Opthea Ltd — Investor Presentation 2024

Apr 3, 2024

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Transforming Patient Outcomes with Superior Vision Gains

Virtual KOL Event | April 3, 2024 NASDAQ (OPT); ASX (OPT.AX)

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Disclaimer

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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”). This presentation is current as at April 3, 2024 (unless otherwise stated herein). 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 estimated market opportunity of the Company's product in development, the viability of future opportunities, future market supply and demand, the expected timing of completion of patient enrollment under the clinical trials and timing of top-line data, our strategy, future operations, future financial position, future revenues, projected costs, prospects, plans and objectives of management, 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. We may not actually achieve the plans, intentions or expectations disclosed in our forward-looking statements, and you should not place undue reliance on our 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 our current views with respect to future events, and we assume no obligation to update any forward-looking 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 September 28, 2023 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, 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 once unmasked, timing of completion of Phase 3 clinical trial patient enrollment and clinical research organization, contract manufacturers and labor costs, intellectual property protections, 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 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.

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Featured Speakers Opthea Management Joined by Clinical and Scientific Thought Leaders

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Fred Guerard PharmD, MS Chief Executive Officer

Arshad M. Khanani MD, MA, FASRS Chief Medical Advisor

Charles C. Wykoff MD, PhD Chief Investigator for COAST Clinical Advisory Board Member

Veeral S. Sheth MD, MBA, FASRS, FACS Principal Investigator for ShORe

• Graybug Vision , CEO

• Novartis , Worldwide Head Ophthalmology

• Alcon , Global Franchise Head Pharmaceuticals

• Led extension of Novartis ophthalmology piplines: Encore Vision, Lubricin[®] , Luxturna[®] , Xiirdra[®]

• Sierra Eye Associates , Managing Partner, Director of Clinical Research, Director of Fellowship

• University of Nevada, Reno School of Medicine , Clinical Professor

• Retina Consultants of Texas , Director of  University Retina and Macula Research Associates , Partner

• Retina Consultants of America ,  University of Illinois at Chicago , Clinical Chairman of Research Assistant Professor

• Blanton Eye Institute, Houston Methodist Hospital , Professor of Clinical Ophthalmology and Deputy Chair of Ophthalmology

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Sozinibercept Has the Potential to Be the First Product in More Than 15 Years to Improve Visual Outcomes

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Addressing High • Wet age-related macular degeneration (wet AMD) is the leading cause of vision loss in the elderly, impacting
~
Unmet Need 3.5 million patients in the US and Europe, despite wide use of anti-VEGF-A standard of care
• First-in-class VEGF-C/D TRAP intended for combination with standard of care anti-VEGF-A therapies
Proprietary
•
Technology Composition of Matter and Methods of Use Patents through 2034; opportunities to extend beyond 2034
Superior • Phase 2b demonstrated superiority in combination with SOC therapy, with well tolerated safety profile
Lead Asset • Sozinibercept has the potential to improve vision for millions of patients with wet AMD
Two Large Pivotal • COAST enrollment complete as of Feb 2024; ShORe estimated 2Q CY2024 (96% enrolled as of 3 April 2024)
Trials Ongoing • Topline data from both trials expected mid-CY 2025
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; not competing with any approved therapy
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MOA – Mechanism of Action; SOC – Standard of care *Potential for Patent Term Extensions & Data and Market Exclusivity (12 Years for Biologic)

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Opthea KOL Event Agenda

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Topic Speaker
Welcome Fred Guerard, PharmD, MS
Wet AMD Unmet Medical Needs and Sozinibercept Market Opportunity Arshad M. Khanani, MD, MA, FASRS
Sozinibercept Phase 2b Wet AMD Data Overview Charles C. Wykoff, MD, PhD
Sozinibercept COAST and ShORe Phase 3 Wet AMD Trial Design Veeral S. Sheth, MD, MBA, FASRS, FACS
Strategic Outlook Fred Guerard, PharmD, MS
Q&A Session All
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Wet AMD Unmet Medical Needs & Sozinibercept Market Opportunity Arshad M. Khanani, MD, MA, FASRS

