Rhythm Pharmaceuticals, Inc. · NASDAQ:RYTM
Rhythm Pharmaceuticals — Investor Presentation (November 2020)
42 slides from Rhythm Pharmaceuticals's investor presentation, November 2020
Slide 1: Rhythm Pharmaceuticals
Rhythm Pharmaceuticals Targeting MC4R pathway and transforming the care of patients with rare genetic disorders of obesity November 2020 ® © Rhythm® Pharmaceuticals, Inc. All rights reserved.
Slide 2: Forward Looking Statements
Forward Looking Statements This presentation contains certain statements that are forward-looking within the meaning of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended, and that involve risks and uncertainties, including witho
Slide 3: Working Toward Changing the Paradigm for the Treatment of Rare Genetic Disorders of Obesity
Working Toward Changing the Paradigm for the Treatment of Rare Genetic Disorders of Obesity Setmelanotide, an investigational drug, has demonstrated potential to dramatically reduce weight and hunger Meaningful Growth Validation Opportunity Potential Secure FDA and EMA Deliver Bardet-Biedl and Estab
Slide 4: Living with Early-onset, Severe Obesity and Hyperphagia
Living with Early-onset, Severe Obesity and Hyperphagia Hallmark Symptoms of Rare Genetic Disorders of Obesity “They are constantly, all day “It causes extreme long saying they are hungry unrelenting hunger and and asking what’s for the excessive eating. As a next meal and what are we child…the frid
Slide 5: MC4R Pathway Regulates Hunger, Caloric Intake, and Energy Expenditure, and, Consequently, Body Weight
MC4R Pathway Regulates Hunger, Caloric Intake, and Energy Expenditure, and, Consequently, Body Weight When signaling cascade is impaired, setmelanotide restores function by replacing MSH stimulating hormone POMC NEURON MC4R-EXPRESSING ALMS1 NEURON Leptin BBSx LEPR RAI1 SH2B1 MC4R Appetite Satiety
Slide 6: Rare Genetic Disorders of Obesity Associated with the MC4R Pathway Comprise a Significant Opportunity
Rare Genetic Disorders of Obesity Associated with the MC4R Pathway Comprise a Significant Opportunity Distinct from General Obesity POMC deficiency obesity ~100-500* LEPR deficiency obesity ~500-2,000* Bardet-Biedl syndrome ~1,500-2,500 * Rhythm is Obesity Alström syndrome ~500-1,000† focused on rar
Slide 7: Validation
Validation Secure FDA and EMA approval for POMC and LEPR deficiency obesities ® 7
Slide 8: Setmelanotide Demonstrated Statistically Significant, Clinically Meaningful Reductions in Weight and Hunger in Phase 3 Trials
Setmelanotide Demonstrated Statistically Significant, Clinically Meaningful Reductions in Weight and Hunger in Phase 3 Trials for POMC and LEPR POMC Phase 3 Topline Data* (n=10) Validation 80% -25.4% -27.8% 31.9kg / • PDUFA date set for Nov. 27, 2020 with priority review >10% weight loss mean weight
Slide 9: Meaningful Opportunity
Meaningful Opportunity Deliver on the potential of setmelanotide to patients with Bardet-Biedl and Alström syndromes and advance disease understanding ahead of pivotal Phase 3 data ® 9
Slide 10: Phase 2 Data in BBS Illustrate Sustained Weight Loss and Hunger Reduction
Phase 2 Data in BBS Illustrate Sustained Weight Loss and Hunger Reduction 0 0 % Change in Body Weight From Baselinea -10 % Change in Most Hunger Scoreb -5.48# -5 -20 -30 -10 -11.26ⱡ -40 -50 -50.93 -15 -16.33§ -60 -63.96 -70 -70.16 -20 -80 -90 -25 -100 Baseline 3 months 6 months 12 months Baseline 3
