VEGF-C And VEGF-D Identified As Biomarkers For Avastin Resistance In Colorectal Cancer Patients

- Data presented at American Society of Clinical Oncology ("ASCO") Annual meeting in Chicago
- Data obtained from 42 patients treated with chemotherapy (5-flourouracil and irinotecan) plus bevacizumab (Avastin®) enrolled in a Phase 2 clinical trial
- VEGF-C shown to be significantly raised just prior to and at the time of disease progression (treatment resistance), while VEGF-D shown to be significantly increased after disease progression.
- Data supports concept of targeting additional VEGF family proteins to improve treatment outcomes

MELBOURNE, Australia, June 6, 2011 /PRNewswire/ - Circadian Technologies Limited (ASX: CIR) announced today the presentation of data at the American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago USA associating resistance to Avastin® with increases in plasma VEGF-C and D concentrations.

The poster presentation entitled "The Association of Alternate VEGF Ligands with Resistance to Anti-VEGF Therapy in Metastatic Colorectal Cancer (mCRC)" is available on Circadian's website at

Resistance to Avastin® is a frequent occurrence in the treatment of certain cancers with resulting loss of response and disease progression. The study, which was led by Drs Lieu and Kopetz at The University of Texas MD Anderson Cancer Center showed that increases in VEGF-family markers in patients with metastatic colorectal cancer are associated with Avastin® resistance. In particular, VEGF-C increases were seen in patients prior to and at the time of disease progression while receiving Avastin® and chemotherapy.

Mr. Mark Sullivan, Head of Development for Circadian, said: "The clinical data provide an important insight into the role that VEGF-C plays in the development of Avastin® resistance. The findings are supportive of our strategy for combining our VEGF-C antibody (VGX-100) with Avastin® to seek better outcomes for patients. The data also provide further rationale for the development of VEGF-C and/or VEGF-D based biomarker tests to monitor cancer therapy."

Scott Kopetz, M.D.,Ph.D. of MD Anderson said: "Our data show that the VEGF-family ligands, other than VEGF itself, are associated with Avastin®-containing chemotherapy resistance in patients with metastatic colorectal cancer. We are planning prospective confirmatory studies to further evaluate and validate these findings."

Mr. Robert Klupacs, CEO of Circadian Technologies, said: "We are extremely heartened by the ever increasing amount of clinical data validating VEGF-C and D as important therapeutic targets. We look forward to continuing our excellent collaboration with Dr Kopetz and colleagues at MD Anderson, and to the commencement of clinical trials in cancer patients with our VEGF-C antibody VGX-100."

Circadian's wholly owned subsidiary, Vegenics, owns worldwide rights to an extensive intellectual property portfolio covering angiogenesis targets VEGF-D, VEGF-C and the receptor protein VEGFR-3.

About Circadian Technologies Limited

Circadian (ASX:CIR) is a biologics drug developer focusing on cancer therapies. It controls exclusive worldwide rights to a significant intellectual property portfolio around Vascular Endothelial Growth Factor (VEGF) C and D. The applications for the VEGF technology, which functions in regulating blood and lymphatic vessel growth, 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 and Company, including the antibody-based drug IMC-3C5 targeting VEGFR-3.

About Circadian's pipeline of treatments for cancer

The clinical and commercial success of Avastin®, an antibody that blocks the activity of VEGF-A, clinically validated antiangiogenic 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 2009 of US$5.7 billion and worldwide sales in excess of US$8.6 billion. Avastin® is approved by the US FDA in the following indications: metastatic colorectal cancer, nonsquamous-cell lung cancer, metastatic breast cancer, glioblastoma, metastatic renal cell carcinoma.

The VEGF-C inhibitor, VGX-100, a key therapeutic in Circadian's portfolio, block this alternative stimulator for VEGFR-2. As such, it has 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 along with the molecule 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 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.

Inherent risks of Investment in Biotechnology Companies

There are a number of inherent risks associated with the development of pharmaceutical products to a marketable stage. The lengthy clinical trial process is designed to assess the safety and efficacy of a drug prior to commercialisation and a significant proportion of drugs fail one or both of these criteria. Other risks include uncertainty of patent protection and proprietary rights, whether patent applications and issued patents will offer adequate protection to enable product development, the obtaining of necessary drug regulatory authority approvals and difficulties caused by the rapid advancements in technology. Companies such as Circadian are dependent on the success of their research and development projects and on the ability to attract funding to support these activities. Investment in research and development projects cannot be assessed on the same fundamentals as trading and manufacturing enterprises. Thus investment in companies specialising in drug development must be regarded as highly speculative. Circadian strongly recommends that professional investment advice be sought prior to such investments.