Rhythm Pharmaceuticals, Inc. · NASDAQ:RYTM
Rhythm Pharmaceuticals — Investor Presentation (January 2023)
51 slides from Rhythm Pharmaceuticals's investor presentation, Jan 9, 2023
Slide 1: Rhythm Pharmaceuticals
© Rhythm® Pharmaceuticals, Inc. All rights reserved. ® January 2023 Rhythm Pharmaceuticals Transforming the lives of patients and their families living with hyperphagia and severe obesity caused by rare MC4R pathway diseases by rapidly advancing care and precision medicines addressing the root cause
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 pro
Slide 3: First and only FDA-approved and EC-authorized therapy targeting root cause of hyperphagia
® 3 First and only FDA - approved and EC - authorized therapy that targets a root cause of hyperphagia and early - onset, severe obesity Strong start to U.S. launch for Bardet - Biedl syndrome (BBS) Expanding addressable patient population with robust clinical development program Achieved access in
Slide 4: Key Milestones in 2022 and Expected in 2023
® 4 Rhythm Achieved Key Milestones in 2022, Laying the Groundwork for Continued Momentum Expected in 2023 x Launched IMCIVREE for BBS in U.S. following FDA approval in June x Granted EC marketing authorization for IMCIVREE for BBS; received early access authorization in France x Announced positive r
Slide 5: Early-onset Hyperphagia and Severe Obesity Impact on Patients and Families
® 5 Early - onset, Hyperphagia and Severe Obesity Have a Significant Impact on Patients with MC4R Pathway Diseases and their Families “My weight is my biggest challenge, and it affects every aspect of my daily activities. When I’m hungry, I can’t stop it because I don’t have the signal from my stoma
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 E
Slide 7: Clinical Development Programs Designed to Expand IMCIVREE Label
® 7 Clinical Development Programs Designed to Expand IMCIVREE Label and Overall Opportunity Entering Phase 3 in 1H 2023 Hypothalamic obesity 5,000 – 10,000 patients in the U.S.* Phase 3 EMANATE Trial** Heterozygous POMC/PCSK1 insufficiency Heterozygous LEPR insufficiency SRC1 deficiency SH2B1 defici
Slide 8: Rhythm Leadership
® 8 David Meeker, MD Chair, President and Chief Executive Officer Hunter Smith Chief Financial Officer Jennifer Chien Executive Vice President, Head of North America Yann Mazabraud Executive Vice President, Head of International Joe Shulman Chief Technology Officer 25 - plus years; focus on rare gen
Slide 9: Bardet-Biedl Syndrome
® 9 Bardet - Biedl Syndrome FDA approval in June 2022 EC authorization in September 2022
Slide 10: Bardet-Biedl Community is Established and Patients are Identified
® 10 Bardet - Biedl Community is Established and Patients are Identified U.S. prevalence estimated to be 1,500 to 2,500 patients More than 600 individuals living with BBS are enrolled in CRIBBS registry
Slide 11: Continued Momentum Across First Full Quarter of Launch
® 11 Continued Momentum Across First Full Quarter of Launch >120 * BBS prescriptions *Cumulative as of September 30, 2022 >80* unique prescribers >40 * Approvals for reimbursement
Slide 12: Rhythm InTune Support Services
® 12 Personalized program to achieve access, set treatment expectations and support patient adherence and continuity of therapy Rhythm InTune Support Services Introduce IMCIVREE Set expectations Discuss therapy with physician Treatment support Injection tips Adherence Goal setting
Slide 13: Multi-channel Engagement to Continue Identifying Patients with BBS
® 13 Multi - channel Engagement to Continue Identifying Patients with BBS Identified and diagnosed Diagnosed not yet known to RYTM Suspected Undiagnosed Territory Manager engagement Congresses and professional societies Educational materials Patient Educations Managers Speaker programs Patient advoc
Slide 14: International Market Access
® 14 International Market Access
