8-K - LXEO - Equibles

UNITED STATESSECURITIES AND EXCHANGE COMMISSIONWASHINGTON, D.C. 20549

FORM 8-K

CURRENT REPORT

Pursuant to Section 13 or 15(d) of the Securities Exchange Act of 1934

Date of Report (Date of earliest event reported): October 07, 2025

Lexeo Therapeutics, Inc.

(Exact name of Registrant as Specified in Its Charter)

Delaware	001-41855	85-4012572
(State or Other Jurisdiction<br>of Incorporation)	(Commission File Number)	(IRS Employer<br>Identification No.)
345 Park Avenue South, Floor 6
New York, New York		10010
(Address of Principal Executive Offices)		(Zip Code)
Registrant’s Telephone Number, Including Area Code: 212 547-9879
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N/A
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(Former Name or Former Address, if Changed Since Last Report)

Check the appropriate box below if the Form 8-K filing is intended to simultaneously satisfy the filing obligation of the registrant under any of the following provisions:

☐Written communications pursuant to Rule 425 under the Securities Act (17 CFR 230.425)

☐Soliciting material pursuant to Rule 14a-12 under the Exchange Act (17 CFR 240.14a-12)

☐Pre-commencement communications pursuant to Rule 14d-2(b) under the Exchange Act (17 CFR 240.14d-2(b))

☐Pre-commencement communications pursuant to Rule 13e-4(c) under the Exchange Act (17 CFR 240.13e-4(c))

Securities registered pursuant to Section 12(b) of the Act:

Title of each class	Trading<br>Symbol(s)	Name of each exchange on which registered
Common Stock, $0.0001 par value per share	LXEO	Nasdaq Global Market

Indicate by check mark whether the registrant is an emerging growth company as defined in Rule 405 of the Securities Act of 1933 (§ 230.405 of this chapter) or Rule 12b-2 of the Securities Exchange Act of 1934 (§ 240.12b-2 of this chapter).

Emerging growth company ☒

If an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period for complying with any new or revised financial accounting standards provided pursuant to Section 13(a) of the Exchange Act. ☐

Item 7.01 Regulation FD Disclosure.

The corporate presentation to be used in connection with the webcast described in Item 8.01 below is attached as Exhibit 99.1 to this Current Report on Form 8-K and incorporated into this Item 7.01 by reference.

The information in this Item 7.01, including Exhibit 99.1 attached hereto, shall not be deemed “filed” for purposes of Section 18 of the Securities Exchange Act of 1934, as amended (the "Exchange Act"), or otherwise subject to the liabilities of that section, nor shall they be deemed incorporated by reference in any filing under the Securities Act of 1933, as amended, or the Exchange Act, except as expressly set forth by specific reference in such filing.

Item 8.01 Other Events.

On October 7, 2025, Lexeo Therapeutics, Inc. (the "Company") issued a press release announcing regulatory updates to key components of an accelerated approval pathway for LX2006 for the treatment of Friedreich ataxia (“FA”) cardiomyopathy based on FDA feedback to date, alongside positive interim Phase 1/2 clinical data for LX2006 for the treatment of FA cardiomyopathy. As part of the press release, the Company announced that it would be hosting a conference call and webcast at 8:00 a.m. ET on October 7, 2025 to discuss regulatory updates and interim Phase 1/2 clinical data of LX2006 for the treatment of FA cardiomyopathy. The press release is attached hereto as Exhibit 99.2 and incorporated by reference herein.

Item 9.01 Financial Statements and Exhibits.

(d) Exhibits

Exhibit<br><br>Number	Description
99.1	Corporate Presentation, October 7, 2025, furnished herewith.
99.2	Press release issued by the Company on October 7, 2025
104	Cover Page Interactive Data File (embedded within the Inline XBRL document)

SIGNATURES

Pursuant to the requirements of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on its behalf by the undersigned hereunto duly authorized.

