MP0533 + azacitidine + venetoclax + obinutuzumab

MP0533 + azacitidine + venetoclax + obinutuzumab is an investigational combination therapy regimen being evaluated for the treatment of acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). The core component, MP0533, is a multispecific DARPin (Designed Ankyrin Repeat Protein) T-cell engager developed by Molecular Partners AG that simultaneously targets CD33, CD123, and CD70 on leukemic cells while engaging CD3 on T-cells to induce tumor cell lysis. This avidity-based targeting is intended to selectively eliminate AML blasts and leukemic stem cells while minimizing impact on healthy hematopoietic stem cells. The regimen incorporates the standard-of-care doublet of azacitidine (a hypomethylating agent) and venetoclax (a BCL-2 inhibitor) to enhance anti-leukemic activity. Obinutuzumab, a type II anti-CD20 monoclonal antibody, is included as a pretreatment to deplete peripheral B-cells, a strategy aimed at reducing cytokine release syndrome (CRS) and improving the safety profile of the T-cell engager.