MP0533 + azacitidine + venetoclax

MP0533 + azacitidine + venetoclax is an investigational combination therapy consisting of MP0533, azacitidine, and venetoclax, being studied for the treatment of relapsed or refractory acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS). MP0533 is a tetra-specific CD3-engaging designed ankyrin repeat protein (DARPin) that targets CD33, CD123, and CD70 on leukemic cells while engaging T-cell CD3 to promote immune-mediated killing of malignant cells co-expressing two or more of the antigens, with the goal of maximizing leukemia stem cell eradication and sparing healthy cells[1][2][3][4][5]. Azacitidine is a DNA methyltransferase inhibitor classified as a hypomethylating agent, interfering with abnormal DNA methylation and inducing apoptosis in abnormal hematopoietic cells. Venetoclax is a selective, orally bioavailable small-molecule BCL-2 inhibitor, promoting apoptosis in BCL-2–dependent cancer cells. This combination is designed to exploit synergistic effects: MP0533 drives targeted T-cell engagement and killing of leukemic cells, while azacitidine and venetoclax disrupt leukemic cell survival and proliferation signals, offering a multi-modal approach to overcome resistance seen with monotherapies. MP0533 is developed by Molecular Partners[2][3], with azacitidine and venetoclax both originally developed by Celgene (acquired by Bristol Myers Squibb) and AbbVie, respectively. As of the latest available data, the combination is being explored in phase 1/2 trials for relapsed/refractory AML and MDS, but MP0533 is primarily tested as a monotherapy in current registered trials[1][3][5].