Lexeo Therapeutics (LXEO) Oppenheimer 36th Annual Healthcare Life Sciences Conference summary

Strategic positioning and platform differentiation

• Focus on precision medicine for inherited cardiac diseases using AAVrh.10 vector, which shows superior heart biodistribution compared to other vectors.

• Clinical validation of cardiotropism and safety profile in both Friedreich's ataxia (FA) and PKP2-associated arrhythmogenic cardiomyopathy (PKP2-ACM) programs.

• Utilization of robust biomarkers and endpoints, including cardiac MRI, LV mass index, troponin, and mFARS, to assess efficacy and safety.

Friedreich's ataxia (FA) program highlights

• FA affects about 15,000 patients globally, with 70% mortality due to cardiac disease; therapy targets both cardiac and neurologic endpoints.

• Clinical data show significant, dose-responsive reductions in LV mass and troponin, with normalization of LVMI in patients with baseline abnormalities.

• Therapy demonstrates meaningful increases in frataxin expression; even small increases are clinically impactful.

• Registrational study will use dual primary endpoints: frataxin increase and >10% LVMI improvement, with LVMI as the key efficacy driver.

• Natural history study accelerates enrollment and provides critical data on untreated disease progression.

Regulatory and clinical development plans

• Final alignment with FDA on pivotal study design and endpoints is underway, targeting early 2026 for data readout.

• Natural history study supports patient identification and site readiness, while also validating lack of spontaneous LVMI improvement.

• Breakthrough designation obtained for FA, with potential for a broad label beyond just cardiomyopathy.

• Therapy may complement or surpass existing treatments like SKYCLARYS by addressing both cardiac and neurologic aspects.