OPT-302...This presentation is not an offeror invitation for subscription or purchase of or a recommendation of securities. It does not take into account the investment objectives,

Developing OPT-302 to improve outcomes for patients with retinal eye diseasesCorporate Presentation, January 2020Megan Baldwin PhD, CEO & Managing Director

Investment in Opthea Limited (‘Opthea’) is subject to investment risk, including possible loss of income and capital invested. Neither Opthea nor anyother member company of the Opthea Group guarantees any particular rate of return or performance, nor do they guarantee the repayment ofcapital.

This presentation is not an offer or invitation for subscription or purchase of or a recommendation of securities. It does not take into account theinvestment objectives, financial situation and particular needs of the investor. Before making any investment in Opthea, the investor or prospectiveinvestor should consider whether such an investment is appropriate to their particular investment needs, objectives and financial circumstances andconsult 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 andtherapeutic potential of the company’s research and development. Any statement describing a goal, expectation, intention or belief of the company isa 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 humantherapeutics and the financing of such activities. There is no guarantee that the Company’s research and development projects and interests (whereapplicable) will receive regulatory approvals or prove to be commercially successful in the future. Actual results of further research could differ fromthose projected or detailed in this presentation. As a result, you are cautioned not to rely on forward-looking statements. Consideration should begiven to these and other risks concerning research and development programs referred to in this presentation.

Disclaimer

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3

Opthea Limited • Public co listed on ASX (ASX:OPT) developing OPT-302 for wet AMD and DME

OPT-302 has a novel mechanism of action

• OPT-302 (sVEGFR-3) is the first ‘Trap’ inhibitor of VEGF-C and VEGF-D designed specifically for the eye • In combination with anti-VEGF-A therapies, completely shuts-down VEGFR-2 and VEGFR-3 activity• Targets mechanisms of resistance and sub-optimal clinical response to existing therapies

Strong & growing commercial potential

• Current & growing market opportunity of $10B+ worldwide• OPT-302 being developed for use in combination with any of the existing anti-VEGF-A agents, biosimilars

or novel therapies in development for wet AMD and DME• A novel approach seeking to provide additional visual acuity benefit over standard of care• Broad development opportunity in wet AMD, DME, RVO and other retinal pathologies

Primary endpoint met in Phase 2b study of OPT-302 in wet AMD

• OPT-302 combination therapy demonstrated superiority in visual acuity over ranibizumab (Lucentis®) at 24 weeks in an international, randomized, controlled, double-masked trial of 366 patients

• Secondary endpoint results also supportive of primary outcome• Phase 2b positive data follows Phase 1/2a trial in 51 wet AMD patients

Ph 2A trial of OPT-302 in persistent DME; Data anticipated

2Q CY 2020

• Fully recruited Phase 2a trial of OPT-302 in combination with aflibercept (Eylea®) for the treatment of persistent centre-involving DME

• Completed Phase 1b dose-escalation trial in 9 persistent DME patients• Dose-responsive improvements in visual acuity, reductions in retinal fluid & swelling

Well tolerated safety profile of OPT-302

• Well tolerated safety profile of OPT-302 administered IVT in combination with ranibizumab & aflibercept• Extensive global clinical dosing experience with repeated IVT administration in >400 patients across

three international clinical studies in two disease indications

Opthea Limited

Share Price Performance (2017 - 2020)

4

Key Financial Details ASX: OPT

Ticker Symbol ASX:OPT

Share Price (Jan 10 2020) ~A$3.02

Total Ordinary Shares on Issue 269,157,769

Market Capitalisation (Jan 10 2020)

~A812m(~USD560m)

Trading Range (last 12 months) A$0.56 – 4.15

52-week Change 406%

Cash Balance (Dec 31 2019) ~A$75m

Top 20 Shareholders Own 75%

Institutional Holders 87%Analyst Coverage (Aust)

Chris Cooper

Financial Position (Unaudited)

Shane Storey Tanushree Jain

AUD

3.00

2.50

2.00

1.50

1.00

0.50

SepMar JulMar2018 May

3.50

2019May Jul Nov Nov 2020Sep

5

Wet AMD & DME are distinct diseases with Unmet Medical Need

Driver:

Primary macular site of pathology:

• Sustained hyperglycaemia• Ageing

• Increasing due to diabetes epidemic

• DME with visual impairment affects ~1 -3% diabetes patients

• ~1.3M – 2M people worldwide, many undiagnosed

• Choroid • Intra-retinal layers

Pathogenesis:

• Increasing prevalence due to ageing population

• ~3M people worldwide, ~1.8M in USA

• Changes in ageing eye

• Upregulation VEGF-A, -C, -D & other cytokines

• Choroidal neovascularization (CNV)

• Sub-retinal, intra-retinal fluid accumulation

• Sustained hyperglycemia

• Upregulation VEGF-A, -C, -D and inflammatory mediators

• Inflammation

• Hyperpermeability & retinal swelling

Prevalence:

Steroids#

VEGF-AVEGF-C/D

Wet Age-Related Macular Degeneration Central-involved Diabetic Macular Edema

6

OPT-302 ongoing clinical trials in wAMD & DME Multiple additional market opportunities

Source: GlobalData; EvaluatePharma; PubMed; Physician Interviews.

3 MWet AMD

850 K RVO

1.3 M DME

U.S. & EUEpidemiologyEdema caused by abnormal vasculature growth which

ultimately results in the loss of visual functionA complication of diabetes that manifests as edema and

hard exudates in the macula and leads to loss of VA

Wet Age-Related Macular Degeneration Diabetic Macular Edema (DME)

Retinal Vein Occlusion (RVO)

Characterized by vascular injury and permeability, which may be followed by active proliferation of new vessels

Diabetic Retinopathy

Characterized by ingrowth of new blood vessels beneath the retina in the myopic eye

May occur secondary to other ophthalmic conditions

Myopic CNV

Other non-AMD associated CNV

Additional market opportunity:

Additional market opportunities:

Characterized by retinal vein blockage, which selectively leads to edema formation and loss of visual acuity

(# patients)

7

Existing Therapies Primarily Target VEGF-AOPT-302 has potential to improve clinical EFFICACY by targeting VEGF-C/D

VEGF-CVEGF-D

• Long-term therapy with selective VEGF-A inhibitors is associated with sub-optimal responses

• Sub-optimal improvements in visual acuity• Persistent retinal fluid

• Resistance to VEGF-A monotherapy may be related to other VEGF family members

• VEGF-C/D signal for angiogenesis and vascular permeability independently of VEGF-A; and

