Opthea Limited · ASX:OPT
Opthea — Ophthalmology Innovation Summit @ AAO 2018
24 slides from Opthea's conference presentation, Oct 26, 2018
Slide 1: Clinical results of OPT-302 (VEGF-C/D 'Trap') Combination Treatment in nAMD and DME
Clinical results of OPT-302 (VEGF-C/D ‘Trap’) Combination Treatment in nAMD and DME Ophthalmology Innovation Summit @ AAO, October 25 2018 Megan Baldwin PhD, CEO & Managing Director
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 Aflibercept Ranibizumab Neovascular AMD 1 VEGF-B VEGF-A VEGF-C OPT-302 66% PlGF VEGF-D 10.00 8.91 9.00 8.00 6.91 Aqueous Humor VEGF-C (pg/ml) 7.00 VEGFR-1 VEGFR-2 VEGFR-3 6.00 5.37 5.00 4.00 3.00 2.00 1.00 0.00 Baseline 1m 2m Bevacizumab Bevacizumab Angiogenesis An
Slide 4: An Unmet Medical Need for nAMD & DME
An Unmet Medical Need for nAMD & DME Despite receiving a VEGF-A inhibitor (Ranibizumab, Aflibercept or Bevacizumab)*: >50% Do not achieve significant vision gains nAMD 2/3 Will continue to have fluid at the back of the eye 25% Will have further vision loss at 12 months 2/3 Do not achieve significant
Slide 5: Mean OPT-302 serum concentrations
OPT-302 Mean OPT-302 serum concentrations • Potent inhibitor of VEGF-C (~5pM) and VEGF-D (~0.5 nM) 100.0 OPT-302 Monotherapy (2 mg) Mean (+SD) OPT-302 Serum • A ‘trap’ that blocks VEGF-C and VEGF-D Concentrations (ng/mL) Combination OPT-302 (2 mg) + Ranibizumab (0.5 mg) binding to the receptors VEGF
Slide 6: Phase 1/2a First-in-Human Study in Neovascular AMD (n=51)
OPT-302 Phase 1/2a First-in-Human Study in Neovascular AMD (n=51) Part 1: Dose-escalation Part 2: Dose-expansion (Open-label) (Randomised 3:1) OPT-302 (2 mg) OPT-302 (2 mg) Monotherapy* Monotherapy* IVT Q4W x 3 IVT Q4W x 3, n=8 pts 24 Cohort 4 Follow-up to week 12 at Week 28 Day DLT window subjects
Slide 7: OPT-302 +/- Ranibizumab - Phase 1/2a Safety Summary
OPT-302 +/- Ranibizumab - Phase 1/2a Safety Summary OPT-302 + Lucentis administered by repeat IVT injection (Baseline, Week 4, Week 8) • No missed doses, safety experience with ~150 intravitreal (ocular) injections of OPT-302 OPT-302 at ocular doses up to 2 mg + Lucentis (0.5 mg): • No dose limiting
Slide 8: Evidence of biological activity in patients treated with intravitreal OPT-302 (2 mg) monotherapy
Evidence of biological activity in patients treated with intravitreal OPT-302 (2 mg) monotherapy • Of the 13 patients who received Mean Change VA from Mean Change in Baseline (letters) Visual Acuity ( M e a n C h a n g e fr o m B a s e lin e ) OPT-302 monotherapy treatment: • 7/13 (54%) did not rece
Slide 9: Gains in Visual Acuity and Reduced Retinal Thickness with OPT-302 + Ranibizumab
Gains in Visual Acuity and Reduced Retinal Thickness in Patients with OPT-302 + Ranibizumab Therapy Change in mean BCVA Change in mean Central Subfield Thickness 15 Time (weeks) Naïve pts (n=18) Change from baseline in Visual Acuity (ETDRS Letters) Prior treated pts (n=20) 0 2 4 6 8 10 12 0 Change f
Slide 10: Reductions in CNV in Treatment-Naïve Patients with OPT-302 + Ranibizumab
Reductions in CNV in Treatment-Naïve Patients with OPT-302 + Ranibizumab Therapy Reduction in CNV Size on FA % Patients with Absent CNV on FA 9 60 % Patients with Absent CNV on FA 7.71 8 50 % 50 7 CNV Size (mm2) 6 40 5 30 27.8 % 4 3.74 3 20 2.03 2 10 1 5.6 %* 0 0 Baseline Week 4 Week 12 Baseline Wee
Slide 11: Phase 2b Trial in Treatment-Naïve nAMD (n=351)
OPT-302 +/- Ranibizumab Phase 2b Trial in Treatment-Naïve nAMD (n=351) OPT-302 (2 mg) + Ranibizumab (0.5 mg) n=117 Week 24 Follow-up Treatment-Naive OPT-302 (0.5 mg) + Ranibizumab (0.5 mg) n=117 Neovascular AMD Sham + Ranibizumab (0.5 mg) n=117 Randomized 1:1:1 to treatment arms IVT dosing at every
Slide 12: Mechanism of Action Supports Investigation in DME
OPT-302 Mechanism of Action Supports Investigation in DME VEGF-C and its interaction with VEGFR-2 and VEGFR-3 plays a functional role in pathogenesis of DME: • OPT-302 has shown evidence of activity to resolve retinal fluid 1 • VEGFR-2 expression is greater in diabetic retina than non-diabetics 2,3,
Slide 13: Phase 1b Dose Escalation study of OPT-302 + Aflibercept in DME
Phase 1b Dose Escalation study of OPT-302 + Aflibercept in DME Phase 1b Dose-Escalation N=9 patients Phase 2a Dose-Expansion (Randomised 2:1 ratio) OPT-302 (2.0 mg) OPT-302 (2.0 mg) + Aflibercept (2.0 mg) + Aflibercept (2.0 mg) 14 Day DLT window IVT Q4W x 3, n=3 IVT Q4W x 3, n=~72 pts Follow-up to w
Slide 14: Baseline Ocular Characteristics – Prior Treated
Baseline Ocular Characteristics – Prior Treated OPT-302 (0.3 mg) + OPT-302 (1 mg) + OPT-302 (2 mg) + Total Number of Characteristic Aflibercept (2.0 mg) Aflibercept (2.0 mg) Aflibercept (2.0 mg) Subjects (n=3) (n=3) (n=3) (N=9) Vision Mean BCVA, ETDRS letters (SD) 64.3 (9) 64.6 (5) 66.7 (3.1) 65 (5.
