Slide 1: Second Quarter 2025 Financial Results and Business Update
Rhythm Pharmaceuticals Second Quarter 2025 Financial Results and Business Update August 5, 2025 ® © Rhythm® Pharmaceuticals, Inc. All rights reserved.
Slide 2: On Today's Call
On Today’s Call • David Connolly, Executive Director of Investor Relations and Corporate Communications • David Meeker, MD, Chair, President and Chief Executive Officer • Jennifer Lee, Executive Vice President, Head of North America • Yann Mazabraud, Executive Vice President, Head of International •
Slide 3: 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 that do not relate to matters of historical fact should be considered forward-looking stat
Slide 4: David Meeker, MD
David Meeker, MD Chair, President and CEO ® 4
Slide 5: Long-term Growth Strategy: Advancing Multiple MC4R Agonists
Long-term Growth Strategy: Advancing Multiple MC4R Agonists in Several Disease States with Significant Unmet Need Q2’25 Highlights Continued solid growth in global IMCIVREE® (setmelanotide) sales in Q2 2025 On track to complete U.S. and EU regulatory submissions for setmelanotide in acquired hypotha
Slide 6: 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 Approved for IMCIVREE Acquired hypothalamic obesity Additional potential (setmelanotide) in U.S., EU,+ 5,000 – 10,000 ~29,000** 4,000 – 5,000* estimated U.S. p
Slide 7: Qualitative Interviews following Ph3 Trial in HO
Qualitative Interviews following Ph3 Trial in HO Advance Disease Understanding, Improvements with Setmelanotide Therapy 30 patients, caregivers share experiences with HO, assessments on weight change, fatigue and physical activity But the weight just came on and it came on drastically...He Setmelano
Slide 8: Exit Interview Participants Report Weight Gain, Increased Hunger and Decreased Energy
Exit Interview Participants Report Weight Gain, Increased Hunger and Decreased Energy with Acquired Hyothalamic Obesity CAREGIVERS OF TRIAL PARTICIPAN TS ADULT TRIAL PARTICIPANTS AGED PARTICIPANTS AGED AGED AGED Total ≥ 12 years to < 18 years ≥ 18 years < 12 years ≥ 12 years (n = 30) (n = 4) (n = 10
Slide 9: Setmelanotide Achieved Significant BMI Reduction in Phase 3 Acquired HO Trial
Setmelanotide Achieved Statistically Significant and Highly Clinically Meaningful Reduction in BMI in Phase 3 Acquired HO Trial 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 P
Slide 10: Bivamelagon Achieved Significant BMI Reductions at All Doses in Phase 2
Bivamelagon Achieved Statistically Significant BMI Reductions at All Doses in 14-week, Phase 2 Trial 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)
Slide 11: Post-hoc Analysis: 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 -10.0 -
Slide 12: IMPROVE 2025 Draws ~150 Physicians and Researchers
IMPROVE 2025 Draws ~150 Physicians and Researchers from 19 Countries with Focus on Rare MC4R Pathway Diseases ® 12
Slide 13: Multiple Anticipated Milestones
Multiple Anticipated Milestones Complete U.S. and EU regulatory submissions for setmelanotide Q3 2025 in acquired hypothalamic obesity Disclose preliminary results from exploratory Ph2 Prader-Willi trial H2 2025 evaluating setmelanotide Complete enrollment in Part C of Ph1 trial evaluating RM-718 in
Slide 14: Jennifer Lee
Jennifer Lee EVP, Head of North America ® 14
Slide 15: Steady Growth in BBS Commercial Performance Continued in Q2
Steady Growth in BBS Commercial Performance Continued in Q2 Consistent demand Increased breadth Growth in Ongoing efforts to growth fueled by and depth prescriptions prepare for productive patient of prescribers for pediatric launching in finding efforts patients <18 acquired HO Disease Clinical Dec
Slide 16: Consistent Growth in IMCIVREE Prescriber Base for Patients with BBS
Consistent Growth in IMCIVREE Prescriber Base for Patients with BBS 38% increase in cumulative prescribers Q2 ‘24 to Q2 ‘25 9% increase in cumulative prescribers Q1 ‘25 to Q2 ‘25 ® 16
Slide 17: Label Expansion down to 2yo Broadens Physician Engagement
Label Expansion down to 2yo Broadens Physician Engagement Q2’25 IMCIVREE prescriptions by age 2 – 12yo 40% 27% 12 – 18yo 33% >18yo ® 17
Slide 18: Update on Commercial Readiness for Acquired Hypothalamic Obesity
Rhythm Update on Commercial Readiness for Acquired Hypothalamic Obesity Event for investors and analysts Date: Sept. 24, 2025 Time/Location: 8:30 a.m. ET in Boston In-person and webcast; registration details to come. ® 18
Slide 19: Yann Mazabraud
Yann Mazabraud EVP, Head of International ® 19
Slide 20: IMCIVREE available in >20 countries outside the United States
IMCIVREE available in >20 countries outside the United States Drivers of Growth Ongoing BBS, POMC/LEPR sales Early-access HO programs in France and Italy Named patient sales ® 20
Slide 21: IMPROVE: Focus on Peer-to-peer Scientific Exchange
IMPROVE: Focus on Peer-to-peer Scientific Exchange and Sharing Best Practices Workshops Care for patients with rare MC4R pathway diseases 43 poster presentations 3 recognized as IMPROVE 2025 winners Erica van den Akker (The Netherlands) & Martin Wabitsch (Germany) Stefanie Zorn, Germany Early childh
Slide 22: Hunter Smith
Hunter Smith Chief Financial Officer ® 22
Slide 23: Well-capitalized Following Oversubscribed, Upsized Stock Offering
Well-capitalized Following Oversubscribed, Upsized Stock Offering in July Cash on-hand does not include: $291M +$189.2M net proceeds from public offering of common stock cash, cash equivalents and short- that closed July 11, 2025 term investments as of LGC in-license milestone paid in June 30, 2025
Slide 24: Q2 '25: Consistent Growth in Patient Demand Continues
Q2 ’25: Consistent Growth in Patient Demand Continues in U.S. and ex-U.S. $48.5M in net product $3.2M $48.5M $3.0M revenue from global sales; $4.6M 29% sequential growth $37.7M Patients on reimbursed therapy grew by ~12% globally QoQ Ex-U.S. growth driven by increased numbers of BBS Q1 2025 Q1-Q2 SP
Slide 25: 2Q 2025 Financial Snapshot
2Q 2025 Financial Snapshot ($ in millions, except per share Three months ended Three months ended data and shares outstanding) June 30, 2025 June 30, 2024 Product revenue, net $48.5M $29.1M R&D expenses $42.3M $30.2M SG&A expenses $45.9M $36.4M Net Loss attributable to common stockholders $(48.0)M $
Slide 26: Operating Expenses in Q2 '25; Reiterate Full-year Guidance
Operating Expenses in Q2 ‘25; Reiterate Full-year Guidance Q2 ‘25 OpEx 2025 OpEx Guidance unchanged $88.2M $285M to $315M anticipated non-GAAP Operating Q2 2025 OpEx Expenses* for 2025 includes: includes $15.9M SG&A: $135M to 145M in stock-based compensation R&D: $150M to $170M $40M LGC in-license m
Slide 27: Questions
Questions Rhythm