Opthea Ltd — AGM Information 2018

Nov 28, 2018

==> picture [245 x 54] intentionally omitted <==

2018 Annual General Meeting

CEO Presentation – 2018 AGM, November 29 2018 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.

==> picture [139 x 32] intentionally omitted <==

2

Opthea is Developing OPT-302 as a Novel Combination Therapy for wet AMD & DME

• OPT-302 blocks VEGF-C and VEGF-D

• Blocks vessel growth and leakage, two of the key disease hallmarks

• Wet AMD: Leading cause of blindness in over 55’s

• DME: Leading cause of vision loss in diabetics

• Both increasing in prevalence

==> picture [290 x 184] intentionally omitted <==

----- Start of picture text -----

Wet AMD
----- End of picture text -----

==> picture [106 x 13] intentionally omitted <==

----- Start of picture text -----

Normal Retina
----- End of picture text -----

==> picture [224 x 147] intentionally omitted <==

==> picture [78 x 193] intentionally omitted <==

----- Start of picture text -----

VEGF-C/D VEGF-C/D
----- End of picture text -----

Extra-Cellular Domains 1-3 hVEGFR-3

==> picture [56 x 15] intentionally omitted <==

----- Start of picture text -----

hIgG1 Fc
----- End of picture text -----

==> picture [139 x 32] intentionally omitted <==

3

Our Goal: To Improve Vision in Diabetic & Elderly Patients

==> picture [387 x 293] intentionally omitted <==

==> picture [394 x 300] intentionally omitted <==

==> picture [139 x 32] intentionally omitted <==

4

Large Socio-Economic Impact of Vision Loss

==> picture [790 x 430] intentionally omitted <==

----- Start of picture text -----

Fear of total blindness, Daily necessities: preparing
feeling isolated, helpless, Psychological meals, shopping,
depression well-being recognising faces
Costs to
health-care
system & Work & Social
Difficult to care for self, support IMPACT
Integration
increased risk of injury services
OF VISION
LOSS
Work: going to work,
Reliance on caregivers,
continued employment
guilt
Physical
Lost
well-being
independence
----- End of picture text -----

5

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

OPT-302 Clinical Program

Two ongoing randomised controlled clinical trials in nAMD & DME

Phase 1 Combination Agent Preclinical Phase 2a Phase 2b Phase 3 Status 1o Data Analysis	Phase 1 Combination Agent Preclinical Phase 2a Phase 2b Phase 3 Status 1o Data Analysis	Phase 1 Combination Agent Preclinical Phase 2a Phase 2b Phase 3 Status 1o Data Analysis	Phase 1 Combination Agent Preclinical Phase 2a Phase 2b Phase 3 Status 1o Data Analysis	Phase 1 Combination Agent Preclinical Phase 2a Phase 2b Phase 3 Status 1o Data Analysis	Phase 1 Combination Agent Preclinical Phase 2a Phase 2b Phase 3 Status 1o Data Analysis	Phase 1 Combination Agent Preclinical Phase 2a Phase 2b Phase 3 Status 1o Data Analysis	Phase 1 Combination Agent Preclinical Phase 2a Phase 2b Phase 3 Status 1o Data Analysis	Phase 1 Combination Agent Preclinical Phase 2a Phase 2b Phase 3 Status 1o Data Analysis
Neovascular AMD
OPT-302 Target: VEGF-C/D OPT-302 Target: VEGF-C/D	Ranibizumab Target: VEGF-A Ranibizumab Target: VEGF-A						Complete Ph 1/2a (n=51) Ongoing Ph 2b (n=366)	April 2017 4Q CY 2019
Diabetic Macular Ed	ema
OPT-302 Target: VEGF-C/D	Aflibercept Target: VEGF-A, PlGF, VEGF-B						Ongoing Ph 1b/2a (n=117)	2H 2019

==> picture [139 x 32] intentionally omitted <==

6

Corporate & Operational Achievements

Phase 2b Wet AMD Trial

• Progressed regulatory submissions with FDA (USA) & Competent Authorities (EU, Israel)

• Initiated and dosed first patient in US (Dec ‘17)

• Dosed first patient in EU & Israel (Mar ‘18)

• DSMB (independent safety monitoring committee) unanimously recommended trial

• continues without modification (July ’18)

• Completed target recruitment of 351 pts in <12 months and ahead of schedule (Nov ‘18)

• Enrolled last patient, 366 pts randomised (Nov ‘18)

