A novel intravenous Hsp90 inhibitor with the potential to target a range of cancers, discovered during a research collaboration with Novartis. Vernalis regained the rights to luminespib (AUY922) in December 2014 following Novartis' decision to cease all development work. Vernalis is reviewing the data, before deciding on next steps and how best to take the programme forward.
- Arises out of research collaboration with Novartis
- Potentially effective against a range of cancers
This molecule arose out of a research collaboration, originally between Vernalis and The Institute of Cancer Research and Cancer Research Technology and then with Novartis, started in 2004. Hsp90 inhibitors such as luminespib (AUY922) have the potential to be effective against a range of cancers
Vernalis is one of the world leaders in the cutting edge fragment-based drug discovery techniques which were employed in the discovery of luminespib (AUY922).
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. Luminespib (AUY922) has now moved into the clinical studies phase of development.
Novartis evaluated luminespib (AUY922) in a number of Phase I and Phase II studies in patients with solid tumours and haematological cancers. In December 2009 Novartis announced that the maximum tolerated dose had been reached. In March 2010 we announced that Novartis had commenced dosing in a phase II proof-of-concept clinical trial in a range of solid tumours. In December 2014 Novartis informed Vernalis that it was ceasing all development work on this programme.