Slide 1: Late-stage Rare Disease Company Treating Hyperinsulinism
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 27A of the Securities Act a
Slide 3: Rare Disease Company Treating Hyperinsulinism
Seasoned management team with demonstrated success from early development through commercialization Each program is a potential >$1B+ market opportunity with additional upside with market expansion Compelling real-world evidence of patient benefit under the Company’s Expanded Access Program Two rare
Slide 4: Management Team
Management Team | 4 Nevan Charles Elam Founder & Chief Executive Officer Brian Roberts Chief Medical Officer Daron Evans Chief Financial Officer Susan Stewart Chief Regulatory Officer Michael Deperro SVP, Corporate Development
Slide 5: Two Phase 3 Rare Disease Indications Targeting Hyperinsulinism
Program Target IND-Enabling Phase 1 Phase 2 Phase 3 Next Milestone Milestone Expected RZ358 (ersodetug) Congenital Hyperinsulinism (cHI) Topline data Mid-2025 RZ358 (ersodetug) Tumor Hyperinsulinism (tHI) Patient enrollment in Phase 3 study 1H 2025 Two Phase 3 Rare Disease Indications Targeting Hype
Slide 6: RZ358 Treatment for Hyperinsulinism (HI) Ersodetug
RZ358 Treatment for Hyperinsulinism (HI) Ersodetug
Slide 7: Antibody Designed to Treat All Forms of HI
GLUT4 INSULIN or IGF-2 GLUCOSE RZ358 Reduces Signaling Increases Available Blood Glucose GLUT4: glucose transporter type 4. | 7 o Ersodetug allosterically binds to the insulin receptor to modulate the signaling effect of insulin and IGF-2 to maintain glucose values in a healthy range o Novel mechani
Slide 8: 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 congenital HI (cHI) tumor HI (tHI) Ersodetug has shown substantial benefit in studies and real-world
Slide 9: Congenital HI
» | vy , REZOLUTE @} Congenital HI
Slide 10: Disease Background
o ~2000 individuals in the U.S. that would be candidates to use ersodetug • 1 in 28,000 live births in the US • 25 years of treatment required on average • ~3500 cases in the US • Often presents within first month of life o Most common cause of persistent hypoglycemia in infants and children o Sympt
Slide 11: Standard of Care for HI is Inadequate
o Diazoxide (DZ) is the current standard of care and only approved treatment for hypoglycemia caused by HI o 50% of patients do not respond to DZ o May experience frequent and serious adverse reactions • FDA black box for pulmonary hypertension o Patients report1 intolerable side effects and would w
Slide 12: Limitations of Current Treatment Options
Marginal efficacy, effects wane with repeat dosing Gastrointestinal side effects Risk of necrotizing enterocolits, particularly in newborns Potential interaction with pituitary hormones (growth and thyroid) Glucagon Current formulations short-acting Temporary measure for emergent glucose correction
Slide 13: 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 SOC o Generally safe and well-tolerated • No adverse drug r
Slide 14: Substantial Improvement in All Hypoglycemia Metrics
Baseline End of Treatment 0 5 10 15 Time by CGM [N=15∧] % Time (Median) -61% p < 0.0005 Baseline End of Treatment 0 5 10 15 Event Rate by BGM (N=15∧) Events Per Week (Median) p < 0.0005 - 74% Hypoglycemia (<70 mg/dL) Severe Hypoglycemia (<50 mg/dL) Baseline End of Treatment 0 1 2 3 4 Time by CGM [N=
Slide 15: Compelling Patient Responses
| 15 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 On Treatment RZ358 6 mg/kg On Treatment Baseline End of Treatment 0 10 20 30 4
Slide 16: Phase 3 sunRIZE Study Overview
o Multi-center, double-blind, randomized, controlled, safety and efficacy registrational study o Patient population (n=56) • Ages 3 months and above who have not achieved adequate glycemic control with standard of care medical management o Primary endpoint: change in average hypoglycemia events per
Slide 17: Immediately Addressable U.S. Market
Immediately Addressable U.S. Market | 17 Diazoxide (DZ) (up to 15 mg/kg/day) Unacceptable Side Effects Tolerated Focal Diffuse After ~5-Day DZ Use: ~30% (420 pts) ~75% (1575 pts) 40% 60% Responsive Unresponsive ~3,500 Diagnosed cHI Patients in US* ~25% (525 pts) ~70% (980 pts) Addressable population
Slide 18: Addressable Worldwide Market
o ~10K individuals in primary markets • 1 in 28,000 live births and up to 1 in 2,500 live births in certain populations due to consanguinity • In addressable patient population, disease persists for more than 25 years on average o At Launch >50% of the market is addressable • <50% of patients are ad
Slide 19: Tumor HI
Tumor HI
Slide 20: Disease Background
o ~1,500 immediately addressable individuals with severe, refractory hypoglycemia in the U.S. 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 Tum
Slide 21: 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 • Suboptima
Slide 22: Real-world Patient Benefit Under EAP
o Multiple ICT patients with severe refractory hypoglycemia • Hospitalized and in life-threatening or hospice-bound condition • Required continuous high volume/concentration intravenous dextrose or nutritional infusion • Tumor-directed therapies (e.g., embolization, radiotherapy, chemotherapy) defer
Slide 23: Phase 3 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-blind, pla
Slide 24: Immediately Addressable U.S. ICT Market
Immediately Addressable U.S. ICT Market | 24 ~300 pts ~30% ~25% ~1,5002 patients ~500 Addressable Patients with Severe/Refractory Hypoglycemia Malignant Insulinoma Hypoglycemia (Hypo) Diagnosis and Treatment Pathway1 ICT: islet cell tumor. Source: 1) Based on analysis of seven years of data from the
Slide 25: Immediately Addressable U.S. NICT Market
Immediately Addressable U.S. NICT Market | 25 ~560 pts ~45% ~25% ~4,5002 patients ~1,000 Addressable Patients with Severe/Refractory Hypoglycemia Hepatocellular Carcinoma + Hypoglycemia (Hypo) Diagnosis and Treatment Pathway1 NICT: non-islet cell tumor. Source: 1) Based on analysis of seven years of
Slide 26: Rare Disease Company Treating Hyperinsulinism
Each program has a potential >$1B+ market opportunity with upside potential Compelling real-world evidence of patient benefit under the Company’s Expanded Access Program RZ358 (ersodetug) is a fully human monoclonal antibody designed to treat hypoglycemia caused by all forms of HI Mission-driven to
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