UBIQUIBODY PLATFORM FOR TARGETED DEGRADATION OF ONCOGENIC FUSION PROTEINS

UbiquiTx is pioneering a novel class of mRNA therapeutics that potently and selectively degrade targets not historically addressable by small-molecule degraders. Ubiquibodies (uAbs) are protein fusions that can bind to a target of interest and tag it for targeted intracellular degradation via the endogenous ubiquitin-proteasome pathway (UPP). These novel molecules promise to fundamentally transform drug discovery and human medicine by co-opting the UPP to achieve targeted protein degradation. UbiquiTx artificial intelligence-driven discovery platform enables in silico design of thousands of protein targets, accelerating the development of protein degraders across a broad range of clinical indications. In this project, UbiquiTx will design specific uAbs to selectively target and degrade FGFR2 fusions, a common genetic event in patients with intrahepatic cholangiocarcinoma (iCCA). Candidates will be encapsulated within LNP formulations to test delivery to iCCA cells and functional degradation capability. The feasibility of our approach is supported by our previous computation-mediated engineering of effective, peptide-based uAbs, as well as our recent work demonstrating the potential therapeutic benefit of FGFR2 degradation for the treatment of iCCA. Notably, the uAbs designed should be effective even in patients with acquired resistance to small molecule FGFR inhibitors because of secondary mutations in the FGFR tyrosine kinase domain.