Opthea Ltd — Capital/Financing Update 2008

Jul 14, 2008

ASX and Media release

15 July 2008

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Circadian to secure 100% ownership of Vegenics

Ludwig Institute for Cancer Research and Licentia Ltd to become substantial shareholders of Circadian on sale of their minority interest in Vegenics to Circadian

Australian biotechnology company Circadian (ASX:CIR) will move to 100 per cent ownership of its subsidiary Vegenics as part of its strategy to move from a biotech incubator to a biologics drug development company.

Circadian has signed a binding memorandum of understanding with its cofounders of Vegenics, the international Ludwig Institute for Cancer Research (LICR) and Licentia Limited (Licentia), to acquire their combined 33 per cent interest in Vegenics.

Circadian will take complete control of the rights to, and development of, Vegenics’ VEGF-C, VEGF-D and VEGFR-3 technologies (VEGF technology) which are primarily for the treatment of cancer as well as for other high unmet medical need disease indications.

Vascular endothelial growth factor proteins C and D help regulate the growth of new blood vessels. Blocking these proteins around tumours may inhibit the growth of existing tumors and prevent the spread of new cancer cells.

Consideration for the acquisition of LICR’s and Licentia’s combined interest in Vegenics is to be settled in two tranches:

• Tranche 1:

• 5,117,430 Circadian shares will be issued to LICR (2,589,635 shares) and Licentia (2,527,795 shares). This will equate to a combined interest of 11.3% after the share issue;

• 50% of the shares will be escrowed for a period of 12 months from date of issue. The remaining 50% will be escrowed for 24 months; and

• o a cash payment of $650,000 to Licentia.

• Tranche 2:

• A further 1,155,000 Circadian shares will be issued to LICR (532,455 shares) and Licentia (622,545 shares) on the earlier to occur of certain product development milestones or the second anniversary of the date of Circadian’s acquisition of LICR’s and Licentia’s interests in Vegenics (subject to shareholder approval, if required, under the ASX Limited Listing Rules).

President of LICR, Mr Ed McDermott Jr., said: “We are very excited to further cement our relationship with Circadian now that it will be focussed on exploiting the VEGF technology, much of which was originally developed by scientists from the Ludwig Institute for Cancer Research and the University of Helsinki.”

“We recognise that the internationally credentialed Circadian team backed by its strong cash position will enable Circadian to drive its drug development strategy.”

Level 1, 10 Wallace Avenue, Toorak ~~Page 1 of 2~~ , Victoria 3142, Australia P: +61 (3) 9826 0399 Circadian Technologies Limited F: +61 (3) 9824 0083 ABN 32 006 340 567 www.circadian.com.au

“We are very pleased to have the opportunity to become key shareholders in Circadian.”

CEO of Licentia, Mr Kari Paukkeri said: “We have been deeply impressed by how far Circadian has been able to advance the VEGF technology to date.”

“We look forward to participating in the ongoing evolution of Circadian as one of its major shareholders.”

LICR and Licentia will also be entitled to nominate one director to join the board of Circadian.

The transaction is expected to close around the end of July 2008.

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 (3) 9826 0399

Media inquiries : Matthew Horan Cato Counsel +61 (2) 9360 6606; +61 (0) 403 934 958

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