Opthea Ltd — AGM Information 2008

Nov 13, 2008

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Developing biological therapeutics for cancer Managing Director’s Presentation AGM 14 November 2008

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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.

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Presentation Outline
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• – 2007/08 Year in Review: Key Events

• Circadian Today

• Ongoing Strategic Directions

• – Circadian The Investment Opportunity

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2007/08 Review: A year of major change
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• Retirement of Leon Serry after 24 Years

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2007/08 Review: A year of major change
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• Transformation of the business model from “biotechnology investor and incubator of early stage technologies” to focused drug development company in cancer

• New leadership, Robert Klupacs MD, expanded management team, expert advisors

• Retirement of long serving directors: John Stocker and James MacKenzie

• Appointments of new directors:

Tina McMeckan (commercialisation of science, corporate fund raising) Carlo Montagner (experience in heading oncology therapeutic businesses) Jonathan Skipper (Ludwig IP executive)

• Acquisition of 100% of Vegenics (Ludwig and Licentia’s minority interest holdings)

• Licentia and Ludwig Institute becoming significant shareholders

• • Divestment of remaining MBP holding

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Key Events ImClone (NASDAQ: IMCL) announces IMC-3C5 is October 2008 product development candidate (licensed VEGFR-3 antibody technology for this product from Vegenics) Arana completes humanisation of Vegenics’ VGX-200 October 2008 series drug candidates Circadian completes 100% acquisition of Vegenics August 2008 Vegenics granted key strategic patent in US covering August 2008 angiogenesis inhibitors “Nature” publication reporting major role of VEGFR-3 July 2008 in angiogenesis – confirming role of target in cancer therapy Circadian establishes a world class team to develop June 2008 cancer drugs using its VEGF technology Robert Klupacs appointed Managing Director March 2008

	Key financials – 30 June 2008 (consolidated) 30 June 2008 $000 13 Nov 2008 (unaudited) $000 Cash 46,217 42,900 Listed investments (market value) 12,754 6,800 Net assets 51,407 Revenue 8,148 Operating costs (incl R&D) (9,264) Loss before tax (1,117) Loss after tax (2,286)	Key financials – 30 June 2008 (consolidated) 30 June 2008 $000 13 Nov 2008 (unaudited) $000 Cash 46,217 42,900 Listed investments (market value) 12,754 6,800 Net assets 51,407 Revenue 8,148 Operating costs (incl R&D) (9,264) Loss before tax (1,117) Loss after tax (2,286)	Key financials – 30 June 2008 (consolidated) 30 June 2008 $000 13 Nov 2008 (unaudited) $000 Cash 46,217 42,900 Listed investments (market value) 12,754 6,800 Net assets 51,407 Revenue 8,148 Operating costs (incl R&D) (9,264) Loss before tax (1,117) Loss after tax (2,286)	Key financials – 30 June 2008 (consolidated) 30 June 2008 $000 13 Nov 2008 (unaudited) $000 Cash 46,217 42,900 Listed investments (market value) 12,754 6,800 Net assets 51,407 Revenue 8,148 Operating costs (incl R&D) (9,264) Loss before tax (1,117) Loss after tax (2,286)
		30 June 2008 $000	13 Nov 2008 (unaudited) $000
	Cash	46,217	42,900
	Listed investments (market value)	12,754	6,800
	Net assets	51,407
	Revenue	8,148
	Operating costs (incl R&D)	(9,264)
	Loss before tax	(1,117)
	Loss after tax	(2,286)
	NTA per share	$1.28
	Cash & listed assetsper share	$1.46	$1.10
	Share price	$0.88	$0.665

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CIRCADIAN TODAY

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Developing therapeutics for cancer and other serious diseases

• Developing angiogenesis-based therapies for cancer and other serious diseases

• World’s most comprehensive patent estate covering key angiogenesis targets VEGF-C, VEGF-D and VEGFR-3

• Partnered programs with leading international biotechs Ark Therapeutics plc (LSE:AKT) – Phase 3 clinical trial ImClone Systems Inc (NSDQ:IMCL) – developing anti-cancer drug

• Strong financial position - $50 million in cash & listed investments

• ASX:CIR

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What is angiogenesis?

