Ubiquitin specific protease 7 (USP7) impacts several important cancer pathways, changing the levels of oncogenes and tumor suppressors including p53 and modulating the immune system through targets such as Tip60 and FoxP3. USP7 is an enzyme that removes a tag called ubiquitin from proteins and stabilizes the levels of those proteins in the cell. For example, through the stabilization of MDM2, USP7 causes a decrease in p53 levels, thus allowing cancer cells to proliferate. FLX Bio has also shown that key aspects of inflammatory responses are modulated by its small-molecule USP7 inhibitors — an effect that may be beneficial to targeting cancers.

Potential for Best-in-Class Oral Small Molecule USP7 Inhibitors

We have developed a novel series of potent, highly-selective small molecule USP7 inhibitors with activity both in vitro and in vivo. We have demonstrated that our USP7 inhibitors activate p53 in a cell-based assays and in vivo proof-of-concept studies have demonstrated that our USP7 inhibitors increase inflammation indicating immune activation. Furthermore, we observed significant cytotoxic potency in tumor cell lines. We believe our USP7 inhibitors are novel immunomodulators with multiple beneficial mechanisms of action.

We expect to select a preclinical candidate in 2018.