Slide 1: Results from a Global, Multi-Center, Phase 2b Study (RIZE) in Congenital Hyperinsulinism
Results from a Global, Multi-Center, Phase 2b Study (RIZE) in Congenital Hyperinsulinism: Characterization of a High Unmet Treatment Need and Glycemic Response to RZ358 Presenting Author: Hüseyin Demirbilek 1 ESPE 2022
Slide 2: Disclosure Statement
DISCLOSURE STATEMENT Dr. Hüseyin Demirbilek I have the following potential conflicts of interest to report: Research Contracts Consulting Employment in the Industry Stockholder of a healthcare company Owner of a healthcare company Other(s) – NONE I declare that I have no potential co
Slide 3: Congenital Hyperinsulinism (HI)
Congenital Hyperinsulinism (HI) Epidemiology • Ultra-rare disease - 1 in 25,000 to 1 in 50,000 live births Disease Characteristics • At least 16 known genetic mutations • 50% of patients with unknown genetics • Dysregulated insulin secretion from pancreatic beta cells regardless of blood sugar level
Slide 4: RZ358: Novel Mechanism for the Treatment of Hyperinsulinism
RZ358: Novel Mechanism for the Treatment of Hyperinsulinism • Humanized IgG2 monoclonal antibody • Negative Allosteric Modulator: reversibly counteracts insulin at a distinct site at the Insulin Receptor − Discovered and developed specifically for hyperinsulinism − Downstream from pancreas, not gene
Slide 5: RZ358-606 (RIZE) Phase 2b Study Design Overview
RZ358-606 (RIZE) Phase 2b Study Design Overview Assessments / Design Key Eligibility Criteria Duration Endpoints -Open-label -CHI 2-45 years old ~26 weeks -Time in Hypoglycemia by • Screening – up to 5 weeks CGM -4 sequential dose cohorts -Continued hypoglycemia on • Treatment – 8 weeks stable backg
Slide 6: RIZE Study: Demographics and Baseline Characteristics
RIZE Study: Demographics and Baseline Characteristics Cohort 1: Cohort 2: Cohort 3: Cohort 4: RZ358 Total Parameter 3 mg/kg (N=4) 6 mg/kg (N=8) 9 mg/kg (N=8) 3-9 mg/g (N=3) (N=23) 6.7 (2-22); Age (Mean, Range) 5.8 (2-12) 9.3 (2-22) 5.8 (2-17) 4.0 (2-6) N=16 ages 2-6 Gender (n, M / F) 4/0 5/3 3/5 1/2
Slide 7: RZ358 Was Generally Safe and Well Tolerated Across Doses
RZ358 Was Generally Safe and Well Tolerated Across Doses • No adverse drug reactions, AEs leading to study discontinuation, or dose-limiting toxicities • 15 subjects experienced a total of 43 treatment-emergent AEs − No dose-response − Generally mild and unrelated to study drug • Three patients expe
Slide 8: Study Pharmacokinetics: Dose-Dependent and Predictable Drug Concentrations
RIZE Study Pharmcokinetics: Dose-Dependent and Predictable Drug Concentrations RIZE Study Concentration-Time Profile (Bi-Weekly Dosing) 400 Plasma RZ358 (μg/ml) 300 C1 (3 mg/kg) C2 (6 mg/kg) 200 C3 (9 mg/kg) C4 (Titrate 3 to 9 mg/kg) 100 0 15 22 29 36 43 50 57 64 71 78 85 92 109 1 8 100 117 124 121
Slide 9: RIZE Study: Significant Dose-Dependent Improvements in Hypoglycemia Events and Time
RIZE Study: Significant Dose-Dependent Improvements in Hypoglycemia Events (BGM) and Time (CGM) RZ358 RZ358 RZ358 RZ358 Titrate RZ358 Mean (Range) 3 mg/kg 6 mg/kg 9 mg/kg (3-9 mg/kg) Total Pooled (n=4) # (n=8) (n=7) ^ (n=3) (n=22) Time in Hypoglycemia (<70 mg/dL) by CGM (%) Baseline 16.1 22.2 26.5 2
Slide 10: RIZE Study: High Patient Response Rate at Clinically-Relevant Correction Thresholds
RIZE Study: High Patient Response Rate at Clinically-Relevant Correction Thresholds RZ358 RZ358 RZ358 RZ358 Titrate RZ358 Total Responders N (%) 3 mg/kg (n=4) # 6 mg/kg (n=8) 9 mg/kg (n=7) ^ 3-9 mg/kg (n=3) (n=22) ≥25% Correction of Hypoglycemia Severe (<50 mg/dL) 3 (75%) 7 (88%) 7 (100%) 2 (67%) 19
Slide 11: RIZE Study: Potential for RZ358 to be an Effective Monotherapy Treatment
RIZE Study: Potential for RZ358 to be an Effective Monotherapy Treatment CGM Range 2 Year Old Patient on Somatostatin Analog ~40% Time Hypoglycemia + RZ358 100 No Time > 180 mg/dL (6 mg/kg) 80 60 + 46% TIR % Time 40 20 - 90% TBR 0 Baseline End of Treatment Time Above Range Baseline CGM period (≥ 10
Slide 12: RIZE Study Summary of Outcomes
RIZE Study Summary of Outcomes • Study was conducted primarily in a young pediatric population: average ~6.5 years of age − Diverse group of patients in the study across gender and genetics − Add-on to SOC therapies • RIZE again showed that SOC therapies are suboptimal for some CHI patients • Patien
Slide 13: Acknowledgements
Acknowledgements: - Patients & families who participated in RIZE - Fellow investigators & authors - Patient advocacy organizations whose work to support families, raise awareness and empower research that is foundational to finding better therapies and outcomes for those living with CHI. 13