Opthea Ltd — Capital/Financing Update 2008

Jun 10, 2008

ASX and Media release

11 June 2008

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Circadian establishes a world class team to develop cancer drugs from its unique VEGF technology portfolio

• Strategy to move from biotech incubator to drug developer centres on cancer drugs using VEGF technology (VEGF-C, VEGF-D, VEGFR-3)

• Product Development Review Group formed utilising international drug development experience of Australian expats

• Expanded and well credentialed management team

• Circadian Group has cash in the bank of $46m and listed investments worth $12.5m.

Circadian Technologies Limited (ASX:CIR) has built up a team of highly qualified, internationally credentialed people to drive its strategy of moving from a biotech incubator to a biologics drug development company.

Circadian has a particularly strong cash position with $46 million (consolidated) as well as $12.5 million in shares in listed companies enabling the development of its VEGF technology portfolio and strength in negotiating future licence arrangements.

The company has established a Product Development Review Group whose members hold or held senior positions with large pharmaceutical or biotechnology companies. They are Dr Errol Malta, Dr George Morstyn, Dr Russell Howard and Mr Carlo Montagner. These people bring extensive experience in international drug development to Circadian in toxicology, clinical development, oncology and antibody experience.

Circadian’s drug development strategy is based on the exploitation of its VEGF-C, VEGF-D and VEGFR-3 technologies (VEGF Technology) of its subsidiary company Vegenics Limited (67 per cent owned by Circadian). This is the company’s strongest asset and will become the centre of its business via commercial development of treatments for cancer and other diseases.

Dr Russell Howard, CEO of Nasdaq listed biotechnology company Maxygen Inc said “I was attracted to joining Circadian’s Review Group as the company through its VEGF Technology has a world class opportunity to develop improved cancer therapies.”

The review group’s Chairman Dr Errol Malta said “I am excited by the potential of Circadian’s VEGF technology which I believe the assembled team has the skills and experience to develop into exciting clinical candidates for the treatment of cancer.”

Existing multi-billion dollar anti-cancer drug Avastin® is a humanised antibody against VEGF-A (an anti-angiogenic therapy) which is sold by Nasdaq listed Genentech Inc and

Level 1, 10 Wallace Avenue, Toorak Page 1 of 4 , 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

Hoffman-La Roche. This drug, which is used in combination with chemotherapy, starves tumours of vital oxygen and nutrients and slows the tumour growth by inhibiting one part of the VEGF receptor pathway (VEGFR-2).

Targeted VEGF-C and VEGF-D have the potential to block another key receptor in that pathway (VEGFR-3) and either alone or in combination with a VEGF-A inhibitor such as Avastin® may provide more effective anti-cancer treatments.

Product Development Review Group and Management Team

The Review Group comprises:

• Dr Errol Malta, whose credentials include working with the largest biotech company in the US, Amgen Inc, for more than 10 years, is chairman of the Review Group. He served as Product Development Team Leader for eight of those years responsible for global drug development and commercialisation in the US, EU and Japan. He was responsible for successful new-molecule IND submissions to the US FDA and other regulatory agencies and for various early stage and late stage human clinical trials.

• Dr George Morstyn former Senior Vice-President and Head of Development at Amgen Inc. He was a member of the executive committee and responsible for global preclinical and clinical development as well as regulatory affairs. Dr Morstyn trained in medical oncology at the National Cancer Institute in the US and was Head of the Clinical Program of the Ludwig Institute for Cancer Research in Melbourne.

• Dr Russell Howard is CEO of US Nasdaq listed Maxygen Inc, a company focussed on human therapeutics with several programs in protein pharmaceuticals. Dr Howard also served as the president and scientific director of Affymax Research Institute, an institute employing combinatorial chemistry and high throughput target screening to discover drug leads.

• Mr Carlo Montagner , is President Oncology Pan Asia for Nasdaq listed Abraxis Bioscience Inc. Carlo has a wealth of experience in heading global oncology businesses for blockbuster chemotherapeutic products. He is former Executive Vice President & Global Head of Schering AG/Berlex Labs USA Oncology Business Unit. He has also held various positions at Aventis Pharma including Head of Oncology & Cardiovascular Business Unit at Sanofi-Aventis Japan and Global Head of Taxanes chemotherapy portfolio.

Circadian Managing Director, Robert Klupacs said: “It is very exciting that these highly experienced Australian expats and former expats, who have gained enormous drug development experience overseas, share our belief in the potential of our technology, and the vision for Circadian to become a prominent international biologics company.”

The Review Group will work with the well-credentialed and experienced management team that has been expanded by Robert Klupacs.

The Circadian management team comprises:

Natalie Korchev , CFO, who has recently taken on the additional role of Head of Operations and has been with Circadian for eight years.

Alex Szabo , Phd, MBA, has extensive experience in business development and marketing with leading US biotechnology companies as well as with Australian biotechnology companies, will join the company in July as Head of Business Development.

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Megan Baldwin , PhD, recently joined from Genentech Inc, is the company’s Scientific Affairs and Projects Manager with more than 10 years experience in researching and developing angiogenesis and therapeutic strategies for oncology indications.

Richard Chadwick , PhD in biochemistry, is a qualified European and Australian Patent Attorney with more than 15 years experience. He is the company’s Intellectual Property Manager.

Sue Foran , has a Master of Pharmacy and extensive experience in the development of nonclinical and clinical development plans and protocols with over 15 years experience in the pharmaceutical and biotechnology industries as well as with clinical research organisations. She is the company’s Product Development Manager,

The company has also retained highly experienced consultants to work with the management team. These include Dr Ralph Smalling, Dr Richard Morgan and Dr Mike Gerometta.

Mr Smalling has held senior positions with Amgen Inc for over 23 years including in regulatory affairs. He has overseen the development of more than 40 antibody and recombinant protein therapies projects through various stages (preclinical to marketing).

Dr Morgan has more than 25 years experience in pharmaceutical research and development including Head of Toxicology at GlaxoWellcome (now GlaxoSmithKline).

Dr Gerometta has more than 17 years experience in the Australian biotechnology industry in particular in antibody manufacturing and development while at Agenix Limited.

Drug Development and Commercialisation Strategy

There is a breadth of product development opportunity using the VEGF Technology. The company is focussing on the development of several antibody and protein products for the treatment of certain cancers, eye disease and other niche disease indications.

The objective is to generate value by undertaking pre-clinical and early human clinical development and partnering further development of major therapeutic indications while retaining the rights to selected niche/orphan indications.

Circadian also has licensees to certain aspects of its VEGF Technology: UK company Ark Therapeutics Group plc (LSE: AKT) and ImClone Systems Inc (NASDAQ: IMCL).

The relevance and importance of this technology has been recognised by these licensees to develop the following products:

• Ark Therapeutics is developing the product Trinam®, a treatment for vascular grafts associated with renal dialysis. This is scheduled to enter Phase III studies during the latter half of 2008. Trinam® is a combination of a VEGF-D gene packaged in an adenoviral vector and a bio-degradable local drug delivery device.

• ImClone is developing a lead antibody to VEGFR-3 for the treatment of solid tumours. ImClone has published a number of studies showing efficacy in a range of animal cancer models.

Circadian earns a minimum annual royalty from Ark Therapeutics and an annual license fee from ImClone and will receive payments on achievement of product development milestones as well as royalties on sales.

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The team established by Circadian is in the process of rolling out its implementation plan to achieve its drug development and commercialisation objectives and the company will advise of developments with respect to this as they occur over the coming months.

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 95

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