Rhythm Pharmaceuticals, Inc. · NASDAQ:RYTM
Rhythm Pharmaceuticals — Investor Presentation (January 2026)
61 slides from Rhythm Pharmaceuticals's investor presentation, Jan 9, 2026
Slide 1: Rhythm Pharmaceuticals Corporate Presentation January 2026
© Rhythm® Pharmaceuticals, Inc. All rights reserved. ® Rhythm Pharmaceuticals Corporate Presentation January 2026 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: Well Positioned to Deliver Long-term, Sustained Growth
® 3 Well Positioned to Deliver Long-term, Sustained Growth As of September 30, 2025, cash, cash equivalents and short-term investments were $416.1 million; sufficient to fund planned operations for at least 24 months Global MC4R Franchise Acquired hypothalamic obesity represents significant, near-te
Slide 4: Continued Growth in IMCIVREE Global Sales
® 4 Continued Growth in IMCIVREE Global Sales ~10% increase in number of patients globally on reimbursed therapy 11% Q4 2025 preliminary unaudited net revenues from global sales of IMCIVREE® (setmelanotide) QoQ increase from Q3 2025** 68% of Q4 2025 revenue from U.S. 69% of FY 2025 revenue from U.S.
Slide 5: MC4R Pathway Biology is Clear
® 5 MC4R Pathway Biology is Clear Adipose tissue Leptin Blood-brain barrier MC4R neuron POMC neuron AgRP neuron AgRP LEPR Upstream Downstream Hypothalamus PCSK1 POMC LEPR MC4R Downstream MC4R activity Low Normal α-MSH β-MSH α-MSH β-MSH AgRP, agouti-related peptide; LEPR, leptin receptor; MC4R, melan
Slide 6: Hyperphagia and Early-onset Obesity Have a Significant Impact on Patients and their Families
® 6 Hyperphagia and Early-onset Obesity Have a Significant Impact on Patients and their Families “I was hungry all day long. I even started sneaking food in the middle of the night because my mind was constantly on my hunger.” “Prior to IMCIVREE, I didn’t realize how much of my mental energy was con
Slide 7: Expanding Pipeline in Rare Neuroendocrine Diseases
® 7 Expanding Pipeline in Rare Neuroendocrine Diseases Regulatory ApprovalPhase 3Phase 1/2Pre-clinicalPatient Population Bardet-Biedl syndrome or biallelic POMC, PCSK1 or LEPR deficiency Acquired hypothalamic obesity Congenital hypothalamic obesity Setmelanotide daily sc injection^ Prader-Willi synd
Slide 8: Significant Market Opportunity for MC4R Agonists
® 8 *Estimated prevalence of U.S. patients based on company estimates; does not include ex-U.S. prevalence estimates. Estimated U.S. patients based on population with early-onset, severe obesity who may benefit from setmelanotide based on sequencing results that factor in variant classifcations, as
Slide 9: Multiple Anticipated Milestones
® 9 Multiple Anticipated Milestones H1 2026 Disclose six-month results from exploratory Ph2 Prader-Willi trial evaluating setmelanotide Mar. 20, 2026 PDUFA goal date for setmelanotide in conditions associated with acquired hypothalamic obesity H1 2026 Complete enrollment in Ph3 congenital hypothalam
Slide 10: IMCIVREE Global Commercial Execution
® 10 IMCIVREE Global Commercial Execution
Slide 11: First and Only FDA- and EMA-approved Therapy that Targets Early-onset, Severe Obesity
