PYX-203

PYX-203 is an antibody-drug conjugate (ADC) developed for the treatment of hematologic cancers. It targets and binds to the interleukin-3 receptor subunit alpha (CD123), a rapidly internalizing target that is overexpressed on leukemic blasts and stem cells in several high need hematologic malignancies, including acute myeloid leukemia (AML) and myelodysplastic syndromes. Upon binding to CD123, PYX-203 is internalized by the cancer cell, where its highly potent cyclopropylpyrroloindoline (CPI) payload—a DNA crosslinking agent—is enzymatically released in lysosomes and trafficked to the nucleus to induce DNA damage. The CPI payload is engineered for enhanced tolerability, resistance to drug efflux pumps, and may allow broader patient access by reducing off-tumor toxicity. The antibody component of PYX-203 also features a modified Fc region designed to mitigate off-tumor effects[1][2][4][5].