Global cancer market is growing at a CAGR of 6.9% with an estimated value of $81bn in 2016. Although the huge R&D investment observed in the past years in the development of new treatments, there is still lack on an effective treatment in many tumour types. In particular, the median survival for glioblastoma multiforme (GBM), a high-grade brain tumour affecting 23,000 patients a year in US and EU, is 14 months and its 5-yr survival less than 5%. It is therefore urgent to develop more effective treatments against this fatal disease.It has been recently demonstrated that Cancer Stem Cells (CSCs) are responsible from tumour initiation, maintenance, relapse and treatment resistance, and therefore therapies targeting CSC should eradicate the tumour. Our team has discovered a molecular pathway critical in the regulation of CSC. The project presented here entails the proof of concept and pre-clinical development of a humanized antibody blocking this pathway. Our murine version of the antibody blocks CSC development in vitro by 54% and tumour recurrence in a mice model by 50%. At the end of the ERC POC project we will have a patent protected and fully humanized antibody active in vivo and in vitro and ready to enter Phase 1 clinical trials in humans to continue its commercialization process. The forecasted annual peak revenue for this therapeutic antibody is $530M with additional sales coming from line extensions in other cancer indications.With the ERC POC project we are dramatically increasing the commercial value of the therapeutic antibody, transforming an R&D finding (CSC are critical for cancer development) into a potential new solution to patients (a therapeutic antibody targeting CSC). Hence, we are de-risking the product, advancing it through the commercialization path and creating a product and a commercial data package with a good expectative in the cancer market that is ready to be out-licensed or transferred to a spin-off previous VC investment.