VIP943

VIP943 is a next-generation antibody-drug conjugate (ADC) targeting CD123, the interleukin-3 receptor alpha chain, which is overexpressed in various hematologic malignancies including acute myeloid leukemia (AML). The drug consists of an anti-CD123 monoclonal antibody linked via a proprietary legumain-cleavable linker to a novel kinesin spindle protein inhibitor (KSPi) payload. Upon binding to CD123 on malignant cells, VIP943 is internalized and trafficked to the lysosome, where legumain cleaves the linker and releases the KSPi payload. This inhibits mitotic spindle formation, leading to cell cycle arrest and cell death. The CellTrapper™ modification ensures that the KSPi payload accumulates within target cells and minimizes off-target toxicity by preventing diffusion into non-target cells. Preclinical studies have demonstrated potent activity against leukemic blasts and stem cells with favorable safety profiles compared to currently approved ADCs such as gemtuzumab ozogamicin. Early clinical data indicate promising efficacy and safety in patients with advanced CD123-positive hematologic malignancies[1][2][3][4][5][6][7][8].