OPT-302:

A Novel Therapy for

Eye DiseasesCorporate & Investor Presentation

ASX Small & Mid-Cap Conference Sydney, September 6 2018

Megan Baldwin PhD, CEO & Managing Director

2

Disclaimer

Investment in Opthea Limited (‘Opthea’) is subject to investment risk, including possible loss of income and capital invested. NeitherOpthea nor any other member company of the Opthea Group guarantees any particular rate of return or performance, nor do theyguarantee 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 intoaccount 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 thedevelopment 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 statementsare subject to certain risks and uncertainties, particularly those inherent in the process of discovering, developing andcommercialising drugs that are safe and effective for use as human therapeutics and the financing of such activities. There is noguarantee that the Company’s research and development projects and interests (where applicable) will receive regulatory approvalsor prove to be commercially successful in the future. Actual results of further research could differ from those projected or detailedin this presentation. As a result, you are cautioned not to rely on forward-looking statements. Consideration should be given tothese and other risks concerning research and development programs referred to in this presentation.

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Corporate Summary

• Novel technology and therapy for eye disease

• OPT-302, a new approach for the treatment of wet AMD and DME

• Market opportunity >USD$10 billion worldwide

• Two existing therapies (a-VEGF-A) are sub-optimally clinically effective in the majority of patients

• Strategy is to develop OPT-302 for use in combination with existing treatments

• Reported Phase 1/2a data in wet AMD patients demonstrated:

• Safety of OPT-302

• Evidence of improved vision and reductions in fluid

• Currently enrolling patients in two randomized, controlled clinical trials

• Phase 2b wet AMD and Phase 1b/2a DME studies• Trials are recruiting patients in US, EU, Israel and Australia

ASX: OPT

Intra-vitrealinjection

4

Financial Position (Unaudited)

Key Financial Details ASX: OPT

Ticker Symbol ASX:OPT

Share Price (Aug 31 2018) ~A$0.62

Total Ordinary Shares on Issue 202,797,888

Options on Issue 46,913,324

Market Capitalisation (Aug 31 2018)

~A$126m(~USD91m)

Trading Range (last 12 months) A$0.42 – 0.80

Cash Balance (Jul 31 2018) ~A$30m

Forecast Net Operating Cash Burn(CY 2018)

~$18m

Top 20 Shareholders Own 69%

Institutional Holders 84%

Details

• Cash positive until end ’20

• Fully-funded through• 351 pt Ph2B wAMD trial

(randomised, statistically powered)

• 117 pt Ph2A DME trial

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

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Shareholders & Analyst Coverage

Share Price Performance (Sept 2016 - Aug 2018) Shareholders by Region

US Funds29%

Australian Funds 35%EU/Other Funds

20%

Retail

16%

AU

D

Analyst Coverage

Shane Storey

Tanushree Jain

0

0.2

0.4

0.6

0.8

1

1.2

1.4

High

6

Fluid

Vessels

Leading cause of blindness in people > 55 years✓

Increasing in prevalence due to aging population✓

Est. >1.8m people in US

Need for new therapies✓

Normal Retina Wet AMD

Wet AMD (Age-Related Macular Degeneration)

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Diabetes: a global epidemic✓

Diabetic Macular Edema (DME)

1/11 adults

with

diabetes worldwide

1/3 will develop diabetic eye disease✓

415M adults worldwide✓

> 2M

worldwide with DME

Increasing prevalence due to growing diabetic population

✓

Large proportion undiagnosed✓

Need for new therapies✓

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Our Goal: To Improve Vision in Diabetic & Elderly Patients

9

Large Socio-Economic Impact of Vision Loss

Psychological well-being

Work & Social Integration

Lost independence

Physical well-being

Costs to health-care

system & support services

Daily necessities: preparing meals, shopping, recognising faces

Work: going to work, continued employment

Reliance on caregivers, guilt

Difficult to care for self, increased risk of injury

Fear of total blindness, feeling isolated, helpless,

depression

International Diabetes Foundation www.idf.org; Fred Hollows Foundation.

