Opthea Limited · ASX:OPT
Opthea — Investor Presentation (March 2021)
47 slides from Opthea's investor presentation, Mar 15, 2021
Slide 1: OPT-302: a Phase 3-ready product to improve outcomes for patients with retinal eye diseases
OPT-302: a Phase 3-ready product to improve outcomes for patients with retinal eye diseases Corporate Presentation, March 2021 Megan Baldwin PhD, CEO & Managing Director
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 (OPT.AX, Nasdaq: OPT)
Opthea Limited (OPT.AX, Nasdaq: OPT) • Public co listed on Nasdaq (OPT) and ASX (OPT.AX) developing OPT-302 for wet AMD Opthea Limited and DME • OPT-302 (sVEGFR-3) is the first ‘Trap’ inhibitor of VEGF-C and VEGF-D designed specifically for the eye OPT-302 has a novel • In combination with anti-VEGF
Slide 4: Opthea Limited (OPT.AX, Nasdaq: OPT) clinical highlights
Opthea Limited (OPT.AX, Nasdaq: OPT) Primary endpoint met • OPT-302 combination therapy demonstrated superiority in visual acuity over ranibizumab in Phase 2b study of (Lucentis®) at 24 weeks in a randomized, controlled, double-masked trial of 366 patients OPT-302 in wet AMD • Secondary endpoint res
Slide 5: Financial Position (Unaudited)
Financial Position (Unaudited) Share Price Performance (2019- 2020) Key Financial Details Nasdaq: OPT 3.50 Ticker Symbol Nasdaq:OPT ASX:OPT 3.00 Share Price (Mar 12 2021) ~US$9.82 2.50 AUD (1 ADS: 8 ASX Ordinary shares) 2.00 ~A1.67 1.50 Total Ordinary Shares on Issue 342,654,600 (incl. 11.6m ADS) 1.
Slide 6: Opthea's Experienced Leadership Team
Opthea’s Experienced Leadership Team Management Team • Joined Opthea in 2008 and has been Chief Executive Officer • Head of Chemistry, Manufacturing and Controls Development Megan and Managing Director since February 2014 Mike since December 2008 Baldwin, PhD • Selected Experience: Over 20 years of
Slide 7: Our Goal and Strategy
Our Goal and Strategy To become a leader in developing & commercializing therapeutics for retinal diseases Conduct pivotal • Advance OPT-302 through two concurrent Phase 3 trials for wet AMD Phase 3 clinical trials • Investigate durability of OPT-302 treatment effect Optimise OPT-302 • OPT-302 to be
Slide 8: Wet AMD & DME are the leading causes of vision loss in the elderly & diabetics
Wet AMD & DME are the leading causes of vision loss in the elderly & diabetics Increasing prevalence; large & growing market opportunity Wet Age-Related Macular Degeneration Diabetic Macular Edema (DME) Epidemiology A complication of diabetes that manifests as Edema caused by abnormal vasculature gr
Slide 9: Two Major Clinical Development Areas in Wet AMD
Two Major Clinical Development Areas in Wet AMD Opthea has the potential to improve EFFICACY and DURABILITY of treatment DURABILITY Next Generation anti-VEGF-A therapies # To reduce # injections Not intended to improve patient responses New Therapies Targeting Novel Pathways EFFICACY “Combination Th
Slide 10: Existing Therapies Primarily Target VEGF-A
Existing Therapies Primarily Target VEGF-A OPT-302 has potential to improve clinical EFFICACY & DURABILITY by targeting VEGF-C/D OPT-302 inhibits VEGF-C/D VEGF-C OPT-302: Rationale VEGF-D Ranibizumab • Long-term therapy with selective VEGF-A (Lucentis®) inhibitors is associated with sub-optimal resp
Slide 11: A Currently Unmet Medical Need for wet AMD and DME
A Currently Unmet Medical Need for wet AMD and DME Clinical data suggest VEGF-C/D may mediate resistance & sub-optimal response to anti-VEGF-A therapy Despite receiving a VEGF-A inhibitor Wet AMD Patients (ranibizumab, aflibercept or bevacizumab)*: >45% Do not achieve significant vision gains wet AM
Slide 12: OPT-302: A 'trap' inhibitor of VEGF-C and VEGF-D
