Slide 1: A Late-stage Ultra-rare Disease Company Treating Refractory Hypoglycemia
A Late-stage Ultra-rare Disease Company Treating Refractory Hypoglycemia Corporate Presentation
Slide 2: Forward Looking Statements
Forward Looking Statements 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 27A of the Securities Act and S
Slide 3: An Ultra-rare Disease Company Treating Refractory Hypoglycemia
An Ultra-rare Disease Company Treating Refractory Hypoglycemia RZ358 (ersodetug) Two late-stage Compelling Total $1B+ global Seasoned is an antibody programs evidence that market opportunity management team designed to treat evaluating ersodetug is active with additional with demonstrated refractory
Slide 4: Late-Stage Clinical Programs Targeting Hyperinsulinism
Late-Stage Clinical Programs Targeting Hyperinsulinism IND- Next Milestone Program Target Phase 1 Phase 2 Phase 3 Enabling Milestone Expected Congenital Pending FDA Ersodetug 2H 2026 Hyperinsulinism discussions Tumor Ersodetug Topline data 2H 2026 Hyperinsulinism GI-Surgery Regulatory Ersodetug Hypo
Slide 5: Ersodetug
Ersodetug Treatment for Hyperinsulinism (HI)
Slide 6: Refractory Hypoglycemia as a Result of HI
Refractory Hypoglycemia as a Result of HI Hypoglycemia o Severe, persistent, life-threatening complication of over activation of the insulin receptor o Lack of effective treatment options Congenital HI GI-Surgery Tumor HI Ultra-rare pediatric genetic Hyperinsulinism mediated by disease characterize
Slide 7: Downstream MOA at Insulin Receptor Addresses any Form of HI
Downstream MOA at Insulin Receptor Addresses any Form of HI • Fully human monoclonal antibody with GLUCOSE a novel mechanism acting downstream INSULIN or IGF-2 from production source (e.g., pancreas) • Allosterically binds to the insulin Ersodetug receptor to counteract excess signaling Increases b
Slide 8: Congenital HI
Congenital HI
Slide 9: Disease Pathophysiology, Incidence, and Clinical Features
Disease Pathophysiology, Incidence, and Clinical Features • Multiple gene causes of dysregulated insulin production and signaling • 1 in 22,000 live births in the US1, translating to approximately 165 new patients per year • Most common cause of persistent hypoglycemia in infants and children • Of
Slide 10: High Unmet Medical Need with Current Standard of Care
High Unmet Medical Need with Current Standard of Care • Diazoxide (DZ) is first line treatment and the only approved medication for hypoglycemia caused by HI • ~60% of patients do not respond to DZ • Can cause frequent and serious adverse reactions including volume overload, heart failure, and pul
Slide 11: Phase 3 sunRIZE Study Highlights
Phase 3 sunRIZE Study Highlights • Study status • Phase 3 pivotal study completed; open-label extension (OLE) ongoing • 100% roll-over to OLE and very high retention rate • Significant number of patients have stopped other therapies and remain on ersodetug as monotherapy • Efficacy (Pivotal, RCT pe
Slide 12: Preliminary PK: Therapeutic and Age-Comparable Concentrations
Preliminary PK: Therapeutic and Age-Comparable Concentrations 1000 RZ358 Serum Concentration (μg/ml) 100 RZ358_5 mg/kg_DB Ph2 (RIZE) [trough] RZ358_10 mg/kg_DB at effective doses 10 0 2 4 6 8 10 12 14 16 18 20 22 24 Study Week @2026 Rezolute, Inc. All Rights Reserved. 12
Slide 13: Decrease in Cleared Insulin Indicates Drug Activity at Insulin Receptor Target
Decrease in Cleared Insulin Indicates Drug Activity at Insulin Receptor Target, and is Comparable to Ph2 RIZE Study Circulating Insulin: Sensitive Biomarker of Drug Activity 300 Mean Insulin Concentration 250 200 (μIU/ml) 150 100 50 0 -4 -2 0 2 4 6 8 10 12 14 16 18 20 22 24 Weeks Dosing (sunRIZE) Do
Slide 14: Study Effect on Unblinded SMBG Occurred Early in Dosing: Primary Endpoint Not Met
Study Effect on Unblinded SMBG Occurred Early in Dosing: Primary Endpoint Not Met (Change in Avg Weekly Hypo Events by SMBG) 20 Percent Change From Baseline (CFB) Observed Values 0 Mean % CFB 15 -20 Hypoglycemia Events RZ358_5 mg/kg -40 RZ358_10 mg/kg (Mean ± SD) Placebo 10 -60 0 4 8 12 16 20 24 Tim
Slide 15: Secondary Endpoint: Reductions in Time in Hypoglycemia (CGM)
Secondary Endpoint: Clinically Significant Reductions in Time in Hypoglycemia (CGM) not Stat. Sig. at Wk24/EOT • Reductions of >50% compared to placebo with • Not statistically significant at SAP-specified Week nominal statistical significance at the noted timepoints 24/EOT analysis window (-32%; p=
Slide 16: Time in Hypoglycemia Reductions More Significant in Per Protocol Set
Time in Hypoglycemia Reductions (CGM) More Significant in the Per Protocol Set (PPS)* (n=41) • Reductions of ~60-80% compared to placebo with • Not statistically significant at SAP-specified Week 24/EOT nominal statistical significance at the noted timepoints analysis window (-55%; p=0.18 at 10 mg/k
Slide 17: Significant Reductions in Average Weekly Hypoglycemia Events by CGM in FAS and PPS
Significant Reductions in Average Weekly Hypoglycemia Events by CGM in FAS and PPS Populations (Pre-Specified Endpoint) Full Analysis Set (FAS) Per Protocol Set (PPS) 80 120 60 100 80 40 60 20 %CFB %CFB ~50-65% LS-Mean Reductions 40 (one or both dose levels) ~50-80% LS Mean Reductions 0 20 (one or b
Slide 18: Consistent Glycemic Improvements Across Multiple CGM Outcomes in Maintenance Phase
Consistent and Significant Glycemic Improvements Across Multiple CGM Outcomes in the Maintenance Phase of Dosing (every 4 weeks) LS-Mean (95% CI) Percent Change from Baseline; FAS Population @2026 Rezolute, Inc. All Rights Reserved. 18
Slide 19: ~1,500 Initially Addressable Pediatric Patients in U.S.
