Rhythm Pharmaceuticals, Inc. · NASDAQ:RYTM
Rhythm Pharmaceuticals — Investor Presentation (February 2021)
41 slides from Rhythm Pharmaceuticals's investor presentation, Feb 3, 2021
Slide 1: Targeting MC4R pathway and transforming the care of patients with rare genetic diseases of obesity
© Rhythm® Pharmaceuticals, Inc. All rights reserved. ® February 2021 Rhythm Pharmaceuticals Targeting MC4R pathway and transforming the care of patients with rare genetic diseases of obesity
Slide 2: Forward Looking Statements
® 2 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 without limitations statem
Slide 3: Living with Early-onset, Severe Obesity and Hyperphagia
® 3 Living with Early - onset, Severe Obesity and Hyperphagia Adalissa and Solomon with their siblings (unaffected) “They are constantly, all day long saying they are hungry and asking what’s for the next meal and what are we eating the next day. We keep a menu planned and if we deviate from that me
Slide 4: Change the Paradigm for the Treatment of Rare Genetic Diseases of Obesity
® 4 Change the Paradigm for the Treatment of Rare Genetic Diseases of Obesity Our mission:
Slide 5: Classic Rare Disease Challenges Apply to Genetic Obesities
® 5 Classic Rare Disease Challenges Apply to Genetic Obesities Lost in the system No treatment Little awareness Little knowledge No tools or testing Worst case: An irritation. It’s your fault. Eat less, exercise more.
Slide 6: MC4R Pathway Biology is Clear and Strong
® 6 MC4R Pathway Biology is Clear and Strong: Regulates Hunger, Caloric Intake, and Energy Expenditure, and, Consequently, Body Weight DOWNSTREAM ACTIVATION MC4R - EXPRESSING NEURON Appetite Weight Energy expenditure POMC NEURON UPSTREAM LEPR Leptin Satiety Signals (e.g. Leptin) MSH MC4R POMC SRC1 S
Slide 7: Rhythm Pipeline Focused on MC4R Pathway Diseases
® 7 Disease Phase 2 Phase 3 Regulatory Submission Approved Obesity due to POMC, PCSK1 or LEPR deficiency* Bardet - Biedl and Alström syndromes Weekly formulation Phase 3 MC4R Pathway Study: HETs, SRC1, SH2B1 Phase 2 Basket Study: HETs, SRC1, SH2B1, MC4R - rescuable, Smith - Magenis syndrome Phase 2
Slide 8: Rare Genetic Diseases of Obesity Associated with the MC4R Pathway Represent a Significant Opportunity
® 8 Rare Genetic Diseases of Obesity Associated with the MC4R Pathway Represent a Significant Opportunity LEPR, leptin receptor, POMC, pro - opiomelanocortin; MC4R, melanocortin - 4 receptor. * Estimated prevalence of U.S. patients based on company estimates; ** Estimated prevalence of U.S. patients
Slide 9: Total Potential Addressable Market for Five Genes in U.S. Exceeds 100K
® 9 Total Potential Addressable Market for Five Genes in U.S. Exceeds 100K * 1.7% of the US population (328M; 2019 US census) presents with severe early onset obesity (Hales et al 2018 Ɨ ); ~95% of individuals with severe early onset obesity remain obese into adulthood (Ward et al 2017) People in th
Slide 10: Now Approved in the United States; Initial Commercialization in 1Q21
® 10 Now Approved in the United States; Initial Commercialization in 1Q21 Obesity due to LEPR deficiency Obesity due to POMC, PCSK1 deficiency ~100 - 500 * ~500 - 2,000 * Approved by the U.S. FDA for chronic weight management in people with obesity due to proopiomelanocortin (POMC), proprotein conve
Slide 11: Bardet-Biedl Syndrome Phase 3 Update
