Cancer: HSP990
Summary
The scientific rationale for Hsp90 as a therapeutic cancer target is based on the hypothesis that many of the signalling proteins that behave aberrantly in cancer cells require Hsp90 as a chaperone molecule to ensure that they are maintained in an active form.
Inhibition of Hsp90 is believed to have significant potential in the treatment of a broad range of cancers. Vernalis has a research collaboration with Novartis utilising Vernalis’ structure-based design technology to identify potent and specific inhibitors of this novel drug target for use against various cancers. Novartis has recently advanced the first compound arising from the collaboration (NVP-AUY 922) into Phase I clinical development.
Background
Hsp90 is essential for the stability and function of several oncogenic proteins associated with key sites of genetic deregulations in human cancer. It is known to be over expressed in human tumours and has the potential to inhibit the hallmark traits of cancer (cell growth, signalling apoptosis avoidance, limitless proliferation, angiogenesis, metastasis). Proof of concept for this target has been established in human tumour xenograft models and in the clinic with first-in-class natural product inhibitors derived from geldanamycin.
Project Status
Vernalis has a research collaboration with Novartis to investigate inhibitors of Hsp90. The companies have two programmes in pre-clinical development; an intra-venous (NVP-AUY 922) and an oral follow on.
NVP-AUY922 is a novel Hsp90 inhibitor for the treatment of a range of cancers, and is being developed with Novartis. It is the first compound from the collaboration with Novartis to enter clinical testing and is currently being evaluated by Novartis in a Phase I programme in patients in a variety of solid tumours and haematological cancers. Vemalis will receive milestone payments as it progresses through development, and royalty payments upon commercialisation.