Rhythm Pharmaceuticals, Inc. · NASDAQ:RYTM

Rhythm Pharmaceuticals — Conference Presentation (April 2025)

27 slides from Rhythm Pharmaceuticals's conference presentation, Apr 7, 2025

  1. Slide 1: Positive Topline Results from Phase 3 Trial Evaluating Setmelanotide in Acquired Hypothalamic Obesity

    Rhythm Pharmaceuticals Positive Topline Results from Phase 3 Trial Evaluating Setmelanotide in Patients with Acquired Hypothalamic Obesity April 7, 2025 ® © 2025. Rhythm Pharmaceuticals, Inc. All rights reserved. Rhythm and its logo are trademarks of Rhythm Pharmaceuticals, Inc.

  2. 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

  3. Slide 3: On Today's Call

    On Today’s Call Susan Phillips, MD David Meeker, MD Hunter C. Smith Pediatric Endocrinologist at Rady Chair, President and Chief Financial Officer Children's Hospital-San Diego Chief Executive Officer Professor of Pediatrics at UC San Diego School of Medicine ® 3

  4. Slide 4: David Meeker, MD

    David Meeker, MD Chair, President and CEO ® 4

  5. Slide 5: Acquired Hypothalamic Obesity Represents Significant Global Opportunity

    Acquired Hypothalamic Obesity Represents Significant Global Opportunity Rare, life-changing Significant Identified, Setmelanotide achieved disease with unmet need actively engaged highly clinically meaningful severe impact and with no approved patient BMI reduction in largest, burden on patients the

  6. Slide 6: Phase 3 TRANSCEND Trial: Largest and Longest Placebo-controlled Trial in Acquired Hypothalamic Obesity

    Phase 3 TRANSCEND Trial: Largest and Longest Placebo-controlled Trial in Acquired Hypothalamic Obesity Trial Primary analysis cohort Dose titration Double-blind, placebo-control 81 Setmelanotide QD (n=80) 120 Open-label extension patients treated with setmelanotide: 39 Placebo QD (n=40) placebo Up t

  7. Slide 7: Demographics of Primary Analysis Cohort

    Demographics of Primary Analysis Cohort BASELINE CHARACTERISTIC Total (n=120) Mean (SD) (Range) 19.9 (13.8) (4 – 66) <12 years old, n 31 (25.8) Age, years >12 years and <18, n 40 (33.3) ≥18 years old, n 49 (40.8) Sex, n (%) Female / Male 72/48 (60/40) Race, n (%) White 100 (83) Hispanic or Latino 14

  8. Slide 8: Vast Majority of Patients Completed Trial, Transitioned to Extension Study

    Vast Majority of Patients Completed Trial, Transitioned to Extension Study PRIMARY ANALYSIS COHORT (N=120) DISCONTINUED Treatment Placebo (n=9) (n=5) 101 PATIENTS AE (n=7) ENROLLED IN Withdrawal (n=7) OPEN-LABEL COMPLETED 52 WEEKS EXTENSION* at therapeutic regimen (n=106) *As of data cutoff, April 3

  9. Slide 9: Setmelanotide Achieved Statistically Significant and Highly Clinically Meaningful Reduction in BMI

    Setmelanotide Achieved Statistically Significant and Highly Clinically Meaningful Reduction in BMI Primary analysis cohort (N=120) -16.5% BMI change from baseline in -19.8% +3.3% BMI change from baseline in Placebo-adjusted Setmelanotide arm difference in BMI reduction Placebo arm (n=81) from baseli

  10. Slide 10: Significant Reductions in BMI Observed in both Adults and Children

    Significant Reductions in BMI Observed in both Adults and Children ≥18 Years Old (n=49) <18 Years Old (n=71) +2.4% +3.9% % Change from Baseline % Change from Baseline 10 20 0 10 0 -10 -10 -20 -20 -30 -40 -16.8% -19.2% Placebo-adjusted -30 -40 -16.3% -20.2% Placebo-adjusted Difference Difference (P<0

  11. Slide 11: Consistent Response to Setmelanotide Therapy Observed across Majority of Patients

    Consistent Response to Setmelanotide Therapy Observed across Majority of Patients 90% Setmelanotide 80% 80% Placebo Proportion of patients 70% 63% 60% 51% 50% 43% 40% 30% 20% 10% 10% 5% 3% 0% 0% 5% 10% 15% 20% P<0.0001 P<0.0001 P<0.0001 P<0.0001 Observed Reduction in BMI at 52 weeks ® 11

  12. Slide 12: Further Explanation on a Few Patient Outliers

    Further Explanation on a Few Patient Outliers Adult patient on Pediatric patients on Adolescent patient setmelanotide setmelanotide on placebo (BMI Z-score reduction of 0.2 considered clinically significant) 23yo female 6yo male 12yo female • No BMI decrease during • BMI decrease of -2.5% during 52-

  13. Slide 13: Setmelanotide Achieved Statistically Significant Reduction in Hunger Compared with Placebo

    Setmelanotide Achieved Statistically Significant Reduction in Hunger Compared with Placebo in Patients ≥12 Years Old 1 0 Change from Baseline -1 -2 -3 -1.2 -4 -5 -1.4 Placebo-adjusted -6 -2.7 Difference (P<0.003) Setmelanotide Placebo (n=57) (n=24) Note: Patients ≥12 years of age were administered t

