Opthea Ltd — AGM Information 2017

Nov 22, 2017

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2017 Annual General Meeting

Corporate Presentation, November 23, 2017 Megan Baldwin PhD, CEO & Managing Director

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 capital.

This presentation is not an offer or invitation for subscription or purchase of or a recommendation of securities. It does not take into account the investment objectives, financial situation and particular needs of the investor. Before making any investment in Opthea, the investor or prospective investor should consider whether such an investment is appropriate to their particular investment needs, objectives and financial circumstances and consult an investment advisor if necessary.

This presentation may contain forward-looking statements regarding the potential of the Company’s projects and interests and the development and therapeutic potential of the company’s research and development. Any statement describing a goal, expectation, intention or belief of the company is a forward-looking statement and should be considered an at-risk statement. Such statements are subject to certain risks and uncertainties, particularly those inherent in the process of discovering, developing and commercialising drugs that are safe and effective for use as human therapeutics and the financing of such activities. There is no guarantee that the Company’s research and development projects and interests (where applicable) will receive regulatory approvals or prove to be commercially successful in the future. Actual results of further research could differ from those projected or detailed in this presentation. As a result, you are cautioned not to rely on forward-looking statements. Consideration should be given to these and other risks concerning research and development programs referred to in this presentation.

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Corporate & Operational Achievements

• ✓ Met primary safety objective in Phase 1/2A wAMD trial (n = 51 patients)

• ✓ Demonstrated safety and tolerability of OPT-302 as monotherapy and in combination with Lucentis®

• ✓ Demonstrated clinical activity of OPT-302 as a monotherapy and in combination with Lucentis® in both treatment naïve patients and prior treated patients

• ✓ Raised A$45m in over-subscribed capital raising (April ‘17)

• $42m in placement to Australian, US and EU based institutional investors

• $3m in Aust/NZ rights issue

• ✓ Strengthened financial position, fully-funded through 2020 and completion of Phase 2b wet AMD trial and two Phase 2a trials

• ✓ Expanded clinical management team

• ✓ Granted key US patent covering OPT-302 and its use (exp. 2034)

• ✓ R&D Tax Incentive anticipated ~$2.7m (Australian & international expenditure)

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Corporate & Operational Achievements

• ✓ Engaged global CRO (contract research organisation) for wAMD & DME

• ✓ Progressed activities for Phase 2b wAMD study

  • ✓ Type C Meeting US FDA

  • ✓ Scientific Advice meetings MHRA (UK), MPA (Sweden)

  • ✓ Protocol finalised & submitted to IND (US FDA)

  • ✓ ClinTrials.gov ID#NCT03345082

• ✓ Progressed activities for Phase 2a DME study

  • ✓ Protocol submitted to IND (US FDA)

• ✓ wAMD and DME trials progressing to schedule

• ✓ Expect to initiate enrolment by end 2017

• ✓ Planning underway for Phase 2A wAMD trial (eg. Prior-Tx patients)

• ✓ Continued to raise company profile in local and international investment and clinical ophthalmology communities

• ✓ Data presented at international conferences and Innovation Summit (OIS/ASRS,

• EURetina) by mgmt, clinical advisory board & investigators

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4

Financial Position (Unaudited)

Key Financial Details	ASX: OPT
Ticker Symbol	ASX:OPT
Share Price (Nov 22 2017)	~A$0.69
Total Ordinary Shares on Issue	200,624,570
Options on Issue	48,086,642
Market Capitalisation (Oct 20 2017)	~A$140m (~USD106m)
Trading Range (last 12 months)	A$0.67– 1.20
Cash Balance (Oct 31 2017)	~A$48.5m
Forecast Net Operating Cash Burn (CY 2017)	~$18m
Top 20 Shareholders Own	69%
Institutional Holders	84%
Details
• Cash positive until end ’20
• Fully-funded through • ~350 pt Ph2B wAMD trial (randomised, statistically powered) • ~90 pt Ph2A DME trial (randomised, statistically powered) • Ph 2A trial (eg. Prior-Tx Patients)
• Accumm. tax and capital losses ~A$15m

Details

• Cash positive until end ’20

• Fully-funded through

  • ~350 pt Ph2B wAMD trial (randomised, statistically powered)

  • ~90 pt Ph2A DME trial (randomised, statistically powered)

  • Ph 2A trial (eg. Prior-Tx Patients)

• 5 • Accumm. tax and capital losses ~A$15m

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Share Price Performance (Nov 2015 - Nov 2017)
1.4
High
1.2
1
0.8
0.6
0.4
0.2
0
AUD
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Shareholders by Region
Retail
16% US Funds
29%
EU/Other Funds Australian Funds 35%
20%
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OPT-302: fully funded through an expanded clinical development program

