VT104

VT104 is a potent, orally bioavailable small molecule inhibitor of the TEAD (transcriptional enhancer-associate domain) family of transcription factors, developed by Vivace Therapeutics. It specifically targets the Hippo signaling pathway by blocking the auto-palmitoylation of TEAD proteins, including TEAD1 and TEAD3. This inhibition prevents the formation of the YAP/TAZ-TEAD transcriptional complex, which is a critical driver of oncogenic gene expression, cell proliferation, and survival in various cancers. VT104 has shown preclinical efficacy as a monotherapy in NF2-deficient mesothelioma and in combination with EGFR inhibitors for EGFR-mutant lung cancer. It is also being investigated for its potential to overcome resistance in mutant KRAS colorectal cancer by targeting the STAT1-YAP1 axis.