CD45-ADC

Moreover, single dose anti-human CD45-ADC given to rhesus macaque nonhuman primates on days -6 or -10 was at least as myeloablative as lethal irradiation. These data suggest that CD45-ADC can potently promote donor alloengraftment and hematopoiesis without significant toxicity or severe GVHD, as seen with lethal irradiation, providing strong support for clinical trial considerations in highly vulnerable FA patients.

A single dose of 3 mg/kg MGTA-45 resulted in long-term disease-free survival in all animals (median >330 days) while control groups (vehicle, isotype-ADC, or cytarabine standard of care) had median survival of 52-64 days (P < 0.005, n=5-8 mice/group).  Targeting CD45-expressing hematopoietic cells with MGTA-45, a novel anti-CD45-ADC, potently depleted HSCs and immune cells in vitro and in vivo and enabled donor cell engraftment in a nonhuman primate transplant model. MGTA-45 also significantly extended survival in a PDX model of AML refractory to standard of care. Overall, targeted conditioning using MGTA-45 could improve the risk-benefit profile of HSCT, expanding the patient population able to receive these potentially curative therapies.