IMPACT OF VISION

LOSS

New Therapies Aim to Improve Vision & Reduce Thickness (Fluid) at Back of Eye

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Visual Acuity SD-OCT

Change in Visual Acuity (# Letters) from BaselineChange in Retinal Subfield

Thickness (CST) from Baseline –(Fluid)

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Large and Growing Market Opportunity

• Existing therapies for wet AMD have same mechanism of action• Target VEGF-A: one signal involved in vessel growth and leakage• OPT-302 is different by targeting VEGF-C & VEGF-D

*Cowen Analyst Report: Ophthotech July 7 2015

2017: ~$9BN USD Off-Label Use60% Market Share40% Market Share

Market Opportunity*:

>$10BNWorldwide

VEGF-A Inhibitors

NovartisGenentech

RegeneronBayer

RocheGenentech

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Large Unmet Medical Need Despite Availability of VEGF-A Inhibitors

* Based on randomised, controlled clinical trial data; # Fail to achieve ≥ 2 lines improvement in BCVA; ^ SD-OCT CST ≥ 300 µM or Time-Domain OCT CST ≥ 250 µM

Do not achieve significant vision gains >50%

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

Will continue to have fluid at the back of the eye

Will have further vision loss at 12 months

Opportunity: New Products that Improve Efficacy and Durability

Wet AMD 2/3

25%

Do not achieve significant vision gains#

Continue to have macula thickening/swelling^

DME

2/3

25%

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OPT-302: Opthea’s Novel Therapy for wet AMD & DME

VE

GF

-C/D

VE

GF

-C/D

hIgG1 Fc

Extra-Cellular Domains 1-3hVEGFR-3

• Existing therapies block VEGF-A

• OPT-302 blocks VEGF-C & VEGF-D

• Distinct members of the same family of signals that control blood vessel growth & leakage

• Not seeking to replace existing therapies, seeking to ‘add-on’, therefore:• >$10bn market opportunity

• Used in combination, can more effectively block pathways involved in disease progression

• OPT-302 has the potential to improve vision & quality of life for patients with leading causes of blindness worldwide

Opthea is the Only Company Working on VEGF-C/D

Unlike many disease areas eg. cancer, there are limited combination therapies in development

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OPT-302 Product Development

OPT-302 Target: VEGF-C/D

OPT-302Target: VEGF-C/D

OPT-302Target: VEGF-C/D

Diabetic Macular Edema

Wet AMD

Phase 1Combination

Agent Preclinical Phase 2a Phase 2b Phase 3 Status1o Data Analysis

Lucentis®Target: VEGF-A

Lucentis®Target: VEGF-A

Eylea®Target: VEGF-A

Complete Ph 1/2a (n=51) April 2017

OngoingPh 2b (n=351) 1H CY2020

OngoingPh 1b/2a (n=117) 2019

Two Ongoing Randomised Controlled Clinical Trials in Two Different Eye Diseases

OPT-302:

Phase 1/2a

wet AMD Clinical Trial Results

15

16

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

OPT-302 Phase 1/2a

OPT-302 Monotherapy

n=13 patientsAdministered OPT-302 alone

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

OPT-302 + Lucentis® Naïve Patients

OPT-302 + Lucentis® Prior-Treated Patients

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

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)

+5.6

0

2

4

6

Vis

ua

l A

cu

ity

(Me

an

Ch

an

ge

fro

m B

as

eli

ne

)

B a s e lin e W e e k 4 W e e k 8 W e e k 1 2

3.8 (10/13)

6.1(9/13)

(7/12)

Mean Change in Visual Acuity in Non-Rescue Patients

Phase 1/2a Monotherapy Patients

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Gains in Visual Acuity in Patients Treated with OPT-302 Monotherapy –Evidence of OPT-302 Biological Activity

18Patients administered OPT-302 + Ranibizumab Q4Wx3. Number of Patients: 18; Mean Baseline VA = 56.5 Letters ; MARINA: Mean Baseline VA = 53.7 letters*Rosenfeld et al., NEJM, 355(14), pp 1419-1431, 2006; # Martin et al., NEJM, 364(20), pp 1897-1908

OPT-302 (0.3, 2 mg) + Ranibizumab (0.5 mg)

OPT-302 + Lucentis Phase 1/2a Treatment-Naïve Patients

Visual Acuity Gains and Reductions in Retinal Fluid Suggestive of Additive Benefit Compared to Historical Data with Lucentis Alone

+10.8

MARINA* 5.9 Letters at Wk12 with Lucentis

+5.9

Mean Change in Visual Acuity from Baseline (letters)

-119 mM

Mean Retinal Thickness (CST) (µM)

0

1

2

3

4

5

6

7

8

9

Baseline Week 4 Week 12

Reduction in CNV Size on FA

CN

V S

ize

(m

m2)