• VEGF-C/D are elevated when VEGF-A is inhibited• OPT-302 combination therapy achieves a more

complete suppression of the VEGF/VEGFR pathway

• OPT-302 targets incomplete response to VEGF-A inhibition

OPT-302: Rationale

Used in combination with a VEGF-A inhibitor, completely blocks VEGFR-2 and VEGFR-3 signalling

VEGFR-1 VEGFR-2 VEGFR-3

Brolucizumab(Beovu®)

Bevacizumab#

(Avastin®)

Aflibercept(Eylea®)

VEGF-A

VEGF-B

PlGF

OPT-302VEGF-C

VEGF-D

# Bevacizumab is used ‘off-label’ for the treatment of nAMD

OPT-302 inhibits VEGF-C/D

Ranibizumab(Lucentis®)

VEGF-A Inhibition Upregulates VEGF-C/D

1 “The association of alternate VEGF ligands with resistance to anti-VEGF therapy in metastatic colorectal cancer” - Lieu et al., 2013.2 “Bevacizumab injection in patients with neovascular age-related macular degeneration increases angiogenic biomarkers.” Cabral T, Lima LH, Mello LGM, et al., Ophthalmology Retina 2018;2:1:31-7.

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BevacizumabBevacizumab

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Clinical data suggest VEGF-C/D may mediate resistance & sub-optimal response to anti-VEGF-A therapy

8

A Currently Unmet Medical Need for wet AMD and DMEWith >$10bn market opportunity

9

Large and Growing Market Opportunity

• Wet AMD and DME are the leading causes of blindness in the elderly and diabetic populations respectively

• Prevalence is increasing

• Market opportunity is growing

• Approved VEGF-A inhibitors (ranibizumab and aflibercept) generated revenues >US$10b in 2018

• Approximately 50% of wet AMD and DME patients worldwide receive bevacizumab as an off-label, less-costly treatment option

>50%

Opportunity: New Products that Improve Efficacy and Durability

2/3

25%

2/3

25%

Do not achieve significant vision gains

Will continue to have fluid at the back of the eye

Will have further vision loss at 12 months

Do not achieve significant vision gains#

Continue to have macula thickening/swelling^

wet AMD

DME

* 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

Despite receiving a VEGF-A inhibitor(ranibizumab, aflibercept or bevacizumab)*:

Opthea’s strategy is to develop OPT-302 as a combination therapy to be administered with any of the approved a-VEGF-A therapies or new VEGF-A inhibitors in development

OPT-302: A ‘trap’ inhibitor of VEGF-C and VEGF-D

10

hIgG1 Fc

Extra-Cellular Domains 1-3hVEGFR-3

VEGF-CVEGF-D

• Comprises the extracellular domains 1-3 of VEGFR-3 and the Fc fragment of human IgG1

• Potent inhibitor of VEGF-C (~5 pM) and VEGF-D (~0.5 nM)

• A ‘trap’ that blocks VEGF-C and VEGF-D binding to the receptors VEGFR-2 and VEGFR-3

• Targets a validated pathway involved in wet AMD progression

• Targets a mechanism of escape from existing therapies that is differentiated to VEGF-A therapies

OPT-302: A soluble form of VEGFR-3 Strategy

• To develop OPT-302 for use in combination with inhibitors of VEGF-A to address the unmet medical need in wet AMD and DME

• To demonstrate superior gains in visual acuity in patients administered OPT-302 in combination with a VEGF-A inhibitor

• Currently administered as a sequential intravitreal injection every 4 weeks (q4w), with the potential to also:

• investigate OPT-302 efficacy and durability in patients receiving less frequent doses (e.g. q8w, q12w), and

• co-formulate with other agents

• Wet AMD and DME landscape includes only a limited number of novel combination therapies that may address the sub-optimal clinical responses that many patients experience on anti-VEGF-A therapies

OPT-302 has comparable ocular biodistribution and PK profile to aflibercept, with low systemic exposure

Ocular Biodistribution and Systemic PK following IVTOPT-302 has comparable ocular biodistribution & PK profile to aflibercept, with low systemic exposure

Non-compartmental OPT-302 PK analysis indicated:• Low systemic exposure• Half-life of 8 ± 2 days• Mean Cmax of ~21 ng/mL at ~31 hours post IVT injection at

a dose of 2 mg• No accumulation• No influence from ranibizumab on the PK profilePhase 2b PK analysis: • Serum quantitation data complete, currently undergoing

noncompartmental analysis• PK similar to that observed in Phase 1/2a study

11

Mean OPT-302 serum concentrations following IVT (Ph1/2a trial data)

1.0

10.0

100.0

0 24 48 72 96 120144168192216240264288312336

OPT-302 Monotherapy (2 mg)

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

Time (hours)

Mea

n (+

SD

) OP

T-30

2 S

erum

C

once

ntra

tions

(ng

/mL)

Ocular Biodistribution OPT-302 vs Aflibercept in Rabbits

OPT-302 Target: VEGF-C/D

OPT-302Target: VEGF-C/D

Phase 1Combination

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

AfliberceptTarget: VEGF-A, PlGF, VEGF-B

April 2017 Primary Endpoint Met (Safety)

August 2019 Primary Endpoint Met (Superior Efficacy)

Diabetic Macular Edema

Wet AMD

OPT-302 Clinical Program

12

RanibizumabTarget: VEGF-A Phase 3

Upcoming Future Milestones

Complete Ph 1/2a (n=51)

PositivePh 2b (n=366)

Fully RecruitedPh 1b/2a (n=117)

PlannedTwo concurrentPh 3 trials (each 2 arms, n=~330 per arm; ~660 total per trial)

• Trial Initiation:Expected 4Q 2020

• Top-line and Final Data Readout:Expected 1H 2023

• Trial Fully Recruited: December 30 2019

• Top-line Data Readout: Expected 2Q CY 2020

Phase 3b

• Trial Initiation:Expected 1H 2021

• Top-line and Final Data Readout:Expected 1H 2023

PlannedPh 3b trial (2 arms, n=~330 per arm; ~660 total)

OPT-302 Target: VEGF-C/D

Aflibercept, BevacizumabTarget: VEGF-A

Phase 3

13

OPT-302 well-tolerated and active in Phase 1/2a study Visual acuity benefit observed as monotherapy & in combination with ranibizumab

we e k 4

we e k 8

we e k 1

2

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-5

0

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Treatment-Naive Prior Treated

MARINA1

Sham Injection at Week 12

MARINA1

Sham Injection at Week 12

1 Rosenfeld et al. N Engl J Med 20062. Phase 1/2a study outcomes: P.Dugel et al., Ophthalmology Retina, In Press, 23 Oct 2019

