Opthea Limited · ASX:OPT
Opthea — Ophthalmology Innovation Summit @ American Academy of Ophthalmology (OIS@AAO) 2019
37 slides from Opthea's conference presentation, Oct 11, 2019
Slide 1: Phase 2b Clinical Results of OPT-302 Combination Treatment in nAMD
Phase 2b Clinical Results of OPT-302 (VEGF-C/D ‘Trap’) Combination Treatment in nAMD Ophthalmology Innovation Summit @ American Academy Ophthalmology (OIS@AAO) Megan Baldwin PhD, CEO & Managing Director October 10 2019
Slide 2: Forward-Looking Statements
Forward-Looking Statements 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
Slide 3: OPT-302 Inhibits VEGF-C and VEGF-D
OPT-302 Inhibits VEGF-C and VEGF-D Ranibizumab VEGF-C OPT-302 VEGF-A VEGF-D Bevacizumab VEGF-B Aflibercept PlGF VEGFR-1 VEGFR-2 VEGFR-3 OPT-302 ‘trap’ blocks VEGF-C and VEGF-D binding to VEGFR-2 and VEGFR-3 receptors 3
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 “Bevacizumab injection in patients with neovascular age-related macular degeneration increases angiogeni
Slide 5: OPT-302 Clinical Program
OPT-302 Clinical Program Combination 1o Data Agent Preclinical Phase 1 Phase 2a Phase 2b Phase 3 Status Analysis Neovascular AMD April 2017 OPT-302 Ranibizumab Complete Primary Endpt Met Target: VEGF-C/D Target: VEGF-A Ph 1/2a (n=51) Safety OPT-302 Ranibizumab Positive August 2019 Target: VEGF-C/D T
Slide 6: 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 113 sites across 10 countries: US, EU, Israel OPT-302-1002; NCT ClinicalTrials.gov Identifier: NCT03345082 6
Slide 7: OPT-302 Phase 2b wAMD Study Design
OPT-302 Phase 2b wAMD 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) 7
Slide 8: 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 9: 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 10: 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 11: 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 (2.0 mg) 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 2.0 mg
Slide 12: Mean Change in BCVA Over Time
Mean Change in BCVA Over Time Additive visual acuity 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 (n=119) (n=122) (n=121) 12 Modified
Slide 13: Vision Gain - Baseline to Week 24
Vision Gain - Baseline to Week 24 Higher proportion of patients gaining ≥15, ≥10 and ≥5 letters of vision in OPT-302 combination group 100 100 100 80 80 80 85.0 75.9 % Participants % Participants % Participants 70.0 60 60 60 57.8 40 45.0 40 40 40.5 20 20 20 0 0 0 % Gaining 15 Letters % Gaining 1
Slide 14: Vision Loss - Baseline to Week 24
Vision Loss - Baseline to Week 24 Fewer patients lose ≥15, ≥10 and ≥5 letters of vision in OPT-302 combination group 8 8 8 6.9 6 6 6 6.0 % Participants % Participants % Participants 4 4 4 4.2 3.4 2 2 2 0.8 0.8 0 0 0 % Losing 15 Letters % Losing 10 Letters % Losing 5 Letters Sham + 0.5 mg ranib
Slide 15: Mean Change in BCVA by Baseline Visual Acuity
Mean Change in BCVA Baseline to Week 24 Vision gain in OPT-302 combination group compared to sham + ranibizumab is independent of baseline VA 20 16.5 Mean change in BCVA (SEM) 15 15.7 13.9 (letters) 12.4 12.1 11.3 10 10.5 9.3 5 29 40 34 26 31 26 25 29 0 45 > 45 to 54 > 54 to 58 > 58 Baseline BCVA
Slide 16: Central Subfield Thickness
