Opthea Ltd — AGM Information 2011

Nov 23, 2011

ANNUAL GENERAL MEETING 24 NOVEMBER 2011 Robert Klupacs, CEO & Managing Director Circadian Technologies (ASX.CIR)

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DISCLAIMER

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Investment in Circadian Technologies Limited (‘Circadian’) is subject to investment risk, including possible loss of income and capital invested. Neither Circadian nor any other member company of the Circadian 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 Circadian, 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 also 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.

CIRCADIAN TECHNOLOGIES LIMITED2011 AGM PRESENTATION OUTLINE

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• Corporate Snapshot & Structure

• Review of achievements since June 2010

• Therapeutic Development

• Oncology

• Ophthamology

• Diagnostics Development

• Expected milestones/value adding events next 6-18 months

• –

• Circadian the investment opportunity

CORPORATE SNAPSHOT

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Developing human therapeutic and diagnostic products from our extensive intellectual property assets in respect of VEGF-C, VEGF-D and VEGFR-3 and key relationships with leading cancer and ocular research organisations.

Circadian Technologies Limited

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Cash Approx $19M at 22 November 2011
Staff
100% 100%
100%
Cancer
Polychip
Vegenics Pty Ltd Therapeutics
Limited
Limited
Oncology Ophthalmology Diagnostics Investments
VGX-100 VEGF-C
VGX-100 (PI Trials Dec ’11) ASX:ANP (Approx 11%)
Front of eye
EIA (Blood test)
VGX-200 (Research) ASX:OIL (Approx 7%)
IHC (Tissue biopsy)
VGX-100
VGX-300 (Research) Syngene Limited [1 ] (Approx 43%)
Back of eye VEGF-D
IMC-3C5 (Being EIA (Blood test) DiMiTech technology (50%
developed by ImClone / owned with Monash)
IHC (Tissue biopsy)
Eli Lilly). (PI Trial
complete Q3 ’12) Cancers of Unknown
Primary (molecular
Controlled &
analysis)
Managed
1./ Syngene is an Investment company in Australian Listed Biotech
Divestment
Companies and an incubator for biomedical developments
Royalty /
Sales Income
Revenue
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1./ Syngene is an Investment company in Australian Listed Biotech Companies and an incubator for biomedical developments

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REVIEW OF ACHIEVEMENTS SINCE JUNE 2010

OBJECTIVES WE SET FOR 2010/2011

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• Advance drug development pipeline toward human clinical trials

• Develop partnerships for the commercialisation of our intellectual property

• Further strengthen and add skill-sets to our management team

PROGRESS ACHIEVED IN EXECUTING BUSINESS STRATEGY

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Advancing our product pipeline - VGX 100: (human anti-VEGF-C antibody):

• Completed IND enabling studies

• IND Filed and cleared by FDA for studies in cancer patients

• Phase 1 trials to commence in USA December

• MD Anderson collaboration identified key role of VEGF-C in Avastin resistance

• Designated a product development candidate for “front-of-eye” disease

• Publication of data showing significant effects in ameliorating dry eye disease in animal models

PROGRESS ACHIEVED IN EXECUTING BUSINESS STRATEGY

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Advancing our product pipeline - IMC 035: (VEGFR-3 Antibody being developed by Eli Lilly):

• Phase 1 Clinical Trials commenced. Results expected Q3’12

• VGX 300: (recombinant VEGFR-3)

• CSIRO alliance has generated second generation molecules with significantly improved characteristics.

• Further confirmatory pre-clinical studies being undertaken as prelude to designation as product development candidate H1 2012.

PROGRESS ACHIEVED IN EXECUTING BUSINESS STRATEGY

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Partnerships

• Healthscope-CUP Test: Good progress. On track for launch in Q1 2012

• Cincinnati Childrens Hospital Medical Centre – VEGF-D Diagnostic for women with respiratory disease: Product launched

• Eli Lilly-IMC-3C5: Phase 1 trials commenced

• Ark Therapeutics: Arbitration settled. Phase 1 studies with VEGF-D gene therapy well underway

• Building the management and advisory team

• Establishment of International Clinical Advisory Group in ocular disease

• Appointment of Director, Clinical Trials – Dr Ian Leitch

FINANCIAL POSITION & SHAREHOLDER BASE

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Top 10 shareholders: 52.8%

Investor	% of issued
	shares
HSBC Custody Nominees	18.88
(Australia)Limited
Licentia Ltd	6.79
Ludwig Institute for Cancer	6.73
Research
HSBC Custody Nominees	4.57
(Australia)Limited GSCO ECA
Cogent Nominees PtyLimited	3.84
Capital Macquarie Pty Limited	2.97
Citicorp Nominees Pty Limited	2.61
Chemical Trustee Limited	2.50
National Nominees Limited	2.38
JFF Steven Pty Ltd	1.54
Total 10 shareholders own	52.8%
Total 20 shareholders own	60.1%

Financial Summary @ 22 November 2011 (unaudited)

