X-ADC

X-ADC is an experimental antibody-drug conjugate (ADC) developed by ImmunoGen for the treatment of acute myeloid leukemia (AML). It consists of a humanized anti-CD123 antibody (G4723A) conjugated to a diimine-containing indolinobenzodiazepine pseudodimer (IGN) payload via a protease-cleavable peptide linker. The IGN payload in X-ADC functions as a DNA-crosslinking agent, providing potent cytotoxicity against CD123-positive AML blasts and leukemic stem cells. In preclinical studies, X-ADC demonstrated high efficacy but was found to be significantly more toxic to normal myeloid progenitors compared to IMGN632 (which uses a mono-alkylating IGN payload), leading to the selection of IMGN632 for clinical development instead of X-ADC.