Slide 11: Bardet Biedl & Alström Syndromes Phase 3 Trial: Enrollment in Pivotal Cohort Completed in December 2019
Bardet Biedl & Alström Syndromes Phase 3 Trial: Enrollment in Pivotal Cohort Completed in December 2019 Topline pivotal data expected in 4Q2020 or early 1Q2021 Double-blind treatment period Open-label treatment Pivotal cohort: Setmelanotide • 32 BBS patients 3 mg • 6 Alström syndrome Screening and S
Slide 12: Opportunity with Established Communities and Unmet Need for Bardet-Biedl and Alström Syndromes
Opportunity with Established Communities and Unmet Need for Bardet-Biedl and Alström Syndromes Rhythm has ongoing relationships Market research points to unmet need with patient advocacy groups to in treatment for BBS and Alström drive awareness, disease syndrome patients understanding and build sup
Slide 13: Growth Potential
Growth Potential Establish proof-of-concept in new indications with Rhythm Engine & Basket Study ® 13
Slide 14: Genetic Testing Expected to Drive Future Growth through Clinical Development
Genetic Testing Expected to Drive Future Growth through Clinical Development UNCOVERING RARE OBESITY Biobanks 101-Gene Panel Identify individuals with clear genetic underlying cause of severe obesity ® 14
Slide 15: Phase 2 Basket Study Key to Advancing to MC4R Pathway Obesity Indication
Phase 2 Basket Study Key to Advancing to MC4R Pathway Obesity Indication Enrolling Multiple Cohorts with Genetic Variants • Seamless integration with Cohort stratification sequencing efforts • Rapid understanding of High impact LOF setmelanotide responsiveness • Efficient path to registration Uncert
Slide 16: Significant Opportunity with MC4R Pathway Disorders Now Enrolling on Phase 2 Basket Study
Significant Opportunity with MC4R Pathway Disorders Now Enrolling on Phase 2 Basket Study ~2,400* ~10,000* >20,000* >23,000* >24,000* Smith-Magenis MC4R POMC or LEPR SRC1 SH2B1 syndrome deficiency heterozygous deficiency deficiency obesity deficiency obesity obesity obesity Total potential patient p
Slide 17: Setmelanotide Generally Well-tolerated Across Development Program
Setmelanotide Generally Well-tolerated Across Development Program Setmelanotide has been evaluated in more than 400 patients with obesity, with individual patient treatment duration now exceeding four years Setmelanotide has been generally well-tolerated Patient experience with setmelanotide* Most A
Slide 18: Interim Data Showed Once-weekly Formulation of Setmelanotide Achieved Comparable Results to Daily
Interim Data Showed Once-weekly Formulation of Setmelanotide Achieved Safety and Efficacy Results Comparable to Daily in Phase 2 Study with 85 Healthy Obese Participants Gel-like depot with slow diffusion, designed to be more patient-friendly and convenient and less burdensome Weekly Daily 10mg/ 20m
Slide 19: Rhythm Executing with Transformational Progress
Rhythm Executing with Transformational Progress Validation with first potential approval for setmelanotide in POMC or LEPR deficiency 1 obesities 1Q: NDA submitted; Priority Review with no Advisory Committee; PDUFA date is Nov. 27, 2020; rare ✓ pediatric disease designations granted for setmelanotid
Slide 20: Appendix
Appendix ® 20
Slide 21: Strong Leadership Team with Broad Biopharma Experience
Strong Leadership Team with Broad Biopharma Experience David Meeker, MD Hunter Smith Yann Mazabraud Jennifer Chien Murray Stewart, MD Simon Kelner Chair, President and Chief Financial Officer Executive Vice President, Executive Vice President, Chief Medical Officer Chief Human Resources Chief Execut
