Opthea Ltd — AGM Information 2016

Nov 27, 2016

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Annual General Meeting

Corporate Presentation, November 28, 2016 Megan Baldwin PhD, CEO & Managing Director

Disclaimer

Investment in Opthea Limited (‘Opthea’) is subject to investment risk, including possible loss of income and capital invested. Neither Opthea nor any other member company of the Opthea Group guarantees any particular rate of return or performance, nor do they guarantee the repayment of capital.

This presentation is not an offer or invitation for subscription or purchase of or a recommendation of securities. It does not take into account the investment objectives, financial situation and particular needs of the investor. Before making any investment in Opthea, the investor or prospective investor should consider whether such an investment is appropriate to their particular investment needs, objectives and financial circumstances and consult an investment advisor if necessary.

This presentation may contain forward-looking statements regarding the potential of the Company’s projects and interests and the development and therapeutic potential of the company’s research and development. Any statement describing a goal, expectation, intention or belief of the company is a forward-looking statement and should be considered an at-risk statement. Such statements are subject to certain risks and uncertainties, particularly those inherent in the process of discovering, developing and commercialising drugs that are safe and effective for use as human therapeutics and the financing of such activities. There is no guarantee that the Company’s research and development projects and interests (where applicable) will receive regulatory approvals or prove to be commercially successful in the future. Actual results of further research could differ from those projected or detailed in this presentation. As a result, you are cautioned not to rely on forward-looking statements. Consideration should be given to these and other risks concerning research and development programs referred to in this presentation.

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Financial Position (Unaudited)

Key Financial Details	ASX: OPT
Ticker Symbol	ASX:OPT
Share Price(as at Nov 25 2016)	~A$0.72
Total Ordinary Shares on Issue	150,237,078
Options on Issue	49,675,922
Market Capitalisation (as at Nov 25 2016)	~A$108m (~USD80m)
Trading Range(last 12 months)	A$0.28 – 0.915
Cash Balance(at 30 June 2016)	~A$14.5m
Listed Investments	~A$0.3m
Top 10 Shareholders Own	69%

		Substantial Shareholders	% Holding
		Biotechnology Value Fund	18%
		(BVF)
		Baker Bros (NY, USA)	9%
		Packer & Co.	8.5%
		Share Price Performance (Nov ‘14 – Nov ‘16)
		Biotechnology Value Fund (BVF)*
		Baker Bros (NY, USA)
		Packer & Co.

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Corporate Achievements

• First year trading under Opthea Limited and ASX:OPT

• Continued execution of strategy to focus on ophthalmology

• Received A$2.6m R&D tax rebate on local & international R&D expenditure

• AusIndustry approval for Advance/Overseas Finding

• Projected R&D activities in both Australia and overseas eligible for the R&D Tax Incentive to June 30 2018

• Completed simplification of Group

• De-registration of subsidiaries

• Completed solvent members’ voluntary liquidation of Syngene Ltd

• Pro-rata allocation of remaining capital to Syngene shareholders

• Returned >A$170k to Opthea Limited

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Operational Achievements

• Met primary safety objective in Phase 1 wAMD trial

• Demonstrated safety and tolerability of OPT-302 as monotherapy and in combination with Lucentis®

• Reported changes in visual acuity (VA) and retinal thickness following the 3 month dosing period demonstrating clinical activity of OPT-302 in both treatment naïve patients and prior treated patients

• Completed recruitment in Phase 2A cohorts

• On-track to report primary analysis of the Phase 2A trial in 1Q’17

• Expanded clinical management team

• Completed 6 month GLP safety/toxicology studies to support Ph 2B trial

• Initiated US FDA & EU regulatory agency interactions to inform Ph 2B wAMD trial

• Continued to raise company profile in local and international investment and clinical ophthalmology communities

• Data presented at international conferences and Ophthalmology Innovation Summit (OIS/ASRS, OIS/AAO, EURetina)

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Milestones

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OPT-302 Wet AMD Program:
Milestones
 Initiated Phase 1b/2a clinical trial:
30 June 2015
Ph 1b Primary Safety Data Analysis:

April 16
Ph 1b Data Analysis (2 [o] Objectives):

July 16
Ph 2a Primary Data Analysis:
1Q17
Initiate Phase 2b clinical trial:
2017
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OPT-302 for Wet AMD

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VEGF-C/D VEGF-C/D
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• The VEGF family is recognised as the most important family of growth factors controlling vessel growth and leakage

Extra-Cellular Domains 1-3 hVEGFR-3

• OPT-302 blocks VEGF-C and VEGF-D

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

hIgG1 Fc

• Leading cause of blindness in over 55’s, increasing prevalence

Wet AMD

Normal Retina

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Our Goal: To Improve Vision

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Monitoring Patients & Endpoints in Wet AMD Trials

SD-OCT

Visual Acuity

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Change in Vision (# letters) from baseline

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Change in Retinal Thickness (CST) from baseline – Indicator of fluid

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Approved therapies target VEGF-A, not VEGF-C or VEGF-D

Our approach is novel and differentiated from existing therapies, yet targets a validated pathway in wet AMD disease progression

Anti-VEGF-A Anti-VEGF-A Anti-VEGF-A

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2015: >$7BN

60% Market Share (Off-label use)