® 11 First and Only FDA- and EMA-approved Therapy that Targets Early- onset, Severe Obesity and Hyperphagia Associated with BBS IMCIVREE is a melanocortin 4 (MC4) receptor agonist indicated for chronic weight management in patients with monogenic or syndromic obesity due to: • Bardet-Biedl syndrome
Slide 12: IMCIVREE available in >25 countries outside the United States
® 12 IMCIVREE available in >25 countries outside the United States Early-access acquired HO programs in France and Italy Ongoing BBS, POMC/LEPR sales Named patient sales Continued execution
Slide 13: Steady Growth in Net Product Revenues since BBS Launch
® 13 FDA approved IMCIVREE for BBS in June 2022 Steady Growth in Net Product Revenues since BBS Launch Global net sales in $M $- $10.00 $20.00 $30.00 $40.00 $50.00 $60.00 2Q 22 3Q 22 4Q 22 1Q 23 2Q 23 3Q 23 4Q 23 1Q 24 2Q 24 3Q 24 4Q 24 1Q 25 2Q 25 3Q 25 4Q 25 US Ex US $4.3M $8.8M $26.0M$24.2M $19.2
Slide 14: Rhythm is Ready for a Successful U.S. Launch in Hypothalamic Obesity
® 14 Rhythm is Ready for a Successful U.S. Launch in Hypothalamic Obesity Significant unmet need Setmelanotide’s demonstrated efficacy Transformative opportunity ~10,000 estimated U.S. prevalence1 1. U.S. estimates based on reported incidence of hypothalamic obesity following craniopharyngioma and l
Slide 15: Hypothalamic Obesity: A Rare, Acquired Form of Obesity
® 15 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 causes reduced energy, hyperphagia and rapid-onset, severe obesity No approved treatments availa
Slide 16: Claims Analysis to Inform Physician Targeting
® 16 Claims Analysis to Inform Physician Targeting Patients with…. ~5,000 Endos potentially caring for a patient with acquired HO ~2,400 Top target physicians Hypothalamic dysfunction Obesity Endo visit within 18 months Tumor + treatment
Slide 17: Field Teams Profiling Physicians and Patients Under Their Care in Advance of Launch
® 17 Field Teams Profiling Physicians and Patients Under Their Care in Advance of Launch Field teams prioritize top tier physicians IDed through claims analysis Ongoing efforts profiling physicians >2,000 potential patients* Suspected to have…. or… diagnosed with acquired hypothalamic obesity *Patie
Slide 18: Hypothalamic Obesity Acquired and Congenital
® 18 Hypothalamic Obesity Acquired and Congenital
Slide 19: Severe, Life-long Burden for Patients with Acquired HO
® 19 Severe, Life-long Burden for Patients with Acquired HO Frequent visits with multiple specialists, a complex regimen of medications, and hospitalization 89% were receiving ≥3 therapies for neuroendocrine dysfunction 22.1 average number of unique medications over 2 years 5.5 average active prescr
Slide 20: HO: Aggressive, Rapid Weight Gain follows Therapy for CP
® 20 HO: Aggressive, Rapid Weight Gain follows Therapy for CP Setmelanotide therapyGLP1 therapy Patient Case Study: Setmelanotide therapy achieved rapid, significant weight loss Patient case of M. Jennifer Abuzzahab, MD, Pediatric Endocrinologist, at Children's Minnesota
Slide 21: TRANSCEND Trial: Largest and Longest Placebo-controlled Trial in Acquired Hypothalamic Obesity
® 21 Phase 3 TRANSCEND Trial: Largest and Longest Placebo-controlled Trial in Acquired Hypothalamic Obesity Setmelanotide QD Double-blind, placebo-control Placebo QD Up to 8 weeks 52 weeks Dose titration Open-label extension patients treated with setmelanotide: placebo 120 Primary analysis cohort +1
