Rezolute, Inc. · NASDAQ:RZLT
Rezolute — Technical Presentation (May 2020)
14 slides from Rezolute's technical presentation, May 30, 2020
Slide 1: Single Dose Studies of RZ358 in Patients with Congenital Hyperinsulinism
Single Dose Studies of RZ358 in Patients with Congenital Hyperinsulinism: Results of Population PK/PD Modeling and Simulation in Adult and Pediatric Patients Daniel Epling1, Brian Roberts2, Yongjun Hu1, Lauren Quinlan1, Kirk Johnson3, Sunny Chapel1 1 Ann Arbor Pharmacometrics Group, Ann Arbor, MI 48
Slide 2: Disclosures
Disclosures • Presenting author (BR) is an employee and stock-option holder of Rezolute, Inc.* • KJ was an employee and stockholder of Xoma, Corp** • DE, YH, and LQ are employees of A2PG (pharmacometrics consultants to Rezolute, Inc.) • SC is founding employee of A2PG and stock-option holder of Rezo
Slide 3: Congenital Hyperinsulinism (CHI): Background
Congenital Hyperinsulinism (CHI): Background Normal Insulin-Glucose Feedback Loop • Ultra-rare disease Glucose in the blood Insulin stimulates stimulates pancreas to removal of glucose from • 1 in 2,500 to 1 in 50,000 live births produce insulin the blood • Caused by one of 11 known 1 2 mutations, l
Slide 4: RZ358 Has Potential to Address Limitations of Current Standard of Care
RZ358 Has Potential to Address Limitations of Current Standard of Care Pancreas Target organs Insulin Glucose Current Standard of Care RZ358 Targeting Beta cells only Insulin receptor/signal on insulin-dependent target organs Development Not developed for CHI Tailored for CHI Impact Marginally effec
Slide 5: Unique Mechanism of RZ358 Attenuates Insulin Effects
Unique Mechanism of RZ358 Attenuates Insulin Effects Pancreas Liver, Fat, Muscle Circulation Orthosteric Site Beta Cells Target • CHI has 11 known Organ Cells distinct genetic mutations • Failure to suppress Insulin • RZ358 dampens insulin secretion results Receptor insulin signaling in hypoglycemia
Slide 6: RZ358 In-Vitro and Human Proof of Mechanism
RZ358 In-Vitro and Human Proof of Mechanism Clinical Studies X358601 and X358604 May 30, 2020 6
Slide 7: Overview of RZ358 Clinical Studies (Contributing to Pop PK-PD Model)
Overview of RZ358 Clinical Studies (Contributing to Pop PK-PD Model) Subjects Subjects Clinical Trial Study Study Design Dose Population on RZ-358 on Placebo Randomized, Double-Blind, 0.1, 0.3, 1, 3 mg/kg X358601 placebo-controlled, single 14 5 ascending dose (SAD) Phase 1 Healthy volunteer Randomiz
Slide 8: RZ358 Population Pharmacokinetics
Key RZ358 Population Pharmacokinetics CI Confidence interval CL Clearance 2-CMT Two-Compartment • POPPK was performed with Primary Estimates CV (%) 95% CI CV Coefficient of Variation NONMEM software (Ver. 7.3) Parameters (Mean ± SE) NONMEM NONlinear Mixed Effects Modeling utilizing all clinical stud
Slide 9: RZ358 Pediatric Pharmacokinetics
RZ358 Pediatric Pharmacokinetics • Allometric scaling of adult CL and V adequately described pediatric PK through use of simulation • 1000 sets of simulated pediatric PK profiles generated from the scaled base model parameters • Observed pediatric concentrations generally fall within the 90% predict
Slide 10: RZ358 Brings CHI Patients into Glucose Target Range
RZ358 Brings CHI Patients into Glucose Target Range Time in Glucose Target Range (70-180 mg/dL) by CGM* 100 Design 80 Daily % Time in Target • Single IV doses of 1 to 9 mg/kg in patients with CHI • 14 patients; ages ≥ 12 in Europe and ≥ 18 in the US 60 Percent Improvement (Median) • CHI patients by
Slide 11: Empirical Exposure Response Model Characterizes RZ358 Target Concentrations
Empirical Exposure Response Model Characterizes RZ358 Target Concentrations Key Half Maximal Effective EC50 Concentration RZ358 ER Exposure Response DOSE (IV Infusion) POPPK Population pharmacokinetics V Volume K12 Effect 1 Glucose Central Peri1 (V2) (V1) K21 Effect 2 Plasma Glucose KE Insulin Gluco
Slide 12: Summary and Conclusions
Summary and Conclusions • CHI is a devastating childhood disease with severe neurological outcomes and suboptimal therapies • RZ358, as an allosteric modulator of the insulin receptor, is ideally suited as a potential universal treatment for CHI • RZ358 was generally safe and well tolerated in clini
Slide 13: Acknowledgements
Acknowledgements • Phase 2a Study Investigators and their Teams: • Diva DeLeon (CHOP, USA) • Indi Banerjee (Royal Manchester Children’s; Manchester, UK) • Pratik Shah (GOSH; London, UK) • Klaus Mohnike (Otto Van Guericke Univ. Hosp; Magdeburg, Germany) • Study Co-Authors / Ann Arbor Pharmacometrics
Slide 14: Questions?
Questions? REZOLUTE @ May 30, 2020