Opthea Ltd — Investor Presentation 2024

Oct 27, 2024

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Transforming Patient Outcomes with Superior Vision Gains

Corporate Overview | October 2024 NASDAQ (OPT); ASX (OPT.AX)

Disclaimer and Forward-looking Statements

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This presentation includes general background information about the activities of Opthea Limited (ABN 32 006 340 567) (“Opthea” or “Company”) and its affiliates and subsidiaries (together, the “Opthea Group”). The information contained in this presentation is in summary form and does not purport to be complete or to contain all material information about the Opthea Group which a prospective investor or purchaser may require in evaluating a possible investment in Opthea or acquisition of securities in Opthea. The information in this presentation remains subject to change without notice. No member of the Opthea Group nor any director, officer, employee, adviser, agent or representative of any member of the Opthea Group (each an Opthea Party and together, the Opthea Parties) has any obligation to update or correct this presentation.

This presentation contains forward-looking statements within the meaning of the U.S. federal securities laws that involve substantial risks and uncertainties. All statements, other than statements of historical facts, contained in this presentation, including statements regarding the therapeutic and commercial potential and size of the estimated market opportunity of the Company’s product in development, the viability of future opportunities, future market supply and demand, the expected timing of top-line data, our expectations about topline data based on masked pooled data, the future cash runway, the financial condition, results of operations and business of Opthea, certain plans, objectives and strategies of management of Opthea, including with respect to the current and planned clinical trials of its product candidate and the future performance of Opthea, are forward-looking statements. The words “anticipate,” “believe,” “estimate,” “expect,” “intend,” “may,” “might,” “plan,” “predict,” “project,” “target,” “potential,” “will,” “would,” “could,” “should,” “continue,” and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. Opthea may not actually achieve the plans, intentions or expectations disclosed in the forward-looking statements, and you should not place undue reliance on the forward-looking statements as predictions of future events. Actual results or events could differ materially from the plans, intentions and expectations disclosed in the forward-looking statements we make. The forward-looking statements contained in this presentation reflect Opthea’s current views with respect to future events, and we assume no obligation to update any forwardlooking statements except as required by applicable law. Please refer to information, including risk factors, set forth in Opthea’s Annual Report on Form 20-F filed with the U.S. Securities and Exchange Commission on August 30, 2024, and other future filings with the U.S. Securities and Exchange Commission for key factors that could cause actual results to differ materially from those projected in the forward-looking statements contained herein including risks associated with: future capital requirements and ability to continue as a going concern, the development, testing, production, marketing and sale of drug treatments, regulatory risk and potential loss of regulatory approvals, ongoing clinical studies to demonstrate sozinibercept safety, tolerability and therapeutic efficacy, additional analysis of data from Opthea’s Phase 3 clinical trials, including once masked pooled data is unmasked, clinical research organization and labor costs, intellectual property protections, future capital requirements, the development, testing, production, marketing and sale of drug treatments, regulatory risk and potential loss of regulatory approvals, ongoing clinical studies to demonstrate sozinibercept safety, tolerability and therapeutic efficacy, and other factors that are of a general nature which may affect the future operating and financial performance of the Company.

This presentation includes statistical and other industry and market data that we obtained from industry publications and research, surveys and studies conducted by third parties as well as our own estimates of potential market opportunities. All of the market data used in this presentation involves a number of assumptions and limitations, and you are cautioned not to give undue weight to such data. Industry publications and third-party research, surveys and studies generally indicate that their information has been obtained from sources believed to be reliable, although they do not guarantee the accuracy or completeness of such information. Our estimates of the potential market opportunities for our product candidates include several key assumptions based on our industry knowledge, industry publications, third-party research and other surveys, which may be based on a small sample size and may fail to accurately reflect market opportunities. While we believe that our internal assumptions are reasonable, no independent source has verified such assumptions.

The information contained in this presentation does not constitute investment or financial product advice (nor taxation or legal advice) and is not intended to be used as the basis for making an investment decision. The presentation is for informational purposes only and is not a prospectus or other disclosure document under Australian law or the law of any other jurisdiction and does not contain all the information which would be required to be disclosed in a prospectus or other disclosure document. The information presented in this presentation may differ materially from that presented in any disclosure document prepared in connection with any offer of securities. It does not take into account the investment objectives, financial situation, taxation position or needs of any particular investor, which should be considered when deciding if an investment is appropriate. You must consider your own investment objectives, financial situation and needs and conduct your own independent investigations and enquiries, including obtaining taxation, legal, financial or other professional advice in relation to the information contained in this presentation as appropriate to your jurisdiction. This presentation should not be relied upon by the Recipient in considering the merits of any particular transaction.