• Brought forward top-line data reporting date to 4Q CY 2019

==> picture [139 x 32] intentionally omitted <==

7

Corporate & Operational Achievements

Phase 1b/2a DME Trial

• Commenced DME Phase 1b trial at US sites (Dec ’17)

• Met primary safety objective in Phase 1b DME study

• OPT-302 well tolerated when administered in combination with aflibercept (Eylea®) (Jul ’18)

• Dosed first patient in Phase 2a DME trial (Jul ’18)

• Dosed first Australian patient in Phase 2a DME (Sep ‘18)

• Reported positive 3-month data from Phase 1b DME study (9 pts) (Oct ‘18)

• Presented Phase 1b data to international clinical & investor forums (Nov ’18)

• Progressed recruitment into Phase 2a (ongoing)

==> picture [139 x 32] intentionally omitted <==

8

Corporate & Operational Achievements

Corporate

• Strengthened cash position to >$37m:

• Received A$12m R&D tax credit (Aust & O/S eligible expenditure)

• 99.4% options exercised generating >$13.3m proceeds

• Company well-funded through clinical milestones in wAMD & DME

• Continued to raise company profile with local and international investors & global pharmaceutical companies

• Opthea KOL forum NYC moderated by Citigroup (Nov ‘18)

• Data presented at international conferences by management, clinical advisory board & investigators

• OIS@American Academy Ophthalmology Conference (Oct ‘18)

• Retina Society, EURetina

==> picture [139 x 32] intentionally omitted <==

9

Financial Position (Unaudited)

Key Financial Details	ASX: OPT
Ticker Symbol	ASX:OPT
Share Price (Nov 27 2018)	~A$0.58
Total Ordinary Shares on Issue	249,413,639
Market Capitalisation (Nov 27 2018)	~A$145m (~USD104m)
Trading Range (last 12 months)	A$0.42 – 0.80
Cash Balance (Oct 31 2018)	~A$37m
Forecast Net Operating Cash Burn (CY 2018)	~$18m
Top 20 Shareholders Own	69%
Institutional Holders	84%

==> picture [434 x 266] intentionally omitted <==

----- Start of picture text -----

Share Price Performance (December 2016 - November 2018)
1.4
1.2
High
1
0.8
0.6
0.4
0.2
0
AUD
----- End of picture text -----

==> picture [139 x 32] intentionally omitted <==

10

wAMD & DME: Large & Growing Market Opportunities

VEGF-A Inhibitors

Novartis Regeneron Roche Genentech Bayer Genentech

Market Opportunity >$10BN Worldwide

2017: ~$9.3BN USD 40% Market Share

Off-Label Use 60% Market Share

==> picture [139 x 32] intentionally omitted <==

11

An Unmet Medical Need for nAMD & DME

: Despite receiving a VEGF-A inhibitor (Ranibizumab, Aflibercept or Bevacizumab)[*]

==> picture [780 x 333] intentionally omitted <==

----- Start of picture text -----

50% Do not achieve significant vision gains
nAMD 2/3 Will continue to have fluid at the back of the eye
25% Will have further vision loss at 12 months
2/3 Do not achieve significant vision gains [#]
DME
25% Continue to have macula thickening/swelling [^]
Opportunity: New Products that Improve Efficacy and Durability
----- End of picture text -----

==> picture [139 x 32] intentionally omitted <==

12

* 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

Presented at Opthea’s KOL Forum NYC: Dr. Arshad Khanani

==> picture [960 x 44] intentionally omitted <==

----- Start of picture text -----

NEOVASCULAR AMD – SHORTCOMINGS OF VEGF-A BLOCKADE
----- End of picture text -----

20/20

==> picture [47 x 155] intentionally omitted <==

>70% VA REMAINS TO BE GAINED

20/100

#1 EFFICACY

Very Few Novel Combination Therapies in Development

DURABILITY (fewer injections) & BIOSIMILARS Targeting Anti-VEGF-A

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

==> picture [650 x 123] intentionally omitted <==

----- Start of picture text -----

Eylea Lucentis Avastin [#] OPT-302 RG7716 REGN910 Fovista
Co-formulated
Bi-specific, with Eylea
also
VEGF-B VEGF-A VEGF-C/D targets ANG-2 PDGF
VEGF-A
VEGFR-1 VEGFR-2 VEGFR-3 Tie2 PDGF-R
----- End of picture text -----

= In Clinical Development

• = Failed to meet primary endpoint or not advancing to Phase 3 = Approved therapies

