Lexeo Therapeutics (LXEO) investor relations material

Program updates and clinical progress

• Friedreich's ataxia program showed consistent improvement in left ventricular mass index and significant reductions in troponin and wall thickness, with plans to start a pivotal study in the first half of 2026 and provide a statistical plan update early that year.

• PKP2 program data update is expected in Q4 2026, with mature 12-month follow-up data and a regulatory update on endpoints for future approval studies.

• PKP2 has shown a 22% reduction in non-sustained ventricular tachycardia at six months and up to 65% at nine months, with a favorable safety profile and no gene therapy-related serious adverse events.

• Both programs utilize low vector doses, achieving strong efficacy and safety by leveraging disease biology and capsid tropism.

• Manufacturing uses a baculovirus Sf9 process at 200-liter scale, yielding high vector titers and low empty capsid ratios, supporting cost-effective clinical and commercial supply.

Regulatory and study design considerations

• Current FDA interactions focus on reducing bias in accelerated approval study design and ensuring confirmatory endpoints align with accelerated approval endpoints, particularly emphasizing cardiac outcomes.

• The pivotal FA study will be powered on left ventricular mass index, a surrogate endpoint linked to mortality, with ongoing discussions about integrating neurologic endpoints like mFARS.

• Study design accounts for patients with and without prior Skyclarys treatment, as Skyclarys shows neurologic benefit but not cardiovascular improvement.

• Commercial and label strategies aim to demonstrate benefit across cardiac and neurologic endpoints to support broad patient access.

Commercial strategy and infrastructure

• U.S. commercial launch for FA is feasible with a modest infrastructure, as most patients are concentrated in fewer than 20 centers of excellence.

• Ex-U.S. commercialization is simpler, with most countries having a single treatment center; final strategy depends on EMA regulatory feedback.

• The company’s leadership has experience launching rare cardiac drugs, supporting confidence in commercial execution.

• Commercial infrastructure for PKP2 will leverage overlap with heart failure specialists, who treat multiple genetic cardiovascular diseases.