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2017 2018 2019 2020
2H ‘17 1H ‘18 2H ‘18 1H ‘19 2H ‘19 1H ‘20 2H ‘20
Topline Data: Phase 2B wet AMD
Initiate 351 Phase 2B wet AMD
patient Phase 2B
wet AMD trial
Topline Data: Phase 2A DME
Initiate ~90 Phase 2A DME
patient Phase
2A DME
Topline Data: Phase 2A wAMD
Phase 2A wAMD
Initiate Phase 2A
wet AMD trial
(eg. Prior-
Treated patients)
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6

Note: Dates provided in timelines are estimates, and indicative only, and subject to change as a result of a number of factors outside of Opthea’s control.

OPT-302 for Wet AMD

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VEGF-C/D VEGF-C/D
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Extra-Cellular
Domains 1-3
hVEGFR-3
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hIgG1 Fc
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• OPT-302 blocks VEGF-C and VEGF-D

• The VEGF family is recognised as the most

• important family of growth factors controlling vessel growth and leakage

• Blocks vessel growth and leakage, two of the

• key hallmarks of wet AMD

• Leading cause of blindness in over 55’s,

• increasing prevalence

Wet AMD

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Normal Retina

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Our Goal: To Improve Vision

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An Unmet Medical Need for Wet AMD

Despite receiving a VEGF-A inhibitor (Lucentis, Eylea or Avastin):

50% Do not achieve significant vision gains 2/3 Will continue to have fluid at the back of the eye 25% Will have further vision loss at 12 months

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Opportunity: New Products that Improve Efficacy and Durability

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Very few novel combination therapies in development

DURABILITY (fewer injections) & BIOSIMILARS

Anti-VEGF-A

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Abicipar pegol Brolucizumab PAN-90806 Ranibizumab Sevacizumab
Anti-VEGF-A (RTH-258) Anti-VEGF-A biosimilar Anti-VEGF-A
Molecular Partners Anti-VEGF-A PanOptica Anti-VEGF-A Apexigen
Allergan Novartis Pfenex
Ranibizumab Squalamine SB11 (Lucentis X-82 RGX-314 Ranibizumab biosimilar
biosimilar Anti-VEGF biosimilar) Anti-VEGF/PDGF Gene therapy Anti-VEGF-A
Anti-VEGF-A Ohr Pharmaceutical Anti-VEGF-A Tyrogenex Regenxbio Lupin Ltd.
Formycon Samsung Bioepis
Mechanism Comparison Of IVT Administered Wet AMD Agents
Eylea Lucentis Avastin [#] OPT-302 RG7716 REGN910 Fovista
Also targets Co-formulated
VEGF-A with Eylea
VEGF-B VEGF-A VEGF-C/D ANG-2 PDGF
VEGFR-1 VEGFR-2 VEGFR-3 Tie 2 PDGF-R
Phase III Phase II Phase I
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• = In Clinical Development = Failed to meet primary endpoint = Approved therapies

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Opthea is the Only Company Working on VEGF-C/D
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10 * Small molecule TKIs such as X-82 (Tyrogenix) and Squalamine (Ohr Pharmaceuticals) are not represented here. Other biologics in development that selectively target VEGF-A include Abicipar Pegol (DARPin, Allergan), RTH258 (Novartis), and a-VEGF-A biosimilars # Avastin is used off-label for the treatment of wet AMD

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OPT-302 Phase 1/2A

Opthea’s Phase 1/2A clinical trial in wet AMD enrolled 51 patients:

OPT-302 Monotherapy

n=13 patients Administered OPT-302 alone

OPT-302 + Lucentis® Naïve Patients

n=18 patients Administered combination therapy to patients who had not previously received wAMD therapy

OPT-302 + Lucentis® Prior-Treated Patients

n=20 patients Administered combination therapy to patients who had previously received wAMD therapy and shown a sub-response

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Phase 1/2A Monotherapy Patients

Mean Change in Visual Acuity in Non-Rescue Patients

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6.1
(9/13)
(7/12)
6
+5.6
3.8
(10/13)
4
2
0
B a s e lin e W e e k 4 W e e k 8 W ee k 12
V is u a l A c u ity
(M e a n C h a n g e fro m B a s e lin e )
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One treatment-naïve patient in the monotherapy cohort with myocardial infarction died (on day 77) prior to the week 12 visit (unrelated to study drugs)

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Phase 1/2A Monotherapy Patients