This presentation does not constitute an offer to sell, or the solicitation of an offer to buy, any securities in the United States or any other jurisdictions in which such an offer would be unlawful prior to registration or qualification under the U.S. Securities Act of 1933, as amended, or the securities laws of any state or other jurisdiction of the United States.

This presentation may contain trademarks and trade names of third parties, which are the property of their respective owners. Third party trademarks and trade names used in this presentation belong to the relevant owners and use is not intended to represent sponsorship, approval or association by or with any of the Opthea Group.

2

Sozinibercept Has the Potential to Be the First Product in 20 Years to Improve Visual Outcomes

• Addressing High Despite wide use of anti-VEGF-A therapy, wet AMD patients still experience loss in vision long term[1] Unmet Need • Every letter of vision counts to improve quality of life and reduce mortality • Proprietary First-in-class VEGF-C/D ‘trap’ inhibitor intended for combination with standard of care anti-VEGF-A therapies Technology • Composition of Matter and Methods of Use Patents through 2034; opportunities to extend beyond 2034*

• Phase 2b demonstrated superiority in combination with SOC therapy, with well tolerated safety profile Superior Lead Asset • Sozinibercept has the potential to improve vision for millions of patients with wet AMD

• Topline data anticipated for COAST (n=998) in early 2Q CY2025 and ShORe (n=986) in mid-CY2025

• Topline Data from

• Pivotal Trials in 2025 • Current cash expected to fund operations into 3Q CY2025[2] Substantial Market • Multibillion dollar commercial opportunity in a growing market with an established clinical practice Opportunity • Sozinibercept developed for use in combination with any anti-VEGF-A; will not compete directly with SOC therapies

AMD – age-related macular degeneration; MOA – Mechanism of Action; SOC – Standard of care

1CATT Research Group; Maguire MG et al. Ophthalmology. 2016 Aug.

2Additional funding will be required to reach commercialization of sozinibercept and to meet obligations under the Development Funding Agreement ("DFA"). As a result of obligations under the DFA and applicable law regarding liquidity, the Company expects to raise or obtain additional capital in one or more transactions, earlier than 3Q CY 2025 or anticipated topline data readout dates. *Potential for Patent Term Extensions & Data and Market Exclusivity (12 Years for Biologic)

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Sozinibercept Designed to Improve Visual Outcomes in Combo with VEGF-A Inhibitors; Potential to Create New Multi-Billion Dollar Class

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Global Marketed VEGF-A Inhibitors

Sozinibercept is a VEGF-C/D “Trap” Inhibitor

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~$15bn Global Market
and Growing
Eylea
Vabysmo
$9.4bn
$2.8bn
Biosimilars Beovu
Lucentis
Avastin ~$2.0bn
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Potential value proposition:

Targeting Improved Visual Function Critical for Patients, Physicians and Payors

Fits Seamlessly into Physician Practice

Potential Use with Any VEGF-A Inhibitor

Multi-Billion Dollar Commercial Opportunity

The $15bn global market comprised of Eylea, Vabysmo, Lucentis revenue plus an estimate for biosimiliars, Avastin off-label, and Beovu of ~$1bn

4

Experienced Leadership Team Expertise and Track Record to Make a Positive Impact on the Retinal Community

Chief Medical Advisor

Management Team

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Arshad M. Khanani, MD, MA, FASRS

Managing Partner, Director of Clinical Research and Director of Fellowship at Sierra Eye Associates, and Clinical Professor at the University of Nevada, Reno School of Medicine

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Fred Guerard, PharmD, MS Chief Executive Officer

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Clinical Advisory Board

Tom Reilly

Chief Financial Officer

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Charles C. Wykoff, MD, PhD

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Director of Research, Retina Consultants of Texas, Chairman of Research and Clinical Trials Committee, Retina Consultants of America

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Parisa Zamiri, MD, PhD

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Chief Medical Officer

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Tim Jackson, PhD, MB, ChB, FRCophth

National Health Service, Consultant at Kings Hospital College Hospital, London

Megan Baldwin, PhD, MAICD Founder, Chief Innovation Officer

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Jason Slakter, MD

Clinical Profession at New York University School of Medicine and partner at Vitreous Retina Macula Consultants of New York

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Mike Campbell

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Chief Commercial Officer

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5

Despite Treatment with Standard of Care Anti-VEGF-A Therapies, the Majority of Patients Achieve Suboptimal Vision Outcomes

Despite treatment with anti-VEGF-A therapy*

>45% do not achieve significant vision gains

>60% will have persisting macular fluid

25% will have further vision loss at 12+ months

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The majority of patients fail to achieve 20/40 vision[1]

Suboptimal vision is associated with decrease in Instrumental Activities of Daily Living (IADL) skills[2]

*Based on randomised, controlled clinical trial data; >45% fail to achieve ≥ 2 lines improvement in Best Corrected Visual Acuity (BCVA); Persisting fluid: SD-OCT CST ≥ 300 µM or Time-Domain OCT CST ≥ 250 µM IADL: Instrumental activities of daily living (complex activities related to the ability to live independently) 1Mettu PS, et al. Prog Retin Eye Res. 2021

• 2Hochberg C, et al. Invest Ophthalmol Vis Sci. 2012 May 31.