7.71

3.74

2.03

OPT-302 + Ranibizumab OPT-302 + Ranibizumab

0

10

20

30

40

50

60

Baseline Week 4 Week 12

% Patients with Absent CNV on FA

% P

atie

nts

wit

h A

bse

nt

CN

V o

n F

A

5.6 %

27.8 %

50 %

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

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Treatment-Naïve Patients: Reductions in CNV

OPT-302 (0.3, 2 mg) + Ranibizumab (0.5 mg)

20Patients administered OPT-302 + Ranibizumab Q4Wx3. Number of Patients: 18; Mean Baseline VA = 56.5 Letters ; MARINA: Mean Baseline VA = 53.7 letters*Rosenfeld et al., NEJM, 355(14), pp 1419-1431, 2006; # Martin et al., NEJM, 364(20), pp 1897-1908

OPT-302 (0.3, 2 mg) + Ranibizumab (0.5 mg)

OPT-302 + Lucentis Phase 1/2a Prior-Treated Patients

Visual Acuity Gains and Reductions in Retinal Fluid in Patients Sub-responsive to anti-VEGF-A Therapy

Mean Change in Visual Acuity from Baseline (letters) Mean Retinal Thickness (CST) (µM)

+4.9

-54 mM

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• OPT-302 met the primary safety objective of its Phase 1/2A study (well tolerated)

• Evidence of clinical activity of OPT-302

• When administered alone as a monotherapy

• As a combination, including in treatment naïve (49%) and heavily pre-treated patients (51%),

• and in a study with a high proportion of patients with occult (73%) wet AMD lesions.

• A consistency of responses in patients:

• With different treatment histories

• Across various secondary outcome measures (visual acuity, retinal thickness)

OPT-302 Phase 1/2a Key Take-Aways

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OPT-302 Product Development

OPT-302 Target: VEGF-C/D

OPT-302Target: VEGF-C/D

OPT-302Target: VEGF-C/D

Diabetic Macular Edema

Wet AMD

Phase 1Combination

Agent Preclinical Phase 2a Phase 2b Phase 3 Status1o Data Analysis

Lucentis®Target: VEGF-A

Lucentis®Target: VEGF-A

Eylea®Target: VEGF-A

Complete Ph 1/2a (n=51) April 2017

OngoingPh 2b (n=351) 1H CY2020

OngoingPh 1b/2a (n=117) 2019

Two Ongoing Randomised Controlled Clinical Trials in Two Different Eye Diseases

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Opthea: Large Potential for Upside

Approved

Phase 3

Phase 2/3

Phase 2

PreClinical

2.3BN

All figures in USD. Valuations shown = Mkt Cap (17.5.18) – Cash/Eq

2.8BN

2.4BN

1.1BN

621M

427M

332M

218M

260M

177M

476M

91M

213M

51M

Approved

Approved

Retinitis Pigmentosa (RP)Gene Therapy

Glaucoma

Glaucoma

wAMD, GA

Phase 3

Phase 3

Phase 3

Phase 3

Phase 3

Phase 2

Phase 2

wAMD, DME

Choroideremia, RPGene Therapy

wAMD

Dry Eye, Ocular Pain

Uveitis, DME, RVOSuprachoroidal delivery

Sealant, Delivery

Dry Eye, Uveitis

A1AT Deficiency, wAMDGene Therapy

DME

Retinitis PigmentosaGene Therapy

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OPT-302: fully funded through a diversified

clinical development program

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.

2018 2019

2H ‘17

Initiate 351 patient Phase 2B

wet AMD trial

2020

Initiate ~117 patient Phase

2A DME

Phase 2b wet AMD

Phase 1b/2a DME

2H ‘181H ‘18 1H ‘19 1H ‘202H ‘19 2H ‘20

Topline Data: Phase 2b wet AMD

Topline Data: Phase 1b/2a DME

2017

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Opthea – Developing OPT-302 for Eye Diseases

• OPT-302 program is diversified in two ocular indications

• Investigates activity in combination with two standard of care therapies

• Targets a validated pathway

• May address large proportion of patients that do not optimally respond to existing therapies

• Very large marked opportunity >$10BN p.a.

• Wet AMD & DME landscape includes only a limited number of novel combination therapies

• OPT-302 met primary safety objective of Phase 1/2a study (well tolerated)

• Clinical activity in a 51 patient Phase 1/2a clinical trial

• Opthea is fully funded through 2020 & its clinical development program:

• Wet AMD: 351 patients

• DME: 117 patients

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

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

www.opthea.com