Opthea Ltd — AGM Information 2010

Nov 10, 2010

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ANNUAL GENERAL MEETING 11 NOVEMBER 2010 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.

Thi s presentat on i i s not an o ff er or i nv tat on i i f or su b scr pt on or purc i i h ase o f or a recommen d at on o i f secur t es. i i I t d oes 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 LIMITED2010 AGM PRESENTATION OUTLINE

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• Corporate Snapshot

• Review of achievements since June 2009

• –

• Circadian a developer of biologics based cancer therapies

• –

• Cancer therapies/diagnostic pipeline product development overview

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

• –

• Circadian the investment opportunity

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CORPORATE SNAPSHOT

DEVELOPER OF BIOLOGICAL CANCER THERAPIES TARGETED TO BLOCK ANGIOGENESIS AND LYMPHANGIOGENESIS

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• Breakthrough technology based on tumour starvation and metastasis inhibition

• Lead program: VGX-100

• Fully human, high affinity, neutralizing monoclonal antibody for VEGF-C

• P re-c li n ca i l d a a emons ra t d t ti ng po en t ti a an l ti T umour gen c an i i d an ti -me as a t t ti c e ff ec s n an ma mo t i i l d e s o l f prostate, pancreatic, and brain cancers

• Partnered programs with existing and increasing royalty streams

• • IMC-3C5: VEGFR-3 antibody molecule for the treatment of solid tumours

  • » Development agreement with ImClone/Eli Lilly Partner

• Cancer of Unknown Primaries (CUP) molecular diagnostic

  • » Development partnership with Healthscope

• VEGF-D diagnostic for respiratory diseases

  • » Development partnership with Cincinatti Childrens Hospital Medical Center

• Dominant and protected IP position

• Strong financial position

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REVIEW OF ACHIEVEMENTS SINCE JUNE 2009

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OBJECTIVES WE SET FOR 2009/2010

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• Extend and strengthen core intellectual property covering VEGFbased therapeutics

• Advance drug development pipeline toward human clinical trials

• Develop partnerships for the commercialisation of our intellectual property

• Further strengthen and add skill-sets to management team

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PROGRESS ACHIEVED IN EXECUTING NEW BUSINESS STRATEGY – TO DATE Extending and strengthen ng our i IP position – Japanese VEGF-C patent granted

• Major US patent covering cancer treatment till September 2023

• European patent covering cancer treatment to be granted Nov 24 2010

• US VEGF-D Diagnostic patent granted

• European VEGF-D protein, gene and antibody patent granted

PROGRESS ACHIEVED IN EXECUTING BUSINESS STRATEGY

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

• cGMP manufacturin of clinical trial material commenced and to be available g Jan 2011

-Major results showing efficacy in animal models of cancer published at AACR. Further promising results in additional models.

-Pilot toxicology studies completed. Formal toxicology studies early 2011

-Collaboration commenced with MD Anderson to examine role of VEGF-C in Avastin resistance

-Harvard collaborators have generated early, but interesting data on VGX100’s ability to significantly improve survival of cornea transplants. Opportunity for develo ment under review. p

• -On track for IND Filing by June 2011

PROGRESS ACHIEVED IN EXECUTING BUSINESS STRATEGY

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Advancing our product pipeline - IMC 035: (VEGFR-3 Antibody being developed by Eli Lilly): - Advised that on track for IND Filing before end 2010 - VGX 200: (humanised anti-VEGF-D antibodies)

- Multi-gram batches made - Currently being assessed in a range of animal cancer models - - VGX 300: (recombinant VEGFR 3)

• Currently being assessed in a range of animal cancer models

• Strategic alliance formed with CSIRO to develop second generation molecules with long half lives

PROGRESS ACHIEVED IN EXECUTING BUSINESS STRATEGY

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Partnerships

– Healthscope – Good progress. On track for launch in H1 2011

– Cincinnati Childrens Hos ital Medical Centre – VEGF-D Dia nostic p g for women with respiratory disease

Building the management and adv sory eami t – Establishment of International Clinical Advisory Group

– Leadin g oncolo gy clinicians from Australia , Canada and USA

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FINANCIAL POSITION & SHAREHOLDER BASE

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Top 10 shareholders: 54.5%

Financial Summary @ 10 November 2010 (unaudited)