• Angiogenesis is the growth of new blood vessels

• Tumour growth is caused by stimulation of new blood vessel growth by proteins (e.g. proteins VEGF-A, C, D)

• Blocking these proteins blocks blood vessel growth, leading to tumour starvation

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Avastin® Story
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• First targeted anti-angiogenesis therapy to become drug (developed & sold by Genentech Inc)

• Antibody that blocks angiogenic protein VEGF-A

• First approved Feb 2004

• 2007 sales: in US $US2.3B, worldwide: $US6B

• Fastest sales growth of any drug

Avastin + chemo extends progression free survival in breast cancer Avastin + chemo extends survival in lung cancer

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Circadian’s approach and technology

Developing four drug programs targeting different mediators of the process of angiogenesis to treat cancer

• We are focused on the two other angiogenic VEGF proteins (VEGF-C & D) which are involved in tumour growth as well as in tumour spread (metastasis).

• By blocking VEGF-C/D - not only starves tumours but has additional .

• major therapeutic potential for inhibiting tumour spread

• Angiogenesis and metastasis blockade are a major area of oncology drug development internationally.

• Drugs complementary to, or improved on Avastin®, are recognised as important areas in drug development.

• Our products target multiple indications – cancer first target.

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Antibodies represent significant market opportunities

• Strong interest in antibodies from pharma in new product opportunities. Recent partnerships/M&A over last 2 years:

• Medimmune/AstraZeneca – US$15.5b

• –

• CAT/AstraZeneca US$1.30b

• Bioinvent/Tx/Roche – US$800m

• –

• Domantis/GSK US$435m

• –

• Adnexus/BMS US$425m

• –

• Morphotek/Eisai US$325m

• 19 antibody drugs on the market

• Current sales of top ten antibodies > US$20bn p.a;

• Total antibody sales growing by >30% annually

Circadian’s products

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VEGF-C / D Blockade: Inhibiting Angiogenesis AND metastasis

VEGF-C/D blockers can block tumour spread through lymph system

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Creating value for shareholders

• Dominant IP position over key mediators of angiogenesis and tumour spread with control over major IP portfolio

• Phase 3 product partnered and pipeline of product opportunities in development

• Significant cash reserves and other financial assets to undertake ongoing development and strength in negotiating future licensing/ partnering deals

• High value space for partnerships – Recent early stage deals (e.g. Roche/Bioinvent) in angiogenic antibody space of US$500M +

• Deal making and drug development expertise to achieve partnering

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Phase 3 Product Trinam®

•

•

Commencing Phase 3 second half 2008

• VEGF-D gene therapy product

• Extends lifetime of dialysis access grafts by keeping veins open for longer. Phase 2 clinical trials: 17 months v 4.5 months.

• • Major patient impact by reduced need for repeated surgery and increased survival time of patients undergoing ongoing dialysis.

• • Market estimates > $US500M+ per annum Collar

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artery
vein
Step 1: Surgical isolation
of vein and artery
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Step 2: Insert flexible plastic tube graft to provide access for dialysis

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Graft Vein
Anastamosis
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Deal-making, drug development and operational track record

Management

• Robert Klupacs (CEO) - Over 3 years in executive position with Circadian. Founder

• and former CEO, ES international and six other early stage companies. Entrepreneur and IP expert with extensive history of industry deals.

• Dr Alex Szabo (Head, Business Development) - Formerly Bionomics, Beckman-

• Coulter, Affymetrix, Pharmacia. Recent deals include Aventis, Eisai, Genmab, LabCorp, Merck-Serono

• Natalie Korchev (CFO & Head of Operations) ACA - Formerly Ernst & Young, global finance, risk management experience. Over 10 years experience in biotech industry – over 8 years with Circadian.