Central Subfield Thickness Reduction in CST in OPT-302 combination group compared to sham + ranibizumab Mean Change in CST – Mean CST at Week 24 Baseline to Week 24 300 -100 277.84 265.57 Mean change in CST (SEM) 250 Mean CST (SEM) -120 (m) (m) -133.80 200 -140 -146.70 150 -160 100 Sham + 0.5 mg r
Slide 17: 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 group compared to sham + ranibizumab % Participants % Participants with with SRF present IR Cysts present 30 30 29.3 25 25 21.6 20 20 % Participants % Participants 18.5 16.8 15 1
Slide 18: Total Lesion Area and CNV Area – Baseline to Week 24
Total Lesion Area and CNV Area – Baseline to Week 24 Greater reduction in Total Lesion and CNV Area in OPT-302 combination group 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 (SEM) -2 -2 (mm2
Slide 19: Polypoidal Choroidal Vasculopathy
Polypoidal Choroidal Vasculopathy Mean change in BCVA to Week 24 in participants with and without PCV at baseline 20 Δ = 2.71 Δ = 6.70 (*p = 0.0491) (*p = 0.0253) Mean change in BCVA (SEM) 15 14.2 13.5 (letters) 11.5 10 6.9 5 98 99 20 22 0 Absent Present PCV Detected at Baseline Sham + 0.5 mg ranibi
Slide 20: Mean Change in BCVA Over Time by Lesion Type
Mean Change in BCVA Over Time by Lesion Type Small number of predominantly classic patients Predominantly Classic Minimally Classic Occult 20 20 20 Mean change in BCVA (SEM) Mean change in BCVA (SEM) Mean change in BCVA (SEM) 15 15 15 (letters) (letters) (letters) 10 10 10 5 5 5 0 0 0 0 4 8 12 16 20
Slide 21: Mean Change in BCVA at Week 24 by Lesion Type
Mean Change in BCVA at week 24 by Lesion Type Greater vision gains at Week 24 in OPT-302 2.0 mg group in minimally classic and occult lesions Minimally Classic Occult 20 20 Δ = 6.0 (*p = 0.0008) Δ = 2.7 Mean change in BCVA (SEM) Mean change in BCVA (SEM) 16.2 15 15 13.7 (letters) (letters) 11.1 10 1
Slide 22: 3-Line Vision Gain at Week 24 by Lesion Type
3-Line Vision Gain at Week 24 by Lesion Type >20% increase in 3-line gainers in participants with occult lesions treated with OPT-302 combination therapy Minimally Classic Occult 60 60 55.8 % Participants % Participants 40 42.3 40 39.6 34.0 20 20 22 21 17 29 0 0 Sham + 0.5 mg ranibizumab (n = 52) Sh
Slide 23: 2-Line Vision Gain at Week 24 by Lesion Type
2-Line Vision Gain at Week 24 by Lesion Type Greater proportion of 2-line gainers in participants with minimally classic and occult lesions following OPT-302 combination therapy Minimally Classic Occult 80 80 76.9 66.0 60 60 58.0 % Participants % Participants 55.8 40 40 20 20 29 35 29 40 0 0 Sham +
Slide 24: 3-Line Vision Loss Baseline to Week 24
3-Line Vision Loss Baseline to Week 24 Fewer patients with minimally classic and occult lesions lose ≥15 letters following OPT-302 combination therapy Minimally Classic Occult 6 6 5.8 % Participants % Participants 4 4 2 2 1.9 2.0 3 1 1 0 0 Sham + 0.5 mg ranibizumab (n = 52) Sham + 0.5 mg ranibizumab
Slide 25: 2-Line Vision Loss Baseline to Week 24
2-Line Vision Loss Baseline to Week 24 Fewer patients with minimally classic and occult lesions lose ≥10 letters following OPT-302 combination therapy Minimally Classic Occult 10 10 9.6 % Participants 8 8 % Participants 6 6 4 4 4.0 2 2 1.9 5 1 2 0 0 Sham + 0.5 mg ranibizumab (n = 52) Sham + 0.5 mg r
Slide 26: Central Subfield Thickness by Lesion Type