Investor	% of issued shares
Packer and Co Limited	16.66
Licentia Ltd	6.79
Ludwig Institute for Cancer	6.73
Research
Select Asset Management	5.10
HSBC Custody Nominees (NY	4.68
Fund) Leon Serry	4.53
HSBC Custody Nomines	3.45
(GSCo) (NY Fund)
Chemical Trustee Limited	3.36
&assoc
JFF Steven PtyLtd	1.76
Primdonn Nominees	1.4
Total 10 shareholders own	54.5%
Total 20 shareholders own	60.5%

Stock code:	CIR
Share price: Shares issued + deferred issue:	60c (AUD) 46,396,928
Market cap: Cash holdings: Listed investments: (ASX: ANP, OIL)	~ A$27 mill ~ A$30 mill A$1.7M
Institutions/Funds: ~ 31% Retail investors: ~ 42%
Professional investors: ~ 27%

KEY FINANCIALS (CONSOLIDATED)

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		30 June 10	9 Nov 2010
		$000	(unaudited) $000
	Cash	31,855	27,482
	Listed investments (market value)	1,922	1,356
	N t t e asse s	31 820 ,
	Revenue	2,265
	Operating expenses (incl. R&D, investment ’	(12,015)
	related exps)
	Loss before tax	(6,839)
	Net cash outflows	(6,936)
	NTA per share	$ 0.77
	Cash & listed assets per share	$0.75	$0.62
	Shareprice	$0.52	$0.59

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CIRCADIAN – A DEVELOPER OF BIOLOGICS BASED CANCER THERAPIES

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MECHANISM OF CIRCADIAN’S DRUGS (1)

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MECHANISM OF CIRCADIAN’S DRUGS (2)

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OUR STRATEGY: A CASH GENERATING ENTITY WHICH UNDERTAKES HIGH VALUE BIOLOGICALS DRUG DEVELOPMENT

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Technology & Cash
Partnered Product Internal Product
Development Development
VGX‐100
‐
VGX 200
Research VGX‐300
Reagents Diagnostics Therapeutics
•Millipore •Healthscope •Eli Lilly VALUE
•R&D systems •Cincinatti •Lymphatix N ew
• Partnerships
Perkin‐Elmer
•Reliatech
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REVENUES
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CIRCADIAN’S DEEP PRODUCT PIPELINE

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IMPROVING ANTI-ANGIOGENESIS A MAJOR COMMERCIAL OPPORTUNITY

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• Avastin®: 2009 Sales $US5.7B

• 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 an io enic factors bein turned on when VEGF-A g g g

  • blocked

    • (i.e. VEGF-C, VEGF-D)

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CANCER THERAPIES/DIAGNOSTIC PIPELINE - PRODUCT DEVELOPMENT OVERVIEW

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VGX-100 SINGLE-AGENT & COMBINATION - THERAPY IN PC 3 PROSTATE CANCER XENOGRAFTS

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2200
Negative isotype Control
2000
Avastin
1800 VGX-100
1600 Docetaxel
Avastin + Docetaxel
1400
VGX-100 + Docetaxel
1200
VGX-100 + Avastin
1000 VGX - 100 + Avastin + Doc e
800
600
400
200
0
0 20 40 60 80 100 120 140 160
Days ost-P Tumor mp antI l
g) +/- SE
Burden (m
ean Tumor
M
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Docetaxel: Weekly IV at 10 mg/kg for 3 weeks. Vehicle: 10% EtOH, 10% Tween 20, 80% water.

MIR1219

U87MG GLIOBLASTOMA TUMOR - XENOGRAFTS: VGX 100 COMBINATION WITH AVASTIN

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2600
Negative Isotype Control
2400
Avastin
2200
2000 VGX-100
1800
1600
1400
1200
1000
VGX-100 + Avastin
800
600
400
200
0
0 10 20 30 40
Days Post-Tumor Implant
mg) +/- SE
or Burden (
Mean Tum
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At Day 49, VGX‐100 + Avastin reduces tumor burden by:

• 42% compared to control IgG

• 33% compared to single‐agent Avastin.

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VEGF‐C‐ Potential in front of the eye disease

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• VGX-100 IMPROVES CORNEAL TRANSPLANT SURVIVAL

• (COLLABORATION WITH HARVARD UNI., SCHEPENS)

• 50000 corneal transplants/yr in USA.

