Opthea Ltd — Investor Presentation 2009

Nov 18, 2009

Robert Klupacs, CEO & Managing Director Circadian Technologies (ASX.CIR)

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 forwardlooking 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.

• Review of achievements since June 2008

• –

• Circadian a developer of biologics based cancer therapies

• –

• Cancer therapies/diagnostic pipeline product development overview

• –

• VEGF‐C/D gene therapy Ark Therapeutics Ltd and Lymphatix Ltd

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

• –

• Circadian the investment opportunity

Transformation of the business model from “biotechnology investor and incubator of early stage technologies” to focused developer of biological cancer therapies

REVIEW OF ACHIEVEMENTS SINCE JUNE 2008

• Extend and strengthen core intellectual property covering VEGF-based therapeutics

• Advance drug development pipeline toward human clinical trials

• Add to list of partnerships for the commercialisation of our intellectual property

• Further strengthen and add skill-sets to management team

• Extending and strengthening IP position

• Acquisition of 100% of Vegenics

• Prosecution of key strategic patents in USA, Europe and Japan

• Advancing our product pipeline

• VGX-100: manufacturing of antibody (AB) drug underway

• – VGX-200: humanisation of AB’s completed

• VGX-300: manufacturing milestone achieved

• Animal studies in cancer models underway for above programs

• Licensee ImClone designated human AB IMC-3C5 as preclinical development candidate

• New partnerships

• Healthscope – developing and to commercialise cancer diagnostic

• Perkin-Elmer granted license – research products market

• Building the management and advisory team – Establishment of Product Development Review Committee Six members with vast experience in international drug development

• Expanded management team Alex Szabo, Head of Business Development Mike Gerometta, Head of Chemistry Manufacturing Control Mark Sullivan, Head of Clinical Development, recently appointed (ex GSK, Gilead Sciences)

• Appointment of new director with drug development background, August 09: Dr Errol Malta (ex Amgen)

• Divestment of non-core assets: Avexa

Key financials (consolidated)

	30 June 09 $000	18 Nov 09 (unaudited) $000
Cash	38,836	35,500
Listed investments (market value)	5,142	9,000
Net assets	38,773
Revenue	3,091
Operating expenses(incl. R&D, investment related exp’s)	(12,966)
Loss before tax	(9,875)
Net cash outflows	(7,329)
NTA per share	$0.86
Cash & listed assets per share	$0.97	$0.98
Share price	$0.73	$0.73

CIRCADIAN – A DEVELOPER OF BIOLOGICS BASED CANCER THERAPIES

• Developing antibody therapies to treat cancer – a major global opportunity

• Break through technology based on

• tumour starvation AND inhibition of spread

• Partnered programs with existing and increasing royalty streams

• leading international biotechs

• Deep pipeline of product opportunity

• Other disease applications

• Dominant IP position

• Objective is to secure pre-clinical partnerships for one or more of our therapeutic programs

• Retain development of one selected therapeutic to proof of efficacy in humans – partner thereafter

• Selectively exploit / commercialise other aspects of portfolio:

– therapeutics outside oncology area

• clinical diagnostics and reagents for early revenues

• Antibodies are one of the most valuable sectors of the market

• 21 antibody drugs on the market

– Mostly in cancer and inflammation – Current sales of top ten antibodies > $US20B pa – Total sales growing by >30% annually – Greater competitive barrier to entry – Targeted profiles = cost vs health economic advantage

By 2014 it is expected that 4 of the top 6 best-selling drugs will be antibodies & the top 10 selling drugs will come from biotech (source: EvaluatePharma®)

Oncology Antibodies: High	Oncology Antibodies: High	Oncology Antibodies: High	Oncology Antibodies: High	Value Pre-clinical	Value Pre-clinical
Deals
	Parties	Date	Size	Technology
	BioInvent/Thrombogenics /Roche	Jun 08	$US800M	Exclusive licence to PlGF Abs in oncology. $US75M upfront. $US700M milestones. Double digit royalties
	Micromet/Bayer-Schering	Jan 09	$US396M	Option to Ab against undisclosed oncology target
	Abbott/LICR	Nov 08	$US150-	Exclusive licence to 2nd generation
			200M	EGFR Ab in oncology which has
				completed 8 person Phase 1 study
	Dyax/Sanofi-Aventis	Feb 08	$US500M	Exclusive licence to Tie-1 Ab DX- 2240 and phage display in selected
				applications
	GSK/OncoMed	Dec 07	$US1.4B	Exclusive licence/co-development of
				4 selected stem cell Abs in cancer