			Lexeo Therapeutics, Inc.
Date:	October 7, 2025	By:	/s/ R. Nolan Townsend
			R. Nolan Townsend, Chief Executive Officer

Lexeo Therapeutics Announces Progress in FDA Discussions for Accelerated Approval Pathway and Positive Interim Clinical Data for LX2006 in FA CardiomyopathyOctober 7, 2025 Exhibit 99.1

Forward Looking Statements This presentation contains “forward-looking statements” within the meaning of the federal securities laws, including, but not limited to, statements regarding Lexeo’s expectations and plans regarding its current product candidates and programs, including statements regarding the structure of and timelines for completion of any current or additional clinical trials required by the FDA, the timing for receipt and announcement of data from any such clinical trials, and the timing and likelihood of potential regulatory developments, trial design changes and approval. Words such as “may,” “might,” “will,” “objective,” “intend,” “should,” “could,” “can,” “would,” “expect,” “believe,” “design,” “estimate,” “predict,” “potential,” “develop,” “plan” or the negative of these terms, and similar expressions, or statements regarding intent, belief, or current expectations, are forward-looking statements. While Lexeo believes these forward-looking statements are reasonable, undue reliance should not be placed on any such forward-looking statements. These forward-looking statements are based upon current information available to the company as well as certain estimates and assumptions and are subject to various risks and uncertainties (including, without limitation, those set forth in Lexeo’s filings with the SEC), many of which are beyond the company’s control and subject to change. Actual results could be materially different from those indicated by such forward looking statements as a result of many factors, including but not limited to: risks and uncertainties related to expectations regarding the initiation, progress, and expected results of Lexeo’s preclinical studies, clinical trials and research and development programs; the unpredictable relationship between preclinical study results and clinical study results; delays in submission of regulatory filings or failure to receive regulatory approval; liquidity and capital resources; and other risks and uncertainties identified in Lexeo’s Quarterly Report on Form 10-Q for the quarterly period ended June 30, 2025, filed with the SEC on August 14, 2025, and subsequent future filings Lexeo may make with the SEC. New risks and uncertainties may emerge from time to time, and it is not possible to predict all risks and uncertainties. Lexeo claims the protection of the Safe Harbor contained in the Private Securities Litigation Reform Act of 1995 for forward-looking statements. Lexeo expressly disclaims any obligation to update or alter any statements whether as a result of new information, future events or otherwise, except as required by law.

FDA Open to Earlier Co-Primary Endpoint Analysis and Pooling Data from Ongoing Phase I/II Studies of LX2006 with Pivotal Data; Potential to Accelerate BLA Submission for Accelerated Approval LVMI, Left Ventricular Mass Index; LFT, liver function tests. (1) Participant 11 6-month visit not conducted due to hurricane; 3-month visit used for mean calculation. FDA is open to a BLA submission 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 Generally well-tolerated across 17 participants dosed to date; no clinically significant complement activation and minimal, transient LFT elevations To enable pooling of these data, Lexeo will submit enhanced manufacturing comparability data to FDA and meet an additional nonclinical requirement prior to initiation of the planned pivotal Interim clinical data show sustained or deepening improvements in the majority of participants across both cardiac and neurologic measures of Friedreich ataxia (FA) Clinically meaningful improvement observed in the modified Friedreich Ataxia Rating Scale (mFARS), indicative of slowed disease progression and improved neurological function Clinically Meaningful Improvements in Cardiac and Neurologic Measures of FA Progress in FDA Discussions for Accelerated Approval Pathway Safety Profile Participants with abnormal LVMI at baseline achieved mean reduction in LVMI of 18%(1) at 6 months and 23% at 12 months, exceeding FDA-aligned threshold of 10% reduction FDA also previously agreed to evaluate co-primary endpoint of LVMI at a time point earlier than 12 months; Lexeo believes collective feedback may reduce size and length of pivotal study

Treatment for FA Cardiomyopathy is Urgently Needed Thank you sincerely to the participants, caregivers, investigators, health care professionals and to the FA community for supporting Lexeo research

Cardiac Complications are the Leading Cause of Death in Friedreich Ataxia Cardiac complications account for up to 80% of deaths in those with FA, with an average life expectancy of 35–40 years(1)(5) FA is a rare, progressive and devastating multisystem disease caused by a loss of function mutation in the FXN gene(1) With a typical age of onset between 5 and 15 years(2), individuals with FA experience a combination of cardiac and neurological manifestations, with cardiac complications accounting for up to 80% of deaths(1) Cardiac dysfunction in FA is associated with a multitude of symptoms but ultimately presents as cardiac hypertrophy and subsequent heart failure(1); hypertrophy in childhood is potentially associated with a more severe phenotype, with earlier progression to end-stage disease(3) The only approved disease-specific treatment for FA demonstrated efficacy on neurological measures but was not evaluated for the treatment of cardiac dysfunction in clinical trials, leaving significant unmet need within FA cardiomyopathy(4) ~15,000 individuals affected by FA worldwide(2) ~5,000 individuals affected by FA in the U.S.(2) FA, Friedreich Ataxia; FXN, Frataxin; LVMI, Left Ventricular Mass Index. (1) Payne R.M. JACC Basic Transl Sci, 2022;13;7(12):1267-1283. (2) Friedreich’s Ataxia Research Alliance, 2024. (3) Norrish G., et al. Arch Dis Child, 2022;107(5), 450–455. (4) Reetz, K., et al. Lancet Neurol, 2025;24(7):614-624. (5) Indelicato, E., et al. Mov Disord, 2024;39(3), 510–518. (6) Clinical Management Guidelines for Friedreich Ataxia. Chapter 4. The heart and cardiovascular system in Friedreich ataxia. 2022. (7) Lexeo Therapeutics, Data on File, 2025. Up to 40% of adults with FA have left ventricular hypertrophy as defined by abnormal LVMI(6)(7)