• ’

• • ‐ ‐ High rate (~50%) of rejection when transplanted into ‘ high risk inflammed and vascularised beds.

• Post‐operative growth of blood and lymphatic vessels into avascular ‘normal‐risk’ recipients increases likelihood of subse uent immune re ection. q j

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- VGX 100 PROMOTES CORNEAL TRANSPLANT SURVIVAL

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

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Building our Revenues

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NEAR TERM REVENUE GENERATING ASSETS

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Cancers of Unknown Primaries (CUP) Molecular Diagnostic

• 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)

NEAR TERM REVENUE GENERATING ASSETS

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Cancers of Unknown Primaries (CUP) Molecular Diagnostic

– Internal Developments throughout the year focused on improving the platform and gene set as well as the analytical software

– Data looks promising with key experiments expected to be completed early 2011

– Appears our approach will provide advantages over existing FDA approved test

– Product launch expected H1 2010

NEAR TERM REVENUE GENERATING ASSETS - VEGF D DIAGNOSTIC FOR RESPIRATORY DISEASE

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VEGF-D a specific serum biomarker for Lymphangioleiomyomatosis (LAM)

• Lymphangioleiomyomatosis (LAM): A disease causing cystic lung lesions in women and has also been linked to genetic disease TSC

• Often degenerative requiring lung transplant

• Frequently fatal

• Primarily affects women of reproductive age

• Estimated 300,000 cases worldwide plus approx 1M sufferers of TSC

• Test Initially targeted at disease monitoring, may extend to screening

• -

• Estimated 50 100 000 test per annum at cost of $200, 400/test

• US marketing through Cincinnati Childrens Hospital Medical Centre under CLIA Waiver expected to commence Jan/Feb 2011

• Europe and Japan under negotiation

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VEGF-D Diagnostics – Respiratory
disease
VEGF‐D is increased in Serum VEGF ‐ D levels distinguishable from other
serum of patients with cystic and chylous lung diseases
LAM
Young et al. NEJM., 358(2), 199‐200, 2008
Seyama et al. Lymphatic Res & Biol., Vol 4, #3, 143‐152, 2006
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EXISTING REVENUE GENERATING ASSETS

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• Imclone/Eli Lilly (VEGFR-3 Antibody) –Annual Licence Fees

• Research Reagent suppliers

• Merck Millipore

• R&D Systems

• Reliatech

• P er ki n El mer

• Lymphatix Ltd (VEGF-C and VEGF-D gene therapy)-Annual Licence Fees and royalties (will be affected by ongoing arbitration)

• 2009/10 - $621,000

• 2010/11 – May be effected by $A , but expected increase from Healthscope, Cincinnati and improved Lymphatix terms if arbitration successful

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EXPECTED NEAR TERM MILESTONES

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NEAR TERM MILESTONES

• VGX‐100 IND Filing with FDA

• VGX‐100 toxicology completion

• VGX‐100 cGMP manufacture

• completion

• IMC‐3C5 IND filing (ImClone/Eli Lilly)

• CUP molecular diagnostic market launch

• VEGF‐D Diagnostic Sales Commence

NEAR TERM MILESTONES

• VGX‐100 non‐cancer indications development commenced

• CUP molecular diagnostic USA and European partnerships in place

• VEGF‐D Diagnostic Partnerships in Europe and Japan

• VEGF‐C Clinical Diagnostic Development Partnered

• Further Reagent Supply partnerships

NEAR TERM MILESTONES

• ‐

• VGX 100 Fi rst Clin ca i l Studies completed

• VGX‐300 Designated Product Development Candidate

• • IMC‐3C5 (ImClone/Eli Lilly) Phase 1 clinical studies completed;

AN INVESTMENT WITH SIGNIFICANT UPSIDE

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Research Report from Morningstar/Huntley’s 3 May 2010

Fair value $2 . 20/share

"CIR is now focused on the development of VEGF-based therapies for the t rea men o cancers an t t f d o th er seases. cenc ng di Li i d ea s a rea l l d y n p ace i l provide a degree of validation of the technology. At present the share price recognises negligilble value for CIR's intellectual property" RECOMMENDATION :

"While unarguably speculative, CIR's cash and extensive IP position relative to its market capitalisation suggest an attractive risk/return ratio for investors exper ence i d i n th e mu lti p e p l itf a ll s th a can accompany t R&D i nves men t t"

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THANK YOU! Q&A

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