Slide 1: RZ358-606 RIZE Study: Open-Label Multiple-Dose Study of RZ358 in Congenital Hyperinsulinism
RZ358-606 RIZE Study An Open-Label Multiple- Dose Study of RZ358 in Patients with Congenital Hyperinsulinism RIZE Data Call May 1, 2022 Nevan Charles Elam and Brian Roberts May 2022 1
Slide 2: Forward Looking Statements
Forward Looking Statements Statements in this presentation that are not descriptions of historical facts are forward-looking statements relating to future events, and as such all forward-looking statements are made pursuant to the Securities Litigation Reform Act of 1995. Statements may contain cert
Slide 3: Congenital Hyperinsulinism: Persistent Hypoglycemia Starves the Brain of Glucose
Congenital Hyperinsulinism: Persistent Hypoglycemia Starves the Brain of Glucose Normal Insulin-Glucose Feedback Loop • Rare: 1 in 25,000 to 50,000 live births Glucose in the blood Insulin stimulates stimulates pancreas removal of glucose • Characterized by excessive and uncontrolled to produce insu
Slide 4: RIZE Study Summary
RIZE Study Summary • 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 − Whether on SOC therapies, patients had to have substantial hypoglycemia to be enrolled • Patients enrolled had an averag
Slide 5: RZ358-606 RIZE Study: Phase 2b Topline Results
RZ358-606 RIZE Study A Phase 2b, Open-Label Multiple-Dose Study of RZ358 in Patients with Congenital Hyperinsulinism Topline Results 5
Slide 6: RZ358-606 Phase 2b (RIZE) Study Design
RZ358-606 Phase 2b (RIZE) Study Design Assessments / Design Population Duration Topline Results Endpoints Open-label, repeat- CHI ≥ 2 years old with ~26 weeks -Hypoglycemia Time by Enable registrational dose study in 4 continued hypoglycemia • Screening – up to 5 CGM Phase 3 planning and sequential
Slide 7: Study Objectives and Endpoints
Study Objectives and Endpoints • Repeat-dose safety and pharmacokinetics (PK) in children • Open-label, dose-ranging (3-9 mg/kg) to inform Phase 3 − Dose or exposure-response relationship to validate the treatment effect − Fixed dose level(s) and dose regimen that optimize treatment and benefit acro
Slide 8: Patient Disposition and Study Status
Patient Disposition and Study Status Disposition N Sites (Countries) that Enrolled 12 (10) Screened 34 Screen Failed 11 Enrolled 23 Completed Treatment and 23 Efficacy Evaluable Period Completed Study* 17 (through 3-month follow-up) Early Terminated 0 *6 of the 23 enrolled patients are still in safe
Slide 9: Patient Demographics and Baseline Characteristics
Patient Demographics and Baseline Characteristics Cohort 1: Cohort 2: Cohort 3: Cohort 4: Parameter RZ358 Total (N=23) 3 mg/kg (N=4) 6 mg/kg (N=8) 9 mg/kg (N=8) 3-9 mg/g (N=3) 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 13
Slide 10: 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 • In RZ358 treated subjects overall, 15 subjects (65%) experienced a total of 43 treatment-emergent AEs, compared to 10 subjects (43%) who experienc
Slide 11: Treatment Emergent Adverse Event Overview
Treatment Emergent Adverse Event Overview Non-TEAE RZ358 RZ358 RZ358 RZ358 RZ358 (Pre/42d Post- 3 mg/kg 6 mg/kg 9 mg/kg Titrate Total TEAE Rx) (n=23) (n=4) (n=8) (n=8) (n=3) (n=23) Subjects with Adverse Events (AEs), n (%) 10 (43%) 2 (50%) 7 (87%) 4 (50%) 2 (50%) 15 (65%) Total AEs 13 2 30# 7 4 43 S
Slide 12: Dose-Dependent and Predictable Drug Concentrations
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 1 09 1 8 100 117 124 121 138 145 142 159 6 9 Dosing
Slide 13: Topline Glycemic Results: Far Exceeded Expectations
Topline Glycemic Results: Far Exceeded Expectations • Low starting dose (3 mg/kg) was selected for safety with minimal expectations for efficacy − Notably, an improvement in hypoglycemia of ~25% was achieved • Improvements in hypoglycemia of ~75% at the mid (6 mg/kg) and top doses (9 mg/kg) and a hi
Slide 14: Expectations of ≥25% Hypoglycemia Correction Were Met and Exceeded
Expectations of ≥ 25% Hypoglycemia Correction (Time and Events) Were Met and Exceeded Across Multiple Metrics Hypoglycemia Event Rate by BGM Hypoglycemia Duration by CGM (Events Per Week <70 mg/dL) [N=21] (Percent Time <70 mg/dL) [N=22] 20 p =0.002 30 p =0.0002 25 15 (Mean ± SEM) (Mean ± SEM 20 # /
Slide 15: Highly Significant Dose-Dependent Improvements in Hypoglycemia Events and Time
Highly Significant Dose-Dependent Improvements in Hypoglycemia Events (BGM) and Time (CGM) Exceeded Study Expectations 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 (%) Ba
Slide 16: High Patient Response Rate at Clinically-Relevant Correction Thresholds
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 (86%) Overa
Slide 17: Potential for RZ358 to be an Effective Monotherapy Treatment
Potential for RZ358 to be an Effective Monotherapy Treatment 2 Year Old Patient on Somatostatin Analog CGM Range ~40% Time Hypoglycemia + RZ358 100 No Time > 180 mg/dL (6 mg/kg) 80 % Time 60 + 46% TIR 40 20 - 90% TBR 0 Baseline End of Treatment Time Above Range Baseline CGM period (≥ 10 days) Treatm
Slide 18: Summary of Results
Summary of Results • RZ358 was safe and effective in a diverse group of congenital HI patients (across age, gender, and genetics) who had continued hypoglycemia and some hyperglycemia on background SOC • Improvements in hypoglycemia of ~75% at the mid (6 mg/kg) and top doses (9 mg/kg) and a high pat