Slide 1: Transforming Patient Outcomes with Superior Vision Gains Virtual KOL Event
Transforming Patient Outcomes with Superior Vision Gains Virtual KOL Event | April 3, 2024 NASDAQ (OPT); ASX (OPT.AX) Exhibit 99.1
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 April 3, 2024 (unless otherwise stated herei
Slide 3: Featured Speakers
Featured Speakers Opthea Management Joined by Clinical and Scientific Thought Leaders Fred Guerard PharmD, MS Arshad M. Khanani MD, MA, FASRS Charles C. Wykoff MD, PhD Veeral S. Sheth MD, MBA, FASRS, FACS Chief Executive Officer Chief Medical Advisor Chief Investigator for COAST Clinical Advisory Bo
Slide 4: Sozinibercept Has the Potential to Be the First Product in More Than 15 Years to Improve Visual Outcomes
First-in-class VEGF-C/D TRAP intended for combination with standard of care anti-VEGF-A therapies Composition of Matter and Methods of Use Patents through 2034; opportunities to extend beyond 2034* Sozinibercept Has the Potential to Be the First Product in More Than 15 Years to Improve Visual Outcom
Slide 5: KOL Event Agenda
Topic Speaker Welcome Fred Guerard, PharmD, MS Wet AMD Unmet Medical Needs and Sozinibercept Market Opportunity Arshad M. Khanani, MD, MA, FASRS Sozinibercept Phase 2b Wet AMD Data Overview Charles C. Wykoff, MD, PhD Sozinibercept COAST and ShORe Phase 3 Wet AMD Trial Design Veeral S. Sheth, MD, MBA
Slide 6: Wet AMD Unmet Medical Needs & Sozinibercept Market Opportunity
Wet AMD Unmet Medical Needs & Sozinibercept Market Opportunity Arshad M. Khanani, MD, MA, FASRS
Slide 7: Current Wet AMD Treatment Landscape
Targets VEGF-A, VEGF-B, & PlGF Targets VEGF-A, & Ang-2 2022 2023 Targets all isoforms of VEGF-A 2019 Current Wet AMD Treatment Landscape Targets VEGF-A, VEGF-B, & PlGF Targets all isoforms of VEGF-A Targets isoform-specific VEGF-A165 inhibition Improved Efficacy 2004 2006 2011 off-label FDA APPROVAL
Slide 8: Majority of Patients Achieve Suboptimal Vision Outcomes with Standard of Care Anti-VEGF-A
do not achieve significant vision gains 25% Despite Treatment with Standard of Care Anti-VEGF-A Therapies, the Majority of Patients Achieve Suboptimal Vision Outcomes *Based on randomised, controlled clinical trial data; >45% fail to achieve ≥ 2 lines improvement in Best Corrected Visual Acuity (BCV
Slide 9: Unmet Needs in the Treatment of Wet AMD
Unmet Needs in the Treatment of Wet AMD *Proportion averaged over Weeks 40, 44, and 48; †proportion at Week 48. BCVA, best-corrected visual acuity; ETDRS, Early Treatment Diabetic Retinopathy Study; nAMD, neovascular age-related macular degeneration; PRN, pro re nata (as needed); VEGF, vascular endo
Slide 10: Greater Durability and Improved Vision Are the Greatest Unmet Needs
Greater Durability and Improved Vision Are the Greatest Unmet Needs ASRS PAT SURVEY 2023 AMD, age-related macular degeneration; ASRS, American Society of Retinal Specialists; DME, diabetic macular edema; Intl, international; PAT, Preferences and Trends; US, United States of America; VEGF, vascular e
Slide 11: Visual Outcomes Are the #1 Factor in Patients' Anti-VEGF-A Preference
Visual Outcomes Are the #1 Factor in Patients’ Anti-VEGF-A Preference Bhagat D, Kirby B, Bhatt H, Jager R, George M, Sheth V. Patient Preferences Associated with Anti-Vascular Endothelial Growth Factor Therapies for Neovascular Age-Related Macular Degeneration and Diabetic Macular Edema. Clin Ophtha
Slide 12: Emerging Treatments for Wet AMD: Better Vision Outcomes or Durability
Better Durability Better Vision Outcomes Emerging Treatments for Wet AMD: Better Vision Outcomes or Durability Sozinibercept (OPT-302) Sozinibercept is the only late-stage drug in development targeting better vision outcomes OTX-TKI CLS-AX EYP-1901 RGX-314 ADVM-022 4D-150 Tyrosine Kinase Inhibitors
