Slides
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© Rhythm® Pharmaceuticals, Inc. All rights reserved. ® February 26, 2026 Rhythm Pharmaceuticals Fourth Quarter and Year End 2025 Financial Results and Business Update
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® 2 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 • Hunter Smith, Chief Financial Officer
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® 3 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-looking statements, including without limitation statements regarding the safety, efficacy, potential benefits of, and clinical design or progress of any of our products or product candidates at any dosage or in any indication, including, setmelanotide, bivamelagon, and RM-718; the potential use of setmelanotide in patients with acquired hypothalamic obesity; our expectations surrounding potential regulatory submissions, progress, or approvals and timing thereof for any of our product candidates, including the March 20, 2026 PDUFA goal date for our sNDA for setmelanotide in acquired hypothalamic obesity; the commercial growth of IMCIVREE; the estimated market size and addressable population for our drug products, including setmelanotide for the treatment of hypothalamic obesity; the future announcement of data from our ongoing clinical trials, including the Japanese cohort of our Phase 3 trial evaluating setmelanotide for patients with acquired hypothalamic obesity, the substudy evaluating setmelanotide for patients with congenital hypothalamic obesity, the Phase 3 EMANATE trial evaluating setmelanotide in genetically caused MC4R pathway diseases; Part C of the Phase 1 trial evaluating RM-718, and the open-label Phase 2 trial evaluating setmelanotide in patients with PWS; the ongoing enrollment in our clinical trials; existing or future collaboration agreements; the Company’s business strategy and plans; our anticipated financial performance and financial position for any period of time, including our estimated Non-GAAP Operating Expenses for the year ending December 31, 2026; and the sufficiency of our cash, cash equivalents and short-term investments to fund our operations for at least 24 months; and the timing of any of the foregoing. Statements using words such as “expect” , “anticipate” , “believe” , “may” , “will” and similar terms are also forward-looking statements. Such statements are subject to numerous risks and uncertainties, including, but not limited to, our ability to enroll patients in clinical trials, the design and outcome of clinical trials, the impact of competition, the ability to achieve or obtain necessary regulatory approvals, risks associated with data analysis and reporting, unfavorable pricing regulations, third-party reimbursement practices or healthcare reform initiatives, risks associated with the laws and regulations governing our international operations and the costs of any related compliance programs, our ability to successfully commercialize setmelanotide, our liquidity and expenses, our ability to retain our key employees and consultants, and to attract, retain and motivate qualified personnel, and general economic conditions, and the other important factors, including those discussed under the caption “Risk Factors” in Rhythm’s Annual Report on Form 10-K for the year ended December 31, 2025 and our other filings with the Securities and Exchange Commission. Except as required by law, we undertake no obligations to make any revisions to the forward-looking statements contained in this press release or to update them to reflect events or circumstances occurring after the date of this press release, whether as a result of new information, future developments or otherwise. Non-GAAP Financial Measures This presentation and the accompanying oral presentation include Non-GAAP Operating Expenses, a supplemental measure of our performance that is not required by, or presented in accordance with, U.S. GAAP and should not be considered as an alternative to operating expenses or any other performance measure derived in accordance with GAAP. We define Non-GAAP Operating Expenses as GAAP operating expenses excluding stock-based compensation and fixed consideration related to in-licensing. We caution investors that amounts presented in accordance with our definition of Non-GAAP Operating Expenses may not be comparable to similar measures disclosed by our competitors because not all companies and analysts calculate this non-GAAP financial measure in the same manner. We have not provided a quantitative reconciliation of forecasted Non-GAAP Operating Expenses to forecasted GAAP operating expenses because we are unable, without making unreasonable efforts, to calculate the reconciling item, stock-based compensation expenses, with confidence. This item, which could materially affect the computation of forward-looking GAAP operating expenses, is inherently uncertain and depends on various factors, some of which are outside of our control. Forward-looking Statements
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® 4 David Meeker, MD Chair, President and CEO
