Rhythm Pharmaceuticals, Inc. · NASDAQ:RYTM
Rhythm Pharmaceuticals — Investor Presentation (January 2025)
48 slides from Rhythm Pharmaceuticals's investor presentation, Jan 10, 2025
Slide 1: Rhythm Pharmaceuticals January 2025
© Rhythm® Pharmaceuticals, Inc. All rights reserved. ® January 2025 Rhythm Pharmaceuticals
Slide 2: Forward-looking statements
® 2 This presentation contains certain forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, and that involve risks and uncertainties, including without limitation statements regarding the potential, safety, efficacy, and regulatory and clinical progr
Slide 3: Rhythm's Value Drivers
® 3 Rhythm’s Value Drivers Significant expansion opportunity in hypothalamic obesity (both acquired and congenital) Advancing setmelanotide clinical development in Prader-Willi syndrome and genetically-defined MC4R pathway diseases Continued BBS global commercial execution 1 2 3 Driving life-cycle m
Slide 4: What's New?
® 4 What’s New? Completed enrollment in supplemental Japanese cohort of Ph 3 trial of setmelanotide in acquired hypothalamic obesity Completed enrollment in two substudies in Phase 3 EMANATE trial in genetically-caused MC4R pathway diseases Plans to initiate new Phase 2 trial exploring setmelanotide
Slide 5: Continued Growth in IMCIVREE Global Sales
® 5 Continued Growth in IMCIVREE Global Sales Increase in number of patients on reimbursed therapy +26% Preliminary unaudited net revenues from global sales of IMCIVREE® (setmelanotide) QoQ increase from Q3 2024 74% of 4Q revenues from U.S. 73% of FY ‘24 revenues from U.S. Drivers of QoQ growth even
Slide 6: MC4R Pathway Biology is Clear and Strong
® 6 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 MC4R Pathway Biology is Clear and Strong: Regulates Hunger, Caloric Intake, Energy Expenditure
Slide 7: Hyperphagia and Early-onset Obesity Impact on Patients and Families
® 7 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 8: Clinical Development Programs Designed to Expand Opportunity
® 8 Clinical Development Programs Designed to Expand Opportunity in Hyperphagia and Severe Obesity 600 – 2,500* POMC, PCSK1 and LEPR deficiencies 4,000 - 5,000* Bardet-Biedl syndrome In ongoing Phase 3 trials ~29,000** EMANATE Lead indications 5,000 - 10,000* Hypothalamic obesity Positive signals ob
Slide 9: Well Capitalized: Cash Sufficient into 2026
® 9 Well Capitalized: Cash Sufficient to Fund Planned Operations into 2026 Guidance Cash on hand expected to be sufficient to fund operations into 2026 61.2 Million Common shares outstanding as of Sept. 30, 2024 1Analyst coverage includes all brokerage firms known by the company as of March 2024 to
Slide 10: Multiple Anticipated Milestones
® 10 Multiple Anticipated Milestones Q1 2025 Begin dosing patients in Ph3 congenital hypothalamic obesity substudy evaluating setmelanotide Q1 2025 Complete enrollment in Ph2 trial evaluating bivamelagon (LB54640) in acquired hypothalamic obesity Q1 2025 Begin dosing patients with acquired hypothala
Slide 11: Rhythm Leadership – Strong Team with Broad Biopharma Experience
® 11 David Meeker, MD Chair, President and Chief Executive Officer Hunter Smith Chief Financial Officer Jennifer Lee Executive Vice President, Head of North America Yann Mazabraud Executive Vice President, Head of International Joe Shulman Chief Technology Officer Alastair Garfield, PhD Chief Scient
Slide 12: Expanding Pipeline in Rare Neuroendocrine Diseases
® 12 Patient Population Pre-clinical Phase 1/2 Phase 3 Regulatory Approval Bardet-Biedl syndrome or biallelic POMC, PCSK1 or LEPR deficiency (2 years of age and older)* Setmelanotide daily formulation Acquired hypothalamic obesity Congenital hypothalamic obesity Prader Willi syndrome Bivamelagon Acq
Slide 13: Hypothalamic Obesity
® 13 Hypothalamic Obesity Acquired and Congenital Setmelanotide, bivamelagon and RM-718
Slide 14: Hypothalamic Obesity: A Rare, Acquired Form of Obesity
® 14 Hypothalamic Obesity: A Rare, Acquired Form of Obesity Following Injury to the Hypothalamic Region Craniopharyngioma 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
Slide 15: Hypothalamic Obesity: A Transformative Opportunity for Rhythm
® 15 Hypothalamic Obesity: A Transformative Opportunity for Rhythm *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., Neu
Slide 16: HO: Aggressive, Rapid Weight Gain follows Therapy for CP
® 16 HO: Aggressive, Rapid Weight Gain follows Therapy for CP Setmelanotide GLP1 therapy 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 17: Setmelanotide Achieved Progressive, Deepening BMI Reduction
® 17 Setmelanotide Achieved Progressive, Deepening BMI Reduction at 16 Weeks, 6 and 12 Months in Patients with Hypothalamic Obesity Error bars are the standard deviation. *Includes all patients who received 16 weeks of setmelanotide in the index trial and ≥12 months of treatment in the long-term ext
Slide 18: Sustained and Deepened BMI Reduction at One Year
® 18 -45 -40 -35 -30 -25 -20 -15 -10 -5 0 Setmelanotide Achieved Sustained and Deepened BMI Reduction in Patients with Hypothalamic Obesity at One Year Adapted from data presented during The Obesity Society Annual Meeting (TOS 2023) on October 17, 2023, in Dallas. BMI % change from index trial basel
Slide 19: Body Composition Data Show Greater Decreases in Fat Mass
® 19 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 Month 12 -35.8 -20.5 -39.1 -23.9 -7 -8.7 -21.6 -29.2 -14.6 -36.6 -42.4 -27.1 -57.