Slide 15: Significant Market Opportunity in Europe
® 15 Significant Market Opportunity for BBS and POMC, PCSK1 and LEPR Deficiencies in Europe Estimated European prevalence ~2,500 > 1,500 individuals identified in EU4 + UK ( ~20 academic medical centers with > 40 BBS patients ) Estimated European prevalence 600 - 2,500 ~1 00 individuals identified i
Slide 16: Global Launch Underway for POMC, PCSK1 and LEPR Deficiency
® 16 Global Launch Underway for POMC, PCSK1 and LEPR Deficiency x United Kingdom Commercial launch in October 2022 following UK NICE recommendation x Germany Launched, first sales in 2Q22 following exemption from G - BA lifestyle drug exclusion list x France Reimbursed since March 2022 via early acc
Slide 17: EC Marketing Authorization Received
® 17 EC Marketing Authorization Received Sept. 6, 2022 IMCIVREE for Treatment of Obesity and Control of Hunger in Patients with Bardet - Biedl Syndrome France Reimbursed early - access program achieved in July 2022 Germany G - BA exemption procedure ongoing Launch expected 1H2023 United Kingdom Subm
Slide 18: Hypothalamic Obesity
Hypothalamic Obesity 12 Rhythms
Slide 19: Hypothalamic Obesity: A Rare, Acquired Form of Obesity
® 19 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 20: Setmelanotide and Hypothalamic Obesity: A Transformative Opportunity
® 20 Setmelanotide and Hypothalamic Obesity: A Transformative Opportunity for Rhythm x Unmet medical need is high; no approved therapies x MC4R pathway deficiency following injury to hypothalamic region x Patients are identified; no genetic testing required x Patients are engaged with the system rec
Slide 21: Patients with CP with hypothalamic involvement develop significant BMI increase
® 21 Patients with CP with hypothalamic involvement develop significant increase in BMI standard deviation Longitudinal Analysis of Patients with Childhood - onset Craniopharyngioma Illustrates Impact of Hypothalamic Involvement in BMI Adapted from Sterkenburg , et. al., Neuro Oncol . 2015; doi : 10
Slide 22: HO: Aggressive, Rapid Weight Gain follows Therapy for CP
® 22 HO: Aggressive, Rapid Weight Gain follows Therapy for CP Setmelanotide therapy GLP1 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 23: Significant BMI Reduction in Hypothalamic Obesity Phase 2 Trial
® 23 Setmelanotide Achieved Significant BMI Reduction at 16 Weeks in Patients with Hypothalamic Obesity in Phase 2 Trial As presented during The Obesity Society’s ObesityWeek ® 2022, November 1 - 4, 2022 in San Diego, CA Full analysis set population (N=18) − 14.5% mean change in BMI at 16 weeks 16 o
Slide 24: Setmelanotide Achieved Consistent BMI Reduction
® 24 Setmelanotide Achieved Consistent BMI Reduction at 16 Weeks a −7.0% last on treatment Week 4. b −8.2% last on treatment Week 12. BMI, body mass index; LOCF, last observation carried forward. Patients not achieving ≥10% reduction of BMI at 16 weeks a - 37.2 - 25.7 - 24.5 - 22.7 - 21.1 - 18.4 - 1
Slide 25: Mean Percent Change in BMI in Long-term Extension Trial
® 25 Mean Percent Change in BMI in Patients With ≥3 Months of Follow - up in the Long - term Extension Trial - 16.8 (n=13) - 21.1 (n=13) - 26.7 (n=5) -45 -40 -35 -30 -25 -20 -15 -10 -5 0 0 4 8 12 16 20 24 28 32 36 40 44 BMI reduction from baseline, % Weeks of index trial treatment Primary study 16 w
Slide 26: Phase 3 Double-blind Randomized Controlled Trial with 120 Patients
® 26 Phase 3 Double - blind, Randomized Controlled Trial with 120 Patients Expected to Begin in Early 2023 BMI, body mass index; QD, once daily. 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 fr
Slide 27: Significant Unmet Need with an Active Patient Community
® 27 Significant Unmet Need with an Active Patients Community Waiting for an Effective Therapy He demonstrated excessive hunger upon returning home from the hospital. He foraged at night. We locked up food to avoid having to stay up all night to monitor his night eating.” -- Caregiver “ Excerpted fr
