Circadian's VGX-100 human antibody improves corneal graft survival

Circadian Technologies Limited (ASX: CIR, OTCQX: CKDXY) announced today the publication of data in the scientific journal, Investigative Ophthalmology & Visual Science (IOVS), showing that VEGF-C expression is markedly up-regulated in corneal graft rejection. Importantly the data also showed that VEGF-C blockade, through administration of Circadian's lead development candidate VGX-100, a human antibody against VEGF-C, significantly improved corneal graft survival in an animal model. The data indicates a major new therapeutic opportunity for VGX-100 to improve corneal graft survival.

The manuscript entitled "Vascular Endothelial Growth Factor-C Promotes Alloimmunity by Amplifying Antigen Presenting Cell Maturation and Lymphangiogenesis" IOVS Papers in Press, published as manuscript iovs.11-8668 is accessible via the Investigative Ophthalmology & Visual Science website (www.iovs.org).

The Eye Bank Association of America reports that more than 40,000 corneal transplants are performed annually in the United States (Statistical Report on Eye Banking activity for 2008. Eye bank Association of America; 1-25, 2009). While most grafts take very well it is estimated that between 10 and 30% of grafts will be rejected within 6-12 months, particularly in "at-risk" patients who have a highly vascularized eye bed or in whom a graft has previously failed. Improving graft survival in these "at-risk" patients is a major unmet clinical need.

The study, which was led by Professor Reza Dana and Dr Amir R. Hajrasouliha, of the Schepens Eye Research Institute, Harvard Medical School Department of Ophthalmology, showed that VEGF-C was markedly up-regulated in rejected corneas and that administration of VGX-100 was able to significantly improve corneal graft survival.

Prof Reza Dana, MD MSc MPH Claes Dohlman Chair in Ophthalmology, Professor of Ophthalmology, Harvard Medical School, Co-Director of Research at Schepens Eye Research Institute and senior author of the study said, "Corneal grafting can have enormously positive results for patients who may otherwise become blind. While grafting success has improved significantly over the past 20 years there are still a large number of grafts which continue to fail. Our findings demonstrating that VEGF-C is up-regulated in graft failure and that blockade of VEGF-C could significantly improve graft survival identify VEGF-C blockade as an exciting new therapeutic possibility for improving corneal graft survival."

Mr. Robert Klupacs, CEO of Circadian Technologies, said: "This very exciting data generated by our collaborators at Schepens provides a significant new therapeutic development opportunity for our VGX-100 program in addition to our ongoing clinical oncology programs. We are currently undertaking additional preclinical studies with VGX-100 in the corneal grafting setting with the aim to commence clinical trials in H1 2013."

Circadian's wholly owned subsidiary, Vegenics Pty Ltd, owns worldwide rights to an extensive intellectual property portfolio covering the angiogenesis and lymphangiogenesis targets VEGF-C, VEGF-D and the receptor protein VEGFR-3. Vegenics has also been granted exclusive worldwide rights to intellectual property filed by Schepens Eye Research Institute covering the use of anti-lymphangiogenc molecules for the treatment of Dry Eye Disease.