Molecular Partners announces preclinical data from MP0621 trial

Molecular Partners announced preclinical proof-of-concept data from MP0621, a multispecific cKit x CD16a x CD47 Switch-DARPin program. The data validates the Switch-DARPin concept in vivo and MP0621’s potential as a next-generation therapeutic supporting hematopoietic stem cell transplantation, or HSCT, initially for the treatment of acute myeloid leukemia, or AML, patients. The data will be presented today in a poster session at the European Hematology Association, or EHA, 2024 Hybrid Congress taking place June 13-16 in Madrid, Spain. The Switch-DARPin platform provides a logic-gated “on/off” function to multispecific DARPin candidates leading to target activation only in the presence of defined antigens. In MP0621, the Switch-DARPin binds to either cellular cKit or to the anti-CD47 DARPin binder. Upon MP0621 binding to cKit on cells, the Switch-DARPin will unmask the anti-CD47 DARPin, which in turn will bind CD47 and block the “don’t-eat-me” signal, leveraging the power of CD47 inhibition without its associated toxicity to healthy cells. The Company is presently conducting preclinical efficacy and safety studies for MP0621 with data expected in H2 2024. In the poster presented, preclinical studies demonstrate that: MP0621 selectively blocks CD47 on cells expressing cKit. Conditional blockade of CD47 enhances efficacy of cKit targeting, with phagocytosis comparable to a combo of anti-cKit and anti-CD47 monoclonal antibodies. MP0621 depleted cKit+ cells in bone marrow of humanized mice without affecting circulating immune cells. PK profile of MP0621 is suitable for HSCT therapy in humans.