Slide 22: Statistically Significant Reduction in BMI in Phase 3 Acquired HO Trial
® 22 Setmelanotide Achieved Statistically Significant and Highly Clinically Meaningful Reduction in BMI in Phase 3 Acquired HO Trial Primary analysis cohort (N=120) -19.8% Placebo-adjusted difference in BMI reduction from baseline (P<0.0001) -16.5% BMI change from baseline in Setmelanotide arm (n=81
Slide 23: Mean BMI Reduction Consistent Across Stratified Age Groups
® 23 -25.00% -20.00% -15.00% -10.00% -5.00% 0.00% 5.00% 10.00% Mean BMI Reduction Consistent Across Stratified Age Groups in Phase 3 Trial Evaluating Setmelanotide in Acquired HO < 12 Yrs -19.5% p <0.0001 (n=31: 20 setmelanotide, 11 placebo) 12 – < 18 Yrs -21.0% p <0.0001 (n=40: 28 setmelanotide, 12
Slide 24: Significant BMI Reductions with Prior Use or Concomitant Use of GLP-1s
® 24 Significant BMI Reductions Observed in Patients with Prior Use or Concomitant Use of GLP-1s -24.7% Placebo-adjusted difference in BMI reduction from baseline Prior use of GLP-1 (n=16) Concomitant GLP-1 (n=15) -27.1% Placebo-adjusted difference in BMI reduction from baseline
Slide 25: Congenital HO Represents Additional Opportunity with Significant Unmet Need
® 25 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 hyperphagia and difficulty managing their weight The weight gain and appetite changes accompanying HO ar
Slide 26: 34-week Substudy in Congenital Hypothalamic Obesity Added to Pivotal Ph3 HO Study
® 26 Independent substudy leverages existing Ph3 trial infrastructure; Enrollment completion expected in H2 2025 34-week Substudy in Congenital Hypothalamic Obesity Added to Pivotal, Ph3 HO Study ~90% power to detect a treatment difference (treatment - placebo) of -12% in percent change of BMI from
Slide 27: SIGNAL Trial: Phase 2 Trial Evaluating Bivamelagon in Hypothalamic Obesity
® 27 ≥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
Slide 28: Overall Baseline Demographics
® 28 Overall Baseline Demographics N=28 46.4% Female 25.4yo Mean Age (13 of 28 <18yo) 38.7 kg/m2 Mean BMI 82.1% Patients with craniopharyngioma 7 years Mean time from hypothalamic injury to trial enrollment Overall bivamelagon population
Slide 29: Bivamelagon Achieved Statistically Significant BMI Reductions at All Doses
® 29 Bivamelagon Achieved Statistically Significant BMI Reductions at All Doses 200 mg -2.68% Mean BMI reduction from baseline (n=6) p-value = 0.0180 400 mg -7.69% Mean BMI reduction from baseline (n=7) p-value = 0.0002 600 mg -9.31% Mean BMI reduction from baseline (n=8) p-value = 0.0004 Placebo +2
Slide 30: Bivamelagon Achieved BMI Reductions Consistent with Setmelanotide
® 30 Bivamelagon Achieved BMI Reductions Consistent with Setmelanotide Week 14 * LOCF (LOCF not performed for Wk12 , patients not included in those means ) Bivamelagon M ea n pe rc en t B M I r ed uc tio n, % -7.7 -9.3 -8.8 -10.1 -15.0 -10.0 -5.0 0.0 5.0 n=7 400 mg n=8 600 mg n=6** 400 mg n=7** 600
Slide 31: AEs consistent with MC4R Mechanism
