ZD6126

ZD6126, originally designated ANG453, is a vascular disrupting agent that acts via tubulin depolymerisation. In an extensive series of preclinical studies this unique compound was shown to selectively shut down tumour blood flow at well-tolerated doses, inducing massive necrosis, particularly within central regions of the tumour. In combination studies, ZD6126 was further shown to enhance the anti-tumour activity of ionising radiation, cytotoxic chemotherapy, targeted therapy and various angiogenesis inhibitors. ZD6126 and its analogues were licenced to AstraZeneca in 1998 for oncology indications. A second licenced compound, selected by AstraZeneca and designated AZ4440 has completed preclinical studies. Several Phase I studies have now been completed and the published results provide convincing evidence that in humans too, ZD6126 can reduce and/or shut down tumour blood flow at tolerated doses. Phase II studies were initiated but were placed on hold pending the results of additional laboratory studies designed to investigate improved methods of administration. These have now been completed and results suggest a clear path for the rapid clinical development of ZD6126 and its analogues.

MN029

MN029 is a novel tubulin-binding vascular disrupting agent with a structure distinct from that of other similar compounds. In preclinical studies MN029 has demonstrated powerful induction of necrosis and antitumour activity both as a single agent and in combination with radiotherapy and chemotherapy. MN029 was licenced to MediciNova Inc. in 2002 and has recently completed Phase I clinical trials.

ANG500 series

This series includes compounds with activity against tumour models resistant to first-generation vascular disrupting agents. Also included are compounds with a dual mode of action - vascular disrupting activity plus NOS inhibition. It is anticipated that these compounds may possess enhanced clinical activity in both the oncology setting and in the treatment of ocular neovascularisation disorders.

ANG700 series

These are Hypoxia Activated Prodrugs arising from our collaboration with the Gray Cancer Institute. We expect a number of development candidates to arise from this promising series within the next year.

All images and text © Angiogene Pharmaceuticals Ltd. Last updated July 15th., 2007