Opthea Ltd — Investor Presentation 2016

Mar 6, 2016

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Corporate Update

Extraordinary General Meeting, March 7 2016

Opthea Limited (ASX:OPT, OTCQX:CKDXY)

Megan Baldwin PhD, CEO & Managing Director megan.baldwin@opthea.com

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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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Opthea Limited

• Clinical stage biotechnology company

• Developing a novel therapy for wet AMD

• Wet AMD is the leading cause of blindness in the Western world in older adults

• Technology is based on targeting signals that control blood vessel growth and leakage

• Lead compound OPT-302 blocks VEGF-C and VEGF-D

• Ongoing Phase 1/2A clinical trial being conducted at US sites in wet AMD patients

• Potential to expand development program in a range of eye diseases

• Investigating OPT-302 as monotherapy and in combination with existing treatments

OPT-302 Wet AMD Program: Milestones

IND Approval for OPT-302 June 2015 

Initiated Phase 1/2A clinical trial: 30 June 2015 

Ph 1 Primary Safety Data Analysis:

• 1Q16 (20 patients)

Ph 2A Primary Data Analysis:

2H16 (~30 patients)

• Combination therapy more completely shuts down pathways involved in disease progression

• Near-term clinical milestones

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Financial Position (Unaudited)

Key Financial Details	ASX: OPT
Ticker Symbol	ASX:OPT
Share Price_(as at Mar 5 2016)_	~A$0.375
Total Ordinary Shares on Issue	150,190,303
Options on Issue	49,722,697
Market Capitalisation (as at Mar 4 2016)	~A$56.3m
Trading Range_(last 12 months)_	A$0.14 – 0.55
Cash Balance_(at 31 Dec 2015)_	~A$17.8m
Listed Investments	~A$0.9m
Top 10 Shareholders Own	69%

Substantial Shareholders	% Holding
Biotechnology Value Fund (BVF)*	18%
Baker Bros (NY, USA)	9%
Packer & Co.	8.5%

Share Price Performance (Feb ‘15 – Feb ‘16) Biotechnology Value Fund (BVF)* Baker Bros (NY, USA) Packer & Co.

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* Increased substantial holding 13% to 17.7% on June 25 2015

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– Corporate Achievements last 12 months

Corporate

• Board renewal

• Company name change

• Continued execution of strategy to focus on ophthalmology

• Prudent financial management post A$17.4m capital raising Nov ‘14

• ~A$3m R&D tax rebate (2014-15) on local & international R&D expenditure

• Regained VEGFR-3 intellectual property licensed to Eli Lilly

• Simplification of the Group by initiation of deregistration of subsidiaries

• Including solvent members’ voluntary liquidation of Syngene Ltd

• Pro-rata allocation of remaining capital to Syngene shareholders

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- Corporate Re Structure

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Circadian Technologies Ltd
ASX:CIR, OTCQX:CKDXY
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Vegenics
Pty Ltd
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PolyChip Pharma
Pty Ltd
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Precision
Diagnostics
Pty Ltd
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Ceres Oncology
Pty Ltd
(VGX-100 for
Cancer)
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Syngene Ltd
(Dimitech platform)
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Simplification of Corporate Structure*

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Opthea Ltd
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Non-Core
Assets
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Vegenics
Pty Ltd
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* Anticipated corporate structure following simplification which may be subject to changes.

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Program Achievements

Opthea

• Completed IND-enabling GLP safety/toxicology studies to support Ph 1/2A trial

• Completed preclinical pharmacokinetic studies to support Ph 1/2A

• Produced clinical grade OPT-302 to US FDA specifications required for Ph 1/2A

• US FDA approval of IND

• Initiation of Phase 1/2A clinical trial for OPT-302 in wet AMD patients

• Continued patient recruitment, 14 trial sites open

• Grown local & international profile

• Presented OPT-302 data at international conferences (ARVO, ASCRS and World Congress on Angiogenesis) and Ophthalmology Innovation Summit (OIS/AAO)

• Established world recognised Clinical Advisory Board

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Program Update - OPT 302 for Wet AMD

- Lead Program: OPT 302 for Wet AMD

• Lead molecule:

• OPT-302 (soluble VEGFR-3, VEGF-C/-D ‘Trap’)

• Mechanism:

• Blocks VEGF-C and VEGF-D:

  • Inhibits blood vessel growth

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 Inhibits vessel leak

• Strategy:

