Slide 1: Topline Results: RZ402-201 Phase 2 Study in Patients with Diabetic Macular Edema (DME)
Topline Results: RZ402 - 201 Phase 2 Study in Patients with Diabetic Macular Edema (DME) May 21, 2024
Slide 2: 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 Section 21E of the Securit
Slide 3: Introduction
Introduction
Slide 4: Kallikrein-Kinin System: an Alternative Pathway to Target DME
o KKS is a 1 st line defense against vascular injury • Promotes vascular permeability, inflammation, and coagulation o Diabetes injures retinal blood vessels • PK over - activation leads to inflammation and macular edema o Preclinical and clinical data implicate KKS as a VEGF - independent cause of
Slide 5: RZ402 Phase 2 Study Topline Results
RZ402 Phase 2 Study Topline Results
Slide 6: RZ402 Study Design Overview
RZ402 - 201 Study Design Overview | 6
Slide 7: Endpoints
o Primary • Safety, including AEs and SAEs, ocular exams, and systemic evaluations (e.g. vitals, ECG, labs) • Efficacy – Change in Central Subthreshold Thickness ( CST) from baseline compared to placebo • A recognized and objective Phase 2 anatomic marker of macular edema o Secondary • Change in bes
Slide 8: Key Eligibility Criteria
o Mild to moderate non - proliferative diabetic retinopathy with center - involved DME o No more than 3 anti - VEGF injections previously • None within 8 weeks of randomization o CST of ≥320 microns in males and ≥305 microns in females o BCVA ≤78 letters on Early Treatment Diabetic Retinopathy Study
Slide 9: Study Disposition and Populations
o 94 Participants Enrolled • 84 Completed, 10 Discontinued (5 for anti - VEGF rescue, 5 Withdrew Consent) o 12 Participants had an eligible/evaluable fellow - eye • 94 Study Eyes, 12 Fellow Eyes o Rescue and/or use of anti - VEGF was uncommon in the study eye overall Study Disposition and Population
Slide 10: Participant Demographics and Baseline Characteristics
Participant Demographics and Baseline Characteristics 50 mg (N=22) 200 mg (N=23) 400 mg (N=24) Placebo (N=24) Total (N=93) Age (Mean, Range) 61 (53 - 76) 60 (31 - 74) 62 (35 - 75) 64 (47 - 74) 62 (31 - 76) Gender (n, M / F) 12 / 10 10 / 13 15 / 9 16 / 8 53 (57%) / 40 (43%) Diabetes History (Mean Dur
Slide 11: RZ402 Was Safe and Well-Tolerated
o AEs were generally mild and rates were comparable to placebo o No adverse events of note that are associated with other PKIs • No liver enzyme abnormalities • No significant GI events o SAEs were uncommon and judged by the Investigator as not related to study drug o ECG, vitals, and safety labs un
Slide 12: Preliminary Pharmacokinetics
o Dose - dependent but not dose - proportional increases in concentrations o Expected concentrations were achieved and profile supports once daily oral dosing o Concentration which resulted in a 90% reduction in macular edema in rodent models of DME (EC90) was exceeded at all dose levels in the pres
Slide 13: Primary Endpoint Met: Clinically Significant Reduction in CST
Primary Endpoint Met: Clinically Significant Reduction in CST 0 2 4 6 8 10 12 -50 -30 -10 10 30 50 Study Week C S T C h a n g e ( μ m ± S E ) 50 mg 200 mg 400 mg Placebo -47 μm (p=0.02) -21 μm (p=0.09) -43 μm (p=0.04) | 13
Slide 14: Participant CST Responses at 200 mg RZ402 Compared to Placebo
Participant CST Responses at 200 mg RZ402 Compared to Placebo | 14 RZ402 200 mg Placebo CST Declines and Increases W o r s e n i n g % P a r t i c i p a n t s I m p r o v e m e n t 25-49 μm CST worsening ≥50 μm CST worsening 25-49 μm CST improvement ≥ 50 μm CST improvement 23% 46% 8% 22% 44% 17% Rep
Slide 15: Summary of Topline Results
o Achieved good systemic exposure and safe and well - tolerated o First PKI and oral therapy of any class to demonstrate a CST improvement in patients with DME • CST improved significantly in Study Eye at all doses compared to placebo (up to ~50 microns) • A pre - specified sub - analysis by CST sev
Slide 16: Thank You
Thank You
Slide 17: Appendix
Appendix June 28, 2024
Slide 18: Repeat-Dose Pharmacokinetics
o Dose - dependent but not dose - proportional increases in concentrations o Target concentrations achieved and profile supports once daily oral dosing o Concentration which resulted in a 90% reduction in macular edema in rodent models of DME (EC90) was exceeded at all dose levels in the present stu
Slide 19: Primary Endpoint Met: Clinically Significant Reduction in Study Eye CST
Primary Endpoint Met: Clinically Significant Reduction in Study Eye CST 0 2 4 6 8 10 12 -50 -30 -10 10 30 50 Study Week C S T C h a n g e ( μ m ± S E ) 50 mg 200 mg 400 mg Placebo -47 μm (p=0.02) -21 μm (p=0.09) -43 μm (p=0.04) | 19 o All doses achieved clinically relevant reduction in CST, the prim
Slide 20: Significant CST Improvements at All Dose Levels in Patients with Baseline CST ≥400 Microns
RZ402 Led to Significant CST Improvements at All Dose Levels in Equivalent Patients (Baseline CST ≥400 microns) 5 0 m g 2 0 0 m g 4 0 0 m g P o o l e d R Z 4 0 2 P l a c e b o -75 -50 -25 0 25 50 M e a n C S T C h a n g e ( μ m ± S E ) 50 mg Pooled RZ402 200 mg 400 mg Placebo n=11 n=10 n=10 n=31 n=9
Slide 21: Proportion of Patients Achieving a Clinically Significant CST Improvement
Proportion of Patients Achieving a Clinically Significant CST Improvement | 21 Pooled RZ402 Placebo CST Declines and Increases W o r s e n i n g % P a r t i c i p a n t s I m p r o v e m e n t 25-49 μm CST worsening ≥50 μm CST worsening 25-49 μm CST improvement ≥ 50 μm CST improvement 21% 31% 8% 22%
Slide 22: Potential for Binocular Benefit Demonstrated in Limited Evaluable Non-Study Eyes
Potential for Binocular Benefit Demonstrated in the Limited Evaluable Non - Study Eyes 5 0 m g 2 0 0 m g 4 0 0 m g P o o l e d R Z 4 0 2 P l a c e b o -250 -200 -150 -100 -50 0 M e a n C S T C h a n g e ( μ m ± S E ) 200 mg 400 mg Placebo 50 mg Pooled RZ402 n=4 n=4 n=8 n=1n=0 o Most Fellow eyes were
Slide 23: CST Declines and Trajectory Would Predict Continued Vision Improvement
CST Declines and Trajectory Would Predict Continued Vision Improvement Over a Longer Study Period 0 2 4 6 8 10 0 2 4 6 8 14 16 Study Week L e t t e r C h a n g e ( ± S E ) 50 mg 200 mg 400 mg Placebo EOT -450 -20 -16 -12 -8 -4 4 8 12 16 -100 -50 50 100 450 Improving BCVA (Letters) Improving CST (% o