Debio 1562M CD37-targeting ADC is highly active and well tolerated in preclinical models of AML and MDS

The leukocyte antigen CD37 is broadly expressed on acute myeloid leukemia (AML) blasts and associated with poor prognosis. We demonstrate that myelodysplastic syndrome (MDS) cells also express CD37, and both AML and MDS cells have favorable internalization properties of this receptor. Debio 1562M is a next-generation antibody-drug conjugate (ADC) that targets CD37 and is optimized to deliver more toxins to tumor cells than the first-generation ADC Debio 1562, while maintaining a good safety profile. Preclinically, Debio 1562M showed robust anti-leukemic activity in AML and MDS primary samples and in AML xenograft models, irrespective of disease stage or genotype. Debio 1562M was able to target leukemic stem cells in vitro and significantly decrease tumor burden in blood and bone marrow, resulting in survival prolongation compared with standard-of-care treatments. These data demonstrate that CD37 is a relevant target for both indications and that Debio 1562M is a promising therapeutic candidate.