  14. Slide 14: Significant BMI Reductions Observed in Patients with Prior Use or Concomitant Use of GLP-1s

    Significant BMI Reductions Observed in Patients with Prior Use or Concomitant Use of GLP-1s Prior use of GLP-1 (n=16) Concomitant GLP-1 (n=15) -24.7% -27.1% Placebo-adjusted Placebo-adjusted difference in BMI difference in BMI reduction from reduction from baseline baseline ® 14

  15. Slide 15: Setmelanotide Generally Well Tolerated with No New Safety Signals

    Setmelanotide Generally Well Tolerated with No New Safety Signals Setmelanotide Placebo Overall Parameter n (%) n (%) n (%) (n=81) (n=39) (n=120) At Least 1 AE 81 (100.0) 35 ( 89.7) 116 ( 96.7) At Least 1 Drug-Related AE 71 ( 87.7) 26 ( 66.7) 97 ( 80.8) At Least 1 Serious AE 23 ( 28.4) 3 ( 7.7) 26 (

  16. Slide 16: Setmelanotide Generally Well Tolerated with No New Safety Signals

    Setmelanotide Generally Well Tolerated with No New Safety Signals Setmelanotide Placebo Overall Most Common (≥20% Overall) n (%) n (%) n (%) (n=81) (n=39) (n=120) Skin hyperpigmentation 45 ( 55.6) 3 ( 7.7) 48 ( 40.0) Nausea 41 ( 50.6) 15 ( 38.5) 56 ( 46.7) Headache 32 ( 39.5) 12 ( 30.8) 44 ( 36.7) V

  17. Slide 17: Susan Phillips, MD

    Susan Phillips, MD Pediatric endocrinologist at Rady Children's Hospital-San Diego; Professor of pediatrics at UC San Diego School of Medicine ® 17

  18. Slide 18: α-MSH Drives MC4R Pathway Signaling to Regulate Energy Balance and Body Weight

    α-MSH Drives MC4R Pathway Signaling to Regulate Energy Balance and Body Weight 1-3 Hypothalamus1-5 Paraventricular Paraventricular nucleus nucleus α-MSH binds MC4R MC4R to MC4Rs Hypothalamus neuron MC4R α-MSH production α-MSH & MC4R expression MC4R signaling within the brain and spinal cord Arcuate

  19. Slide 19: Hypothalamic Damage Can Impair MC4R Pathway Signaling and Lead to Acquired Hypothalamic Obesity

    Hypothalamic Damage Can Impair MC4R Pathway Signaling and Lead to Acquired Hypothalamic Obesity 1-3 Hypothalamus4-7 Paraventricular Paraventricular nucleus nucleus MC4R Hypothalamus MC4R MC4R activation by neuron Hypothalamic DYSREGULATION DOWNSTREAM α-MSH MC4R Damage α-MSH production α-MSH of homeo

  20. Slide 20: Acquired Hypothalamic Obesity: Rare Disease with Accelerated Weight Gain Following Various Injuries

    Acquired Hypothalamic Obesity: Rare Disease with Accelerated Weight Gain Following Various Injuries to the Hypothalamic Region MC4R pathway deficiency following injury to Tumor Frequency in the International Registry hypothalamic region causes reduced energy, of Hypothalamic Obesity Disorders (IHROD

  21. Slide 21: Patient Case Report: 16yo Female Achieved 22.7% BMI Reduction at 16 Weeks

    Patient Case Report: 16yo Female Achieved 22.7% BMI Reduction at 16 weeks on Setmelanotide Therapy in Phase 2 Trial 8yo: Diagnosed with craniopharyngioma -22.7% 2014 2015 BMI reduction at surgical resection radiotherapy week 16 16yo: Enters Setmelanotide Ph2 trial in 2021 41.1kg/m 2 31.8kg/m 2 122.8

  22. Slide 22: AUGUST

    2013 AUGUST 7yo before AUGUST 2024 tumor 2021 diagnosis ® 22

  23. Slide 23: David Meeker, MD

    David Meeker, MD Chair, President and CEO ® 23

  24. Slide 24: Hypothalamic Obesity: A Potentially Transformative Opportunity

    Hypothalamic Obesity: A Potentially Transformative Opportunity 5,000 – 10,000 ✓ Unmet medical need is high estimated U.S. prevalence1 ✓ Patients are identified 3,500 – 10,000 ✓ Patients engaged with system estimated European prevalence2 5,000 – 8,000 ~500 Estimated incidence in each U.S., Europe and

  25. Slide 25: Focus on Global Regulatory Strategy

    Focus on Global Regulatory Strategy US EU UK CANADA JAPAN Regulatory submissions in the U.S. and EU expected to be completed in Q3 2025 ® 25

  26. Slide 26: Additional Important Milestones and Data Readouts Anticipated

    Additional Important Milestones and Data Readouts Anticipated RM-718 Setmelanotide Bivamelagon First patient to be dosed in First patient to be dosed in Ph3 Topline data from Ph1, Part C in acquired HO congenital HO substudy Phase 2 trial in acquired HO anticipated in anticipated in anticipated in A

  27. Slide 27: Questions?

    Questions? Rhythm

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