February 2022 H A L F - Y E A R F I N A N C I A L R E P O R T 3 1 D E C E M B E R 2 0 2 1 In accordance with Listing Rule 4.2A, we enclose the Half-Year Financial Report (reviewed) on the consolidated results of Opthea L

F - Y E A R F I N A N C I A L R E P O R T 3 1 D E C E M B E R 2 0 2 1

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 2021. The previous corresponding periods are the

financial year ended 30 June 2021 and the half-year ended 31 December 2020.

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 2021.

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

www.opthea.com ABN 32 006 340 567

O P T H E A L I M I T E D

N 3 2 0 0 6 3 4 0 5 6 7

REPORTING PERIOD: HALF-YEAR ENDED 31 DECEMBER 2021

PREVIOUS CORRESPONDING PERIOD: HALF-YEAR ENDED 31 DECEMBER 2020

This half-year report is to be read in conjunction with the Company s 2021 Annual Report.

Note: The financial figures provided are in United States dollars.

R E S U L T S F O R A N N O U N C E M E N T T O T H E

The consolidated results of Opthea Limited for the six months ended 31 December 2021 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

S H A R E H O L D E R D I S T R I B U T I O N S

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

S T A T U S O F R E V I E W O F A C C O U N T S

The financial report for the half-year ended 31 December 2021 has been reviewed. The auditor s review report is included at page 22 of the financial

2022 Half-Year Report

Focused on what matters most

5 AUDITOR S INDEPENDENCE DECLARATION

6 CONDENSED CONSOLIDATED STATEMENT OF PROFIT OR LOSS

AND OTHER COMPREHENSIVE INCOME FOR THE HALF-YEAR ENDED 31 DECEMBER 2021

7 CONDENSED CONSOLIDATED STATEMENT OF FINANCIAL POSITION AS AT

8 CONDENSED CONSOLIDATED STATEMENT OF CHANGES IN EQUITY FOR THE HALF-YEAR ENDED 31 DECEMBER 2021

9 CONDENSED CONSOLIDATED STATEMENT OF CASH FLOWS FOR THE HALF-YEAR ENDED 31 DECEMBER 2021

10 NOTES TO THE CONDENSED CONSOLIDATED FINANCIAL STATEMENTS FOR THE HALF-YEAR ENDED 31 DECEMBER 2021

20 FORWARD-LOOKING STATEMENTS

21 DIRECTORS DECLARATION

22 INDEPENDENT AUDITOR S REVIEW REPORT

IBC CORPORATE INFORMATION

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 2021. 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 & F I N A N C I A L R E V I E W

Financial performance

For the half-year ended

31 December 2021, the Company s net loss before tax attributable to members is $40,629,360 (31 December 2020: $28,277,254). The increased loss compared to the prior period is mainly due to the increase in research and

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

Set out below are other factors affecting financial performance:

on the Company s financial position are:

O P T H E A : C O R P O R A T E O V E R V I E W

Opthea Limited (ASX: OPT; NASDAQ: OPT) is a biopharmaceutical company developing a novel therapy, OPT-302, to address the unmet need in the treatment of highly

prevalent and progressive retinal diseases, including neovascular age-related macular degeneration (wet AMD).

Opthea s mission is to expeditiously

develop therapies to improve vision outcomes for patients, leading to better quality of life.

Opthea: Working to address the unmet need in wet AMD

Wet AMD is a progressive, chronic disease of the central retina and the leading cause of visual impairment in the elderly. Progressive vision loss

associated with wet AMD contributes to significant healthcare and economic costs globally and greatly impacts ability to perform routine daily activities such as driving and reading.

The hallmark of wet AMD is choroidal neovascularization, which occurs when abnormal blood vessels grow beneath the macula, a region of 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 retina distortion and fibrous scarring, and often rapid loss of vision.

A member of the vascular endothelial growth factor (VEGF) family of proteins, VEGF-A, plays an important role in regulating the growth of abnormal new blood

vessels and choroidal neovascularization in wet AMD, and inhibitors of VEGF-A are now standard of care treatments for the disease. The two leading commercially available VEGF-A inhibitors for the treatment of wet AMD are ranibizumab (Lucentis ) and aflibercept (Eylea ), with bevacizumab (Avastin ), a VEGF-A inhibitor used

off-label for the treatment of wet AMD, accounting for approximately 46% of intravitreal injections for wet AMD administered worldwide. Lucentis and Eylea generate combined revenues annually in excess of US$12 billion, reflecting the prevalence of retinal disease worldwide and the importance of preserving and improving visual acuity for quality of

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

Although VEGF-A inhibitor therapies improve outcomes for many people with wet AMD, at least 45% of patients

exhibit a suboptimal response to currently available therapies and still have further opportunity for visual acuity gain. As such, there remains a very large commercial opportunity for novel therapies that address the unmet medical need for wet AMD