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

==> picture [139 x 32] intentionally omitted <==

14

# Avastin is used off-label for the treatment of wet AMD

The Opportunity for OPT-302

==> picture [471 x 263] intentionally omitted <==

• To increase the number of patients who experience a significant gain in vision

• To increase the magnitude of the vision gain

• To prolong response to therapy and prevent visual decline

• Potential to reduce dosing frequency

==> picture [139 x 32] intentionally omitted <==

15

OPT-302 Phase 1/2a First-in-Human Study in Neovascular AMD (n=51)

==> picture [804 x 386] intentionally omitted <==

----- Start of picture text -----

Part 1: Dose-escalation Part 2: Dose-expansion
(Open-label) (Randomised 3:1)
OPT-302 (2 mg) OPT-302 (2 mg)
Monotherapy Monotherapy
IVT Q4W x 3 IVT Q4W x 3, n=8 pts
Cohort 4
OPT-302 (2 mg)
OPT-302 (2 mg) +
+ Ranibizumab (0.5 mg)
Ranibizumab (0.5 mg)
IVT Q4W x 3 IVT Q4W x 3, n=23 pts
Cohort 3
OPT-302 (1 mg) +
Ranibizumab (0.5 mg)
IVT Q4W x 3
Cohort 2
OPT-302 (0.3 mg) +
Ranibizumab (0.5 mg)
IVT Q4W x 3
Cohort 1
28 Day DLT window Follow-up to week 12
Primary Analysis after all
subjects complete 12 weeks
Long term follow-up at Week 24
----- End of picture text -----

• Comprises of 4 treatment cohorts of 5 subjects each

• *Access to rescue anti-VEGF-A Tx

ClinTrials Identifier NCT 02543229

==> picture [139 x 32] intentionally omitted <==

16

OPT-302 +/- Ranibizumab - Phase 1/2a Safety Summary

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

• No missed doses, safety experience with ~150 intravitreal (ocular) injections of OPT-302

• OPT-302 at ocular doses up to 2 mg + Lucentis (0.5 mg):

• No dose limiting toxicities (MTD was not reached)

• No drug-related serious adverse events or systemic adverse events

Majority of ocular emergent adverse events primarily related to IVT injection procedure

• (31 / 51 patients; 59%); majority Grade 1 / Mild or Grade 2 / Moderate and Manageable

Two patients (4%) had ocular adverse events related to OPT-302 study drug

• AEs were Grade 1 / Mild inflammation indicative of anterior uveitis in the low- and mid-dose combination

  • groups

• No OPT-302 related AEs observed in the high dose (2mg) combination or monotherapy treated patients (n=41)

• No clinically significant changes in IOP, ECG’s, blood pressure, vitals No evidence of OPT-302-related immunogenicity

OPT-302 has consistently demonstrated a favourable safety profile +/- ranibizumab

==> picture [139 x 32] intentionally omitted <==

17

Evidence of biological activity in patients treated with intravitreal OPT-302 (2 mg) monotherapy

• Of the 13 patients who received OPT-302 monotherapy treatment:

• 7/13 (54%) did not receive anti-VEGF-A rescue therapy through week 12

• An additional 5/13 (38%) received only 1 rescue injection through week 12

• One subject (8%) received 2 rescue injections.

• The mean time to rescue therapy was 58 days.

• Use of rescue therapy in 4/6 cases was based on Investigator discretion

==> picture [536 x 314] intentionally omitted <==

----- Start of picture text -----

Mean Change VA from Baseline (letters) Mean Change in Visual Acuity
6
+5.6 letter s
+4.4 letters
4
+2.8 letters
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 )
----- End of picture text -----

Mean Baseline VA = 55.7 Letters

Ranibizumab rescue therapy available week 2 through week 12 at investigator discretion or if patients met pre-defined criteria: <10% decrease in CST and ≥5 letter loss of BCVA

==> picture [139 x 32] intentionally omitted <==

18

Gains in Visual Acuity and Reduced Retinal Thickness in Patients with OPT-302 + Ranibizumab Therapy