Central Subfield Thickness by Lesion Type Reduction in CST in participants with occult lesions treated with OPT-302 combination compared to sham + ranibizumab Minimally Classic Occult -80 -80 -100 -100 -103.5 Mean change in CST (SEM) Mean change in CST (SEM) -120 -120 ( m) ( m) -134.6 -140 -140 -1
Slide 27: Sub-Retinal Fluid at Week 24 by Lesion Type
Sub-Retinal Fluid at Week 24 by Lesion Type Fewer participants with minimally classic & occult lesions have SRF at week 24 following OPT-302 combination therapy Minimally Classic Occult 30 30 30.0 23.1 % Participants % Participants 20 21.2 20 17.3 10 10 12 11 15 9 0 0 Sham + 0.5 mg ranibizumab (n =
Slide 28: Intra-Retinal Cysts at Week 24 by Lesion Type
Intra-Retinal Cysts at Week 24 by Lesion Type Fewer participants with minimally classic & occult lesions have intra-retinal cysts following OPT-302 combination therapy Minimally Classic Occult 25 25 22.6 20 20.8 20 19.6 % Participants % Participants 15 15 10 10 7.5 5 5 12 11 10 4 0 0 Sham + 0.5 mg r
Slide 29: Total Lesion Area at Week 24 in Minimally Classic and Occult Lesions
Total Lesion Area at Week 24 in Minimally Classic and Occult Lesions Greater reductions in Total Lesion Area following OPT-302 combination therapy Minimally Classic Occult 0 0 Mean change in Total Lesion Area (SEM) Mean change in Total Lesion Area (SEM) -2 -2 (mm2) (mm2) -3.3 -3.9 -4 -4 -4.4 -4.9 -6
Slide 30: CNV Area at Week 24 in Minimally Classic and Occult Lesions
CNV Area at Week 24 in Minimally Classic and Occult Lesions Greater reductions in CNV Area following OPT-302 combination therapy Minimally Classic Occult 0 0 Mean change in CNV Area (SEM) Mean change in CNV Area (SEM) -2 -2 (mm2) (mm2) -3.4 -4 -4 -4.4 -4.6 (p = 0.0555) -5.6 -6 -6 Sham + 0.5 mg ranib
Slide 31: Lesion classification at Baseline and at Week 24
Lesion classification at Baseline and at Week 24 Lesions shift to an occult, quiescent biology or no CNV following treatment Lesion Classification Lesion Classification at Baseline at Week 24 50 50 45 44 44 45 40 43 40 41 % Participants % Participants 35 30 30 31 20 20 17 14 10 13 12 10 0 0 Predomin
Slide 32: Retinal Angiomatous Proliferation (RAP) Lesions
Retinal Angiomatous Proliferation (RAP) Lesions Mean change in BCVA to Week 24 in participants without RAP at baseline 20 Δ = 4.4 *p = 0.0025 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 ranibizumab 32 mITT; RAP – retinal angiomato
Slide 33: Mean Change in BCVA Over Time by Lesion Type, RAP Absent
Mean Change in BCVA Over Time by Lesion Type, RAP Absent In RAP absent participants, +4.7 letter gain in minimally classic and +6.5 letter gain in occult participants treated with OPT-302 combination therapy compared to sham + ranibizumab Minimally Classic Occult 20 20 Mean change in BCVA (SEM) Mean
Slide 34: Mean Change in BCVA at Week 24 by Lesion Type, RAP Absent
Mean Change in BCVA at Week 24 by Lesion Type, RAP Absent Minimally Classic Occult 20 20 Δ = 6.5 Δ = 4.7 *p = 0.0005 *p = 0.0415 Mean change in BCVA (SEM) Mean change in BCVA (SEM) 16.7 (letters) 15 15.4 15 (letters) 10 10.7 10 10.1 5 5 40 39 47 49 0 0 Sham + 0.5 mg ranibizumab 2.0 mg OPT-302 + 0.5
Slide 35: 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 36: Conclusions – OPT-302 Phase 2b nAMD Trial
Conclusions – OPT-302 Phase 2b nAMD 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 outc
Slide 37: 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
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