Opthea Limited · ASX:OPT
Opthea — Investor Presentation (January 2017)
40 slides from Opthea's investor presentation, January 2017
Slide 1: OPT-302: A novel therapy for Wet AMD
OPT-302: A novel therapy for Wet AMD Corporate Presentation, January 2017 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: Corporate Summary
Corporate Summary OPT-302 Wet AMD Program: Milestones • OPT-302 blocks VEGF-C and VEGF-D • • In development for treatment of wet AMD Potential in a range of eye diseases Initiated Phase 1/2A clinical trial: 30 June 2015 • Combination therapy with approved a-VEGF-A therapies to more completely shut
Slide 4: Financial Position (Unaudited)
Financial Position (Unaudited) Key Financial Details ASX: OPT Share Price Performance (Jan 2015 - Jan 2017) Ticker Symbol ASX:OPT 1.00 0.90 Share Price (Jan 5 2017) ~A$0.875 0.80 Total Ordinary Shares on Issue 150,237,078 0.70 Options on Issue 49,675,922 0.60 AUD 0.50 Market Capitalisation ~A$131m 0
Slide 5: Board of Directors & Executive Management
Board of Directors & Executive Management Megan Baldwin, PhD, MAICD CEO and Managing Director Appointed CEO Feb ’14, joined company in 2008. Over 20 years experience in research and drug development of therapies targeting angiogenesis. Previously held roles at Genentech (now Roche) in US, in R&D and
Slide 6: The Disease Process of Wet AMD
The Disease Process of Wet AMD Normal Retina Choroid ‘Wet’ AMD 6 Figure: The Angiogenesis Foundation
Slide 7: Monitoring Patients & Endpoints in Wet AMD Trials
Monitoring Patients & Endpoints in Wet AMD Trials SD-OCT Visual Acuity Change in Visual Acuity Change in Retinal Subfield Thickness (# letters) from Baseline (CST) from Baseline – Indicator of fluid 7
Slide 8: Large and Growing Market Opportunity
Large and Growing Market Opportunity • Wet AMD is the leading cause of blindness in the western world in people >55 yrs • Increasing prevalence due to ageing population • Estimated 1.8m in US have wet AMD* • Prevalence expected to double by 2020 • Existing therapies targeting VEGF-A are sub-optimall
Slide 9: Lucentis Phase 3 Registrational Studies
Lucentis® Phase 3 Registrational Studies In MARINA trial (Phase 3 registrational): ~6 letters gain in vision compared to baseline at Week 12 in patients with minimally classic/occult wet AMD lesions treated with Lucentis® (ranibizumab) Wk12 MARINA Ph3 Trial Rosenfeld et al., NEJM, 355;14, pp 1419-14
Slide 10: An Unmet Medical Need for Wet AMD
An Unmet Medical Need for Wet AMD Despite receiving a VEGF-A inhibitor (Lucentis®, Eylea® or Avastin®): >50% do not achieve significant vision gain 2/3 will continue to have fluid at the back of the eye 25% will have further vision loss at 12 mos 10
Slide 11: OPT-302 for Wet AMD
OPT-302 for Wet AMD • Lead molecule: VEGF-C/D VEGF-C/D Extra-Cellular OPT-302 (soluble VEGFR-3, VEGF-C/-D ‘Trap’) Domains 1-3 hVEGFR-3 • Mechanism: Blocks VEGF-C and VEGF-D: • Inhibits blood vessel growth hIgG1 Fc • Inhibits vessel leak • Strategy: To develop OPT-302 for use in combination wit
Slide 12: Resistance to anti-VEGF-A Monotherapy
Resistance to anti-VEGF-A Monotherapy • Long-term single-agent therapy with OPT-302 EyleaTM LucentisTM VEGF-A inhibitors is associated with sub-optimal response VEGF-B VEGF-C PIGF VEGF-A VEGF-D Sub-optimal improvements in visual acuity (<15-letter gain) Persistent retinal fluid • Resistance to V
Slide 13: VEGF-A inhibition upregulates VEGF-C/-D in Cancer
VEGF-A inhibition upregulates VEGF-C/-D in Cancer “The association of alternate VEGF “Mechanisms of evasion to antiangiogenic ligands with resistance to anti-VEGF therapy in glioblastoma” therapy in metastatic colorectal Rose et al., 2010. cancer” - Lieu et al., 2013. 13
Slide 14: Elevated VEGF-C in Wet AMD Patients
Elevated VEGF-C in Wet AMD Patients • VEGF-C levels in the retina increase with disease severity • Aqueous levels of VEGF-C are significantly increased at 1 and 2 months following IVT injection of Avastin® (a-VEGF-A mAb) to wet AMD pts* (pg/ml) 66% pg/ml 14 * ARVO (Association for Research in Vision
