Opthea Limited · ASX:OPT
Opthea — Opthea Equity Raising Presentation
57 slides from Opthea's investor presentation, Dec 2, 2019
Slide 1: Equity Raising Presentation
Not for distribution or release in the United States Equity Raising Presentation Institutional Placement 2 December 2019
Slide 2: Important Notice and Disclaimer
Important Notice and Disclaimer IMPORTANT: You must read the following before continuing. By accepting or viewing this presentation you represent and warrant that you are entitled to receive or access the presentation in accordance with the restrictions below and agree to be bound by the limitations
Slide 3: Important Notice and Disclaimer (cont'd)
Important Notice and Disclaimer (cont’d) Future performance / forward-looking statements This presentation contains certain forward-looking statements. The words "expect", "anticipate", "estimate", "intend", "believe", "guidance", "should", "could", "may", "will", "predict", "plan" and other similar
Slide 4: Important Notice and Disclaimer (cont'd)
Important Notice and Disclaimer (cont’d) Each institution or person that reviews the information contained in this presentation represents and agrees (a) that each such institution or person is outside the United States (within the meaning of Regulation S under the U.S. Securities Act) and (b) that
Slide 5: Table of Contents
Table of Contents Section Page Placement Overview 6 Company Overview 10 OPT-302 Phase 2B wet AMD Data 18 Ongoing Clinical Trials 42 Appendix – Key Risks 48 Appendix – Foreign Selling Restrictions 55 5
Slide 6: Placement Overview
Placement Overview QOPTHEA
Slide 7: Placement Details
Placement Details Issuer ● Opthea Limited (“Opthea ”) Ticker / Exchange ● OPT / ASX ● Opthea has undertaken a non-underwritten private placement to a certain small number of professional and sophisticated investors in Australia and the United Kingdom and has received commitments which will raise app
Slide 8: Sources and Uses of Funds
Sources and Uses of Funds Sources and uses of Placement funds Funding commitments from capital raise • Proceeds from the Placement will be used to: Sources of funds A$m − fund further clinical development of OPT-302 as a therapy for wet AMD through Placement 50(1) commencement of two concurrent Phas
Slide 9: Timetable
Timetable Event Date Participating investors execute Placement Agreements Sunday , 1 December 2019 Announcement of the Placement Monday, 2 December 2019 Settlement of Placement Thursday, 5 December 2019 Allotment and trading of New Shares under the Placement Friday, 6 December 2019 9 Note: The timet
Slide 10: Company Overview
Company Overview QOPTHEA
Slide 11: Business Snapshot
Business Snapshot • Public company listed on ASX (ASX:OPT) developing OPT-302 for wet AMD and Diabetic Macular Edema (“DME”) Opthea Limited • Market capitalisation prior to capital raise of A$683m at 29 November 2019 and cash on hand of A$30m at 30 October 2019 OPT-302 has a novel • OPT-302 (sVEGFR-
Slide 12: OPT-302 Clinical Program
OPT-302 Clinical Program Combination 1o Data Upcoming Agent Preclinical Phase 1 Phase 2a Phase 2b Phase 3 Status Analysis Future Milestones Wet AMD April 2017 Complete Primary Endpoint Met Ph 1/2a (n=51) (Safety) August 2019 Primary Positive Endpoint Met Ph 2b (n=366) (Superior Efficacy) OPT-302 Ran
Slide 13: Wet AMD and DME are Leading Causes of Vision Loss in the Elderly and Diabetic Populations
Wet AMD and DME are Leading Causes of Vision Loss in the Elderly and Diabetic Populations Respectively VEGF-A VEGF-C/D Wet AMD DME Driver: Ageing Sustained hyperglycaemia Prevalence: • Increasing prevalence due to ageing population • Increasing due to diabetes epidemic • ~3M people worldwide, includ
Slide 14: Existing Therapies Primarily Target VEGF-A
Existing Therapies Primarily Target VEGF-A OPT-302 inhibits VEGF-C/D VEGF-C OPT-302: Rationale VEGF-D • Long-term therapy with selective VEGF-A Ranibizumab inhibitors is associated with sub-optimal (Lucentis®) responses VEGF-C OPT-302 • Sub-optimal improvements in visual acuity Bevacizumab# VEGF-A V
Slide 15: A Currently Unmet Medical Need for wet AMD and DME
A Currently Unmet Medical Need for wet AMD and DME Despite receiving a VEGF-A inhibitor (ranibizumab, aflibercept or bevacizumab)*: Large and Growing Market Opportunity • Wet AMD and DME are the leading causes of blindness in the >50% Do not achieve significant vision gains elderly and diabetic popu
Slide 16: OPT-302: A 'trap' inhibitor of VEGF-C and VEGF-D