LX2006 Has the Potential to Treat the Root Cause of FA Cardiomyopathy: The Significant Decrease in Frataxin in the Heart FXN mutation FXN Deficiency Mitochondria Functional FXN FA Cardiomyopathy LX2006 Mechanism Cardiomyocyte Transfer of FXN gene to cardiomyocytes is intended to increase frataxin levels in the mitochondria and improve cardiac muscle cell function FXN deficiency results in mitochondrial dysfunction and leads to deficient energy production in hypertrophic cardiomyocytes Mitochondria Cardiomyocyte AAV, Adeno-Associated Virus; CAG, Chicken Beta‐Actin; cDNA, Copy DNA; FA, Friedreich Ataxia; FXN, Frataxin; Poly-A, Poly Adenosine. Ubiquitous promoter FXN cDNA (full length gene) CAG FXN gene Poly-A Rabbit β-globin polyA LX2006 Construct AAVrh10.hFXN Iron cluster Frataxin with iron

LX2006 is Being Evaluated in Parallel Lexeo-Sponsored SUNRISE-FA and Weill Cornell Investigator Initiated Trials SUNRISE-FA and Weill Cornell trials share a similar study design, enabling data from the two studies to be evaluated together 2 Key Inclusion Criteria 3 Key Measurements 1 Study Design & Objective Design: 52-week open-label study with a 4-year long term follow up Objective: To assess the safety and efficacy of LX2006 in individuals with cardiomyopathy associated with Friedreich ataxia Adults (18-50 years) Evidence of FA cardiomyopathy Neutralizing anti-AAVrh.10 titer cutoff Cardiac Structure & Function (LVMI, hsTnI, other measures) Functional / Reported Outcomes (mFARS, KCCQ) FXN Protein Expression Assessed Only in SUNRISE-FA LVMI, Left Ventricular Mass Index; hsTnI, High Sensitivity Troponin I; mFARS, Modified Friedreich Ataxia Rating Scale; KCCQ, Kansas City Cardiomyopathy Questionnaire; FXN, Frataxin. Note: LX2006 administered systemically; participants receive immune suppression with prednisone beginning on the day prior to treatment through 14 weeks following LX2006 administration. Note: In April 2024, Lexeo announced a license agreement with Cornell University for intellectual property rights including current and future clinical data from the ongoing Weill Cornell Medicine investigator-initiated trial of AAVrh10.hFXN (LX2006). Lexeo-sponsored SUNRISE-FA trial and Weill Cornell Medicine investigator-initiated trial utilize identical drug product manufactured at Weill Cornell for these ongoing studies. Cohort 1 1.8x1011 vg/kg Cohort 2 5.6x1011 vg/kg Cohort 3 1.2x1012 vg/kg

Lexeo Believes Collective Regulatory Feedback Could Reduce Size and Length of Planned Pivotal Study, Possibly Accelerating Overall Timeline to BLA Submission FDA open to BLA submission that includes LVMI data from ongoing Phase I/II studies pooled with new clinical data generated in planned pivotal, following enhanced manufacturing comparability data and an additional nonclinical requirement FDA also agreed to evaluate LVMI co-primary endpoint at time point earlier than 12 months >10% reduction remains target threshold; Phase I/II results exceeding threshold at 6 and 12 months FDA Feedback to Date LVMI, Left Ventricular Mass Index; LCMS, Liquid chromatography mass spectrometry. Co-primary Endpoints in Pivotal Study for Accelerated Approval LVMI Phase I/II studies used adherent HEK293 process, but future clinical and commercial supply will be produced using optimized Sf9-baculovirus manufacturing platform Lexeo will submit enhanced manufacturing comparability data to support pooling of LVMI data, including analytical comparability and nonclinical data to be shared prior to initiating the pivotal study from a murine bridging study using pre- and post-change drug product Manufacturing Comparability Frataxin Protein Expression Frataxin expression must be assessed with validated assay in the upcoming pivotal study; in Phase I/II studies, frataxin expression assessed with academic LCMS assay Any increase from baseline expression remains target threshold for planned pivotal study

