticals Florida ® 3 Phase 2 Trial Evaluating Setmelanotide in PWS ӏ ENDO 2026
Slide 4: David Meeker, MD
David Meeker, MD Chairman, President & Chief Executive Officer ® 4
Slide 5: Setmelanotide Achieves Consistent Six-Month Results in Phase 2 Trial in Patients with PWS
Setmelanotide Achieves Consistent Six-Month Results in Phase 2 Trial in Patients with Prader-Willi Syndrome Further validates MC4R agonism potential to address significant unmet need and treat patients with Prader-Willi syndrome (PWS) Reduction in BMI Preservation of Improvement in and BMI-Z scores
Slide 6: MC4R Agonism Development Across Three Pillars
MC4R Agonism Development Across Three Pillars Next-generation MC4R agonists Genetic MC4R Pathway Diseases RM-718 Bivamelagon (weekly injection) (daily oral) Hypothalamic Obesity Global commercial foundation Prader-Willi Syndrome driven by IMCIVREE in BBS ® 6 Phase 2 Trial Evaluating Setmelanotide in
Slide 7: Significant Unmet Need in Prader-Willi Syndrome
Significant Unmet Need in Prader-Willi Syndrome Births 1:8,000 to 1:10,000 Survival rate 80-90% of PWS patients per year1 Incidence2,3 by age4 with MC4R pathway impairment5,6 12,500 – 16,000 8,500 – 12,750 PWS prevalence in each of U.S. and Europe PWS patients living with hyperphagia/obesity in each
Slide 8: Setmelanotide Achieves Compelling, Durable and Consistent Interim Results at Six Months
Setmelanotide Achieves Compelling, Durable and Consistent Interim Results at Six Months in Phase 2 Trial in Patients with PWS -3.06% -4.19% +0.74% mean BMI reduction from baseline (n=17) mean fat loss mean gain in 80% lean mass 8 of 10 patients -3.11% -0.35 Showing preservation of lean mass in patie
Slide 9: Exploratory Phase 2, Open-label Trial of Setmelanotide in PWS
Exploratory Phase 2, Open-label Trial of Setmelanotide in PWS 18 patients with PWS and obesity aged 6 to 65 years old enrolled Daily dose of setmelanotide escalated up to 5 mg/day as tolerated for 52 weeks Dose to therapeutic Prespecified Interim regimen Analysis at Month 6 Primary endpoints: safety
Slide 10: Baseline Demographics
Baseline Demographics Parameter Statistic Overall (N=18) N=18 Mean (SD) (range) 17.1 (5.6) (6 – 23) Patients enrolled <12 years old, n (%) 3 (16.7) Age, years >12 years and <18, n (%) 4 (22.2) ≥18 years old, n (%) 11 (61.1) n=1 discontinued (withdrawal Sex, n (%) Female / Male 8/10 (44.4/55.6) by pa
Slide 11: Setmelanotide Achieved BMI Reductions from Baseline in 17 Patients with PWS at Month 6
Setmelanotide Achieved BMI Reductions from Baseline in 14 of 17 Patients with PWS at Month 6 6 4 Mo 6 % change from baseline, BMI 2 0 -2 -4 -6 -3.06% mean BMI reduction from -8 baseline at Month 6 (n=17) -10 Patient #: 13 11 17 3 18 2 15 14 8 7 6 12 10 9 16 5 1 Age/sex: 23/F 8/F 22/M 23/F 6/M 18/F 1
Slide 12: Consistent BMI, Fat Mass Reductions Observed in Adult Patients at Month 6
Consistent BMI, Fat Mass Reductions Observed in Adult Patients at Month 6 9/10 patients achieved BMI reduction; mean BMI % change: -3.11% (n=10) 10 5.15 % change from 5 baseline BMI 0 -0.78 -5 -2.58 -2.92 -2.19 -2.22 -4.83 -5.83 -6.40 -10 -8.50 6/9 patients with DEXA data achieved >5% reduction in f
Slide 13: Consistent BMI Z-Score Reductions and Gains in Muscle Mass in Pediatric Patients
Consistent BMI Z-Score Reductions and Gains in Muscle Mass Observed in Pediatric Patients at Month 6 6/7 patients achieved BMI z-score reduction of ~0.2 or greater; mean BMI z-score change: -0.35 (n=7) 0 -0.01 -0.2 Change from -0.19 baseline BMI -0.22 -0.26 -0.4 z-score -0.40 -0.6 -0.65 -0.8 -0.75 5
Slide 14: Improvements in Hyperphagia and Anxiety Scores Observed in Adult Patients at Month 6