OPT-302: A ‘trap’ inhibitor of VEGF-C and VEGF-D VEGF-C OPT-302: A soluble form of VEGFR-3 Strategy VEGF-D • Comprises the extracellular domains 1-3 of VEGFR-3 and the Fc • To develop OPT-302 for use in combination with inhibitors of VEGF-A fragment of human IgG1 to address the unmet medical need in
Slide 17: OPT-302 Intellectual Property
OPT-302 Intellectual Property Summary covering sVEGFR-3 for Eye Disease COMPOSITION OF MATTER TERM Covering OPT-302 molecule • Granted patents in the USA, Japan, Russia, Australia, South Africa and Singapore 2034* • Patents accepted for grant in Europe, Malaysia and Mexico • Applications pending in
Slide 18: OPT-302: Phase 2b wet AMD
OPT-302: Phase 2b wet AMD A dose-ranging study of intravitreal OPT-302 in combination with ranibizumab, compared with ranibizumab alone, in participants with wet AMD (OPT-302-1002; NCT ClinicalTrials.gov Identifier: NCT03345082 113 sites across 10 countries including the US, EU and Israel) 18
Slide 19: Study Outcomes - OPT-302 Phase 2b wet AMD Trial
Study Outcomes - OPT-302 Phase 2b wet AMD Trial Phase 2b trial met primary endpoint • OPT-302 (2.0mg) combination therapy demonstrated superiority in visual acuity over ranibizumab + sham • Vision gain of +3.4 letters • Statistically significant (p=0.0107) • Ranibizumab control arm performed excepti
Slide 20: Study Overview
Study Overview Treatment naïve patients with Wet AMD Key Inclusion Criteria 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 clinically sig
Slide 21: 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 22: 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) 20 Mean change in BCVA (SEM) Mean change in BCVA (SEM) 15 15 14.22 (letters) (letters) 10 10.84
Slide 23: Vision Gain and Vision Loss - Baseline to Week 24
Vision Gain and Vision Loss - Baseline to Week 24 More patients gain, and fewer patients lose, ≥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 ³ 1
Slide 24: 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 (µm) (µm) -133.80 200 -140 -146.70 150 -160 100 Sham + 0.5 mg r
Slide 25: 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 26: 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 27: 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 28: 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 29: 2-Line and 3-Line Vision Gain at Week 24 by Lesion Type
2-Line and 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 Minimally Classic Occult 80 80 60 60 76.9 55.8 66.0 60 60 58.0 % Participants % Participants % Participants %
Slide 30: 2-Line and 3-Line Vision Loss at Week 24 by Lesion Type
2-Line and 3-Line Vision Loss at Week 24 by Lesion Type Fewer patients with minimally classic and occult lesions lose ≥10 and ≥15 letters following OPT-302 combination therapy Minimally Classic Occult Minimally Classic Occult 10 10 6 6 9.6 5.8 8 8 % Participants % Participants % Participants % Parti
Slide 31: 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 (µ m) (µ m) -134.6 -140 -140 -1
Slide 32: Sub-Retinal Fluid and Intra-Retinal at Week 24 by Lesion Type
Sub-Retinal Fluid and Intra-Retinal at Week 24 by Lesion Type Fewer participants with minimally classic and occult lesions have retinal fluid at week 24 following OPT-302 combination therapy % Patients with Sub-Retinal Fluid Present % Patients with Intra-Retinal Fluid Present Minimally Classic Occul
Slide 33: 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 34: 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 35: 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 36: 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 36 mITT; RAP – retinal angiomato
Slide 37: 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 38: 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 15 15.4 15 (letters) (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 39: 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 40: Planned: OPT-302 Pivotal Phase 3 Program
Planned: OPT-302 Pivotal Phase 3 Program Efficacy Phase Safety Phase Ranibizumab (0.5 mg) + OPT-302 (2.0 mg) Ranibizumab (0.5 mg) + OPT-302 (2.0 mg) Safety Follow –up Endpoint Week 48 Primary Efficacy IVT q4w x 48 weeks IVT q4w or q8w* x 48 weeks Week 96 Wet AMD Naïve Pts Ranibizumab (0.5 mg) + Sham
Slide 41: Ongoing Clinical Trials
Ongoing Clinical Trials Phase 1b/2a DME Phase 1b/2a study of OPT-302 in combination with aflibercept for persistent central-involved diabetic macular edema 41
Slide 42: The Majority of DME Patients Sub-Optimally Respond to Current Therapies