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Every Letter Counts When Loss of Vision Potentially Leads to Increased Mortality Risk

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Hazard for All-cause Mortality[1 ] Higher in People with Vision Impairment

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89%
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43%
29%
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< 20/40 vs. ≥ 20/40 < 20/60 vs. ≥ 20/60 < 20/200 vs. ≥ 20/60

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Better Vision Worse Vision
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Decrease of 1 ETDRS letter per year increases mortality risk by 16%[2] associated exclusively with IADL levels

IADL – Instrumental activities of daily living; ETDRS – Early Treatment Diabetic Retinopathy Study chart

1Ehrlich JR et al. “Association between vision impairment and mortality: a systematic review and meta-analysis.” Lancet Glob Health. 2021.

• 2Christ SL, et al. “Longitudinal relationships among visual acuity, daily functional status, and mortality: the Salisbury Eye Evaluation Study.” JAMA Ophthalmol. 2014.

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Sozinibercept Has Demonstrated Improvement in Vision Gains and Reduction in Vision Loss

Opportunity in Wet AMD Market for an Overall Shift Towards Superior Visual Outcomes

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High QoL
Lucentis remains the standard of care for visual improvements
20/40
VEGF-C/D Inhibitor
in Combination with
Standard of Care
Low QoL
Tyrosine Kinase Inhibitors Gene Therapy
Current Treatments Emerging Treatments
SOZINIBERCEPT
Visual Acuity (OFF LABEL)
LUCENTIS AVASTIN EYLEA BEOVU VABYSMO EYLEA HD OTX-TKI CLS-ASX EYP-1901 RGX-314 ADVM-022 4D-150
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QoL – Quality of Life

8

Jackson, Timothy L., et al. “A randomized controlled trial of OPT-302, a VEGF-C/D inhibitor for neovascular age-related macular degeneration.” Ophthalmology. June 2023.

Sozinibercept, a Proprietary VEGF-C/D “Trap” Inhibitor, Has the Potential to Address the Limitations of Anti-VEGF-A Therapies

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SOZINIBERCEPT
Faricimab
(Vabysmo®) [1]
The Solution
with any VEGF-A inhibitor,
sozinibercept
blocks
VEGFR-3 signaling.
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The Problem Wet AMD is a multi-factorial disease . Treatment with VEGF-A inhibitors upregulates VEGF-C/D , driving angiogenesis and vascular permeability.

When used in combination with any VEGF-A inhibitor, sozinibercept completely blocks VEGFR-2 and VEGFR-3 signaling.

1 Faricimab also has inhibitory effect on Ang-2. a Bevacizumab is used ’off-label’ for the treatment of neovascular (wet) AMD

9

Published Evidence Supports Broader VEGF Pathway Inhibition with Sozinibercept

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Circulating VEGF-C Levels Significantly
VEGF-C Stimulates RetinalAngiogenesis^ Elevated in AMD Patients [⍭]
300
Control
AMD Additive Benefit of VEGF-A and
200 VEGF-C/D Inhibition in
Mouse Wet AMD Model
100
70%
600000
0 78%
VEGF-A VEGF-C VEGF-D
91%
VEGF-A and VEGF-C Induce 400000
Elevated VEGF-C in Aqueous HumorFollowing
Vascular Leakage/permeability [#]
Anti-VEGF-Atherapy in Wet AMD Patients
10
VEGF-A VEGF-C 8.9 200000

8
6.9 66%
6 5.4 0
Control Sozinibercept Aflibercept Aflibercept
4 Antibody + sozinibercept
2
0
Baseline 1 month 2months
Bevacizumab Bevacizumab
Plasma concentrations (pg/ml)
CNVArea
Aqueous Humor VEGF-C (pg/ml)
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Sozinibercept Is Designed to Integrate into Current Anti-VEGF-A Clinical Practice

