Slide 1: Transforming Patient Outcomes with Superior Vision Gains
Transforming Patient Outcomes with Superior Vision Gains Corporate Presentation | March 2024 NASDAQ (OPT); ASX (OPT.AX)
Slide 2: Disclaimer
Disclaimer This presentation includes general background information about the activities of Opthea Limited (ABN 32 006 340 567) (“Opthea” or “Company”) and its affiliates and subsidiaries (together, the “Opthea Group”). This presentation is current as at March 4,2024 (unless otherwise stated herein
Slide 3: Opthea: Transforming Patient Outcomes with Superior Vision Gains
Opthea: Transforming Patient Outcomes with Superior Vision Gains Our Vision Our Mission Advancing bold therapeutic Dedicated to improving and innovation and inspiring protecting vision in people transformation in the global with retinal diseases. retinal community. 3
Slide 4: Investment Highlights
Investment Highlights Potential to be the first product in more than 15 years to improve vision loss Addressing High • Wet age-related macular degeneration (wet AMD) is the leading cause of vision loss in the elderly, Unmet Need impacting ~3.5 million patients in the US and Europe, despite wide use
Slide 5: Experienced Leadership Team
Experienced Leadership Team Expertise and Track Record to Make a Positive Impact on the Retinal Community Management Team Chief Medical Advisor Arshad M. Khanani, MD, MA, FASRS Fred Guerard, PharmD, MS Managing Partner, Director of Clinical Research and Director of Fellowship at Sierra Eye Chief Exe
Slide 6: Better Vision Gains is an Unmet Medical Need in Wet AMD
Better Vision Gains is an Unmet Medical Need in Wet AMD The Leading Cause of Irreversible Blindness, Impacting ~3.5M Patients in the US & EU Despite treatment with anti-VEGF-A therapy* The majority1 of patients fail to achieve >45% do not achieve significant vision gains 20/40 vision >60% will have
Slide 7: Sozinibercept, a Proprietary VEGF-C/D Trap Inhibitor
Sozinibercept, a Proprietary VEGF-C/D “Trap” Inhibitor, Has the Potential to Address the Limitations of Anti-VEGF-A Therapies Faricimab (Vabysmo®)1 The Problem The Solution Wet AMD is a multi-factorial When used in combination disease. Treatment with VEGF-A with any VEGF-A inhibitor, inhibitors upre
Slide 8: Published Evidence Supports Broader VEGF Pathway Inhibition with Sozinibercept
Published Evidence Supports Broader VEGF Pathway Inhibition with Sozinibercept Elevated VEGF-C in Aqueous Humor Following VEGF-C Stimulates RetinalAngiogenesis^ Anti-VEGF-Atherapy in Wet AMD Patients* 10 8.9 Additive Benefit of VEGF-A and Aqueous Humor VEGF-C (pg/ml) 8 6.9 66% VEGF-C/D Inhibition in
Slide 9: Improved Efficacy
Sozinibercept Has the Potential to be the First Therapy in More Than 15 Years to Improve Visual Outcomes in Patients with Wet AMD Sozinibercept has demonstrated strong clinical evidence of superior patient visual outcomes Sozinibercept 2006 2011 2022 Improved Efficacy Novel MOA off-label targeting V
Slide 10: Sozinibercept Being Developed to Tap into Entire VEGF-A Inhibitor Market
Sozinibercept is Being Developed to Tap into the Entire VEGF-A Inhibitor Market Branded VEGF-A Inhibitors Sozinibercept Biosimilar / Off-label ~$14B Branded ~$9B VEGF-A Inhibitors Biosimilars / Off-label ~$5B* Global wAMD Revenues of ~35% of patients Anti-VEGF-A Inhibitors Potential Addressable rece
