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  • Preclinical studies support the clinical development of pipeline programs, including novel gene therapies for the treatment of genetically defined cardiovascular and central nervous system diseases

NEW YORK, May 03, 2022 (GLOBE NEWSWIRE) — LEXEO Therapeutics (LEXEO), a clinical-stage gene therapy company advancing a pipeline of adeno-associated virus (AAV)-based gene therapy candidates for the cardiovascular system and genetically defined central nervous (CNS), today announced that new preclinical data supporting its plakophilin-2 (PKP2) Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC) Program, Friedreich’s Ataxia (FA) Cardiomyopathy Program, and Second Generation Cardiomyopathy Program APOE4 The Alzheimer’s disease program will be presented on the 25and Annual Meeting of the American Society of Gene & Cell Therapy (ASGCT), held live in Washington, DC and virtually May 16-19, 2022.

“This year, we are presenting important preclinical data supporting our most advanced cardiovascular gene therapy programs in FA and CRVA,” said Nolan Townsend, CEO of LEXEO. “Advances from these and other programs will help strengthen our leadership position in the cardiovascular gene therapy category.”

Four abstracts, including two oral presentations, were selected for the ASGCT. The details of each presentation are as follows:

Title: Plakophilin-2 gene therapy prevents and rescues arrhythmogenic right ventricular cardiomyopathy in a novel mouse model harboring patient genetics
Presenter: Farah Sheikh, Ph.D., University of California San Diego, School of Medicine
Date hour : Tuesday, May 17, 2022 at 5:30 p.m. ET
Session title: AAV Vectors – Preclinical and Proof of Concept Studies II
Abstract number: 543

  • Abstract Highlights: A preclinical study of a mutated novel PKP2 knock-in mouse model that recapitulates all the classic hallmarks of ARVC disease revealed that early and late administration of PKP2 via AAV represents an effective and clinically relevant approach to prevent and rescue the development of ARVC disease. The study researchers hypothesized that the dose of PKP2 protein is a critical factor in ARVC, and that PKP2 gene therapy via AAV strategies can prevent and rescue the development of ARVCs. The data suggest that a single administration of early-stage AAV-PKP2 was sufficient to restore PKP2 protein to wild-type levels and completely prevent (i) dissolution of cardiac desmosomes and gap junction, (ii) right and left cardiac mechanical dysfunction, (iii) cardiac electrical dysfunction and (iv) pathological remodeling of cardiac tissue (fibrosis) in adults PKP2 mutant mice at 4 weeks of age. Survival analyzes further demonstrated 100% adult survival PKP2 mutant mice up to 6 months of age with administration of early-stage AAV-PKP2, and that a single administration of late-stage AAV-PKP2 (4-week-old mice) had a immediate benefit with 100% survival 4 months after injection.

Title: Identification of the minimal therapeutic intravenous dose of AAVrh.10hFXN to treat cardiac manifestations of Friedreich’s ataxia
Presenter: Carlos Munoz Zuluaga, MD, Weill Cornell Medicine
Date hour : Wednesday, May 18, 2022 at 5:30 p.m. ET
Session title: AAV Vectors – Preclinical and Proof of Concept Studies III
Abstract number: 936

  • Abstract Highlights: This preclinical study identified a therapeutically effective dose of AAVrh10 expressing human FXN (AAVrh.10hFXN) that has the potential to be clinically relevant for the treatment of cardiac manifestations of FA. Evaluation by echocardiography showed that a dose of 1.8×1012 gc/kg (qPCR determined) led to a beneficial outcome with significant improvement in ejection fraction and fractional shortening compared to untreated mice. This dose resulted in a 21.5% improvement in mortality. In non-human primates, levels in the heart were comparable to the levels estimated to be necessary to convert homozygous FA to heterozygous FA, which, based on previous research, shows no clinical manifestation of FA.

Here are more presentations highlighting LEXEO’s pipeline and platform technology:

Title: Second-generation AAV-mediated gene therapy to mitigate Alzheimer’s disease risk in APOE4 homozygotes
Presenter: Rachel A. Montel, Ph.D., Weill Cornell Medicine
Date hour : Wednesday, May 18, 2022 at 5 p.m. ET
Session title: New therapeutic targets to treat CNS disorders
Abstract number: 665

Title: I-124 Positron Emission Tomography Labeled AAV Assessment of CSF to Blood Diffusion and Consequent Systemic Distribution of AAV Capsids Following Administration of AAV Vectors into CSF
Presenter: JB Rosenberg, Ph.D., Weill Cornell Medicine
Date hour : Tuesday, May 17, 2022 at 5 p.m. ET
Session title: Improved AAV targeting
Abstract number: 890

All summaries of the ASGCT Annual Meeting are available on the ASGCT website.

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:
Evan Feeley
(619) 849-5392
[email protected]