Rhythm Pharmaceuticals, Inc. · NASDAQ:RYTM
Rhythm Pharmaceuticals — Conference Call: Interim results from Phase 2 trial in Hypothalamic Obesity (July 2022)
35 slides from Rhythm Pharmaceuticals's conference presentation, Jul 12, 2022
Slide 1: Interim results from Phase 2 Clinical Trial Evaluating Setmelanotide in Hypothalamic Obesity
Rhythm Pharmaceuticals Interim results from Phase 2 Clinical Trial Evaluating Setmelanotide in Hypothalamic Obesity July 12, 2022 ® CONFIDENTIAL
Slide 2: Agenda
• David Connolly Executive Director, Investor Relations and Corporate Communications • David Meeker, MD Agenda Chairman, President and CEO • M. Jennifer Abuzzahab, MD Pediatric Endocrinologist at Children's Minnesota • Hunter Smith Chief Financial Officer 2
Slide 3: Forward Looking Statements
Forward Looking Statements 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 regula
Slide 4: David Meeker, MD
David Meeker, MD Chairman, President and CEO Rhythm Pharmaceuticals 4
Slide 5: First and only FDA-approved and EC-authorized therapy targeting a root cause of hyperphagia
First and only FDA-approved and EC- authorized therapy that targets a root cause of hyperphagia and early-onset, severe obesity Launch for Bardet-Biedl Achieve market access Expand addressable syndrome (BBS) in U.S. throughout EU with patient population with underway EC authorization for BBS robust
Slide 6: Hypothalamic Obesity: Severe Disease Burden with Significant Unmet Need
Hypothalamic Obesity: Severe Disease Burden with Significant Unmet Need Established patient Biology of No effective treatment population actively hypothalamic obesity for rapid weight gain seeking and is tied to from injury to advocating for an melanocortin-4 hypothalamus effective therapy receptor
Slide 7: Setmelanotide Achieved Proof of Concept in Interim Analysis of Hypothalamic Obesity Phase 2 Trial
Setmelanotide Achieved Proof of Concept in Interim Analysis of Hypothalamic Obesity Phase 2 Trial Full analysis set population (n=11) 11 of 11 −17.2 patients achieved mean % change primary endpoint of >5% reduction in BMI in BMI over 16 weeks (P<0.0001) (SD, 9.0%) Interim analysis as of the data cut
Slide 8: MC4R Pathway Biology is Clear and Strong
MC4R Pathway Biology is Clear and Strong: Regulates Hunger, Caloric Intake, Energy Expenditure and, Consequently, Body Weight Setmelanotide can address MC4R pathway impairment contributing to early-onset, severe obesity POMC NEURON MC4R-EXPRESSING ALMS1 NEURON Leptin BBSx LEPR RAI1 SH2B1 MC4R Appe
Slide 9: Hypothalamic Obesity Represents a Significant U.S. Market Opportunity
Hypothalamic Obesity Represents a Significant U.S. Market Opportunity 5,000 – 10,000* patients ~500* Estimated U.S. prevalence additional cases diagnosed in U.S. each year 2,500 - 7,500 >1,000 >1,500 HO related to HO related to HO related to craniopharyngioma astrocytoma other tumor types *To estima
Slide 10: M. Jennifer Abuzzahab, MD
M. Jennifer Abuzzahab, MD Pediatric Endocrinologist at Children's Minnesota 10
Slide 11: Patient Journey with Hypothalamic Obesity
Patient Journey with Hypothalamic Obesity • Damage to the ventromedial hypothalamic nucleus HO-related • Most often have craniopharyngioma, other suprasellar tumors, event related surgeries, or radiation1 Rapid weight gain, • Strongest increase in weight within the first 6-12 months following HO eve
Slide 12: Hypothalamic Obesity: A Rare, Acquired Form of Obesity Following Injury to the Hypothalamic Region
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 considered the most common cause MC4R pathway deficiency following injury to hypothalamic
