Molecular Partners to preent updated data from MP0533 trial at EHA congress

Molecular Partners (MOLN) announced a poster presentation with updated data from a Phase 1/2a trial of the tetraspecific T-cell engager MP0533 in relapsed/refractory acute myeloid leukemia, at the 30th European Hematology Association Congress, taking place in Milan on June 12-15. The poster outlines the impact of accelerated step-up dosing regimen of MP0533 on exposure and clinical responses in cohort 8, providing the rationale for further optimization to the dosing regimen implemented in the ongoing cohort 9. Data from cohort 8 show that 3 of 8 evaluable patients achieved a clinical response after the first cycle, with one patient achieving a complete response and two patients a complete response with partial hematologic recovery as best overall response. Two patients maintained a response for more than 3 months and one patient remains on treatment, maintaining a response beyond 6 months at the time of data cutoff. Cohort 8 implemented a higher starting dose than cohorts 1-7, and the inclusion of an additional day of dosing, reaching the target dose by day 12, as opposed to day 15 previously. Cohort 8 data indicate that patients maintained exposure to MP0533 for a longer period of time within the predicted therapeutic range through the accelerated step-up dosing scheme, within the first cycle. Data show that patients reached over 4 days of relevant exposure, with 5 out of 8 patients displaying greater than 50% blast reduction. MP0533 shows an acceptable safety profile after adjustment of the target dose in cohort 8. In cohorts 1-7, where step-up dosing reached target dose by day 15, exposure to predicted therapeutic doses was limited to roughly 2 days in the first cycle, most likely due to target-mediated-drug deposition. This prior treatment protocol, despite demonstrating initial blast reductions in ~30% of patients, resulted in limited responses. Based on the encouraging antitumor activity observed in cohort 8, the amended protocol for cohort 9 and beyond includes further acceleration of the step-up dosing to reach therapeutically-relevant doses faster, increased frequency of dosing for higher cumulative MP0533 exposure, and the introduction of anti-CD20 premedication to mitigate loss of exposure, with the objective to further increase the depth and duration of responses in patients. Cohort 9 is currently dosing patients and initial data from the amended dosing scheme are expected in H2 2025. Additionally, future study cohorts will evaluate the combination of azacitidine/venetoclax with MP0533.