Slide 22: Setmelanotide: Investigational MC4R agonist
Setmelanotide: Investigational MC4R agonist Eight-amino-acid cyclic peptide FDA Breakthrough Therapy Designation POMC deficiency obesity Daily subcutaneous injection; LEPR deficiency obesity once-weekly formulation in Bardet-Biedl syndrome development Alström syndrome FDA Orphan Drug Designa
Slide 23: Rhythm Pipeline Focused on MC4R Pathway Disorders
Rhythm Pipeline Focused on MC4R Pathway Disorders Disorder Early-stage development Phase 2 Phase 3 Registration POMC deficiency obesity LEPR deficiency obesity Pivotal Studies Bardet-Biedl syndrome Alström syndrome POMC or LEPR heterozygous Setmelanotide deficiency obesity SRC1 deficiency obesity SH
Slide 24: Cash Expected to be Sufficient to Fund Operations Through at Least End of 2021
Cash Expected to be Sufficient to Fund Operations Through at Least End of 2021 SHARES OUTSTANDING 44,204,745 (basic share count) as of 10/23/2020 CASH, CASH EQUIVALENTS AND SHORT-TERM INVESTMENTS $ 201.8 million as of 09/30/2020 ® 24
Slide 25: POMC Phase 3 Trial – Change in Weight and Hunger Over 1 Year
POMC Phase 3 Trial – Change in Weight and Hunger Over 1 Year with Substantial Weight Gain and Hunger Increase During Placebo Withdrawal Change in Weight* Change in Hunger Score*† 0 10 During Placebo Period: 9 Daily Hunger Score (Most in 24 hours) -10 8 Change in weight (kg) Mean +5.5 Change in Weigh
Slide 26: LEPR Phase 3 Trial – Change in Weight and Hunger Over 1 Year
LEPR Phase 3 Trial – Change in Weight and Hunger Over 1 Year with Substantial Weight Gain and Hunger Increase During Placebo Withdrawal Change in Weight* Change in Hunger Score *† 0 0 Daily Hunger Score - (Most in 24 hours) During Placebo Period: -5 Change in weight (kg) -2 Mean +4.9 Change in Weigh
Slide 27: Strong Phase 2 Data in BBS Showed Substantial Weight Loss and Hunger Control
Strong Phase 2 Data in BBS Showed Substantial Weight Loss and Hunger Control, Supporting Advancement into Phase 3 Published in Diabetes Obesity and Metabolism 2020* BMI change Hunger Score Weight Change from Duration from baseline Change from Baseline Baseline** 3 months -5.5% −5.5% -50.9% 90% CI, −
Slide 28: Phase 2 Data in Alström Syndrome
Phase 2 Data in Alström Syndrome* Age at % Weight % Hunger • Patient 1 has reached Baseline healthy body weight enroll Treatment, Change Score Change Weight ment/ weeks from from • Patient 3 maintaining weight (kg) Sex Baseline Baseline† and reduced hunger – HbA1c decreased by 3% 12/M 78.6 95 -20% -
Slide 29: BBS and Alström Syndrome Pivotal Trial Statistical Approach
BBS and Alström Syndrome Pivotal Trial Statistical Approach Primary endpoint Three key secondary endpoints (after ~52 weeks of treatment) Proportion of patients (≥12 Proportion of patients (≥12 Body weight percent Daily hunger score percent years old) who achieve years old ) who achieve a change fro
Slide 30: Sequencing Yield for Genetically-identified Indications Points to Significant Opportunity
Sequencing Yield for Genetically-identified Indications Points to Significant Opportunity Yield for genetically- Individuals with identified indications**: severe obesity sequenced 13,567* POMC or LEPR High-impact HETs MC4R n = 269; SH2B1 n = 245; SRC1 n = 335; n = 29; n = 97; 2.0% 1.8% 2.5% 0.2% 0.