OPT-302: First investigational medicine targeting VEGF-C/D for wet AMD

Opthea is pioneering the first investigational medicine that targets VEGF-C and VEGF-D. VEGF-C and VEGF-D are members of the VEGF family that stimulate blood

vessel growth and vascular leakage and are implicated in the progression of retinal diseases. VEGF-C and VEGF-D function independent of, but in parallel with, VEGF-A to drive these biological processes. In addition, treatment with VEGF-A inhibitors

upregulates VEGF-C and VEGF-D levels, which can compensate for VEGF-A inhibition, which may represent an important mechanism of clinical resistance to anti-VEGF-A therapy.

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 signaling pathways that contribute to the pathophysiology of retinal diseases can be achieved, which may improve visual acuity and retinal

swelling in patients. Furthermore, given the role that VEGF-C and VEGF-D may play in mediating resistance to VEGF-A inhibitors, OPT-302 combination therapy may result in both improved and more durable clinical responses.

The majority of agents currently in clinical development for wet AMD are seeking to reduce the frequency of patient treatments, rather than provide superior

vision gains for those affected by retinal diseases. OPT-302 is a differentiated product in this development landscape, with a key objective to improve vision outcomes in patients. Our approach means we are complementary to, and not competitive

with, the class of VEGF-A targeted therapies. By targeting a novel mechanism of action through VEGF-C and VEGF-D inhibition, OPT-302 is the most advanced product in clinical development with demonstrated potential to improve patient visual outcomes

and tap into an expanding market opportunity of > US$12 billion per annum.

Opthea s Phase 2b clinical data supports the hypothesis that combining

OPT-302 with a VEGF-A inhibitor results in more complete and effective inhibition of angiogenesis and vascular leakage in eyes with wet AMD compared with VEGF-A alone. Statistically superior vision gains in patients with treatment-na ve wet AMD

were achieved with the intravitreal combination of 2.0 mg OPT-302 and Lucentis (+14.22 letters, p=0.0107), compared with standard of care, Lucentis monotherapy (+10.84 letters), representing an additional and statistically superior +3.4 letter gain in the total patient population. Furthermore, an additional mean gain of +5.7 letters

(p=0.0002) was observed in patients with minimally classic and occult lesions, lesion types that are typically more difficult to treat with standard of care anti-VEGF-A therapies and which represented approximately 80% of patients enrolled in the

Phase 2b trial. The results of our Phase 2b clinical trial have informed the design and analysis strategy for our pivotal Phase 3 clinical development program which is now actively ongoing.

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

currently recruiting patients into two concurrent, global, multicenter, randomized, sham-controlled Phase 3 clinical trials referred to as ShORe: Study of OPT-302 in combination with Ranibizumab and COAST:

Combination OPT-302 with Aflibercept STudy . Each trial will enroll approximately 990 treatment na ve patients and will investigate the mean change in best corrected visual acuity from baseline to week 52 for

OPT-302 combination therapy administered on an every 4-week, and on an every 8-week, dosing cycle, compared to standard of care ranibizumab (Lucentis ) in the ShORe trial or aflibercept (Eylea ) in COAST. 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 enrollment into

our Phase 3 trials was initiated in March 2021, and since that time we have continued to activate clinical trial sites and recruit patients in multiple countries globally. Opthea is now actively recruiting patients for participation in the Phase 3

program from all major geographical regions around the world. Our first sites to open were in the US and within months we reported the initiation of patient recruitment in Canada (August 2021), Europe (October 2021) and Asia-Pacific (October 2021).

When fully activated, we expect over 200 clinical trial sites to participate in each of the ShORe and COAST studies respectively.

months, the Company will continue to work with a global Clinical Trial Organization (CRO) to accelerate clinical trial activations and engagements with trial sites and investigators, activities which have been challenged in part by the COVID-19

pandemic and administrative delays, to identify eligible patients for enrollment into the ShORe and COAST trials. We expect to complete patient recruitment in the Phase 3 Clinical trials by mid-2023, with topline data to be reported when all

patients complete the 52-week treatment period for the primary analysis. If the topline results at the completion of the primary efficacy phase are favorable, we intend to file for marketing approval for OPT-302 for the treatment of wet AMD in the

United States, European Union and other territories.

Over the past 6 months, as the Phase 3 clinical trials have progressed, Opthea has increasingly

focused on building the profile of the company globally, by expanding its operations and building a US-based team of senior executives and strengthening its Board with US-based directors. In January 2022, Ms. Judith Robertson stepped down as a

non-executive member of the Opthea Board of Directors to become the Company s first Chief Commercial Officer. As an accomplished commercial executive with an extensive track record for building, leading and launching several commercial