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Treatment-Naïve Prior-Treated
2 5 2 5
2 0 2 0
1 5 1 5
1 0 1 0
5 5
0 0
MARINA MARINA
-5 -5
Sham injection at Sham injection at
Wk12 Wk12
-1 0 -1 0
w e e k 4 w e e k 8w e e k 1 2 s h a m w e e k 4 w e e k 8w e e k 1 2 s h a m
V is u a l A c u ity
(M e a n C h a n g e fro m B a s e lin e )
V is u a l A c u ity
(M e a n C h a n g e fro m B a s e lin e )
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Gains in Visual Acuity in Patients Treated with OPT-302 Monotherapy

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* Rosenfeld et al., NEJM, 355;14, pp 1419-1431, 2006

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Gains in Visual Acuity in Patients Treated - with OPT 302 Combination Therapy

Treatment Naïve Patients Mean Change in Visual Acuity from Baseline (letters)

Prior-Treated Patients Mean Change in Visual Acuity from Baseline (letters)

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+4.9
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+10.8
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Improved Visual Acuity in both Treatment-Naïve and Prior-Treated Patients Treated with OPT-302 + Lucentis Combination Therapy

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Number of Patients: 18; Mean Baseline VA = 56.5 Letters (MARINA: Mean Baseline VA = 53.7 letters)

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* Rosenfeld et al., NEJM, 355;14, pp 1419-1431, 2006

Reductions in Retinal Fluid in Patients Treated with OPT-302 Combination Thera py

Prior-Treated Patients

Treatment Naïve Patients

Mean Sub-Retinal Fluid

Mean Sub-Retinal Fluid

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51%
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83%
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• 16% patients had 100% resolution of SRF

• SRF reduced by 83% by Week 12

• 72% patients had 100% resolution of SRF by Week 12

• 47% had >50% resolution of SRF by Week 12

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Treatment-Naïve Patients: Reductions in CNV

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Reduction in CNV Size on FA % Patients with Absent CNV on FA
9 60
7.71
8
50 %
50
7
6 40
5
27.8 %
30
3.74
4
3 20
2.03
2
10
1 5.6 %
0 0
Baseline Week 4 Week 12 Baseline Week 4 Week 12
)
2
CNV Size (mm
% Patients with Absent CNV on FA
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OPT-302 + Ranibizumab

OPT-302 + Ranibizumab

50% of Treatment-Naïve Patients had no detectable CNV after 12 weeks

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CNV: Choroidal Neovascularisation; Treatment Naïve Patients: n = 18; OPT-302 (0.3, 2.0 mg) + ranibizumab (0.5 mg)

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Case-Study: Treatment-Naïve Patient (Occult)

OPT-302 (2 mg) + Ranibizumab (0.5 mg)

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Baseline Week 4 Week 12
VA: 53 letters VA: 64 letters VA: 73 letters
CNV: 3.11 mm [2] CNV: 2.91 mm [2] CNV: 0 mm [2]
CST: 279 µM CST: 217 µM CST: 233 µM
SRF: 192 µM SRF: 0 µM SRF: 0 µM
SHRMw: 1053 µM SHRMw: 0 µM SHRMw: 0 µM
SHRMh: 194 µM SHRMh: 0 µM SHRMh: 0 µM
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Case-Study: Prior-Treated Patient (Occult)

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OPT-302 (2 mg) + Ranibizumab (0.5 mg) Prior-treatment: Ranibizumab (0.5 mg) x28
Baseline Week 4 Week 12
VA: 65 letters VA: 72 letters VA: 78 letters
CNV: 11 mm [2] CNV: 5.28 mm [2] CNV: 8.04 mm [2]
CST: 303 µM CST: 249 µM CST: 248 µM
SRF: 140 µM SRF: 41 µM SRF: 0 µM
SHRMw: 1042 µM SHRMw: 0 µM SHRMw: 0 µM
SHRMh: 133 µM SHRMh: 0 µM SHRMh: 0 µM
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OPT-302 Phase 2B Trial in wet AMD (n=351)

Combination OPT-302 + Lucentis vs Sham + Lucentis

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OPT-302 (Dose 1) + Lucentis (0.5 mg)
Wet AMD
OPT-302 (Dose 2) + Lucentis (0.5 mg)
Naïve Pts
Sham + Lucentis (0.5 mg)
Randomized 1:1:1 to treatment arms : IVT dosing at every 4 weeks (x 6)
Week 24 Follow-up
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• Primary Objective:

• Mean change from baseline in BCVA (visual acuity) (ETDRS) at week 24

• Secondary Objectives:

• The proportion of patients gaining ≥15 or more ETDRS letters from baseline at week 24

• Area under the BCVA over time curve

• The proportion of patients losing ≥15 or more ETDRS letters from baseline at week 24

• Change in central subfield thickness (CST) from baseline at week 24 (SD-OCT)

