CD37 is a Relevant Target for AML and MDS Treatment with Debio 1562M Antibody Drug Conjugate (ADC)

Presented at EHA2024

Lisa Ivanschitz1, Josée Hue-Perron1, Selena Vigano2, Sebastien Lofek2, Noemie Luong1, Léo Marx2, Riccardo Colombo1

1 Debiopharm, Lausanne, Switzerland
2 Debiopharm Research & Manufacturing, Martigny, Switzerland  


CD37 relevance as an attractive therapeutic target for immune based therapies has been confirmed in clinical trials for B cell malignancies. In acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS), CD37 expression profile has been less investigated and is more controversial. Here, we demonstrate that CD37 is broadly expressed in diverse AML and MDS models, including patient samples. Debio 1562M, a new CD37-targeting ADC, is efficiently internalized in these models, at a similar extent as in healthy or malignant B cells. With only one administration, Debio 1562M successfully triggers tumor regression of several cell-derived xenograft (CDX) models and strongly improves animal survival compared to venetoclax and azacitidine standard of care (SoC). In patient-derived xenograft (PDX) models, Debio 1562M significantly reduces tumor burden, similarly as venetoclax and azacitidine SoC treatment, or better in a SoC resistant model. In the absence of cross-reactive preclinical species, GLP toxicology study was performed in mice and demonstrated a safe profile related to known payload’s toxicities.