Slide 28: Clinical Development
® 28 Clinical Development Meaningful Expansion of Addressable Patient Population
Slide 29: Multiple Ongoing and Planned Clinical Trials Evaluating Setmelanotide
® 29 Multiple Ongoing and Planned Clinical Trials Evaluating Setmelanotide Weekly Formulation Phase 3 Switch Trial Pediatrics Trial Phase 3 Patients aged 2 to <6 years Phase 2 Trial Phase 3 Trial Enrollment complete Hypothalamic obesity Phase 3 Trial planned for 1Q2023 Weekly Formulation Phase 3 de
Slide 30: EMANATE and DAYBREAK to Expand Addressable Market
® 30 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 seq uencing results, current estimat
Slide 31: Setmelanotide Generally Well-tolerated Across Development Program
® 31 Setmelanotide has been evaluated in 639 patients with obesity, with some individual patient treatment durations now exceeding five years Setmelanotide has been generally well - tolerated Most AEs are mild: • Mild injection site reactions • Hyperpigmentation and skin lesions, mediated by the clo
Slide 32: Rhythm's Strategic Priorities for 2023
® 32 Rhythm’s Strategic Priorities for 2023 Execute on U.S. commercial strategy with BBS launch Achieve access and launch IMCIVREE for both BBS and POMC, PCSK1 and LEPR in select international markets Expand IMCIVREE opportunity through additional studies : • EMANATE Ph 3 • Pediatrics Ph 3 • Weekly
Slide 33: Well Capitalized: Cash Sufficient into at least 2025
® 33 Well Capitalized: Cash Sufficient to Fund Planned Operations into at least 2025 $347.8 Million * Cash, cash equivalents and short - term investments as of 09/30/22 Guidance * Cash on hand expected to be sufficient to fund operations into 2025 55.8 Million Common shares outstanding * P artial ex
Slide 34: Appendix
® 34 Appendix
Slide 35: Additional Supporting Slides
® 35 Additional Supporting Slides
Slide 36: Phase 3 EMANATE Trial Across Four Genetic Subtypes
® 36 Phase 3 EMANATE 3 Trial to Evaluate Setmelanotide Across Four Genetic Subtypes Four independent sub - studies : allows for independent data readouts and potential registrations Targeted patient populations: Patients with pathogenic, likely pathogenic or suspected pathogenic variants • ~ 5.1% pa
Slide 37: Proof of Concept in HETs, SRC1 and SH2B1 Phase 2 Basket Study
® 37 Proof of Concept in HETs, SRC1 and SH2B1 Established in Exploratory Phase 2 Basket Study with Clinically - meaningful Weight Loss at Month 3 34.3% of patients (12/35) achieved the primary endpoint of ≥5% weight loss from baseline at Month 3 Responses to setmelanotide were maintained through 6 a
Slide 38: Long-term BMI Reductions in HETs, SRC1 and SH2B1
® 38 Long - term BMI Reductions at 12 Months on Setmelanotide Therapy in HETs, SRC1 and SH2B1 Supportive of Success in Phase 3 EMANATE Trial SRC1 Deficiency Obesity SH2B1 Deficiency Obesity HETs Obesity POMC/PCSK1/LEPR Heterozygous Deficiency - 8.7% mean BMI reduction (n=17) at 12 months on therapy
Slide 39: ACMG Variant Classification and MC4R Pathway Deficit
® 39 ACMG Variant Classification Can Inform MC4R Pathway Deficit and Potentially Setmelanotide Response Pathogenic Likely pathogenic VUS Likely benign Benign Number of variants Pathway impact science *ACMG Guidelines Richards et al, 2015 Variants of Uncertain Significance • Largest category of rare
Slide 40: Phase 3 EMANATE Trial Comprised of Four Independent Sub-studies
® 40 Design allows for independent data readouts in each sub - study and potential registration for each gene Each sub - study : Patients randomized 1:1 Phase 3 EMANATE Trial Comprised of Four Independent Sub - studies a. POMC/ PCSK1 * 86 patients • Pathogenic • Likely pathogenic • VUS* - Suspected
Slide 41: EMANATE Sub-studies Powered to Show Treatment Effect vs Placebo
