Clinical Candidates
Astex's current development programmes address validated therapeutic targets in cell cycle control and tumour cell proliferation - cyclin-dependent kinases (CDKs), aurora kinases, JAK2 and heat shock proteins (HSPs).
AT7519
Astex's lead drug candidate, AT7519 is a potent cell cycle inhibitor that targets key CDKs. AT7519 entered clinical development during the second half of 2005 in a Phase I dose escalation study designed to evaluate the safety and tolerability of the compound delivered intravenously in patients with advanced solid tumours. A Phase I/IIa clinical study in patients with haematological tumours started during Q4 2006 and a further Phase I clinical study in patients with solid tumours commenced during Q1 2007.
AT9283
AT9283 is an inhibitor of mitosis (cell division) and is the second most progressed drug candidate in the Astex portfolio having received both IND and CTA approvals to commence clinical studies in the USA and Europe during 2006. Patient dosing began in a Phase I/IIa clinical study in patients with haematological tumours in Q3 2006 in the US and a Phase I clinical study in patients with solid tumours commenced at two sites in the UK in Q4 2006 with a further Phase I study in patients with solid tumours commencing at study centres in Canada in Q1 2007 . AT9283 is a potent inhibitor of aurora kinases A and B, JAK2 and abl and has been shown to arrest tumour growth in a range of tumour models. The aurora kinases play a key role in mitotic checkpoint control in cell division and are over-expressed in many human tumours. JAK2 activity has recently been identified as a key driver of several haematological malignancies and as such its inhibition has considerable potential in the treatment of a spectrum of myeloproliferative diseases.
AT9311
AT9311 is an orally active cell cycle inhibitor which inhibits selected CDKs with a differentiated biological profile in comparison to Astex's other clinical candidates. AT9311 was selected for formal preclinical development in 2005. The compound is exclusively licensed to Novartis under a Collaboration and License Agreement announced in December 2005.
AT13387
AT13387 is a potent non-ansamycin inhibitor of Heat Shock Protein 90 (HSP90). HSPs are molecular chaperones that enable folding, processing and/or maturation of a variety of so called ‘client proteins’. HSP90 is a co-chaperone for a number of client proteins which are known oncogenes associated with cancer (e.g., raf-1, PKB, cdk4, Met, POLO-1, mutant p53). An effective inhibitor of HSP90 could provide for a broad spectrum agent in clinical oncology and for a molecularly-targeted agent for cancers dependent on a subset of mutant and wild type client proteins. AT13387 is Astex's fourth clinical candidate and was selected for formal preclinical development in June 2006.