• Change in intra-retinal fluid and sub-retinal fluid from baseline to week 24 (SD-OCT)

• Safety and tolerability

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Primary data analysis:
est. early 2020
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Diabetic Macular Edema

Diabetic macular edema (DME) is an ophthalmic complication of diabetes and is the leading cause of blindness in diabetics

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Hard exudates
Retina
Microaneurysm
Fovea Macula
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Leaky
retinal
vessel
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• DME is the build-up of fluid (edema) and hard exudates in the macula

• Diabetes can trigger inflammatory responses & lead to microvascular damage in the retina (diabetic retinopathy) which can develop into DME

• Edema leads to blurred vision, darkened & distorted vision

• Increasing prevalence of diabetes in working age adults, growing mkt

• Anti-VEGF-A therapies (Lucentis, Eylea) are the preferred treatment, poor or non-responders often switched to steroids or laser

~1.3M have DME in US and EU

• ~Half of patients exhibit no response or suboptimal response to anti-VEGF-A therapy

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Note: Dates provided in timelines are estimates, and indicative only, and subject to change as a result of a number of factors outside of Opthea’s control.

OPT-302 MOA supports investigation in DME

Published data indicates that VEGF-C and its interaction with VEGFR-2 and VEGFR-3 plays a functional role in pathogenesis of DME

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Hard exudates
Retina
Microaneurysm
Fovea Macula
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Leaky
retinal
vessel
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• OPT-302 has shown evidence of activity to resolve retinal fluid

• VEGFR-2 expression is greater in diabetic retina than non-diabetics

• VEGF-C is elevated in diabetic retinopathy

• Vitreous levels of VEGF-D are elevated in diabetes

• VEGF-C expression is elevated by glucose & proinflammatory cytokines

• Inhibition of VEGF-C and VEGF-D in adipose tissue of mice improves metabolic parameters and insulin sensitivity

VEGF-C/D signaling pathway is implicated in diabetes

• Advanced glycation end products accumulate faster in diabetics and stimulate VEGF-C expression and secretion from the RPE

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OPT-302 Phase 2a Trial in Diabetic Macular Edema

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Phase 1b Dose-escalation Phase 2A: Dose-expansion
(Open-label) (Randomised 2:1)
Sham +
anti-VEGF-A (2.0 mg)
IVT Q4W x 3
OPT-302 ( TBD ) +
anti-VEGF-A (2.0 mg)
IVT Q4W x 3
OPT-302 (2 mg) +
anti-VEGF-A (2.0 mg)
IVT Q4W x 3
OPT-302 (1 mg) + Cohort 3
anti-VEGF-A (2.0 mg)
IVT Q4W x 3
OPT-302 (0.3 mg) + Cohort 2
anti-VEGF-A (2.0 mg)
IVT Q4W x 3
Cohort 1
SOC anti-VEGF-A to week 24
Follow-up to week 12
PRN
then
14 Day DLT window
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• Males & females, ≥ 18 years of age

• Diabetes mellitus (Type 1 or Type 2)

• Recurrent / persistent central-involved DME despite prior anti-VEGF-A therapy with a suboptimal response

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Milestones

OPT-302 Wet AMD Program:

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Phase 1/2a Data Analysis
✓
$45m Cap. Raise
April ‘17
Phase 2b wAMD
First Patient Dosed (USA)
4Q’17
Publication Ph1/2a trial results
in peer-reviewed journal
2Q’18
Phase 2a wAMD Trial (eg. Prior-Tx
Pts) Design Finalised/Initiation
1H’18
Phase 2b wAMD
Primary Data Analysis
1H’20
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OPT-302 DME Program:

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Phase 1b/2a DME Trial
Initiation
4Q’17
Phase 1b/2a DME Trial
Primary Data Analysis
1Q’19
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OPT-302 Program Highlights

• Broad development potential

• Targets validated pathway

• Targets incomplete response to existing a-VEGF-A therapies

• Large unmet medical need for wet AMD & market opportunity

• Phase 1/2a study:

• Demonstrated OPT-302 safety & tolerability (met primary objective)

• Evidence of clinical activity in all treatment groups:

  • Treatment naïve, prior-treated pts

  • Monotherapy & combination therapy

• Consistency of responses across multiple endpoints

• Phase 2b wAMD and Phase 2a DME trials on-track for FPI 4Q’17

• Additional Phase 2a trial in wet AMD to initiate 1H’18

• Multiple near-term and long-term milestones

• Fully-funded through 2020 and clinical trial program

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Suite 0403, Level 4, 650 Chapel Street, South Yarra 3141 Victoria Australia

T +61 (3) 9826 0399 E megan.baldwin@opthea.com

www.opthea.com