® 31 AEs consistent with MC4R Mechanism, Setmelanotide Trials in Acquired Hypothalamic Obesity Placebo (N=7) BIVA 600mg (N=8) BIVA 400mg (N=7) BIVA 200mg (N=6)n (%) 6 (86)8 (100)7 (100)6 (100)Any AEs 1 (14)01 (14)0 (0)Serious AEs 3 (43)8 (100)7 (100)6 (100)Treatment-Related AEs 001 (14)0 Treatment-R
Slide 32: Prader-Willi Syndrome
® 32 Prader-Willi Syndrome
Slide 33: Revisiting Prader-Willi Syndrome
® 33 Revisiting Prader-Willi Syndrome * Driscoll DJ, Miller JL, Cassidy SB. Prader-Willi Syndrome. In: Adam MP, Bick S, Mirzaa GM, et al, eds. GeneReviews®. 1998:1-41. Updated December 5, 2024. Accessed December 10, 2025. https://www.ncbi.nlm.nih.gov/books/NBK1330/ PWS is a complex, multi-system dis
Slide 34: Exploratory Phase 2, Open-label Trial of Setmelanotide in PWS
® 34 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 Key secondaries: assessments on BMI, hyperphagia, body composition and pharmacokinetics Exploratory Phase 2,
Slide 35: Baseline Demographics
® 35 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 36: Setmelanotide Achieved BMI Reductions in Patients with PWS After 3 and 6 Months
® 36 -4.8 -3.8 -3.7 -2.8 -2.7 -1.3 2 2.4 -5.9 -5.6 -2.6 0.5 4.2 -8 -6 -4 -2 0 2 4 6 Pt 8 Pt 7 Pt 3 Pt 2 Pt 6 Pt 5 Pt 4 Pt 1 Mo3 Mo 6 Setmelanotide Achieved BMI Reductions from Baseline in Patients with PWS After 3 and 6 Months of Treatment Age/Sex/BMI 12/F/32.6 23/M/37.4 23/F/42.2 18/F/44.6 23/M/45.
Slide 37: HQ-CT1 Scores Showed Meaningful Hyperphagia Reductions
® 37 HQ-CT1 Scores Showed Meaningful Hyperphagia Reductions from Baseline Observed in 6 of 7 Evaluable Patients at Month 3 14 6 10 0 7 18 24 20 1 4 0 0 4 22 10 11 0 5 10 15 20 25 30 Pt 8 Pt 7 Pt 3 Pt 2 Pt 6 Pt 5 Pt 4 Pt 1 Baseline Month 3 H Q -C T Sc or e 1. The Hyperphagia Questionnaire for Clinica
Slide 38: Positive Body Composition Changes from Baseline to Month 6
® 38 Positive Body Composition Changes from Baseline to Month 6 Note: There are no DEXA data for Patient 1 (exceeded table’s weight limits) -7.9 -7.2 -10.1 3.2 -6.3 -0.1 -1 -0.2 -12 -10 -8 -6 -4 -2 0 2 4 Pt 3 Pt 2 Pt 6 Pt 5 Fat Mass Lean Mass % C ha ng e fr om B as el in e
Slide 39: EMANATE and DAYBREAK Genetically-defined MC4R Pathway Diseases
® 39 EMANATE and DAYBREAK Genetically-defined MC4R Pathway Diseases
Slide 40: EMANATE and DAYBREAK Studies to Drive Significant Expansion of Addressable Market
® 40 Phase 3 EMANATE Trial€ EMANATE and DAYBREAK Studies to Drive Significant Expansion of Setmelanotide’s Potential Addressable Market *† EsƟmated U.S. paƟents based on populaƟon* with early-onset, severe obesity who may benefit from setmelanotide based on sequencing results, current estimated resp
Slide 41: Phase 3 EMANATE Trial Comprised of Four Independent Sub-studies
® 41 Each sub-study: Patients randomized 1:1 Phase 3 EMANATE Trial Comprised of Four Independent Sub-studies ACMG Classification Enrolled patients Genetic substudy • Pathogenic • Likely pathogenic • VUS*-Suspected pathogenic n=79 POMC/ PCSK1* • Pathogenic • Likely pathogenic • VUS-Suspected pathogen
Slide 42: DAYBREAK 2-Stage Design
® 42 DAYBREAK 2-Stage Design: 16-Week Run-in Followed by 24-week Randomized Withdrawal and Double-blind, Placebo-controlled ≥12 years starting dose 2 mg 6 to <12 years starting dose 1 mg 6 to <12 years dose titration to 2 mg Open-label dose titration 2 weeks Screening 2-8 weeks 14 weeks Open-label t