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• Superior visual outcomes meaningfully improves patients’ lives Patients • Intended to be administered at same anti-VEGF-A visit • Retina Better vision outcomes is a high unmet medical need • Specialists Designed to be agnostic to anti-VEGF-A treatment type, including biosimilars Payors / • Better clinical outcomes represent better health economics Insurance • Visual benefits a key driver in reimbursement Companies

Concentrated prescriptions in U.S. enables potential self-commercialization opportunity with lean and targeted organization

11

Physicians Willing to Administer Second Injection to up to 41% of Their Patients for Additional BCVA Improvement

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BCVA BCVA BCVA BCVA
improvement improvement improvement improvement
over 5 of 4.1 - 5 of 3.0 - 4 under 3
Average Percentage
of Patients Treated
41% 32% 25% 24%
with Second Injection [1]
What percentage of your Wet AMD patients would you use a second injection (anti-VEGF C/D) immediately after an anti-VEGF-A
injection at various levels of BCVA improvement of the combination over SoC? (Among Total Respondents, Avg. % of Patients, n=125)
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Estimate 1% Share of Wet AMD TAM Equals ~$100M+ in Sales Per Annum

TAM – Total Addressable Market

1Source: InCrowd Awareness Trial and Usage (ATU) Report, June 2024

*Averages calculated using the midpoints of each % prescribing allocation group. Callouts indicate statistical significance between groups at 90% CI.

12

Long-term Value Opportunities for Sozinibercept Main Patent Family Extends through 2034, with Expansion Opportunities Beyond 2034*

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DEVELOPMENT PHASE
ANTICIPATED
PROGRAM
RESEARCH / MILESTONES
PHASE 1 PHASE 2 PHASE 3
PRECLINICAL
Wet Age-Related Macular Degeneration (Wet AMD)
Sozinibercept Topline data:
For use in combination with COAST (in early 2Q CY2025)
anti-VEGF-A therapies ShORe (in mid-CY2025)
Diabetic Macular Edema (DME)
Sozinibercept
For use in combination with Phase 3 ready
anti-VEGF-A therapies
Co-formulation (Sozinibercept + VEGF-A Inhibitor)
Sozinibercept
Co-formulation with VEGF-A Feasibility underway
Inhibitor
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13

*Potential for Patent Term Extensions & Data and Market Exclusivity (12 Years for Biologic)

Robust Phase 2b Trial in Wet AMD Demonstrated Superiority in Visual Outcome

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Treatment naïve patients
with neovascularAMD
Key Inclusion Criteria Key Exclusion Criteria
Screening • Active CNV/ minimally classic / occult > 50% lesion, classic •• Subfoveal fibrosis or >25% of totallesionHaemorrhage >50% total lesion
• BCVA ≥ 25 and ≤ 60 letters • Other clinically significant ocular disease
Randomised (n=366)
Allocation sham + Sozinibercept 0.5 mg + Sozinibercept 2 mg +
0.5 mg ranibizumab 0.5 mg ranibizumab 0.5 mg ranibizumab
ITT Population
IVT Q4W x 6 IVT Q4W x 6 IVT Q4W x 6
n=121 n=122 n=123
Completed Study Completed Study Completed Study
Follow-up
n=116 (95.9%) n=112 (91.8%) n=120 (97.6%)
Analysis Analysed Analysed Analysed
mITT Population n=119 n=122 n=121
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CNV – choroidal neovascularisation; IVT – intravitreal; Q4W – once very 4 weeks; ITT – Intent to Treat Population, all participants who were randomised into the study irrespective of whether study medication was administered or not; Safety 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

14

Phase 2b Primary and Secondary Endpoints

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Primary Endpoint

Mean change from baseline in BCVA at week 24

Key Secondary Endpoints

Proportion of patients gaining ≥15 letters from baseline at week 24

Change in central subfield thickness (CST) from baseline at week 24 Change in intra-retinal and sub-retinal fluid from baseline to week 24

Safety and tolerability

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Select Pre-specified Subgroups

Predominantly classic, minimally classic, & occult lesions (Stratification Factor)

Retinal Angiomatous Proliferation (RAP ) detected/not detected at baseline

Polypoidal Choroidal Vasculopathy (PCV) detected/not detected at baseline

15

Phase 2b Trial Demographics and Baseline Characteristics

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Sham + 0.5 mg sozinibercept + 2 mg sozinibercept +
Demographic/Baseline Disease Characteristic ranibizumab ranibizumab ranibizumab
n=121 n=122 n=123
Mean Age – years ± SD 76.1 ± 9.48 78.8 ± 8.16 77.8 ± 8.82
Male 48 (39.7%) 49 (40.2%) 45 (36.6%)
Sex – n (%)
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 - mm [2 ] ± SD 6.08 ± 3.21 6.48 ± 3.30 6.62 ± 3.39
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%)
Lesion Type
PCV detected [1 ] –n (%) 20 (16.5%) 24 (19.7%) 22 (17.9%)
RAP detected [2 ] – 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%
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Intent-to-Treat (ITT) population; SD – standard deviation; BCVA – Best Corrected Visual Acuity 1PCV - polypoidal choroidal vasculopathy, detected by SD-OCT, FA and fundus photography.