Stock code:	CIR
Share price: Shares issued: Market cap: Cash holdings: Listed investments: (ASX: ANP, OIL)	50.0c(AUD) 46,396,928 ~ A$23.2mill ~ A$19.1mill A$3.5mill

Institutions/Funds: ~ 32%

Retail investors: ~ 40%

Professional investors: ~ 28%

KEY FINANCIALS (CONSOLIDATED)

	30 June 11 $000	22 Nov 2011 (unaudited) $000
Cash	22,104	19,100
Listed investments (market value)	1,432	3,548
Net assets	21,824
Revenue	1,850
Operating expenses (incl. R&D, investment related exp’s)	(12,893)
Loss before tax	(11,043)
Net cash outflows	(9,477)
NTA per share	$0.47
Cash & listed assets per share	$0.48	$0.49
Shareprice	$0.53	$0.50

FINANCIALS

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value generating activity and continued streamlining of business activities to reduce Administrative expenses

FINANCIALS

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Our goal is to have a ratio of R&D/IP Expense to Administrative/Other better than 80/20 on an annual basis

FINANCIALS – CASH FLOWS

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• Current Cash - $19.1m (Unaudited)

• Value of Listed Holdings - $3.5M (Unaudited)

• Conservative Cash Burn 2011/12 and 2012/13 - $9.0M p.a

• Well positioned to achieve key value adding milestones

• Does not take into consideration:

• Increased R&D Tax Credit

• Royalties on Sales of Diagnostics

• Potential non-dilutive grant income (applications under review)

• Further partnership income

• Income from divestment of investments

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THERAPEUTIC DEVELOPMENT Oncology & Eye Disease

COMBINATION THERAPY OF TARGETED AGENTS IS BECOMING THE NEW PARADIGM IN CANCER THERAPY

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IMPROVING ANTI-ANGIOGENESIS A MAJOR COMMERCIAL OPPORTUNITY

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• Avastin®: 2010 Sales $US7.2B

• Effective but not in all patients

• Not all patients respond to therapy (30-50% response rate)

• 25-50% of responders become “resistant” within 12 to 18 months

• Potential reasons:

  • Tumour growth due to factors other than VEGF-A; and/or

  • Other angiogenic factors being turned on when VEGF-A blocked

    • (i.e. VEGF-C, VEGF-D)

HAVE NOW SHOWN THAT VEGF-C MAY BE A PREDICTIVE BIOMARKER FOR AVASTIN RESISTANCE

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[ ]

VEGF-C levels begin to rise Significantly BEFORE tumours Stop responding to Avastin. Highlights major potential for improving therapy by combining VEGF-A and VEGF-C blockade

C.Lieu et al., "The Association of Alternate VEGF Ligands with Resistance to Anti-VEGF Therapy in Metastatic Colorectal Cancer (mCRC)“ , J.Clin.Oncol. 19 29:2011 (suppl; Abstract #3533).

VGX-100 REDUCES METASTASIS IN AN ORTHOTOPIC PROSTATE CANCER MODEL

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VGX-100 ONCOLOGY CLINICAL DEVELOPMENT

VGX-100 TARGET PRODUCT PROFILE IN ONCOLOGY

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• Indication:

• Co-administered with anti-angiogenic agent eg (Sutent[®] , Nexavar[®] , Avastin[® ] ) and standard of care

• Targeting glioblastoma and colorectal cancer as first indications

• To develop through collaborations at least one of breast, lung, renal and/or potentially ovarian cancer in combination with antiangiogenic agents most likely to be Avastin[® ]

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GLIOBLASTOMA - A MAJOR UNMET CLINICAL NEED

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• In the US in 2010[1]

• Estimated diagnosed: 22,020

• Estimated fatalities: 13,140

• The most aggressive malignant primary brain tumor in adults

• Nearly always fatal

• Possibility for fast track registration based on Phase 2b study.

• Phase 2b study aim to complete HI ’15.

• Fast track approval possible by H2 ’15.

• Very strong interest from Key Opinion leaders worldwide

1 Howlader N, Noone AM, Krapcho M, et al. SEER Cancer Statistics Review, 1975-2008 , National Cancer Institute. seer.cancer.gov/csr/1975_2008/ based on November 2010 SEER data submission, posted to the SEER web site, 2011.

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PHASE I AND II CLINICAL PROGRAM

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Phase I VGX-100 and VGX-100 + Avastin[® ] Arm A (mono), Arm B (combo) Phase II VGX-100 + Avastin[®] + selected standards of care Part A Metastatic Lung Breast Renal cell Gliocolorectal cancer cancer cancer blastoma cancer NonMetastatic Phase II Phase II squamous HER2 Lung, Breast, Part B non-small negative Renal and other cell Indications to be (with (with (with (with (with Avastin [® ] Avastin [®] , Avastin [®] Avastin [®] Avastin [®] ) Developed through + paclitaxel and and Collaborative studies FOLFOX) and carbo.) paclitaxel) interferon alpha)

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VGX-100 OCULAR DEVELOPMENT OPPORTUNITY LEVERAGING VGX-100 ONCOLOGY DEVELOPMENT

DEVELOPMENT OPPORTUNITY

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• Significant development opportunity for VGX-100 as a treatment for ‘front of the eye’ disease.

