Molecular Partners AG presented clinical data from the ongoing phase 1/2a dose-escalation study of MP0533 and preclinical data on MP0621 at the American Society of Hematology (ASH) annual meeting in San Diego, CA.
The data highlight the potential of MP0533 in treating relapsed/refractory acute myeloid leukemia (AML) and MP0621 as a next-generation conditioning regimen for hematopoietic stem cell transplantation (HSCT).
MP0533: Safety and Activity in AML
MP0533 is a novel tetraspecific T cell engaging DARPin designed to target CD33, CD123, and CD70 on AML cells and CD3 on T cells. The drug aims to selectively kill AML cells expressing any combination of these tumor-associated antigens while sparing healthy cells.
The ongoing phase 1/2a study included 37 patients with relapsed/refractory AML or myelodysplastic syndrome (MDS)/AML. The data presented at ASH 2024 showed that MP0533 has an acceptable safety profile, with most adverse events being infusion-related reactions and cytokine release syndrome. Initial pharmacodynamic data confirmed target engagement and immune activation.
Despite lower than anticipated drug exposure, four responders were reported across the first seven cohorts, with encouraging blast reductions observed in patient bone marrow, particularly in those with lower disease burden.
"We are at a unique crossroads with the MP0533 program. Data from our Ph1/2a study indicate antitumor and pharmacodynamic activity despite currently sub-optimal exposure levels, mostly driven by target-mediated drug disposition," said Patrick Amstutz, Ph.D., CEO of Molecular Partners.
Based on these findings, Molecular Partners is amending the study protocol to optimize the dosing schedule and improve MP0533 exposure, aiming for higher response rates and improved response quality and duration.
MP0621: HSC Depletion for Transplantation
MP0621 is a Switch-DARPin candidate designed to induce the killing of hematopoietic stem cells (HSCs) as a conditioning regimen for HSCT. The Switch-DARPin platform allows for target activation only in the presence of defined antigens. MP0621 binds to cKit on HSCs, unmasking an anti-CD47 DARPin that blocks the "don't-eat-me" signal, enhancing cKit-targeting efficacy while reducing off-target effects associated with systemic anti-CD47 blockade.
Preclinical results support MP0621's mechanism of action, suggesting its potential as a viable approach for HSC depletion. However, non-human primate data do not support its use as a treatment for AML, as previously hypothesized. Molecular Partners is currently evaluating partnering opportunities for MP0621, aligning with its focus on oncology therapeutics.