==> picture [900 x 409] intentionally omitted <==

----- Start of picture text -----

Change in mean BCVA Change in mean Central Subfield Thickness
Time (weeks)
15
Naïve pts (n=18)
0 2 4 6 8 10 12
Prior treated pts (n=20)
0
-20
+10.8 letters
10
-40
-54 µM
-60
-80
5 + 4.9 letters
-100
-120 -119 µM
-140
Naïve pts (n=18)
0 Prior treated pts (n=20)
-160
0 4 8 12
Time (weeks) Treatment Naïve Patients: n = 18; OPT-302 (0.3, 2.0 mg) + ranibizumab (0.5 mg) Prior-Treated Patients:n = 20 (wk 4, 8), 19 (wk 12); OPT-302 (0.3-2.0 mg) + ranbizumab (0.5 mg)
Error Bars: SEM
Mean Baseline VA = 56.5 Letters Mean Baseline VA = 64.5 Letters; Mean number prior anti-VEGF-A injections = 17
Change from baseline in CST (µM)
Change from baseline in Visual Acuity (ETDRS Letters)
----- End of picture text -----

19 Error Bars: SEM

OPT-302 +/- Ranibizumab Phase 2b Trial in Treatment-Naïve nAMD (n=366)

==> picture [683 x 293] intentionally omitted <==

----- Start of picture text -----

OPT-302 (2 mg) + Ranibizumab (0.5 mg) n=~122
Treatment-Naive
OPT-302 (0.5 mg) + Ranibizumab (0.5 mg) n=~122
Neovascular AMD
Sham + Ranibizumab (0.5 mg) n=~122
Randomized 1:1:1 to treatment arms
IVT dosing at every 4 weeks (x 6)
Week 24 Follow-up
----- End of picture text -----

==> picture [139 x 32] intentionally omitted <==

ClinTrials Identifier NCT 03345082

20

Development of DME

==> picture [691 x 342] intentionally omitted <==

----- Start of picture text -----

Increased VEGF-A, VEGF-C/D
----- End of picture text -----

==> picture [139 x 32] intentionally omitted <==

21

An Unmet Medical Need for DME

• DME is the leading cause of vision loss in working-age adults in the US & Europe

• An estimated 2M people are affected by DME worldwide

• Increasing prevalence due to growing global health epidemic of diabetes, high proportion of patients not diagnosed

• For those that are treated with anti-VEGF-A therapy, many do not achieve 20/40 or better vision

• Approved therapies for wet AMD & DME target VEGF-A, but not VEGF-C or VEGF-D

• VEGF-C and VEGF-D activate the same, as well as independent, pathways to VEGF-A

• o VEGF-C and VEGF-D may mediate resistance to VEGF-A inhibitors (Lucentis, Eylea, Avastin)

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

==> picture [158 x 109] intentionally omitted <==

----- Start of picture text -----

35%
1/3
----- End of picture text -----

Fail to achieve significant vision gains[#]

Continue to have macular thickening / swelling ^

==> picture [601 x 32] intentionally omitted <==

Our objective with OPT-302 is to address the unmet medical need for patients who experience persistent DME despite treatment with a VEGF-A inhibitor

==> picture [139 x 32] intentionally omitted <==

22

* 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

We Know Very Quickly Whether or Not Patients Will Respond to Anti-VEGF-A

==> picture [827 x 357] intentionally omitted <==

----- Start of picture text -----

20
16.5
13.8
15.2
15
10
6.9 8.2 8.2
p<0.001
5
2.8 3.0
0
-0.3
-5
BL 12 16 20 24 28 32 36 40 44 48 52 . .. … 68 . .. … 84 . .. … …. 104 . .. 120 . .. 136 . . . .. . … . …. 156
… …
Weeks
<5 letters 5-9 letters ≥10 letters
at 12w (N=135) at 12w (N=79) at 12w (N=126)
BCVA Change from Baseline
----- End of picture text -----

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.

==> picture [139 x 32] intentionally omitted <==

23

OPT-302 Mechanism of Action Supports Investigation in DME

VEGF-C and its interaction with VEGFR-2 and VEGFR-3 plays a functional role in pathogenesis of DME:

• OPT-302 has shown evidence of activity to resolve retinal fluid[1]

• VEGFR-2 expression is greater in diabetic retina than non-diabetics[2,3,4]

• VEGF-C is elevated in diabetic retinopathy[4]

• Vitreous levels of VEGF-D are elevated in diabetes[5]

• VEGF-C expression is elevated by glucose & pro-inflammatory cytokines[6,7]

• Inhibition of VEGF-C and VEGF-D in adipose tissue of mice improves metabolic parameters and insulin sensitivity[8,9]

• Advanced glycation end products accumulate faster in diabetics and stimulate VEGF-C expression and secretion from the RPE[6]