Visual Acuity Gains (Baseline to Wk 12) following Monotherapy OPT-302 (q4w x3)

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

• Study (n=51) recruited treatment naïve (49%) and heavily pre-treated patients (51%), and a high proportion of patients with occult (73%) wet AMD lesions:

• Naïve Patients:

o Mean gain in visual acuity at week 12 from baseline was +10.8 letters vs. +5.9 letters for Lucentis alone in the MARINA trial and +6.1 letters for each of Avastin and Lucentisalone in the CATT*study

• Prior Treated Patients:

o Patients had received an average of 17 prior injections, equating to prior treatment over an average ~1.3 years#

o Mean gain in visual acuity at week 12 from baseline was +4.9 letters o Mean reductions in CST and SRF at week 12 of 54 um and 62 um (51%), respectively,

from baseline• Monotherapy Patients:

o Evidence of clinical activity and visual acuity gains without background standard of care

o Mean gain in visual acuity at week 12 from baseline of +5.6 letters for patients who did not require “rescue” therapy (7/13, or 54% of patients)

• A consistency of responses in patients with different treatment histories & across various secondary outcome measures (VA, OCT)

• Phase 1/2a trial results supportive of progressing to larger, randomised, controlled Phase 2b study

Combination OPT-302 + ranibizumab (q4w x3)

Treatment-Naive Prior-Treated

OPT-302 Phase 1/2a Key Take-Aways2

14

Phase 2b A multicenter, randomized, double-masked, sham controlled study of intravitreal OPT-302 in combination with ranibizumab, in participants with neovascular (wet) AMD

Conducted at 113 sites across 10 countries: US, EU, Israel

OPT-302-1002; NCT ClinicalTrials.gov Identifier: NCT03345082

15

OPT-302 Phase 2b wet AMDPatients randomised 1:1:1 to treatment arms with intravitreal dosing every 4 weeks (x 6)

Wet AMD Naïve Pts OPT-302 (0.5 mg) + ranibizumab (0.5 mg)

Sham + ranibizumab (0.5 mg)

Wee

k 24

Fol

low

-up

OPT-302 (2.0 mg) + ranibizumab (0.5 mg)

Primary Outcome:

• Mean change from Baseline in ETDRS best corrected visual acuity at Week 24

Key Secondary Outcomes at Week 24:• Patients gaining ≥15 or more ETDRS letters• Patients losing ≥15 or more ETDRS letters• Change in central subfield thickness (SD-OCT)• Change in subretinal fluid and intraretinal fluid (SD-OCT)

Key Exploratory Outcomes at Week 24:• Change in total lesion area and choroidal neovascularisation (CNV) area (FA)

Key Safety Outcome:• Safety and tolerability

ETDRS – Early Treatment Diabetic Retinopathy Study; SD-OCT – spectral domain optical coherence tomography; FA – fluorescein angiography

ClinicalTrials.gov Identifier: NCT03345082

16

Study Overview

ScreeningTreatment naïve patients

with neovascular AMD Key Exclusion Criteria • Subfoveal fibrosis or >25% of total lesion• Haemorrhage >50% total lesion • Other clinically significant ocular disease

Key Inclusion Criteria • Active CNV >50% lesion, classic /

minimally classic / occult• BCVA ≥ 25 and ≤ 60 letters

CNV – choroidal neovascularisation; IVT – intravitreal; Q4W – once very 4 weeksITT – Intent to Treat Population, all participants who were randomised into the study irrespective of whether study medication was administered or notSafety Population - all participants in the ITT but excluding those who did not receive at least one dose of study medication mITT – Modified ITT Population, all participants in the Safety Population but excludes any participant without a Baseline VA score and/or any participant who did not return for at least one post-baseline visit

Allocation

Follow-up

Analysis

Randomised (n=366)

OPT-302 0.5 mg +0.5 mg ranibizumab IVT

Q4W x 6n=122

sham +0.5 mg ranibizumab IVT

Q4W x 6n=121

OPT-302 2.0 mg +0.5 mg ranibizumab IVT

Q4W x 6n=123

Completed Studyn=112 (91.8%)



Analysedn=122

Analysedn=119

Analysedn=121

mITT Population

ITT Population

17

Demographic / Baseline Disease Characteristic Sham +ranibizumab

N=121

0.5 mg OPT-302 +ranibizumab

N=122

2.0 mg OPT-302 + ranibizumab

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%)

Female 73 (60.3%) 73 (59.8%) 78 (63.4%)

Caucasian Race – n (%) 117 (99.2%) 119 (99.2%) 117 (97.5%)

Mean Visual Acuity (BCVA) – letters ± SD 50.7 ± 10.21 51.1 ± 8.96 49.5 ± 10.26

Mean Total Lesion Area - mm2 ± SD 6.08 ± 3.21 6.48 ± 3.30 6.62 ± 3.39

Lesion Type Predominantly classic – n (%) 15 (12.4%) 15 (12.3%) 16 (13.0%)

Minimally classic – n (%) 53 (43.8%) 51 (41.8%) 53 (43.1%)

Occult - n (%) 53 (43.8%) 56 (45.9%) 54 (43.9%)

PCV detected1 – n (%) 20 (16.5%) 24 (19.7%) 22 (17.9%)

RAP detected2 – n (%) 15 (12.7%) 22 (18.5%) 14 (11.8%)

Mean central subfield thickness (CST) - mm ±SD 412.10 ± 110.62 425.18 ± 120.45 414.12 ± 123.25

Sub-retinal fluid (SRF) present – % participants 89.3% 84.4% 87.8%

Intra-retinal cysts present – % participants 57.9% 63.9% 56.1%

Intent-to-Treat (ITT) population; SD: standard deviation; BCVA: Best Corrected Visual Acuity1PCV - polypoidal choroidal vasculopathy, detected by SD-OCT, FA and fundus photography2RAP - retinal angiomatous proliferation, detected by SD-OCT, FA and fundus photography

Study Demographics and Baseline Characteristics

0

5

10

15

20

14.22

9.4410.84

Mea

n ch

ange

in B

CVA

(SEM

)(le

tters

)

18

Δ = +3.4 (p=0.0107)

OPT-302 (2.0 mg) Combination Therapy Demonstrated Superiority in Visual Acuity over Ranibizumab

mITT; BCVA – best corrected visual acuityLeft: Difference in Least Square Means, using Model for Repeated Measures (MRM) analysis. Right: Graph represents “as observed” data and SEM

Sham + 0.5 mg ranibizumab(n=119)