Slide 31: Stratifying Patients Based on Loss of Function (LOF) Variant – HET Example
Stratifying Patients Based on Loss of Function (LOF) Variant – HET Example U.S. prevalence approximately 1 million for • Patients present with severe, early-onset individuals with heterozygous POMC or LEPR obesity and hyperphagia variants, and >20,000 high-impact LOF patients in U.S.* • Basket Study
Slide 32: Phase 2 Data in HET Patients Based on LOF Variant
Phase 2 Data in HET Patients Based on LOF Variant All high-impact LOF patients appear setmelanotide-responsive; other subgroups have more variable responses Total treatment Baseline Weight Weight Loss Change in Hunger Hunger score Weight loss duration2 (weeks) (kg/(lbs)) (kg/(lbs)) Score (10 pt scal
Slide 33: Rhythm's Approach Enables Deep Understanding of Rare Genetic Disorders of Obesity
Rhythm’s Approach Enables Deep Understanding of Rare Genetic Disorders of Obesity and Optimizes Registration/Commercial Strategy Rhythm’s Sequencing Database U.S. Prevalence Estimate Phase 2 Basket Study Conservative projection of individuals Facilitates understanding of whose obesity is likely due
Slide 34: Translating Rhythm Sequencing Data to U.S. Prevalence Estimates
Translating Rhythm Sequencing Data to U.S. Prevalence Estimates Most stringent criteria for variant classification to establish baseline estimates of US prevalence Rhythm database: Obese individuals with a variant 1 Functional and computational Rare variant filters Variant High-impact loss-of-functi
Slide 35: New MC4R Pathway Indications Based on Supported Scientific Rationale
New MC4R Pathway Indications Based on Supported Scientific Rationale UPSTREAM DOWNSTREAM POMC NEURON MC4R-EXPRESSING NEURON Leptin LEPR RAI1 SH2B1 MC4R Appetite Satiety Signals SRC1 ACTIVATION Weight (Leptin) MSH Energy expenditure POMC PCSK1 ® 35
Slide 36: SRC1 is a Transcriptional Coactivator that Drives POMC Expression
SRC1 is a Transcriptional Coactivator that Drives POMC Expression Pathway Relevance: Drives POMC Expression • Transcriptional coactivator activated downstream of LEPR POMC NEURON • Found in POMC neurons Leptin Autosomal Dominant • Obesity arises due to heterozygous gene variants LEPR Clinical Presen
Slide 37: SH2B1 is an Adapter Protein that Regulates LEPR Activity
SH2B1 is an Adapter Protein that Regulates LEPR Activity Pathway Relevance: Regulates LEPR activity POMC NEURON • Adapter protein • Found in POMC neurons Leptin Autosomal Dominant • Obesity arises due to heterozygous gene variants or LEPR chromosomal deletions + SH2B1 MC4R Clinical Presentation Sati
Slide 38: MC4R: Receptor for POMC Ligand MSH
MC4R: Receptor for POMC Ligand MSH Pathway Relevance: Receptor for POMC ligands • Required for satiety effects of α/β-MSH Autosomal Dominant MC4R-EXPRESSING NEURON • Obesity arises due to heterozygous gene variants Clinical Presentation • Early onset obesity and hyperphagia MC4R Setmelanotide Appe
Slide 39: Smith-Magenis Syndrome: RAI1 Affects POMC Expression
Smith-Magenis Syndrome: RAI1 Affects POMC Expression Pathway Relevance: Decreased Pathway Function Upstream of MC4R POMC NEURON • Causal gene is RAI1 Leptin • Transcription factor for a number of pathway genes Autosomal Dominant LEPR RAI1 • Gene variants and chromosomal MC4R deletions Satiety Signal
Slide 40: POMC and LEPR Deficiency Obesities Characterized by Early-onset Obesity, Unrelenting Hunger
POMC and LEPR Deficiency Obesities Characterized by Early-onset Obesity, Unrelenting Hunger POMC Deficiency Hyperphagia Hyperphagia LEPR Deficiency Obesity Obesity Developmental delays Results from loss-of- Results from loss-of- function homozygous or function homozygous or biallelic variants in the
Slide 41: Bardet-Biedl and Alström Syndromes Associated with Severe Obesity and Hunger
Bardet-Biedl and Alström Syndromes Associated with Severe Obesity and Hunger Bardet-Biedl Hyperphagia Hyperphagia Alström syndrome2,3 syndrome1 Progressive vision Progressively worsening Rare ciliopathy disorder impairment/loss vision and hearing associated with ALMS1 Rare ciliopathy disorder result
Slide 42: Rhythm Pharmaceuticals
PHARMACEUTICALS
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