February 2021 HALF-YEAR FINANCIAL REPORT 31 DECEMBER 2020 In accordance with Listing Rule 4.2A, we enclose the Half-Year Financial Report (reviewed) on the consolidated results of Opthea Limited ( Opthea or Group ) for t

HALF-YEAR FINANCIAL REPORT 31 DECEMBER 2020

In accordance with Listing Rule 4.2A, we enclose the Half-Year

Financial Report (reviewed) on the consolidated results of Opthea Limited ( Opthea or Group ) for the half-year ended 31 December 2020. The previous corresponding periods are the financial year ended 30 June 2020 and

the half-year ended 31 December 2019.

Information in relation to the operational performance, financial performance, cash flows and financial

position is included in the attached Appendix 4D Half-Year Financial Report.

This Half-Year Financial Report should be read in conjunction with the

Company s Annual Report for the year ended 30 June 2020.

Level 4, 650 Chapel Street, South Yarra, Victoria 3141 Australia T +61 (3) 9826 0399

www.opthea.com ABN 32 006 340 567

HALF-YEAR FINANCIAL REPORT

REPORTING PERIOD: HALF-YEAR ENDED 31 DECEMBER 2020

PREVIOUS CORRESPONDING

PERIOD: HALF-YEAR ENDED 31 DECEMBER 2019

This half-year report is to be read in conjunction with the Company s 2020 Annual Report

Note: The financial figures provided are in Australian dollars.

RESULTS FOR ANNOUNCEMENT TO THE MARKET

The consolidated results of Opthea Limited for the six months ended 31 December 2020 are as follows:

Revenues and results from ordinary activities

An explanation of the figures reported above are contained in the Directors Report under the heading Financial

SHAREHOLDER DISTRIBUTIONS

No dividends have been paid or declared by the entity since the beginning of the current reporting period.

STATUS OF REVIEW OF ACCOUNTS

The financial report for the half-year ended 31 December 2020 has been reviewed. The auditor s review report is included at page 17 of

the financial report.

Opthea Limited and Controlled Entity ABN 32 006 340 567

Half Year Report for the half-year ended 31 December 2020 OUR TOMORROW STARTS TODAY

WITHIN SIGHT CONTENTS 1 Directors Report 4

Auditor s Independence Declaration 5 Condensed Consolidated Statement of Profit or Loss and Other Comprehensive Income for the Half-Year Ended 31 December 2020 6 Condensed Consolidated Statement of Financial Position as at 31 December

2020 7 Condensed Consolidated Statement of Changes in Equity for the Half-Year Ended 31 December 2020 8 Condensed Consolidated Statement of Cash Flows for the Half-Year Ended 31 December 2020 9 Notes to the Condensed Consolidated Financial

Statements for the Half-Year Ended 31 December 2020 16 Directors Declaration 17 Independent Auditor s Review Report TO IMPROVE THE VISION OF MILLIONS

D I R E C T O R S R E P O R T

The directors of Opthea Limited submit herewith the financial report of Opthea Limited and its subsidiaries (Opthea, the Company and the Group) for the half-year ended

31 December 2020. In order to comply with the provisions of the Corporations Act 2001, the directors report as follows:

The names of the Company s Directors in office during the half-year and until the date of this report are:

O P E R A T I N G A N D F I N A N C I A L R E V I E W

Financial performance

half-year ended 31 December 2020, the Company s net loss before tax attributable to members is $38,505,045 (31 December 2019: $11,465,210). The increased loss compared to the prior year is mainly due to the increase in research and

development (R&D) spending, which can be attributed to the manufacturing of OPT-302 and planning of the Phase 3 clinical trials of OPT-302 in wet AMD.

Set out below are other factors affecting financial performance:

Points to note on the

Company s financial position are:

Opthea: Company Overview

Opthea is committed to the development of new therapies for the treatment of serious eye diseases that affect the back-of-the-eye, or retina, and lead to vision loss.

Wet (neovascular) age-related macular degeneration (wet AMD) is a progressive, chronic disease of the central retina and in developed nations, is the leading cause of visual impairment in the elderly. Wet AMD is associated with blood

vessel dysfunction and proliferation in the macula, a region of the retina which is needed for sharp, central vision. New blood vessels break through layers of the retinal tissue, leaking fluid, lipids and blood, leading to fibrous scarring and loss

of vision. Vision loss associated with wet AMD can be rapid and is generally severe, impacting patient independence and contributing to significant healthcare and economic costs worldwide.

Although the underlying cause and biology of wet AMD is complex, inhibition of vascular endothelial growth factor-A, or VEGF-A, has been shown to play an important role in the growth and leakage of vessels associated with the disease, and inhibitors of VEGF-A are now standard of care treatments

for wet AMD. The VEGF-A inhibitors ranibizumab (Lucentis ) and aflibercept (Eylea ), approved for the treatment of wet AMD, together

generated revenues in excess of 11 billion USD in 2019. Such commercial success reflects the widespread use of the VEGF-A inhibitor class of therapies and the importance that physicians and patients alike attribute to the preservation and

improvement of visual acuity for quality of life.

However, despite many patients experiencing gains or stabilisation of vision, at least 45% of patients with wet

AMD exhibit a suboptimal response to therapies that selectively target VEGF-A. As such, there remains a very large commercial opportunity for novel therapies that address the unmet medical need for patients

who have further room for improvement in visual acuity despite regular administration of currently available therapies.

