Opthea Limited · ASX:OPT
Opthea — Investor Presentation (May 2023)
25 slides from Opthea's investor presentation, May 2023
Slide 1: Leading Therapeutic Innovation in Retinal Diseases
Leading Therapeutic Innovation in Retinal Diseases May 2023 Megan Baldwin, Chief Executive Officer Timothy Morris, Chief Financial Officer OPTHEA.COM | @OptheaLimited | 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”). The information contained in this presentation is in summary form and does not
Slide 3: Opthea Limited
Opthea Limited Developing OPT-302, VEGF-C/D “trap” inhibitor for wet AMD Company Financial Highlights • 1984: Founded; 1985: ASX listed • Project funding agreement with • 2007: acquired VEGF-C/D, VEGFR-3 IP portfolio (Uni.Helsinki, LICR Melb) Carlyle/Abingworth for up to $170M • 2014: Ophthalmology
Slide 4: Wet AMD & DME Are the Leading Causes of Vision Loss in the Elderly and Diabetics
Wet AMD & DME Are the Leading Causes of Vision Loss in the Elderly and Diabetics Diabetic Macular Increasing prevalence- Edema (DME) large & growing market opportunity A complication of diabetes that manifests as inflammation, edema, and hard exudates in the macula and leads to loss of VA Epidemiolo
Slide 5: OPT-302 Combination Therapy Achieves Broad Blockade of the Validated Pathway in Wet AMD
OPT-302 Combination Therapy Achieves Broad Blockade of the Validated Pathway in Wet AMD Used in combination with any VEGF-C VEGF-A inhibitor, OPT-302 Ranibizumab completely blocks VEGFR-2 (Lucentis®) VEGF-A VEGF-A VEGF-D OPT-302 and VEGFR-3 signaling, Brolucizumab VEGF-B VEGF-B inhibiting the most i
Slide 6: Role of VEGF-C in Wet AMD
Role of VEGF-C in Wet AMD Published Data Suggest VEGF-C May Contribute to Sub-optimal Responses to Anti-VEGF-A Therapy Elevated VEGF-C and its receptors R2 Elevated VEGF-C in aqueous humor following VEGF-C stimulates retinal angiogenesis^ and R3 in wet AMD clinical specimens ⍭ anti-VEGF-A therapy in
Slide 7: OPT-302 is the Next Transformational Step in Treatment for Retinal Diseases
OPT-302 is the Next Transformational Step in Treatment for Retinal Diseases There have been no new targeted therapies with novel mechanisms approved for wet AMD since the approval of the first VEGF-A inhibitor >15 years ago New Mechanism of Action: OPT-302 targets VEGF-C/D Off-label use Most advance
Slide 8: Large and Growing Market Opportunity in Wet AMD
Large and Growing Market Opportunity in Wet AMD OPT-302 Is Anti-VEGF-A and Durability Agnostic >$16B ~50% treated patients receive Avastin ® Potential Addressable >US$8B Off-label use Wet AMD ~50% treated patients receive Market Lucentis® or Eylea® Wet AMD Implied Total Addressable Market for OPT-30
Slide 9: A Need for New Therapies for Wet AMD
A Need for New Therapies for Wet AMD Impact of Vision Loss Phase 3 Registrational Trials Real-World Data Socio-economic impact includes: Despite regular anti-VEGF-A therapy: Patient cohort receiving anti- VEGF-A therapy (after loading • Reduced quality-of-life, • Majority of patients do not doses pr
Slide 10: OPT-302 Combination Therapy Clinical Program
OPT-302 Combination Therapy Clinical Program Now Recruiting Completed Completed Completed ShORe COAST Phase 1/2a Phase 1b/2a Phase 2b Phase 3 Phase 3 wet AMD DME wet AMD wet AMD wet AMD (n=51) (n=153) (n=366) (n=990) (n=990) Comparator Comparator Comparator Comparator Comparator Ranibizumab Afliberc
Slide 11: Phase 2b Study Overview
Phase 2b Study 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 12: Phase 2b Study Demographics and Baseline Characteristics
Phase 2b Study 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 13: OPT-302 (2.0 mg) Combination Therapy Demonstrated Superiority in Visual Acuity over Ranibizumab Monotherapy
OPT-302 (2.0 mg) Combination Therapy Demonstrated Superiority in Visual Acuity over Ranibizumab Monotherapy • Primary endpoint Mean Change in Best Corrected Visual Acuity Baseline to Week 24 achieved 20 All Comers Mean change in BCVA (SEM) 15 +14.2 Δ = +3.4 (p=0.0107) (letters) 10 +10.8 5 0 0 4 8 12
Slide 14: OPT-302 Combination Therapy Mean Visual Acuity Higher Relative to Previous VEGF-A Inhibitor Trials
