TY-2719

TY-2719 is an orally bioavailable, broad-spectrum EGFR-targeting proteolysis-targeting chimera (PROTAC) developed by TYK Medicines. It is specifically designed to overcome acquired resistance to third-generation EGFR tyrosine kinase inhibitors (TKIs), such as osimertinib, in patients with non-small-cell lung cancer (NSCLC). TY-2719 functions by inducing the degradation of mutant forms of EGFR, including the L858R mutation and complex resistance mutations like L858R/T790M/C797S and Exon 19 deletion/C797S. Notably, TY-2719 spares wild-type EGFR, which may reduce the incidence of common EGFR-TKI side effects such as skin rash and diarrhea. In addition to its potential as a monotherapy for resistant NSCLC, TY-2719 has demonstrated synergistic efficacy when combined with KRAS inhibitors in preclinical models of NSCLC and pancreatic ductal adenocarcinoma (PDAC).