Lexeo Therapeutics, Inc. · NASDAQ:LXEO
Lexeo Therapeutics — Investor Presentation (June 2026)
31 slides from Lexeo Therapeutics's investor presentation, Jun 15, 2026
Slide 1: Lexeo Therapeutics Corporate Overview June 2026
Lexeo Therapeutics Corporate Overview June 2026 Exhibit 99.3
Slide 2: Forward-looking statements
Forward-looking statements This presentation contains “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 and the timing for receipt and announcement of dat
Slide 3: Reshaping heart health with pioneering science
Dedicated to reshaping heart health by applying pioneering science to fundamentally change how cardiovascular disease is treated Genetic medicine leader with rare cardiac disease focus Proven experience in the clinic Platform designed for safety and scalability Individuals and families impacted by F
Slide 4: Building a leading cardiac gene therapy platform
Building a leading cardiac gene therapy platform Differentiated AAVrh10 capsid Proven cardiac tropism allows for lower doses and improved therapeutic index Innovative AAV manufacturing Optimized Sf9 baculovirus manufacturing platform designed to support future commercial scale-up Genetic cardiac dis
Slide 5: Advancing cardiac genetic medicines in diseases with high unmet need
Advancing cardiac genetic medicines in diseases with high unmet need Lexeo cardiac programs and expertise: Clinical: LX2006 Friedreich Ataxia Cardiomyopathy LX2020 PKP2 Arrhythmogenic Cardiomyopathy Proven clinical experience with 27 patients treated using AAVrh10 Cardiomyopathies have few disease-m
Slide 6: Lexeo's AAVrh10 is a highly differentiated capsid
Yucatan Minipig Biodistribution(1) NHP Biodistribution(2) I-124 Vector Levels (% total body) Compelling Cardiac Tropism Greater Trends of Functional Improvement Versus AAV9 in PKP2-ACM Model(1) Greater Increase in EF Greater Reduction in EDV Greater Reduction in ESV +61% +32% -28% -18% -37% -23% Not
Slide 7: Lexeo manufactures AAVrh10 utilizing an optimized Sf9 baculovirus process
Lexeo manufactures AAVrh10 utilizing an optimized Sf9 baculovirus process Optimal potency Higher yields (1.0E15 vg/L) Greater downstream recovery (>55%) Fewer empty AAV capsids (<25%) Improved genomic purity owing to lack of plasmid transfections Scalable manufacturing Sustainable and defined starti
Slide 8: Lexeo's two clinical stage programs address devastating cardiac diseases
Lexeo’s two clinical stage programs address devastating cardiac diseases Leveraging gene therapy to address devastating cardiac diseases with no existing disease-modifying treatments Focus: LX2006 Only program with clinical-stage data in FA cardiomyopathy, which accounts for death in up to 80% of pe
Slide 9: Our pipeline
Our pipeline 1 - Friedreich ataxia. 2 - Plakophilin 2 Arrhythmogenic Cardiomyopathy. 3 - Desmoplakin. Programs: Indication: Gene: Phase I/II Phase II/III 2026 milestones: CARDIOVASCULAR FXN PKP2 CX43 TNNI3 Lexeo retains global rights across all programs. ~5K US prevalence ~60K US prevalence ~35K US
Slide 10: Friedreich Ataxia Cardiomyopathy (FA-CM) LX2006
Friedreich Ataxia Cardiomyopathy (FA-CM) LX2006
Slide 11: Cardiac complications are the leading cause of death in Friedreich Ataxia
Cardiac complications are the leading cause of death in Friedreich Ataxia 1 - Payne R.M. JACC Basic Transl Sci, 2022;13;7(12):1267-1283. - Friedreich’s Ataxia Research Alliance, 2024. - Norrish G., et al. Arch Dis Child, 2022;107(5), 450–455. - Reetz, K., et al. Lancet Neurol, 2025;24(7):614-624. FA
Slide 12: Timely, multidisciplinary care is critical to diagnose and manage FA-CM
Timely, multidisciplinary care is critical to diagnose and manage FA-CM There are no approved treatments for the cardiomyopathy of FA. Time is of the essence. Ron Bartek, Co-founder of FARA Ron Bartek and his son, Keith, who passed from FA cardiomyopathy at age 24 - Regner S, et al. American Journal
