Ting Liu

Ting Liu from UBS Group asked for clarification on whether the 10% IHC cutoff for the biomarker analysis was pre-specified and if the amended breast cancer study would pre-specify a similar threshold.

Answer

CEO Jason Lettmann clarified that while looking at CD47 expression was pre-planned, the specific 10% cutoff was not pre-specified, and its robustness was confirmed by testing multiple different cutoffs. He also confirmed the amended breast cancer study will not predefine a cutoff, as the goal is to use the study's data to determine the optimal threshold for a future registrational trial.

Ting Liu from UBS asked for Acumen's perspective on recent data from Roche's trontinemab showing reductions in synaptic biomarkers and requested an updated view on sabirnetug's competitive positioning.

Answer

CEO Daniel O'Connell highlighted that Acumen's Phase I INTERCEPT study showed meaningful changes in synaptic markers over a short duration, positioning the Phase II ALTITUDE-AD study for a potentially impactful readout. Dr. Eric Siemers, Chief Medical Officer, added that Acumen was among the first to measure and demonstrate effects on these synaptic biomarkers and will continue to evaluate them.

Ting Liu asked for more details on the use of the P-tau217 fluid biomarker for patient screening in the Phase II trial, how P-tau217 positivity correlates with tau pathology detected by PET scans, and whether the ALTITUDE-AD patient baseline is comparable to that of the donanemab Phase III trial.

Answer

Dr. Eric Siemers, Chief Medical Officer, explained that plasma P-tau217 serves as a highly effective screening tool for amyloid positivity prior to PET or CSF confirmation, which significantly improved enrollment efficiency by reducing the number of negative PET scans by approximately half. He clarified that while it's a powerful screener, it may not yet fully replace confirmatory tests.