Rhythm Pharmaceuticals, Inc. · NASDAQ:RYTM
Rhythm Pharmaceuticals — Corporate Update (March 2019)
17 slides from Rhythm Pharmaceuticals's corporate update, Mar 28, 2019
Slide 1: 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 state
Slide 2: Executive Summary
Executive Summary Stratifying MC4R pathway heterozygous (HET) patients into cohorts based on genetic variants and believed impact on pathway function Estimate >20,000 high-impact loss-of-function (LOF) HET patients in the United States Updated data shows greater, more consistent weight loss in HET p
Slide 3: Rhythm Focus: Genetic Defects in the MC4R Pathway
Upstream XXXX XXXX XXXX XXXX XXXX XXXX XXXX XXXX ALMS1 BBSx LEPR PCSK1 POMC LEPR deficiency Alström syndrome POMC deficiency Bardet-Biedl syndrome Heterozygous dysfunction MC4R pathway genes Activation MC4R MC4R Expressing Neuron Setmelanotide Rhythm Focus: Genetic Defects in the MC4R Pathway MSH Ge
Slide 4: Defining MC4R Pathway Heterozygosity
Defining MC4R Pathway Heterozygosity Wildtype Homozygote Heterozygote No genetic variant1 The same loss-of-function genetic variant present on both copies of a gene One loss-of-function genetic variant present on one copy of a gene No POMC deficiency obesity e.g. POMC deficiency obesity2 e.g. POMC h
Slide 5: Stratifying HET Patients Based on Genetic Variant: Significant Population
Stratifying HET Patients Based on Genetic Variant: Significant Population INITIAL SUBGROUP FOCUS: Well-characterized, published high-impact variants, expected to be most responsive to setmelanotide Genetic Focus: Truncations (nonsense); frame shift; splice site variants; as well as well-characterize
Slide 6: All High-Impact LOF Patients Appear Setmelanotide-Responsive
Preliminary data – March 2019 Patient Total treatment duration1 (weeks) Baseline Weight (kg/(lbs)) Weight Loss (kg/(lbs)) Weight loss Change in Hunger Score (10 pt scale) Hunger score reduction 1 37 204 (451) 18.4 (40.5) 9.0% -9 90.0% 2 29 129 (284) 22.3 (49.0) 17.3% -5 71.4% 3 4 187 (412) 7.1 (15.6
Slide 7: High-Impact LOF Patients
High-Impact LOF Patients #1 & 2 22 yr old female Starting weight = 203.8 kg Starting BMI = 79.6 Starting hunger score (worst) = 10.0 pts1 40 yr old female2 Starting weight = 128.8 kg Starting BMI = 41.6 Starting hunger score (worst) = 7.0 pts Weight Change (kg) Worst Hunger Score 1.0 Weeks 0 2 4 6 8
Slide 8: Patients in Other Subgroups Have More Variable Responses
1Two of these patients were reported in June 2018. 2 Total treatment duration including any titration period, which can last 6-12 weeks. 3These three patients were reported in June 2018. AE = adverse event Four patients discontinued treatment: One patient due to lack of efficacy at 14 weeks3 Three p
Slide 9: Safety & Tolerability Data Consistent with Prior Experience
Safety profile for all 13 HET patients: Setmelanotide continues to be well-tolerated No serious adverse events (AEs) reported No new discontinuations due to AEs since those reported in June 2018 Overall safety profile remains consistent with previous updates Safety & Tolerability Data Consistent wit
Slide 10: Meet Katy: HET Patient with Severe, Early-Onset Obesity & Hyperphagia
Meet Katy: HET Patient with Severe, Early-Onset Obesity & Hyperphagia “[My disease] causes extreme unrelenting hunger and excessive eating. As a child the fridge and food was controlled massively but nobody could understand that I was desperately hungry and just wanted to stop that feeling.” INFANCY
Slide 11: Key Imperatives for Execution of HET Development Plan
Key Imperatives for Execution of HET Development Plan Screen and classify potential new and uncharacterized variants: Computational model for assessing variants Biochemical analysis of variants in POMC, PCSK1, LEPR Rhythm estimates thousands of potential new and uncategorized HET variants in MC4R pa
Slide 12: Rhythm Expects Significant Progress in 2019 and 2020
Updated interim data for HET obesity 3Q19 Topline data from both POMC and LEPR Phase 3 studies 4Q19-1Q20 Initial NDA submission filings for setmelanotide in POMC and LEPR 2H19 Complete pivotal enrollment in BBS and Alström Phase 3 study 2019 Update on ongoing efforts to increase patient identificati
Slide 13: Conclusions
Conclusions Updated data shows promising and consistent weight loss in HET patients with high-impact LOF variants Rhythm believes there is a significant, distinct opportunity for setmelanotide in high-impact HET patients Rhythm is exploring the potential for opportunities among broader HET populatio
Slide 14: Conclusions
Conclusions Updated data shows promising and consistent weight loss in HET patients with high-impact LOF variants j Rhythm believes there is a significant, distinct opportunity for setmelanotide in high-impact HET patients | Rhythm is exploring the potential for opportunities among broader HET popul
Slide 15: Scientific Support for HET Contribution to Obesity
1Penetrance: translation of a genetic variant to an obesity/hyperphagia phenotype, or symptomatology Preclinical Data: MC4R pathway heterozygous (+/-) mice show intermediate levels of obesity versus knockout and wild-type mice Clinical and Genetic Evidence: The HET population is larger and more comp
Slide 16: Composite HET: Multiple Impairments of the MC4R Pathway
Composite HET: Multiple Impairments of the MC4R Pathway Strong genetic evidence that composite HET variants impact obesity1 Potential setmelanotide-responsive subgroup of HET obesity from among other HET genetic variants Wildtype Homozygote Heterozygote Composite Heterozygote No genetic variant The
Slide 17: Composite HET: Multiple Impairments of the MC4R Pathway
Composite HET: Multiple Impairments of the MC4R Pathway id Gaui Wildtype Homozygote Heterozygote Composite Heterozygote : _Ateast one ns-lucton gente Definition Variantineoch of two diferent goes POMC >< POMC >< POMC >< ‘POMC ii (09, MCAR-pathway composite obesity * Strong genetic evidence that comp
Rhythm Pharmaceuticals — Corporate Update (March 2019) on 6ix