The Majority of DME Patients Sub-Optimally Respond to Current Therapies • DRCR Protocol I evaluated response to anti-VEGF-A from baseline to 156 weeks • Lucentis and sham injections every 4 weeks to week 12, then as needed • At week 12: Ø 40% patients gained < 5 letters (mean -0.3) by week 12 Ø > 60
Slide 43: Phase 1b/2a Dose Escalation study of OPT-302 + Aflibercept in DME
Phase 1b/2a Dose Escalation study of OPT-302 + Aflibercept in DME Phase 1b Dose-Escalation Phase 2a Dose-Expansion (Complete- data reported) (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 pt
Slide 44: OPT-302 + aflibercept in DME: Phase 1b Safety Results
OPT-302 + aflibercept in DME: Phase 1b Safety Results OPT-302 (0.3 mg) + OPT-302 (1 mg) + OPT-302 (2 mg) + • OPT-302 (0.3, 1 or 2 mg) + aflibercept (2 mg) Selected Adverse Events: Total Number of Aflibercept (2.0 mg) Aflibercept (2.0 mg) Aflibercept (2.0 mg) administered by IVT injection (Baseline,
Slide 45: OPT-302 + aflibercept in DME: Gains in Visual Acuity at Week 12
OPT-302 + aflibercept in DME: Gains in Visual Acuity at Week 12 Visual Acuity Retinal Thickness Dose Response Relationship and Reductions in Retinal Swelling in Phase 1b 45 Error Bars: SEM; Mean Baseline CST = 434 µm
Slide 46: Patients with Bilateral DME
Patients with Bilateral DME Gains in Visual Acuity and Reductions in Retinal Thickness in OPT-302 + Aflibercept Treated Eyes Mean Change in BCVA Baseline Mean Change in CST (uM) to Week 12 Baseline to Week 12 • 5/9 patients enrolled in the Phase 1b trial had bilateral DME (DME in both eyes) • Study
Slide 47: Appendix – Key Risks
Appendix — Key risks QOPTHEA
Slide 48: Key Risks
Key Risks This section outlines some of the key risks associated with an investment in Opthea, together with the risks relating to participation in the Placement. Opthea’s business is subject to a number of risk factors both specific to its business and of a general nature which may impact on its fu
Slide 49: Key Risks – Business Risks (cont'd)
Key Risks – Business Risks (cont’d) Opthea maintains sensitive clinical data. Opthea may be subject to a cyber security attack or data breaches by employees or external parties with either permitted or unauthorised access. There is therefore a risk that sensitive data may be exposed to the public or
Slide 50: Key Risks – Business Risks (cont'd)
Key Risks – Business Risks (cont’d) The Opthea business model requires ongoing re-investment into clinical trials with no revenues currently contracted. As such, Opthea will continue to rely upon cash, raised Access to capital through equity or debt, to fund the business as an on-going concern, incl
Slide 51: Key Risks – Business Risks (cont'd)
Key Risks – Business Risks (cont’d) Opthea is unable to predict the risk of financial failure or default by a participant in any joint venture to which Opthea may become a party or the insolvency or managerial failure Joint venture parties, by any of the contractors used by Opthea in any of its acti
Slide 52: Key Risks – Offer and General Risks
Key Risks – Offer and General Risks Offer and General Risks The market price of Opthea shares will fluctuate due to various factors, many of which are non-specific to Opthea and beyond the control of Opthea, including recommendations by brokers and analysts, Australian and international general econ
Slide 53: Key Risks – Offer and General Risks (cont'd)
Key Risks – Offer and General Risks (cont’d) Opthea prepares its general purpose financial statements in accordance with Australian International Financial Reporting Standards (AIFRS) and the Corporations Act 2001 (Cth), Accounting standards which may differ significantly from the accounting standar
Slide 54: Appendix – Foreign Selling Restrictions
Appendix – Foreign Selling Restrictions 54
Slide 55: Foreign Selling Restrictions
Foreign Selling Restrictions Foreign selling restrictions This document does not constitute an offer of New Shares of the Company in any jurisdiction in which it would be unlawful. In particular, this document may not be distributed to any person, and the New Shares may not be offered or sold, in an
Slide 56: Foreign Selling Restrictions (cont'd)
Foreign Selling Restrictions (cont’d) United States This document may not be distributed or released in the United States. This document does not constitute an offer to sell, or a solicitation of an offer to buy, securities in the United States or in any other jurisdiction in which such an offer wou
Slide 57: Megan Baldwin CEO and Managing Director
Megan Baldwin CEO and 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