OPT-302 Combination Therapy Mean Visual Acuity Higher Relative to Previous VEGF-A Inhibitor Trials Efficacy at 6 months is typically maintained or greater at 12 months in Phase 3 trials with VEGF-A inhibitors 20 OPT Phase 2b Min. classic & Occult lesions only OPT-302 + Ranibizumab OPT Phase 2b 16.1
Slide 15: Neovascular (Wet) AMD Lesion Types
Neovascular (Wet) AMD Lesion Types Differ in Vessel Location, Leakiness, and Responsiveness to VEGF-A Inhibitors PREDOMINANTLY OCCULT MINIMALLY CLASSIC CLASSIC LEAST RESPONSIVE MODERATELY RESPONSIVE HIGHLY RESPONSIVE to VEGF-A inhibition to VEGF-A inhibition to VEGF-A inhibition A majority of wet AM
Slide 16: Patients with Minimally Classic and Occult Lesions Responded Best in Phase 2b
Patients with Minimally Classic and Occult Lesions (RAP Absent) Responded Best in Phase 2b Minimally Classic and Occult • Achieved greatest vision 20 benefit Mean Change in BCVA (SEM) • Represents primary analysis +16.1 population in OPT-302 15 Δ = 5.7 Phase 3 program *p = 0.0002 (Letters) 10 +10.3
Slide 17: Higher Proportion of Patients with 20/40 Vision or Better in OPT-302 Combination Group
BCVA (Snellen Equivalent) at Week 24 (Min.Classic & Occult, RAP Absent) Higher Proportion of Patients with 20/40 Vision or Better in OPT-302 Combination Group 80 42% relative increase in % of patients with 20/40 vision at week 24 compared to ranibizumab control 60 % Participants 48.9 40 34.5 20 0 ≥7
Slide 18: Reduced Retinal Thickness and Better 'Retinal Drying' With OPT-302 Combination Therapy
Reduced Retinal Thickness and Better ‘Retinal Drying’ With OPT-302 Combination Therapy in Min.Classic & Occult, RAP Absent Patients Mean Change in CST % of Participants with % of Participants with IR Baseline to Week 24 SRF at Week 24 Cysts at Week 24 -60 40 40 85 86 Mean Change in CST (SEM) % Parti
Slide 19: Greater Reduction in Total Lesion Area in OPT-302 2.0 mg Combination Group
Total Lesion Area at Week 24 (Min.Classic Occult, RAP Absent) Greater Reduction in Total Lesion Area in OPT-302 2.0 mg Combination Group Mean Change in Total Lesion Mean Change in CNV Area Area at Week 24 at Week 24 0 0 80 81 80 81 Total Lesion Area (SEM) -2 -2 Mean Change in CNV Area (SEM) Mean Cha
Slide 20: OPT-302 Combination Therapy: Potential to Improve Vision Outcomes in Patients with PCV Lesions
OPT-302 Combination Therapy: Demonstrated potential to improve vision outcomes in patients with PCV lesions 20 Polypoidal Choroidal Vasculopathy Δ = 6.7 (PCV) is a difficult-to-treat wet AMD *p = 0.0253 subtype with a large unmet need Mean Change in BCVA (SEM) 15 In Phase 2b, OPT-302 combination the
Slide 21: OPT-302 Was Well-tolerated with Very Low Incidence of Ocular Inflammation
OPT-302 Was Well-tolerated with Very Low Incidence of Ocular Inflammation, Comparable to Standard-of-Care Therapy Sham + 0.5 mg OPT-302 + 2.0 mg OPT-302 + N Participants (%) ranibizumab ranibizumab ranibizumab n=121 n=120 n=124 Treatment emergent AEs (TEAEs) 84 (69.4%) 87 (72.5%) 93 (75.0%) Ocular A
Slide 22: OPT-302 Phase 3 Pivotal Program
OPT-302 Phase 3 Pivotal Program Topline Primary Data Analysis • Opthea intends to submit Biologics License Application (BLA) and Marketing Authorization Application (MAA) with the FDA and EMA, respectively, following completion of the primary efficacy phase of the trials Efficacy Phase Safety Phase
Slide 23: Phase 3 Clinical Program Is Informed by Phase 2b and Optimized for Success
Phase 3 Clinical Program Is Informed by Phase 2b and Optimized for Success Enrichment of patient population Maximizing commercial opportunity • Exclusion of retinal angiomatous proliferation • OPT-302 investigated in combination with (RAP) lesions two standard-of-care treatments to be positioned as
Slide 24: Summary
Summary OPT-302 for Wet AMD ü Differentiated MOA to improve efficacy • OPT-302 is a biologic VEGF-C/D “trap” Summary • First and only therapy directly targeting VEGF-C&D inhibiting angiogenic signaling through VEGFR-2 and -3 ü Strong Phase 2b Data • Superior vision gains of OPT-302 combination thera
Slide 25: Megan Baldwin, PhD CEO and Managing Director Opthea Limited
Megan Baldwin, PhD Timothy Morris CEO and Managing Director CFO Opthea Limited Opthea Limited Level 4, 650 Chapel Street 103 Carnegie Center, Suite 300 South Yarra 3141 Princeton, New Jersey, Victoria, Australia 08540 U.S.A. P: +61 9826 0399 M: +61 447 788 674 M: +1 650 400 6874 E: megan.baldwin@opt