MGTA-117 is a humanized monoclonal antibody that targets CD117. It carries an amanitin payload and is used to synthesize antibody-drug conjugates (ADC). MGTA-117 demonstrates potent antitumor activity, enhancing survival in three acute myeloid leukemia (AML) xenograft models [Kasumi-1, AML PDX 1, and AML PDX 2]. It is applicable for AML, myelodysplastic syndromes with excess blasts (MDS-EB), and preconditioning for hematopoietic stem cell transplantation (HSCT) in gene therapy.

MGTA-117, at doses ranging from 0.1 to 1.0 mg/kg, rapidly and selectively binds to and eradicates CD117+ cells, which include human hematopoietic stem cells and AML tumor cells, with an IC50 of less than 10 pM. In mouse models of AML, MGTA-117 effectively eliminates over 95% of human hematopoietic progenitor cells (HSPCs).

Administered intravenously at a dose of MGTA-117 (0.1 mg/kg) once daily for 21 days, this compound exhibits a short half-life of 91 hours, effectively depleting ≥95% of HSPCs in humanized NSG (hNSG) mice. In the Kasumi-1 xenograft hNSG mouse model, MGTA-117 at doses of 3 and 10 mg/kg, or 3 mg/kg administered every other day for two doses (QODx2), significantly enhances survival by 2.4 to 2.7 times. Additionally, MGTA-117 at 3 and 10 mg/kg, administered once, is shown to considerably reduce peripheral tumor burden, slow tumor progression, and enhance survival in AML PDX 1 and AML PDX 2 xenograft hNSG mouse models by 2-3.3-fold and 1.3-1.8-fold, respectively.