Slide 13: 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 The Problem The Solution Wet AMD is a multi-factorial disease. Treatment with VEGF-A inhibitors upregulates VEGF-C/D, driving angiogenesis and vascular permeability. When use
Slide 14: Published Evidence Supports Broader VEGF Pathway Inhibition with Sozinibercept
Published Evidence Supports Broader VEGF Pathway Inhibition with Sozinibercept VEGF-A and VEGF-C Induce Vascular Leakage/permeability# VEGF-A VEGF-C VEGF-C Stimulates Retinal Angiogenesis^ Circulating VEGF-C Levels Significantly Elevated in AMD Patients ⍭ Elevated VEGF-C in Aqueous Humor Following A
Slide 15: Sozinibercept Potential First Therapy in 15+ Years to Improve Visual Outcomes
Novel MOA targeting VEGF-C/D Sozinibercept Targets VEGF-A, VEGF-B, & PlGF Targets VEGF-A, & Ang-2 Targets all isoforms of VEGF-A Sozinibercept Has the Potential to Be the First Therapy in More Than 15 Years to Improve Visual Outcomes in Patients with Wet AMD Targets VEGF-A, VEGF-B, & PlGF Targets al
Slide 16: Sozinibercept Seamlessly Integrates into Current Anti-VEGF-A Clinical Practice
Sozinibercept Seamlessly Integrates into Current Anti-VEGF-A Clinical Practice Superior visual outcomes meaningfully improves patients’ lives Intended to be administered at same anti-VEGF-A visit Patients Better vision outcomes is a high unmet medical need Designed to be agnostic to anti-VEGF-A trea
Slide 17: Sozinibercept Phase 2b Wet AMD Data Overview
Sozinibercept Phase 2b Wet AMD Data Overview Charles C. Wykoff, MD, PhD
Slide 18: 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 Ranibizumab (Lucentis®); Aflibercept (Eylea®) COAST Phase 3 - wet AMD (treatment naïve) n=~990 Comparator: Aflibercept (Eylea®) once every two months after three monthly doses
Slide 19: Phase 2b Wet AMD Trial Overview
Phase 2b Wet AMD Trial Overview Treatment naïve patients with neovascular AMD Key Exclusion Criteria Subfoveal fibrosis or >25% of total lesion Haemorrhage >50% total lesion Other clinically significant ocular disease Key Inclusion Criteria Active CNV >50% lesion, classic / minimally classic / occul
Slide 20: Phase 2b Primary and Secondary Endpoints
Phase 2b Primary and Secondary Endpoints Select Pre-specified Subgroups Primary Endpoint Key Secondary Endpoints Mean change from baseline in BCVA at week 24 Proportion of patients gaining ≥15 letters from baseline at week 24 Change in central subfield thickness (CST) from baseline at week 24 Change
Slide 21: Demographic/Baseline Disease Characteristics
Demographic/Baseline Disease Characteristic 2.0 mg OPT-302 + ranibizumab n=123 Mean Age – years ± SD 76.1 ± 9.48 78.8 ± 8.16 77.8 ± 8.82 Sex – n (%) Male 48 (39.7%) 49 (40.2%) 45 (36.6%) Female 73 (60.3%) 73 (59.8%) 78 (63.4%) Caucasian Race – n (%) 117 (99.2%) 119 (99.2%) 117 (97.5%) Mean Visual Ac
Slide 22: Sozinibercept 2.0 mg Combination Demonstrated Superiority in Visual Acuity over Ranibizumab Monotherapy
Sozinibercept 2.0 mg Combination Therapy Demonstrated Superiority in Visual Acuity over Ranibizumab Monotherapy Jackson, Timothy L., et al. “A randomized controlled trial of OPT-302, a VEGF-C/D inhibitor for neovascular age-related macular degeneration.” Ophthalmology, vol. 130, no. 6, June 2023, pp
Slide 23: Wet AMD Lesion Types Differ in Responsiveness to VEGF-A Inhibitors
Wet AMD Lesion Types Differ in Vessel Location, Leakiness, and Responsiveness to VEGF-A Inhibitors LEAST RESPONSIVE to VEGF-A inhibition MODERATELY RESPONSIVE to VEGF-A inhibition HIGHLY RESPONSIVE to VEGF-A inhibition Predominantly Classic MINIMALLY CLASSIC OCCULT ~75% of Wet AMD Patients Have Occu