Slide 15: OPT-302
OPT-302 • OPT-302: a soluble form of VEGFR-3 • Comprises the extracellular domains 1-3 of VEGFR-3 and the Fc Fragment of human IgG1 • Potent inhibitor of VEGF-C (~5pM) and VEGF-D (~0.5 nM) • A ‘trap’ that binds and neutralises the activity of VEGF-C and VEGF-D, blocking binding to the receptors VEGF
Slide 16: Ocular Biodistribution & PK of OPT-302 Comparable to EYLEA in Rabbits
The Ocular Biodistribution & PK of OPT-302 is Comparable to EYLEA® in Rabbits OPT-302 has comparable ocular biodistribution and PK profile in rabbits to EYLEA®. Retina 250,000 200,000 150,000 OPT-302 OPT-302 Retina VGX-300 100,000 Aflibercept Retina Eylea (EYLEA®) 50,000 0 1hr 12hr 24hr 72hr 168hr 3
Slide 17: OPT-302 Activity in Mouse Wet AMD Model
OPT-302 Activity in Mouse Wet AMD Model Combined inhibition of VEGF-A (Eylea®), VEGF-C and VEGF-D (OPT-302) is more effective than inhibition of VEGF-A alone Control OPT-302 70% 78% 91% EYLEA™ OPT-302 + EYLEA® * * Pairwise comparison: OPT-302 vs Eylea + OPT-302 (p<0.02) Eylea vs Eylea + OPT-302 (p<0
Slide 18: The Opportunity for OPT-302
The Opportunity for OPT-302 • To increase the number of patients who experience a significant gain in vision • To increase the magnitude of the vision gain • To prolong response to therapy and prevent visual decline • Potential to reduce dosing frequency 18
Slide 19: OPT-302 Phase 1/2A Trial Design
OPT-302 Phase 1/2A ClinTrials.gov ID#: NCT02543229 Dose-escalation & dose-expansion of repeated IVT injections Phase 1: Dose-escalation Phase 2A: Dose-expansion (Open-label) (Randomised) OPT-302 (2.0 mg) OPT-302 (2.0 mg) Monotherapy* Monotherapy* 24 IVT Q4W x 3, n=5 IVT Q4W x 3, n=23 pts at Week Fol
Slide 20: OPT-302 Phase 1/2A Study Objectives
OPT-302 Phase 1/2A Study Objectives • Primary Objectives: To evaluate the safety and establish the dose of OPT-302 administered by intravitreal (IVT) injection in combination with IVT Lucentis® in subjects with wet AMD • Secondary Objectives: Mean change in BCVA (visual acuity) (ETDRS) from base
Slide 21: OPT-302 Phase 1: Patient Demographics
OPT-302 Phase 1: Patient Demographics • Run under FDA IND at 14 clinical sites in the US • 20 pts (mean age 74.8) • 14/20 females, 6/20 males • 17/20 occult, 2/20 min classic, 1/20 predominantly classic • Each patient received 3 intravitreal injections of Lucentis® of OPT-302 either alone or in comb
Slide 22: OPT-302 Safe & Well Tolerated in Phase 1 Study
OPT-302 Safe & Well Tolerated in Phase 1 Study • OPT-302 successfully met primary safety objective in Phase 1 dose escalation study • No dose limiting toxicities (and MTD not reached) through week 12 in: • OPT-302 monotherapy (2.0 mg), and • Cohorts of OPT-302 (0.3, 1, 2 mg) in combination with Luce
Slide 23: Phase 1 Secondary Endpoints
Phase 1 Secondary Endpoints • Overall, 16/19 evaluable pts maintained or gained vision from baseline to week 12 • No patient lost more than 3 letters. All of the patients that lost VA from baseline received combination OPT-302 + Lucentis® therapy. 23
Slide 24: Naïve Patients
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Slide 25: Treatment-Naïve Patients: Visual Acuity
Treatment-Naïve Patients: Visual Acuity Mean Change in Visual Acuity at Week 12 from Baseline 18 16.5 Mean change in Visual Acuity from 16 Baseline at Wk 12 (# letters) 14 12 10 9.5 8.7 Letters Fovista® + Lucentis® W12 (Ophthotech Ph2b) 8 6 5.9 Letters Lucentis® W12 (MARINA Ph3) 5.1 Letters Lucentis
Slide 26: Treatment-Naïve Patients: Retinal Thickness
Treatment-Naïve Patients: Retinal Thickness Mean Central Subfield Thickness (CST) 600 500 Central Subfield Thickness (M) 400 214 uM (42.7%) 300 200 100 0 Baseline Week 12 OPT-302 + Lucentis® (n=4) 26
Slide 27: Prior-Treated Patients
Prior-Treated Patients (Sub-responsive to anti-VEGF-A) 27
