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– In initial clinical data from the low-dose cohort of the ongoing trial, we observed that LX1001 expressed the protective protein APOE2 in the CNS and decreased key biomarkers linked to Alzheimer’s disease –

– No serious adverse events reported to date, indicating an emerging favorable safety profile –

– Initial data from the mid-dose cohort, with additional 12-month follow-up data from the low-dose cohort, expected in the second half of 2022 –

NEW YORK, March 02, 2022 (GLOBE NEWSWIRE) — LEXEO Therapeutics (LEXEO), a clinical-stage gene therapy company advancing a deep and diverse pipeline of adeno-associated virus (AAV)-based gene therapy candidates for cardiovascular and genetically defined diseases of the central nervous system (CNS), today announced positive baseline and biomarker expression data from the low-dose cohort (Cohort 1) of its Phase 1/2 clinical trial in progress on LX1001. LX1001 is an investigational AAV-based gene therapy designed to deliver the protective apolipoprotein E2(APOE2) gene in the CNS of APOE4 homozygous patients with Alzheimer’s disease to halt or slow the progression of the disease.

“Initial data showed significant results APOE2 target cerebrospinal fluid biomarker engagement and decline, supporting our belief that LX1001 has therapeutic potential for APOE4-associated Alzheimer’s disease,” said Jay A. Barth, MD, Executive Vice President and Chief Medical Officer of LEXEO. “There is an urgent need for new treatments for this devastating disease, and we are extremely grateful to the patients, their families and caregivers, and to the researchers participating in the trial.

“LX1001 is the lead program in our gene therapy portfolio for Alzheimer’s disease. These encouraging data support our unique approach to target the genetics of Alzheimer’s disease with multiple gene therapy candidates,” said R. Nolan Townsend, CEO of LEXEO. “We will continue to advance this clinical-stage program and others at the pre-clinical stage that are at the forefront of current Alzheimer’s disease research.”

The Phase 1/2 clinical trial is an open-label dosing study evaluating the safety and tolerability of LX1001 in approximately 15 patients with Alzheimer’s disease aged 50 or older who each have two copies of the APOE4 allele (APOE4 homozygous patients). The trial consists of three dose-escalating cohorts. Secondary endpoints include assessment of the conversion of cerebrospinal fluid (CSF) from the APOE4 profile homozygous to a APOE4/E2 CSF profile and biomarkers. This trial is recruiting patients with clinical diagnoses ranging from mild cognitive impairment to mild or moderate dementia. Patients must also show evidence of amyloid plaques and CSF biomarkers consistent with Alzheimer’s disease to be included in the trial.

Below are key initial results from four patients evaluated in Cohort 1 of the Phase 1/2 clinical trial:

  • expression of protection APOE2 CSF protein in all patients assessed with follow-up data at three months or longer (two patients with data up to the 3 month visit and two patients with data up to the 12 month visit)
    • Increases in CSF APOE2 reference levels, relative to their respective CSF APOE4 levels in all patients assessed with follow-up data at the 3 month visit
    • Increases in CSF APOE2 reference levels, relative to their respective CSF APOE4 levels in both patients with follow-up data at the 12 month visit

  • Decreased levels of total tau (T-tau) and phosphorylated tau (P-tau) of baseline CSF biomarkers from baseline in both patients with data at the 12-month visit
    • T-tau and P-tau protein levels are widely accepted biomarkers that reflect major pathological changes in the brain of patients with Alzheimer’s disease, such as the accumulation of tau protein that occurs during the process neurodegenerative

  • Generally well tolerated with no serious adverse events to date

Initial data from the mid-dose cohort (Cohort 2) and additional 12-month follow-up data from Cohort 1 are expected in the second half of the year and will be presented at a future medical conference.

About LX1001
LX1001 is an AAV-based gene therapy candidate designed as a one-time treatment providing protection APOE2 gene in the CNS for the treatment of APOE4-associated Alzheimer’s disease. LX1001 is designed to express protection APOE2 gene in the CNS of APOE4 homozygous patients to potentially halt or slow the progression of Alzheimer’s disease. LX1001 is being evaluated in an open-label, dose-escalating Phase 1/2 clinical trial and has received Fast Track designation from the United States Food and Drug Administration.

On APOE4-Associated Alzheimer’s disease
Alzheimer’s disease is the leading cause of cognitive decline in late adulthood and is characterized by a complex underlying CNS pathology. Currently, there are no approved treatments for modifying Alzheimer’s disease. Apolipoprotein E, or APOE, a lipid transport protein, is the main transporter of cholesterol in the brain. Predominant APOE alleles include APOE4, APOE3 and APOE2with the E4 allele increasing risk and reducing age of onset and E2 allele decreasing the risk and considerably delaying the age of onset of the disease. APOE4 homozygous patients, individuals who have two copies of the E4 allele, are most at risk and are approximately 15 times more likely to develop Alzheimer’s disease than the general population.

About LEXEO Therapeutic
LEXEO Therapeutics is a New York-based clinical-stage gene therapy company focused on some of the most devastating genetically defined cardiovascular and central nervous system diseases affecting both rare and prevalent patient populations. LEXEO’s basic science stems from partnerships and exclusive licenses with leading academic laboratories at Weill Cornell Medical College and the University of California, San Diego, two preeminent institutions at the forefront of gene therapy research. LEXEO is advancing a deep and diverse pipeline of AAV-based gene therapy candidates in rare cardiovascular diseases, APOE4associated with Alzheimer’s disease and CLN2 Batten’s disease, and is led by pioneers and experts with decades of collective experience in genetic medicines, rare disease drug development, manufacturing and commercialization . For more information, please visit or LinkedIn.

Investor contacts:
Courtney Turiano, IR Stern
(212) 698-8687
[email protected]

Media response:
Sheryl Seapy, real chemistry
(949) 903-4750
[email protected]