2.0 mg OPT-302 + 0.5 mg ranibizumab(n=121)


0 4 8 12 16 20 240

5

10

15

20

WeeksM

ean

chan

ge in

BC

VA (S

EM)

(lette

rs)

Primary Endpoint Achieved: Mean Change in Best Corrected Visual Acuity Baseline to Week 24

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Vision Gain & Vision Loss - Baseline to Week 24More patients gain, and fewer patients lose, ≥15, ≥10 and ≥5 letters of vision in OPT-302 combination group

Modified Intent-to-Treat (mITT) population; as observedSham + 0.5 mg ranibizumab(n=116)


0

20

40

60

80

100

45.040.5

% Gaining ≥ 15 Letters

% P

artic

ipan

ts

0

20

40

60

80

100

70.0

57.8


% P

artic

ipan

ts

0

20

40

60

80

100

85.0

75.9


% P

artic

ipan

ts

0

2

4

6

8

0.8

3.4

% Losing ≥ 15 Letters

% P

artic

ipan

ts

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2

4

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8

0.8

6.0


% P

artic

ipan

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% P

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ipan

ts

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Central Subfield ThicknessReduction in CST in OPT-302 combination group compared to sham + ranibizumab

-160

-140

-120

-100

-146.70

-133.80

Mea

n ch

ange

in C

ST (S

EM)

(µm

)

Mean CST at Week 24Mean Change in CST –Baseline to Week 24

Modified Intent-to-Treat (mITT) population; as observed; CST – central subfield thickness



100

150

200

250

300

265.57277.84

Mea

n C

ST (S

EM)

(µm

)

21

Sub-retinal Fluid and Intra-retinal Cysts at Week 24Fewer participants with retinal fluid present in OPT-302 combination group compared to sham + ranibizumab

% Participants with SRF present

% Participants with IR Cysts present

0

5

10

15

20

25

30

18.5

29.3

% P

artic

ipan

ts

0

5

10

15

20

25

30

16.8

21.6

% P

artic

ipan

tsModified Intent-to-Treat (mITT) population; as observed; SRF – sub-retinal fluid; IR – intra-retinal



22

Total Lesion Area and CNV Area – Baseline to Week 24Greater reduction in Total Lesion and CNV Area in OPT-302 combination group compared to sham + ranibizumab

Mean Change in CNV Area

Mean Change in Total Lesion Area

-6

-4

-2

0

-4.3

-3.1

Mea

n c

hang

e in

Tot

al L

esio

n Ar

ea (S

EM)

(mm

2 )

p=0.0137

-6

-4

-2

0

-5.0

-3.6

Mea

n c

hang

e in

CNV

Are

a (S

EM)

(mm

2 )

p=0.0055

Modified Intent-to-Treat (mITT) population; as observed; CNV – choroidal neovascularisation; Difference in Least Square Means



23

Phase 2b A multicenter, randomized, double-masked, sham controlled study of intravitreal OPT-302 in combination with ranibizumab, in participants with neovascular (wet) AMD

Pre-Specified Subgroup Analyses

OPT-302-1002; NCT ClinicalTrials.gov Identifier: NCT03345082

24

60% of the World’s Population is Asian

Polypoidal Choroidal Vasculopathy (PCV)• Most common sub-type of

neovascular (wet) AMD in Asian populations

• Estimated to be the most prevalent form of wet AMD world-wide

• PCV lesions typically less responsive to anti-VEGF-A therapy

25

Polypoidal Choroidal VasculopathyParticipants with PCV at baseline gained +6.7 letters by week 24 following OPT-302 combination treatment

Δ = 6.70(*p = 0.0253)

Δ = 2.71(*p = 0.0491)

mITT; PCV – polypoidal choroidal vasculopathy; Least square means determined using Model for Repeated Measures (MRM) analysis (adjusted for baseline vision and lesion type (randomisation) as covariates).PCV determination by SD-OCT, FA and fundus photography

Sham + 0.5 mg ranibizumab 2.0 mg OPT-302 + 0.5 mg ranibizumab

Absent Present0

5

10

15

20

99

14.2

22

13.5

98

11.5

20

6.9

PCV Detected at Baseline

Mea

n ch

ange

in B

CVA

(SEM

)(le

tters

)

26

Neovascular (wet) AMD Lesion TypesDiffer in vessel location, leakiness and responsiveness to VEGF-A inhibitors

Occult

• Vessels 100% beneath RPE• Least responsive to a-VEGF-A• Lesions shift to occult following a-VEGF-A

(largest population)

~44%

Predominantly Classic

~44%

• <50% of vessels are above the RPE• Occult vessels may be present• Moderately responsive to a-VEGF-A

Minimally Classic

• >50% of vessels are above the RPE• Highly responsive to a-VEGF-A

~12%

Percentages shown are the proportion of patients with each lesion type randomised into Opthea’s Phase 2b clinical trial

27mITT; as observed

Small number of predominantly classic patientsMean Change in BCVA Over Time by Lesion Type

Predominantly Classic

Sham + 0.5 mg ranibizumab (n = 15)

2.0 mg OPT-302 + 0.5 mg ranibizumab (n = 15)

0 4 8 12 16 20 240

5

10

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20

Weeks

Mea

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Minimally Classic

0 4 8 12 16 20 240

5

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20

Weeks

Mea

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(SEM

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Occult

0 4 8 12 16 20 240

5

10

15

20

Weeks

Mea

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in B

CVA

(SEM

)(le

tters

)



0

5

10

15

20

53

16.2

51

10.2

Mea

n ch

ange

in B

CVA

(SEM

)(le

tters

)28

mITT; Least square means determined using Model for Repeated Measures (MRM) analysis (adjusted for baseline vision and lesion type (randomisation) as covariates).