DIRECTORS REPORT (CONT.)

OPT-302: Opthea s Phase 3 ready candidate for the

treatment of Wet AMD

Approved therapies for wet AMD block VEGF-A, whereas

OPT-302 targets alternative members of the VEGF family of proteins, namely VEGF-C and VEGF-D, that also stimulate blood vessel

growth and vascular leakage and are implicated in the progression of retinal diseases.

Opthea is developing OPT-302 as a

complementary treatment to be used in conjunction with VEGF-A inhibitors for the treatment of wet AMD and other retinal diseases. By combining administration of OPT-302 with a VEGF-A inhibitor, broader

blockade of important signalling pathways that contribute to the pathophysiology of retinal diseases can be achieved, which may improve visual acuity and retinal swelling in patients. In addition, inhibition of

VEGF-A results in compensatory upregulation of VEGF-C and VEGF-D that may limit the efficacy of selective VEGF-A inhibitors. OPT-302 blocks this mechanism of resistance to existing therapies which may then result in improved and more durable clinical responses.

Opthea s lead product candidate OPT-302 is well-differentiated with a key objective to improve clinical efficacy and the

potential to also produce more sustained, durable clinical outcomes for patients. The majority of agents currently in clinical development are seeking to reduce the frequency of patient treatments, rather than provide superior vision gains for those

affected by retinal diseases.

With a scarcity of combination therapies in development that may offer improved outcomes for retinal disease patients, and with

positive Phase 2b data in wet AMD, OPT-302 is a promising drug candidate with large commercial potential as it advances into the final stage of clinical development, Phase 3 pivotal studies.

O P E R A T I O N A L U P D A T E

Despite the challenges posed by the events of 2020, for Opthea Limited the past 6 months has been one of scientific and financial validation.

In respect of our science, the company successfully completed End-of-Phase 2 meetings

with the U.S. Food and Drug Administration (FDA), and a Scientific Advice meeting with the European Medicines Agency (EMA). The regulatory engagement provided Opthea with guidance on our Phase 3 clinical program for

OPT-302 in wet AMD and a clear regulatory pathway to support filing for marketing approvals in the US and Europe. Following the agreement by the FDA and EMA on key aspects of the proposed Phase 3 clinical

trial designs, the design of two concurrent, global, multicentre, randomised, sham-controlled trials evaluating OPT-302 in combination with either ranibizumab (the ShORe trial) or aflibercept (the COAST

trial), were finalised.

ShORe and COAST will enrol treatment-na ve patients and assess the efficacy

and safety of 2.0 mg of OPT-302 in combination with ranibizumab or aflibercept, compared to ranibizumab or aflibercept monotherapy in each respective trial. In addition, to understand the durability of OPT-302 treatment effect with less frequent dosing, each trial will compare the clinical efficacy of OPT-302 administered in combination with the applicable VEGF-A inhibitor

on an every four-week and every eight-week dosing regimen. The ShORe and COAST Phase 3 trials build upon and maintain key features of our successful Phase 2b clinical trial of OPT-302 combination therapy for

the treatment of wet AMD, while evaluating the administration of OPT-302 combination therapy over a longer treatment period and in a greater number of patients.

Patient recruitment in the Phase 3 trials is on-track to initiate in the 1Q CY 2021 and topline data is expected in CY 2023. If

the topline results at the completion of the primary efficacy phase are favourable, we intend to file for marketing approval for OPT-302 for the treatment of wet AMD in the United States, European Union and

Further validating Opthea s scientific approach with OPT-302, we reported data in June 2020 from

the company s Phase 2a trial of OPT-302 in a second ophthalmic disease indication, diabetic macular edema (DME). DME is a complication of diabetic retinopathy, a condition caused by chronically elevated

glucose levels in diabetics that damages the retina. DME can cause blurred vision, severe vision loss and blindness.

In our Phase 1b/2a clinical trial of OPT-302 in combination with aflibercept in patients with treatment-refractory DME, we observed evidence of improved clinical outcomes following OPT-302 combination therapy.

This data builds on the company s successful Phase 1/2a and Phase 2b clinical trials in wet AMD and our conviction that OPT-302 has the potential to deliver therapeutic benefit in DME patients. Of

relevance to our Phase 3 COAST trial, our DME trial results informed the safety profile of OPT-302 in combination with aflibercept. Opthea now has extensive clinical dosing experience with OPT-302 in approximately 400 patients, across three international clinical studies in two disease indications and in combination with the two leading standard of care VEGF-A

inhibitors ranibizumab or aflibercept.

In the financial sphere, in October 2020 Opthea raised net proceeds of $164.9 million equity capital in a US initial

public offering (IPO) and NASDAQ listing supported by Australian, US and UK based institutional investors. Opthea is now dual listed on the ASX and NASDAQ where its American Depositary Shares (ADS) are listed at a ratio of 8 ordinary shares to one

ADS. The proceeds of the financing will primarily be used to progress OPT-302 into the Phase 3 clinical program and to develop a co formulation of OPT-302 with a

biosimilar anti-VEGF-A therapy. We believe that a co-formulated OPT-302 and VEGF-A

inhibitor product has the potential to be a market-leading treatment for wet AMD that offers the convenience of a single-injection to achieve broader inhibition of the VEGF signalling pathway, including

VEGF-A, VEGF-C and VEGF-D.

To facilitate the progression of Opthea s clinical development program, Opthea has entered into research and