• Our technology is centred on two members of the VEGF family of proteins: VEGF-C & VEGF-D and their activation on VEGF receptors VEGFR-2 and VEGFR-3

• • These proteins promote blood and lymphatic vessel development

• • Targeting this process has major potential to limit tumour growth and spread

• • Also has applications in other diseases such as eye diseases

• Avastin®: Effective but not across the board

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

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

• – Likely 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)

Avastin Major Our technology effective but = opportunity builds upon the has limitations for CIR Avastin application

Mechanism of Circadian’s Drugs (1)

Mechanism of Circadian’s Drugs (2)

CANCER THERAPIES/DIAGNOSTIC PIPELINE - PRODUCT DEVELOPMENT OVERVIEW

Circadian’s Deep Product Pipeline

• 11 different animal studies ongoing; more planned-initial results H1 2010

• Manufacturing methods being developed to produce compounds for clinical use (cGMP)

• • FDA pre-IND review H1 2010

• IND filing expected H1 2011

• Significant animal proof of principal established in cancer models

• • Designated formal clinical development candidate

• IND filing expected H2 2010

NSCLC xenograft model (NCI-H292)

AACR 2009 Abstract #4089 O’Mahoney et al

• Development partnered with Healthscope (ASX:HSP)

• US incidence of CUP 60,000 to 100,000 per annum

• Test to sell for between US$2-4K due to significant health cost savings

• – CIR retains ownership and exclusive commercialisation rights in US, Europe and Japan; receive royalty on Healthscope sales

• – Healthscope (Aus, NZ, Singapore, Malaysia)

– Product launch expected H2 2010

VEGF-C/D GENE THERAPY: Ark Therapeutics Ltd & Lymphatix Ltd

• Ark Therapeutics (2001)– non exclusive licence to VEGF-D gene used in combination with Ark delivery device for treatment of stenosis (“Trinam”)

• Lymphatix Ltd (2004) – exclusive licence for VEGF-C and VEGF-D gene therapy excluding cancer and excluding rights previously granted to Ark.

• Ark acquired Lymphatix in January 2008

Ark’s Phase 3 Product Trinam®

• 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 > $US750M+ per annum

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Collar
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artery
vein
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Graft Vein
Anastamosis
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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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• Post Lymphatix acquisition Ark asserts it no longer requires original 2001 licence and does not pay annual fee

• Circadian subsidiary terminates Ark licence for non-payment of licence fees in October 2009

• • Circadian initiates arbitration under Lymphatix agreement to clarify scope

• Circadian confident of its position

• Expect resolution in 6-12 months

EXPECTED MILESTONES/VALUE ADDING EVENTS NEXT 6 to 18 months

• VGX-100 cancer drug development

program

• Animal tumour model evaluation

• FDA pre-IND review

• – Toxicology completion

• – IND Filing

• IND filing: IMC-3C5 for cancer (ImClone/Eli Lilly partner)

• CUP molecular diagnostic

H1 2010 H1 2010 H2 2010 H1 2011 H2 2010 H2 2010

– Market launch

• ANP (listed investment*) milestone – Antisense Therapeutics’ (ASX:ANP) partner Teva to advise of decision to progress MS treatment ATL/TV 1102 into late stage clinical studies

• Resolution of unlicensed gene therapy development by third parties

Q1 2010

H2 2010

• CIR’s direct+indirect interest in ANP: 21.8%

• Therapeutic antibodies

– Major focus of big pharma

– High value early stage deal opportunities and M&A opportunities

• Deep diverse product pipeline

– Diagnostic product in late stage development – Potential multi-million dollar royalties

– Royalty flows possible <12 months

• Angiogenesis - significant product opportunity validated

• Dominant and protected IP position

• World-class drug development expertise and management

• Strong financial position

US Investment bank Merriman Curhan Ford published analyst opinion 5 November 2009:

“ We believe the current valuation of Circadian represents an attractive entry point for investors based on the potential of its product candidates . ”