Slide 20: All Patients Achieved a Decrease in Obesity Severity at One Year
® 20 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 patients reported as %BMI95. †Or BMI ≥40 kg/m2 (whichever is lower). ‡Or BMI ≥35 to <40 kg/m2 (whichever is lowe
Slide 21: Positive Real-world Data from French Early-access Program
® 21 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 Setmelanotide
Slide 22: Positive Real-world Data from French Early-access Program
® 22 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 Setmelanotide
Slide 23: Phase 3 Hypothalamic Obesity Trial: Enrollment Complete
® 23 Phase 3 Hypothalamic Obesity Trial: Enrollment Complete, Top-line Data Expected in H1 2025 Setmelanotide QD (n=80) Double-blind, placebo-control Placebo QD (n=40) Up to 8 weeks 52 weeks Dose titration Primary endpoint: Mean % change in BMI from baseline to after approximately 52 weeks on a ther
Slide 24: Congenital HO Represents Additional Opportunity
® 24 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 are often unresponsive to existing therapies for obesity No approved therapies
Slide 25: Real-world Case Reports Suggest Effectiveness in Congenital HO
® 25 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 26: 34-week Substudy in Congenital Hypothalamic Obesity
® 26 Independent substudy leverages existing Ph3 trial infrastructure; Enrollment expected to begin in Q1 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 ba
Slide 27: Advancing Next-generation MC4R Agonists in Acquired HO
® 27 Bivamelagon (LB54640) • Global rights acquired from LG Chem in January 2024 • Daily oral, highly selective MC4R agonist • Compelling Phase 1 data in healthy, obese volunteers • No hyperpigmentation observed • IP protection out to 2045, assuming patent term extension RM-718 • Developed in-house
Slide 28: Bivamelagon Showed Dose-response Body Weight Loss
® 28 Bivamelagon Showed Dose-response Body Weight Loss Healthy Volunteers with General Obesity As presented by LG Chem at The Obesity Society’s ObesityWeek® 2022. Favorable safety profile • No serious adverse events • No skin pigmentation, adrenal, or genitourinary adverse events observed • Mild to
Slide 29: SIGNAL Trial: Phase 2 Trial Evaluating Bivamelagon
® 29 Enrollment to be complete in Q1 2025 SIGNAL Trial: 14-week, Phase 2 Open-label Trial Evaluating Bivamelagon in Patients with Hypothalamic Obesity Placebo Low dose Middle dose High dose Open-label extension N=28 patients with hypothalamic obesity Randomized 1:1:1:1 Inclusion criteria • ≥18yo BMI
Slide 30: Three-part Phase 1 Study Evaluating RM-718
® 30 Part C dosing of patients with acquired HO expected to begin in Q1 2025 Three-part Phase 1 Study Evaluating RM-718 QW Ongoing Part A: SAD RM-718 QW Part B: MAD RM-718 QW 4 doses Part C: MAD Hypothalamic Obesity RM-718 QW 16 weeks Screening: 28 days 9 cohorts X 6 subjects >18yo n=54 Randomized 2
Slide 31: EMANATE and DAYBREAK Genetically-defined MC4R Pathway Diseases
® 31 EMANATE and DAYBREAK Genetically-defined MC4R Pathway Diseases
Slide 32: EMANATE and DAYBREAK to Expand Addressable Market
® 32 Phase 3 EMANATE Trial€ EMANATE and DAYBREAK Studies to Drive Significant Expansion of Setmelanotide’s Potential Addressable Market *† Estimated U.S. patients based on population* with early-onset, severe obesity who may benefit from setmelanotide based on sequencing results, current estimated r
Slide 33: Phase 3 EMANATE Trial: Four Independent Sub-studies