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® 5 Steady growth in global IMCIVREE® (setmelanotide) sales in Q4 2025 primarily driven by Bardet-Biedl syndrome U.S. team in place and ready to launch setmelanotide for acquired HO, pending FDA approval on March 20th Early-access for HO in Europe reinforces confidence in global opportunity Positive update on Bivamelagon open-label extension data in acquired hypothalamic obesity and end-of-Phase 2 meeting with FDA Well Positioned to Deliver Long -term, Sustained Growth Business Highlights
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® 6 ≥18yo BMI ≥30 kg/m2 12-<18 yo >95th percentile Setmelanotide-naive SIGNAL Trial: 14-week, Phase 2 Open -label Trial Evaluating Bivamelagon in Patients with Hypothalamic Obesity Inclusion criteria Screening Long-term Extension (LTE) Trial Placebo 200 mg 200 mg 400 mg 200 mg 400 mg 600 mg Week 15 Week 16 Week 40 Week 52 200 mg 400 mg 600 mg 2 weeks 12 weeks RDZ 1:1:1:1 Open-label Week 0 Week 2 Week 14
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® 7 ENROLLED (n=28) Vast Majority of Patients Transitioned to Open -label Extension and Have Remained on Bivamelagon Therapy DISCONTINUED 1 discontinuation due to SAE in Week 1 26 of 27 eligible participants transitioned to open-label extension (OLE) phase for up to 38 weeks OLE participants retitrated from 200mg to maximum 600mg dose, as tolerated, to preserve blind 26 patients entered OLECOMPLETED (n=27)
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® 8 Placebo Patients Titrated to 600mg Achieved Meaningful Reductions in BMI at Week 28 and Deepening Responses at Week 40 -4.5 -8.5 -5.5 -7.6 -15.9 -9.8 -18 -16 -14 -12 -10 -8 -6 -4 -2 0 Wk14 to 28 Wk14 to 40 Percentage Change in BMI, % PI suspects non- compliance Age/Sex: 12/F 13/M 15/M 19/F 21/M 43/M 66/F -8.2 NOTE: Preliminary data; pending source verification Ph2 Trial of Bivamelagon in hypothalamic obesity: Open-label extension
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® 9 Patients Initially Randomized to 200mg and Titrated to 600mg Achieved Meaningful Reductions in BMI at Weeks 28 and 40 5.9 -18.0 -3.1 -14.5 -8.2 -8.9 -20 -15 -10 -5 0 5 10 Wk0 to Wk14 Wk0 to Wk28 Wk0 to Wk40 Percentage Change in BMI, % Retained dropout PI suspects non- compliance Age/Sex: 12/F 14/M 15/F 21/F 22/M 37/M NOTE: Preliminary data; pending source verification Ph2 Trial of Bivamelagon in hypothalamic obesity: Open-label extension
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® 10 1.3 -12.0 -17.5 -13.6 -10.4 -12.4 -25 -20 -15 -10 -5 0 5 Wk0 to Wk14 Wk0 to Wk28 Wk0 to Wk40 Patients* Titrated from 400mg to 600mg Achieved Deepened, Sustained BMI Reduction at Weeks 28 and 40 Percentage Change in BMI, % PI suspects non- compliance Age/Sex: 12/F 14/F 16/F 20/M 23/F 28/M NOTE: Preliminary data; pending source verification; * One 34-yr-old male patient discontinued after Visit 1 and is not shown -10.8% Mean BMI reduction at week 40 from baseline at Week 0 (n=6) Ph2 Trial of Bivamelagon in hypothalamic obesity: Open-label extension
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® 11 Patients on 600mg Achieved Deepened and Sustained BMI Reduction at Week 40 -18.4 7.5 -4.9 -16.3 -23.2 -29.8 -15.1 -35 -30 -25 -20 -15 -10 -5 0 5 10 Wk0 to Wk14 Wk0 to Wk28 Wk0 to Wk40 Percentage Change in BMI, % PI suspects non- compliance Age/Sex: 13/M 14/M 14/F 14/M 29/M 39/F 64/M 68/F Pt did not consent to OLE -14.3% Mean BMI reduction at week 40 from baseline at Week 0 (n=6) NOTE: Preliminary data; pending source verification Ph2 Trial of Bivamelagon in hypothalamic obesity: Open-label extension
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12 ® Open-label extension data show persistent, deepening BMI reductions at 6- and 9-months Extension safety and tolerability generally consistent with 14- week results End of Phase 2 meeting with FDA completed On track to initiate Phase 3 aHO study by the end of 2026 Bivamelagon Long-term Extension Data Demonstrated Sustained Efficacy
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13 ® Multiple Anticipated Milestones H2 2026 Disclose six-month results from exploratory Ph2 trial evaluating setmelanotide in Prader- Willi syndrome Mar. 20, 2026 PDUFA goal date for setmelanotide in conditions associated with acquired hypothalamic obesity H1 2026 Complete enrollment in Ph3 substudy evaluating setmelanotide in congenital hypothalamic obesity Q1 2026 Complete enrollment in Part C of Ph1/2 trial evaluating RM-718 in acquired hypothalamic obesity Q1 2026 Topline data from Ph3 EMANATE trial evaluating setmelanotide in four genetically- defined, rare MC4R pathway diseases Q1 2026 Topline data from 12-patient Japanese cohort of Ph3 trial evaluating setmelanotide in acquired hypothalamic obesity H2 2026 Initiate pivotal Ph3 trial evaluating oral bivamelagon in acquired hypothalamic obesityYE 2026 Complete enrollment in Part D of Ph1/2 trial evaluating RM-718 in PWS
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® 14 Jennifer Lee EVP , Head of North America
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® 15 Anticipated US Launch of IMCIVREE in Acquired Hypothalamic Obesity Significant unmet need without an approved therapy Estimated US Prevalence of ~10,000 patients1 Team in place and ready to launch PDUFA goal date of March 20, 2026 1. U.S. estimates based on reported incidence of hypothalamic obesity following craniopharyngioma and long-term survival rates, (Zacharia, et al., Neuro-Oncology 14(8):1070–1078, 2012. doi:10.1093/neuonc/nos142; and Muller, et al., Neuro-Oncology 17(7), 1029–1038, 2015 doi:10.1093/neuonc/nov044.);