Slide 24: Best Responding Phase 2b Patients Represent Primary Analysis Population in Phase 3
Best Responding Phase 2b Patients Represents Primary Analysis Population in the Pivotal Phase 3 Trials to Maximize Probability of Success Sham + 0.5 mg ranibizumab (n=87) 2.0 mg OPT-302 + 0.5 mg ranibizumab (n=88) +10.3 +16.1 Δ = +5.7 p = 0.0002* Occult & Minimally Classic Lesions (RAP Absent) *Unad
Slide 25: Control Arm in Phase 2b Overperformed MARINA Trial at Week 24
Trial: Treatment: Number of Patients: 88 87 240 Baseline BCVA in Letters: 50.5 50.5 53.7 Control Arm in Phase 2b Overperformed MARINA Trial at Week 24 in in Similar Lesion Type Patient Population OPT PHASE 2B +Ran 0.5 q4w +Ran 0.5 q4w Ran 0.5 q4w OPT-302 + Ranibizumab Ranibizumab OPT PHASE 2B MARINA
Slide 26: Reduced Retinal Thickness and Better Retinal Drying With Combination Therapy
Reduced Retinal Thickness and Better Retinal Drying With Combination Therapy in Occult & Minimally Classic (RAP Absent) Patients Mean Change in CST Baseline to Week 24 Sham + 0.5 mg ranibizumab 2.0 mg OPT-302 + 0.5 mg ranibizumab % of Participants with IR Cysts at Week 24 % of Participants with SRF
Slide 27: Greater CNV and Lesion Regression With Combination Therapy
Greater CNV and Lesion Regression With Combination Therapy in Occult & Minimally Classic (RAP Absent) Patients mITT; as observed; top of bar – statistic, bottom of bar – n. CNV: Choroidal Neovascular. Mean Change in Total Lesion Area at Week 24 Mean Change in CNV Area at Week 24 -6 -4 -2 0 81 -4.4 8
Slide 28: Superior Vision Gains in Pre-Specified PCV Subgroup
Sozinibercept Further Demonstrated Superior Vision Gains in a Pre-Specified Subgroup of PCV Lesion Patients Sham + 0.5 mg ranibizumab (n=20) 2.0 mg OPT-302 + 0.5 mg ranibizumab (n=22) Δ +6.7 p = 0.0253* 0 5 10 15 20 22 13.5 20 6.9 Mean Change in BCVA (SEM) (Letters) Polypoidal Choroidal Vasculopathy
Slide 29: Phase 2b Safety: Combination Therapy Well Tolerated
N Participants (%) Sham + ranibizumab N=121 0.5 mg OPT-302 + ranibizumab N=120 2.0 mg OPT-302 + ranibizumab N=124 Treatment emergent AEs (TEAEs) 84 (69.4%) 87 (72.5%) 93 (75.0%) Ocular AEs - Study Eye – related to study product(s)1 17 (14.0%) 17 (14.2%) 19 (15.3%) Ocular AEs - Stu
Slide 30: 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 N Participants (%) OPT-302 Any dose* N=399 (N=1,842 injections) OPT-302 2.0 mg N=263 (N=1,121 injections) Sham + anti-VEGF-A control N=170 (N=854 injections) Ocular TEAEs - St
Slide 31: Very Low Intraocular Inflammation Observed Across Completed OPT-302 Trials
N Participants (%) OPT-302 Any dose* N=399 (N=1,842 injections) OPT-302 2.0 mg N=263 (N=1,121 injections) Sham + anti-VEGF-A control N=170 (N=854 injections) Intraocular Inflammation1 7 (1.8%) 3 (1.1%) 3 (1.8%) OPT-302-1001 (Phase 1/2a wet AMD) 2 0 0 Uveitis with anterior chamber cell 1+ 1 0 0 Uveit
Slide 32: Only Drug in Development Having Demonstrated Superiority in Combination with Anti-VEGF-A
Sozinibercept Is the Only Drug in Development Having Demonstrated Superiority in Combination with Anti-VEGF-A Therapy for Wet AMD 1 Superior vision gains observed for combination therapy over Lucentis® alone Safety profile similar to standard of care observed in over 1,800 injections 2 3 Consistent
Slide 33: Sozinibercept COAST and ShORe Phase 3 Wet AMD Trial Design
Sozinibercept COAST and ShORe Phase 3 Wet AMD Trial Design Veeral S. Sheth, MD, MBA, FASRS, FACS
Slide 34: Phase 3 Clinical Program Is 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 (RAP absent), followed by total patient population Two robust pivotal trials studying sozinibercept in combi
