Opthea Limited · ASX:OPT
Opthea — Investor Presentation (October 2021)
31 slides from Opthea's investor presentation, Oct 19, 2021
Slide 1: Leading Therapeutic Innovation in Retinal Diseases
Leading Therapeutic Innovation in Retinal Diseases 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: OPT-302 has the potential to revolutionize the treatment of wet AMD
First and only retina asset with strong clinical evidence of better visual outcomes over anti-VEGF-A therapy for wet AMD, with well tolerated safety profile Currently available treatment options and those in development focus only on OPT-302 has the potential to reducing burden of care, OPT-302 is d
Slide 4: Opthea's Experienced Leadership Team
Opthea’s Experienced Leadership Team Management Team Non-Executive Board Members Megan Karen Adams Jeremy Levin, DPhil, MB BChir Daniel Spiegelman, BA, MBA Baldwin, PhD VP Finance & Chairman Director, Chair Audit & Risk Committee CEO & Managing Company • Appointed Chairman in October 2020 • Appointe
Slide 5: Pipeline
Pipeline Clinical Trials & Research/ Anticipated Commercial Product Phase 1 Phase 2a Phase 2b Phase 3 Combination Agent(s) Preclinical Milestone Rights Wet Age-Related Macular Degeneration (Wet AMD) (Est. patients US and EU: 3.5 million) March 2021: Completed Phase 2b: Initiated two Ranibizumab conc
Slide 6: The Problem, The Cause, The Solution
THE PROBLEM THE CAUSE THE SOLUTION The majority of wet AMD patients Wet AMD is a multi-factorial OPT-302 has the potential to be experience an incomplete disease and driven by more the next transformative step in response to VEGF-A inhibitors than just VEGF-A the treatment of wet AMD • 45% do not ac
Slide 7: Improved Efficacy is the #1 Unmet Medical Need in Wet AMD
Improved EFFICACY is the #1 Unmet Medical Need in Wet AMD INCREASED IMPORTANCE Improved initial & sustained visions Improved Efficacy gains and/or lesion morphology Maintained or improved Excellent Safety safety/tolerability Extended Dosing intervals Less frequent dosing visits Boulanger-Scemama E,
Slide 8: OPT-302: A "Trap" Inhibitor of VEGF-C and VEGF-D
OPT-302 : A “Trap” Inhibitor of VEGF-C and VEGF-D A ‘trap' comprising the extracellular domains 1-3 of VEGFR-3 and the Fc fragment of IgG1 Potent inhibitor of VEGF-C and VEGF-D 140 kDa Comparable ocular biodistribution and similar ocular PK to Eylea OPT-302 has characteristics to ‘match’ extended do
Slide 9: 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-A inhibitor, OPT-302 completely blocks VEGFR-2 and VEGFR-3 signaling, inhibiting the most important pathways driving angiogenesis and vascular leakage VEGF-A inhibition elevates
Slide 10: Comparison with Other Trials
Comparison with Other Trials Mean visual acuity higher vs 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 All lesi
Slide 11: 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 New Mechanism inhibitor >15 years ago of Action: OPT-302 targets VEGF-C/D Off-label Most advanced us
Slide 12: Potential Total Addressable Market
Large & Growing Market Opportunity in Retinal Diseases >$24B OPT-302 to be administered OPT-302 uniquely positioned to tap into entire with any anti- VEGF-A inhibitor market VEGF-A therapy: Potential Total Addressable Market Anti-VEGF-A & $12B Off-label use DURABILITY All Retinal Diseases agnostic $
Slide 13: Strong OPT-302 Commercial Value Drivers
Strong OPT-302 Commercial Value Drivers 1 Large growing patient population 2 3 Favorable competitive High unmet need Highly differentiated asset landscape Large market opportunity • 3.5 M wet AMD patients (US & EU) • First and only VEGF-C/D ‘trap’ • No other asset with potential to disrupt treatment
Slide 14: Strong OPT-302 Stakeholder Value Drivers
Strong OPT-302 Stakeholder Value Drivers PATIENTS RETINA SPECIALISTS PAYERS • Superior gains in visual acuity over • Potential to maximise visual acuity and • Payers want better efficacy outcomes standard of care treatments meaningfully improve long-term outcomes for patients from retinal therapy im
Slide 15: Clinical Data
Clinical Data: Phase 1/2a trial in treatment naïve and prior treated wet AMD patients (n=51) Phase 2b randomized, controlled, double-masked & statistically powered wet AMD trial (n=366) Phase 1b/2a trial in prior-treated DME patients 15
Slide 16: 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 Aflibe
Slide 17: Phase 2b
Phase 2b A multicenter, randomized, double-masked, sham controlled study of intravitreal OPT-302 in combination with ranibizumab, in participants with neovascular (wet) AMD Conducted at 109 sites across 10 countries: US, EU, Israel OPT-302-1002; NCT ClinicalTrials.gov Identifier: NCT03345082 17