Slide 11: Long-term Value Opportunities for Sozinibercept
Long-term Value Opportunities for Sozinibercept Main Patent Family Extends through 2034, with Expansion Opportunities Beyond 2034* DEVELOPMENT PHASE ANTICIPATED PROGRAM RESEARCH / MILESTONES PHASE 1 PHASE 2 PHASE 3 PRECLINICAL Wet Age-Related Macular Degeneration (Wet AMD) Sozinibercept Complete enr
Slide 12: Sozinibercept Wet AMD Clinical Summary
Sozinibercept Wet AMD Clinical Summary
Slide 13: Near-term Focus is on Sozinibercept Phase 3 Execution
Near-term Focus is on Sozinibercept Phase 3 Execution Pivotal Program Design Informed by Phase 2b and Optimized for Success Ongoing Phase 3 Trials Topline data from both trials anticipated in mid-CY 2025 Completed Phase 1-2 Trials Enrollment Complete Anticipated CY 2Q 2024 Phase 2b (n=366) COAST ShO
Slide 14: Phase 2b Trial Overview
Phase 2b Trial Overview Treatment naïve patients with neovascular AMD Key Inclusion Criteria Key Exclusion Criteria • Active CNV >50% lesion, classic • Subfoveal fibrosis or >25% of total lesion Screening / minimally classic / occult • Haemorrhage >50% total lesion • BCVA ≥ 25 and ≤ 60 letters • Oth
Slide 15: Phase 2b Trial Demographics and Baseline Characteristics
Phase 2b Trial Demographics and Baseline Characteristics Sham + 0.5 mg OPT-302 + 2.0 mg OPT-302 + Demographic/Baseline Disease Characteristic ranibizumab ranibizumab ranibizumab n=121 n=122 n=123 Mean Age – years ± SD 76.1 ± 9.48 78.8 ± 8.16 77.8 ± 8.82 Male 48 (39.7%) 49 (40.2%) 45 (36.6%) Sex – n
Slide 16: Sozinibercept 2.0 mg Combination Therapy Demonstrated Superiority
Sozinibercept 2.0 mg Combination Therapy Demonstrated Superiority in Visual Acuity over Ranibizumab Monotherapy Phase 2b Primary Endpoint Achieved Mean Change in BCVA (SEM) (Letters) 20 Total Patient Population 15 +14.2 Δ = +3.4 (p=0.0107) 10 +10.8 5 0 0 4 8 12 16 20 24 Weeks Sham + 0.5 mg ranibizum
Slide 17: Best Responding Phase 2b Patients Represent Primary Analysis Population
Best Responding Phase 2b Patients Represents Primary Analysis Population in the Pivotal Phase 3 Trials to Maximize Probability of Success Occult & Minimally Classic Lesions (RAP Absent) 20 BCVA (SEM) (Letters) Mean change in BCVA (SEM) +16.1 Phase 2b demonstrated superior efficacy of 15 +5.7 letter
Slide 18: Control Arm in Phase 2b Overperformed MARINA Trial
Control Arm in Phase 2b Overperformed MARINA Trial at Week 24 in in Similar Lesion Type Patient Population Mean Change in BCVA from Baseline at Week 24 – OPT-302 Phase 2b vs. MARINA Trial Occult and Minimally Classic Lesions 16.1 +5.7 Letter Gain OPT-302 + Ranibizumab Over Standard of Care Ranibizum
Slide 19: Wet AMD Lesion Types
Wet AMD Lesion Types Differ in Vessel Location, Leakiness, and Responsiveness to VEGF-A Inhibitors OCCULT MINIMALLY CLASSIC PREDOMINANTLY CLASSIC LEAST RESPONSIVE MODERATELY RESPONSIVE HIGHLY RESPONSIVE to VEGF-A inhibition to VEGF-A inhibition to VEGF-A inhibition ~75% of Wet AMD Patients have Occu
Slide 20: Reduced Retinal Thickness and Better Retinal Drying
Reduced Retinal Thickness and Better Retinal Drying With Combination Therapy in Occult & Minimally Classic (RAP Absent) Patients Mean Change in CST % of Participants with SRF % of Participants with IR Cysts Baseline to Week 24 at Week 24 at Week 24 -60 40 40 85 86 Mean Change in CST (SEM) (µm) -100
