Opthea Limited · ASX:OPT
Opthea — Investor Presentation (July 2020)
25 slides from Opthea's investor presentation, Jul 27, 2020
Slide 1: Switching to combination OPT-302 with aflibercept in persistent DME
Switching to combination OPT-302 with aflibercept from prior anti-VEGF-A monotherapy in eyes with persistent diabetic macula edema (DME) Clinical results from Opthea’s Phase 1b/2a trial Data presented at ASRS Virtual Meeting, July 25 2020
Slide 2: Disclaimer
Disclaimer Investment in Opthea Limited (‘Opthea’) is subject to investment risk, including possible loss of income and capital invested. Neither Opthea nor any other member company of the Opthea Group guarantees any particular rate of return or performance, nor do they guarantee the repayment of ca
Slide 3: Diabetic Macular Edema
Diabetic Macular Edema Up to 10% diabetics develop DME which is responsible for most of the central vision loss in the diabetic population Standard of Care Treatments & An Unmet Medical Need • VEGF-A inhibitors are first-line standard of care therapy for DME • Aflibercept (Eylea) & ranibizumab (Luce
Slide 4: Patients With Persistent DME Are a Significant Unmet Need
Financial Patients With Persistent Disclosures DME Are a Significant Unmet Need There is a need for novel therapeutic approaches to improve clinical outcomes Many patients have limited gains despite regular anti-VEGF-A monotherapy* In Protocol I, patients with DME received ranibizumab + sham injecti
Slide 5: OPT-302: Inhibitor of VEGF-C and -D
OPT-302: Inhibitor of VEGF-C and -D Intravitreal OPT-302 combination therapy may improve outcomes in DME OPT-302 • OPT-302 is a soluble VEGFR-3 ‘trap’ fusion protein Extra-Cellular • Potent inhibitor of VEGF-C/-D interaction with VEGFR-2 & VEGFR-3 Domains 1-3 hVEGFR-3 • Existing therapies target VEG
Slide 6: Phase 1b/2a Trial of OPT-302 Combination Therapy for Persistent DME
Phase 1b/2a Trial of OPT-302 Combination Therapy for Persistent DME All patients enrolled had persistent center-involved DME despite prior anti-VEGF-A treatment Phase 1b: • Patients received escalating doses of OPT-302 (0.3, 1 or 2 mg) + aflibercept (2 mg) across 3 cohorts (total of 9 patients) • Tr
Slide 7: 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=~108) 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 8: OPT-302 Phase 1b/2a Financial Disclosures
OPT-302 Phase 1b/2a Financial Disclosures Phase 1b dose escalation and Phase 2a randomised, controlled, double masked, proof-of-concept study • Heterogeneous all comer’s population for prior anti-VEGF-A history (aflibercept / ranibizumab / bevacizumab) in patients with persistent DME • Variable trea
Slide 9: Phase 1b Dose Escalation
Phase 1b Dose Escalation Dose-responsive gains in visual acuity following OPT-302 combination therapy and reductions in retinal thickness 9
Slide 10: Summary of results
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 11: Phase 2a Trial of OPT-302 Combination Therapy for Persistent DME
Phase 2a Trial of OPT-302 Combination Therapy for Persistent DME Total “Per Protocol” patient population with variable prior anti-VEGF-A treatment history of aflibercept / ranibizumab / bevacizumab 11
Slide 12: Baseline Demographics
Financial Disclosures Baseline Demographics Well balanced across treatment groups in Phase 2a Aflibercept (2mg) + Sham Aflibercept (2mg) + OPT-302 (2 mg) Characteristic (N = 48) (N = 96) Mean age, years (SD) 61.2 (9.40) 61.8 (10.07) Male, n (%) 30 (62.5%) 60 (62.5%) Race, n (%) American Indian or Al
Slide 13: Baseline Demographics
Financial Disclosures Baseline Demographics Well balanced across treatment groups in Phase 2a Characteristic 2.0 mg aflibercept + 2.0 mg aflibercept + Sham (N=48) 2.0 mg OPT-302 (N=96) Vision Mean best corrected visual acuity (BCVA) – letters (±SD) 63.9 (9.44) 63.3 (8.31) >55 letters vision - n (%)
Slide 14: 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 15: 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 16: Primary Efficacy Endpoint: Response Rate of ≥ 5 letter gain to Week 12
Financial Primary Efficacy Endpoint: Disclosures Response Rate of ≥ 5 letter gain to Week 12 Previously anti-VEGF-A treated DME patients after switching to OPT-302 + aflibercept combination therapy 100 80 % Participants 60 52.8 40 Pre-specified response rate for clinical activity* 20 0 ≥ 5 letter BC
Slide 17: Measures of Visual Function
Financial Disclosures Measures of Visual Function Persistent DME patients: Prior anti-VEGF-A therapy of aflibercept /ranibizumab / bevacizumab Mean BCVA at Baseline ≥10 Letter Gain ≥15 Letter Gain ≥ 5 Letter Loss and change at Week 12 At Week 12 At Week 12 At Week 12 75 30 30 20 26.7 70 +6.1 15 +5.9
Slide 18: Mean change in Retinal Thickness
Mean Change in Retinal Thickness Persistent DME patients: Prior anti-VEGF-A therapy of aflibercept /ranibizumab / bevacizumab Mean Change in CST Mean Change in CST Baseline to Week 12 At Week 12 Weeks 0 4 8 12 0 0 -10 Mean change in CST (SEM) Mean change in CST (SEM) -20 -20 -34.9 -30 (m) (m) -4
Slide 19: Phase 2a Trial of OPT-302 Combination Therapy for Persistent DME
Phase 2a Trial of OPT-302 Combination Therapy for Persistent DME Exploratory subgroup analysis in patient population receiving prior aflibercept therapy 19
Slide 20: OPT-302 Phase 2a DME Study Disclosures
Financial OPT-302 Phase 2a DME Study Disclosures Exploratory subgroup analysis in patient population receiving previous aflibercept • More homogeneous population of anti-VEGF-A prior treatment history of previous aflibercept in patients with persistent DME • Less variable prior treatment history & g
Slide 21: 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 22: 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 23: 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 24: Conclusions
Conclusions Financial Disclosures OPT-302 Combination therapy in Previously Treated Patients with Persistent DME • Primary safety endpoint met: • The safety profile of OPT-302 combination therapy is favorable and consistent across two eye indications where a total of >1850 intravitreal injections ha
Slide 25: Authorised for release to the ASX by Megan Baldwin
Authorised for release to the ASX by: Megan Baldwin CEO & Managing Director T +61 (3) 9826 0399 E megan.baldwin@opthea.com Suite 0403, Level 4, 650 Chapel Street, South Yarra 3141 Victoria Australia www.opthea.com