Slide 13: Damage to the Hypothalamus Can Impair MC4R Pathway Signaling
Damage to the Hypothalamus Can Impair MC4R Pathway Signaling Leading to Hyperphagia, Decreased Energy Expenditure and Rapid-onset Obesity1-4 Hypothalamus Upstream Downstream Downstream AgRP neuron MC4R activity Low Normal LEPR AgRP Tumor Adipose Hyperphagia tissue PCSK1 MC4R Obesity MC4R neuron α-MS
Slide 14: Patient case of M. Jennifer Abuzzahab, MD
Patient case of M. Jennifer Abuzzahab, MD, Pediatric Endocrinologist, at Children's Minnesota 14
Slide 15: Patient case of M. Jennifer Abuzzahab, MD
Patient case of M. Jennifer Abuzzahab, MD, Pediatric Endocrinologist, at Children's Minnesota 15
Slide 16: HO: Aggressive, Rapid Weight Gain follows Therapy for CP
HO: Aggressive, Rapid Weight Gain follows Therapy for CP Weight for age 2 - 20 years old Boys BMI for age 2 - 20 years old Boys Tumor recurrence & radiation therapy Typical growth pattern of a patient with HO following CP therapy, with persistent weight gain. The first plotted point is diagnosis at
Slide 17: HO: Aggressive, Rapid Weight Gain follows Therapy for CP
HO: Aggressive, Rapid Weight Gain follows Therapy for CP Patient Case Study: Setmelanotide therapy achieved rapid, significant weight loss Setmelanotide GLP1 therapy therapy Patient case of M. Jennifer Abuzzahab, MD, Pediatric Endocrinologist, at Children's Minnesota 17
Slide 18: Longitudinal Analysis of Patients with Childhood-onset Craniopharyngioma
Longitudinal Analysis of Patients with Childhood-onset Craniopharyngioma Illustrates Impact of Hypothalamic Involvement in BMI Patients with CP with hypothalamic involvement develop significant increase in BMI standard deviation +0.80 +4.29 Median change Median change in BMI SD in BMI SD Patients wi
Slide 19: No Effective Treatment Options for Hypothalamic Obesity
No Effective Treatment Options for Hypothalamic Obesity Patients with HO No pharmaceutical Bariatric treatment Current are unresponsive agent for treatment with invasive , recommendations to lifestyle and has been approved nonreversible are limited to diet modifications by the FDA or methods in hypo
Slide 20: David Meeker, MD
David Meeker, MD Chairman, President and CEO Rhythm Pharmaceuticals 20
Slide 21: Phase 2 Open-label Trial Designed to Evaluate Setmelanotide's Therapeutic Effect
Phase 2 Open-label Trial Designed to Evaluate Setmelanotide’s Therapeutic Effect in Patients with Hypothalamic Obesity PATIENTS 6-16 YEARS OLD 1 mg 2 mg 3 mg setmelanotide Primary Screening PATIENTS 16- 40 YEARS OLD efficacy Open-label extension assessment 2 mg 3 mg setmelanotide 2-8 weeks 16 weeks
Slide 22: Disposition of Patients Enrolled in Phase 2 Study
Disposition of Patients Enrolled in Phase 2 Study All patients enrolled in Ph 2 study Today’s interim analysis Interim analysis set Enrolled Full analysis set (n=11) (N=18) Discontinued due to AE (n=2) Completed 16 weeks, Discontinued due but chose not to to AE (n=2) continue therapy (n=1) Withdrawa
Slide 23: Interim Data Analysis is Based on Enrollment of 11 Patients
Interim Data Analysis is Based on Enrollment of 11 Patients Baseline characteristic Total (n=11) Age, years Mean (SD) 14.6 (4.8) Range 6-23 <18 years old, n 9 ≥18 years old, n 2 Sex, n (%) Female / Male 5 (45.5) / 6 (54.5) Race, n (%) White 11 (100) Ethnicity, n (%) Hispanic or Latino 2 (18.2) Not H
Slide 24: Setmelanotide Resulted in Mean BMI Reduction of -19.5% in 9 Completers at 16 Weeks
Setmelanotide Resulted in Mean BMI Reduction of -19.5% in 9 Completers at 16 Weeks FAS population (n=11) Completers (n=9) −17.2 −19.5 mean % change mean % change in BMI over 16 weeks in BMI over 16 weeks (SD, 9.0%) (SD, 8.2%) −15.8 mean % change −17.8 mean % change in body weight after 16 weeks of i
