- Unique avidity driven mechanism engages CD3 on T cells when binding either two or three tumor-associated antigens to enhance selectivity for AML cells
- Preclinical data demonstrated that MP0533 can selectively target and kill both leukemic blast cells and stem cells, while sparing healthy cells
“AML is a notoriously difficult cancer to treat, in large part due to the overlapping targets which are expressed on both healthy, and leukemic cells. Our team has worked relentlessly over the past 3 years to develop a molecule intended to target these cancerous cells, while avoiding healthy cells. MP0533’s mechanism represents a new level of precision targeting in complex cancers that may permit greater use of the immunostimulatory power of CD3,” said
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
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.
About Molecular Partners’ Oncology Product Candidates
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