Opthea Limited · ASX:OPT
Opthea — Investor Presentation (September 2024)
34 slides from Opthea's investor presentation, Sep 9, 2024
Slide 1: Transforming Patient Outcomes with Superior Vision Gains
Transforming Patient Outcomes with Superior Vision Gains Corporate Overview | September 2024 NASDAQ (OPT); ASX (OPT.AX)
Slide 2: Disclaimer and Forward-looking Statements
Disclaimer and Forward-looking Statements 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”). The information contained in this presentation i
Slide 3: Sozinibercept Has the Potential to Be the First Product in 20 Years to Improve Visual Outcomes
Sozinibercept Has the Potential to Be the First Product in 20 Years to Improve Visual Outcomes Addressing High • Despite wide use of anti-VEGF-A therapy, wet AMD patients still experience loss in vision long term1 Unmet Need • Every letter of vision counts to improve quality of life and reduce morta
Slide 4: Sozinibercept Designed to Improve Visual Outcomes in Combo with VEGF-A Inhibitors
Sozinibercept Designed to Improve Visual Outcomes in Combo with VEGF-A Inhibitors; Potential to Create New Multi-Billion Dollar Class Global Marketed VEGF-A Inhibitors Sozinibercept is a VEGF-C/D “Trap” Inhibitor Potential value proposition: Targeting Improved Visual Function ~$15bn Global Market Cr
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: Despite Treatment with Standard of Care Anti-VEGF-A Therapies, Majority Achieve Suboptimal Vision
Despite Treatment with Standard of Care Anti-VEGF-A Therapies, the Majority of Patients Achieve Suboptimal Vision Outcomes Despite treatment with anti-VEGF-A therapy* The majority of patients fail to achieve 20/40 vision1 >45% do not achieve significant vision gains >60% will have persisting macular
Slide 7: Every Letter Counts When Loss of Vision Potentially Leads to Increased Mortality Risk
Every Letter Counts When Loss of Vision Potentially Leads to Increased Mortality Risk Hazard for All-cause Mortality1 Higher in People with Vision Impairment 89% Decrease of 1 ETDRS letter per year 43% increases mortality risk by 16%2 29% associated exclusively with IADL levels < 20/40 vs. ≥ 20/40 <
Slide 8: Sozinibercept Has Demonstrated Improvement in Vision Gains and Reduction in Vision Loss
Sozinibercept Has Demonstrated Improvement in Vision Gains and Reduction in Vision Loss Opportunity in Wet AMD Market for an Overall Shift Towards Superior Visual Outcomes High QoL SOZINIBERCEPT Lucentis remains the standard of care for visual improvements Visual Acuity 20/40 AVASTIN (OFF LABEL) VAB
Slide 9: 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 SOZINIBERCEPT 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, i
Slide 10: Published Evidence Supports Broader VEGF Pathway Inhibition with Sozinibercept
Published Evidence Supports Broader VEGF Pathway Inhibition with Sozinibercept Circulating VEGF-C Levels Significantly VEGF-C Stimulates RetinalAngiogenesis^ Elevated in AMD Patients ⍭ 300 Plasma concentrations (pg/ml) Control ** AMD Additive Benefit of VEGF-A and 200 VEGF-C/D Inhibition in Mouse We
Slide 11: Sozinibercept Is Designed to Integrate into Current Anti-VEGF-A Clinical Practice
Sozinibercept Is Designed to Integrate into Current Anti-VEGF-A Clinical Practice • Superior visual outcomes meaningfully improves patients’ lives Patients • Intended to be administered at same anti-VEGF-A visit Retina • Better vision outcomes is a high unmet medical need Specialists • Designed to b
Slide 12: Physicians Willing to Administer Second Injection to up to 1% of Their Patients
Physicians Willing to Administer Second Injection to up to 41% of Their Patients for Additional BCVA Improvement BCVA BCVA BCVA BCVA improvement improvement improvement improvement over 5 of 4.1 - 5 of 3.0 - 4 under 3 Average Percentage of Patients Treated 41% 32% 25% 24% with Second Injection1 What
Slide 13: 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 Topline data
Slide 14: Robust Phase 2b Trial in Wet AMD Demonstrated Superiority in Visual Outcome
Robust Phase 2b Trial in Wet AMD Demonstrated Superiority in Visual Outcome 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
Slide 15: Phase 2b Primary and Secondary Endpoints
Phase 2b Primary and Secondary Endpoints Primary Endpoint Select Pre-specified Subgroups Mean change from baseline in BCVA at week 24 Predominantly classic, minimally classic, & occult lesions (Stratification Factor) Key Secondary Endpoints Retinal Angiomatous Proliferation (RAP) Proportion of patie
Slide 16: Phase 2b Trial Demographics and Baseline Characteristics
Phase 2b Trial Demographics and Baseline Characteristics Sham + 0.5 mg sozinibercept + 2 mg sozinibercept + 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%
Slide 17: Sozinibercept Combination Therapy Demonstrated Superiority in Visual Acuity over Ranibizumab Monotherapy
Sozinibercept 2 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 +10.8 (p=0.0107) 10 5 0 0 4 8 12 16 20 24 Weeks Sham + 0.5 mg ranibizumab
Slide 18: Best Responding Phase 2b Patients Represent Primary Analysis Population in Phase 3
To Maximize Probability of Success, Best Responding Phase 2b Patients Represents Primary Analysis Population in the Pivotal Phase 3 Trials Occult & Minimally Classic Lesions (RAP Absent) BCVA (SEM) (Letters) 20 Mean change in BCVA (SEM) Phase 2b demonstrated superior efficacy of +16.1 15 +5.7 letter
Slide 19: 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 – Sozinibercept Phase 2b vs. MARINA Trial Occult and Minimally Classic Lesions 16.1 +5.7 Letter Gain Sozinibercept + ranibizumab Over Standard of Ca
Slide 20: In a Disease Where Every Letter Counts, More Sozinibercept Patients Gained Substantial Vision
In a Disease Where Every Letter Counts, a Greater Proportion of Sozinibercept Patients Gained Substantial Vision and Fewer Experienced Vision Loss Change from Baseline to Week 24 (ETDRS Letters, Individual Participants) Occult and Minimally Classic Lesions (RAP Absent) Vision Loss >30 Letter Gain 2.
