Slide 1: A Late-stage Rare Disease Company Treating Hyperinsulinism
A Late - stage Rare Disease Company Treating Hyperinsulinism Corporate Presentation NASDAQ: RZLT
Slide 2: Forward Looking Statements
Forward Looking Statements | 2 This presentation, like many written and oral communications presented by Rezolute and our authorized officers, may contain certain forward - looking statements regarding our prospective performance and strategies within the meaning of Section 27 A of the Securities Ac
Slide 3: A Rare Disease Company Treating Hyperinsulinism
Seasoned management team with demonstrated success from early development through commercialization Total $1B+ global market opportunity with additional upside with market expansion Compelling real - world evidence of patient benefit under the Company’s Expanded Access Program Two rare disease Phase
Slide 4: Two Phase 3 Indications Targeting Hyperinsulinism
Milestone Expected Next Milestone Phase 3 Phase 2 Phase 1 IND - Enabling Target Program December 2025 Topline data Congenital Hyperinsulinism RZ358 (e rsodetug ) 2H 2026 Topline data Tumor Hyperinsulinism RZ358 (e rsodetug ) Two Phase 3 Indications Targeting Hyperinsulinism | 4
Slide 5: RZ358 Treatment for Hyperinsulinism (HI): Ersodetug
RZ358 Treatment for Hyperinsulinism (HI) E rsodetug
Slide 6: Hypoglycemia as a Result of HI
Rare disease caused by tumors that produce insulin or insulin - like substances such as IGF - 2 Rare pediatric genetic disease characterized by excessive insulin production Hypoglycemia as a Result of HI c ongenital HI t umor HI Ersodetug has shown substantial benefit in studies and real - world use
Slide 7: Antibody Designed to Treat All Forms of HI
| 7 o Fully human monoclonal antibody with a novel mechanism acting downstream from production source (e.g. pancreas) o Allosterically binds to the insulin receptor to counteract excess signaling by insulin or related hormones (e.g. IGF) o Modulating effect helps maintain glucose values in a healthy
Slide 8: Congenital HI
Congenital HI Congenital HI
Slide 9: Disease Background
o 1 in 28,000 live births in the US 1 , translating to approximately 130 new patients per year o Often presents within first month of life o Most common cause of persistent hypoglycemia in infants and children o Requires constant monitoring as serious hypoglycemic lows are often missed o Risk of com
Slide 10: Current Treatment Options and Unmet Need
o Diazoxide (DZ) is first line treatment and the only approved medication for hypoglycemia caused by HI • 60% of patients do not respond to DZ • May experience frequent and serious adverse reactions including volume overload, heart failure, and pulmonary hypertension • Patients report 1 intolerable
Slide 11: Therapies in Development
Therapies in Development 11 Clinical Barriers HI Indication Dosing Stage Mechanism Asset N/A Congenital, Tumor, PBH 2 IV 1 , once monthly Phase 3 Insulin receptor allosteric modulator Ersodetug • Utility in chronic use unproven; likely need to combine with other therapies Congenital Continuous Infus
Slide 12: sunRIZE Phase 3 Study Overview
o Global, multi - center, double - blind, randomized, controlled, safety and efficacy registrational study o Patient population (n=56) • Ages 3 months + who do not have adequate glycemic control with standard of care medical management o Primary endpoint: change in average hypoglycemia events per we
Slide 13: sunRIZE: Patient Demographics
o Inclusion criteria • Age: ≥3m - 45y • Patients on SOC medications* and/or nutritional supplementation: • ≥2 months of stable treatment • OR had previously discontinued SOC medication due to adverse effects and/or failure to respond • Persistent hypoglycemia o Baseline characteristics (n=63) • 3.4y
Slide 14: Phase 2b RIZE Study Results
o 23 participants • Average age ~6.5 ( 16 participants were between 2 - 6 years of age) • Diverse group across gender and genetics o ~20 % average daily time in hypoglycemia and 13 hypoglycemia events per week at baseline • Participants were on standard of care o Predictable and dose - dependent pha
Slide 15: Substantial Improvement in All Hypoglycemia Metrics