Slide 43: Data Highlights from Stage 2 of DAYBREAK Phase 2 Trial
® 43 84% or 27 of 32 patients on setmelanotide Data Highlights from Stage 2 of DAYBREAK Phase 2 Trial * Analyses were limited by the small number of PBO-treated pts -12.4% Mean BMI change from baseline (SD: 8.0%; range 1.2%-35.0%) n=32 patients on continuous setmelanotide therapy* VS. 29% or 5 of 17
Slide 44: Variable Responses Observed in DAYBREAK Stage 2 in Different Genetic Cohorts
® 44 *One adult and one pediatric SEMA3G patient dropped out of S2 prior to having any data and are not shown Several genetically defined subgroups may merit further study with next-generation MC4R agonists Variable Responses Observed in DAYBREAK Stage 2 in Different Genetic Cohorts Early bridging t
Slide 45: Well Capitalized: Cash Sufficient to Fund Planned Operations for at least 24 Months
® 45 Well Capitalized: Cash Sufficient to Fund Planned Operations for at least 24 Months $416.1M Cash, cash equivalents and short-term investments as of September 30, 2025 Guidance RYTM expects cash to be sufficient to fund planned operations for at least 24 months 66.3 Million Weighted average comm
Slide 46: Rhythm Leadership – Strong Team with Broad Biopharma Experience
® 46 Alastair Garfield, PhD Chief Scientific Officer Joe Shulman Chief Technology Officer Yann Mazabraud Executive Vice President, Head of International Jennifer Lee Executive Vice President, Head of North America Hunter Smith Chief Financial Officer David Meeker, MD Chair, President and Chief Execu
Slide 47: Appendix
Appendix Rhython 47
Slide 48: German Investigator-led Observational Study in Bardet-Biedl Syndrome
® 48 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. Adapted from Hühne, T., et al. (2025). Impact of the melanocortin-4 recepto
Slide 49: Real-world Data from French Early-access Program in Adult Acquired HO
® 49 Positive Real-world Setmelanotide Data Reported from French Early- access Program in Adult Patients with Acquired Hypothalamic Obesity *50% male; all aged ≥18 years, with a previous resection of craniopharyngioma (n=7) or of Rathke cleft cyst (n=1); Adapted from “3-Month Real-World Setmelanotid
Slide 50: Real-world Case Reports Suggest Setmelanotide may be Effective for Congenital HO
® 50 Case reports presented at 62nd annual meeting of the European Society for Paediatric Endocrinology (EPSE) Real-world Case Reports from French Early-access Program Suggest Setmelanotide may be Effective Treatment for Congenital HO Adapted from ‘3-Month real-world setmelanotide hunger and weight
Slide 51: Rapid and Statistically Significant Hunger Reduction in Patients with HO
® 51 2457n= *Weekly average of daily scores. participants ≥12 years of age who were able to self-report were administered the questionnaire. Participants were asked to rate their most hunger on an 11-point numerical rating scale from 0 to 10, where 0 = not hungry at all and 10 = hungriest possible v
Slide 52: Significant Reductions in BMI in both Adults and Children
® 52 -40 -30 -20 -10 0 10 20 % C ha ng e fr om B as el in e -16.3% +3.9% -40 -30 -20 -10 0 10 Significant Reductions in BMI Observed in both Adults and Children in Phase 3 Trial Evaluating Setmelanotide in Acquired HO ≥18 Years Old (n=49) (P<0.0001) Setmelanotide Placebo % C ha ng e fr om B as el in
