Lexeo Therapeutics (LXEO) investor relations material

Program updates and clinical progress

• Completed enrollment of Phase 1/2 study for Friedreich's ataxia (FA) and moving to a registrational study next year.

• Arrhythmogenic cardiomyopathy program to complete Phase 1/2 enrollment this year, with next steps planned for 2026 and beyond.

• Recent clinical data in FA show significant improvements in cardiovascular and neurologic endpoints.

• All six patients with abnormal LVMI in Phase 1 normalized their heart mass, with some showing up to 50% reduction.

• Cardiac gene therapy field is expected to expand rapidly, with AAV vectors seen as leading technology.

Regulatory and trial design insights

• Agreement with FDA on an expedited path to accelerated approval for FA, including pooling Phase 1/2 and pivotal data.

• FDA open to evaluating endpoints earlier than 12 months, likely shortening pivotal study duration.

• Pivotal trial for FA will enroll patients with abnormal LVMI and use mFARS as co-primary endpoints.

• Study powered to detect a 10% reduction in LV mass, a clinically meaningful threshold agreed upon with FDA.

• Propensity matching and identical inclusion criteria used to ensure comparability between treatment and natural history arms.

Mechanistic and durability considerations

• FA cardiomyopathy linked to mitochondrial dysfunction due to frataxin deficiency, leading to increased heart mass.

• Therapy aims to restore frataxin, reducing mitochondrial hyperplasia and normalizing heart structure.

• Durable gene expression expected in non-dividing cardiac cells, supporting long-term benefit.