• Single nucleotide polymorphisms (SNPs) in diabetic patients indicate that genetic variation in the VEGF-C gene is associated with diabetic retinopathy and diabetic macular edema[10]

VEGF-C/D Signaling Pathway is Implicated in Diabetes

1. Phase 1/2a OPT-302 trial results: www.opthea.com; 2. Sun et al., 2014; 3. Witmer et al., 2002; 4. Zhao et al., 2007; 5. Kovacs et al., 2015; 6. Puddu et al., 2012; 7. Nagineni et al., 2011;

8. Karaman et al., 2014; 9. Karaman et al., 2016; 10. Kaidonis et al., 2015

==> picture [139 x 32] intentionally omitted <==

24

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

==> picture [779 x 271] intentionally omitted <==

----- Start of picture text -----

Phase 1b Dose-Escalation N=9 patients Phase 2a Dose-Expansion
(Randomised 2:1 ratio)
OPT-302 (2.0 mg) OPT-302 (2.0 mg)
+ Aflibercept (2.0 mg) + Aflibercept (2.0 mg)
IVT Q4W x 3, n=3 IVT Q4W x 3, n=~72 pts
Cohort 3
OPT-302 (1.0 mg) N=
Aflibercept (2.0 mg)
+ Aflibercept (2.0 mg)
IVT Q4W x 3, n=~36 pts
IVT Q4W x 3, n=3
Cohort 2
OPT-302 (0.3 mg)
+ Aflibercept (2.0 mg)
IVT Q4W x 3, n=3
ClinTrials Identifier
Cohort 1 NCT 03397264
14 Day DLT window Week 12 to 24
PRN anti-VEGF-A Primary Analysis after all
Follow-up to week 12 subjects complete 12 weeks
----- End of picture text -----

Key Inclusion Criteria

Key Exclusion 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.

• 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

==> picture [139 x 32] intentionally omitted <==

25

Baseline Ocular Characteristics – Prior Treated

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) 64.3(9) 64.6(5) 66.7(3.1) 3(100%) 3(100%) 3(100%) 0(0%) 0(0%) 0(0%) 460(103) 410(26) 432(24) 1(33%) 3(100%) 2(67%) 2(67%) 0(0%) 1(33%) 14 (7.9) 17.3 (13) 10.9 (12.6) 5 (2.6) 7.3 (2.5) 6.7 (2.3) 42(0) 33.7(7.2) 31(4.4) 7.5(2.4) 7.1(0.3) 7.4(1.4)	Total Number of Subjects (N=9)
Vision
Mean BCVA, ETDRS letters(SD)		65(5.5)
Better than 55 letters vision, n(%)		9(100%)
Worse than 55 letters vision, n(%)		0(0%)
Anatomic
Mean CST, µm (SD)		434(58)
CST ≤ 450µm, n(%)		6(67%)
CST ≥ 450µm, n(%)		3(33%)
Mean duration of diabetes at screening, years (SD)		14.1 (10.3)
Mean prior intravitreal injections of anti-VEGF-A therapy, number (SD)		6.3 (2.4)
**Mean time fromprior Tx to day 1, days **		35.6(6.5)
Mean HbA1c*, %(SD)		7.3(1.4)

==> picture [139 x 32] intentionally omitted <==

26

*HbA1c = glycated hemoglobin

OPT-302 + Aflibercept Safety Results

• 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 + 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)

==> picture [139 x 32] intentionally omitted <==

27

OPT-302 + Aflibercept – Safety Summary of selected AEs

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) 0 0 0 0 0 0 0 0 0 0 0 0 1* 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 13.0;15.7(2.7) 17.3;15.3(-2.0) 16.7;17.0(0.3)	Total Number of Subjects (N=9)
Intraocular inflammation		0
Endophthalmitis		0
Retinal detachment		0
Vitreous hemorrhage		0
Hypertension		1*
APTC events#
Nonfatal myocardial infarction		0
Nonfatal stroke		0
Vascular or cardiac death or death of unknown cause		0
Combined APTC events		0
Any other death		0
IOP, mmHg: Baseline, week 12; (change from baseline)		15.7;16.0(0.3)

• No safety signals or unexpected findings

#APTC = Antiplatelet Trialists' Collaboration

*Determined by treating investigator as unrelated to study drug(s)