® 33 Each sub-study: Patients randomized 1:1 Phase 3 EMANATE Trial Comprised of Four Independent Sub-studies Genetic substudy Enrolled patients ACMG Classification POMC/ PCSK1* n=79 • Pathogenic • Likely pathogenic • VUS*-Suspected pathogenic LEPR* n=23 • Pathogenic • Likely pathogenic • VUS-Suspect
Slide 34: DAYBREAK 2-Stage Design
® 34 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 35: DAYBREAK Baseline Demographics
® 35 DAYBREAK Baseline Demographics N=49 n Mean (SD) Range % of S1 starters BMI, kg/m2 Adult Baseline 25 46.1 (7.2) 40.4 - 69.9 23% Adult Stage 2 start 25 42.6 (7.0) 36.2 - 66.3 - BMI-Z (CDC) Pediatric Baseline 24 2.5 (0.3) 1.83 - 2.97 44% Pediatric Stage 2 start 24 2.25 (0.4) 1.48 - 2.92 - Sex, N=4
Slide 36: Data Highlights from Stage 2 of DAYBREAK
® 36 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 37: Variable Responses Observed in DAYBREAK Stage 2
® 37 *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 38: Prader-Willi Syndrome
Prader-Willi Syndrome 38 Phutha
Slide 39: Revisiting Prader-Willi Syndrome
® 39 PWS is a complex, multi-system disorder Constant sense of hunger usually begins at 2yo; if not managed by stringent food restrictions and environmental controls, often results in life-threatening obesity Currently no approved therapies that effectively reduce the extreme hyperphagia or address
Slide 40: Exploratory Phase 2 Trial of Setmelanotide in PWS
® 40 Single, US-site Up to 20 patients with PWS and obesity aged 6 to 65 years old Daily dose of setmelanotide escalated to 5 mg/day as tolerated for 26 weeks Primary endpoints: safety and tolerability Key secondaries: assessments on weight, hyperphagia, behavior and pharmacokinetics Initiating Expl
Slide 41: IMCIVREE Global Commercial Execution
® 41 IMCIVREE Global Commercial Execution
Slide 42: First and Only FDA- and EMA-approved Therapy for BBS
® 42 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 43: Steady Growth in Net Product Revenues since BBS Launch
® 43 FDA approved IMCIVREE for BBS in June 2022 Steady Growth in Net Product Revenues since BBS Launch Global net sales in $M $- $5,000 $10,000 $15,000 $20,000 $25,000 $30,000 $35,000 $40,000 $45,000 3Q 22 4Q 22 1Q 23 2Q 23 3Q 23 4Q 23 1Q 24 2Q 24 3Q 24 4Q 24 US Ex US $4.3M $8.8M $26.0M $24.2M $22.5
Slide 44: Bardet-Biedl Syndrome Opportunity in U.S. and Europe
® 44 Bardet-Biedl Syndrome Opportunity in U.S. and Europe U.S. prevalence estimated to be 4,000 to 5,000* patients EU + UK prevalence estimated to be 4,000 to 5,000 * patients *BBS prevalence estimates vary between populations, from 1 in 100,000 in northern European populations with higher prevalenc
Slide 45: Continued Progress in Securing Market Access for IMCIVREE
® 45 Continued Progress in Securing Market Access for IMCIVREE EARLY ACCESS OR NAMED PATIENT SALES LAUNCHED IMCIVREE is available in >15 countries outside the United States
Slide 46: Reimbursed Early-access Programs in France and Italy
® 46 Setmelanotide Benefiting Patients with Hypothalamic Obesity through Reimbursed Early-access Programs in France and Italy France • Steady uptake since first available in early 2024 • Access granted by joint federal multidisciplinary committee monthly • Positive responses reported in adult patien
Slide 47: BBS Commercial Launch Underway in England and Wales
® 47 BBS Commercial Launch Underway in England and Wales in Q4 2024 England and Wales • NICE recommended NHS reimbursement for patients younger than 18yo with BBS • 4 NHS BBS specialized clinics: 2 for adult patients, 2 for pediatric patients • Patients to be trained in hospital setting with at-home
Slide 48: Thank you
® 48 Thank you
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