Improvements in Hyperphagia and Anxiety Scores Observed in Adult Patients at Month 6 10 5.15 % chng from BL 0 BMI -0.78 -2.19 -2.22 -2.58 -2.92 -4.83 -5.83 -10 -6.40 -8.50 6/6 patients with baseline values >7 achieved clinically meaningful improvement in HQ-CT score 40 29 BL 20 18 score 20 Mo6 15 14
Slide 15: Improvements in Hyperphagia and Anxiety Scores Observed in Pediatric Patients at Month 6
Improvements in Hyperphagia and Anxiety Scores Observed in Pediatric Patients at Month 6 0 -0.01 chng from BL -0.19 -0.22 -0.26 BMI -0.5 -0.40 z-score -0.65 -0.75 -1 3/5 patients with baseline values >7 achieved clinically meaningful improvement in HQ-CT score 20 18 19 15 BL Mo6 18 14 14 15 8 score
Slide 16: Most Common Adverse Events for All Patients (N=18)
Most Common Adverse Events for All Patients (N=18) Overall Adverse Events n (%) (n=18) Injection site reaction 11 (61.1) Skin hyperpigmentation 10 (55.6) Fatigue 6 (33.3) Norovirus infection 2 (11.1) Hypothyroidism 2 (11.1) Diabetes mellitus 2 (11.1) Note: As of May 7, 2026 ® 16 Phase 2 Trial Evalua
Slide 17: Discussion with Dr. Jennifer Miller
Discussion with Dr. Jennifer Miller ® 17
Slide 18: Historical Context: Beloranib Trial Results in PWS
Historical Context: Beloranib Trial Results in PWS: Changes in Weight, HQ-CT Scores at Week 26 Diabetes Obes Metab. 2017;19:1751–1761. ® 18
Slide 19: Questions?
Questions? ® 19
Slide 20: Appendix
Appendix ® 20
Slide 21: Published Epidemiology Estimates for PWS Are Readily Available, With Some Considerations
Published Epidemiology Estimates for PWS Are Readily Available, With Some Considerations • Estimates are relatively consistent, but often because of iterative Notable public benchmarks referencing rather than citing primary epidemiology studies 1:15,000 births • Estimates most often cite birth incid
Slide 22: To Estimate The Addressable PWS Prevalence, We Leverage Incidence Combined with Survival Rate
To Estimate The Addressable PWS Prevalence, We Leverage The PWS Incidence Combined with Survival Rate A B C Survival rate Share of patients Number of births PWS incidence among PWS with a disrupted per year rate population at each MC4R pathway age Addressable PWS prevalence ® 22
Slide 23: Published PWS Incidence Rates Are Very Broad; Estimated at 1:8,000 to 1:10,000
A Published PWS Incidence Rates Are Very Broad But When Leveraging Primary Studies, The PWS Incidence Is Estimated at 1:8,000 to 1:10,000 • Published PWS birth incidence rates most often cited in a range of 1:10,000-30,00001-5 • Reviews and publications often utilize overlapping references from olde
Slide 24: Mean Life Expectancy Is Estimated To Be Around 30 Years
Mean Life Expectancy Is Estimated To Be Around 30 Years With 25- B 35% of The Death Occurring During Childhood Kaplan-Meier survival estimates derived from age-based mortality rates1 100% The premature death is patients with PWS has 90% been consistently reported in several studies: 36% of the death
Slide 25: Share of Addressable Patients with Hyperphagia and Obesity Estimated at 80%-90%
C Share of Addressable Patients with Hyperphagia and Obesity is Estimated to Be 80% - 90% With An Age of Onset Between 4 - 6 Years ➢ Few sources are consistently reporting hyperphagia frequency across different age groups, yet the Irish patient association has reported a survey (N=61)1: Presence of
Slide 26: Estimated Addressable PWS Prevalence is 8,500 – 12,750 in the US & EU
The Estimated Addressable PWS Prevalence is Estimated to be 8,500 – 12,750 in the US & EU with Children Accounting for ~34% Breakdown of the prevalence by age group Survival rate Share of Number of PWS incidence among PWS patients with a 3.079 births per year1 rate population at disrupted MC4R each