Slide 1: OPT-302 Phase 2b in wet AMD
OPT-302 Phase 2b in wet AMD A multicenter, randomized, double-masked, sham controlled study of intravitreal OPT-302 in combination with ranibizumab, in participants with wet AMD Data presented by Professor Timothy Jackson PhD., FRCOphth., King’s College London EURETINA Congress, Thursday 5th Septemb
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: OPT-302 Inhibits VEGF-C and VEGF-D
OPT-302 Inhibits VEGF-C and VEGF-D Extra-Cellular Domains 1-3 Ranibizumab hVEGFR-3 (Lucentis®) VEGF-C OPT-302 Bevacizumab# VEGF-A VEGF-D hIgG1 Fc (Avastin®) VEGF-B Aflibercept PlGF (Eylea®) • Potent inhibitor of VEGF-C (~5pM) and VEGF-D (~0.5 nM) • A ‘trap’ that blocks VEGF-C and VEGF-D binding to t
Slide 4: VEGF-A Inhibition Upregulates VEGF-C/D
VEGF-A Inhibition Upregulates VEGF-C/D Upregulation in Neovascular AMD 1 10.0 66% Aqueous Humor VEGF-C (pg/ml) 8.91 8.0 6.91 VEGF-C 6.0 5.37 4.0 2.0 0.0 Baseline 1m 2m Bevacizumab Bevacizumab 4 1 Cabral et al., Bevacizumab injection in patients with neovascular Age-Related Macular Degeneration incre
Slide 5: OPT-302-1002 Study Overview
OPT-302-1002 – Study Overview ClinicalTrials.gov Identifier: NCT03345082 Randomised 1:1:1 to treatment arms : intravitreal dosing every 4 weeks (x 6) OPT-302 (2.0 mg) + ranibizumab (0.5 mg) Week 24 Follow-up Wet AMD OPT-302 (0.5 mg) + ranibizumab (0.5 mg) Naïve Pts Sham + ranibizumab (0.5 mg) 5
Slide 6: 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 7: Study Outcome Measures
Study Outcome Measures Primary Outcome: • Mean change from Baseline in ETDRS best corrected visual acuity at Week 24 Key Secondary Outcomes at Week 24: • Patients gaining ≥15 or more ETDRS letters • Patients losing ≥15 or more ETDRS letters • Change in central subfield thickness (SD-OCT) • Change in
Slide 8: Study Demographics and Baseline Characteristics
Study Demographics and Baseline Characteristics Evenly balanced across groups 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
Slide 9: Primary Analysis – Mean Change in BCVA Baseline to Week 24
Primary Analysis – Mean Change in BCVA Baseline to Week 24 Primary endpoint achieved OPT-302 Combination Therapy Demonstrated Superiority in Visual Acuity over Ranibizumab 20 Δ = +3.4 (p=0.0107) Mean change in BCVA (SEM) 15 14.22 (letters) 10 10.84 9.44 5 0 Sham + 0.5 mg ranibizumab 0.5 mg OPT-302 +
Slide 10: Mean Change in BCVA Over Time
Mean Change in BCVA Over Time Additive benefit of OPT-302 evident from 8-weeks 20 Mean change in BCVA (SEM) 15 (letters) 10 5 0 0 4 8 12 16 20 24 Weeks Sham + 0.5 mg ranibizumab 0.5 mg OPT-302 + 0.5 mg ranibizumab 2.0 mg OPT-302 + 0.5 mg ranibizumab 10 mITT; graph represents “as observed” data and S
Slide 11: Mean Change in Central Subfield Thickness - Baseline to Week 24
Mean Change in Central Subfield Thickness - Baseline to Week 24 Reductions in CST in OPT-302 combination groups compared to sham + ranibizumab -100 Mean change in CST (SEM) -120 ( m) -133.8 -140 -147.8 -146.7 -160 Sham + 0.5 mg ranibizumab 0.5 mg OPT-302 + 0.5 mg ranibizumab 2.0 mg OPT-302 + 0.5 mg
Slide 12: Sub-retinal Fluid and Intra-retinal Cysts at Week 24
Sub-retinal Fluid and Intra-retinal Cysts at Week 24 Fewer participants with retinal fluid present in OPT-302 combination groups compared to sham + ranibizumab % Participants with SRF % Participants with IR Cysts present present 40 40 30 30 29.3 % Participants % Participants 23.2 20 20 21.6 19.6 18.
Slide 13: Mean Change in Total Lesion Area and CNV Area – Baseline to Week 24
Mean Change in Total Lesion Area and CNV Area – Baseline to Week 24 Greater reduction in Total Lesion and CNV Area in OPT-302 combination groups compared to sham + ranibizumab 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
Slide 14: Safety – Adverse Events (AEs)
Safety – Adverse Events (AEs) 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 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 -
Slide 15: Thank you to all study participants and over 100 sites across 10 countries
Thank you to all study participants and over 100 sites across 10 countries Czech Republic – 3 sites France – 6 sites Hungary – 5 sites Italy – 5 sites Israel – 8 sites Latvia – 4 sites Poland – 7 sites Spain – 8 sites United Kingdom – 7sites United States – 56 sites 15
Slide 16: Conclusions
Conclusions • 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 outcomes were supportive of the pr
Slide 17: Megan Baldwin CEO & Managing Director
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