Lexeo Therapeutics reported interim results from its HEROIC‑PKP2 Phase I/II trial of the LX2020 gene‑therapy candidate for plakophilin‑2‑associated arrhythmogenic cardiomyopathy (PKP2‑ACM). The open‑label, dose‑escalating study enrolled ten participants, with three receiving a low dose of 2 × 10^13 viral genomes per kilogram and seven receiving a high dose of 6 × 10^13 vg/kg.
Safety data indicated that LX2020 was well tolerated. No clinically significant complement activation was observed, and transduction and transcription were robust. PKP2 protein expression rose 93 % in the low‑dose cohort and 162 % in the high‑dose cohort. Arrhythmia burden improved in the majority of participants, with mean reductions of 22 % in non‑sustained ventricular tachycardia and 14 % in premature ventricular contractions at the latest visit.
Elevations in liver function tests were noted in five high‑dose participants; these were successfully managed with a protocol of prednisone and sirolimus. A single serious adverse event—a sustained ventricular tachycardia episode—occurred in a high‑dose participant three months post‑dose and was deemed consistent with the natural history of PKP2‑ACM.
The HEROIC‑PKP2 trial reached enrollment completion in Q4 2025. Twelve‑month data for all high‑dose participants are expected in Q4 2026, and regulatory engagement is anticipated in 2026. LX2020 has received FDA orphan drug and fast‑track designations, underscoring the regulatory support for this first‑in‑class therapy.
These interim findings validate Lexeo’s AAV‑based platform for delivering functional PKP2 to cardiac tissue and demonstrate measurable clinical benefit in a rare, high‑unmet‑need disease. The data support progression to pivotal trials and accelerate the company’s roadmap toward regulatory submission. Lexeo’s CEO, R. Nolan Townsend, emphasized the encouraging safety profile and the promising trends in protein expression and arrhythmia reduction, expressing confidence in advancing LX2020 toward the next development milestones.
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