Greater vision gains at Week 24 in OPT-302 2.0 mg group in minimally classic and occult lesionsMean Change in BCVA at week 24 by Lesion Type


Δ = 6.0(*p = 0.0008)

Δ = 2.7

Minimally Classic Occult

0

5

10

15

20

53

13.7

53

11.1

Mea

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29mITT; as observed. 5 letters on ETDRS eye chart = 1 line


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

0

20

40

60

39.642.3

% P

artic

ipan

ts

0

20

40

60

55.8

34.0

% P

artic

ipan

ts

172122 290

20

40

60

8076.9

58.0%

Par

ticip

ants

0

20

40

60

80

66.0

55.8

% P

artic

ipan

ts

40293529


% Gaining ≥ 15 letters % Gaining ≥ 15 letters % Gaining ≥ 10 letters % Gaining ≥ 10 letters


30mITT; as observed. 5 letters on ETDRS eye chart = 1 line


2-Line and 3-Line Vision Loss at Week 24 by Lesion TypeFewer patients with minimally classic and occult lesions lose ≥10 and ≥15 letters following OPT-302 combination therapy


% Losing ≥ 15 letters % Losing ≥ 15 letters % Losing ≥ 10 letters % Losing ≥ 10 letters 0

2

4

6

2.0% P

artic

ipan

ts

0

2

4

6

1.9

5.8

% P

artic

ipan

ts


0

2

4

6

8

10

4.0% P

artic

ipan

ts

0

2

4

6

8

10

1.9

9.6

% P

artic

ipan

ts

215 113

31

Central Subfield Thickness by Lesion TypeReduction in CST in participants with occult lesions treated with OPT-302 combination compared to sham + ranibizumab

Modified Intent-to-Treat (mITT) population; as observed; CST – central subfield thickness






-180

-160

-140

-120

-100

-80

-154.9

-163.6Mea

n ch

ange

in C

ST (S

EM)

(µm

)

-180

-160

-140

-120

-100

-80

-134.6

-103.5

Mea

n ch

ange

in C

ST (S

EM)

(µm

)

0

10

20

30

17.3

30.0

% P

artic

ipan

ts

0

10

20

30

21.223.1

% P

artic

ipan

ts

32 mITT; as observed

Sub-Retinal Fluid & Intra-Retinal at Week 24 by Lesion Type

9151112


0

5

10

15

20

25

20.822.6

% P

artic

ipan

ts

0

5

10

15

20

25

7.5

19.6

% P

artic

ipan

ts

4101112


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


33 mITT; as observed

Total Lesion Area at Week 24 in Minimally Classic and Occult Lesions






Greater reductions in Total Lesion Area following OPT-302 combination therapy

-6

-4

-2

0

-4.4

-3.3

Mea

n c

hang

e in

Tot

al L

esio

n Ar

ea (S

EM)

(mm

2 )

-6

-4

-2

0

-4.9

-3.9

Mea

n c

hang

e in

Tot

al L

esio

n Ar

ea (S

EM)

(mm

2 )

-6

-4

-2

0

-4.6

-3.4

Mea

n c

hang

e in

CNV

Are

a (S

EM)

(mm

2 )34

mITT; as observed; p based on difference in least square means determined using Model for Repeated Measures (MRM) analysis (adjusted for baseline vision and lesion type (randomisation) as covariates).

CNV Area at Week 24 in Minimally Classic and Occult Lesions






Greater reductions in CNV Area following OPT-302 combination therapy

(p = 0.0555)

-6

-4

-2

0

-5.6

-4.4

Mea

n c

hang

e in

CNV

Are

a (S

EM)

(mm

2 )

35mITT; as observed

Lesion Classificationat Week 24

Lesion Classificationat Baseline



Predominently Classic

MinimallyClassic

Occult0

10

20

30

40

50

12

44 44

13

45 43

% P

artic

ipan

ts

Predominently Classic

MinimallyClassic

Occult Quiescent No CNV0

10

20

30

40

50

45

31

17

41

35

14

% P

artic

ipan

ts

Lesion classification at Baseline and at Week 24Lesions shift to an occult, quiescent biology or no CNV following treatment

36

Retinal Angiomatous Proliferation (RAP) LesionsHave a distinct biology and vessel proliferation occurs within the retina (not the choroid)

Nb. RAP lesions were excluded from: e.g. Phase 3 Ophthotech trials, Abicipar (Allergan) Phase 2 study, early conbercept studies* Tsai AS et al., Surv Ophthalmology, 2017 Jul-Aug; 62(4):462-92. de Jong et al., Ophthalmologica 2019; 241:143-153.

• No consensus of which treatment is optimal for RAP lesions*• Favorable short-term results with anti-VEGF-A treatments but long-term results are conflicting

0

5

10

15

20

103

15.0

102

10.6

Mea

n c

hang

e in

BC

VA (S

EM)

(lette

rs)

37

Δ = 4.4*p = 0.0025

mITT; RAP – retinal angiomatous proliferation; Least square means (LSM) determined using Model for Repeated Measures (MRM) analysis (adjusted for baseline vision and lesion type as used in the randomisation as covariates).


Improved Visual Acuity in OPT-302 + ranibizumab treated patients Mean change in BCVA to Week 24 in participants without RAP at baseline (>86% study participants)

38mITT, as observed, Δ based on least square means determined using Model for Repeated Measures (MRM) analysis (adjusted for baseline vision and lesion type (randomisation) as covariates).

Minimally Classic

0 4 8 12 16 20 240

5

10

15

20

Weeks

Mea

n ch

ange

in B

CVA

(SEM

)(le

tters

)

+10.0

+14.9

In participants without RAP at baseline, +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

Δ = 4.7*p = 0.0415



Occult

0 4 8 12 16 20 240

5

10

15

20

Weeks

Mea

n ch

ange

in B

CVA

(SEM

)(le

tters

)

+10.2

+16.8

Δ = 6.5*p = 0.0005



Mean Change in BCVA Over Time by Lesion Type (RAP Absent)

39mITT; Least square means (LSM) determined using Model for Repeated Measures (MRM) analysis (adjusted for baseline vision and lesion type as used in the randomisation as covariates).



Mean Change in BCVA at Week 24 by Lesion Type (RAP Absent)

Δ = 4.7*p = 0.0415

Δ = 6.5*p = 0.0005

0

5

10

15

20

49

16.7

47

10.1

Mea

n ch

ange

in B

CVA

(SEM

)(le

tters

)

0

5

10

15

20

39

15.4

40

10.7

Mea

n ch

ange

in B

CVA

(SEM

)(le

tters

)

40mITT; Least square means (LSM) determined using Model for Repeated Measures (MRM) analysis (adjusted for baseline vision and lesion type as used in the randomisation as covariates).

