Circadian Technologies

Circadian Technologies Limited is an emerging leader in the field of angiogenesis-based treatments for cancer. Focusing on a class of drug targets called Vascular Endothelial Growth Factors (VEGFs), we seek to develop truly novel therapies to extend and improve the lives of cancer sufferers. Circadian’s strengths are the following:

Intellectual Property – Circadian owns the world’s largest and most comprehensive intellectual property estate covering the key angiogenesis targets VEGF-C, VEGF-D and VEGFR-3. These IP rights include over 50 patent families, 200 granted patents and 500 patents pending worldwide.

Pipeline – Circadian has an internal product pipeline comprising biologics-based drugs to three angiogenesis targets. Circadian’s most advanced program, VGX-100, an antibody-drug targeting VEGF-C, is expected to enter clinical trials in 2011.

Partners – Circadian has commercial partnerships with other leading biotechnology companies for the development of products based on the company’s technology. Ark Therapeutics is evaluating Trinam® in Phase 3 clinical trials. ImClone Systems, a subsidiary of Eli Lilly and Company, is conducting preclinical studies of an anti-VEGFR-3 antibody for cancer treatment.

Our Technology

In order to grow larger than 1 mm in size, tumours secrete growth factors of the VEGF family to stimulate the development of supporting blood vessels (upper image).  Circadian’s anti-body-based drugs in development block two key factors, VEGF-C and VEGF-D, potentially inhibiting blood vessel development (lower image).  Circadian’s drugs are also intended to block supporting lymphatic vessel development, thereby preventing cancer spread (metastasis).

Trinam®

Trinam® is a VEGF-D-based gene therapy product intended to extend the lifetime of access grafts used in kidney dialysis. Patients requiring chronic kidney dialysis typically undergo surgery for the placement of a plastic tube or “access graft” in the forearm. However, these grafts have a tendency to become blocked by scar tissue. Trinam® greatly reduces the tendency of access grafts to scar and become blocked. In a Phase 2 clinical trial, Trinam® increased the average useful lifetime of access grafts from 4.5 months to 17 months. This significant improvement may lead to fewer surgeries, reduced risk of complications and improved quality of life for dialysis patients. Circadian’s partner, Ark Therapeutics, is initiating a Phase 3 clinical trial of Trinam® to support an application for marketing authorization. The potential market for Trinam® is about US$500 million.

VEGFR-3 antibody

Circadian’s partner, ImClone Systems, is developing an anti-VEGFR-3 antibody as treatment for solid tumours. In November 2008, the antibody was formally designated a product development candidate. In June 2008, an article by Circadian’s collaborator, Prof. Kari Alitalo in the leading scientific journal Nature demonstrated that anti VEGFR-3 antibodies significantly inhibited blood vessel supply to tumours and blocked tumour growth. Circadian receives annual milestone payments and will receive royalties on the sale of the VEGFR-3 antibody product. ImClone Systems is now a subsidiary of Eli Lilly and Company.
   
VGX-100

VGX-100 is a fully human monoclonal antibody targeting the VEGF-C protein. Preclinical studies have demonstrated that it inhibits the growth of a variety of tumour types including prostate and glioma. Additionally, VGX-100 has been shown to dramatically reduce the frequency of tumour metastatic spread in certain animal models. Preliminary toxicology studies have identified no serious adverse effects of VGX-100 treatment in animals. VGX-100 is covered by a variety of US and international patents extending beyond 2022. VGX-100 is currently undergoing IND enabling preclinical studies and manufacturing scale-up. Circadian intends to initiate human clinical trials of VGX-100 in 2010.

VGX-200 series

The VGX-200 series is a set of humanized monoclonal antibodies targeting the VEGF-D protein. Circadian is currently evaluating a number of lead candidates with high binding affinity for VEGF-D (Kd below 1nM). Selection of a product development candidate and initiation of formal preclinical studies will occur in the first half of 2009. Circadian intends to initiate human clinical trials of VGX-200 in 2011. Patent coverage of the VGX-200 extends beyond 2025.

VGX-300

VGX-300 is a soluble form of VEGFR-3. It functions by capturing and blocking the activity of both VEGF-C and VEGF-D. VGX-300 consists of extracellular domains of human VEGFR-3 fused to the Fc-domain. In addition to cancer, Circadian is evaluating VGX-300 in models of eye disease. Circadian’s patent protection covering soluble VEGFR-3 extends beyond 2025. Circadian plans to initiate human clinical trials of VGX-300 in 2011.

Technology

Please CLICK HERE to see how Circadian's technology works.

Circadian is developing a variety of drugs to block the interaction between VEGF Receptor-3 (VEGFR-3)[for further information please CLICK HERE] and its ligands VEGF-C [for further information please CLICK HERE] and VEGF-D [for further information please CLICK HERE]. Drugs blocking this pathway would represent a novel and potentially revolutionary treatment approach for cancer patients. VEGFR-3 inhibitors may treat cancer by two mechanisms: First, inhibition of the ligands VEGF-C and VEGF-D blocks tumour angiogenesis, suppressing blood vessel development, starving tumours of oxygen and nutrients needed to grow. Second, tumours are known to metastasize through the lymphatic system. Tumour metastasis is often the direct factor leading to patient mortality. Blocking VEGFR-3 activation stops lymphangiogenesis, which in turn reduces the ability of tumours to spread. This approach to cancer treatment is potentially more effective than chemotherapy and may have greatly reduced side-effects. Circadian holds an extensive intellectual property position protecting its rights as the exclusive developer of this class of drugs.

Robert Klupacs, MAIPA
Managing Director & CEO

Natalie Korchev, ACA
CFO, Company Secretary and Head of Operations

Alexander Szabo, PhD, MBA
Head of Business Development

Megan Baldwin, PhD
Head of Preclinical Research & Development

Richard Chadwick, PhD
Head of Intellectual Property

Susan Foran, M Pharm
Head of Toxicology and Project Management

Mike Gerometta, PhD
Head of CMC Development

No info available.