Lexeo Gene Therapy Shows Early Promise in Tackling Rare Genetic Heart Disease

NEW YORK, NY – January 12, 2026 – Lexeo Therapeutics today unveiled encouraging interim data for its experimental gene therapy, LX2020, offering a potential new front in the fight against a rare and life-threatening genetic heart condition. The early results from a Phase I/II clinical trial suggest the one-time treatment is not only generally well-tolerated but also successfully boosts a critical heart protein and shows signs of reducing the dangerous arrhythmias that define the disease.

The announcement provides a significant glimmer of hope for individuals with PKP2-associated arrhythmogenic cardiomyopathy (PKP2-ACM), a condition for which no disease-modifying treatments currently exist. The data, drawn from the first ten patients in the HEROIC-PKP2 study, indicates that LX2020 is performing as designed by addressing the underlying genetic defect of the disease.

“These interim data from ten participants reinforce the favorable safety profile of LX2020 and demonstrate promising trends in transduction, protein expression, and reduction in arrhythmia burden at the high dose,” said R. Nolan Townsend, Chief Executive Officer of Lexeo Therapeutics, in a statement. “We are encouraged by these preliminary results and look forward to advancing development of LX2020 given its therapeutic potential and ability to address the underlying cause of cardiac dysfunction and disease progression in PKP2-ACM.”

A New Approach for a Devastating Condition

Arrhythmogenic cardiomyopathy (ACM) is an inherited disease where the heart muscle is progressively replaced by fibrotic scar tissue and fat. This structural decay disrupts the heart's electrical signaling, leading to abnormal heart rhythms (arrhythmias) and increasing the risk of heart failure and sudden cardiac death. For many, a sudden cardiac event is the first sign of the disease.

The most common genetic cause of ACM, responsible for about half of all cases, are mutations in the plakophilin-2 (PKP2) gene. This gene provides the instructions for a protein essential for holding heart muscle cells together in a structure called the desmosome. Without sufficient PKP2 protein, these cellular connections become weak and unstable, leading to cell death and the devastating progression of PKP2-ACM, a condition estimated to affect 60,000 people in the United States alone.

Current treatments are limited to managing symptoms. Patients are often prescribed anti-arrhythmic drugs and typically require an implantable cardioverter-defibrillator (ICD) to shock the heart back into a normal rhythm during a life-threatening event. These interventions, while life-saving, do not halt the underlying disease, leaving patients in a state of constant vigilance and anxiety.

LX2020 aims to fundamentally change this paradigm. It is an AAV-based gene therapy that uses a modified, harmless adeno-associated virus (specifically the AAVrh10 serotype, known for its affinity for muscle tissue) as a delivery vehicle. The therapy is administered as a single intravenous infusion, carrying a functional copy of the PKP2 gene directly to the heart's muscle cells, or cardiomyocytes. The goal is to restore the production of the PKP2 protein, rebuild the desmosomes, and thereby halt or even reverse the disease process at its source.

Promising Signals of Protein Restoration and Clinical Stability

The interim data from the HEROIC-PKP2 trial provides the first clinical evidence that this approach may be working in humans. The study dosed ten participants across a low-dose and a high-dose cohort. The results, particularly from the high-dose group, are compelling.

Cardiac biopsies taken three months after treatment revealed a substantial, dose-dependent increase in PKP2 protein expression. Patients in the low-dose cohort saw a mean increase of 93%, while those in the high-dose cohorts experienced a remarkable mean increase of 162%. This biochemical evidence is a critical proof-of-concept, confirming that the gene therapy is successfully reaching the heart tissue and producing the intended protein.

More importantly, these molecular changes appear to be translating into clinical benefits. The company reported that the burden of arrhythmia stabilized or improved in the majority of participants with at least six months of follow-up. Specifically, the high-dose cohorts showed a mean improvement of 22% in non-sustained ventricular tachycardia (NSVT) and 14% in premature ventricular contractions (PVCs)—two key measures of electrical instability in the heart. Furthermore, four out of five high-dose participants reported feeling an improvement in their condition based on a patient-reported outcome scale, suggesting a tangible impact on quality of life.

Understanding the Safety Profile and Path Forward

For any novel gene therapy, the safety profile is paramount. Lexeo reported that LX2020 was generally well-tolerated across all ten participants. Notably, there was no clinically significant activation of the complement system, an immune pathway that can sometimes be a concern with AAV therapies.

As is common with systemically delivered AAV gene therapies, which are largely processed by the liver, five participants in the high-dose cohort experienced temporary elevations in liver function tests. The company stated these events were successfully managed with steroids per the trial protocol and resolved without complication. One serious adverse event of sustained ventricular tachycardia was observed in a single participant three months after dosing. While assessed as possibly related to the treatment, Lexeo noted the event is also consistent with the natural course of the disease. The patient was treated successfully with medication and discharged.

While these early results are highly encouraging, it is important to recognize their context. The data comes from a small, open-label Phase I/II study, and longer-term follow-up is needed to confirm the durability of the treatment's effect and its long-term safety. The company is moving steadily toward that goal.

Lexeo has already completed enrollment for the trial and anticipates having 12-month follow-up data for all high-dose participants in the fourth quarter of 2026. The therapy's potential has been recognized by the U.S. Food and Drug Administration (FDA), which has granted it both Orphan Drug and Fast Track designations. These designations are intended to expedite the development and review of treatments for serious conditions with high unmet medical need, potentially smoothing the regulatory path forward as Lexeo plans for engagement with the agency later this year.