P65-047

**P65-047** is a first-in-class proteolysis-targeting chimera (PROTAC) degrader of TEAD transcription factors (TEAD1, TEAD4, and pan-TEAD), developed by Beactica Therapeutics AB using their Eclipsor™ platform. It binds to the interface 3 pocket of TEAD, inducing ternary complex formation with E3 ligase to promote ubiquitination and proteasomal degradation of TEAD, thereby disrupting Hippo pathway dysregulation in cancer. P65-047 outperforms palmitoylation inhibitors (e.g., VT-103, IK-930) in reducing TEAD-regulated gene expression (e.g., CTGF, CYR61), inhibiting proliferation in TEAD-dependent mesothelioma cell lines (e.g., NCI-H226 NF2-deficient, NCI-H2052 NF-mutant), and shows synergy with FGFR, mTOR, MEK1, ALK, HSP90, CDK8, PI3K-alpha, ABL1, and XPO1 inhibitors. It exhibits high plasma and lung exposure in mice via intraperitoneal administration and is positioned for monotherapy in niche cancers and combinations in solid tumors.[1][2][3][4]