Opthea Ltd — Investor Presentation 2011

Jan 10, 2011

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11 January 2011

The Companies Section The Australian Stock Exchange Limited 530 Collins Street MELBOURNE VIC 3000

US Investor presentation

Circadian Technologies Limited (ASX:CIR) today announced its CEO, Mr Robert Klupacs, will present a company update at the Biotech Showcase 2011 in San Francisco, USA.

The presentation will take place at 4.15pm in the Stockton Room, Parc 55 Wyndham, Union Square, San Francisco.

As part of activities surrounding the 29th JP Morgan Healthcare Conference, briefings will also be given to US institutional investors and pharmaceutical companies.

The presentation can be found on Circadian’s website www.circadian.com.au.

Yours faithfully

Susan Madden

Company Secretary

Circadian Technologies Limited

Level 1 10 Wallace Avenue Toorak Victoria 3142 Australia T +61 (3) 9826 0399 F +61 (3) 9824 0083 www.circadian.com.au

ABN 32 006 340 567

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2011 BIOTECH SHOWCASE PARC 55 WYNDHAM SAN FRANCISCO 11 JANUARY 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.

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.

CORPORATE SNAPSHOT

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• Developer of biological cancer therapies targeted to block angiogenesis and lymphangiogenesis

• Breakthrough technology based on tumour starvation and metastasis inhibition

• Lead program: VGX-100

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

– anti-Tumourigenic and anti-metastatic effects in animal models of prostate, pancreatic, and brain cancers • Partnered programs w ti h ex st ng ani i d increas ng roya ty streamsi l

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

  • » Development agreement with ImClone/Eli Lilly Partner

• C ancer o f U n k nown r mar es P i i (CUP) mo ecu ar agnost c l l di i

  • » Development partnership with Healthscope

• VEGF-D Diagnostic for respiratory diseases

  • » P artnere d w t i h Ci nc natt i i Child rens H osp ta i l M e di ca l C entre

• Dominant and protected IP position

• Strong financial position

3

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
Diagnostics Therapeutics
Research VGX‐300
Reagents •Healthscope •Eli Lilly
••R&D systemsMillipore (CUP Test) •Cincinatti (VEGFR3 Ab) •Lymphatix N ew VALUE
• (VEGF‐ (VEGF‐D gene Partnerships
Perkin‐Elmer
•Reliatech D/LAM) therapy)
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REVENUES

MECHANISM OF ACTION

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Angiogenesis & Lymphangiogenesis

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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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VEGF-C –well recognised survival prognostic factor in a number of tumour types Some examples

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VEGF‐C levels correlate with lymph node mets and decreased survival in cancer gastric

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VEGF-C
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91 Gastric Adenocarcinomas

VEGF‐C correlated with:

• LN metastases

• Decreased survival

VEGFR‐3 is an independent prognosti markers

Graph shows DFS

Juttner et al., JCO, 24(2): 228‐240, 2006.

Non Small Cell Lu Cancer Poor prognosis for ng ‐ ‐ patients expressing VEGF C and VEGFR 3

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180 NSCLCs

5yr survival rates for patients: ‐ VEGF C iti ve: 47% pos VEGF‐C negative: 70%

VEGF‐C and VEGFR‐3 correlated with:

• Decreased survival

• Pts with positive staining for both

• had poorest prognosis

Arinaga et al., Cancer, 97(2): 457‐464, 2004.

VEGF‐C is a risk factor for colorectal cancer

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69 CRC

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VEGF‐C correlated with:
• LN Metastases
L ow VEGF - C
•
Clinical Stage
‐
Elevated VEGF C assoc atei d w ti h:
High VEGF-C
•
Decreased DFS
•
Decreased OS
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Hu et al., Eur Surg Res, 39: 229‐238, 2007.

‐ VGX 100 Program

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

• Development and clinical program designed to address resistance and non-res onsiveness to anti-an io enic thera ies for cancer p g g p

• Preclinical data in animal models of prostate, pancreatic, and brain cancers demonstrate:

• Dose-responsive inhibition of primary tumour growth in several mouse xenograft models

• P o t en ti a as an l ti T umour gen c i i an d an ti -me t as t a ti c agen t

• Exciting potential for front of eye disease

• Orphan drug designations likely

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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 osP t Tumor mp anI l t
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.

CLINICAL DEVELOPMENT CONCEPT

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• 2 interlinked target product profiles on a tumour by tumour basis

• VGX-100 plus standard of care chemotherapy in Avastin or anti-angiogenic therapy refractory patients

• • • Concept supported by VEGF C being predictive marker for

• Sutentresponse and MD Anderson data (unpublished)

• VGX-100 in combination with SOC + Avastin(based on biomarker stratification)

• -NB Cost of treatment to patient of this approach to be no more than current Avastincosts based on assumption that generic bevacizumabwill be available 2017/18 onward

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- VGX 100 PHASE 1 & PHASE 2 CLINICAL TRIAL PLAN

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• Phase 1a Ascending Dose Study plus SOC in Avastin untreated late stage patients

• “3+3” design

• Performed under IND

• Phase 1b Ascending Dose Study plus SOC in Avastin treated late stage patients

• To be started 2 cohorts behind 1a

• Phase 2 randomised study VGX-100 plus Avastinplus SOC V Avastin plus SOC in selected indications, supported by investigator led studies in other indications

• Avastin refractory CRC currently most likely;

• Also reviewing niche tumour types

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- VGX 100 DEVELOPMENT STATUS JANUARY 2011

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• -cGMP manufacturing of clinical trial material commenced and to be available Jan 2011

• -Ma j or results showin g efficac y in animal models of cancer published at AACR. Further promising results in additional models obtained

• -Pilot toxicolo studies com leted. Formal GLP toxicolo studies gy p gy

• early 2011

• -Collaboration with MD Anderson to examine role of VEGF-C in Avastinresistance initial ositive findin s p g

• -Harvard collaborators have generated early, but interesting data on VGX-100’s ability to significantly improve survival of cornea trans p lants. O pp ortunit y for develo p ment under review.