Slide 28: Prior-Treated Patients: Visual Acuity
Prior-Treated Patients: Visual Acuity • Majority of vision gain in Lucentis® treated patients occurs within 3 months • Plateau “ceiling effect”of response with no other treatment options • Difficult to treat patient population, very large market opportunity • Mean number of Prior anti-VEGF-A therapi
Slide 29: Prior-Treated Patients: Visual Acuity & Retinal Thickness
Prior-Treated Patients: Visual Acuity & Retinal Thickness Mean Change Visual Mean Central Subfield Thickness Acuity from Baseline 400 at Wk 12 Central Subfield Thickness (M) 4.5 4 letters 390 Mean change in Visual Acuity from 4 Baseline at Wk 12 (# letters) 380 3.5 42 uM (10.8%) 3 370 2.5 360 2 1.5
Slide 30: Prior-Treated Patient: OPT-302 (0.3 mg) + Lucentis (0.5 mg)
Prior-Treated Patient: OPT-302 (0.3 mg) + Lucentis® (0.5 mg) • Male aged 64 • Occult lesion • Prior treatment: Eylea®/REGN-910-3 x6 Baseline Week 4 Week 12 VA: 77 letters VA: 83 letters VA: 79 letters CST: 365 µM CST: 281 µM CST: 298 µM 30
Slide 31: Prior-Treated Patient: OPT-302 (1.0 mg) + Lucentis (0.5 mg)
Prior-Treated Patient: OPT-302 (1.0 mg) + Lucentis® (0.5 mg) • Female aged 71 • Occult lesion • Prior treatment: Avastin® x10 Baseline Week 4 Week 12 VA: 74 letters VA: 74 letters VA: 84 letters CST: 270 µM CST: 258 µM CST: 255 µM 31
Slide 32: OPT-302 Monotherapy
fj We OPT-302 Monotherapy
Slide 33: OPT-302 Monotherapy
OPT-302 Monotherapy • OPT-302 monotherapy included to identify clinical activity without a background standard of care • Natural history of wet AMD: without treatment, often chronic, rapid decline in visual acuity and increase in retinal fluid • a-VEGF-A rescue therapy offered to patients at physici
Slide 34: Phase 1 Secondary Endpoints: VA and OCT Data Summary
Phase 1 Secondary Endpoints: VA and OCT Data Summary • Overall, 16/19 evaluable pts maintained or gained vision from baseline to week 12 Treatment Mean VA gain at Wk12 Mean Reduction in Central from Baseline (# letters) Subfield Thickness at Wk12 from Baseline Combo OPT-302 + Lucentis® in both Naïve
Slide 35: OPT-302 Proposed Phase 2B in Wet AMD
OPT-302 Proposed Phase 2B in Wet AMD Combination OPT-302 + Lucentis® vs Lucentis® OPT-302 (Dose 1) + Lucentis® (0.5 mg) Primary Endpoint: Mean Change in Visual Acuity from Baseline at Week 24/36 Wet AMD Secondary Naïve Pts OPT-302 (Dose 2) + Lucentis® (0.5 mg) Endpoints: Retinal Thickness (SD-OCT, w
Slide 36: Wet AMD Landscape of Novel Targets (non-VEGF-A)
Wet AMD Landscape of Novel Targets (non-VEGF-A) Phase 1 Phase 2 Phase 3 REGN2176-3 VEGF-C/-D (Regeneron)* OPT-302 (Opthea) Marketed PDGF/VEGF-A DS-7080 REGN910-3 (Daiichi Sankyo) (Regeneron) ROBO-4 Ang2/VEGF-A HI-con1 (Iconic) RG7716 (Roche) Tissue Factor Ang2/VEGF-A Fovista® (Ophthotech)* OHR-102 (
Slide 37: OPT-302 Intellectual Property
OPT-302 Intellectual Property Summary covering sVEGFR-3 for eye disease COMPOSITION OF MATTER TERM Covering sVEGFR-3 (inc. OPT-302) • Granted Patents: Europe, Japan, Canada, Australia 2022 • Granted Patent: USA 2026 Covering OPT-302 ~2034 • Recently filed new specific composition of matter PCT inter
Slide 38: OPT-302 Program Highlights
OPT-302 Program Highlights • OPT-302 has broad development potential in a range of eye diseases • Targets validated pathway involved in wet AMD progression and mechanism of escape from existing therapies that is differentiated to a-VEGF-A therapies • Large unmet medical need for wet AMD, current tre
Slide 39: Snapshot
Snapshot OPT-302: OPT-302 + a-VEGF-A achieves more - Soluble form VEGFR-3 complete blockade of VEGF pathway Asset - A ‘trap’ similar to Eylea™ with distinct MOA Strategy - Targets a mechanism of a-VEGF-A resistance Inhibits VEGF-C & VEGF-D - Trial investigating monotherapy and Mechanism - Anti-angio
Slide 40: Contact details
Suite 0403, Level 4, 650 Chapel Street, South Yarra 3141 Victoria Australia T +61 (3) 9826 0399 E [email protected] www.opthea.com