Lexeo Therapeutics (LXEO) 2024 Cantor Fitzgerald Global Healthcare Conference summary

Pipeline overview and upcoming milestones

• Three clinical-stage gene therapy programs target genetic cardiac diseases and APOE4-associated Alzheimer's, with data readouts expected in the next 12-18 months.

• The Friedreich's ataxia (FA) program is the most advanced, with interim Phase 1 data showing promising biomarker improvements.

• Arrhythmogenic cardiomyopathy (PKP2) and APOE4 Alzheimer's programs are progressing, with data from dose cohorts and biomarker analysis expected this year.

• APOE4 program will present biomarker and cognitive data at the CTAD conference.

Friedreich's ataxia program: biology, trial design, and results

• FA is characterized by mitochondrial dysfunction due to frataxin deficiency, leading to cardiac hypertrophy.

• Mouse models show normal cardiac output with as little as 5% of normal frataxin; human biopsies reveal patients have less than 2% in the heart.

• Phase 1 trial uses escalating doses, measuring safety, LV mass, wall thickness, and troponin as endpoints.

• Cohort 1 (6 patients) showed biomarker improvements below 5% frataxin; Cohort 2 (9 patients) reached ~5% by mass spec and ~50% cell transduction by IHC.

• Clinically meaningful improvements: 11.4% LVMI reduction at 12 months, 18% at 18 months, 14% wall thickness, and 50% troponin reduction.

Biomarker measurement and regulatory considerations

• Mass spectrometry quantifies frataxin protein; IHC measures distribution across cells, with IHC having more regulatory precedent.

• IHC may better correlate with clinical improvements and is likely to be the preferred endpoint in future pivotal trials.

• Next data update for FA program expected in 2025 after Cohort 3 biopsies.