~1,500 Initially Addressable Pediatric Patients in U.S. Verified in the claims database1 • Hypoglycemia + SOC congenital HI medical therapies* 3,000 Initial market after removing ~40% DZ responsive patients 1,800 Initial market after removing ~5% patients with a 1,650 surgically curable focal lesion
Slide 20: Tumor HI
Tumor HI
Slide 21: Pathophysiology and Clinical Presentation
Pathophysiology and Clinical Presentation • Hypoglycemia caused by two distinct tumor categories: • 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 par
Slide 22: High Unmet Medical Need with Current Standard of Care
High Unmet Medical Need with Current Standard of Care • Unmet need for medical therapies to directly treat hypoglycemia over the entire course of the patient cancer journey • Therapies to treat hypoglycemia caused by malignant insulinoma are often ineffective or poorly tolerated • Diazoxide (DZ) is
Slide 23: Real-world Patient Benefit in Expanded Access Program of Ersodetug
Real-world Patient Benefit in Expanded Access Program of Ersodetug • Multiple tumor HI patients with severe refractory hypoglycemia • Hospitalized and in life-threatening or hospice-bound condition • Required continuous high volume/concentration parenteral glucose • Tumor-directed therapies (e.g
Slide 24: Ongoing Phase 3 (upLIFT) Study
Ongoing Phase 3 (upLIFT) Study • Global, multi-center, single-arm, open-label registrational study • Patient population (n=~16) • Adult ICT and NICT patients with HI who have not achieved adequate hypoglycemia control with SOC therapies • Primary endpoint: number of participants achieving ≥50% r
Slide 25: ~1500 Initially Addressable Malignant Insulinoma Patients in the U.S.
~1500 Initially Addressable Malignant Insulinoma Patients in the U.S. Malignant insulinoma patients identified in claims 3,000 (includes two or more C25.4 or E31.21+) ~40% patients refractory to surgery and medical management 1,200 including DZ Initial commercial effort: refractory patient populatio
Slide 26: ~1,500 Initially Addressable NICTH Patients in the U.S.
~1,500 Initially Addressable NICTH Patients in the U.S. Severe NICTH patients identified in claims* 6,000 (Tumor Diagnosis + Hypoglycemia + Steroids + Hospitalization) ~40% patients refractory to SOC (tumor-directed and/or steroids) and requiring hospital stays + IV glucose* 2,400 Initial commercial
Slide 27: Combined Commercial Opportunity in Congenital and Tumor HI Indications
Combined Commercial Opportunity in Congenital and Tumor HI Indications
Slide 28: Weight-based Dosing Applies to Both Indications
Weight-based Dosing Applies to Both Indications Tumor HI patients require ~3X more vials compared to congenital HI patients • Each vial is 80 mg/mL • Congenital HI maintenance dose: 10 mg/kg • Pediatric patient average weight: ~24 kg • Patients will use 3 vials per infusion • 39 vials per year per p
Slide 29: Initial Combined U.S. Market Opportunity: 4,500 Patients
Initial Combined U.S. Market Opportunity: 4,500 Patients • Congenital HI Market • Pediatric ultra-rare disease pricing • Lead indication establishes clinical effectiveness and payer access pathway for ersodetug in HI • Addressable market of ~1,500 pediatric patients • Tumor HI Market • Malignant Ins
Slide 30: An Ultra-rare Disease Company Treating Refractory Hypoglycemia
An Ultra-rare Disease Company Treating Refractory Hypoglycemia Mission-driven to RZ358 (ersodetug) Ersodetug has Total $1B+ global improve outcomes is an antibody been studied in market opportunity for individuals with designed to treat clinical trials and with additional refractory refractory used
Slide 31: Rezolutebio.com
€ Rezolutebio.com