Lexeo Therapeutics (LXEO) Piper Sandler 36th Annual Healthcare Conference summary

Company overview and pipeline focus

• Clinical-stage gene therapy pipeline targets genetic cardiovascular diseases and APOE4-associated Alzheimer's disease, with three programs in clinical development and additional preclinical assets.

• Lead program addresses cardiac pathology in Friedreich's ataxia, a major cause of mortality in this population, with interim data already read out and further milestones expected.

• Second program targets arrhythmogenic cardiomyopathy (ACM) due to PKP2 mutation, with first cohort enrolled and data readout expected by early 2025.

• Alzheimer's program targets APOE4 homozygous patients using APOE2 gene, showing biomarker improvements and no ARIA side effects in early data.

• Pipeline is designed to address high unmet needs where no approved therapies exist, aligning with successful gene therapy commercialization models.

Scientific and clinical approach

• Cardiac gene therapy programs use AAVrh.10 capsid, selected for superior heart tropism and validated in multiple animal models and early clinical data.

• Lower vector doses (10^11–10^12 vg/kg) are used to enhance safety, with prophylactic immune suppression to further reduce risk.

• Efficacy endpoints include MRI-based measures (left ventricular mass index, wall thickness) and blood biomarkers (troponin), with significant improvements observed.

• Neutralizing antibody exclusion rates are similar to other AAV serotypes, estimated at around 15%.

• Two parallel FA trials (company-sponsored and investigator-initiated) use the same drug product, with the company trial including cardiac biopsies for direct tissue assessment.

Key data and regulatory alignment

• FA program interim data show 11.4% reduction in left ventricular mass index and 44% frataxin expression, exceeding FDA-aligned thresholds for pivotal studies.

• Safety profile is favorable, with no treatment-related serious adverse events and only one case of asymptomatic myocarditis.

• High-dose cohort in FA program fully enrolled; cardiac biopsy data expected in the first half of next year, guiding final dose selection.

• ACM program (HEROIC-PKP2) is a dose-escalation study, with initial focus on biodistribution and safety; efficacy endpoints to be assessed over longer term.

• Alzheimer's program demonstrated Tau reduction comparable to approved therapies but without ARIA, with plans to advance in partnership due to scale.