Lexeo Therapeutics (LXEO) Study Update summary

Disease background and unmet need

• Friedreich's ataxia (FA) is a rare, progressive disorder caused by frataxin (FXN) gene mutations, leading to neurological and cardiac complications, with cardiomyopathy as the leading cause of death in up to 80% of patients.

• FXN deficiency impairs mitochondrial function in cardiomyocytes, resulting in cardiac hypertrophy and cell death.

• Cardiac hypertrophy, measured by LVMI and wall thickness, is linked to poor outcomes and does not improve spontaneously.

• No currently approved therapies exist for FA cardiomyopathy; omaveloxolone is approved for neurological symptoms but not cardiac dysfunction.

• Cardiac biomarkers such as LVMI, wall thickness, and hs-troponin I are validated predictors of outcomes in FA and other cardiomyopathies.

Study background and rationale

• LX2006 is an AAVrh10-based gene therapy designed to restore frataxin expression in the heart, targeting the root cause of FA cardiomyopathy.

• Small increases in frataxin levels are expected to yield clinical benefits, as shown in preclinical models and analogous genetic diseases.

• FDA has granted Rare Pediatric Disease, Fast Track, and Orphan Drug designations for LX2006 in FA cardiomyopathy.

Study design and methodology

• Two ongoing Phase 1/2 trials: Lexeo-sponsored SUNRISE-FA and Weill Cornell Medicine investigator-initiated, both using identical LX2006 drug product.

• Open-label, 52-week studies with long-term follow-up, enrolling adults (18–50 years) with FA cardiomyopathy.

• Both studies use cardiac MRI, echocardiography, CPET, and biomarkers for assessment; cardiac biopsies for frataxin expression are performed only in SUNRISE-FA.

• 13 participants dosed across both studies as of July 15, 2024, with baseline characteristics reflecting typical FA cardiac phenotype.

• Cohort 3 (highest dose) enrollment has begun in SUNRISE-FA; Weill Cornell trial is enrolling Cohort 2.