Baseline End of Treatment 0 5 10 15 Time by CGM [N=15 ∧ ] % T i m e ( M e d i a n ) -61% p < 0.0005 Baseline End of Treatment 0 5 10 15 Event Rate by BGM (N=15 ∧ ) E v e n t s P e r W e e k ( M e d i a n ) p < 0.0005 - 74% Hypoglycemia (<70 mg/dL) Severe Hypoglycemia (<50 mg/dL) Baseline End of Trea
Slide 16: Compelling Patient Responses
| 16 2 - Year - Old on SSA 6 - Year - Old; Failed meds, pancreatectomy Average Daily Time in Hypoglycemia ~40% Average Daily Time in Hypoglycemia ~45% Baseline CGM period (≥10 days) Treatment Evaluable CGM (2 - weeks) RZ358 9 mg/kg RZ358 6 mg/kg On Treatment On Treatment SSA: Somatostatin Analog. CG
Slide 17: Addressable U.S. Market Driven by Both Diazoxide-Responsive and Unresponsive Patients
| 17 Side Effects w/ DZ DZ Tolerated Surgery for Focal Disease Current SoC: Pancreatectomy Responsive to Diazoxide Unresponsive to Diazoxide ~130 cHI Patients Diagnosed in US per Year 1 ~20 pts/yr Addressable population of ~1,500 (up to 15 years of therapy) Source: 1) The birth prevalence of congeni
Slide 18: Tumor HI
REZOLUTE ©} Tumor HI
Slide 19: Disease Background
o Hypoglycemia caused by two distinct tumor types: • Islet Cell Tumors (ICT) • Excessive secretion of insulin • Malignant insulinomas are the most common ICTs that cause hypoglycemia • Non - Islet Cell Tumors (NICT) • Produce and secrete insulin - like substances such as IGF - 2 that over - activ
Slide 20: Treatment Options and Unmet Need
o Tumor - directed therapies do not directly treat hypoglycemia • Adequate hypoglycemia management is required prior to initiation of tumor - targeted therapies o Therapies to treat malignant insulinoma are often ineffective or poorly tolerated • Diazoxide (DZ) is the only approved treatment • Subop
Slide 21: Real-world Patient Benefit in Expanded Access Program of Ersodetug
o Multiple ICT patients with severe refractory hypoglycemia • H ospitalized and in life - threatening or hospice - bound condition • Required continuous high volume/concentration intravenous dextrose or nutritional infusion • T umor - directed therapies (e.g., embolization, radiotherapy, chemotherap
Slide 22: Phase 3 Single-arm Study Overview (ICT and NICT)
o Global, multi - center, single - arm, open - label registrational study o Patient population (n=~16) • Adult ICT and NICT patients with HI who have not achieved adequate hypoglycemia control with SOC therapies o Primary endpoint: number of participants achieving ≥50% reduction from baseline IV glu
Slide 23: Phase 3 Randomized Study Overview
Phase 3 Study Overview o Multi - center, double - blind, randomized, controlled, safety and efficacy registrational study o Patient population (n= up to 48) • Adult ICT and NICT patients with HI who have not achieved adequate hypoglycemia control with SOC therapies • 24 participants in double - blin
Slide 24: Immediately Addressable U.S. ICT Market
Immediately Addressable U.S. ICT Market | 24 ~25 % 5 - Year Prevalence ~1,500 2 patients >500 Immediately Addressable Patients with Severe/Refractory Hypoglycemia Malignant Insulinoma Hypoglycemia (Hypo) Diagnosis and Treatment Pathway 1 ICT: islet cell tumor. Source: 1) Based on analysis of seven y
Slide 25: Immediately Addressable U.S. NICT Market
Immediately Addressable U.S. NICT Market | 25 ~40 % 5 - Year Prevalence ~4,000 2 patients >1,000 Immediately Addressable Patients with Severe/Refractory Hypoglycemia No Medical Management ~4 0% Further surgery or other de - bulking Two or More HI Treatments Require Medical Management ~20 % Refractor
Slide 26: Commercial Opportunity
o Potential to Address Two Rare Disease Markets • ~1,500 addressable cHI patients in US; equivalent patient population in Europe • >500 islet cell tumor patients and >1,000 n on - islet c ell tumor patients addressable in the US o Highly Concentrated Physician Base for cHI • 60% of patients are diag
Slide 27: A Rare Disease Company Treating Hyperinsulinism
Total $1B+ global market opportunity with additional upside with market expansion Compelling real - world evidence of patient benefit under the Company’s Expanded Access Program RZ358 ( ersodetug ) is an antibody designed to treat hypoglycemia caused by all forms of HI Mission - driven to improve ou
Slide 28: Rezolute
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