2RAP - retinal angiomatous proliferation, detected by SD-OCT, FA and fundus photography.

16

Sozinibercept 2 mg Combination Therapy Demonstrated Superiority in Visual Acuity over Ranibizumab Monotherapy

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Phase 2b Primary Endpoint Achieved
20
Total Patient Population
15
+14.2
Δ = +3.4
(p=0.0107)
+10.8
10
5
0
0 4 8 12 16 20 24
Weeks
Sham + 0.5 mg ranibizumab 0.5 mg sozinibercept + 0.5 mg ranibizumab 2 mg sozinibercept + 0.5 mg ranibizumab
(n=119) (n=122) (n=121)
Mean Change in BCVA (SEM) (Letters)
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17

To Maximize Probability of Success, Best Responding Phase 2b Patients Represents Primary Analysis Population in the Pivotal Phase 3 Trials

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Occult & Minimally Classic Lesions (RAP Absent)

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20
+16.1
15
Δ = +5.7
p = 0.0002
10 +10.3
5
0
0 4 8 12 16 20 24
Weeks
Sham + 0.5 mg ranibizumab 2 mg sozinibercept + 0.5 mg ranibizumab
(n=87) (n=88)
in BCVA (SEM)
(letters)
change
Mean
Mean Change in BCVA (SEM) (Letters)
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Phase 2b demonstrated superior efficacy of +5.7 letter gain over standard of care , based on a pre-specified analysis

This patient population (minimally classic & occult) represents ~75% of wet AMD patients

18

*Unadjusted p-value

Control Arm in Phase 2b Overperformed MARINA Trial at Week 24 in in Similar Lesion Type Patient Population

Mean Change in BCVA from Baseline at Week 24 – Sozinibercept Phase 2b vs. MARINA Trial Occult and Minimally Classic Lesions

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16.1
+5.7 Letter Gain Sozinibercept + ranibizumab
Over Standard of Care
Ranibizumab
10.3
6.5
Trial: OPT PHASE 2B OPT PHASE 2B MARINA
Treatment: Sozinibercept 2 mg SHAM Ran 0.5 q4wMARINA
+Ran 0.5 q4w +Ran 0.5 q4w
Number of Patients: 88 87 240
Baseline BCVA in Letters: 50.5 50.5 53.7
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MARINA was a Phase 3 registrational trial. Baseline BCVA values across trials vary. Number of patients randomised to treatment group (n, bottom table). Mean change in Best Corrected Visual Acuity (BCVA) from baseline shown in ETDRS letters (top of bars).

19

In a Disease Where Every Letter Counts, a Greater Proportion of Sozinibercept Patients Gained Substantial Vision and Fewer Experienced Vision Loss

Change from Baseline to Week 24 (ETDRS Letters, Individual Participants) Occult and Minimally Classic Lesions (RAP Absent)

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30 Letter Gain
Vision Loss
9.2%
2.3%
2 mg sozinibercept
+ ranibizumab
N=87
sham
+ ranibizumab
N=85
Vision Loss >30 Letter Gain
12.9% 2.4%
≥15 Loss 10-14 Loss 5-9 Loss 1-4 Loss +0-5 Gain +6-10 Gain +11-15 Gain +16-20 Gain +21-25 Gain +26-30 Gain + >30 Gain
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Legend (ETDRS Letter Change from Baseline to Week 24)

20

Greater Proportion of Sozinibercept Patients Achieved Minimum Driving-level of Vision (≥20/40)

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Percentage of Participants with 20/40 Vision or Greater at Week 24

Occult and Minimally Classic, RAP Absent 42% relative increase compared to ranibizumab control

Total Patient Population 18% relative increase compared to ranibizumab control

48.9%

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34.5%
sham+0.5 mg ran (n=87) 2 mg sozinibercept+0.5 mg ran (n=88)
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41.7% 35.3% sham+0.5 mg ran (n=116) 2 mg soziniberecpt+0.5 mg ran (n=120)

21

Sozinibercept Reduced the Proportion of Patients Experiencing Vision Loss by 82%

Percentage of Participants with any Vision Loss ≥1 ETDRS Letter at Week 24

Occult and Minimally Classic Lesions (RAP Absent) 82% relative decrease compared to ranibizumab control

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12.9%
2.3%
sham+0.5 mg ran (n = 85) 2 mg sozinibercept+0.5mg ran (n = 87)
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Decrease of 1 ETDRS letter per year increases mortality risk by 16%[2] associated exclusively with IADL levels

Modified Intent-to-Treat (mITT) population; as observed.