® 11 Bardet - Biedl Syndrome Phase 3 Update
Slide 12: Working to Change the Paradigm for the Treatment of Rare Genetic Diseases of Obesity
® 12 Working to Change the Paradigm for the Treatment of Rare Genetic Diseases of Obesity Drive COMMUNITY BUILDING and GENETIC SEQUENCING Established proof - of - concept in new indications in Phase 2 Basket Study Growth Potential Positive topline results in Bardet - Biedl syndrome Meaningful Opport
Slide 13: Setmelanotide achieved statistical significance and clinically meaningful weight loss and hunger reduction
® 13 Setmelanotide achieved statistical significance and delivered clinically meaningful weight loss and hunger reduction Phase 3 Bardet - Biedl and Alström Syndromes Trial Met Primary and All Key Secondary Endpoints Phase 3 Topline Data (n=31 a ) 34.5% b p=0.0024 ≥10% weight loss - 6.2% p<0.0001 me
Slide 14: A Closer Look at Patients with Bardet-Biedl Syndrome
® 14 A Closer Look at Patients with Bardet - Biedl Syndrome patients achieved ≥10% weight loss: • Mean actual weight loss: - 17.2 kg • Mean percentage weight loss: - 14.7% • 8 of 11 were adults 11 BBS (38.1%) a 28 BBS Patients included in primary analysis set • Mean actual weight loss: - 8.7 kg • Me
Slide 15: Setmelanotide and BMI-Z Scores for Pediatric BBS Patients in Phase 3 Trial
® 15 BMI - Z score, or BMI standard deviation score, represents the number of standard deviations from median BMI by child age and sex. Setmelanotide achieved statistically significant and clinically meaningful improvements in BMI - Z scores in pediatric patients with obesity due to POMC, PCSK1 or L
Slide 16: BMI-Z Score Explained
® 16 Chart adapted from Kleinendorst et al 2017 Data on file. Image used with permission. At 2 years of age, the patient’s BMI was 38.7 kg/m 2 BMI - Z Score or BMI standard deviation score: Number of Standard Deviations from Median BMI by Child Age and Sex
Slide 17: Reductions in BMI-Z Score in Participants with BBS Under 18
® 17 Setmelanotide was Associated with Reductions in BMI - Z Score in Participants with BBS (<18 Years Old) Over ~1 Year at Therapeutic Dose BMI, body mass index. Error bars are the standard error of the mean, which was calculated by dividing the standard deviation by the square root of n. 3.74 2.98
Slide 18: Phase 2 Basket Study Results
® 18 Phase 2 Basket Study Results
Slide 19: 2021 Highlights: Delivered on Proof of Concept in Basket Indications
® 19 2021 Highlights : Delivered on Proof of Concept in Basket Indications with Significant Market Opportunity Rhythm’s largest data readout from five genetic cohorts with 65 patients Proof of concept achieved in five MC4R pathway genes U.S. target patient population across these five genes expanded
Slide 20: Phase 2 Basket Study Evaluated Response at Three Months of Therapy
® 20 Phase 2 Basket Study Evaluated Response at Three Months of Therapy Adult starting dose 2 mg Adolescent starting dose 1 mg Adult therapeutic dose 3 mg Adolescent titration dose 2 mg Open - label dose - titration 4 weeks Final visit or bridge to extension study Screening 2 - 8 weeks 10 weeks Open
Slide 21: HETs Patient Demographics – Full Analysis Set
® 21 HETs Patient Demographics – Full Analysis Set Baseline Characteristics HETs patients (N=35) Mean age (years) at enrollment (SD) Range 39 (18) 15, 68 Female Male 68.6% 31.4% Mean weight lbs (SD) Range lbs 315.9 (65.7) 210, 459 Mean weight kg (SD) Range kg 143.3 (29.8) 95, 208 BMI Mean kg/m 2 (SD
