Opthea Ltd — Capital/Financing Update 2008

Oct 13, 2008

ASX and Media release

14 October 2008

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Vegenics’ licensee ImClone designates VEGFR-3 antibody (IMC-3C5) as product development candidate for oncology indications

Circadian Technologies Limited (ASX:CIR) announces today that its 100% owned subsidiary company Vegenics Limited has been advised by its licensee, New York based ImClone Systems Incorporated, that ImClone has designated the human therapeutic antibody IMC-3C5 as a formal pre-clinical development candidate for oncology indications. IMC-3C5 is an antibody which neutralises VEGFR-3. Vascular endothelial growth factor, or VEGF, and its receptors play a pivotal role in normal and pathologic angiogenesis and are expressed in many solid and hematologic malignancies.

ImClone has exclusive rights from Vegenics to develop the VEGFR-3 antibody in return for annual license fees and royalties on potential future product sales.

ImClone will now undertake formal pre-clinical studies of IMC-3C5. The first indications to be investigated will be in solid tumours.

Scientists from ImClone together with Vegenics’ collaborator scientists recently published in the prestigious scientific journal Nature that VEGFR-3 has a previously unknown role in directing the formation of blood supply to tumours as well as to the retina (i.e. it has a role in signalling blood vessel ‘sprouting’ - angiogenesis).

Using antibodies to block both receptors VEGFR-2 and VEGFR-3, the research team found an additive effect in inhibition of tumour growth in animals by effectively starving the cancer cells. Prior to this finding VEGFR-3’s only known role was in mediating the growth of lymphatic tissues.

The findings as published in Nature[1] indicate that the efficacy of existing anti-angiogenic therapies, such as the multi-billion dollar cancer drug Avastin®, may be improved by the addition of agents which inhibit VEGFR-3 mediated angiogenesis such as VEGF-C or VEGF-D antibodies.

Circadian and Vegenics CEO, Mr Robert Klupacs commented “ImClone is one of the most experienced developers of therapeutic antibodies for cancer therapies in the world today. Being able to partner the development of our VEGFR-3 technology with ImClone is a tremendous validation for our technology.”

1 Nature 2008 Jul 31; 454 (7204); 656-60 Epub 2008 June 25.

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

Circadian Technologies Limited ABN 32 006 340 567

“It is also a key step in Circadian’s strategy to becoming an international biologics drug development company based on our VEGF technology.”

About Circadian Technologies Limited

Circadian (ASX:CIR) is repositioning itself as a biologics drug developer to take advantage of the significant intellectual property portfolio around Vascular Endothelial Growth Factor (VEGF) C and D that it has accumulated in its unlisted subsidiary Vegenics. The applications for the VEGF technology, which functions in regulating blood supply, are substantial and broad. Circadian is focussed on developing novel anti-cancer therapeutics in the first instance. Circadian, through Vegenics, has existing relationships with licensees UK company Ark Therapeutics Group plc (LSE: AKT) and ImClone Systems Inc (NASDAQ:IMCL). Ark’s product Trinam®, a treatment for vascular grafts associated with renal dialysis, is expected to enter Phase 3 clinical trials in 2008 and ImClone is developing a lead antibody to VEGFR-3 for the treatment of solid tumours. The VEGF patent portfolio developed by LICR and Licentia has been assigned to Circadian’s subsidiary Vegenics. Vegenics also has rights to CoGenesys Inc/Human Genome Sciences Inc’s VEGF-C IP.

About VEGF Technology

In Cancer

The clinical and outstanding commercial success of Avastin®, an antibody that blocks the activity of VEGF-A, clinically validated anti-angiogenic drugs as an effective means of inhibiting solid tumour growth. By blocking the interaction of VEGF-A with its receptors, primarily VEGFR-2, the multi-billion dollar cancer therapeutic slows tumour growth by inhibiting blood vessel recruitment into the tumour, effectively starving tumours of essential nutrients and oxygen required for growth. Avastin® which is sold by Genentech Inc and Hoffman-La Roche had US sales in 2007 of $US2.3B and worldwide sales in excess of $US6B.

VEGF-C and VEGF-D inhibitors, key therapeutics in the portfolio of Circadian’s unlisted subsidiary Vegenics, blocks the alternative ligands for VEGFR-2. As such, they have the potential to block blood vessel growth in tumours resistant to anti-VEGF-A therapy and when used in combination with drugs like Avastin® , may completely shut down angiogenesis (the growth of blood vessels) mediated by VEGFR-2, resulting in greater clinical efficacy.

VEGF-C and VEGF-D also bind and activate VEGFR-3 which drives lymphatic vessel and tumour-associated blood vessel growth. Inhibitors of VEGF-C, VEGF-D and VEGFR-3 thus have therapeutic potential to inhibit not only primary tumour growth through their anti-angiogenic activities, but to also inhibit tumour spread or metastasis via the lymphatic vessels - a mechanism of tumour dissemination that is often the deadliest aspect of many tumour types and a mechanism that is not effectively blocked by anti-VEGF-A or anti-VEGFR-2 therapeutics.

Other Disease Applications

VEGF Technology also has applications in other diseases, where shutting down angiogenesis and/or lymphatic vessel growth is important, such as eye diseases including age related macular degeneration and diabetic retinopathy.

For further information:

Investors Robert Klupacs Managing Director +61 (0) 3 9826 0399