IADL – Instrumental activities of daily living; ETDRS – Early Treatment Diabetic Retinopathy Study chart

1Christ SL, et al. “Longitudinal relationships among visual acuity, daily functional status, and mortality: the Salisbury Eye Evaluation Study.” JAMA Ophthalmol. 2014.

22

Sozinibercept Reduced Retinal Thickness and Dried the Retina Better With Combination Therapy in Occult & Minimally Classic (RAP Absent) Patients

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Mean Change in CST % of Participants with SRF % of Participants with IR Cysts
Baseline to Week 24 at Week 24 at Week 24
40
-60 40
85 86
28.2
-100
20
20
-126.8 19.8
-133.5 18.4
-140 14.8
85 86
0 87 88
-180 0
% Participants
% Participants
Mean Change in CST (SEM) (µm)
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Sham + 0.5 mg ranibizumab

2 mg sozinibercept + 0.5 mg ranibizumab

23

mITT; as observed; top of bar – statistic, bottom of bar – n. CST: Central Subfield Thickness; SRF: Subretinal fluid; IR: Intra-retinal.

Sozinibercept Demonstrated Greater CNV and Lesion Regression With Combination Therapy in Occult & Minimally Classic (RAP Absent) Patients

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Mean Change in Total Lesion Area Mean Change in CNV Area
at Week 24 at Week 24
0 0
80 81 80 81
-2 -2
-3.5
-3.9
-4 -4
-4.4
-5.0
-6 -6
Sham + 0.5 mg ranibizumab 2 mg sozinibercept + 0.5 mg ranibizumab
(n=80) (n=81)
)
2
)
2
Mean Change in CNV Area (SEM) (mm
Mean Change in Total Lesion Area (SEM) (mm
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mITT; as observed; top of bar – statistic, bottom of bar – n. CNV: Choroidal Neovascular.

Sozinibercept Demonstrated Superior Vision Gains in a Pre-Specified Subgroup of Hard-To-Treat PCV Lesion Patients

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20 PCV Lesions
Polypoidal Choroidal Vasculopathy ( PCV ) is a
Δ +6.7
difficult-to-treat wet AMD subtype; it is often
p = 0.0253
described as the most prevalent form of
15 wet AMD worldwide
13.5
10 PCV is highly prevalent in Asian populations
(up to ~60%), while ~8-13% prevalence in
Caucasians
6.9
5
20 22 Phase 3 ShORe and COAST trials enrolled
0
patients with PCV [1]
Sham + 0.5 mg ranibizumab 2 mg sozinibercept + 0.5 mg ranibizumab
(n=20) (n=22)
Mean Change in BCVA(SEM) (Letters)
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*Unadjusted p-value

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1 Evaluated by color fundus photography (FP), fluorescein angiography (FA), and spectral domain optical coherence tomography (SD-OCT)

Pooled Safety for Completed Sozinibercept Trials Combination Therapy Well Tolerated and Comparable to Standard of Care Monotherapy

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Sozinibercept Sozinibercept Sham + anti-VEGF-A
Any dose 2 mg control
N Participants (%) N=399 N=263 N=170
(N=1,842 injections) (N=1,121 injections) (N=854 injections)
Ocular TEAEs - Study Eye – related to study product(s) 41 (10.2%) 22 (8.4%) 20 (11.8%)
Ocular TEAEs - Study Eye – Severe 4 (1.0%) 2 (0.8%) 2 (1.2%)
Intraocular inflammation – Study Eye 7 [1,2,3] (1.8%) 3 [1] (1.1%) 3 [1] (1.8%)
Participants with AEs leading to treatment discontinuation 4 [2,4-6] (1.0%) 1 [4] (0.4%) 2 [7,8] (1.2%)
Any APTC event 4 [4,5,9,10] (1.0%) 3 [5,9,10] (1.1%) 2 [11,12] (1.2%)
Deaths 2 [10,13] (0.5%) 2 [10,13] (0.8%) 2 [14,15] (1.2%)
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• Pooled safety analysis of 399 patients for completed sozinibercept trials

• Data Monitoring Committee (“DMC”) regularly reviews data from ongoing Phase 3 COAST and ShORe studies

• Safety data from our completed sozinibercept trials show sozinibercept combination therapy has a safety and tolerability profile comparable to standard of care anti-VEGF-A monotherapy.