Slide 35: Phase 3 Wet AMD Trials COAST and ShORe Are Well Advanced
Phase 3 Wet AMD Trials COAST and ShORe Are Well Advanced Complete Enrollment Anticipated in Q2 CY2024 | Topline Data Mid-CY2025 Design Multi-center, double-masked, randomized (1:1:1), sham control Treatment naïve wet AMD patients Regulatory Quality ~90% power, 5% type I error rate Sample Size ~990 p
Slide 36: Phase 3 Primary and Secondary Endpoints
Phase 3 Primary and Secondary Endpoints Primary Efficacy Endpoint at Week 52 to Support BLA Submission Primary Endpoint Key Secondary Endpoints (Baseline to Week 52) Mean change from baseline in BCVA at week 52 Proportion of participants gaining ≥15 letters Proportion of participants gaining ≥10 let
Slide 37: Phase 3 Trial Design Supports Potential Broad Label
Phase 3 Trial Design Supports Potential Broad Label for Use With Any Anti-VEGF-A Therapy Ranibizumab q4w + Sozinibercept q4w Ranibizumab q4w + Sham q4w Ranibizumab q4w + Sozinibercept q8w Primary Efficacy Endpoint Week 52 Aflibercept q8w + Sozinibercept q4w Aflibercept q8w + Sham q4w Aflibercept q8w
Slide 38: Sozinibercept Has the Potential to Transform Wet AMD Clinical Practice
1 Design supports potential broad label for combination with any anti-VEGF-A therapy and provides data on sozinibercept durability Only late-stage therapy targeting superior visual outcomes with topline data Mid-CY2025 2 3 Well powered, robust pivotal trials optimized for success with primary analys
Slide 39: Strategic Outlook
Strategic Outlook Fred Guerard, PharmD
Slide 40: Advancing Bold Therapeutic Innovations to Transform Patient Outcomes
Advancing Bold Therapeutic Innovations to Transform Patient Outcomes with Superior Vision Gains We are dedicated to advancing sozinibercept to improve patients’ visual outcomes Clinical Milestones Manufacturing Scale-up Regulatory Preparations Commercial Readiness Complete enrollment in 2nd Phase 3
Slide 41: Addressing Unmet Need in a Potential ~$14B Market
Addressing unmet medical need of improved efficacy in large wet AMD patient population in a potential ~$14B market 1 Sozinibercept Is Not Competing with Any Approved Drug Differentiated Combination Approach Targeting Better Visual Outcomes Drives Commercial Value First and only therapy to have demon
Slide 42: Sozinibercept Builds on Wet AMD Market as a Potential Combination Therapy
Branded VEGF-A Inhibitors Sozinibercept Builds on Wet AMD Market as a Potential Combination Therapy with Any VEGF-A Inhibitor Potential Addressable wAMD Market ~$9B ~$5B* Sozinibercept *potential market size assuming branded pricing ~35% of patients receive off-label AVASTIN® Global wAMD Revenues of
Slide 43: Development Program and Anticipated Milestones
PROGRAM DEVELOPMENT PHASE ANTICIPATED MILESTONES PROGRAM RESEARCH / PRECLINICAL PHASE 1 PHASE 2 PHASE 3 ANTICIPATED MILESTONES Wet Age-Related Macular Degeneration (Wet AMD) Sozinibercept For use in combination with anti-VEGF-A therapies Complete enrollment of pivotal trials: Q2 CY 2024 Topline data
Slide 44: Question & Answer Session
Question & Answer Session OOOPTHEA
Slide 45: Featured Speakers
Featured Speakers Opthea Management Joined by Clinical and Scientific Thought Leaders Fred Guerard PharmD, MS Arshad M. Khanani MD, MA, FASRS Charles C. Wykoff MD, PhD Veeral S. Sheth MD, MBA, FASRS, FACS Chief Executive Officer Chief Medical Advisor Chief Investigator for COAST Clinical Advisory Bo
Slide 46: Thank you!
Thank you! For IR and BD contacts: info@opthea.com OPTHEA.COM | @OptheaLimited FOLLOW US ON: X and LinkedIn NASDAQ (OPT) | ASX (OPT.AX)