Minimally Classic & Occult


0

5

10

15

20

88

16.1

87

10.3

Mea

n ch

ange

in B

CVA

(SEM

)(le

tters

)Δ = 5.74

*p = 0.0002

+10.3

+16.1

Δ = 5.7*p = 0.0002

0 4 8 12 16 20 240

5

10

15

20

WeeksM

ean

chan

ge in

BC

VA (S

EM)

(lette

rs)

Minimally Classic & Occult

Improved Visual Acuity in patients with Occult-containing lesions (RAP Absent)71% study participants had occult-containing lesions with RAP absent at baseline

41

N Participants (%) Sham + 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 - Study Eye – Severe2 1 (0.8%) 2 (1.7%) 1 (0.8%)

Serious AEs 10 (8.3%) 16 (13.3%) 7 (5.6%)

Ocular SAEs in Study Eye 0 (0.0%) 23 (1.7%) 0 (0.0%)

Intraocular inflammation4 – Study Eye 0 (0.0%) 23 (1.7%) 15 (0.8%)

Participants with AEs leading to study IP discontinuation only 2 (1.7%) 3 (2.5%) 0 (0.0%)

Participants with AEs leading to study discontinuation 16 (0.8%) 0 (0.0%) 0 (0.0%)

Any APTC event 0 (0.0%) 17 (0.8%) 0 (0.0%)

Deaths 28 (1.7%) 0 (0.0%) 0 (0.0%)

Safety population analysed according to medication received1 Assessed by investigator to be “possibly related”, “probably related” or “definitely related” to administration of study drug(s)2 Assessed by Investigator to be National Institutes of Health (NIH) Common Terminology Criteria for Adverse Events (CTCAE) grade 3 or above, or, if CTCAE grade is unavailable, an AE assessed as “causing an inability to perform normal daily activities”3 SAE of endophthalmitis, with AEs of hypopyon and anterior chamber cell (n=1), SAE of vitritis (n=1)4 AEs considered to be indicative of intraocular inflammation, defined prior to database lock as: Endophthalmitis, iritis, vitritis, iridocyclitis, uveitis, hypopyon, viral iritis, or anterior chamber inflammation5 Anterior chamber cell (trace 1-4 cells)6 Squamous cell carcinoma of the lung diagnosed shortly after Baseline visit7 Non-fatal myocardial infarction8 Pneumonia (n=1), infective endocarditis (n=1)

Safety – Adverse Events (Aes)OPT-302 well tolerated with very low incidence of ocular inflammation

42

Conclusions – OPT-302 Phase 2b wet AMD Trial

• Phase 2b trial met primary endpoint• OPT-302 (2.0 mg) combination therapy demonstrated superiority in visual acuity over ranibizumab + sham• Vision gain of 3.4 letters• Statistically significant (p=0.0107)• High ranibizumab control arm

• Secondary outcomes were supportive of the primary endpoint:• Vision

• More patients gained ≥ 15 letters of vision• Fewer patients lost ≥ 15 letters of vision

• Retinal anatomical improvements • Reductions in CST, subretinal and intraretinal fluid• Greater decreases in Total Lesion Area and CNV Area

• Exploratory & pre-specified subgroup analyses • Suggest greater activity of OPT-302 in lesion-types considered more difficult to treat with anti-VEGF-A therapy &

highest unmet need

• Promising evidence of activity in polypoidal AMD (PCV) and minimally classic/occult lesions that are less responsive to VEGF-A inhibitors

• Favourable safety profile similar to ranibizumab alone

43

Ongoing Clinical TrialsPhase 1b/2a DMEPhase 1b/2a study of OPT-302 in combination with aflibercept for persistent central-involved diabetic macular edema

44

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• Ranibizumab (Lucentis) and sham injections every 4 weeks to week 12, then as needed• At week 12:

40% patients gained < 5 letters (mean -0.3) by week 12 > 60% patients gained < 10 letters of improvement in mean BCVA after 3 injections

Response Category

(Mean Change BCVA BL to Wk 12)

Mean Change BCVA at Wk 12 in Response Category

# and % Eyes in Response Category at Wk 12

< 5 Letters - 0.3 Letters 39.7%(135/340 eyes)

5 – 9 Letters 6.9 Letters 23.2%(79/340 eyes)

≥ 10 Letters 15.2 Letters 37%(126/340)

Am J Ophthalmol. 2016 Dec;172:72-79. Early and Long-Term Responses to Anti-Vascular Endothelial Growth Factor Therapy in Diabetic Macular Edema: Analysis of Protocol I Data. Gonzalez VH, Campbell J, Holekamp NM, Kiss S, Loewenstein A, Augustin AJ, Ma J, Ho AC, Patel V, Whitcup SM, Dugel PU.

Phase 1b Dose Escalation study of OPT-302 + aflibercept in DME

N=

14 D

ay D

LT w

indo

w

Cohort 3

Cohort 2

Cohort 1

Phase 1b Dose-Escalation (Complete. Data reported)

OPT-302 (0.3 mg)+ Aflibercept (2.0 mg)

IVT Q4W x 3, n=3

• HbA1c ≥ 12%• Uncontrolled hypertension ≥ 180 mmHg systolic or

≥ 110 mmHg diastolic• Eyes needing PRP within 3 months of screening • Concurrent / prior use of intravitreal injections of

steroids within 4 months of study start• Concurrent / prior use of dexamethasone or

fluocinolone implant in study eye

Key Exclusion Criteria


IVT Q4W x 3, n=3


IVT Q4W x 3, n=3

Key Inclusion Criteria• Age ≥ 18 years; centre-involving DME• CST ≥ 335 µm*• BCVA 73 – 24 ETDRS letters (20/40 – 20/320 Snellen)• Prior exposure to anti-VEGF-A therapy with sub-optimal

therapeutic response• ≥ 3 intravitreal injections• Last injection ≤ 6 wks prior to study day 1• Prior bevacizumab only allowed if switched to IVT aflibercept or

ranibizumab prior to study

*CST as measured by Spectralis (Heidelberg) at screening, ≥ 320 µm for Cirrus.

45

• 3 sequential treatment cohorts of 3 patients per group

• Dose escalating levels of OPT-302 (0.3, 1 or 2 mg) in combination with aflibercept (2 mg)

• Administered via separate IVT injections every 4 weeks for 3 doses

• All participants have received prior anti-VEGF-A therapy (minimum of 3 prior IVT injections, maximum treatment history of 24 months)

• Phase 1b Met Primary Objective: Safety & tolerability of OPT-302 in combination with aflibercept in DME

Phase 1b: Baseline Ocular CharacteristicsGenerally well-balanced across treatment groups

*HbA1c = glycated hemoglobin

Characteristic

OPT-302 (0.3 mg) + Aflibercept (2.0

mg) (N=3)

OPT-302 (1 mg) + Aflibercept (2.0

mg)(N=3)

OPT-302 (2 mg) + Aflibercept (2.0

mg) (N=3)

Total Number of Subjects (N= 9)

Vision

Mean BCVA, ETDRS letters (SD) 64.3 (9) 64.6 (5) 66.7 (3.1) 65 (5.5)

Better than 55 letters vision, n (%) 3 (100%) 3 (100%) 3 (100%) 9 (100%)