• Dr Megan Baldwin (Scientific Affairs) – PhD in angiogenesis with over 10 years experience in the field; ex Genentech R&D

• Ms Sue Foran (Product Development Manager) – Over 15 years experience in drug development. Ex GlaxoSmithKline and Kendle

• Dr Mike Gerometta (CMC and Manufacturing Manager) – Over 18 years experience in diagnostic and antibody therapeutic development. Ex Agenix

• Dr Richard Chadwick (IP Counsel) - European and Australian patent attorney. Over 15 years experience in patent management with multi-nationals and biotechs. Ex FB Rice & Co

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Deal-making drug development and operational track record

Product Development Advisory Committee

• Dr Errol Malta ex Amgen Team leader for cancer drug Neulasta and other projects.

• Dr George Morstyn - Formerly CMO and Head of Development Amgen

• Mr Ralph Smalling – Formerly Head of Amgen Regulatory Affairs

• Dr Russell Howard – ex Head R&D Affymax, currently CEO Nasdaq listed Maxygen Inc

• Dr Richard Morgan – Formerly Head of Toxicology Glaxo Wellcome (now GlaxoSmithKline)

• Mr Carlo Montagner – Circadian Director. Formerly Head of Oncology Franchises at Aventis, Schering AG and Abraxis.

Over 150 drug development projects collective experience of above members of the Committee.

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Deal-making drug development and operational track record

Board of Directors

• Ms Dominique Fisher – Entrepreneur, professional director - Pacific Brands, ex AIG, various private cos

• Mr Don Clarke – Partner Minter Ellison. Professional director - Metabolic, Webjet, various private companies

• Ms Tina McMeckan – Strategist, corporate fund-raising specialist. Professional director – Vision CRC, Melbourne Zoo, ex Alinta, various other companies

• Dr Jonathan Skipper – Executive Director IP & Licensing Ludwig Institute for Cancer Research

• Mr Carlo Montagner (see previous slide)

• Mr Robert Klupacs (see management slide)

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Ongoing Strategic Directions

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Our strategy

• Develop at least one therapeutic to proof of efficacy in Phase II trials

• Subsequent clinical development with partners – large pharmaceutical/biotechnology companies

• However seize opportunity for earlier partnerships if and when appropriate

• Selectively exploit/commercialise parts of portfolio not in angiogenesis area at earlier stages (e.g. similar to the Ark Therapeutics partnership)

• Prudently manage our cash. Our objective is net cash outflows of $10-12M p.a. with increases in activities subject to increased revenue/ other cash inflows

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Our Strategy Addresses Financial Market Challenges
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• Market conditions are likely to adversely effect capital raisings for biotechs over the short to medium term.

• We are addressing this through prudent cash management and pursuing earlier partnerships where appropriate as stated in the previous slide.

• This, however, needs to be balanced against astute value adding investments.

• Although healthcare industry deal making still seems relatively stable, our plans consider the possibility of slow-down or reduction in industry deal value metrics.

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Expected Milestones (next 6 to 18 months)
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• Commencement of Phase 3 studies with licensee’s product Trinam®

• Imclone/Eli Lilly commence clinical studies with IMC-3C5

• Successful divestment of listed investments

• VGX-100 completes pre-clinical developments

• VGX-200 series lead designated product development candidate

• VGX-300 designated product development candidate

• At least one strategic partnership in place

• Scientific presentations at leading international conferences on successful animal trials with VGX candidates

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Why Circadian is a major investment opportunity
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Competitive IP - Dominant IP position over key mediators of angiogenesis and tumour spread

• People – Track record of deal making & drug development success

Cash – $50m cash/listed investments. Among a handful of biotechs in strong financial position

• Product Advantages – Compelling advantages over existing treatments

• Trinam® – 4-fold increase in kidney dialysis graft lifetime

• VGX-Compounds – Potential to inhibit both tumour growth and metastasis

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Why Circadian is a major investment opportunity (cont)
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Pipeline - Four drug development programs targeting different mediators of cancer

Partnership opportunities

• 2 existing deals

• High value for early deals in angiogenesis space: e.g. Roche/Bioinvent antibody US$500M (Phase 1) – see separate slide for other deals in the sector

Revenue stream – existing and increasing royalty flow News flow – Potential for many upcoming product development/scientific/partnership milestones Value

“Exceptional Cash Resources” and a “stand out offering” ( Bioshares , 10 Oct, 2008)

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Questions

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