Rhythm Pharmaceuticals, Inc. · NASDAQ:RYTM

Rhythm Pharmaceuticals — Investor Presentation (September 2026)

66 slides from Rhythm Pharmaceuticals's investor presentation, September 2026

  1. Slide 1: Rhythm Pharmaceuticals Corporate Presentation

    Rhythm Pharmaceuticals Corporate Presentation September 2026 ® © Rhythm® Pharmaceuticals, Inc. All rights reserved.

  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: 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 established by IMCIVREE in BBS ® 3

  4. Slide 4: IMCIVREE: First and Only Therapy Approved for Acquired HO

    IMCIVREE: First and Only Therapy Approved for Acquired HO ✓ U.S. launch underway following March 19th FDA Approval ✓ Japan’s MHLW Granted Marketing Authorization; launch anticipated by year-end 2026 ✓ European Commission Granted Marketing Authorization; country-level launches expected to begin in 20

  5. Slide 5: MC4R Pathway Biology is Clear

    MC4R Pathway Biology is Clear Hypothalamus Upstream Downstream Downstream AgRP neuron MC4R activity Low Normal LEPR AgRP Adipose Hyperphagia tissue PCSK1 MC4R Obesity MC4R neuron α-MSH POMC α-MSH Leptin β-MSH β-MSH Blood-brain POMC Energy barrier neuron Expenditure LEPR AgRP, agouti-related peptide;

  6. Slide 6: Patient Spotlight: Living with Acquired Hypothalamic Obesity

    Patient Spotlight: Living with Acquired Hypothalamic Obesity Setmelanotide Patient Isaac "Everything with day-to-day life was harder for him. Dealing with hyperphagia on top of that…he would suffer, his quality of life was not good" “He was so overweight that everything was a struggle." - Brenda, mo

  7. Slide 7: Expanding Pipeline in Rare Neuroendocrine Diseases

    Expanding Pipeline in Rare Neuroendocrine Diseases Patient Population Pre-clinical Phase 1/2 Phase 3 Regulatory Approval Setmelanotide1 Acquired hypothalamic obesity US, EU, UK, Japan daily sc injection Bardet-Biedl syndrome or US, EU, UK, Canada biallelic POMC, PCSK1 or LEPR deficiency Setmelanotid

  8. Slide 8: Significant Market Opportunity for MC4R Agonists

    Significant Market Opportunity for MC4R Agonists U.S. patent protection for next-generation assets bivamelagon and RM-718 extends into 2040s IMCIVREE approved in IMCIVREE approved in U.S., Prader-Willi U.S., EU,+ EU, Japan for acquired HO syndrome 4,000 – 5,000* ~10,000 8,500 -12,750 Bardet-Biedl sy

  9. Slide 9: Well Capitalized: Cash Sufficient to Fund Planned Operations for at least 24 Months

    Well Capitalized: Cash Sufficient to Fund Planned Operations for at least 24 Months $330.9M Guidance 68.6 Million Cash, cash equivalents RYTM expects cash to Common shares and short-term be sufficient to fund outstanding as of investments as of planned operations June 30, 2026 June 30, 2026 for at l

  10. Slide 10: Rhythm Leadership – Strong Team with Broad Biopharma Experience

    Rhythm Leadership – Strong Team with Broad Biopharma Experience David Meeker, MD Hunter Smith Jennifer Lee Yann Mazabraud Joe Shulman Alastair Garfield, AJ Joshi, MD Chair, President and Chief Financial Officer Executive Vice Executive Vice Chief Technology PhD Chief Medical Officer Chief Executive

  11. Slide 11: Multiple Anticipated Milestones

    Multiple Anticipated Milestones Complete enrollment in the Ph1/2, Part D trial evaluating RM-718 H2 2026 (weekly injectable) in Prader-Willi syndrome Complete enrollment in substudy evaluating setmelanotide in H2 2026 congenital HO YE 2026 Launch IMCIVREE for acquired HO in Japan YE 2026 Initiate pi

  12. Slide 12: IMCIVREE Global Commercial Execution

    IMCIVREE Global Commercial Execution ® 12

  13. Slide 13: IMCIVREE available in >25 countries outside the United States

    IMCIVREE available in >25 countries outside the United States for BBS and/or POMC/LEPR Deficiencies Supporting Long-Term Growth Established global commercial infrastructure Upcoming Ex-US Launches in aHO Focused on reaching more patients globally ® 13