Slide 21: Greater CNV and Lesion Regression
Greater CNV and Lesion Regression With Combination Therapy in Occult & Minimally Classic (RAP Absent) Patients Mean Change in Total Lesion Area Mean Change in CNV Area at Week 24 at Week 24 Mean Change in Total Lesion Area (SEM) (mm2) 0 0 80 81 80 81 Mean Change in CNV Area (SEM) (mm2) -2 -2 -3.5 -3
Slide 22: Superior Vision Gains in Pre-Specified PCV Sub-group
Sozinibercept Further Demonstrated Superior Vision Gains in a Pre-Specified Sub-group of PCV Lesion Patients 20 PCV Lesions Polypoidal Choroidal Vasculopathy (PCV) is a Δ = +6.7 difficult-to-treat wet AMD subtype; it is often Mean Change in BCVA(SEM) (Letters) p = 0.0253* described as the most preva
Slide 23: Pooled Safety for Completed OPT-302 Trials
Pooled Safety for Completed OPT-302 Trials Combination Therapy Well-tolerated and Comparable to Standard of Care Monotherapy OPT-302 OPT-302 Sham + anti-VEGF-A Any dose* 2.0 mg control N Participants (%) N=399 N=263 N=169 (N=1,842 injections) (N=1,121 injections) (N=854 injections) Ocular TEAEs - St
Slide 24: Phase 3 Enrollment Expected to Complete in Q2 CY2024
Phase 3 Enrollment Expected to Complete in Q2 CY2024 Trial Highlights Potential to Use Sozinibercept in Combination With Any Anti-VEGF-A Therapy Trials in Treatment Naïve Efficacy Phase Primary efficacy endpoint to Wet AMD Patients 3x Loading Doses (12w) OPT-302 dosing every 4 and 8 weeks (40w) supp
Slide 25: Phase 3 Clinical Program Informed by Phase 2b Results
Phase 3 Clinical Program Is Informed by Phase 2b Results and Optimized for Success Hierarchical primary analysis first conducted in the high-responding occult and minimally classic population, followed by total patient population Phase 3 designed to support label for use in combination with any VEGF
Slide 26: Corporate Activities Summary and Financial Snapshot
Corporate Activities Summary and Financial Snapshot
Slide 27: Next Steps
Advancing Bold Therapeutic Innovations to Transform Patient Outcomes with Superior Vision Gains We are dedicated to advancing sozinibercept to improve and protect patients’ vision • Complete enrollment in 2nd Phase 3 trial (ShORe) in Q2 CY2024 Clinical Milestones • Mid-CY2025 topline data from both
Slide 28: Financial Snapshot & Corporate Activities
Financial Snapshot & Corporate Activities Financial Overview Development Funding Agreement (DFA) Ticker OPT (ASX/NASDAQ) • Total funding drawn under DFA: US$170M • Provides non-dilutive funding for development of 662.8M (Ordinary)/ sozinibercept Shares Outstanding1 82.9M (ADSs equivalents) • If sozi
Slide 29: Investment Highlights
Investment Highlights Potential to be the first product in more than 15 years to improve vision loss Addressing High • Wet age-related macular degeneration (wet AMD) is the leading cause of vision loss in the elderly, Unmet Need impacting ~3.5 million patients in the US and Europe, despite wide use
Slide 30: Thank you!
Thank you! Fred Guerard, PharmD, MS, CEO Peter Lang, CFO For IR and BD contacts: info@opthea.com OPTHEA.COM | @OptheaLimited FOLLOW US ON: X and LinkedIn NASDAQ (OPT) | ASX (OPT.AX) 30