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Current Wet AMD Treatment Landscape

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Last therapy to improve visual outcomes for wet AMD patients was launched over 15 years ago

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2006 2011 2019 2022 2023
off-label
2004
Targets all isoforms of Targets VEGF-A, Targets all isoforms of Targets VEGF-A, Targets VEGF-A,
VEGF-A VEGF-B, & PlGF VEGF-A & Ang-2 VEGF-B, & PlGF
Targets isoform-
specific
Legend:
VEGF-A165 inhibition FDA APPROVAL
Improved Efficacy
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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[1] of patients fail to achieve 20/40 vision

Most patients cannot resume routine daily activities, such as driving or reading

1 Mettu PS, et al. Prog Retin Eye Res. 2021

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*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

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Unmet Needs in the Treatment of Wet AMD

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Efficacy Durability Disease Progression
TENAYA/LUCERNE Pooled [1]
10
8
57.7
6
44.2
40.4
4
28.8
2 Faricimab 6 mg (N=665) 21.2
Aflibercept 2 mg (N=664)
0 0
0 8 16 24 32 40 48 56 64 72 80 88 96 104 112
Baseline 6 months 1 year 2 years 3 years Final
Time (weeks) examination
Follow-up
Faricimab trials in wet AMD – Year 1 [2] :
High treatment burden with frequent Patients still develop inflammation,
• 20% gained ≥15 letters anti-VEGF-A injections leads to fibrosis, atrophy, and ischemia
• 57% [†] with ≥20/40 (driving vision) sub-optimal vision gains in the real world [3] despite anti-VEGF-A therapy [4]
• 9% [†] with vision ≤20/200
Patients developing atrophy (%)
Adjusted mean BCVA change from baseline (ETDRS letters)
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*Proportion averaged over Weeks 40, 44, and 48;[†] proportion at Week 48. BCVA, best-corrected visual acuity; ETDRS, Early Treatment Diabetic Retinopathy Study; nAMD, neovascular age-related macular degeneration; PRN, pro re nata (as needed); VEGF, vascular endothelial growth factor. 1. Khanani AM, et al. Presented at Angiogenesis 2023; 2. Guymer R, et al, presented at the Angiogenesis, Exudation, and Degeneration 2022 Virtual Congress; 3. Summaries/composites from various clinical trials; 4. Sitnilska V, et al. Ophthalmologica. 2019;241:154–60

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Greater Durability and Improved Vision Are the Greatest Unmet Needs ASRS PAT SURVEY 2023

What are the greatest unmet needs in treating wet AMD and DME? n=1,012

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US 78.6%
Greater durability
Intl 74.3%
US 50.4%
Improved vision
Intl 55.2%
US 47.1%
Longer VEGF suppression
Intl 58.2%
US 29.5%
Stable anatomy
Intl 45.5%
US 1.1%
None of the above
Intl 0.0%
US 1.5%
Other
Intl 0.4%
0 10 20 30 40 50 60 70 80 90 100
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AMD, age-related macular degeneration; ASRS, American Society of Retinal Specialists; DME, diabetic macular edema; Intl, international; PAT, Preferences and Trends; US, United States 10 of America; VEGF, vascular endothelial growth factor; Hahn P, ed. ASRS 2023 Preferences and Trends Membership Survey. Chicago, IL. American Society of Retina Specialists; 2023

Visual Outcomes Are the #1 Factor in Patients’ Anti-VEGF-A Preference

Relative Importance of Treatment Attributes for Patients Receiving Anti-VEGF-A Monotherapy n=300

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75
63 18-39 years (n=4)
40-64 years (n=62)
60
65-79 years (n=132)
≥80 years (n=102)
43
45
39 39
30 26
23 24 23
19
17 16
14 14
15 12
9 9
5
3 2
0
0
Vision Cost to patient Drug label status Treatment frequency Cost to insurance
provider
Treatment Attribute
Relative Importance (%)
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Bhagat D, Kirby B, Bhatt H, Jager R, George M, Sheth V. Patient Preferences Associated with Anti-Vascular Endothelial Growth Factor Therapies for Neovascular Age-Related Macular Degeneration and Diabetic Macular Edema. Clin Ophthalmol. 2020 Oct 1;14:2975-2982. doi: 10.2147/OPTH.S273564. PMID: 33061283; PMCID: PMC7534869.