• -On track for IND Filing by Q3 2011

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IMC‐035 Program Imclone/Eli Lilly

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• Fully human, high affinity, neutralizing monoclonal antibody for VEGFR3

• Being developed by Imclone/Eli Lilly

• Circadian receives Licence Fees and ro alties y

• Preclinical data in animal models of lung and head and neck

• Being developed to treat solid tumours: Head & Neck most likely

• Phase1 first dosing commencement expected Q1 2011

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VEGFR-3 AB (MF4-31C1) +/- CHEMO IN NON-SMALL CELL LUNG CANCER XENOGRAFT MODEL

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NSCLC xenograft model
(NCI-H292)
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AACR 2009 Abstract #4089 O’Mahoney et al

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NEAR TERM REVENUE GENERATING ASSETS CANCERS OF UNKNOWN PRIMARIES ( CUP ) MOLECULAR DIAGNOSTIC

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• 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

• Advantages over existing tests

• – Launch expected HI 2011

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

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

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

• Test Initially targeted at disease monitoring, may extend to

• i

• screen ng

• Estimated 20-50,000 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

A STRONG FINANCIAL POSITION & SHAREHOLDER BASE

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Top 10 shareholders: 54.5%

Financial Summary @ 10 January2011 (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 &assoc	3.36
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% Cash Burn estimate 2011/12 $10-12m
Retail investors: ~ 42% Professional investors: ~ 27%

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EXPECTED NEAR TERM MILESTONES

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NEAR TERM MILESTONES

• VGX‐100 toxicology completion

• VGX‐100 cGMP manufacture completion

• • ‐ IMC 3C5 Phase 1 commencement (ImClone/Eli Lilly)

• • CUP molecular diagnostic market launch

• VEGF‐D Diagnostic Sales Commence

NEAR TERM MILESTONES

• VGX‐100 IND Filing with FDA

• VGX‐100 Phase 1 commencement

• VGX‐100 non‐cancer indications development commenced

• CUP molecular diagnostic USA and European partnerships in place

• VEGF‐D Diagnostic Partnerships in Europe and Japan

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;

INVESTMENT HIGHLIGHTS

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• Developer of biological therapies targeted to block angiogenesis and lymphangiogenesis

• Breakthrou h technolo based on tumour starvation and metastasis g gy

• inhibition

• Cancer Focus but with wealth of non-oncology applications

• Partnered programs with existing and increasing royalty streams

• D om nant an i d protecte d IP pos t on i i

• Strong financial position

• Imminent market re-rating likely (currently valued on earlier incarnation as Listed Biotech Fund)

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APPENDIX

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VEGF‐C‐ Has a key role in front of the eye disease

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VGX-100 IMPROVES CORNEAL TRANSPLANT SURVIVAL

• (COLLABORATION WITH HARVARD UNI., SCHEPENS)

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• 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

• Ingrowth of lymphatics enables trafficking of APCs and antigenic material to regional LNs and accelerates host sensitization to graft antigens.

REJECTED CORNEAS ARE INFILTRATED BY BLOOD AND LYMPHATIC VESSELS AND OVER-EXPRESS VEGF-C AND VEGFR-3

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VEGF‐C expression increased 2‐fold in rejected vs accepted allografts, and 4.8 fold over non‐trans p lanted corneas.

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3 weeks post‐transplantation

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

VGX‐100 reduces blood and lymphatic vessel in corneas density transplanted

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Day 7 post‐transplant ARVO Annual Meeting 2010. Program#/Poster#1554/D995

VGX‐100 Promotes Corneal Transplant Survival

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

DOMINANT AND PROTECTED IP POSITION

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• Granted IP rights in major territories to VEGF-C/D proteins and VEGFR-3 and blockers

• Freedom to operate through deals with HGS and Chugai

• IP rights over product candidates extend beyond September 2023

• Further strategic IP filings being made to extend patent life

• Over 500 granted and pending patents worldwide

• Protection through US and European market exclusivity provisions

- WORLD CLASS DRUG DEVELOPMENT EXPERTISE AND MANAGEMENT

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• .

• Robert Klupacs (CEO) Entrepreneur & IP expert Over 24 years biotech experience. Extensive history of industry deals including Sanofi, Baxter, Aventis, Pharmacia, Novartis, Alexion, Pfizer

• Dr Mark Sullivan (Head of Clinical Development) Formerly GSK , Gilead Sciences. Over 18 years pre-clinical and clinical drug development experience

• Dr Megan Baldwin (Head of Preclinical R&D) Formerly Genentech Over 10 years experience in angiogenesis research

• .

• Dr Richard Chadwick (Head of Intellectual Property) European and .

• Australian patent attorney Over 15 years biotech experience

• Dr Mike Gerometta (Head of CMC Development) Formerly Agenix. Over 17 years biotech experience

• Ms Sue Foran (Head of Toxicology) Formerly GSK, Kendle. Over 10 years biotech/drug development experience

- WORLD CLASS DRUG DEVELOPMENT EXPERTISE AND MANAGEMENT (CONT)

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• Product Development Review Committee Six members with vast experience in international drug development & oncology:

• Dr Errol Malta

• Dr George Morstyn

• Dr Russell Howard

• Mr Carlo Montagner

• Mr Ralph Smalling

• Dr Richard Morgan

Past roles have included positions with Amgen, GSK, Aventis, Schering, Affymax, Maxygen. Over 150 drug development experience.

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