Lexeo Therapeutics (LXEO) investor relations material

Finalized pivotal trial design and regulatory pathway

• Pivotal SUNRISE-FA 2 trial for LX2006 in Friedreich's ataxia finalized, targeting accelerated approval with an open-label design enrolling 13 treated and 13 untreated participants aged 16 and older, with random allocation to reduce bias.

• Untreated control group will not receive placebo or sham; design mirrors a natural history control and was shaped by FDA feedback.

• Primary endpoint is LVMI reduction at 6 months, with secondary endpoints including mFARS, KCCQ, troponin I, and lateral wall thickness to capture cardiac and neurologic benefits.

• Enrollment is progressing, with 19 sites active across eight countries and over 60% of participants enrolled in the last two months; study initiation set for Q2 2026.

• Top-line data readout expected in H2 2027, with BLA submission planned for H1 2028.

Clinical data and study rationale

• Phase I/II data show 18–23% mean LVMI reduction at 6–12 months, with higher doses achieving up to 33% reduction and durable improvements in cardiac structure and biomarkers up to three years post-treatment.

• Statistically significant improvements in mFARS scores compared to matched controls, indicating neurological benefit even in patients on background SKYCLARYS therapy.

• 16 of 17 participants showed reduced or stable troponin I, and LX2006 was generally well-tolerated with no Grade 3 treatment-related SAEs or new safety signals.

• Cardiac function improvement observed even in later-stage cardiomyopathy cases, with single-patient data showing dramatic improvement in advanced disease.

• Durable LVMI improvement maintained up to three years post-treatment.

Study design details and regulatory considerations

• Random allocation from the CLARITY-FA natural history study ensures balanced baseline characteristics and minimizes selection bias.

• Untreated control group will not receive placebo; after six months, controls may cross over to receive LX2006.

• Study powered to detect a 15% or greater LVMI reduction at 6 months, with historical data supporting the likelihood of meeting this endpoint.

• FDA recommended removing cardiac frataxin expression as a co-primary endpoint, reducing participant burden and supporting enrollment.

• Pediatric cohorts (ages 6–16) will be evaluated for safety after adult data, with plans for label expansion following initial adult approval.