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11
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Emerging Treatments for Wet AMD: Better Vision Outcomes or Durability

Sozinibercept is the only late-stage drug in development targeting better vision outcomes

Better Vision Outcomes Sozinibercept (OPT-302)

Better Durability

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Tyrosine Kinase Inhibitors Gene Therapy
OTX-TKI RGX-314
CLS-AX ADVM-022
EYP-1901 4D-150
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Sozinibercept, a Proprietary VEGF-C/D “Trap” Inhibitor, Has the Potential to Address the Limitations of Anti-VEGF-A Therapies

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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.

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Faricimab
(Vabysmo®) [1]
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The Solution
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When used in combination with any VEGF-A inhibitor, OPT-302 completely blocks VEGFR-2 and VEGFR-3 signaling.

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

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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 OPT-302 Aflibercept Aflibercept
4 Antibody + OPT302
2
0
Baseline 1 month 2 months
Bevacizumab Bevacizumab
Plasma concentrations (pg/ml)
CNVArea
Aqueous Humor VEGF-C (pg/ml)
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^Tammela et al., Nature Cell Biology, 2011; # Zhou et al. BMC Ophthalmology (2020) 20:15; # Cao et al,. Circ Res., 2004; ⍭ Lashkari et al, 2013 ARVO Annual Meeting, 4999-A0128; *Cabral et al,. 2018 Ophthalmology Retina (2018).

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Sozinibercept Has the Potential to Be the First Therapy in More Than 15 Years to Improve Visual Outcomes in Patients with Wet AMD

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Sozinibercept has demonstrated strong clinical evidence of superior patient visual outcomes
Sozinibercept
2006 2011 2019 2022 2023
Novel MOA
off-label targeting VEGF-C/D
2004
Targets all isoforms Targets VEGF-A, Targets all isoforms Targets VEGF-A, Targets VEGF-A,
of VEGF-A VEGF-B, & PlGF of VEGF-A & Ang-2 VEGF-B, & PlGF
Targets isoform-
specific
Legend:
VEGF-A165 inhibition
FDA APPROVAL
Improved Efficacy
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Jackson, Timothy L., et al. “A randomized controlled trial of OPT-302, a VEGF-C/D inhibitor for neovascular age-related macular degeneration.” Ophthalmology, vol. 130, no. 6, June 2023, pp. 588–597, https://doi.org/10.1016/j.ophtha.2023.02.001.; MOA – Mechanism of Action

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Sozinibercept Seamlessly Integrates 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 • Better clinical outcomes represent better health economics Payers • Visual benefits a key driver in reimbursement

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Sozinibercept Phase 2b Wet AMD Data Overview Charles C. Wykoff, MD, PhD

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Near-term Focus Is on Sozinibercept Phase 3 Execution Pivotal Program Design Informed by Phase 2b and Optimized for Success

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Ongoing Phase 3 Trials

Topline data from both trials anticipated in mid-CY 2025

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Anticipated CY 2Q 2024
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Completed Phase 1-2 Trials Enrollment Complete Phase 2b (n=366) COAST Treatment naïve wet AMD Phase 3 - wet AMD OPT-302: 6 x monthly dosing (treatment naïve) n=~990 Comparator: Ranibizumab (monthly) Comparator: Phase 1b/2a (n=153) Prior-treated DME Aflibercept (Eylea®) once every two months OPT-302 : 3 x monthly dosing after three monthly doses Comparator: Aflibercept (monthly)

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Enrollment Complete
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ShORe Phase 3 - wet AMD (treatment naïve) n=~990 Comparator:

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Aflibercept (Eylea®) Ranibizumab (Lucentis®)
once every two months once every month
after three monthly doses
Standard Dosing Extended Dosing Standard Dosing Extended Dosing
OPT-302 OPT-302 OPT-302 OPT-302
once every month once every two once every month once every two
months after three months after three
monthly doses monthly doses
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Phase 1/2a: (n=51) Treatment Naïve/Prior-treated wet AMD OPT-302 + Ranibizumab : 3 x monthly dosing

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Ranibizumab (Lucentis®); Aflibercept (Eylea®)

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Phase 2b Wet AMD Trial Overview

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Treatment naïve patients
with neovascularAMD
Key Inclusion Criteria Key Exclusion Criteria
Screening • / minimally classic / occultActive CNV > 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 + OPT-302 0.5 mg + OPT-302 2.0 mg +
ITT Population 0.5 mg ranibizumab 0.5 mg ranibizumab 0.5 mg ranibizumab
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

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19

Phase 2b Primary and Secondary Endpoints

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Primary Endpoint

Select Pre-specified Subgroups

Mean change from baseline in BCVA at week 24

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

Key Secondary Endpoints

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

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

Change in central subfield thickness (CST) from baseline at week 24

Change in intra-retinal and sub-retinal fluid from baseline to week 24

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

Safety and tolerability

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Phase 2b Trial Demographics and Baseline Characteristics

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Sham + 0.5 mg OPT-302 + 2.0 mg OPT-302 +
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%)
Lesion Type Occult - n (%) 53 (43.8%) 56 (45.9%) 54 (43.9%)
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.[1] PCV - polypoidal choroidal vasculopathy, detected by SD-OCT, FA and fundus photography. 2RAP - retinal angiomatous proliferation, detected by SD-OCT, FA and fundus photography.

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21

Sozinibercept 2.0 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
+10.8 (p=0.0107)
10
5
0
0 4 8 12 16 20 24
Weeks
Sham + 0.5 mg ranibizumab 0.5 mg OPT-302 + 0.5 mg ranibizumab 2.0 mg OPT-302 + 0.5 mg ranibizumab
(n=119) (n=122) (n=121)
Mean Change in BCVA (SEM) (Letters)
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Jackson, Timothy L., et al. “A randomized controlled trial of OPT-302, a VEGF-C/D inhibitor for neovascular age-related macular degeneration.” Ophthalmology, vol. 130, no. 6, June 2023, pp. 588–597, https://doi.org/10.1016/j.ophtha.2023.02.001.

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Wet AMD Lesion Types Differ in Vessel Location, Leakiness, and Responsiveness to VEGF-A Inhibitors

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OCCULT MINIMALLY CLASSIC PREDOMINANTLY CLASSIC
LEAST RESPONSIVE MODERATELY RESPONSIVE HIGHLY RESPONSIVE
to VEGF-A inhibition to VEGF-A inhibition to VEGF-A inhibition
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~75% of Wet AMD Patients Have Occult or Minimally Classic Lesions

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

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 2.0 mg OPT-302 + 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-determined analysis

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

*Unadjusted p-value

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24

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 – OPT-302 Phase 2b vs. MARINA Trial Occult and Minimally Classic Lesions

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16.1
+5.7 Letter Gain OPT-302 + Ranibizumab
Over Standard of Care
Ranibizumab
10.3
6.5
Trial: OPT PHASE 2B OPT PHASE 2B MARINA
Treatment: OPT-302 2.0 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).

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25

Reduced Retinal Thickness and Better Retinal Drying 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
-100 28.2
20
-126.8 19.8 20
-133.5 18.4
-140 14.8
85 86
0 87 88
-180 0
Sham + 0.5 mg ranibizumab 2.0 mg OPT-302 + 0.5 mg ranibizumab
mITT; as observed; top of bar – statistic, bottom of bar – n. 26
CST: Central Subfield Thickness; SRF: Subretinal fluid; IR: Intra-retinal.
% Participants
% Participants
Mean Change in CST (SEM) (µm)
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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 2.0 mg OPT-302 + 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.

