• Arises out of research collaboration with Novartis
• Potentially effective against a range of cancers
• Maximum tolerated dose should be next development milestone

This is a follow-up compound, part of the current collaboration between Vernalis and Novartis, which entered clinical testing in 2009. Hsp90 inhibitors such as HSP990 have the potential to be effective against a range of cancers.

Inhibiting heat shock proteins

may inhibit tumour growth

Heat shock proteins such as Hsp90 are molecular chaperones, with their expression increased in stressed tissues. They may help tumour cells survive in hostile microenvironments and tolerate internal mutations, so driving tumour growth. Inhibiting such proteins may therefore inhibit growth in a wide range of tumour types.

Over-expressed in cancer cells, Hsp90 is essential for the stability and function of several proteins that are mutated into cancer-driving forms in tumours. Inhibition of Hsp90 has the potential to stop cancer progression at multiple levels by inhibiting cell growth and limitless proliferation, promoting cell death, reversing angiogenesis and restricting invasion and metastasis.

A range of pre-clinical studies confirm the theoretical effect of Hsp90 inhibition. 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. HSP990 has now moved into the clinical studies phase of development.

In July 2009 Novartis announced that it was initiating a Phase I clinical study with this compound. This triggered a milestone payment to Vernalis of US$1.5 million.

Pre-clinical studies completed. Phase I clinical studies now being undertaken by Novartis. Vernalis receives milestone payments during development and royalties on commercialisation of HSP990.