IMGN632 exhibits potent antitumor efficacy in multiple AML xenograft models. (A) Nude mice bearing EOL-1 subcutaneous xenografts were treated with vehicle or a single dose of either IMGN632 (240 μg/kg), control nonbinding ADC (240 μg/kg), unconjugated antihuman CD123 antibody (G4723A, 240 μg/kg), active payload catabolite (FGN849, 3 μg/kg), or a regimen of cytarabine (75 mg/kg, daily × 5) or azacitidine (3.75 mg/kg, every 3 days × 5). Complete regressions (8/8) in the IMGN632 group were monitored to the end of the study (day 116). (B) Kaplan-Meier analysis of overall survival in a disseminated Molm-13 xenograft model where tumor-bearing nude mice were treated with either vehicle (purple) or a single dose of a control nonbinding ADC (80 μg/kg) or IMGN632 (8 or 80 μg/kg), as indicated. Survival was monitored to day 152. (C) Kaplan-Meier analysis of overall survival (left) and bioluminescent images of mice (right; day 27) in a disseminated Kasumi-3-Luc-mCh-Puro xenograft model where tumor-bearing NSG mice were treated with either vehicle or 2 doses (on days 7 and 41) of a control nonbinding ADC (800 μg/kg) or IMGN632 (240 or 800 μg/kg) as indicated. Survival was monitored to day 118. (D) Mice bearing a primary patient-derived AML model were treated with a single dose of either a control nonbinding ADC (800 μg/kg) or IMGN632 (800 μg/kg). All animals were euthanized 15 days posttreatment, and cells from peripheral blood, bone marrow, and spleen were harvested and stained for murine CD45, human CD45, and human CD33 and analyzed by flow cytometry. Percentage of human CD45⁺/human CD33⁺/murine CD45⁻ of all viable cells is presented on the graphs.