® 41 Heterozygous POMC/PCSK1 and LEPR sub - studies are 90% powered to show >8% treatment effect vs. placebo SRC1 and SH2B1 sub - studies are 90% powered to show >7% treatment effect vs. placebo Assumption to achieve mean treatment effect v placebo: • The placebo group is not expected to lose weight
Slide 42: EMANATE Secondary Endpoints
® 42 EMANATE Secondary Endpoints to Illustrate Effect on Weight and Hunger Secondary endpoints • Proportion of patients who achieve at least 5% reduction in BMI at 52 weeks compared to placebo • Proportion of patients who achieve at least 10% reduction in BMI at 52 weeks compared to placebo • Differ
Slide 43: Daybreak Trial to Evaluate Setmelanotide Across 10 New Genes
® 43 Relevance to MC4R Pathway : Rhythm’s ClinGen - based framework suggests all 10 genes have very strong relevance to MC4R Pathway Efficient, two - stage trial design • 16 - week, open - label run - in in allows for fast signal - seeking in individual gene cohorts • 24 - week, double - blind treat
Slide 44: Phase 2 DAYBREAK Trial Design
® 44 Phase 2 DAYBREAK Trial Designed to Evaluate Setmelanotide Therapy in 10 Genes with Strong or Very Strong Relevance to MC4R Pathway ≥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 10 we
Slide 45: Enrollment Completed in Phase 3 Trial in Pediatric Patients Ages 2 to 6
® 45 International one - year, open - label study Enrollment complete with 12 patients • Half with biallelic POMC, PCSK1 or LEPR deficiency • Half with BBS Primary endpoint: Responder analysis based on proportion of patients who experience a decrease in BMI - Z of ≥0.2 Secondary endpoints : S afety
Slide 46: Phase 3 Weekly Formulation Switch and De Novo Studies
® 46 Phase 3 randomized, double - blind “switch study” initiated in 4Q 2021 • Enrollment: 30 patients with BBS or biallelic or heterozygous POMC, PCSK1 or LEPR deficiency who have who have been on open - label QD setmelanotide treatment for at least 6 months • Randomized 1:1 for 13 weeks of double -
Slide 47: DAYBREAK Phase 2 Trial Design and Endpoints
® 47 Primary endpoint is the proportion of patients by gene who enter Stage 2 and are responders compared to placebo • Responders > 18 years who achieve 10% or greater body weight reduction from baseline • Responders <18 years who achieve BMI reduction of > 0.3 from baseline Secondary endpoints by g
Slide 48: Vast Majority of BBS Patients Had Clinically Meaningful Response
® 48 Vast Majority of BBS Patients * had Clinically Meaningful Response to Setmelanotide at One Year on Therapy in Pivotal Study *A total of 28 patients were older than 12 years old and included in the primary analysts set, 15 adults and 13 patients betw een the ages of 12 and 18; ** One patient was
Slide 49: Setmelanotide Led to Significant BMI Reduction in BBS Versus Placebo
® 49 Phase 3 Trial: Setmelanotide Led to Significant BMI Reduction in Patients with BBS Versus Placebo at Week 14 As presented at ESPE 2021 – 59th Annual European Society for Paediatric Endocrinology Meeting, September 2021. Difference: - 3.8% P <0.05 Patients with BBS treated with setmelanotide ach
Slide 50: Improvements in Health-related Quality of Life in Patients with BBS
® 50 Phase 3 Trial Setmelanotide Achieved Clinically Meaningful Improvements in Health - related Quality of Life (HRQOL) in Patients with BBS 85% of patients reported clinically meaningful improvements or preserved non - impaired health related quality of life status Adults ( > 18 years old) Childre
Slide 51: Mean % Change in Body Weight; US and EU Approvals Based on Phase 3 Data
® 51 Mean % Change in Body Weight Visit BL V2 V3 V4 V5 V6 V7 V8 V9 V10 V11 V12 FV 0% – 5% – 10% – 15% – 20% – 25% Mean % Change in Body Weight BL V2 V3 V4 V5 V6 V7 V8 V9 V10 V12 FV 0% – 2% – 4% – 6% – 8% – 12% – 10% U.S. and EU Approvals of IMCIVREE Based on Phase 3 Data from Largest Studies Conduct
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