LX2020 for Arrhythmogenic Cardiomyopathy due to Plakophilin-2 (PKP2) pathogenic variant

Lexeo is currently conducting a Phase 1/2 clinical trial called HEROIC- PKP2 to evaluate the safety and efficacy of LX2020, an investigational gene therapy in patients with PKP2-ACM

About HEROIC-PKP2

• The main goal of this trial is to learn about the safety and tolerability of 2 different doses of the investigational gene therapy, LX2020.
• All trial participants will receive a one-time intravenous injection of LX2020.

Key Eligibility Criteria

• Adults aged 18-65.
• Clinical diagnosis of ACM meeting the 2010 revised Task Force Criteria (TFC)
• Genetic testing documenting a pathogenic or likely pathogenic variant in PKP2.
• Frequent premature ventricular complexes (PVCs)
• Implantable cardioverter-defibrillator (ICD) implantation ≥ 12 weeks prior to consent
• Left ventricular ejection fraction ≥ 50%.

Full eligibility criteria will be evaluated by the clinical trial doctor to determine if an individual is the right candidate for this trial.

Study Duration

Duration of the Study is 52 weeks.  Long term safety and efficacy will be evaluated for an additional four years following completion of the initial trial.

Participation Support

• The investigational gene therapy and all trial-related assessments will be provided at no cost to study participants.
• Any reasonable trial-related expenses such as fees for parking and meals will be covered by the study Sponsor, Lexeo.
• Travel and accommodation will be arranged for participants in the trial and for one caregiver.

Arrhythmogenic Cardiomyopathy Overview

Arrhythmogenic cardiomyopathy (ACM) is a rare, serious heart condition caused by genetic mutations affecting proteins that hold heart cells together. One of the most common forms, known as PKP2-ACM stems from changes in a gene called PKP2. PKP2-ACM primarily affects the heart's electrical system, leading to irregular heartbeats and an increased risk of sudden cardiac arrest. Over time, the condition can progress, damaging the heart muscles and leading to heart failure. Symptoms of PKP2-ACM include palpitations, dizziness, fainting, and chest pain, especially during physical activity.

Historically referred to as arrhythmogenic right ventricular dysplasia (ARVD), and more recently as arrhythmogenic right ventricular cardiomyopathy (ARVC), the newer term of ACM represents the current understanding of the underlying cause and pathology of the disease.

Although not specifically approved to treat ACM, current medications and management methods are focused on relieving symptoms and preventing sudden cardiac death and do not address the underlying cause of PKP2-ACM.

LX2020 Approach

LX2020 is an investigational gene therapy using an AAV, vector, that aims to deliver a functional PKP2 gene to cardiac cells to restore PKP2 protein levels, thereby potentially improving the clinical outcomes for patients with PKP2-ACM.

To learn more about gene therapy, visit the Gene Therapy Overview page.