  14. Slide 14: Steady Growth in Net Product Revenues since BBS Launch

    Steady Growth in Net Product Revenues since BBS Launch FDA approved IMCIVREE for BBS in June 2022 $71.3M $70 $60.1M $60 $57.3M Global net sales in $M $51.3M $48.5M $50 $41.8M $40 $37.7M $33.3M $29.1M $26.0M $30 $24.2M $22.5M $19.2M $20 $11.5M $8.8M $10 $4.3M $2.3M $- 2Q 22 3Q 22 4Q 22 1Q 23 2Q 23 3Q

  15. Slide 15: HO US Launch: Strong Patient Demand and Early Uptake

    HO US Launch: Strong Patient Demand and Early Uptake in first 14 weeks Start Forms Patients by age Hypothalamic injury 12% >400 18-21yo ~15% Patient Start Forms 50% within two years >22yo 18% Inclusive of 66 start forms from 12-17yo ~50% >​10 years clinical trial patients 21% 4-11yo Note: Between FD

  16. Slide 16: HO US Launch: Broad Prescriber Activation and Engagement

    HO US Launch: Broad Prescriber Activation and Engagement Prescribers Specialty Priority Accounts ~300 43% ~65% Adult Endocrinologist Activated Unique prescribers ~20% 37% ~25% Repeat aHO Prescribers Pediatric Endocrinologist of Prescriptions Note: Between FDA approval on March 19, 2026 and June 30,

  17. Slide 17: HO US Launch: Encouraged by Early Payer Engagement

    HO US Launch: Encouraged by Early Payer Engagement Payers Majority of early approvals came at prior authorization without aHO specific policy in place Positive policies secured 25% Payer engagement continues with majority of P&T of Medicaid covered lives meetings expected by year end 35% of commerci

  18. Slide 18: Setmelanotide in Hypothalamic Obesity

    Setmelanotide in Hypothalamic Obesity Acquired and Congenital ® 18

  19. Slide 19: Hypothalamic Obesity: A Rare, Acquired Form of Obesity

    Hypothalamic Obesity: A Rare, Acquired Form of Obesity Following Injury to the Hypothalamic Region Craniopharyngioma (CP) and other suprasellar brain tumors and treatment – tumor resection surgery and radiation – is most common cause MC4R pathway deficiency following injury to hypothalamic region ca

  20. Slide 20: Severe, Life-long Burden for Patients with Acquired HO

    Severe, Life-long Burden for Patients with Acquired HO Frequent visits with multiple specialists, a complex regimen of medications, and hospitalization “Treatment of patients with tumor/treatment- 3.7 average hospitalizations during the two years following index; 12 average number of general practit

  21. Slide 21: IMCIVREE Approval Supported By Significant BMI Reduction in Phase 3

    IMCIVREE Approval Supported By Statistically Significant and Highly Clinically Meaningful BMI Reduction in Phase 3 Acquired HO Trial Primary analysis cohort (N=142) -16.4% BMI change from baseline in -18.8% +2.4% BMI change from baseline in Placebo-adjusted Setmelanotide arm difference in BMI reduct

  22. Slide 22: BMI Reductions with Prior or Concomitant GLP-1 Use

    Significant BMI Reductions Observed in Patients Treated with Setmelanotide 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 baselin

  23. Slide 23: HO: Aggressive, Rapid Weight Gain follows Therapy for CP

    HO: Aggressive, Rapid Weight Gain follows Therapy for CP Patient Case Study: Setmelanotide therapy achieved rapid, significant weight loss Setmelanotide GLP1 therapy therapy Patient case of M. Jennifer Abuzzahab, MD, Pediatric Endocrinologist, at Children's Minnesota ® 23

  24. Slide 24: Mean BMI Reduction Consistent Across Stratified Age Groups

    Mean BMI Reduction Consistent Across Stratified Age Groups in Phase 3 Trial Evaluating Setmelanotide in Acquired HO < 12 Yrs 12 – < 18 Yrs ≥ 18 Yrs -19.5% -21.0% -19.2% p <0.0001 p <0.0001 p <0.0001 (n=31: 20 setmelanotide, 11 placebo) (n=40: 28 setmelanotide, 12 placebo) (n=49: 33 setmelanotide, 16