Worse than 55 letters vision, n (%) 0 (0%) 0 (0%) 0 (0%) 0 (0%)

Anatomic

Mean CST, µm (SD) 460 (103) 410 (26) 432 (24) 434 (58)

CST ≤ 450 µm, n (%) 1 (33%) 3 (100%) 2 (67%) 6 (67%)

CST ≥ 450 µm, n (%) 2 (67%) 0 (0%) 1 (33%) 3 (33%)

Mean duration of diabetes at screening, years (SD) 14 (7.9) 17.3 (13) 10.9 (12.6) 14.1 (10.3)

Mean prior intravitreal injections of anti-VEGF-A therapy, number (SD) 5 (2.6) 7.3 (2.5) 6.7 (2.3) 6.3 (2.4)

Mean time from prior Tx to day 1, days 42 (0) 33.7 (7.2) 31 (4.4) 35.6 (6.5)

Mean HbA1c*, % (SD) 7.5 (2.4) 7.1 (0.3) 7.4 (1.4) 7.3 (1.4)

46

OPT-302 + aflibercept in DME: Phase 1b Safety Results

#APTC = Antiplatelet Trialists' Collaboration*Determined by treating investigator as unrelated to study drug(s)

47

Selected Adverse Events: Ocular or Systemic

OPT-302 (0.3 mg) + Aflibercept (2.0 mg)

(N=3)

OPT-302 (1 mg) + Aflibercept (2.0 mg)

(N=3)

OPT-302 (2 mg) + Aflibercept (2.0 mg)

(N=3)

Total Number of Subjects (N= 9)

Intraocular inflammation 0 0 0 0

Endophthalmitis 0 0 0 0

Retinal detachment 0 0 0 0

Vitreous hemorrhage 0 0 0 0

Hypertension 1* 0 0 1*

APTC events# (Non-Fatal Stroke, Myocardial Infarction, Vascular/Cardiac Death)

Combined APTC Events 0 0 0 0

IOP, mmHg: Baseline, week 12; (change from baseline) 13.0; 15.7 (2.7) 17.3; 15.3 (-2.0) 16.7; 17.0 (0.3) 15.7; 16.0 (0.3)

• 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 drug related adverse events

• Ocular AEs in the study eye primarily related to IVT injection procedure (Mild/moderate, resolved)

• No clinically significant changes in IOP, ECG’s, or vitals.

• OPT-302 was generally safe and well tolerated when administered in combination with aflibercept

OPT-302 has a favorable safety profile when administered with aflibercept (DME) expanding upon similar results when given as monotherapy or in combination with ranibizumab

(wet AMD)

48

OPT-302 + aflibercept in DME: Gains in Visual Acuity at Week 12Dose response relationship & reductions in retinal swelling in Phase 1b

Error Bars: SEM; Mean Baseline CST = 434 µm

Visual Acuity Retinal Thickness

49

Patients with Bilateral DME Gains in visual acuity and reductions in retinal thickness in OPT-302 + aflibercept treated eyes

*Patients with bilateral disease and persistent DME in the fellow eye receiving anti-VEGF-A (ranibizumab or aflibercept) monotherapyPrior anti-VEGF-A therapy in Fellow Eyes BL to Wk 12: 3x Aflibercept, 3x Ranibizumab, 1x Ranibizumab, 4x Ranibizumab, 3x Aflibercept

Mean baseline BCVA, CST: Study Eyes (63 letters, 445 µM); Fellow Eye (73 letters, 389 µM)# Excess foveal thickness was determined by using 300 µm Spectralis scan values and 285 µm Cirrus scan values

Mean Change in CST (uM) Baseline to Week 12

Study Eye

Fellow Eye

Mean Change in BCVA Baseline to Week 12

Study Eye Fellow Eye

Study Eye: 0.3 – 2mg OPT-302 + 2 mg Aflibercept Fellow Eye: Anti-VEGF-A Monotherapy*

• 5/9 patients enrolled in the Phase 1b trial had bilateral DME (DME in both eyes)

• Study eyes: • Received 3 doses OPT-302 +

aflibercept q4w

• Fellow eyes:• Received standard-of-care

anti-VEGF-A therapy*

Phase 2a OPT-302 + aflibercept in persistent DMEFully enrolled, primary data analysis 2Q CY 2020

50

Prior-Treated DME patients

Wee

k 12

Fol

low

-up

(Prim

ary

Endp

oint

)OPT-302 (2.0 mg) + aflibercept (2.0 mg) IVT Q4w x3, n=~72 pts

ClinicalTrials.gov Identifier: NCT03397264

ETDRS – Early Treatment Diabetic Retinopathy Study; CST: Central Subfield Thickness. * Participants included in the Per Protocol population are considered ‘evaluable’ participants.

Sham + aflibercept (2.0 mg) IVT Q4w x3, n=~36 pts

Prim

ary

Anal

ysis

aft

er a

ll

subj

ects

com

plet

e 12

wee

ks

PRN

ant

i-VEG

F-A

Wee

k 12

to 2

4

• Randomised, double-masked, dose-expansion study enrolled patients diagnosed with persistent centre-involved DME despite regular administration of prior anti-VEGF-A monotherapy

• Primary Outcome: • Clinical response rate, defined as the proportion of evaluable patients receiving combination OPT-302 and aflibercept achieving a ≥ 5 letter gain

in visual acuity at week 12 compared to baseline• The primary endpoint analysis will be performed using the Per-Protocol study population – those patients who were compliant with study

medication and considered sufficiently compliant with the protocol*

• Key Secondary Outcomes:• Mean change from Baseline in ETDRS best-corrected visual acuity at Week 12• Mean change from baseline to week 12 in CST and macular volume• Improvement in ETDRS diabetic retinopathy score

• Key Safety Outcome: Safety & tolerability

• 144 participants randomised#: 91 (63%) male, 55 (37%) female

• Mean Age: 61 years

51* Preliminary available Masked Study Data – data presented is subject to change pending data processing activities and further data collection as study progresses# Evaluable patients included in the calculation of the primary endpoint are those randomised that were sufficiently compliant with the trial protocol and are in the Per Protocol population. Determination of the Per Protocol population is made by a study team that is ‘masked’ to treatment group allocation.

