Molecular Partners AG announced that the first patient has been treated in a Phase 1 first-in-human study evaluating the safety, tolerability, and efficacy of MP0533, the company's candidate for acute myeloid leukemia (AML). MP0533 is designed to focus an immune attack against AML in a new way that preferentially spares healthy cells, which has been a historic challenge for CD3-targeting therapeutics. MP0533 simultaneously targets three surface proteins, CD33, CD123, and CD70, that are vastly more likely to appear together on AML blast cells and leukemic stem cells over healthy cells.

It also targets an immunostimulatory protein, CD3, on cytotoxic T cells, which will only activate when at least two of the surface proteins are bound. This novel mechanism is intended to greatly favor CD3 activation in proximity to leukemic stem cells rather than the systemic activation seen in previous CD3-based T cell engagers. The Phase 1 open-label dose escalation study will enroll patients with relapsed/refractory AML and higher-risk myelodysplastic syndromes (MDS).

It is designed to assess the safety, tolerability, and efficacy of MP0533 in addition to a range of secondary endpoints, such as the effect on LSCs, pharmacodynamics, T-cell activation, and cytokine release. Between 20-45 patients are expected to be enrolled across five sites in Switzerland and the Netherlands in collaboration with certain sites within the HOVON cooperative group. Additional clinical sites are planned as well.

MP0533 preclinical data demonstrates its greatly increased avidity for cells expressing two or three of the tumor associated antigens (TAAs) compared to cells expressing a single TAA. MP0533 also demonstrated an ability to induce T cell activation and killing of AML cells in samples from newly diagnosed and previously treated patients. 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, endothelial cells, and T cells.