  25. Slide 25: TRANSCEND Results: Data from 12-patient Japanese Cohort

    Phase 3 TRANSCEND Results: Data from 12-patient Japanese Cohort Consistent with Full Data Set -18.8%* -13.0%* p <0.0001 p = 0.0388 (n=142: 94 setmelanotide, 48 placebo) (n=12: 8 setmelanotide, 4 placebo) 10% LLSM Percent Change from BL (SE) 5% 2.4% -0.9% 0% -5% -10% -15% -13.9% -16.4% -20% All Patie

  26. Slide 26: Congenital HO Represents Additional Opportunity with Significant Unmet Need

    Congenital HO Represents Additional Opportunity with Significant Unmet Need Congenital HO occurs due to dysfunction or damage to the hypothalamus from birth, with patients often experiencing >1,000 hyperphagia and difficulty managing their weight Patients The weight gain and appetite changes accompa

  27. Slide 27: 34-week Substudy in Congenital Hypothalamic Obesity

    34-week Substudy in Congenital Hypothalamic Obesity Added to Pivotal, Ph3 HO Study Independent substudy leverages existing Ph3 trial infrastructure; Enrollment completion expected in H2 2026 Dose titration Double-blind, placebo-control 39 Setmelanotide QD (n=26) patients randomized Open-label extens

  28. Slide 28: Bivamelagon (Daily Oral MC4R Agonist) in aHO

    Bivamelagon (Daily Oral MC4R Agonist) in aHO ® 28

  29. Slide 29: SIGNAL Trial: Phase 2 Trial Evaluating Bivamelagon

    SIGNAL Trial: 14-week, Phase 2 Open-label Trial Evaluating Bivamelagon in Patients with Hypothalamic Obesity RDZ 1:1:1:1 200 mg 200 mg 400 mg Long-term Screening 200 mg 400 mg 600 mg Extension (LTE) Trial 200 mg 400 mg 600 mg Placebo 2 weeks 12 weeks Open-label Week 0 Week 2 Week 14 Week 15 Week 16

  30. Slide 30: Overall Baseline Demographics

    Overall Baseline Demographics N=28 38.7 kg/m2 Mean BMI Overall bivamelagon 46.4% 82.1% population Female Patients with craniopharyngioma 25.4yo 7 years Mean Age Mean time from hypothalamic (13 of 28 <18yo) injury to trial enrollment ® 30

  31. Slide 31: Bivamelagon Achieved Statistically Significant BMI Reductions at All Doses

    Bivamelagon Achieved Statistically Significant BMI Reductions at All Doses Placebo 200 mg 400 mg 600 mg +2.18% -2.68% -7.69% -9.31% Mean BMI increase Mean BMI reduction Mean BMI reduction Mean BMI reduction from baseline from baseline from baseline from baseline (n=7) (n=6) (n=7) (n=8) p-value = 0.0

  32. Slide 32: Bivamelagon BMI Reductions Consistent with Setmelanotide

    Post-hoc analysis: Bivamelagon Achieved BMI Reductions Consistent with Setmelanotide Setmelanotide Bivamelagon Phase 2+3 combined* All patients Removing 2 patients with documented non-compliance 400 600 400 600 5.0 mg mg mg mg Mean percent BMI reduction, % n=59 n=64† n=8 n=7** n=7 n=6** 0.0 -5.0 -10

  33. Slide 33: AEs consistent with MC4R Mechanism

    AEs consistent with MC4R Mechanism, Setmelanotide Trials in Acquired Hypothalamic Obesity BIVA 200mg BIVA 400mg BIVA 600mg Placebo n (%) (N=6) (N=7) (N=8) (N=7) Any AEs 6 (100) 7 (100) 8 (100) 6 (86) Serious AEs 0 (0) 1 (14) 0 1 (14) Treatment-Related AEs 6 (100) 7 (100) 8 (100) 3 (43) Treatment-Rel

  34. Slide 34: RM-718 (Weekly Injectable MC4R Agonist) in aHO

    RM-718 (Weekly Injectable MC4R Agonist) in aHO ® 34

  35. Slide 35: Baseline Demographics

    Baseline Demographics N=11 Parameter Statistic Overall (N=11) patients enrolled Mean (SD) (range) 26.7 (13.1) (12 – 48) n=8 Age, years >12 years and <18, n (%) 4 (36.4) remain on ≥18 years old, n (%) 7 (63.6) active therapy* n=7 Sex, n (%) Female / Male 9/2 (81.8/18.2) reached Week 16 n=2 White 10 (