OPT-302 Phase 2a in DME: Demographics & Safety Summary*

Aflibercept + OPT-302 administered by repeat IVT injection (Baseline, Week 4, Week 8)

• >250 intravitreal (IVT, ocular) injections of OPT-302 (2.0 mg) following aflibercept (2.0 mg) IVT have been administered

Data Safety Committee Reviews

• All available masked safety data reviewed upon 30, 60 and 90 participants being randomized and completing at least 14 days follow-up post first injection

• No safety concerns observed and study progressing as per protocol

Aflibercept + OPT-302 safety profile to date*:

• Generally well tolerated

• No ocular SAEs reported

• 86% adverse events reported as mild or moderate

• 94% adverse events reported as not study drug related or not injection related

• Mean Number of Prior Anti-VEGF-A Injections: ~ 8

• Mean Duration of Prior Anti-VEGF-A Injections: ~ 11.3 months

52

OPT-302 Safety & Dosing SummaryOPT-302 well tolerated safety profile in wet AMD & DME, in combination with both ranibizumab & aflibercept

295

DME

1554

153 297*

* At 7 Jan 2020, based on Masked Study Data – data presented is subject to change pending data processing activities and further data collection as study progresses

Participants dosed with OPT-302 in Phase 1/2a and Phase 2b clinical trials

Participants dosed with OPT-302 in Phase 1b/2a clinical trial

Total OPT-302 doses administered in Phase 1/2a and Phase 2b clinical trials

Total OPT-302 doses administered in Phase 1b/2a clinical trial*

Wet AMD

53

Planned: Pivotal Phase 3 ProgramTrial initiation 4Q CY 2020

Prim

ary

Effic

acy

Endp

oint

Wee

k 48

• Two studies of similar design: Multi-centre, double-masked, randomised (1:1), sham controlled

• Regulatory quality: 90% power, 5% type I error rate

• Sample size: Approx. 330 patients per arm, 660 per study

• Primary Objective: Mean change from Baseline in BCVA (visual acuity) (ETDRS) at Week 48

Wet AMD Naïve Pts

Ranibizumab (0.5 mg) + OPT-302 (2.0 mg)IVT q4w x 48 weeks

Ranibizumab (0.5 mg) + ShamIVT q4w x 48 weeks

Safe

ty F

ollo

w –

upW

eek

96

Efficacy Phase Safety Phase

*dosing every 4 or 8 weeks based on clinical signs of disease progression

Ranibizumab (0.5 mg) + OPT-302 (2.0 mg)IVT q4w or q8w* x 48 weeks

Ranibizumab (0.5 mg) + ShamIVT q4w or q8w* x 48 weeks

54

Activity / Milestone Approx. Date

2019

Phase 2b Positive Aug ‘19

50m AUD Financing Dec ‘19

Progress cGMP Manufacturing Ph3 Commenced

Phase 3 Planning Commenced

Complete Patient Recruitment Ph2a DME Dec ‘19

2020

End of Phase 2b Meeting FDA 2Q ‘20

EU regulatory meeting/s 2/3Q ‘20

Primary Analysis Phase 2a DME 2Q ‘20

Phase 2b Results Published Peer-Reviewed Journal 2Q ‘20

Initiate Recruitment Pivotal Phase 3 Trials wet AMD 4Q ‘20

Opthea: Upcoming Milestones

All dates represent Calendar Year dates; AUD: Australian Dollars; DME: Diabetic Macular Edema; FDA: Food & Drug Administration; EU: European

55

Opthea – Developing OPT-302 for Eye Diseases

• OPT-302 has broad development potential in a range of eye diseases, including wet AMD and DME

• Targets validated VEGF/VEGFR pathway and mechanism of escape from existing therapies that is differentiated to VEGF-A inhibitors and other agents in development; Pan-VEGF (A, C and D) inhibition may offer benefits that exceed the inhibition of VEGF-A alone

• Wet AMD & DME landscape includes only a limited number of novel combination therapies that may address the sub-optimal clinical responses that many patients experience on anti-VEGF-A therapies; majority of agents in development seeking to improve durability of VEGF-A inhibition rather than address deficiencies in EFFICACY with existing agents

• OPT-302 met primary endpoint of a large 366 patient Phase 2b clinical trial: demonstrating superior vision gain in patients treated with OPT-302 combination therapy compared to standard of care alone (p = 0.0107)

• Demonstrated safety & evidence of clinical activity in a 51 pt Phase 1/2a wAMD clinical trial that enrolled treatment-naïve and prior treated patients administered OPT-302 monotherapy and OPT-302 in combination with Lucentis®

• Fully recruited, randomised, double-masked, Phase 1b/2a clinical trial of OPT-302 + Eylea® compared to Eylea® alone in ~117 DME patients. Trial recruited patients from US, Israel, Latvia & Australia

• Evidence of a dose response for OPT-302 combination treatment on gains in BCVA in persistent DME & reduction in fluid

• OPT-302 has demonstrated a favourable safety profile in combination with both ranibizumab (Lucentis) and aflibercept (Eylea)

• Primary data reporting for Phase 2a DME 2Q CY 2020

• Fully funded through DME trial outcome and Phase 3 preparations for wet AMD

56

COMPOSITION OF MATTER TERM

Covering OPT-302 molecule• Granted patents in the USA, Japan, Russia, Australia, South Africa & Singapore• Patents accepted for grant in Europe, Malaysia & Mexico• Applications pending in a further 10 jurisdictions including China, Brazil & India

2034*

Covering sVEGFR-3 molecules (incl. OPT-302)• Granted Patent in Europe, Japan, Canada, Australia• Granted Patent in the USA

20222026

• Separate US Patent granted covering generic use of sVEGFR-3 capable of binding VEGF-C to inhibit blood vessels in mammal having disease characterised by expression of VEGFR-3 in blood vessels

2023

PATENT TERM EXTENSION / DATA EXCLUSIVITY

*Patent Term Extension Up to 5 years additional patent term is available under patent term extension rules in most(PTE) jurisdictions including the USA, Europe and Japan

Data Exclusivity (DE) & Once approved, OPT-302 will be entitled to DE, and potentially also ME, in many jurisdictions:Market Exclusivity (ME) USA 12 years Data Exclusivity for biologics

Europe 10 years made up of 8 years Data Exclusivity + 2 years Market ExclusivityJapan Up to 8 years de facto Data ExclusivityCanada Up to 8 years incl. up to 6 years Data Exclusivity + 2 years Market Exclusivity

OPT-302 Intellectual Property

Summary covering sVEGFR-3 for Eye Disease

Megan BaldwinCEO & Managing Director

T +61 (3) 9826 0399E [email protected]

Suite 0403, Level 4,650 Chapel Street,South Yarra 3141 Victoria Australia www.opthea.com

mailto:[email protected]

Documents

OPT-302...This presentation is not an offeror invitation for subscription or purchase of or a recommendation of securities. It does not take into account the investment objectives,