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U.S. Food and Drug Administration (FDA) open to pooling data from ongoing Phase I/II studies of LX2006 with pivotal data to support a Biologics License Application (BLA) for Accelerated Approval Interim clinical data show sustained or deepening improvements in the majority of participants across both cardiac and neurologic measures of Friedreich ataxia Participants with abnormal left ventricular mass index (LVMI) at baseline achieved 18% mean reduction in LVMI at 6 months and 23% mean reduction at 12 months, exceeding FDA-aligned target threshold of 10% reduction Clinically meaningful improvement observed in the modified Friedreich Ataxia Rating Scale (mFARS), indicative of slowed disease progression and improved function Company to host webcast today at 8:00 AM ET Oct. 07, 2025 -- Lexeo Therapeutics, Inc. (Nasdaq: LXEO), a clinical stage genetic medicine company dedicated to pioneering novel treatments for cardiovascular diseases, today announced updates to key components of an Accelerated Approval pathway for LX2006 in Friedreich ataxia (FA) cardiomyopathy, alongside new interim clinical data from ongoing Phase I/II studies. “We are encouraged by our recent dialogue with the FDA on LX2006, and we appreciate the Agency’s collaborative spirit as we work to deliver a potentially life-changing therapy to the FA community as efficiently as possible,” said R. Nolan Townsend, Chief Executive Officer of Lexeo Therapeutics. “Given the highly compelling data to date that demonstrate clinically meaningful improvements across both cardiac and neurologic measures of FA, we are now pursuing a development strategy that could enable a smaller pivotal study, given the potential to pool data with the ongoing Phase I/II trials, as well as potentially assessing the co-primary endpoint of LVMI earlier than 12 months. This approach could accelerate our overall timeline toward a BLA submission for LX2006 under the Accelerated Approval pathway.” In response to questions from the Company regarding the possibility of a faster path to a BLA, the FDA has indicated openness to a BLA submission for accelerated approval that includes clinical data from the ongoing Phase I/II studies of LX2006 pooled with new clinical data to be generated in the planned pivotal study. To enable pooling of these data to support licensure, Lexeo will submit enhanced manufacturing comparability data and meet an additional nonclinical requirement prior to the initiation of the planned pivotal study, given the Company’s intention to leverage its optimized, high-yield Sf9-baculovirus manufacturing platform for future clinical and commercial drug supply, compared to the adherent HEK293 process used for Phase I/II clinical supply. The FDA also previously agreed to evaluate the co-primary endpoint of LVMI at a time point earlier than 12 months. Lexeo continues to engage with the FDA on the pivotal protocol and comparability. In discussions to date, there have been no changes to the previously disclosed alignment with the FDA on key parameters related to the LX2006 planned registrational study. Collectively, Lexeo believes this regulatory feedback has the potential to reduce the size and length of the planned pivotal study, possibly accelerating the overall timeline to BLA submission. Lexeo plans to initiate the LX2006 pivotal study as soon as possible in the first half of 2026, pending finalization of the trial protocol. FDA has previously granted Breakthrough Therapy, Regenerative Medicine Advanced Therapy (RMAT), Orphan Drug and Fast Track designations to LX2006, and admitted LX2006 into the CMC Development and Readiness Pilot (CDRP) program. Updated interim clinical data from both ongoing Phase I/II studies of LX2006 continue to show encouraging safety and efficacy, exceeding the thresholds