Slide 25: Clinically Meaningful Reductions Observed in All Patients by 16 Weeks
Clinically Meaningful Reductions Observed in All Patients by 16 Weeks 0 -5 * ** −5% change -7.02 -8.18 -10 Mean % Change BMI -10.03 -10% change -15 -12.70 -12.79 -16.12 -20 -18.39 -21.10 -25 -22.73 -24.46 -30 -35 -37.19 -40 Interim analysis as of the data cutoff date of May 6, 2022; BMI, body mass i
Slide 26: Setmelanotide Resulted in 17.8% Reduction in Body Weight at 16 Weeks
Setmelanotide Resulted in 17.8% Reduction in Body Weight at 16 Weeks Baseline mean (SD) weight: 107.8 kg (29.9)/ 237.7 lb (65.9) Completers (n=9) 16-week mean (SD) weight: 90.0 kg (27.7)/ 198.4 lb (61.1) 0 Mean % (SD) weight change at 16 weeks: 17.8 (7.9) Mean weight reduction at 16 weeks: -17.8 kg
Slide 27: Statistically Significant Reduction in BMI Z Score in All Patients <18 Years Old
Setmelanotide Treatment Resulted in Statistically Significant Reduction in BMI Z Score in All Patients <18 Years Old −1.1 point mean change in BMI Z score 3.56 2.48 -30.2% Mean BMI Z Mean BMI Z Mean % after 16 weeks of at baseline at 16 weeks change in BMI setmelanotide Z at 16 weeks (n=9; SD, 1.24
Slide 28: Meaningful Reduction in Most Hunger Score at 16 Weeks
Setmelanotide Achieved Meaningful Reduction in “Most” Hunger Score at 16 Weeks in Patients with HO >12 years old 16 weeks on Change from Baseline (n=8) therapy (n=7) baseline Mean “Most” 7.18 4.55 -2.66 hunger (0-10) (5.4, 8.7) (1.0, 7.6) (-7.0, 0.4) (Min, Max) Interim analysis as of the data cutoff
Slide 29: Safety and Tolerability Was Consistent With Setmelanotide Data
Safety and Tolerability Was Consistent With Setmelanotide Data N=11 N=11 n (%) n (%) Treatment-related AEs 11 (100.0) Treatment-emergent AEs occurring in ≥20% of patients Serious AEs 2 (18.2) Nausea 7 (63.6) Serious treatment-related AEs 1 (9.1) Vomiting 5 (45.5) Treatment-related AEs leading to dru
Slide 30: Disposition of 18 Patients Enrolled in Phase 2 Study
Disposition of 18 Patients Enrolled in Phase 2 Study Enrolled (N=18) Discontinued due to AE (n=2) • Hyperpigmentation (wk 13) • Elevated liver enzymes (wk 8) Completed 16 weeks, but chose not to continue therapy (n=1) Withdrawal (n=1) • Non-compliance of therapy Continuing on setmelanotide therapy*
Slide 31: Rhythm Advancing Setmelanotide towards Potential Registration for Hypothalamic Obesity
Rhythm Advancing Setmelanotide towards Potential Registration for Hypothalamic Obesity Planning to End of Phase 2 Initiate Phase 3 present full data meeting with FDA trial in 1H2023 from 18 patients anticipated in to support in Phase 2 trial 2H2022 potential in Fall of 2022 registration 31
Slide 32: Appendix
Appendix Rhythm
Slide 33: An Estimated 2,500 – 7,500 Patients Live with HO Related to Craniopharyngioma
An Estimated 2,500 – 7,500 Patients Live with HO Related to Craniopharyngioma in the United States 325,719,1781 U.S. population, all ages, in 2020 ~600 3 5,000 – 15,000 2 Estimated U.S. incidence 1. US census. American Community Survey – DP05 ACS demographic estimates 2020; Estimate of based on pati
Slide 34: An Estimated ~1,000 Patients Live with HO Related to Astrocytoma
An Estimated ~1,000 Patients Live with HO Related to Astrocytoma 1 in the United States 82,519,0402 U.S. population, children 1. Includes pilocytic astrocytoma [incl. optic nerve glioma], diffuse astrocytoma, anaplastic astrocytoma, oligoastrocytic tumors, unique ~14,3003 ~1,1004 astrocytoma variant
Slide 35: Rhythm Pharmaceuticals
PHARMACEUTICALS