OPT-302: A ‘trap’ inhibitor of VEGF-C and VEGF-D OPT-302 combination therapy may improve treatment EFFICACY and DURABILITY OPT-302: A soluble form of VEGFR-3 Addressing EFFICACY & DURABILITY • A ‘trap’ comprising the extracellular domains 1-3 of VEGFR-3 and the Fc • Potential for prolonged clinical
Slide 13: Pipeline
Pipeline Clinical Trials & Next Combination Research/ Anticipated Commercial Product Agent(s) Preclinical Phase 1 Phase 2a Phase 2b Phase 3 Milestone Rights Wet Age-Related Macular Degeneration (Wet AMD) 1H 2021: OPT-302 Completed Phase 2b: Initiation of two Target: VEGF-C/D Ranibizumab concurrent (
Slide 14: Phase 3 Pivotal Trials in Wet AMD
Phase 3 Pivotal Trials in Wet AMD Initiated March 2021 Topline Data 2H 2023 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 com
Slide 15: OPT-302 Phase 3 Pivotal Program
OPT-302 Phase 3 Pivotal Program Trial initiations early 2021 ShORe Study of OPT-302 in combination with Ranibizumab COAST Combination OPT-302 with Aflibercept STudy • Design: Multi-centre, double-masked, randomised (1:1:1), sham control • Sample size: 330 patients per arm, 990 per study 15 • Regulat
Slide 16: Opthea's Clinical Data
Opthea’s 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 16
Slide 17: Phase 1/2a study: OPT-302 well-tolerated and active in wet AMD (Summary)
Phase 1/2a study: OPT-302 well-tolerated and active in wet AMD (Summary) Visual acuity benefit observed as monotherapy & in combination with ranibizumab Visual Acuity Gains (Baseline to Wk 12) following OPT-302 Phase 1/2a Key Take-Aways2 Monotherapy OPT-302 (q4w x3) 25 Treatment-Naive 25 Prior Treat
Slide 18: 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 18
Slide 19: Study Overview
Study Overview Treatment naïve patients Key Inclusion Criteria with neovascular AMD Key Exclusion Criteria Screening • Active CNV >50% lesion, classic / • Subfoveal fibrosis or >25% of total lesion minimally classic / occult • Haemorrhage >50% total lesion • BCVA ≥ 25 and ≤ 60 letters • Other clinic
Slide 20: 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 21: OPT-302 Combination Therapy Demonstrated Superiority in Visual Acuity over Ranibizumab
OPT-302 (2.0 mg) Combination Therapy Demonstrated Superiority in Visual Acuity over Ranibizumab Primary Endpoint Achieved: Mean Change in Best Corrected Visual Acuity Baseline to Week 24 20 Δ = +3.4 (p=0.0107) 20 Mean change in BCVA (SEM) Mean change in BCVA (SEM) 15 15 14.22 Δ = +3.4 (p=0.0107) (le
Slide 22: Reduced Retinal Thickness & Better 'Retinal Drying' With OPT-302 Combination Therapy
Reduced Retinal Thickness & Better ‘Retinal Drying’ With OPT-302 Combination Therapy Mean Change in CST – % Participants % Participants with Baseline to Week 24 with SRF present IR Cysts present -100 30 30 29.3 25 25 Mean change in CST (SEM) 21.6 -120 20 20 % Participants % Participants 18.5 (m) 16
Slide 23: Greater Reduction in Total Lesion and CNV Area With OPT-302 Combination Therapy
Greater Reduction in Total Lesion and CNV Area With OPT-302 Combination Therapy Mean Change in Mean Change in Total Lesion Area CNV Area 0 0 Mean change in Total Lesion Area (SEM) Mean change in CNV Area (SEM) -2 -2 (mm2) (mm2) -3.1 -3.6 -4 -4.3 -4 -5.0 -6 -6 Sham + 0.5 mg ranibizumab 2.0 mg OPT-302
Slide 24: 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 . .. .. ≥50% vessels above RPE . 100% beneath RPE Least responsive to VEGF-A inhibition <50% vessels above RPE Moderately responsive to VEGF-
Slide 25: Mean Change in Visual Acuity Over Time by Lesion Type