Slide 53: Rapid and Significant BMI Percent Reduction Starting at Week 4
® 53 Rapid and Significant BMI Percent Reduction Starting at Week 4 M ea n BM I p er ce nt c ha ng e (9 5% C I) A Higher Proportion Achieved Percent BMI Reductions for All BMI Thresholds -3.7 -10.6 -15.5 -17.5 -18.3 -18.7 -19.6 -18.3 0.2 0.9 1.9 2.0 2.0 2.6 2.8 3.5 -25 -20 -15 -10 -5 0 5 10 Weeks EO
Slide 54: 25.5% Mean BMI Reduction at One Year in Long-term Extension Trial
® 54 Hypothalamic Obesity: Patients Achieved 25.5% Mean BMI Reduction at One Year of Setmelanotide Therapy in Long-term Ext. Trial -21.1 0.8 -10.8 -25 -20 -15 -10 -5 0 5 0 2 4 6 8 10 12 14 16 18 20 BM I c ha ng e fr om b as el in e, % Off treatment Reinitiated treatment -29.2 -8.7 -14.6 -20.5 -21.6
Slide 55: Body Composition Data Show Greater Decreases in Total Fat Mass vs. Lean Muscle Mass
® 55 Body Composition Data Show Greater Decreases in Total Fat Mass vs. Lean Muscle Mass 121110987654321Patient number 241615151413121110996Age at baseline -27.1-42.4-36.6-14.6-29.2-21.6-8.7-7-23.9-39.1-20.5-35.8 Percent change in BMI from baseline to Month 12 -5 7. 8 -2 3. 7 -3 6. 5 -1 2. 2 -5 .0 -
Slide 56: All Patients Achieved a Decrease in Obesity Severity at One Year
® 56 Three of 11 pediatric patients achieved normal weight at one year based on NIH, WHO weight classifications All Patients Achieved a Decrease in Obesity Severity at One Year *Pediatric paƟents reported as %BMI95. †Or BMI ≥40 kg/m2 (whichever is lower). ‡Or BMI ≥35 to <40 kg/m2 (whichever is lower
Slide 57: Consistent Response to Setmelanotide Therapy in Phase 3 Trial
® 57 0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 5% 10% 15% 20% Pr op or tio n of p at ie nt s Consistent Response to Setmelanotide Therapy Observed across Majority of Patients in Phase 3 Trial in Acquired HO 5% 3% 51% 0% 43% Setmelanotide Placebo 10% 80% 63% P<0.0001 P<0.0001 P<0.0001 P<0.0001 Observed
Slide 58: Individual Percentage Change in BMI from Baseline to Week 14
® 58 Individual Percentage Change in BMI from Baseline to Week 14 *LOCF (BIVA 400mg participant discontinued Tx Week 1, BIVA 600mg participant Week 10). BIVA, Bivamelagon. BIVA 200mg (n=6) BIVA 400mg (n=7) BIVA 600mg (n=8) Placebo (n=7) -1.7 -0.1 1.5 1.8 2.1 5.2 6.5 -8.0 -4.2 -3.2 -3.0 1.0 1.3 -13.7
Slide 59: Patients Achieved BMI Reductions of at least 5%, 10% at Week 14
® 59 Patients Achieved BMI Reductions of at least 5%, 10% at Week 14 0.0% 16.7% 71.4% 75.0% 0.0% 0.0% 14.3% 37.5% 0 10 20 30 40 50 60 70 80 90 100 Placebo (N=7) 200mg BIVA (N=6) 400mg BIVA (N=7) 600mg BIVA (N=8) Achieved a >=5% Reduction Achieved a >=10% Reduction 1 1. P=0.0105 2. P= 0.0056 vs place
Slide 60: Bivamelagon Achieved Meaningful Reductions in Most Hunger Scores at Week 14
® 60 Bivamelagon Achieved Meaningful Reductions in ‘Most’ Hunger Scores at Week 14 Ch an ge in m os t h un ge r s co re Bivamelagon QD Placebo QD (n=7) 600mg (n=8)400mg (n=6*)200mg (n=6) -0.8 -2.1 -2.8 -2.8-3.0 -2.0 -1.0 0.0 Weekly average of daily scores on a 10-point scale with 10 being ‘most’ hun
Slide 61: Thank you
Thank you Rhython 61
Rhythm Pharmaceuticals — Investor Presentation (January 2026) on 6ix