previously agreed with FDA for co-primary endpoints LVMI and frataxin expression. Left ventricular mass index (LVMI): Among participants with abnormal baseline LVMI (key inclusion criteria for pivotal study; n=6): 6 of 6 participants achieved LVMI measurements within the normal range as of latest visit 5 of 6 participants achieved >10% improvement by 12 months 18% mean improvement in LVMI at 6 months and 23% mean improvement at 12 months, exceeding 10% FDA-aligned threshold for pivotal study 28% mean improvement in LVMI at 6 months and 33% mean improvement at 12 months in mid- and high-dose cohorts (n=3), suggesting dose-dependent improvement Among participants with normal baseline LVMI (n=10), the majority demonstrated LVMI improvement or stabilization over time Secondary cardiac biomarkers: 14 of 16 participants achieved >25% reduction in high-sensitivity troponin I from baseline at latest visit 14 of 16 participants achieved reduction or stabilization in lateral wall thickness (LWT) from baseline at latest visit Modified Friedreich Ataxia Rating Scale (mFARS): 2.0-point mean improvement from baseline at latest visit across all participants with >6-months of follow-up (n=16) 11 of 16 participants achieved reduction or stabilization in mFARS from baseline at latest visit Previously reported data from Lexeo’s ongoing SUNRISE-FA trial (n=8) showed that all study participants achieved increases in frataxin protein expression from baseline at 3 months, with dose-dependent increases observed across cohorts. Treatment with LX2006 has been generally well tolerated with no Grade 3+ SAEs to date No clinically significant complement activation Minimal, transient liver function test (LFT) elevations No signs of frataxin over-expression observed in cardiac tissue No participants discontinued from either study One previously disclosed, possibly treatment-related Grade 2 event of asymptomatic myocarditis observed one year after dosing Lexeo Therapeutics will host a webcast at 8:00 AM ET today, October 7, 2025. Analysts and investors can participate by accessing the webcast live on the News & Events page in the Investors section of Lexeo’s website, www.lexeotx.com. The webcast will be archived on the company’s website following completion of the call, and presentation materials will be available on the Presentations page of the website. LX2006 is an AAV-based gene therapy candidate for the treatment of FA cardiomyopathy, the leading cause of death in individuals with FA which affects approximately 5,000 people in the United States. LX2006 is designed to systemically deliver a functional frataxin gene to promote the expression of the frataxin protein and restore mitochondrial function in myocardial cells. LX2006 is being evaluated in two clinical trials, the Lexeo-sponsored SUNRISE-FA Phase 1/2 clinical trial (NCT05445323) and the Weill Cornell Medicine investigator-initiated Phase 1A trial (NCT05302271). LX2006 has been granted Breakthrough Therapy, Regenerative Medicine Advanced Therapy, Orphan Drug, Rare Pediatric Disease and Fast Track designations by the FDA, admitted into the FDA CMC Development and Readiness Pilot (CDRP) program, and granted orphan medicinal product designation by the European Commission. Lexeo Therapeutics is a New York City-based, clinical stage genetic medicine company dedicated to reshaping heart health by applying pioneering science to fundamentally change how cardiovascular diseases are treated. The Company is advancing a portfolio of therapeutic candidates that take aim at the underlying genetic causes of conditions, including LX2006 in Friedreich ataxia (FA) cardiomyopathy, LX2020 in plakophilin-2 (PKP2) arrhythmogenic cardiomyopathy, and others in devastating diseases with high unmet need. The content above comes from the network. if any infringement, please contact us to modify.