Mean Change in Visual Acuity Over Time by Lesion Type Patients with minimally classic & occult lesions have best response; small number predominantly classic patients Occult Minimally Classic Predominantly Classic 20 20 20 Mean change in BCVA (SEM) Mean change in BCVA (SEM) Mean change in BCVA (SEM)
Slide 26: Retinal Angiomatous Proliferation (RAP) Lesions
Retinal Angiomatous Proliferation (RAP) Lesions Have a distinct biology and vessel proliferation occurs within the retina (not the choroid) STAGE 1 STAGE 2 STAGE 2 with PED STAGE 3 Intraretinal neovascularization Subretinal neovascularization Subretinal neovascularization with Choroidal neovasculari
Slide 27: Improved Visual Acuity in OPT-302 + ranibizumab treated patients
Improved Visual Acuity in OPT-302 + ranibizumab treated patients Mean change in Visual Acuity to Week 24 in participants without RAP at baseline (>86% study participants) 20 Δ = 4.4 Mean change in BCVA (SEM) 15 15.0 (letters) 10 10.6 5 102 103 0 Sham + 0.5 mg ranibizumab 2.0 mg OPT-302 + 0.5 mg rani
Slide 28: Greater visual acuity gain in patients with lesions consisting of a majority of occult vessels
Greater visual acuity gain in patients with lesions consisting of a majority of occult vessels (RAP Absent) Occult Minimally Classic 20 20 Mean change in BCVA (SEM) Mean change in BCVA (SEM) +16.8 15 15 +14.9 Δ = 6.5 Δ = 4.7 (letters) (letters) 10 +10.2 10 +10.0 5 5 0 0 0 4 8 12 16 20 24 0 4 8 12 16
Slide 29: Improved Visual Acuity in patients with Min.Classic/Occult lesions (RAP Absent)
Improved Visual Acuity in patients with Min.Classic/Occult lesions (RAP Absent) Represents primary analysis patient population in planned Phase 3 trials Minimally Classic & Occult Minimally Classic & Occult 20 Δ = 5.7 20 Mean change in BCVA (SEM) Mean change in BCVA (SEM) 16.1 +16.1 15 15 Δ = 5.7 (l
Slide 30: Safety
Safety OPT-302 well tolerated with very low incidence of ocular inflammation 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 Eye – related to study pro
Slide 31: Conclusions – OPT-302 Phase 2b wet AMD Trial
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 • Vision gain of +3.4 letters • Statistically significant (p=0.0107) • High ranibizumab control arm • Secondary
Slide 32: Phase 3 Pivotal Trials
Phase 3 Pivotal Trials Wet AMD 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
Slide 33: OPT-302 Phase 3 Pivotal Program
OPT-302 Phase 3 Pivotal Program Trial initiations early 2021 ShORe Study of OPT-302 in combination with Ranibizumab COAST Combination OPT-302 with Aflibercept STudy • Design: Multi-centre, double-masked, randomised (1:1:1), sham control • Sample size: 330 patients per arm, 990 per study 33 • Regulat
Slide 34: Opthea's Phase 3 design is Optimised for Success based on Ph2b outcomes
Opthea’s Phase 3 design is Optimised for Success based on Ph2b outcomes • We know the patients which respond best: • Analyse these patients first (min.classic & occult) • Maximises opportunity to demonstrate most compelling vision benefit • In Phase 2b, +5.7 letters superior benefit of OPT-302 combi
Slide 35: Phase 1b/2a Trial of OPT-302 Combination Therapy for Persistent DME
Phase 1b/2a Trial of OPT-302 Combination Therapy for Persistent DME Phase 1b/2a study of OPT-302 in combination with aflibercept for persistent central-involved diabetic macular edema 35
Slide 36: OPT-302 DME Trial Design
OPT-302 DME Trial Design Previously anti-VEGF-A-treated patients with persistent DME, a difficult-to-treat population Phase 1b Dose Escalation (N=9) Phase 2a Dose Expansion: Randomized 2:1 (N=115#) OPT-302 (2.0 mg) OPT-302 (2.0 mg) + Aflibercept (2.0 mg) + Aflibercept (2.0 mg) Follow-up to week 12 1
Slide 37: Phase 1b/2a Clinical Analyses of OPT-302 Combination Therapy