Slide 22: Response Rate and Weight Loss at Month 3 (Overall) HETs
® 22 Response Rate and Weight Loss at Month 3 (Overall) POMC/PCSK1/LEPR Heterozygous Deficiency Obesity 34.3% of patients (12/35) achieved the primary endpoint of ≥5% weight loss from baseline at Month 3* Baseline Month 3 Percent change from baseline Mean (SD) body weight: Overall (n=35) 143.3 kg (2
Slide 23: Response Rate and Weight Loss at Month 3 (Responder/Nonresponder) HETs
® 23 -16 -12 -8 -4 0 4 Responders (n=12) Non-responders (n=23) Response Rate and Weight Loss at Month 3 (Responder/ Nonresponder ) POMC/PCSK1/LEPR Heterozygous Deficiency Obesity Mean Weight change, % Responders (n=12) Nonresponders (n=23) Data as of Dec. 17, 2020; Error bars represent the 90% confi
Slide 24: Percent Weight Loss Over Time HETs
® 24 Percent Weight Loss Over Time POMC/PCSK1/LEPR Heterozygous Deficiency Obesity -16 -12 -8 -4 0 4 2 3 4 5 6 Mean weight change, % Visit Data as of Dec. 17, 2020; Error bars represent the 90% confidence interval. Responders Nonresponders
Slide 25: Change in Most Hunger Score at Month 3 and Over Time
® 25 Change in Most Hunger Score at Month 3 and Over Time POMC/PCSK1/LEPR Heterozygous Deficiency Obesity Data as of Dec. 17, 2020; Responder is defined by Month 3 weight loss; CI, confidence interval; Error bars represent the 90% CI. Mean change in most hunger score at Month 3 Responders (n=12) - 4
Slide 26: Weight Loss at Month 3 by ACMG Subgroup
® 26 Weight Loss at Month 3 by ACMG Subgroup POMC/PCSK1/LEPR Heterozygous Deficiency Obesity Responders, n (%) a Nonresponders , n (%) Pathogenic/likely pathogenic (n=8) 4 (50.0) 4 (50.0) Variant of uncertain significance (n=19) 4 (21.1) 15 (78.9) N221D (n=8) 4 (50.0) 4 (50.0) Data as of Dec. 17, 20
Slide 27: SRC1 and SH2B1 Patient Demographics – Completers Set
® 27 SRC1 and SH2B1 Patient Demographics – Completers Set Baseline Characteristics SRC1 (N=13) SH2B1 (N=17) Mean age (years) at enrollment (SD) Range 32 (18) 12, 66 30 (15) 12, 60 Female Male 77% 23% 58% 41% Mean weight lbs (SD) Range lbs 258 (44) 168, 313 272 (60) 161, 357 Mean weight kg (SD) Range
Slide 28: Response Rate and Weight Loss at Month 3 (Overall) SRC1
® 28 Response Rate and Weight Loss at Month 3 (Overall) SRC1 Deficiency Obesity – Completers Set 30.8% of patients (4/13) achieved the primary endpoint of ≥5% weight loss from baseline at Month 3 Baseline Month 3 Percent change from baseline Mean (SD) body weight: Overall (n= 13) 117.1 kg (20.3) 112
Slide 29: Response Rate and Weight Loss at Month 3 (Responder/Nonresponder) SRC1
® 29 Response Rate and Weight Loss at Month 3 (Responder/ Nonresponder ) SRC1 Deficiency Obesity – Completers Set Data as of Dec. 17, 2020; Error bars represent the 90% confidence interval. -14 -12 -10 -8 -6 -4 -2 0 Responders (n=4) Non-responders (n=9) Responders (n=4) Nonresponders (n=9) - 8.4 (90
Slide 30: Response Rate and Weight Loss at Month 3 (Overall) SH2B1
® 30 Response Rate and Weight Loss at Month 3 (Overall) SH2B1 Deficiency Obesity – Completers Set 52.9% of patients (9/17) achieved the primary endpoint of ≥5% weight loss from baseline at Month 3 Baseline Month 3 Percent change from baseline Mean (SD) body weight: Overall (n=17) 123.4 kg (27.4) 118
