Molecular Partners AG presented new preclinical data showing its DARPin T-cell engager MP0533 can induce preferential killing of cells expressing two or three tumor-associated antigens (TAAs) compared to cells expressing a single TAA. The data was disclosed in an oral presentation at the 64th Annual American Society of Hematology Meeting in New Orleans. MP0533 engages CD3 on T cells while binding up to three tumor-associated antigens (CD33, CD70, and CD123) on AML cells.

By modulating the affinity to each TAA, Molecular Partners designed MP0533 to induce T cell-mediated killing preferentially when the cancer cells express two or three of the TAAs. This avidity-driven T cell activation ensures preferential killing of AML cells, that consistently expresses two or three of the target antigens. At the same time, it reduces the damage to healthy cells, which tend to express only one of the target antigens.

Such damages have been a recurrent issue with other T-cell engagers in AML. As presented on December 12, 2022, MP0533 was able to activate T-cells and destroy AML cells in samples from newly diagnosed and previously treated AML patients with different TAA expressions. Humanized mouse models confirmed MP0533's ability to activate intra-tumoral T-cells and control tumor growth.

The research also showed that MP0533 was able to directly target and kill LSCs while sparing a variety of healthy cells including hematopoietic stem cells. The unique safety profile of MP0533 was further supported by several other parameters including a lower level of cytokine release relative to benchmark mono-targeted T cell engagers, both in vitro in a whole blood assay and in vivo in the humanized mouse AML models.