• Initial indications:

• Corneal Neovascularisation (CNV)

  - Estimated that up to 4-5% of patients at eye clinics have CNV

  - • Potential market >$1B p.a

  - Very limited competition

• High-Risk Corneal Allograft Rejection

  • 10000 grafts/yr in USA

  • Potential market >$300M p.a

  • Major unmet clinical need

  • Existing anti-rejection drugs limited effects

  • Very high likelihood of accelerated approval

• Local ocular administration via subconjunctival injection as a single-agent. 26

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26
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AND LYMPHATIC VESSELS AND OVER-EXPRESS VEGF-C and VEGFR-3

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Transplanted Corneas: 3 wks Post-Transplant
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ACCEPTED REJECTED
Photomicrographs
Flat-mount
IHC stained corneas:
LYVE-1 (lymphatics)
CD31 (blood vessels)
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VEGF-C expression
increased 2-fold in
rejected vs accepted
allografts, and 4.8 fold
over non-transplanted
corneas.
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ARVO Annual Meeting 2010. Program#/Poster#1554/D995 27

VGX-100 PROMOTES CORNEAL TRANSPLANT SURVIVAL

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Our Goal is to commence clinical studies by Q1 ‘13 with fast track approval application lodged by H2’15

ARVO Annual Meeting 2010. Program#/Poster#1554/D995 28

OUR DIAGNOSTICS PORTFOLIO

DIAGNOSTICS – A SOURCE OF NEAR TERM REVENUE

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• VEGF-D Diagnostics

• VEGF-C Diagnostics

• Cancers of Unknown Primaries

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DIAGNOSTICS – A SOURCE OF NEAR TERM REVENUE

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VEGF-D Diagnostics

• Marketed as biomarker test for LAM (degenerative lung disease in women) in USA by Cincinatti Children’s

• Market expected to expand to 25-50,000 tests p.a within 2-3 years

• $10-20M market (with 20-25% royalty)

• Sales significantly increasing over past 2 months following KOL marketing.

• Expansion into drug monitoring cancer sector ongoing-CLIA waiver launch around end 2012 with PMA lodged Q1 2013

• Based on results of MILES Sirolimus LAM Trial a significant opportunity for VEGF-D to be used a biomarker to monitor mTOR therapy

• Lead drug in class, Affinitor estimated to have sales >$3B in next 2-3 years

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DIAGNOSTICS – A SOURCE OF NEAR TERM REVENUE

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VEGF-C Diagnostics

– Development accelerated

• Based on MD Anderson study appears to be a major biomarker to monitor anti-angiogenic therapy “resistance”

• Key product requirement for US re-imbursement agencies

• Possible market 250,000 tests worldwide at $200-300/test

• Generating further clinical data in larger cohorts

• Targeting CLIA waiver launch Q4 2012

• PMA with FDA by H1 2014.

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DIAGNOSTICS – A SOURCE OF NEAR TERM REVENUE

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Cancers of Unknown Primary Origin

• » Market launch in Aust, NZ, Malaysia, Singapore expected Q1 2012

• » Market size 10,000 tests p.a

• » Pricing at $1000-1500/test (Royalty > 15%)

• » Circadian retains rights to test to ROW

• » Partnership discussions ongoing

• » Existing Competitive Test selling for $3000/test

• » Market in USA/Europe/Japan estimated to be 150,000 tests p.a

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EXPECTED NEAR TERM MILESTONES

NEAR TERM MILESTONES

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H1 2012

• VGX-100 Phase 1 trials commenced

• CUP molecular diagnostic market launch

• VGX-100 monotherapy safety demonstrated

NEAR TERM MILESTONES

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• VGX-100 & Avastin combination safety and acceptable toxicity demonstrated

• demonstrated

• H2 • VGX-100 Phase 1 studies complete

• • IMC-3C5 Phase 1 studies complete

• • VEGF-C CLIA waivered diagnostic

• 2012 available • VGX-100 corneal allograft IND lodged

• VGX-100 Phase 1 studies complete

NEAR TERM MILESTONES

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• VGX-100 Phase 2 oncology studies commence

H1 oncology studies commence • VGX-100 Phase ½ corneal allograft studies commenced 2013 • CUP Test ROW partnership in place

AN INVESTMENT WITH SIGNIFICANT UPSIDE

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Research Report from van Leeuwenhoeck Research 7 October 20100

• “… Based on sum-of-the-parts valuation, we believe Circadian is gravely undervalued at the current share price of AUD 0.47.

Using our valuation model, the Company’s total value is AUD 91 million, or AUD 1.97 per share. This represents more than 300% upside from the current share price…”

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THANK YOU!

Q&A