Slide 18: Study Overview
Study Overview Treatment naïve patients Key Inclusion Criteria with neovascular AMD 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 • Other clinic
Slide 19: Study Demographics and Baseline Characteristics
Study Demographics and Baseline Characteristics Demographic / Baseline Disease Characteristic Sham + 0.5 mg OPT-302 + 2.0 mg OPT-302 + 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 Sex – n (%) Male 48 (39.7%) 49 (40.2%) 45 (36.6%) Fem
Slide 20: Neovascular (wet) AMD Lesion Types
Neovascular (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 A majority of wet AMD
Slide 21: Best Responders: Minimally Classic & Occult
Best Responders: Minimally Classic & Occult 20 Minimally Mean change in BCVA (SEM) Classic & Occult 15 +16.1 Δ = 5.7 lesions *p = 0.0002 (letters) (RAP Absent) 10 +10.3 Achieved greatest vision benefit 5 Represents primary analysis population in OPT-302 phase 3 program 0 0 4 8 12 16 20 24 Weeks Sham
Slide 22: Polypoidal Choroidal Vasculopathy (PCV)
• PCV is highly prevalent in Asian populations (up to ~60%) • Described as the most prevalent form of wet AMD worldwide 20 Polypoidal Δ = 6.7 *p = 0.0253 Choroidal Mean change in BCVA (SEM) 15 Vasculopathy 13.5 (PCV) (letters) 10 10.9 PCV is a difficult-to-treat wet AMD 6.9 subtype, with large unmet
Slide 23: Combination Therapy: Superiority in Visual Acuity over Ranibizumab
Mean Change in Best Corrected Visual Acuity Baseline to Week 24 OPT-302 (2.0 mg) Combination Therapy: 20 Mean change in BCVA (SEM) Superiority in 15 Visual Acuity over Δ = +3.4 (p=0.0107) (letters) Ranibizumab 10 Primary endpoint achieved 5 0 0 4 8 12 16 20 24 Weeks Sham + 0.5 mg ranibizumab 0.5 mg
Slide 24: Secondary Endpoints Supportive of Visual Acuity Improvement
Secondary Endpoints Supportive of Visual Acuity Improvement Vision: More patients gained ≥ 15, ≥10 and ≥5 letters of vision Fewer patients lost vision Retinal anatomical improvements: Greater reductions in: Retinal thickness Subretinal fluid Intraretinal fluid Lesion size Neovascular a
Slide 25: Safety
Safety OPT-302 well-tolerated with very low incidence of ocular inflammation, comparable to SoC therapy N Participants (%) Sham + 0.5 mg OPT-302 + 2.0 mg OPT-302 + ranibizumab ranibizumab ranibizumab N=121 N=120 N=124 Treatment emergent AEs (TEAEs) 84 (69.4%) 87 (72.5%) 93 (75.0%) Ocular AEs - Study
Slide 26: Conclusions: OPT-302 Phase 2b wet AMD Trial
Phase 2b trial met primary endpoint OPT-302 (2.0 mg) combination therapy demonstrated superiority in visual acuity over ranibizumab + sham Conclusions Additional +5.7 letter gain observed in high responder subgroup (minimally classic & occult lesions, RAP absent, >70% study population), represen
Slide 27: Phase 3 Pivotal Trials
Phase 3 Pivotal Trials Two concurrent, randomized, controlled, 3-arm Phase 3 studies investigating OPT-302 administered every four-weeks and every- eight weeks in combination with standard of care anti-VEGF-A therapy: ShORe: Study of OPT-302 in combination with Ranibizumab (Study OPT-302-1004) COAST
Slide 28: OPT-302 Phase 3 Pivotal Program
OPT-302 Phase 3 Pivotal Program Opthea intends to submit Biologics License and Marketing Authorization Applications with the FDA and EMA, respectively, following Topline primary data analysis 2H CY 2023 completion of the Primary Efficacy Phase of the trials Efficacy Phase Safety Phase Ranibizumab (0
Slide 29: Opthea's Phase 3 Program is Optimised for Success
Opthea’s Phase 3 Program is Optimised for Success We know the patients which respond best OPT-302 positioned for use in combination with any VEGF-A inhibitor • Patients with minimally classic & occult lesions are the majority (~80%) of the wet AMD population Investigates OPT-302 standard and extende
Slide 30: OPT-302: The potential to revolutionize the treatment of wet AMD
OPT-302: The potential to revolutionize the treatment of wet AMD and improve and preserve vision 1 2 • Large treated (80%) wet AMD market (2.7M patients#) in a US$12B dollar anti-VEGF-A category Market Background • Standard of Care is anti–VEGF-A injections once per month or every two months by intr
Slide 31: Megan Baldwin, PhD CEO & Managing Director Opthea Limited
Megan Baldwin, PhD CEO & Managing Director Opthea Limited Level 4, 650 Chapel Street South Yarra 3141 Victoria Australia P: +61 9826 0399 M: +61 447 788 674 E: megan.baldwin@opthea.com 31