• To investigate activity as a monotherapy

• To develop OPT-302 for use in combination with existing VEGF-A inhibitors for the treatment of wet AMD

• Achieve complete blockade of the VEGF pathway

• Blocks a mechanism of ‘escape’ from existing therapies

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The disease process of ‘wet’ (neovascular) AMD

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Normal Retina
Choroid
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‘Wet’ AMD

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Figure: The Angiogenesis Foundation

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Large and growing market opportunity

• Wet AMD is the leading cause of blindness in the western world

• Increasing prevalence due to ageing population

• Prevalence expected to double by 2020

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1/7 ~1.8m
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• Approved therapies for wet AMD target VEGF-A, but not VEGF-C or VEGF-D

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

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*: Market Opportunity

$10BN Worldwide

2015: >$7BN

60% Market Share

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*Cowen Analyst Report: Ophthotech July 7 2015

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- An unmet medical n a A eed despite vailability of VEGF inhibitors

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

50%

do not achieve significant vision gain

2/3

will continue to have fluid at the back of the eye

25%

will have further vision loss at 12 mos

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- The opportunity for OPT 302:

- - An unmet medical need remains despite anti VEGF A therapy

• To increase the number of patients who experience a significant gain in vision

• To increase the magnitude of the vision gain

• To prolong response to therapy and prevent visual decline

• Potential to reduce dosing frequency

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30-50% of patients
achieve 15 letter
10
After 2-4 years of treatment,
5
vision gains can be lost and
continue to decline
Visual Acuity from
Baseline
0
(Letters)
68% of patients still exhibit
signs of active disease,
98% exhibit signs of
-5 macular atrophy
0 1 2 3 4 5 6 7
Years
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- Significant additive activity of OPT 302 & Eylea® in mouse AMD

Combined inhibition of VEGF-A (Eylea®), VEGF-C and VEGF-D (OPT-302) is more effective than inhibition of VEGF-A alone

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Control OPT-302
EYLEA ™ OPT-302 + EYLEA [®]
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70%
78%
91%

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• Pairwise comparison: OPT-302 vs Eylea + OPT-302 (p<0.02) Eylea vs Eylea + OPT-302 (p<0.05)

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- - - OPT 302 Phase 1/2A: Protocol: OPT 302 1001

• • Dose escalation & dose expansion of repeated IVT injections

Phase 2A: Dose-expansion (Randomised)

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Phase 1: Dose-escalation
(Open-label) (Randomised)
OPT-302 (2.0 mg) OPT-302 (2.0 mg)
Monotherapy Monotherapy
IVT Q4W x 3 IVT Q4W x 3, ~n=15 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=15 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
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Primary Analysis after all
subjects complete 12 weeks
Long term follow-up at Week 24
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*Access to rescue anti-VEGF-A Tx

• Comprises of 4 treatment cohorts of 5 subjects each.

• Should a dose limiting toxicity (DLT) occur, 3 additional subjects will be enrolled in that cohort.

• OPT-302 and ranibizumab given as separate IVT injections (each 0.05 mL) once every 4 weeks at day 1, 29 and 57.

• When used in combination, the ranibizumab IVT injection will be given 30 mins prior to sequential IVT OPT-302.

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Phase 1/2A Trial Endpoints

Primary Endpoint of Phase 1/2A trial:

• Safety

Secondary Endpoints:

• Preliminary measures of clinical activity

• Vision (Eye-Chart)

• Size of lesion

• Fluid

• Need for ‘rescue therapy’ in monotherapy cohort

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Anatomical Changes by Imaging (OCT,FA)
(Retinal fluid, thickness, area)
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• Need for a-VEGF-A therapy in long-term follow-up

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Visual Acuity Eye Chart

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- In combination with a VEGF A inhibitor, - OPT 302 achieves more effective VEGF suppression

• OPT-302 is a novel ‘trap’ that blocks the alternative VEGF-C/VEGF-D pathway

• Used in combination, OPT-302 can achieve more effective VEGF suppression and target a key mechanism of sub-responsiveness to existing therapies

• Combination OPT-302 + a-VEGF-A therapy may:

• improve visual acuity outcomes

• reduce retreatment rates

• lead to larger treatment free intervals for patients

• Potential for:

  • Improved patient responses

  • Reduced treatment burden

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Megan Baldwin , PhD CEO & Managing Director Opthea Limited (ASX:OPT, OTCQX:CKDXY)

Megan.baldwin@opthea.com +61 (0) 447 788 674

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