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® 16 Pituitary Centers Use Multiple Care Models for HO Tumor treatment Endocrinopathy management Treatment of HO Neurosurgery Radiation Neuro-oncology Clinical nutrition/ Supportive care Community Providers (PCP, ABOM)Endocrinology Weight management / Metabolic medicine Endocrinology
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® 17 Ready to Launch Upon FDA Approval ® Establish IMCIVREE as the foundational treatment for aHO Access team engaging with payers Patient services team engaging with patients, families
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® 18 Yann Mazabraud EVP , Head of International
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® 19 >100 employees in 13 countries 64 abstracts at 12 international scientific congresses Eight countries added in 2025 Continued execution IMCIVREE available in >25 countries outside the United States Ongoing BBS, POMC/LEPR sales and Early-access aHO programs in France and Italy
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® 20 Early-onset Obesity Model published in Obesity Facts Journal Obesity Facts. 2025 Nov 14:1-15. doi: 10.1159/000549499
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® 21 Top-line Phase 3 Data expected in March 2026 Preparing to Launch Setmelanotide for Acquired Hypothalamic Obesity in Japan and Europe EMA Authorization expected in H2 2026 5,000 – 8,000 estimated Japanese prevalence1 ~10,000 estimated European prevalence2 1. Rhythm estimates the prevalence of acquired hypothalamic obesity in Japan to be approximately 5,000 to 8,000 based on our review of tumor registries and claims data 2. European estimates limited to the EU4 (Germany, France, Spain, Italy), UK and the Netherlands and prevalence of 0.1-0.3 in 10,000 people
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® 22 Hunter Smith Chief Financial Officer
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® 23 Q4 2025: Continued Growth in IMCIVREE Global Sales 12% QoQ increase from Q3 2025** 68% of Q4 2025 revenue from U.S. 69% of FY 2025 revenue from U.S. $57.3M* Q4 2025 $194.8M FY 2025 * Q4 2025 revenue from vials shipped to U.S. specialty pharmacy in excess of vials dispensed to patients was approximately $1.7M; **Reminder: During Q3 2025, Rhythm recorded a one-time $3.2 million charge following a final agreement with French authorities for reimbursement for IMCIVREE for POMC/LEPR and BBS. ~10% increase in number of patients globally on reimbursed therapy
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® 24 Q3 to Q4 ’25: Consistent Growth in Global Patient Demand Continues -$1.3M $51.3M $2.1M $5.2M $57.3M Q3 2025 Product Revenue Q4 2025 Product Revenue Q3-Q4 inventory effect at U.S. specialty pharmacy Ex-US revenue in Q3 2025 included a one-time $3.2M charge due to French reimbursement pricing agreement for the paid, early-access program initiated in 2022 Revenue growth from product dispensed to US patients * Q4 2025 revenue from vials shipped to U.S. specialty pharmacy in excess of vials dispensed to patients was approximately $1.7M, compared to $3M in Q3 2025; *
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® 25 Q4, Full-year 2025 Financial Snapshot ($ in millions, except per share data and shares outstanding) Three months ended December 31, 2025 Three months ended December 31, 2024 Year ended December 31, 2025 Year ended December 31, 2024 Product revenue, net $57.3M $41.8M $194.8M $130.1M R&D expenses $42.0M $41.2M $167.3M $238.0M SG&A expenses $57.5M $38.1M $194.9M $144.3M Net Loss attributable to common stockholders $(48.8)M $(44.6)M $(201.9)M $(264.6)M Weighted average common shares outstanding 66,876,883 61,596,442 64,984,361 60,995,204 Net Loss per share attributable to common stockholders – basic and diluted $(0.73) ($0.72) $(3.11) ($4.34) Cash, cash equivalents and short-term investments position (period end) $388.9M $320.6M $388.9M $320.6M
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® 26 $295.5M* Non-GAAP1 OpEx $362.3M 2025 GAAP OpEx, which includes $66.8M in stock-based compensation 4Q, Full -year 2025 Financial Highlights * Non-GAAP Operating Expenses is a non-GAAP financial measure. We define Non-GAAP Operating Expenses as GAAP operating expenses excluding stock-based compensation and fixed consideration related to in-licensing. For more information, see slide 3 – Non-GAAP Financial Measures; 1. Non-GAAP OpEx of $295.5 million in 2025 excludes $66.8 million in stock-based compensation; 2. As of Feb. 24, 2026. 68,285,039 Common shares outstanding2 including 729,164 shares of common stock converted from preferred shares
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® 27 2026 OpEx Guidance $385M to $415M anticipated non-GAAP Operating Expenses* for 2026 includes: R&D: $197M to $213M SG&A: $188M to $202M * Non-GAAP Operating Expenses is a non-GAAP financial measure. We define Non-GAAP Operating Expenses as GAAP operating expenses excluding stock-based compensation and fixed consideration related to in-licensing and related milestone payments. For more information, see slide 3 – Non-GAAP Financial Measures
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® 28 Questions