Molecular Partners Announces Publication in Cancer Immunology Research of Preclinical Data Supporting MP0533’s Proposed Mechanism of Action
ZURICH-SCHLIEREN, Switzerland and CONCORD, Mass., April 29, 2024 (GLOBE NEWSWIRE) — Molecular Partners AG (SIX: MOLN; NASDAQ: MOLN), a clinical-stage biotech company developing a new class of custom-built protein drugs known as DARPin therapeutics, today announced a comprehensive, peer-reviewed publication of preclinical data supporting MP0533’s proposed unique mechanism of action (MoA) for the treatment of acute myeloid leukemia (AML) in Cancer Immunology Research, a journal of the American Association for Cancer Research. The publication collates and discusses multiple studies undertaken to characterize MP0533’s preclinical profile and evaluate its therapeutic potential.
Developing safe and efficacious targeted therapies for patients with AML has proven challenging as AML cells share many of the relevant target antigens with healthy cells. Through its unique MoA, MP0533 was designed to simultaneously target the proteins CD33, CD123, and CD70, which are commonly co-expressed on AML cells and rarely on healthy cells. MP0533’s binding strength increases with the number of target proteins present, leading to increased engagement of T cells when at least two of the targets are present. This results in preferential killing of AML cells.
The data published by Bianchi et al in Cancer Immunology Research in collaboration with the University of Bern build on the results presented at the American Society of Hematology (ASH) Annual Meeting and Exposition in December 2021 and 2022, and support MP0533’s intended MoA. MP0533 induces selective T cell-mediated killing of AML cell lines, as well as patient bone marrow-derived AML blasts and leukemic stem cells (LSCs) expressing two or three of the target antigens, while sparing healthy hematopoietic stem cells, blood and endothelial cells. MP0533 also demonstrated reduced risk of T cell fratricide observed with other CD70-targeting agents related to CD70’s upregulation on activated T cells. MP0533 was equivalent to non-CD70 targeting therapies in terms of impact on T cell count and viability, further supporting its potentially favorable on-target, off-tumor profile.
MP0533 led to tumor-localized T-cell activation and efficacious tumor regression in an antigen-dependent manner across different in vivo models. Notably, when compared to other T cell engagers that target single antigens, MP0533 led to lower levels of cytokine release, findings that were confirmed through in vitro, in vivo, and ex vivo studies. This included IL-6, a cytokine known as a primary driver of cytokine release syndrome, a systemic toxicity that has so far limited the development of T cell engagers as potential treatment options of AML. Finally, an evaluation of MP0533 in combination with azacitidine and venetoclax, two chemotherapeutic drugs used in AML, suggest the MoAs may be synergistic in terms of LSC killing.
MP0533 is currently being evaluated in a Phase 1/2a trial in patients with relapsed/refractory AML or myelodysplastic syndrome (MDS/AML), and the Company presented positive initial data from the first four dosing cohorts at the ASH Annual Meeting and Exposition in December 2023. The trial is currently dosing patients in cohort 7. The Company expects to present an update from the study in H1 2024.
For more information about the publication, visit:
Reference:
Bianchi M et al. Cancer Immunol Res 2024. Epub ahead of print April 29, 2024.