Lexeo Therapeutics said that it could apply for an even earlier accelerated approval of its gene therapy to treat heart muscle disease in people with Friedreich’s ataxia. The FDA was open to the idea of pooling clinical data from its current Phase 1/2 gene therapy trial with results from its planned pivotal trial, the company said Tuesday. This means that the company could run a smaller pivotal study, Lexeo CEO R. Nolan Townsend said in a statement. The gene therapy, codenamed LX2006, is being studied to treat Friedreich’s ataxia cardiomyopathy. The FDA previously agreed that one of the primary endpoints, called left ventricular mass index (LVMI), in the pivotal trial could be evaluated earlier than one year. Higher LVMI indicates an abnormal thickening of the heart wall, which means it’s harder for the heart to pump blood. Lexeo’s shares $LXEO jumped 30% at market open Tuesday. In order for Lexeo to use pooled data, it has to submit manufacturing comparability analysis as well as nonclinical results since its future gene therapy manufacturing process is different compared to the Phase 1/2 study. On Tuesday, Lexeo also reported updated results from its Phase 1/2 trial, showing that five of six patients saw greater than 10% improvement on LVMI by one year and that all six reached LVMI measures within normal range as of their latest visit. In 17 participants, it was reported that the gene therapy “has been generally well tolerated” with “minimal, transient” elevations on liver enzyme tests. The gene therapy is currently being studied in two clinical trials: the Phase 1/2 study sponsored by Lexeo called SUNRISE-FA, as well as an investigator-sponsored Phase 1a study at Weill Cornell Medicine. The biotech plans to start its pivotal trial in the first half of next year. Friedreich’s ataxia is a rare disease caused by a deficiency in a protein called frataxin, which is needed for the mitochondria to function properly. The disease can lead to problems with movement and balance, as well as heart dysfunction, which is the leading cause of death in people with the rare degenerative condition. Lexeo’s gene therapy uses viral envelopes called AAVs to deliver a functional frataxin gene to heart cells.

iStock, Nuthawut Somsuk Despite tolerability concerns, nomlabofusp’s overall efficacy represents a “large win” for Larimar, according to analysts at William Blair, who lauded the therapy’s functional benefits. Larimar Therapeutics’ investigational frataxin therapy nomlabofusp significantly improved functional outcomes in an ongoing open-label study of patients with Friedreich’s ataxia—but safety signals have left investors disappointed. The biotech was down 33% at market close on Monday. Data reported Monday showed that patients treated with daily nomlabofusp saw a substantial increase in frataxin levels at 6 months, with skin concentrations matching those in asymptomatic carriers. The drug also led to a “consistent directional improvement” in key functional outcomes, including fatigue and activities of daily living, findings that Larimar said suggest a “potential clinical benefit across a broad spectrum of patients” with Friedreich’s ataxia (FA). Analysts at William Blair appeared to agree, telling investors in a Monday note that the frataxin improvement is “a large win” for nomlabofusp, while its functional benefits “have not been seen in an interventional FA trial to our knowledge.” Taken together, these results paint an “impressive” clinical efficacy pro nomlabofusp, the analysts wrote. Tolerability results, however, were mixed. In its news release on Monday, Larimar claimed that nomlabofusp was “generally well-tolerated” but revealed that seven of 39 treated patients had experienced anaphylaxis and needed to be pulled from the study. Following these cases, the biotech has decided to modify its starting dose regimen for nomlabofusp, which the FDA has agreed to. Despite regulatory alignment on the changes, the anaphylaxis episodes “are undoubtedly a concern for investors,” William Blair said on Monday, noting that risks will remain “somewhat unknown” as Larimar moves toward a biologics license application in the second quarter of 2026. Still, “the unmet need in FA remains high with no disease-modifying therapy currently available, and we still see a path forward for nomlabofusp approval here given impressive efficacy/biomarker data,” the analysts wrote. Friedreich’s ataxia is a rare mitochondrial disorder that affects 1 in 50,000 people in the U.S. The disease is characterized by a deficiency in the frataxin protein, which is crucial for mitochondrial function. Patients with FA experience motor and other movement difficulties, fatigue and problems with speech or swallowing, among other symptoms. Leading the FA space is Biogen with its Nrf2 agonist Skyclarys, which won the FDA’s approval in 2023 . The drug has since become a major product for Biogen, bringing in $382.5 million worldwide last year. Also in the FA game is PTC Therapeutics and its small-molecule drug vatiquinone, which inhibits key disease pathways. The drug’s development has been rocky, however. In May 2023, vatiquinone failed the Phase III MOVE-FA study when it did not significantly improve disease progression versus placebo. Last month, the FDA rejected vatiquinone, noting that “substantial evidence of efficacy was not demonstrated.”