ACM

Disease Overview

ACM, also known as ARVC, is a genetic heart disease primarily characterized by myocardial cell loss and the replacement of heart muscle with fibrotic tissue and fatty deposits.

ACM can result from pathogenic variants (or mutations) in several desmosomal genes. These genetic pathogenic variants impair the structure and function of cardiac desmosomes, which are membrane protein complexes engaged in cell-to-cell adhesion and the structural integrity of the ventricular myocardium. Lack of functioning cardiac desmosomes can lead to myocardial cell death and fibrosis, heart dysfunction, rhythm abnormalities, and sudden death.

We estimate that ACM has an estimated prevalence in the US population of approximately 130,000 patients and estimate that over half of all ACM patients have a genetic form of the disease. We believe that five desmosomal genes account for nearly all genetic cases of ACM. Pathogenic variants in the PKP2 gene, are the most commonly known genetic cause of ACM with an estimated prevalence of 60,000 patients in the US.

No effective disease-modifying treatments for ACM exist, and thus, strategies targeted at elevating PKP2 protein levels represent a potential avenue to treat a large portion of ACM populations.

LX2020 Mechanism

We are developing LX2020 as an AAV-based gene therapy designed to intravenously deliver a fully functional PKP2 gene to cardiac muscle for the treatment of ACM due to pathogenic variants in the PKP2 gene (PKP2-ACM).

LX2020 is designed to increase desmosomal PKP2 protein levels, reassemble desmosomes and restore myocardial cell function.