  36. Slide 36: RM-718 Achieved Clinically Meaningful BMI Reduction at Week 16

    RM-718 Achieved Clinically Meaningful BMI Reduction in Patients with Acquired HO at Week 16 -11.6% mean BMI reduction from baseline at Week 16 (n=7) BMI, body mass index. ® 36

  37. Slide 37: RM-718 Comparable Reductions to Setmelanotide and Bivamelagon

    RM-718 Exhibited Comparable Reductions to Setmelanotide and Bivamelagon Setmelanotide Bivamelagon 030+040 Per-protocol, 600 mg RM-718 Wk16 Wk14 Wk16 0.0% n=7 n=7 n=64 -2.0% Mean percent change in BMI -4.0% -6.0% -8.0% -10.0% -10.1% -10.1% -12.0% -11.6% ® 37

  38. Slide 38: Four Patients Achieved Deepening BMI Reductions at 28-40 Weeks

    Four Patients Achieved Deepening BMI Reductions at 28-40 Weeks on Therapy with RM-718​ Percent change in BMI Weeks ® 38

  39. Slide 39: Most Common Adverse Events for All Patients (N=11)

    Most Common (≥2 Patients) Adverse Events for All Patients (N=11) All Patients Adverse Events, n (%) (N=11) Injection site reactions 9 (81.8) Nausea 6 (54.5) Vomiting 3 (27.3) Abdominal pain 2 (18.2) Anxiety 2 (18.2) Cough 2 (18.2) Decreased appetite 2 (18.2) Depression 2 (18.2) Fatigue 2 (18.2) Head

  40. Slide 40: Prader-Willi Syndrome

    Prader-Willi Syndrome ® 40

  41. Slide 41: 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

  42. Slide 42: 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 Treatment period (52 weeks) escalated up to 5 mg/day as tolerated for 52 weeks Primary endpoints: safety and tolerability Key secondaries: assess

  43. Slide 43: 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

  44. Slide 44: Setmelanotide Interim Results at Six Months in PWS

    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

  45. Slide 45: 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

  46. Slide 46: Consistent BMI, Fat Mass Reductions 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

  47. Slide 47: BMI Z-Score Reductions and Muscle Mass Gains 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

  48. Slide 48: Improvements in Hyperphagia and Anxiety Scores in Adults

    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

  49. Slide 49: Improvements in Hyperphagia and Anxiety Scores in Pediatric Patients

    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

  50. Slide 50: 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 ® 50 Phase 2 Trial Evalua

  51. Slide 51: Appendix

    Appendix Rhythm

  52. Slide 52: New Diagnostic Algorithm Supports Diagnosis of BBS

    New Diagnostic Algorithm Supports Diagnosis of BBS Expert consensus, evidence-based diagnostic algorithm Supports earlier recognition and diagnosis Aligns around current clinical and genetic evidence ® 52

  53. Slide 53: German Observational Study of Setmelanotide in BBS: MASLD, Kidney Function

    German Investigator-led Observational Study Showed Setmelanotide associated with Improvement in Measures of MASLD, Kidney Function in Patients with BBS 26 patients with BBS completed six months on setmelanotide therapy. 100% >80% of patients (N=26) with of patients exhibited both BBS and metabolic e

  54. Slide 54: Real-world Setmelanotide Data from French Early-access Program

    Positive Real-world Setmelanotide Data Reported from French Early- access Program in Adult Patients with Acquired Hypothalamic Obesity -5.6% -12.8% -21.3% N=8* Mean BMI reduction Mean BMI reduction Mean BMI reduction patients ◼ Month 1 ◼ Month 3 ◼ Month 6 19.3 years #1 #2 #3 #4 #5 #6 #7 #8 Mean age

  55. Slide 55: Real-world Case Reports Suggest Setmelanotide May Help Congenital HO

    Real-world Case Reports from French Early-access Program Suggest Setmelanotide may be Effective Treatment for Congenital HO Case reports presented at 62nd annual meeting of the European Society for Paediatric Endocrinology (EPSE) Adapted from ‘3-Month real-world setmelanotide hunger and weight outco

  56. Slide 56: Rapid and Significant Hunger Reduction in Patients with HO Aged ≥12

    Rapid and Statistically Significant Hunger Reduction in Patients with HO Aged ≥12 Years Reduction in Most Hunger Score* Over Time 0.0 52-Week Most Hunger Score* Mean change in maximal daily hunger score (95% CI) ◼ Setmelanotide ◼ Placebo Reduction Change in maximal daily hunger n= 57 24 0.0 -0.5 sco