Slide 31: Response Rate and Weight Loss at Month 3 (Responder/Nonresponder) SH2B1
® 31 Response Rate and Weight Loss at Month 3 (Responder/ Nonresponder ) SH2B1 Deficiency Obesity – C ompleters Set Data as of Dec. 17, 2020; Error bars represent the 90% confidence interval. -10 -8 -6 -4 -2 0 2 4 Responders (n=9) Non-responders (n=8) Responders (n=9) Nonresponders (n=8) - 7.1 (90%
Slide 32: Setmelanotide Generally Well-tolerated Across Development Program
® 32 Setmelanotide has been evaluated in 590 patients with obesity, with some individual patient treatment duration 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 clos
Slide 33: Safety: Hyperpigmentation, Nausea and Vomiting Events Occurred Early in Treatment
® 33 Safety: Hyperpigmentation, Nausea and Vomiting Events Occurred Early in Treatment Number of Events 342 100 35 27 12 8 2 3 4 3 7 2 0 40 80 120 160 200 240 280 320 360 1 2 3 4 5 6 7 8 9 10 11 12 Hyperpigmentation 175 22 11 13 1 3 6 1 0 0 3 2 0 20 40 60 80 100 120 140 160 180 1 2 3 4 5 6 7 8 9 10
Slide 34: Setmelanotide Achieves Proof of Concept in HETs, SRC1 and SH2B1
® 34 Setmelanotide Achieves Proof of Concept in HETs, SRC1 and SH2B1 Overall: Approximately 35% of patients responded with > 5% weight loss at 12 weeks Strong separation between responders and non - responders validates three - step approach Responders mean weight loss of 10% for HETs, 8% for SRC1 a
Slide 35: Future Clinical Plans
® 35 Future Clinical Plans
Slide 36: Targeted but Simple Approach to Treating Obesity
® 36 STEP 1 STEP 2 STEP 3 Targeted but Simple Approach to Treating Obesity Phenotype Genotype Setmelanotide response • Early - onset, severe obesity • Adults: BMI>40 • Children: <18 yrs weight >97th percentile • Genetic variants in the MC4R pathway • ACMG variant classifications • 5% weight loss in
Slide 37: Phase 3 Basket Study Designed to Evaluate Response Compared to Placebo After 24 Weeks
® 37 Phase 3 Basket Study Designed to Evaluate Response Compared to Placebo After 24 Weeks of Treatment Setmelanotide QD Dose titration to 3 mg a Placebo QD Randomized, double - blind, placebo - controlled period (24 weeks) Final visit or bridge to extension study Randomization 1:1 Week 2 Visit 8 We
Slide 38: Phase 2 MC4R Pathway Exploratory Study
® 38 Baseline - 5% BL weight - 10% BL weight Randomized to active Failure for purposes of primary endpoint Rescued with open - label treatment Randomized to placebo Enroll Open - Label Primary Endpoint Diagnostic Therapeutic Randomized 1:1 “Top of the funnel” Phase 2 MC4R Pathway Exploratory Study
Slide 39: Transformational Progress Expected in 2021
® 39 Transformational Progress Expected in 2021 1H 2021 ض Proof - of - concept data in HET patients, SRC1 and SH2B1 deficiency obesities ض Update on genetic sequencing and epidemiology data IMCIVREE commercially available in U.S. for POMC, PCSK1 and LEPR deficiency obesities Initiate Phase 2 trial i
Slide 40: Rhythm Leadership – Strong Team with Broad Biopharma Experience
® 40 David Meeker, MD Chair, President and Chief Executive Officer Hunter Smith Chief Financial Officer Yann Mazabraud Executive Vice President, Head of International Jennifer Chien Executive Vice President, Head of North America Murray Stewart, MD Chief Medical Officer Simon Kelner Chief Human Reso
Slide 41: Rhythm Pharmaceuticals
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