Slide 15: OPT-302 + Aflibercept Safety Results
OPT-302 + Aflibercept Safety Results • OPT-302 (0.3, 1 or 2 mg) + aflibercept (2 mg) administered by IVT injection (Baseline, Week 4, Week 8) • OPT-302 intravitreal doses up to 2 mg in combination with aflibercept (2 mg) • No dose limiting toxicities (Maximum Tolerated Dose not reached) • No study d
Slide 16: OPT-302 + Aflibercept – Safety Summary of selected AEs
OPT-302 + Aflibercept – Safety Summary of selected AEs Selected Adverse Events: OPT-302 (0.3 mg) + OPT-302 (1 mg) + OPT-302 (2 mg) + Total Number of Ocular or Systemic Aflibercept (2.0 mg) Aflibercept (2.0 mg) Aflibercept (2.0 mg) Subjects (n=3) (n=3) (n=3) (N=9) Intraocular inflammation 0 0 0 0 End
Slide 17: Dose Response in BCVA changes from Baseline to Week 12
Dose Response in BCVA changes from Baseline to Week 12 Mean Change in BCVA Baseline to Week 12 Mean Change from baseline in BCVA (Letters) 20 Aflibercept (2 mg) + OPT-302 15 + 14.3 2 mg 1 mg 0.3 mg 10 + 5.7 5 + 3.0 0 -5 0 2 4 8 12 17 Week Error Bars: SEM
Slide 18: Dose Response Relationship + Aflibercept: Gains in BCVA at Week 12
OPT-302 + Aflibercept: Gains in BCVA at Week 12 Dose Response Relationship Mean Change from baseline in BCVA (Letters) +14.3 20 Dose of OPT-302 % of pts with Mean # prior + Aflibercept BCVA gain anti-VEGF-A 15 (2 mg) ≥ 5 letters injections 0.3 mg 1/3 (33%) 5 1 mg 2/3 (67%) 7.3 10 +7.7 2 mg 3/3 (100%
Slide 19: Mean changes in CST from Baseline to Week 12
OPT-302 (0.3-2 mg) + Aflibercept (2 mg): Mean changes in CST from Baseline to Week 12 20 0 Mean Change from Baseline in CST on SD-OCT (µm) -20 -40 -60 - 71 µM -80 -100 0 2 4 8 12 Week 19 Error Bars: SEM; Mean Baseline CST = 434 µm
Slide 20: DME Patients with Bilateral Disease
DME Patients with Bilateral Disease* Study Eye vs Fellow Eye (N=5) Mean Change in BCVA Baseline Mean Change in CST (uM) Baseline % Pts with ≥ 50% Reduction in to Week 12 to Week 12 Excess Foveal Thickness OPT-302 + Anti-VEGF-A OPT-302 + Anti-VEGF-A OPT-302 + Anti-VEGF-A Aflibercept Monotherapy Aflib
Slide 21: Phase 2a Randomised Dose Expansion study of OPT-302 + Aflibercept in Persistent DME
Phase 2a Randomised Dose Expansion study of OPT-302 + Aflibercept in Persistent DME Phase 1b Dose-Escalation Phase 2a Dose-Expansion (Randomised 2:1 ratio) OPT-302 (2.0 mg) OPT-302 (2.0 mg) + Aflibercept (2.0 mg) + Aflibercept (2.0 mg) 14 Day DLT window IVT Q4W x 3, n=3 IVT Q4W x 3, n=~72 pts Follow
Slide 22: OPT-302 Clinical Program
OPT-302 Clinical Program • Two ongoing randomised controlled clinical trials in nAMD & DME Combination 1o Data Agent Preclinical Phase 1 Phase 2a Phase 2b Phase 3 Status Analysis Neovascular AMD OPT-302 Ranibizumab Complete Target: VEGF-C/D Target: VEGF-A Ph 1/2a (n=51) April 2017 OPT-302 Ranibizuma
Slide 23: Conclusion
Conclusion • Current treatments target primarily VEGF-A; OPT-302 inhibits VEGF-C/D • The successful dose escalation of OPT-302 in combination with aflibercept in DME builds upon the similar favourable safety profile in combination with ranibizumab in nAMD • Evidence of a dose response for OPT-302 co
Slide 24: Megan Baldwin, PhD CEO & Managing Director
Megan Baldwin, PhD CEO & Managing Director T +61 (3) 9826 0399 M +61 447 788 674 E megan.baldwin@opthea.com www.opthea.com Suite 0403, Level 4, 650 Chapel Street, South Yarra 3141 Victoria Australia