RET Inhibitors

The aim of the project is to deliver a RET selective inhibitor for the treatment of cancers with a RET activating mutation, found in 1-2% of non-small cell lung cancer (NSCLC), medullary thyroid cancer (MTC) and others. The efficacy of non-selective tyrosine kinase inhibitors with RET activity is hypothesised to be restricted by dose limiting toxicity associated with more potent activity versus other targets, specifically KDR (VEGFR2) in the case of cabozantinib and vandetanib. Recent clinical data has supported this hypothesis. A RET selective inhibitor would therefore be a best-in-class agent for the treatment of these cancers.

A potent orally bioavailable development candidate has been identified and the RET project is in pre-clinical development. The project has a strong intellectual property portfolio and a rapid and focused development route to drug approval.

CPF acquired worldwide rights to the project in November 2014 and exclusively licensed worldwide rights to develop and commercialize a novel, oral, selective small molecule RET kinase inhibitor to Stemline Therapeutics. The RET inhibitor has been designated SL-1001 and is expected to enter the clinic in 2020.

The CRUK Manchester Institute Drug Discovery Unit.