In Phase I/II Studies, Baseline Characteristics Are Consistent with Cardiac Phenotype of FA Cohort 1 (1.8x1011 vg/kg) Cohort 2 (5.6x1011 vg/kg) Cohort 3 (1.2x1012 vg/kg) Participant Characteristic Participant # Participant # Participant # #1 #2 #3 #4 #5 #6 #7 #8 #9 #10 #11 #13 #17 #12 #14 #15 #16 Gender F M F F M M F M F F F F F M F M F LVMI, g/m2 81 109 53 65 60 86 63 74 57 66 100 110 44 85 49 72 56 LWT, mm 12 11 8 11 9 9 9 10 7 10 9 13 8 8 6 7 7 Hs Troponin I, pg/ml 224 148 108 2023 5 22 38 376 820 650 115 2518 498 25 11 11 42 Cardiac Biopsy                  mFARS Score 72 73 69 91 63 52 79 68 42 73 53 55 68 27 60 70 56 SKYCLARYS® Use During Trial                  Follow-up, months 24 24 21 21 18 24 12 12 24 21 12 12 <6 12 9 9 9 Abnormal(1) High-normal(1) (1) For cardiac imaging, abnormal defined as values 2 standard deviations (SD) above mean and high-normal defined as values 1SD above mean for respective gender (from healthy volunteers) as referenced in Kawel‑Boehm et al. J Cardiovasc Magn Reson (2020) 22:87 and for hs-troponin I abnormal defined as 99th percentile and high-normal defined as level above the threshold to detect individuals at risk of future CV events as referenced in Zeller at al. European Heart Journal (2014) 35, 271–281. Normal LVMI range for males: 39-85 g/m2 and normal LVMI range for females: 30-68 g/m2. 6 of 17 participants dosed to date have abnormal LVMI at baseline; remains key inclusion criteria for future pivotal study Safety data summarized for all 17 participants dosed to date; efficacy data inclusive of 16 participants with > 6 months of follow-up Normal(1)

Treatment with LX2006 Has Been Generally Well Tolerated to Date LFT, liver function tests. No clinically significant complement activation Minimal, transient LFT elevations after dosing; no participants above 3X upper limit of normal 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 Safety Summary

LVMI % Change Participants with Abnormal LVMI at Baseline, LVMI: Sustained or Deepening Improvement in LVMI Over Time Cohort 1 (n=3) Cohort 2 (n=2) Cohort 3 (n=1) Note: Participant had less elevated LVMI baseline Mid- and high-dose participants maintain LVMI improvements at 12 months 6 of 6 participants reach normal LVMI range at last follow up Change in LVMI (%) for Participants with Abnormal LVMI at Baseline NEW Pivotal Co-Primary Endpoint 10064 8574 8166 10995 8681 11054 (1) Participant 11 6-month visit not conducted due to hurricane; 3-month visit used for mean calculations. 9-month visits not conducted in Weill Cornell trial. Mean LVMI Change Participants at 12-mo visit -23% Participants at 6-mo visit1 (n=6) -18% Cohorts 2 and 3 at 12-mo visit -33% Cohorts 2 and 3 at 6-mo visit1 (n=3) -28%