Slide 21: Greater Proportion of Sozinibercept Patients Achieved Driving-level Vision (≥20/40)
Greater Proportion of Sozinibercept Patients Achieved Minimum Driving-level of Vision (≥20/40) Percentage of Participants with 20/40 Vision or Greater at Week 24 Occult and Minimally Classic, RAP Absent Total Patient Population 42% relative increase compared to ranibizumab control 18% relative incre
Slide 22: Sozinibercept Reduced the Proportion of Patients Experiencing Vision Loss by 82%
Sozinibercept Reduced the Proportion of Patients Experiencing Vision Loss by 82% Percentage of Participants with any Vision Loss ≥1 ETDRS Letter at Week 24 Occult and Minimally Classic Lesions (RAP Absent) 82% relative decrease compared to ranibizumab control 12.9% Decrease of 1 ETDRS letter per yea
Slide 23: Sozinibercept Reduced Retinal Thickness and Dried the Retina Better
Sozinibercept Reduced Retinal Thickness and Dried the Retina Better 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
Slide 24: Sozinibercept Demonstrated Greater CNV and Lesion Regression
Sozinibercept Demonstrated 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 Are
Slide 25: Sozinibercept Demonstrated Superior Vision Gains in PCV Subgroup
Sozinibercept Demonstrated Superior Vision Gains in a Pre-Specified Subgroup of Hard-To-Treat PCV Lesion Patients 20 PCV Lesions Polypoidal Choroidal Vasculopathy (PCV) is a Mean Change in BCVA(SEM) (Letters) Δ +6.7 difficult-to-treat wet AMD subtype; it is often p = 0.0253* described as the most pr
Slide 26: Pooled Safety for Completed Sozinibercept Trials
Pooled Safety for Completed Sozinibercept Trials Combination Therapy Well Tolerated and Comparable to Standard of Care Monotherapy Sozinibercept Sozinibercept Sham + anti-VEGF-A Any dose* 2 mg control N Participants (%) N=399 N=263 N=170 (N=1,842 injections) (N=1,121 injections) (N=854 injections) O
Slide 27: Intraocular Inflammation Observed Across Completed Trials Similar to Standard of Care
Intraocular Inflammation Observed in Combination Therapy Across Completed Sozinibercept Trials Similar to Standard of Care Sozinibercept Sozinibercept Sham + anti-VEGF-A Any dose* 2 mg control N Participants (%) N=399 N=263 N=170 (N=1,842 injections) (N=1,121 injections) (N=854 injections) Intraocul
Slide 28: Phase 3 Clinical Program Is Informed by Phase 2b Results and Optimized for Success
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 (RAP absent), followed by total patient population Two robust pivotal trials studying sozinibercept in combi
Slide 29: Phase 3 Wet AMD Trials COAST and ShORe Are Well Advanced
Phase 3 Wet AMD Trials COAST and ShORe Are Well Advanced Topline Data Anticipated for COAST in Early 2Q CY 2025 and ShORe in Mid-CY2025 • Multi-center, double-masked, randomized (1:1:1), sham control Design • Treatment naïve wet AMD patients Sample Size • COAST n=998; ShORe n=986 Comparators • 2 mg
Slide 30: Phase 3 Primary and Secondary Endpoints
Phase 3 Primary and Secondary Endpoints Primary Efficacy Endpoint at Week 52 to Support BLA Submission Primary Endpoint Mean change from baseline in BCVA at week 52 Key Secondary Endpoints (Baseline to Week 52) Proportion of participants gaining ≥15 letters Proportion of participants gaining ≥10 let
Slide 31: Phase 3 Trial Design Supports Potential Broad Label for Use With Any Anti-VEGF-A Therapy
Phase 3 Trial Design Supports Potential Broad Label for Use With Any Anti-VEGF-A Therapy Topline Data Efficacy Phase Anticipated in Loading Doses (12w) Maintenance Dosing (40w) Early 2Q CY2025 Aflibercept + Sozinibercept q4w Aflibercept q8w + Sozinibercept q4w Aflibercept + Primary Efficacy Safety F
Slide 32: Next Steps
Advancing Therapeutic Innovations to Transform Patient Outcomes with Superior Vision Gains We are dedicated to advancing sozinibercept to improve patients’ visual outcomes • Phase 3 program enrolled 1,984 patients across COAST and ShORe Clinical Milestones • Topline data anticipated for COAST in ear
Slide 33: Recent Financings Anticipated to Provide Cash Runway Through Both Pivotal Topline Data Readouts
Recent Financings Anticipated to Provide Cash Runway Through Both Pivotal Topline Data Readouts Financial Overview Development Funding Agreement (DFA) Ticker OPT (ASX/NASDAQ) • Total funding drawn under DFA: US$170M • Provides non-dilutive funding for development of Ordinary Shares: 1,231.1M sozinib
Slide 34: Sozinibercept Will Not Compete Head-to-Head with Anti-VEGF-A
Sozinibercept Will Not Compete Head-to-Head with Anti-VEGF-A Differentiated Combination Approach Targeting Better Visual Outcomes Drives Commercial Value Addressing unmet medical need of improved efficacy in large wet AMD 1 patient population in a potential ~$15B market First and only therapy to hav