Executives from Lexeo Therapeutics (NASDAQ:LXEO) outlined regulatory plans, clinical data, and manufacturing updates for its lead gene therapy programs during a presentation at Guggenheim’s 2026 Emerging Outlook Biotech Summit.
Company focus: genetic medicines for cardiac disease
CEO Nolan Townsend described Lexeo as a “cardiac genetic medicines” company focused on AAV gene therapies for genetically driven cardiovascular diseases. The company’s most advanced program, LX2006, is being developed for Friedreich’s ataxia (FA), with an emphasis on FA cardiomyopathy. Townsend said the therapy is showing “meaningful” effects on cardiac pathology and also signals of improvement in neurological disease.
Friedreich’s ataxia: LVMI effects and FDA alignment
On LX2006 in FA cardiomyopathy, Townsend highlighted left ventricular mass index (LVMI) as the key cardiac biomarker, calling cardiac hypertrophy the hallmark of FA heart disease and cardiac MRI the most sensitive way to track it. He said that among patients who entered with abnormal heart mass, “they’ve all returned into the normal range.” He also cited reductions at the higher dose of 28% in LV mass, with a 30% reduction at six months and a 30% reduction at 12 months, noting trade-offs when considering earlier follow-up time points for an accelerated approval study.
Townsend said Lexeo previously met with the FDA, and the agency was open to pooling patients from the existing Phase I/II study with a yet-to-be-conducted registrational study, provided Lexeo submits an acceptable statistical plan. He described the work as a “relatively complicated exercise” and said Lexeo expects to provide an update on the final statistical plan and study design in early 2026. He added that prior guidance on study size and study length remains unchanged.
He also said the FDA is open to a follow-up time point shorter than 12 months, but the company is weighing the impact of potentially smaller treatment effects at earlier assessments. Townsend emphasized the company’s goal of “the fastest, most de-risked path to an accelerated approval.”
Regarding what constitutes clinical meaningfulness, Townsend said Lexeo and regulators have agreed on a 10% improvement in LV mass as a clinically meaningful threshold. He added that literature links that level of change to a “20% risk of mortality,” framing LVMI as a surrogate with a clear link to outcomes. He said there was “no guidance changed with respect to LVMI.”
Neurologic signals and potential treatment population
Townsend said Lexeo is seeing about a 2-point improvement on the Modified Friedreich’s Ataxia Rating Scale (mFARS), which he noted was also the clinical endpoint used for the approval of the existing commercial therapy in FA and produced a similar magnitude of improvement. He argued this neurologic signal could be meaningful even for patients earlier in cardiac disease progression.
On who may be treated first, he suggested patients with LVMI more than two standard deviations above normal are likely to be early adopters because they are closer to later-stage heart disease. However, he said Lexeo’s Phase I experience included 11 patients without abnormal LVMI at baseline, many of whom had elevated troponin and wall thickness. He said the company observed improvements in lateral wall thickness and “meaningful improvements in troponin,” which could support treating patients before LVMI becomes abnormal. He also said Lexeo does not expect any eventual label to be limited only to patients meeting the abnormal LVMI threshold used for study inclusion.
On physician adoption, Townsend said cardiologists are likely to be early adopters given the cardiac manifestations and because some sites already track patients with cardiac MRI. At the same time, he noted all principal investigators in the Phase I study were neurologists, reflecting the role neurologists can play in treatment decisions.
ACC “late breaker” presentations and conference goals
Townsend said Lexeo has two late-breaking presentations at the American College of Cardiology (ACC) meeting. He indicated investors should not expect a “materially incremental” update for FA versus prior disclosures, describing the story as already clear on LVMI and troponin. He added that ACC would be the first academic conference presentation for LX2006 and said a key objective is introducing the therapy and its relevance to cardiologists.
Manufacturing, natural history, and PKP2 program updates
Townsend said Lexeo is using a dose of 1 × 1012 vector genomes per kilogram for LX2006, paired with a “relatively low dose” prednisone regimen for immunosuppression, which he described as not onerous. He also stated the program has had a “very compelling safety profile” at this dose and that Lexeo expects to include adolescent and pediatric cohorts.
On manufacturing, Townsend said Lexeo has completed production of a clinical batch for the pivotal study using its final commercial process, describing it as a high-yield approach. He said the company transitioned from a HEK293 adherent process to an Sf9 suspension process for clinical and commercial material and completed a comparability study. He added that the FDA has approved the comparability protocol, allowing Lexeo to proceed with dosing in the pivotal study. He also said Lexeo received a CDRP designation related to process validation requirements and is discussing PPQ expectations with the FDA with the aim of enabling a rapid path to a BLA after a pivotal study readout.
Townsend also discussed Lexeo’s prospective natural history study in FA, saying it has identical inclusion criteria to the treatment study and can serve as a feeder by helping sites identify eligible patients and begin screening and operations earlier.
For the PKP2 arrhythmogenic cardiomyopathy program, Townsend said Lexeo completed enrollment in a Phase I/II study with 10 total patients, including seven at the high dose. He cited earlier data showing a 22% reduction in non-sustained ventricular tachycardia (NSVT) versus a 20% worsening in the natural history cohort, which he described as a 42% delta. He also pointed to a patient at the nine-month time point showing a 65% reduction in NSVT, which he compared against a 22% worsening in natural history. He said the longest-followed patient showed a 30% improvement in ejection fraction, which he argued would be clinically meaningful.
Townsend said Lexeo observed one serious adverse event (SAE) of sustained ventricular tachycardia, clarifying that it occurred in a patient with a prior history of sustained VT before entering the study. He added that no patients have had implantable cardioverter-defibrillators (ICDs) fire during the trial. He also said the program has not shown SAEs related to complement activation or liver injury.
On biomarker and biopsy findings in the PKP2 study, Townsend said Lexeo observed a dose-dependent response across biopsy endpoints (vector copy number, mRNA, and protein) and reported achieving roughly three to five vector copies per cell in some cases. He said variability across measures on a patient-to-patient basis was expected because the endpoints come from different tissue samples and because disease-related fibrosis can affect tissue quality. He also suggested biopsies are unlikely to be pivotal endpoints, with a greater focus on clinical endpoints such as ventricular tachycardia as Lexeo considers a registrational pathway and future discussions with the FDA.
About Lexeo Therapeutics (NASDAQ:LXEO)
Lexeo Therapeutics, Inc is a clinical‐stage biotechnology company dedicated to developing novel, precision‐designed therapies for central nervous system disorders. The company’s research platform leverages advanced medicinal chemistry to create next‐generation psychedelic-inspired compounds aimed at treating a range of mental health conditions, including anxiety, depression and substance use disorders.
The company’s pipeline features proprietary synthetic molecules engineered to target specific neural pathways while improving safety and tolerability profiles over traditional treatments.