==> picture [139 x 32] intentionally omitted <==

28

OPT-302 + Aflibercept: Gains in BCVA at Week 12 Dose Response Relationship

0 5 1 0 1 5 2 0 0.3 mg OPT-302 1 mg OPT-302 2 mg OPT-302 0.3 - 2 mg OPT-302 (N=9) (N=3) (N=3) (N=3) +7.7 +14.3 +3.0 +5.7
	Dose of OPT-302 + Aflibercept (2 mg) % of pts with BCVA gain ≥ 5 letters Mean # prior anti-VEGF-A injections
	0.3 mg 1/3 (33%) 5
	1 mg 2/3 (67%) 7.3
	2 mg 3/3 (100%) 6.7
	0.3 to 2 mg 6/9 (67%) 6.3

==> picture [139 x 32] intentionally omitted <==

+ 2 mg Aflibercept

29

Error Bars: SEM

OPT-302 (0.3-2 mg) + Aflibercept (2 mg): Mean changes in CST from Baseline to Week 12

==> picture [640 x 363] intentionally omitted <==

----- Start of picture text -----

20
0
-20
-40
-60
- 71 µM
-80
-100
0 2 4 8 12
Week
CST on SD-OCT (µm)
Mean Change from Baseline in
----- End of picture text -----

==> picture [139 x 32] intentionally omitted <==

Error Bars: SEM; Mean Baseline CST = 434 µm

30

DME Patients with Bilateral Disease* Study Eye vs Fellow Eye (N=5)

==> picture [588 x 379] intentionally omitted <==

----- Start of picture text -----

Mean Change in BCVA Baseline Mean Change in CST (uM) Baseline
to Week 12 to Week 12
OPT-302 + Anti-VEGF-A OPT-302 + Anti-VEGF-A
Aflibercept Monotherapy Aflibercept Monotherapy
+10.0
-6 µM
+2.6
-80 µM
Study Eye:
0.3 – 2mg OPT-302 + 2 mg Aflibercept
Mean Change CST (µM)
Mean Change BCVA (Letters)
----- End of picture text -----

==> picture [190 x 65] intentionally omitted <==

----- Start of picture text -----

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

*Patients with bilateral disease and persistent DME in the fellow eye receiving anti-VEGF-A (ranibizumab or aflibercept) monotherapy Prior 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

==> picture [139 x 32] intentionally omitted <==

31

Phase 2a Randomised Dose Expansion study of OPT-302 + Aflibercept in Persistent DME

==> picture [779 x 272] intentionally omitted <==

----- Start of picture text -----

Phase 1b Dose-Escalation Phase 2a Dose-Expansion
(Randomised 2:1 ratio)
OPT-302 (2.0 mg) OPT-302 (2.0 mg)
+ Aflibercept (2.0 mg) + Aflibercept (2.0 mg)
IVT Q4W x 3, n=3 IVT Q4W x 3, n=~72 pts
Cohort 3
OPT-302 (1.0 mg)
Aflibercept (2.0 mg)
+ Aflibercept (2.0 mg)
IVT Q4W x 3, n=~36 pts
IVT Q4W x 3, n=3
Cohort 2
OPT-302 (0.3 mg)
+ Aflibercept (2.0 mg)
IVT Q4W x 3, n=3
ClinTrials Identifier
Cohort 1 NCT 03397264
14 Day DLT window Week 12 to 24
PRN anti-VEGF-A Primary Analysis after all
Follow-up to week 12 subjects complete 12 weeks
----- End of picture text -----

• Phase 2a currently enrolling patients in US and Australia

• Primary data analysis 2H CY 2019

==> picture [139 x 32] intentionally omitted <==

32

Opthea Program Highlights & Upcoming Milestones

• OPT-302 targets validated pathway & may address mechanisms of incomplete response to existing standard of care treaments

• Large unmet medical need & market opportunity – will ‘add-on’ to existing therapy rather than ‘replace’

• Clinical data to date demonstrates:

• Favourable safety profile in combination with ranibizumab in wAMD and in combination with aflibercept in DME

• Clear evidence of clinical activity of OPT-302 in both wet AMD and DME across multiple endpoints, including visual acuity gains and reductions in retinal thickness

• • Two Phase 2 primary data readouts in 2019:

• ~108 patient randomised controlled Phase 2a trial in DME (2H CY 2019)

• 366 patient randomised controlled Phase 2b trial in wAMD (4Q CY 2019)

==> picture [139 x 32] intentionally omitted <==

33

==> picture [188 x 41] intentionally omitted <==

Megan Baldwin, PhD CEO & Managing Director