• Masked data from patients that have completed the week 52 visit in the ongoing Phase 3 clinical trials show greater mean BCVA increases from baseline than results with standard of care anti-VEGF-A monotherapy from Opthea’s Phase 2b study**

1Transient anterior chamber cell (trace 1-4 cells); 2 SAE of endophthalmitis, with AE’s of hypopyon and anterior chamber cell (n=1; 0.5 mg); 3 SAE of vitritis (n=1; 0.5 mg); 4Non-fatal myocardial infarction; 5Cerebrovascular accident; 6Enteritis; 7Abdominal pain;

[8] Increased IOP;[9 ] Non-fatal angina pectoris;[10] Fatal congestive heart failure/myocardial infarction;[11] Non-fatal arterial embolism;[12] Embolic stroke;[13] Metatstaic ovarian cancer;[14 ] Pneumonia;[15] infective endocarditis. *Any dose (sozinibercept 0.3 mg, 0.5 mg, 1 mg or 2 mg)

**Masked data represent pooled data from both sozinibercept combination and standard of care monotherapy treatment arms. The Phase 3 clinical trial masked data are incomplete and subject to additional analysis once unmasked. There is no assurance that standard of care monotherapy in our Phase 3 clinical trials will yield similar results to our prior clinical trials or previously published clinical trials with anti-VEGF-A monotherapies. As a result, there can be no assurance that topline results for sozinibercept from the Phase 3 clinical trial, if completed, will be consistent with results from masked data available to date.

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Intraocular Inflammation Observed in Combination Therapy Across Completed Sozinibercept Trials Similar to Standard of Care

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

Sozinibercept Sozinibercept Sham + anti-VEGF-A
Any dose 2 mg control
N Participants (%)
N=399 N=263 N=170
(N=1,842 injections) (N=1,121 injections) (N=854 injections)
Intraocular Inflammation [1] 7 (1.8%) 3 (1.1%) 3 (1.8%)
OPT-302-1001 (Phase 1/2a wet AMD) 2 0 0
Uveitis with anterior chamber cell 1+ 1 0 0
Uveitis with anterior chamber cell 2+ 1 0 0
OPT-302-1002 (Phase 2b wet AMD) 3 1 2 [a]
Endophthalmitis with anterior chamber 1+ and hypopyon 1 0 0
Vitritis 1 0 0
Anterior chamber cell, trace 1 1 2 [a]
OPT-302-1003 (Phase 1b/2a DME) 2 [b] 2 [b] 1
Iritis with keratic precipitates and anterior chamber cell 2+ 1 1 0
Iritis with anterior chamber cell 2+ 0 0 1
Anterior chamber cell 4+, associated with cataract extraction/ intraocular
1 [b] 1 [b] 0
lens implant and hyphema
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Safety population

1AEs observations considered to be indicative of intraocular inflammation, defined prior to database lock aObserved during ophthalmic examination, but not reported as TEAEs bConsidered associated with lens extraction and not reported as TEAEs

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Phase 3 Clinical Program Is Informed by Phase 2b Results and Optimized for Success

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Hierarchical primary analysis first conducted in the high-responding occult and minimally classic population (RAP absent) , followed by total patient population

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Two robust pivotal trials studying sozinibercept in combination with Eylea[®] and Lucentis[®] in treatment naïve patients with wet AMD

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Phase 3 designed to support broad label for use in combination with any VEGF-A inhibitor for all wet AMD patients (treatment naïve and prior treated)

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Phase 3 Wet AMD Trials COAST and ShORe Are Well Advanced Topline Data Anticipated for COAST in Early 2Q CY 2025 and ShORe in Mid-CY2025

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• Multi-center, double-masked, randomized (1:1:1), sham control

• Design • Treatment naïve wet AMD patients

• •

• Sample Size COAST n=998; ShORe n=986 •

• Comparators 2 mg Eylea[®] q8w (COAST) & 0.5 mg Lucentis[®] q4w (ShORe) Regulatory • ~90% power, 5% type I error rate

• Quality

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Phase 3 Primary and Secondary Endpoints Primary Efficacy Endpoint at Week 52 to Support BLA Submission

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Primary Endpoint Mean change from baseline in BCVA at week 52 Key Secondary Endpoints (Baseline to Week 52) Proportion of participants gaining ≥15 letters Proportion of participants gaining ≥10 letters Change in choroidal neovascularization area Proportion of participants with absence of both sub-retinal fluid and intra-retinal cysts

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Phase 3 Trial Design Supports Potential Broad Label for Use With Any Anti-VEGF-A Therapy

