Opthea Ltd — Regulatory Filings 2009

Dec 21, 2009

ASX release

22 December 2009

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Commencement of Circadian non-executive director share plan

Circadian advises that its Non-Executive Director Share Plan (NED Share Plan), which was approved by shareholders at the Company’s 2008 Annual General Meeting, has now been implemented.

Under the NED Share Plan, the non-executive directors may elect to sacrifice their director's fees to receive ordinary shares in Circadian (Plan Shares). Plan shares will either be issued by Circadian or purchased on the ASX on behalf of participants by a third party.

Participation in the NED Share Plan is optional. Non-executive directors may opt in or out of the NED Share Plan and set the level of their participation every six months. The minimum participation level is 20% of a director's remuneration. There is no maximum participation limit.

Importantly, the NED Share Plan does not entitle any non-executive director to additional remuneration, all Plan Shares will be acquired at market value and, subject to limited exceptions, all directors will be required to hold their Plan Shares for a minimum of three years.

The Board anticipates that the first issue of Plan Shares under the NED Share Plan will be made on or about 26 February 2010. For the first six month's operation of the NED Share Plan, Plan Shares to a value of around $45,000 are expected to be acquired on behalf of the participating non-executive directors.

The terms of the NED Share Plan are available on the Company's website at www.circadian.com.au.

Company enquiries

Robert Klupacs Managing Director - Circadian Tel: +61 (0) 3 9826 0399 or robert.klupacs@circadian.com.au

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

About Circadian Technologies Limited

Circadian (ASX:CIR) is a biologics drug developer utilising the significant intellectual property portfolio around Vascular Endothelial Growth Factor (VEGF) C and D that it has accumulated in its unlisted wholly owned subsidiary Vegenics. The applications for the VEGF technology, which functions in regulating blood supply, are substantial and broad. Circadian’s internal product development programs are focussed on novel anti-cancer therapeutics for large unmet needs. Circadian has also licensed rights to some parts of its intellectual property portfolio for the development of other products to ImClone Systems (a wholly owned subsidiary of Eli Lilly & Company - NYSE: LLY). ImClone Systems is currently developing an antibody-based drug targeting VEGFR-3 for the treatment of solid tumours.

The VEGF patent portfolio developed by the Ludwig Institute for Cancer Research Ltd and Licentia Ltd has been assigned to Vegenics. Vegenics also has rights to CoGenesys Inc/Human Genome Sciences Inc’s VEGF-C intellectual property.

About Circadian’s pipeline of treatments for 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, now part of Roche, had U.S. sales in 2008 of US$2.7 billion and worldwide sales in excess of US$7.5 billion.

VEGF-C and VEGF-D inhibitors, VGX-100, VGX-200 and VGX-300, are key therapeutics in the portfolio of Circadian’s unlisted subsidiary Vegenics, which block these alternative stimulators 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 are also the only known proteins to 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.