Slide 1: Positive Interim Six-month Results from Phase 2 Trial Evaluating Setmelanotide in PWS
® © Rhythm® Pharmaceuticals, Inc. All rights reserved. June 13, 2026 Rhythm Pharmaceuticals Positive Interim Six-month Results from Phase 2 Trial Evaluating Setmelanotide in Patients with Prader-Willi Syndrome EXHIBIT 99.2
Slide 2: Forward-Looking Statements
2 ® 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 considered forward-look
Slide 3: On Today's Call
3 ® On Today’s Call David Meeker, MD Chairman, President & Chief Executive Officer, Rhythm Pharmaceuticals Jennifer Miller, MD Professor of Pediatric Endocrinology, University of Florida Phase 2 Trial Evaluating Setmelanotide in PWS ӏ ENDO 2026
Slide 4: David Meeker, MD
4 ® David Meeker, MD Chairman, President & Chief Executive Officer
Slide 5: Setmelanotide Achieves Consistent Six-Month Results in Phase 2 Trial in PWS
5 ® Reduction in BMI and BMI-Z scores Improvement in hyperphagia and anxiety Preservation of lean mass with loss in fat mass Setmelanotide Achieves Consistent Six-Month Results in Phase 2 Trial in Patients with Prader-Willi Syndrome Further validates MC4R agonism potential to address significant unm
Slide 6: MC4R Agonism Development Across Three Pillars
6 ® MC4R Agonism Development Across Three Pillars Global commercial foundation driven by IMCIVREE in BBS Next-generation MC4R agonists RM-718 (weekly injection) Bivamelagon (daily oral) Genetic MC4R Pathway Diseases Prader-Willi Syndrome Hypothalamic Obesity Phase 2 Trial Evaluating Setmelanotide in
Slide 7: Significant Unmet Need in Prader-Willi Syndrome
7 ® 12,500 – 16,000 PWS prevalence in each of U.S. and Europe 8,500 – 12,750 PWS patients living with hyperphagia/obesity in each of U.S. and Europe Significant Unmet Need in Prader-Willi Syndrome 1) National Center for Health Statistics (CDC), Final Natality Data (1954–2023); 2. Gallagher L, et al.
Slide 8: Setmelanotide Achieves Durable and Consistent Interim Results at Six Months
8 ® -3.06% mean BMI reduction from baseline (n=17) -3.11% mean BMI reduction in adults (n=10) -0.35 mean BMI-Z score reduction in pediatrics (n=7) -4.19% mean fat loss +0.74% mean gain in lean mass Setmelanotide Achieves Compelling, Durable and Consistent Interim Results at Six Months in Phase 2 Tri
Slide 9: Exploratory Phase 2, Open-label Trial of Setmelanotide in PWS
9 ® 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 Primary endpoints: safety and tolerability Secondary endpoints: assessments on BMI, BMI z-score, hyperphagia, body composition and pharmacokinetics Expl
Slide 10: Baseline Demographics
10 ® Baseline Demographics N=18 Patients enrolled Overall (N=18)StatisticParameter 17.1 (5.6) (6 – 23) 3 (16.7) 4 (22.2) 11 (61.1) Mean (SD) (range) <12 years old, n (%) >12 years and <18, n (%) ≥18 years old, n (%) Age, years 8/10 (44.4/55.6)Female / MaleSex, n (%) 15 (83.3) 2 (11.1) 1 (5.6) White
Slide 11: BMI Reductions from Baseline in 14 of 17 Patients at Month 6
11 ® -10 -8 -6 -4 -2 0 2 4 6 M o 6 % c ha ng e fr om b as el in e, B M I Setmelanotide Achieved BMI Reductions from Baseline in 14 of 17 Patients with PWS at Month 6 Phase 2 Trial Evaluating Setmelanotide in PWS ӏ ENDO 2026 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
Slide 12: Consistent BMI, Fat Mass Reductions in Adult Patients at Month 6
12 ® Patient #: 1 2 3 6 7 9 10 12 13 17 Age/sex: 20/F 18/F 23/F 23/M 23/M 18/F 20/M 20/M 23/F 22/M Vykat (Y/N): N N N Y Y Y Y N Y Y -7.22 -7.92 -10.12 -3.94 1.39 -13.34 -4.10 -15.99 -5.80 -0.13 -6.33 -1.04 0.03 2.17 1.51 -1.64 -1.52 -0.57 -20 -10 0 10 % c ha ng e fr om B L FM LM 5.15 -4.83 -5.83 -2.