Financial Disclosures Phase 1b/2a Clinical Analyses of OPT-302 Combination Therapy All patients enrolled had persistent center-involved DME despite prior anti-VEGF-A treatment ✓ Favorable tolerability profile in combination with aflibercept ✓ Dose-responsive improvements in visual acuity, reductions
Slide 38: Summary of results: Phase 1b Dose Escalation
Summary of results Financial Phase 1b Dose Escalation Disclosures of OPT-302 Combination Therapy Previously anti-VEGF-A treated patients with center-involved DME (N=9) OPT-302 (0.3 mg) OPT-302 (1 mg) OPT-302 (2 mg) OPT-302 + aflibercept (2 mg) + aflibercept (2 mg) + aflibercept (2 mg) Monotherapy IV
Slide 39: Prior Treatment History Study Eye
Prior Treatment History Study Eye Approximately one third of patients received regular prior aflibercept therapy Characteristic 2.0 mg aflibercept + 2.0 mg aflibercept + Sham (N=40) 2.0 mg OPT-302 (N=75) Mean Duration of Diabetic Macular Edema – years (±SD) 1.6 (1.70) 1.3 (1.30) Mean Number of Prior
Slide 40: Visual Acuity Gain following OPT-302 combination therapy
Visual Acuity Gain following OPT-302 combination therapy Financial Disclosures Exploratory Subgroup Analysis in patient population with a prior treatment history of aflibercept Mean Change in BCVA Mean Change in BCVA Baseline to Week 12 Baseline to Week 12 10 10 Δ = +3.2 8 8 Mean change in BCVA Mean
Slide 41: Gains in Visual Function, Reduced Vision Loss with OPT-302
Financial Gains in Visual Function, Disclosures Reduced Vision Loss with OPT-302 Exploratory Subgroup Analysis in patient population with a prior treatment history of aflibercept ≥10 Letter Gain ≥15 Letter Gain ≥ 1 Letter Loss At Week 12 At Week 12 At Week 12 30 30 30 27.3 23.1 20 20 20 % Patients %
Slide 42: Reduction of Retinal Thickness
Reduction of RetinalFinancial Thickness Disclosures Exploratory Subgroup Analysis in patient population with a prior treatment history of aflibercept Mean Change in CST Mean Change in CST % Patients ≤300 µm CST Baseline to Week 12 At Week 12 At Week 12 Weeks 40 0 25 4 8 12 22.7 20 -15.5 % Patients w
Slide 43: Safety
Safety Financial Disclosures Well tolerated & consistent with previous OPT-302 Phase 1 and Phase 2b clinical trials in wet AMD Aflibercept (2mg) + Sham Aflibercept (2mg) + OPT-302 (2 mg) Selected Adverse Events (N = 49) (N =95) Study Eye or Systemic, n (%) Intraocular inflammation 1 (2.0%) 1 (1.1%)
Slide 44: Safety – Intraocular Inflammation – Study Eye (All OPT-302 Trials)
Safety – Intraocular Inflammation – Study Eye (All OPT-302 Trials) Incidence of intraocular inflammation similar to control Study Eye OPT-302 2.0 mg OPT-302 Sham + anti- Any dose VEGF-A control N Participants (%) N=399 N=263 N=169 Inj=1,842 Inj=1,121 Inj=854 Intraocular inflammation1 7 (1.8%) 3 (1.1
Slide 45: Our Pipeline Includes Co-Formulation & Opportunities in PCV, RVO
Our Pipeline Includes Co-Formulation & Opportunities in PCV, RVO • Co-formulate OPT-302 with a VEGF-A inhibitor • A single injection to inhibit VEGF-A/C/D • Program to generate/acquire biosimilar VEGF-A inhibitor and co-formulate with OPT-302 Co-Formulation • Manufacture and advance co-formulation t
Slide 46: Opthea – Developing OPT-302 for Eye Diseases
Opthea – Developing OPT-302 for Eye Diseases • OPT-302 has broad development potential in a range of eye diseases, including wet AMD and DME • Targets validated VEGF/VEGFR pathway and mechanism of escape from existing therapies that is differentiated to VEGF-A inhibitors and other agents in developm
Slide 47: Megan Baldwin, PhD CEO & Managing Director
Megan Baldwin, PhD CEO & Managing Director T +61 (3) 9826 0399 E [email protected] Suite 0403, Level 4, 650 Chapel Street, South Yarra 3141 Victoria Australia www.opthea.com