LEXEO Gene Therapy Decreases Alzheimer Disease Biomarkers


All patients in the first cohort exhibited increases in APOE2 CSF protein expression.

LEXEO Therapeutics’ LX1001 decreased core Alzheimer disease (AD) biomarkers in patients treated with the gene therapy, according to data from the first cohort of its phase 1/2 clinical trial (NCT03634007).

The investigational adeno-associated virus (AAV) gene therapy LX1001 is designed to deliver the APOE2 gene into the central nervous system in patients with APOE4 homozygous AD to halt or slow disease progression. The phase 1/2 clinical trial is planning to enroll around 15 patients with this type of AD who are 50 years of age or older, with mild cognitive impairment to mild or moderate dementia.

“Initial data have shown meaningful APOE2 target engagement and declines in cerebrospinal fluid biomarkers, which support our belief that LX1001 has therapeutic potential for APOE4-associated Alzheimer’s disease,” Jay A. Barth, MD, executive vice president and chief medical officer, LEXEO, said in a statement.1 “There is an urgent need for new treatments for this devastating condition, and we are extremely grateful to patients, their families and caregivers, as well as investigators who are participating in the trial.”

The trial, which is reporting data from its first cohort, has 3 planned dose-ascending cohorts. It is primarily assessing safety as measured by adverse events (AEs) or serious AEs. Secondary endpoints will assess cerebrospinal fluid (CSF) homozygous APOE4 conversion to an APOE4/E2 profile and CSF biomarkers.

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The therapy was generally well-tolerated in the first 4 patients in the first cohort dosed so far, with no serious AEs. All patients exhibited increased APOE2 protein expression in the CSF for at least 3 months of follow-up (range, 3-12) from baseline. Investigators also observed decreases in biomarkers such as total tau and phosphorylated tau relative to baseline in the 2 patients that have had their 12-month follow-up visit.

LEXEO plans to announce data from cohort 2 as well as further, 12-month follow-up data from cohort 1 in the second half of 2022 and these data will be presented at future scientific meetings.

“LX1001 is the lead program in our Alzheimer’s disease gene therapy portfolio. These encouraging data support our unique approach to target the genetics of Alzheimer’s disease with multiple gene therapy candidates,” R. Nolan Townsend, chief executive officer, LEXEO, added to the statement.1 “We will continue to advance this clinical stage program and others at the preclinical stage which are on the cutting edge of today’s Alzheimer’s disease research.”

LEXEO is also developing a gene therapy for the potential treatment of Friedreich’s ataxia cardiomyopathy, LX2006. The company’s investigational new drug application for this candidate was approved in February 2022 following promising preclinical data. LEXEO plans to initiate a phase 1/2 clinical trial in mid-2022.2

1. LEXEO Therapeutics announces positive initial data from ongoing phase 1/2 clinical trial of AAV-based gene therapy candidate LX1001 in P=patients with Alzheimer’s disease. News release. LEXEO Therapeutics. March 2, 2022. https://www.biospace.com/article/releases/lexeo-therapeutics-announces-positive-initial-data-from-ongoing-phase-1-2-clinical-trial-of-aav-based-gene-therapy-candidate-lx1001-in-patients-with-alzheimer-s-disease/
2. LEXEO Announces FDA Clearance of IND Application for LX2006 for Friedreich’s Ataxia Cardiomyopathy. News release. LEXEO Therapeutics. February 16, 2022. https://www.lexeotx.com/post/lexeo-announces-fda-clearance-of-ind-application-for-lx2006-for-friedreich-s-ataxia-cardiomyopathy
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