Molecular Partners' Radio-DARPin MP0712 Enters Clinical Trials for DLL3-Expressing Tumors
Key Insights
Molecular Partners' Radio-DARPin MP0712, targeting DLL3 (search), is set to begin first-in-human trials in 2025, marking a key advancement in targeted cancer therapy.
The collaboration between Molecular Partners and Orano Med (search) expands to ten Radio-DARPin programs, enhancing their pipeline of targeted alpha therapies.
Clinical data for MP0533 in relapsed/refractory AML (search) shows improved response rates with intensified dosing, with further updates expected in 2025.
Molecular Partners AG, in collaboration with Orano Med (search), is advancing its Radio-DARPin program with MP0712, a targeted therapy against DLL3 (search)-expressing tumors, slated to enter first-in-human studies in 2025. This move signifies a crucial step forward in the development of targeted alpha therapies for cancer, potentially offering a new treatment avenue for patients with limited options. The announcement was made at the 43rd Annual J.P. Morgan Healthcare Conference in San Francisco, California.
Advancing Radio-DARPin Technology
The Investigational New Drug (IND) application for MP0712, a 212Pb Radio-DARPin candidate, is currently under preparation, with ongoing discussions with the U.S. Food and Drug Administration (FDA). The submission is supported by robust preclinical data demonstrating MP0712's high affinity and specificity for DLL3 (search), a tumor-associated protein highly expressed in small cell lung cancer (search) and other tumors. DLL3's limited expression in healthy tissues makes it an attractive target for radiopharmaceutical therapy.
Expanding the Radio-DARPin Pipeline
Molecular Partners and Orano Med (search) have expanded their strategic partnership to co-develop up to ten 212Pb-based Radio-DARPins. This collaboration leverages Molecular Partners' DARPin technology and Orano Med's expertise in targeted alpha-particle therapies (TAT) using lead-212 (212Pb). The second Radio-DARPin program targets mesothelin (MSLN), a glycoprotein overexpressed in several cancers, including ovarian cancer (search). Molecular Partners has developed Radio-DARPins that selectively bind to the membrane-proximal portion of MSLN, overcoming challenges posed by shed MSLN.
MP0533 Shows Promise in R/R AML
Clinical data from the ongoing Phase 1/2a trial of MP0533 in relapsed/refractory acute myeloid leukemia (search) (AML (search)) and myelodysplastic syndrome (search)/AML (ClinicalTrials.gov: NCT05673057) indicate improved response rates and depth in cohort 8, where a steeper step-up and more frequent dosing schedule was introduced. Preliminary data from cohort 8, with a data cutoff of December 16, 2024, showed that three out of the first eight evaluable patients demonstrated responses. Molecular Partners has submitted an amendment to the study protocol to further improve the exposure profile of MP0533, with additional data expected in 2025.
Switch-DARPin Platform for Solid Tumors
Preclinical proof-of-concept data for the Switch-DARPin platform, a novel T cell engager, was presented at the Annual Meeting of the Society for Immunotherapy of Cancer (SITC). The data demonstrated conditional T cell activation and potent co-stimulation in solid tumors, with reduced cytokine release in healthy tissues. Further in vivo data on the CD3 (search) Switch-DARPin is planned for presentation at the AACR Annual Meeting in Q2 2025.
Financial Position
As of December 31, 2024, Molecular Partners reported cash and cash equivalents of CHF 149 million (unaudited). Full year financial results are scheduled to be released on March 6, 2025.