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27

Sozinibercept Further Demonstrated Superior Vision Gains in a Pre-Specified Subgroup of 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 2.0 mg OPT-302 + 0.5 mg ranibizumab
(n=20) (n=22)
Mean Change in BCVA(SEM) (Letters)
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*Unadjusted p-value 1 Evaluated by color FP, FA and SD-OCT

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28

Phase 2b Safety Combination Therapy Well Tolerated and Comparable to Standard of Care

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N Participants (%) Sham + 0.5 mg OPT-302 + 2.0 mg OPT-302 +
ranibizumab ranibizumab ranibizumab
N=121 N=120 N=124
Treatment emergent AEs (TEAEs) 84 (69.4%) 87 (72.5%) 93 (75.0%)
Ocular AEs - Study Eye – relatedto study product(s) [1] 17 (14.0%) 17 (14.2%) 19 (15.3%)
Ocular AEs - Study Eye – Severe [2] 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%) 2 [3] (1.7%) 0 (0.0%)
Intraocular inflammation [4] – Study Eye 2 [5,6] (1.7%) 2 [3] (1.7%) 1 [5] (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 1 [7] (0.8%) 0 (0.0%) 0 (0.0%)
Any APTC event 0 (0.0%) 1 [8] (0.8%) 0 (0.0%)
Deaths 2 [9] (1.7%) 0 (0.0%) 0 (0.0%)
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Safety population analysed according to medication received

1 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 inflammation;[5 ] Transient anterior chamber cell (trace 1-4 cells);[6 ] Not reported as a TEAE;[7] Squamous cell carcinoma of the lung diagnosed shortly after Baseline visit;[8 ] Non-fatal myocardial infarction;[9 ] Pneumonia (n=1), infective endocarditis (n=1)

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29

Pooled Safety for Completed OPT-302 Trials Combination Therapy Well Tolerated and Comparable to Standard of Care Monotherapy

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OPT-302 OPT-302 Sham + anti-VEGF-A
Any dose 2.0 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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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;[5] Cerebrovascular accident;[6] Enteritis;[7] Abdominal pain;[8] Increased IOP;[9 ] Non-fatal angina pectoris;[10] Fatal congestive heart failure/myocardial infarction;[11] Nonfatal arterial embolism;[12] Embolic stroke;[13] Metatstaic ovarian cancer;[14 ] Pneumonia;[15] infective endocarditis. * Any dose (OPT-302 0.3 mg, 1 mg or 2 mg)

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30

Very Low Intraocular Inflammation Observed in Combination Therapy Study Eye Across Completed OPT-302 Trials

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OPT-302 OPT-302 Sham + anti-VEGF-A
Any dose 2.0 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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31

Sozinibercept Is the Only Drug in Development Having Demonstrated Superiority in Combination with Anti-VEGF-A Therapy for Wet AMD

1 Superior vision gains observed for combination therapy over Lucentis[®] alone 2 Consistent anatomical improvements further validate novel MOA 3 Safety profile similar to standard of care observed in over 1,800 injections

MOA – Mechanism of Action; SOC – Standard of care

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32

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Sozinibercept COAST and ShORe Phase 3 Wet AMD Trial Design Veeral S. Sheth, MD, MBA, FASRS, FACS

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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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34

Phase 3 Wet AMD Trials COAST and ShORe Are Well Advanced Complete Enrollment Anticipated in Q2 CY2024 | Topline Data Mid-CY2025

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

• Design • Treatment naïve wet AMD patients • ~990 per trial

• Sample Size • ~330 patients per arm: 2 mg sozinibercept q4w & q8w, or sham control •

• 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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35

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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36

