Slide 1: Body Mass Index and Weight Reductions in Patients With Obesity Due to Heterozygous Variants
Body Mass Index and Weight Reductions in Patients With Obesity Due to Heterozygous Variants in POMC, PCSK1, or LEPR After 1 Year of Setmelanotide Sadaf Farooqi, PhD 1; Jennifer Miller, MS, MD 2; Christopher Still, DO, FACP 3; Cecilia Scimia, MD, PhD4; Olga Ohayan, RN, BA, MSc 4; Guojun Yuan, PhD 4;
Slide 2: The MC4R Pathway Regulates Energy Balance
The MC4R Pathway Regulates Energy Normal signaling in the MC4R pathway1 Balance1 Hypothalamus Upstream Downstream AgRP Heterozygous variants in key genes upstream of MC4R neuron (POMC, LEPR, PCSK1) may impair signaling in the MC4R LEPR AgRP pathway2 leading to early-onset, severe obesity3 LEP PCSK1
Slide 3: Phase 2 Trial for Long-Term Extension of Setmelanotide
Phase 2 Trial (NCT03651765) for Long-Term Extension of Setmelanotide for Patients Who Have Completed a Trial of Setmelanotide Index Trial (NCT03013543) Long-term Extension (NCT03651765) Open-label treatment Open-label treatment At week 12: • Clinical benefit per investigator Screening QD setmelanoti
Slide 4: Disposition and Baseline Demographics
Disposition and Baseline Demographics Enrolled in index trial Index trial baseline Total N=35 characteristics (N=35) Age, years Mean (SD) 39.46 (14.64) Range 15-68 Sex, n (%) Discontinued (n=13) • AE (n=5) Female 11 (31.4) • Voluntary withdrawal (n=5) Male 24 (68.6) • Lost to follow-up (n=2) Race, n
Slide 5: Setmelanotide Treatment Was Associated With BMI Reduction
Setmelanotide Treatment Was Associated With BMI Reduction in Patients With Heterozygous Variants in POMC, PCSK1, or LEPR −8.7% mean change in BMI after 12 months of treatment % change at % change at % change at Index baseline Month 6 Month 9 Month 12 (N=35) (n=16) (n=17) (n=17) 50.4 kg/m2 −7.9 −9.0
Slide 6: Setmelanotide Treatment Was Associated With Reduction in Body Weight in Patients ≥18
Setmelanotide Treatment Was Associated With Reduction in Body Weight in Patients ≥18 Years Old After 12 Months of Treatment After 12 months: −10.2% mean change in body weight in patients ≥18 years olda 53.3% achieved ≥10% loss in body weight % change at % change at % change at Index baseline Month 6
Slide 7: Setmelanotide Treatment Was Generally Well Tolerated
Setmelanotide Treatment Was Generally Well Tolerated in Patients With Heterozygous Variants in POMC, PCSK1, or LEPR Treatment-emergent AEs n (%) Treatment-emergent AEs occurring in n (%) Treatment related 34 (97.1) ≥20% of patientsa Skin hyperpigmentation 20 (57.1) Serious 3 (8.6) Fatigue 14 (40) Se
Slide 8: Summary and Conclusions
Summary and Conclusions • In patients with obesity due to heterozygous variants in POMC, PCSK1, or LEPR, setmelanotide treatment was associated with reduced BMI and weight loss • Setmelanotide demonstrated continued efficacy for up to 12 months of treatment • Setmelanotide was generally well tolerat