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40% Market Share

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Large and Growing Market Opportunity

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An Unmet Medical Need for Wet AMD

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

50%

do not achieve significant vision gain

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2/3
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will continue to have fluid at the back of the eye

25%

will have further vision loss at 12 mos

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OPT-302 Phase 1/2A

ClinTrials.gov ID#: NCT02543229

Dose-escalation & dose-expansion of repeated IVT injections

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Phase 1: Dose-escalation Phase 2A: Dose-expansion
(Open-label) (Randomised)
OPT-302 (2.0 mg) OPT-302 (2.0 mg)
Monotherapy Monotherapy
IVT Q4W x 3 IVT Q4W x 3, ~n=8 pts
Cohort 4
OPT-302 (2.0 mg) OPT-302 (2.0 mg)
+ Lucentis® (0.5 mg) + Lucentis® (0.5 mg)
IVT Q4W x 3 IVT Q4W x 3, ~n=23 pts
Cohort 3
OPT-302 (1.0 mg)
+ Lucentis® (0.5 mg)
IVT Q4W x 3
Cohort 2
OPT-302 (0.3 mg)
+ Lucentis® (0.5 mg)
IVT Q4W x 3
Cohort 1 Access to rescue anti-VEGF-A Tx
28 Day DLT window Follow-up to week 12
Primary Analysis after all
subjects complete 12 weeks
Long term follow-up at Week 24
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• Comprises of 4 treatment cohorts of 5 subjects each

• Both treatment-naïve and prior-treated patients were recruited

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OPT-302 Safe & Well Tolerated in Phase 1 Study

• OPT-302 successfully met primary safety objective in Phase 1 dose escalation study

• No dose limiting toxicities (and MTD not reached) through week 12 in:

• OPT-302 monotherapy (2.0 mg), and

• Cohorts of OPT-302 (0.3, 1, 2 mg) in combination with Lucentis® (0.5 mg)

• No signs of infection (endophthalmitis)

• No clinically significant changes in:

• Intraocular pressure

• ECGs

• Blood pressure

• Blood chemistry or other vital signs

• No evidence of drug-related immunogenicity

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OPT-302 Phase 1 Secondary Endpoints

• Overall, 16/19 evaluable pts maintained or gained vision from baseline to week 12

• No patient lost more than 3 letters

• All of the patients that lost vision from baseline received combination OPT-302 + Lucentis® therapy

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Treatment-Naïve Patients: Visual Acuity

Mean Gain VA from Baseline

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18 16.5
16
14
12
9.5
10
8
6
4
2
0
OPT-302 + OPT-302 (2mg)
Lucentis® + Lucentis®
(n=4) (n=2)
from Baseline (# letters)
Mean gain in Visual Acuity
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Treatment-Naïve Patients: Retinal Thickness

Mean Central Subfield Thickness

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600
500
400
214 uM (42.7%)
300
200
100
0
Baseline Week 12
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OPT-302 + Lucentis®
(n=4)
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Prior-Treated Patients: Visual Acuity

• Majority of vision gain in Lucentis® treated patients occurs within 3 months

• Plateau “ceiling effect”of response with no other treatment options

• Difficult to treat patient population, very large market opportunity

• Mean number of Prior anti-VEGF-A therapies: 10.5 (Mean 3 – 55)

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MARINA Phase 3 in wet AMD. Rosenfeld et al., NEJM, 355;14, pp 1419-1431, 2006

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Prior-Treated Patients: Visual Acuity & Retinal Thickness

Mean Change VA from Baseline

Mean Central Subfield Thickness

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4.5 400
4 letters
4
390
3.5 42 uM (10.8%)
380
3
2.5 370
2
360
1.5
350
1
340
0.5
0 330
Week 12 Baseline Week 12
OPT-302 + Lucentis® OPT-302 + Lucentis®
(n=10) (n=10)
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Prior-Treated Patient: OPT-302 + Lucentis[®] (0.3 mg) (0.5 mg)

• Male aged 64

• Occult lesion

• Prior treatment: Eylea®/REGN-910-3 x6

Baseline

Week 4

Week 12

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VA: 77 letters CST: 365 µM

VA: 83 letters CST: 281 µM

VA: 79 letters CST: 298 µM

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Prior-Treated Patient: OPT-302 + Lucentis[®] (1.0 mg) (0.5 mg)

• Female aged 71

• Occult lesion

• Prior treatment: Avastin® x10

Baseline

Week 4

Week 12

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VA: 74 letters CST: 270 µM

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VA: 74 letters CST: 258 µM

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VA: 84 letters CST: 255 µM

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OPT-302 Program Highlights

• Broad development potential

• Targets validated pathway

• Targets incomplete response to existing therapies

• Large unmet medical need for wet AMD & mkt opportunity

• Phase 1 study: safe & well tolerated

• Evidence of clinical activity

• Consistency of responses across multiple endpoints

• Warrants investigation Ph2B

• Phase 2A fully enrolled – primary analysis 1Q’17

• Planning for Phase 2B in 2017

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Suite 0403, Level 4, 650 Chapel Street, South Yarra 3141 Victoria Australia T +61 (3) 9826 0399 E megan.baldwin@opthea.com

www.opthea.com