US-based gene therapy company LEXEO Therapeutics has received the US Food and Drug Administration (FDA) approval for its Investigational New Drug (IND) application for LX2020.

LEXEO is engaged in developing adeno-associated virus (AAV)-based gene therapies for genetically defined cardiovascular diseases and a sub-group of Alzheimer’s disease.

Its LX2020 is an AAVrh10-based gene therapy designed for the treatment of Arrhythmogenic Cardiomyopathy (ACM) caused by variants in the PKP2 gene (PKP2-ACM).

The drug works by intravenously delivering a functional PKP2 gene to the cardiac muscle.

The PKP2 gene increases the levels of plakophilin 2 (PKP2) protein in the cardiac desmosome, which is essential for cell adhesion to strengthen the myocardium (heart muscle).

LEXEO chief scientific officer Eric Adler said: “This IND clearance marks an important step in advancing a potential one-time treatment for individuals with PKP2-ACM, who are in need of more effective options for this devastating disease.

“Current clinical management strategies are only marginally effective and primarily focus on symptom management.

“LX2020 seeks to address the underlying cause of this disease by delivering a functional PKP2 gene to halt the progression and reverse the disease phenotype. We look forward to initiating the Phase 1/2 clinical trial and rapidly advancing the program through the clinic.”

LEXEO said that the LX2020 development programme is based on collaborative research led by Farah Sheikh at the University of California, San Diego School of Medicine.

The research used a genetic mouse model of PKP2-ACM that displays the disease phenotype.

In the preclinical studies, LX2020 showed restoration of integrity in desmosome and cell-cell junctions, improving the cardiac tissue composition.

The drug also showed to prevent arrhythmias, along with improvement in the right and left ventricular function resulting in increased survival.

LEXEO will conduct Phase ½ HEROIC-PKP2 trial, a first in human, 52-week open-label, dose-escalating, multicentre clinical study, to determine the safety and tolerability of LX2020 in adults.

The drug candidate will be administered as a one-time intravenous infusion to patients in two ascending-dose cohorts of three patients each, with plans for cohort expansion.

In the study, preliminary efficacy measures will evaluate myocardial protein expression, and biomarkers measuring cardiac structure and function, and arrhythmia burden.

Furthermore, the long-term safety and efficacy of the drug will be evaluated for an additional four years, following the completion of the initial clinical trial, said the US drugmaker.