Cohort Participant # | LVMI(1) at Baseline Latest Visit (months) ∆ LVMI (g/m2) Baseline  LV ∆ LWT (cm) Baseline  LV ∆ Hs-TNI (pg/ml) Baseline  LV Cohort 1 (1.8E11 vg/kg) Participant #3 (F) Normal 24 -17.0% 53  44 +25.0% 0.8  1.0 -50.9% 108  53 Participant #4 (F) High normal 21 -3.1% 65  63 -9.1% 1.1  1.0 -50.8% 2023  996 Participant #5 (M) Normal 21 0.0% 60  60 0.0% 0.9  0.9 -40.0% 5  3 Cohort 2 (5.6E11 vg/kg) Participant #7 (F) High normal 12 -11.1% 63  56 +11.1% 0.9  1.0 -65.8% 38  13 Participant #8 (M) High normal 12 -14.9% 74  63 -10.0% 1.0  0.9 -54.3% 376  172 Participant #9 (F) Normal 24 +3.0% 57  59 -12.3% 0.7  0.6 -93.8% 820  51 Participant #10(1) (F) High normal 21 +63.4% 66  107 +56.8% 1.0  1.5 +472.8%(1) 650  3723 Cohort 3 (1.2E12 vg/kg) Participant #14 (F) Normal 9 -9.4% 49  44 -1.8% 0.6  0.6 +45.5% 11  16 Participant #15 (M) High Normal 9 -12.1% 72  63 -1.4% 0.7  0.7 -27.3% 11  8 Participant #16 (F) Normal 9 -15.7% 56  47 -11.3% 0.7  0.6 -52.4% 42  20 Improved Stabilized Worsened Participants with Normal LVMI at Baseline: Improvement or Stabilization in Key Clinical Parameters at Latest Visit; All Participants Remained in Normal LVMI Range Excluding Participant #10 Normal LVMI range for males: 39-85 g/m2 and normal LVMI range for females: 30-68 g/m2. Approximately 1 year post treatment Participant #10 experienced possible focal myocarditis. Participant #10 also experienced interruption of immunosuppression regimen in first three months following treatment due to multiple pneumonias. Biomarkers potentially confounded by myocarditis. Most recent troponin result included from safety monitoring, other values correspond to 21-month visit.

All Participants (n=16), LVMI: All Participants Excluding Participant #10 Reached or Remained in the Normal Range for LVMI at Latest Visit Cohort 1 (n=3) Cohort 2 (n=1) Cohort 3 (n=2) LVMI (g/m2) for All Male Participants LVMI (g/m2) for All Female Participants LVMI (g/m2) Cohort 1 (n=3) Cohort 2 (n=5) Cohort 3 (n=2) LVMI (g/m2) Note: Normal LVMI range for males: 39-85 g/m2 and normal LVMI range for females: 30-68 g/m2. Participant 11 6-month visit not conducted due to hurricane. 9-month visits not conducted in Weill Cornell trial. Approximately 1 year post treatment Participant #10 experienced possible focal myocarditis. Participant #10 also experienced interruption of immunosuppression regimen in first three months following treatment due to multiple pneumonias. Biomarkers potentially confounded by myocarditis. Normal Range Participant 10(1) Normal Range

All Participants (n=16), Supportive Endpoints: Improvements in Lateral Wall Thickness and High-Sensitivity Troponin I Across Participants Regardless of Baseline LVMI Change from Baseline (mm) *Participant 10 not included in Hs-TNI chart due to scale. Values are +29% at 6M, +45% at 9M, +2,702% at 12M, +1,857% at 18M, +1,620% at 21M, and +473% as of most recent safety monitoring. Participant 11 6-month visit not conducted due to hurricane. 9-month visits not conducted in Weill Cornell trial. Change in Lateral Wall Thickness (2D Measurement) Change in High-Sensitivity Troponin I* Change from Baseline (%) Cohort 1 (n=6) Cohort 2 (n=6) Cohort 3 (n=4) Cohort 1 (n=6) Cohort 2 (n=5) Cohort 3 (n=4) Participant 10

All Participants (n=16), mFARS: Functional Improvement Over Time Using the Modified Friedreich Ataxia Rating Scale (mFARS) Compared to Natural History Mean Change from Baseline Change in mFARS: All Participants (n=16) FA-COMS Natural History(2) (16-40yrs Cohort) LX2006 (18-35yrs) n=16 n=16(1) n=13 n=8 n=4 mFARS clinical scale measures FA neurological progression across four sub-scales: upright stability, upper limb coordination, lower limb coordination and bulbar function 11 of 16 participants improved or stabilized relative to baseline at latest visit Evidence of neurological functional improvement, compared to natural history progression of disease Note: Natural history for illustrative purposes only. Differences exist between trial designs and participant characteristics, and caution should be exercised when comparing data across unrelated studies. 11) Participant 11 6-month visit not conducted due to hurricane; 3-month visit used for mean calculations. (2) Patel, M. et al. Ann Clin Transl Neurol, 2016. 3: 684-694. Progression of Friedreich ataxia: quantitative characterization over 5 years.https://doi.org/10.1002/acn3.332

