MGTA-117

To investigate the activity of CD117-ADC in non-human primates, we administered a single injection of ADC without HSC infusion, resulting in a >99% depletion of CD34+CD90+ bone marrow cells in cynomolgus macaques (n=2 of 3 in 0.1 mg/kg and n=3 in 0.3 mg/kg); similar to the ablation observed with 4 doses of myeloablative busulfan (Bu) (n=3). The transplanted animals with ADC maintained their fertility. Overall, these data indicate that an ADC-based targeted approach offers safer conditioning and could improve the risk-benefit profile in HSC gene therapy.

P1/2, N=22, Terminated, Magenta Therapeutics, Inc. | N=55 --> 22 | Trial completion date: Oct 2023 --> Feb 2023 | Recruiting --> Terminated | Trial primary completion date: Oct 2023 --> Feb 2023; Sponsor Decision

MGTA-117 has been well tolerated with no unexpected safety concerns. It has shown proof-of-mechanism (robust receptor binding, selective target cell depletion) and rapid clearance with in vivo stability. Further dose escalation continues, and progress is being made toward development of MGTA-117 to enable HSCT in AML/MDS and gene therapy indications.

MGTA-117 has been well tolerated with no unexpected safety concerns. Preliminary data show in vivo stability of the ADC with rapid clearance from blood, robust binding of MGTA-117 on CD117+ cells, and early evidence of single-agent biological activity. The observed PK/PD profile in humans is highly consistent with predictions based on data from studies in preclinical species.

P1/2, N=55, Recruiting, Magenta Therapeutics, Inc. | N=42 --> 55

CD117 receptor occupancy by MGTA-117 will be measured and MSBE dose will be based on safety and receptor occupancy. The study is designed with the possibility that subjects would proceed to HSCT >28 days after MGTA-117 administration, if eligible per the local transplant practices.

P1/2, N=42, Recruiting, Magenta Therapeutics, Inc.

In the CD117-expressing Kasumi-1 cell line derived xenograft model (Figure 1C), MGTA-117, both as a single dose (3 & 10 mg/kg) and as a multi-dose (3 mg/kg QODx2), resulted in a 2.4-2.7-fold increase in median survival compared to vehicle (PBS), isotype-ADC, or standard of care (SOC) cytarabine (ARA-C, 30 mg/kg QDx5).  These data demonstrate that MGTA-117 has potential to be a potent targeted conditioning and anti-leukemia agent. Together with prior reports demonstrating MGTA-117 as an effective conditioning agent in an animal model, this targeted ADC approach has the potential to improve HSCT outcomes in AML by reducing leukemic burden peri-transplant and may decrease the toxicities associated with current conditioning regimens.

In the CD117-expressing Kasumi-1 cell line derived xenograft model (Figure 1C), MGTA-117, both as a single dose (3 & 10 mg/kg) and as a multi-dose (3 mg/kg QODx2), resulted in a 2.4-2.7-fold increase in median survival compared to vehicle (PBS), isotype-ADC, or standard of care (SOC) cytarabine (ARA-C, 30 mg/kg QDx5).  These data demonstrate that MGTA-117 has potential to be a potent targeted conditioning and anti-leukemia agent. Together with prior reports demonstrating MGTA-117 as an effective conditioning agent in an animal model, this targeted ADC approach has the potential to improve HSCT outcomes in AML by reducing leukemic burden peri-transplant and may decrease the toxicities associated with current conditioning regimens.

In the CD117-expressing Kasumi-1 cell line derived xenograft model (Figure 1C), MGTA-117, both as a single dose (3 & 10 mg/kg) and as a multi-dose (3 mg/kg QODx2), resulted in a 2.4-2.7-fold increase in median survival compared to vehicle (PBS), isotype-ADC, or standard of care (SOC) cytarabine (ARA-C, 30 mg/kg QDx5).  These data demonstrate that MGTA-117 has potential to be a potent targeted conditioning and anti-leukemia agent. Together with prior reports demonstrating MGTA-117 as an effective conditioning agent in an animal model, this targeted ADC approach has the potential to improve HSCT outcomes in AML by reducing leukemic burden peri-transplant and may decrease the toxicities associated with current conditioning regimens.

In the CD117-expressing Kasumi-1 cell line derived xenograft model (Figure 1C), MGTA-117, both as a single dose (3 & 10 mg/kg) and as a multi-dose (3 mg/kg QODx2), resulted in a 2.4-2.7-fold increase in median survival compared to vehicle (PBS), isotype-ADC, or standard of care (SOC) cytarabine (ARA-C, 30 mg/kg QDx5).  These data demonstrate that MGTA-117 has potential to be a potent targeted conditioning and anti-leukemia agent. Together with prior reports demonstrating MGTA-117 as an effective conditioning agent in an animal model, this targeted ADC approach has the potential to improve HSCT outcomes in AML by reducing leukemic burden peri-transplant and may decrease the toxicities associated with current conditioning regimens.