Molecular Partners Announces Publication in Cancer Immunology Research of Preclinical Data Supporting MP0533’s Proposed Mechanism of Action - Seite 2

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. 

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The CD33xCD123xCD70 Multispecific CD3-Engaging DARPin MP0533 Induces Selective T Cell–Mediated Killing of AML Leukemic Stem Cells

Reference:
Bianchi M et al. Cancer Immunol Res 2024. Epub ahead of print April 29, 2024.

About MP0533
MP0533 is a novel tetra-specific T cell-engaging DARPin, which simultaneously targets the antigens CD33, CD123 and CD70 on AML cells as well as the immune activator CD3 on T cells. AML cells commonly co-express at least two of the three target antigens, whereas most healthy cells only have one or none. MP0533 binds with increasing avidity as the number of its target antigens present increases, dramatically favoring binding to AML cells over healthy cells. This unique avidity-driven mode of action is designed to enable T cell-mediated killing of AML cells while preserving a therapeutic window that minimizes damage to healthy cells.

About DARPin Therapeutics
DARPin (Designed Ankyrin Repeat Protein) therapeutics are a new class of custom-built protein drugs based on natural binding proteins that open new dimensions of multi-functionality and multi-target specificity in drug design. The flexible architecture, intrinsic potential for high affinity and specificity, small size and high stability of DARPins offer benefits to drug design over other currently available protein-based therapeutics. DARPin candidates can be radically simple, with a single DARPin unit acting as the delivery vector to a specific target; or multispecific, with the possibility of engaging more than five targets, and combining multiple and conditional functionalities in a unique DARPin drug candidate. The DARPin platform is a rapid and cost-effective drug discovery engine, producing drug candidates with optimized properties and high production yields. DARPin therapeutics have been clinically validated across several therapeutic areas and developed through to the registrational stage.