All Participants (n=16), mFARS: 11 of 16 Participants Improved or Stabilized Relative to Baseline at Latest Visit Change in mFARS by Dose Cohort (n=16) Change from Baseline (# points) Cohort 1 (n=6) Cohort 2 (n=6) Cohort 3 (n=4) Change in mFARS by SKYCLARYS® Utilization (n=16) Change from Baseline (# points) SKYCLARYS® use at time of dosing (n=3) No SKYCLARYS® use during study (n=8) SKYCLARYS® initiated at 7-12 mo (n=5) FA-COMS(1) Natural History (16-40yrs Cohort) Mean Change from Baseline Note: Natural history for illustrative purposes only. Differences exist between trial designs and participant characteristics, and caution should be exercised when comparing data across unrelated studies. Participant 11 6-month visit not conducted due to hurricane. (1) Patel, M. et al. Ann Clin Transl Neurol, 2016. 3: 684-694. Progression of Friedreich ataxia: quantitative characterization over 5 years.https://doi.org/10.1002/acn3.332

Summary and Next Steps for LX2006 LX2006 (AAVrh10.hFXN) has been generally well tolerated to date with no clinically significant complement activation and minimal, transient LFT elevations Sustained or deepening improvements in the majority of participants across both cardiac and neurologic measures of FA: Participants with abnormal baseline LVMI achieved 18% mean reduction at 6 months and 23% mean reduction at 12 months Reductions in LVMI supported by improvements in other markers of cardiac structure and health, including lateral wall thickness and high-sensitivity troponin I Clinically meaningful improvement in mFARS, indicative of slowed disease progression and improved neurologic function FDA open to BLA submission for Accelerated Approval that includes clinical data from ongoing Phase I/II studies pooled with clinical data to be generated in planned pivotal study, with enhanced manufacturing comparability Continued discussions on pivotal trial protocol and comparability, including analytical and nonclinical, expected into early 2026 Lexeo plans to initiate pivotal study in first half of 2026

Thank you

EX-99.2

Exhibit 99.2

Lexeo Therapeutics Announces Progress in FDA Discussions for Accelerated Approval Pathway and Positive Interim Clinical Data for LX2006 in Friedreich Ataxia Cardiomyopathy

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

NEW YORK – October 7, 2025 (GLOBE NEWSWIRE) – 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.”

FDA Feedback to Date

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.

LX2006 Interim Clinical Update (n=16 participants with >6-months of follow-up)

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.

LX2006 Interim Safety Update (n=17 participants)

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

Corporate Webcast Details 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.

About LX2006 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.

About Lexeo Therapeutics

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.

Cautionary Note Regarding Forward-Looking Statements Certain statements in this press release may constitute “forward-looking statements” within the meaning of the federal securities laws, including, but not limited to, Lexeo’s expectations and plans regarding its current product candidates and programs, the structure of and timelines for completion of any current or additional clinical trials required by the FDA, the timing for receipt and announcement of data from any such clinical trials, and the timing and likelihood of potential regulatory developments, trial design changes and approval. Words such as “may,” “might,” “will,” “objective,” “intend,” “should,” “could,” “can,” “would,” “expect,” “believe,” “design,” “estimate,” “predict,” “potential,” “develop,” “plan” or the negative of these terms, and similar expressions, or statements regarding intent, belief, or current expectations, are forward-looking statements. While Lexeo believes these forward-looking statements are reasonable, undue reliance should not be placed on any such forward-looking statements. These forward-looking statements are based upon current information available to the company as well as certain estimates and assumptions and are subject to various risks and uncertainties (including, without limitation, those set forth in Lexeo’s filings with the U.S. Securities and Exchange Commission (SEC)), many of which are beyond the company’s control and subject to change. Actual results could be materially different from those indicated by such forward-looking statements as a result of many factors, including but not limited to: risks and uncertainties related to global macroeconomic conditions and related volatility; expectations regarding the initiation, progress, and expected results of Lexeo’s preclinical studies, clinical trials and research and development programs; the unpredictable relationship between preclinical study results and clinical study results; delays in submission of regulatory filings or failure to receive regulatory approval; liquidity and capital resources; and other risks and uncertainties identified in Lexeo’s Quarterly Report on Form 10-Q for the quarterly period ended June 30, 2025, filed with the SEC on August 14, 2025, and subsequent future filings Lexeo may make with the SEC. New risks and uncertainties may emerge from time to time, and it is not possible to predict all risks and uncertainties. Lexeo claims the protection of the Safe Harbor contained in the Private Securities Litigation Reform Act of 1995 for forward-looking statements. Lexeo expressly disclaims any obligation to update or alter any statements whether as a result of new information, future events or otherwise, except as required by law.

Media Response:

Media@lexeotx.com

Investor Response:

Carlo Tanzi, Ph.D.

ctanzi@kendallir.com