Lexeo Therapeutics, Inc. announced positive interim data of LX2006 for the treatment of Friedreich ataxia (FA) cardiomyopathy. Across both the Lexeo SUNRISE-FA Phase 1/2 clinical trial (NCT05445323) and the Weill Cornell Medicine investigator-initiated Phase 1A trial (NCT05302271), LX2006 was well tolerated with no treatment-related serious adverse events, and clinically meaningful improvements in cardiac biomarkers were observed with increasing improvement over time. FA cardiomyopathy is a devastating, rare, and progressive disorder caused by loss of function mutations in the frataxin gene.

Thus far in participants in the SUNRISE-FA trial with cardiac biopsies, low levels of frataxin have been found in the heart at baseline, estimated to be 2% or less of normal. In terms of clinical presentation, FA cardiomyopathy is typically characterized by left ventricular hypertrophy ultimately progressing to heart failure, and cardiac dysfunction is the cause of death in up to 80% of individuals with FA. A new natural history subset analysis conducted by Lexeo showed elevated left ventricular mass index (LVMI) in adults with FA cardiomyopathy, and LVMI remained stable or increased with age without spontaneous improvement.

Elevated LVMI is an indicator of left ventricular hypertrophy and correlated with mortality in multiple cardiovascular conditions including FA cardiomyopathy. Interim Safety Results: LX2006 was well tolerated with no treatment-related serious adverse events to date in either study, No signs of complement activation or other immunogenicity observed, No cardiac or hepatic safety signals observed, All adverse events were transient and resolved, No participants discontinued from either study. Interim Clinical Results (from 8 participants with > 6-months of follow-up) Left ventricular mass index (LVMI): Of participants with elevated LVMI at baseline, 75% achieved >10% reduction at 12 months (n=4).

Of all participants, 50% achieved >10% reduction in LVMI at 12 months (n=6). Among the participants with elevated LVMI at baseline, mean reduction in LVMI was 11.4% at 12 months (n=4) and 18.3% at 18 months (n=2). Left ventricular (LV) lateral wall thickness: wall thickening, an early indicator of left ventricular hypertrophy, was reduced by 13.6% on average in all participants at 12 months (n=6).

High-sensitivity Troponin I (hsTnI): troponin I, a biomarker of myocardial injury, was reduced by 53.3% on average in all participants at 12 months (n=5). Frataxin protein expression evaluated via myocardial biopsy: observed increased frataxin levels compared to baseline following treatment with LX2006 in all participants evaluated to date utilizing two distinct measurements: LCMS: frataxin increase observed in 3 of 3 evaluable participants. IHC: frataxin increase observed in 2 of 2 evaluable participants.

Dosing Update and Next Steps: As of July 15, 2024, 13 participants dosed to date across two trials: Cohort 1 (1.8x1011vg/kg): n=6, Cohort 2 (5.6x1011 vg/kg): n=6, Cohort 3 (1.2x1012 vg/kg): n=1. SUNRISE-FA independent Data and Safety Monitoring Board endorsed proceeding to Cohort 3 dose level (1.2x1012vg/kg). This cohort has started enrollment with 1 participant dosed to date and will include at least 3 participants. The Weill Cornell investigator-initiated trial is currently enrolling in Cohort 2. Lexeo expects to share further details of these interim results, including an additional cardiac biopsy from Cohort 2, at a scientific conference in Fall 2024.