Lexeo Therapeutics announces positive results from Phase 1/2 study of LX1001

Lexeo Therapeutics (LXEO) announced positive interim results from the Phase 1/2 study of LX1001 for the treatment of APOE4-associated Alzheimer’s disease, or AD. Treatment with LX1001 led to dose-dependent increases in APOE2 protein expression and improvements in AD-associated tau biomarkers, measures which have been closely correlated with cognitive outcomes. LX1001 also demonstrated a favorable safety profile with no reports of ARIA1. The data were presented in a late-breaking oral presentation at the Clinical Trials on Alzheimer’s Disease conference in Madrid, Spain and expand the body of evidence on LX1001 as a potential therapy for the more progressive course of Alzheimer’s seen in APOE4 homozygotes. LX1001 is an AAVrh10-based gene therapy candidate designed to deliver the protective APOE2 allele into the central nervous system of APOE4 homozygous patients, who have two copies of the toxic APOE4 allele. APOE2 is associated with a significantly lower risk of Alzheimer’s onset and slower disease progression. The study’s primary objective was to assess safety and tolerability, with secondary outcomes including cerebrospinal fluid APOE2 protein expression and change in tau and amyloid biomarkers. The interim Phase 1/2 data include follow-up through 12-months for dose Cohorts 1 through 3 and follow-up through 6-months for dose Cohort 4, demonstrating: CSF APOE2 protein expression in all participants, with dose- and time-dependent increases in expression and durability out to 12 months; Stabilization of amyloid pathology in the majority of participants, with minimal change from baseline in Ass42/40 ratio and amyloid PET; Consistent reductions across CSF tau biomarkers including CSF T-tau, P-tau181, P-tau2172 and P-tau2312, in over two thirds of participants relative to baseline and natural history; Reductions at 6 months in global tau PET3 SUVR in 5 of 6 participants and in regional SUVR in a majority of participants across all brain regions; Participants with moderate AD (n=4) generally demonstrated the most improvement across various biomarker endpoints; Four SAEs were reported, with three deemed unrelated to treatment and one event of mild-moderate sensorineural hearing loss assessed as possibly related to treatment with repeat audiometry pending. The Company has initiated engagement with FDA on these data and expects to provide an update on regulatory interactions and further LX1001 development plans in 2025.