VBC229

VBC229 is a first-in-class, biparatopic DLL3-targeting T-cell engager-topoisomerase I inhibitor (TCE-TOPO1i) fusion molecule developed by Vincerx Pharma for the treatment of small cell lung cancer (SCLC). This novel therapeutic modality combines the mechanisms of a T-cell engager and an antibody-drug conjugate (ADC) to achieve deeper and more durable responses. VBC229 features a biparatopic architecture for enhanced binding to DLL3-positive tumor cells and a proprietary CD3-binding arm designed to induce potent cytotoxicity while limiting excessive T-cell activation and cytokine release syndrome (CRS). The molecule is conjugated to a topoisomerase I inhibitor payload via a proprietary linker that minimizes peripheral release and avoids detectable cytotoxicity against peripheral blood mononuclear cells (PBMCs). Preclinical studies have demonstrated a superior therapeutic window compared to conventional DLL3-targeting T-cell engagers like tarlatamab.