  57. Slide 57: Significant BMI Reductions in Adults and Children in Phase 3

    Significant Reductions in BMI Observed in both Adults and Children in Phase 3 Trial Evaluating Setmelanotide in Acquired HO ≥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

  58. Slide 58: Rapid and Significant BMI Percent Reduction Starting at Week 4

    Rapid and Significant BMI Percent A Higher Proportion Achieved Percent Reduction Starting at Week 4 BMI Reductions for All BMI Thresholds ◼ Setmelanotide ◼ Placebo ◼ Setmelanotide ◼ Placebo 100 10 n=81 n=39 Percent of participants achieving BMI percent 2.6 2.8 90 1.9 2.0 2.0 Mean BMI percent change

  59. Slide 59: 25.5% Mean BMI Reduction at One Year in Long-term Extension

    Hypothalamic Obesity: Patients Achieved 25.5% Mean BMI Reduction at One Year of Setmelanotide Therapy in Long-term Ext. Trial Patient who discontinued Patients on treatment at Month 12 Patient lost to follow-up (n=1) treatment because of an AE (n=1) (n=12) 0 5 Reinitiated 5 Dose Off treatment Dose O

  60. Slide 60: Body Composition: Greater Decreases in Fat Mass vs. Lean Mass

    Body Composition Data Show Greater Decreases in Total Fat Mass vs. Lean Muscle Mass Patient number 1 2 3 4 5 6 7 8 9 10 11 12 Age at baseline 6 9 9 10 11 12 13 14 15 15 16 24 Percent change in BMI from baseline to -35.8 -20.5 -39.1 -23.9 -7 -8.7 -21.6 -29.2 -14.6 -36.6 -42.4 -27.1 Month 12 40 17.5 1

  61. Slide 61: All Patients Achieved a Decrease in Obesity Severity at One Year

    All Patients Achieved a Decrease in Obesity Severity at One Year Three of 11 pediatric patients achieved normal weight at one year based on NIH, WHO weight classifications Adults WHO Classification BMI, kg/m2 Pediatric patients (n=11)* BMI percentile6 (n=1) (NIH5) 190 ≥50 50 166 157 158 Obesity clas

  62. Slide 62: Consistent Response to Setmelanotide Across Majority of Patients

    Consistent Response to Setmelanotide Therapy Observed across Majority of Patients in Phase 3 Trial in Acquired HO 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

  63. Slide 63: Individual Percentage Change in BMI from Baseline to Week 14

    Individual Percentage Change in BMI from Baseline to Week 14 10 6.5 5.2 5 Percentage Change in BMI,% 2.1 1.5 1.8 1.0 1.3 0.4 0 -0.1 * -1.7 -1.4 -3.2 -3.0 -3.5 -5 -4.2 -4.2 -6.9 -8.0 -7.8 -10 -9.3 -8.9 -9.0 -9.0 -9.6 -13.7 * -15 -14.8 -14.5 -16.4 -20 Placebo BIVA 200mg BIVA 400mg BIVA 600mg (n=7) (n=

  64. Slide 64: Patients Achieved BMI Reductions of at least 5%, 10% at Week 14

    Patients Achieved BMI Reductions of at least 5%, 10% at Week 14 100 Percentage of patients achieving BMI% 90 2 80 71.4% 1 75.0% 70 reduction cut point, % 60 50 40 37.5% 30 20 16.7% 14.3% 10 0.0% 0.0% 0.0% 0 Placebo 200mg BIVA 400mg BIVA 600mg BIVA (N=7) (N=6) (N=7) (N=8) Achieved a >=5% Reduction Ac

  65. Slide 65: Bivamelagon Achieved Meaningful Reductions in Most Hunger Scores

    Bivamelagon Achieved Meaningful Reductions in ‘Most’ Hunger Scores at Week 14 Bivamelagon QD Placebo QD (n=7) Change in most hunger score 200mg (n=6) 400mg (n=6*) 600mg (n=8) 0.0 -1.0 -0.8 -2.0 -2.1 -3.0 -2.8 -2.8 Weekly average of daily scores on a 10-point scale with 10 being ‘most’ hungry. *One p

  66. Slide 66: Thank you

    hank you Rhythm

Rhythm Pharmaceuticals — Investor Presentation (September 2026) on 6ix