Lexeo Therapeutics (LXEO) Baird's 2024 Global Healthcare Conference summary

Program overview and development pipeline

• Focus on gene therapies for genetic cardiovascular diseases and APOE4-associated Alzheimer's, with three clinical-stage programs: two cardiac (Friedreich's Ataxia, arrhythmogenic cardiomyopathy) and one CNS (APOE4 Alzheimer's).

• All programs are in phase I/II, with data updates expected in 2024 and 2025.

• Utilization of the AAVrh10 vector, which offers superior cardiac transduction and safety profile compared to AAV9, validated in both preclinical and clinical settings.

Friedreich's Ataxia (FA) cardiac program (LX2006)

• Targets frataxin deficiency in cardiac muscle; phase I/II SUNRISE-FA study focuses on safety, frataxin expression, and cardiac biomarkers.

• Majority of FA patients die from cardiomyopathy; 70% have heart failure as the cause of death.

• Biopsies confirm frataxin expression and distribution; early cohorts show up to 50% of normal by IHC and near 5% by mass spec.

• Clinical data show 10–11% reduction in LV mass, 14% improvement in wall thickness, and 50% drop in troponin, all exceeding regulatory thresholds.

• Accelerated approval pathway targeted, with LVMI and protein expression as co-primary endpoints; pivotal study design to be finalized after Cohort 3 biopsy data.

Arrhythmogenic cardiomyopathy (LX2020)

• Addresses PKP2 deficiency, a major cause of arrhythmogenic cardiomyopathy affecting 60,000–80,000 US patients.

• Phase I study uses higher AAVrh10 dose and cardiac-specific promoter; primary focus on safety and tissue transduction.

• Key clinical endpoint is reduction in premature ventricular contractions (PVCs), supported by regulatory guidance.

• Two dose cohorts planned; early data will focus on safety and biodistribution, with efficacy data expected as both cohorts mature.

• Differentiation based on AAVrh10's cardiac tropism and safety profile, aiming for best-in-class status.