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

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Efficacy Phase
Loading Doses (12w) Maintenance Dosing (40w)
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=~990
Aflibercept +
Aflibercept q8w + Sham q4w
Sham q4w
Enrollment Complete
Efficacy Phase
Loading Dosing (12w) Maintenance Dosing (40w)
Ranibizumab +
Ranibizumab q4w + Sozinibercept q4w
Sozinibercept q4w
Ranibizumab + Primary Efficacy Safety Follow-up
Wet AMD Ranibizumab q4w + Sozinibercept q8w
Tx-Naïve Patients Sozinibercept q4w Endpoint Week 52 Week 100
N=~990
Ranibizumab +
Ranibizumab q4w + Sham q4w
Sham q4w
Anticipated 2Q CY24
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Standard of care administered according to approved dosing schedule: aflibercept (2.0 mg IVT q8w after 3 loading doses) and ranibizumab (0.5 mg IVT q4w after 3 loading doses). Sozinibercept dosed at 2.0 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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37

Sozinibercept Has the Potential to Transform Wet AMD Clinical Practice

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1

Design supports potential broad label for combination with any anti-VEGF-A therapy and provides data on sozinibercept durability

2

Well powered, robust pivotal trials optimized for success with primary analysis on high responding patient population

3

Only late-stage therapy targeting superior visual outcomes with topline data Mid-CY2025

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38

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Strategic Outlook

Fred Guerard, PharmD

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Advancing Bold Therapeutic Innovations to Transform Patient Outcomes with Superior Vision Gains

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

• Complete enrollment in 2[nd] Phase 3 trial (ShORe) in Q2 CY2024 Clinical Milestones • Mid-CY2025 topline data from both pivotal Phase 3 studies Manufacturing • Production of validation batches supportive of BLA filing and launch Scale-up 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

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40

Sozinibercept Is Not Competing with Any Approved Drug Differentiated Combination Approach Targeting Better Visual Outcomes Drives Commercial Value

1

Addressing unmet medical need of improved efficacy in large wet AMD patient population in a potential ~$14B market

2

First and only therapy to have demonstrated superior visual outcomes 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

4

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

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41

MOA – Mechanism of Action

Sozinibercept Builds on Wet AMD Market as a Potential Combination Therapy with Any VEGF-A Inhibitor

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Branded VEGF-A Inhibitors Sozinibercept
~$14B
Branded
Biosimilars
VEGF-A
~$9B / Off-label
Inhibitors
Global wAMD Revenues of
Anti-VEGF-A Inhibitors Potential Addressable
wAMD Market
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Biosimilar / Off-label
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Branded VEGF-A Inhibitors
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~$5B
~35% of patients
receive off-label AVASTIN [®]
potential market size assuming branded pricing
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42

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)
Complete enrollment of
Sozinibercept
For use in combination with pivotal trials : Q2 CY 2024
anti-VEGF-A therapies Topline data: mid-CY 2025
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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43

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

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Question & Answer Session

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Featured Speakers Opthea Management Joined by Clinical and Scientific Thought Leaders

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Fred Guerard PharmD, MS Chief Executive Officer

Arshad M. Khanani MD, MA, FASRS Chief Medical Advisor

Charles C. Wykoff MD, PhD Chief Investigator for COAST Clinical Advisory Board Member

Veeral S. Sheth MD, MBA, FASRS, FACS Principal Investigator for ShORe

• Graybug Vision , CEO

• Novartis , Worldwide Head Ophthalmology

• Alcon , Global Franchise Head Pharmaceuticals

• Led extension of Novartis ophthalmology piplines: Encore Vision, Lubricin[®] , Luxturna[®] , Xiirdra[®]

• Sierra Eye Associates , Managing Partner, Director of Clinical Research, Director of Fellowship

• University of Nevada, Reno School of Medicine , Clinical Professor

• Retina Consultants of Texas , Director of  University Retina and Macula Research Associates , Partner

• Retina Consultants of America ,  University of Illinois at Chicago , Clinical Chairman of Research Assistant Professor

• Blanton Eye Institute, Houston Methodist Hospital , Professor of Clinical Ophthalmology and Deputy Chair of Ophthalmology

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45

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Thank you!

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For IR and BD contacts: info@opthea.com OPTHEA.COM | @OptheaLimited FOLLOW US ON: X and LinkedIn NASDAQ (OPT) | ASX (OPT.AX)

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