Slide 13: Consistent BMI Z-Score Reductions and Muscle Mass Gains in Pediatric Patients
13 ® 3.24 3.23 -8.08 -5.83 -5.65 9.15 3.96 -0.22 0.28 2.95 5.63 3.30 4.15 3.25 -10 0 10 20 % c ha ng e fr om B L FM LM -0.01 -0.19 -0.40 -0.22 -0.26 -0.65 -0.75-0.8 -0.6 -0.4 -0.2 0 Ch an ge fr om ba se lin e 6/7 patients achieved BMI z-score reduction of ~0.2 or greater; mean BMI z-score change: -0
Slide 14: Improvements in Hyperphagia and Anxiety Scores in Adult Patients
14 ® 20 0 10 7 6 15 29 0 18 14 8 0 0 3 1 5 10 1 1 5 0 20 40 sc or e BL Mo6 5.15 -4.83 -5.83 -2.58 -2.92 -0.78 -2.19 -2.22 -8.50 -6.40-10 0 10 % c hn g fr om B L Patient #: 1 2 3 6 7 9 10 12 13 17 Age/sex: 20/F 18/F 23/F 23/M 23/M 18/F 20/M 20/M 23/F 22/M Vykat (Y/N): N N N Y Y Y Y N Y Y 26 29 42 12
Slide 15: Improvements in Hyperphagia and Anxiety Scores in Pediatric Patients
15 ® Improvements in Hyperphagia and Anxiety Scores Observed in Pediatric Patients at Month 6 -0.01 -0.19 -0.40 -0.22 -0.26 -0.65 -0.75-1 -0.5 0 ch ng fr om B L 38 35 20 33 18 31 21 33 25 7 14 6 11 23 0 10 20 30 40 sc or e 18 14 14 15 2 18 7 19 8 6 5 0 5 4 0 5 10 15 20 sc or e BL Mo6 Patient #: 5 8
Slide 16: Most Common Adverse Events for All Patients
16 ® Overall n (%) (n=18) Adverse Events 11 (61.1)Injection site reaction 10 (55.6)Skin hyperpigmentation 6 (33.3)Fatigue 2 (11.1)Norovirus infection 2 (11.1)Hypothyroidism 2 (11.1)Diabetes mellitus Most Common Adverse Events for All Patients (N=18) Phase 2 Trial Evaluating Setmelanotide in PWS ӏ EN
Slide 17: Discussion with Dr. Jennifer Miller
17 ® Discussion with Dr. Jennifer Miller
Slide 18: Historical Context: Beloranib Trial Results in PWS
18 ® Historical Context: Beloranib Trial Results in PWS: Changes in Weight, HQ-CT Scores at Week 26 Diabetes Obes Metab. 2017;19:1751–1761.
Slide 19: Questions?
Questions? Rhython 19
Slide 20: Appendix
Appendix Rhython 20
Slide 21: Published Epidemiology Estimates for PWS
21 ® 1:15,000 births 1:15,000-25,000 births 350,000 worldwide 1:15,000-25,000 births 1:10,000-30,000 incidence 350,000-400,000 worldwide • Estimates are relatively consistent, but often because of iterative referencing rather than citing primary epidemiology studies • Estimates most often cite birth
Slide 22: Estimating Addressable PWS Prevalence
22 ® To Estimate The Addressable PWS Prevalence, We Leverage The PWS Incidence Combined with Survival Rate Number of births per year PWS incidence rate Survival rate among PWS population at each age Addressable PWS prevalence Share of patients with a disrupted MC4R pathway A B C
Slide 23: Published PWS Incidence Rates
23 ® • 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 older primary sources and include a range of populations (ex: Australia, France, UK, Sweden, US)6-10 • Several recent primary studies rep
Slide 24: Mean Life Expectancy Estimated Around 30 Years
24 ® The premature death is patients with PWS has been consistently reported in several studies: French expert center2: Median age at death: 30 years (N=104 death) Yet, childhood death has been reported at a lower rate 25% of the death occurring before the age of 20 yo USA 40-years mortality
Slide 25: Share of Addressable Patients with Hyperphagia and Obesity
25 ® Few sources are consistently reporting hyperphagia frequency across different age groups, yet the Irish patient association has reported a survey (N=61)1: In different reviews, the rate of hyperphagia/obesity is reported in the range of 90%-100%2 Share of Addressable Patients with Hyperphag
Slide 26: Estimated Addressable PWS Prevalence in the US & EU
26 ® PWS prevalence is estimated to be: 12,500 – 16,000 with an addressable prevalence of 8,500 – 12,750 (pts with PWS living with hyperphagia/obesity) In absence of any evidence supporting any ethnics differences, the addressable prevalence is expected to be the same across different geographies Th