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

Topline Data
Efficacy Phase Anticipated in
Loading Doses (12w) Maintenance Dosing (40w) Early 2Q CY2025
Aflibercept +
Aflibercept q8w + Sozinibercept q4w
Sozinibercept q4w
Aflibercept + Primary Efficacy Safety Follow-up
Wet AMD Aflibercept q8w + Sozinibercept q8w
Tx-Naïve Patients Sozinibercept q4w Endpoint Week 52 Week 100
N=998
Aflibercept +
Aflibercept q8w + Sham q4w
Sham q4w
Enrollment Complete
Topline Data
Efficacy Phase Anticipated in
Loading Dosing (12w) Maintenance Dosing (40w) Mid-CY2025
Ranibizumab +
Ranibizumab q4w + Sozinibercept q4w
Sozinibercept q4w
Ranibizumab + Primary Efficacy Safety Follow-up
Wet AMD Ranibizumab q4w + Sozinibercept q8w
Sozinibercept q4w Endpoint Week 52 Week 100
Tx-Naïve Patients
N=986
Ranibizumab +
Ranibizumab q4w + Sham q4w
Sham q4w
Enrollment Complete
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Standard of care administered according to approved dosing schedule: aflibercept (2 mg IVT q8w after 3 loading doses) and ranibizumab (0.5 mg IVT q4w after 3 loading doses). Sozinibercept dosed at 2 mg. Note that Sham administered at visits when sozinibercept is not administered. Maintenance dosing continued through end of the safety follow-up.

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Advancing Therapeutic Innovations to Transform Patient Outcomes with Superior Vision Gains

We are dedicated to advancing sozinibercept to improve patients’ visual outcomes

• Phase 3 program enrolled 1,984 patients across COAST and ShORe Clinical Milestones • Topline data anticipated for COAST in early 2Q CY2025 and ShORe in mid-CY2025 • DS PPQ campaign completed Sep-2024; update on DP PPQ in early CY2025 Manufacturing • Scale-up PPQ validation batches supportive of BLA filing and launch Regulatory • FDA Fast Track designation allows rolling submission of completed BLA modules Preparations • Commercial Strengthen medical expert engagement and develop market access strategy Readiness • Complete development of product launch plan

DS: Drug Substance; DP: Drug Product

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Recent Financings Anticipated to Provide Cash Runway Through Both Pivotal Topline Data Readouts

Financial Overview

Development Funding Agreement (DFA)

Ticker

OPT (ASX/NASDAQ)

• Total funding drawn under DFA: US$170M

Ordinary Shares: 1,231.1M Shares Outstanding[1] ADS equivalents: 153.9M

Cash/Cash Equivalents[2] US$207.3M

• Provides non-dilutive funding for development of sozinibercept

• If sozinibercept is approved, repayment is capped at 4x investment and split between fixed payments and variable payments at 7% of revenues

Offices

Melbourne, Australia Princeton, NJ

• No amounts owed if the clinical trials do not meet the primary endpoint or if regulatory approval is not received[3]

• 1As of June 30, 2024, pro-forma for the 2024 Retail Entitlement Offer which closed in July 2024.

• 2Includes $172.5M as of June 30, 2024 and $34.8M net proceeds from the 2024 Retail Entitlement Offer which closed in July 2024.

• 3In certain circumstances, upon or following the termination of the DFA, the Company may owe the DFA investors a multiple of amounts paid to the Company under the DFA. Please refer to the description of the DFA included in the Company’s Form 6-K filed with the SEC on August 15, 2022 and the DFA filed as Exhibit 4.14 to the Company’s Annual Report on Form 20-F filed with the SEC on September 29, 2022 for more information. Note: Additional funding will be required to reach commercialization of sozinibercept and to meet obligations under the Development Funding Agreement ("DFA"). As a result of obligations under the DFA and applicable law regarding liquidity, the Company expects to raise or obtain additional capital in one or more transactions, earlier than 3Q CY 2025 or anticipated topline data readout dates.

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Sozinibercept Will Not Compete Head-to-Head with Anti-VEGF-A Differentiated Combination Approach Targeting Better Visual Outcomes Drives Commercial Value

Addressing unmet medical need of improved efficacy in large wet AMD 1 a patient population in potential ~$15B market

First and only therapy to have demonstrated superior visual outcomes 2 over anti-VEGF-A therapy with a novel and highly differentiated MOA

Only asset in near or long-term pipeline with potential to disrupt 3 treatment paradigm on basis of efficacy in wet AMD

Concentrated prescriptions in U.S. enables potential self4 commercialization opportunity with lean and targeted organization

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MOA – Mechanism of Action