Slide 13: LX2006 has the potential to treat the root cause of FA cardiomyopathy
LX2006 has the potential to treat the root cause of FA cardiomyopathy: significant decrease in frataxin in the heart Frataxin deficiency results in mitochondrial dysfunction and leads to deficient energy production in hypertrophic cardiomyocytes Transfer of FXN gene to cardiomyocytes is intended to
Slide 14: Elevated LVMI predicts mortality in FA
Elevated LVMI predicts mortality in FA and is not expected to decrease significantly without intervention HR - Hazard Ratio; CI - Confidence Internal; LVMI - Left Ventricular Mass Index. Note: 10g/m2 represents approximately 10% change in LVMI based on echocardiography measurements of upper bound of
Slide 15: LX2006 clinical data show sustained or deepening improvements across cardiac measures
LX2006 clinical data show sustained or deepening improvements across cardiac measures of FA; LX2006 generally well tolerated LX2006 generally well tolerated across 17 participants dosed with no Grade 3 treatment-related SAEs to date No clinically significant complement activation Minimal, transient
Slide 16: Cardiac function improvement observed in individual with later stage cardiomyopathy
Cardiac function improvement observed in individual with later stage cardiomyopathy Effect of LX2006 on Cardiac Function Majority of Participants (16/17) Baseline LVEF: Normal Post therapy: No change One Participant (#13) with later stage cardiomyopathy Baseline LVEF: Low (35%) Post Therapy: Signifi
Slide 17: Change in mFARS: Open Label Cohort vs. UNIFAI Matched Control
Mean Change from Baseline (95% CI) Change in mFARS: Open Label Cohort (n=16) vs. UNIFAI Matched Control (n=45) mFARS validated clinical scale measures FA neurological progression; higher scores represent disease worsening Majority of LX2006-treated participants demonstrate mFARS improvement or stabi
Slide 18: Finalized SUNRISE-FA pivotal protocol and SAP for LX2006
Finalized SUNRISE-FA 2 pivotal protocol and SAP for LX2006 Study design: Open-label pivotal study with untreated control arm (no placebo or sham) Dose: 1.2x1012 vg/kg, one-time IV infusion Sample Size: 26 participants, 13 participants treated with LX2006 Key Eligibility Criteria: Adults (16yrs+): Ab
Slide 19: Plakophilin Arrhythmogenic Cardiomyopathy (PKP2-ACM) LX2020
Plakophilin 2 Arrhythmogenic Cardiomyopathy (PKP2-ACM) LX2020
Slide 20: Arrhythmogenic cardiomyopathy caused by mutations in the PKP2 gene
Arrhythmogenic cardiomyopathy caused by mutations in the PKP2 gene: devastating genetic heart disease with clearly defined mechanism PKP2-ACM is a rare, genetic cardiac disease caused by loss of function mutations in the PKP2 gene Progressive replacement of cardiac muscle with fatty fibrotic tissue,
Slide 21: LX2020 delivers a full-length PKP2 gene to cardiomyocytes, restoring the desmosome
Mutations in the PKP2 gene are the most common genetic cause of ACM; LX2020 delivers a full-length PKP2 gene to cardiomyocytes, restoring the desmosome ACM, arrhythmogenic cardiomyopathy. PKP2 cDNA (full length gene) Rabbit β-globin polyA AAVrh.10hPKP2 LX2020 construct: Cardiac-specific promoter Pro
Slide 22: Individuals with ACM experience high arrhythmia burden with a spectrum of severity
Individuals with ACM experience high arrhythmia burden with a spectrum of severity Early indicator of electrical instability that can trigger more severe/sustained arrhythmia >3 ventricular beats in a row, lasting under 30 seconds; self-terminating Closely associated with increased risk of sustained
Slide 23: PVCs may trigger ventricular tachycardia
Premature ventricular contractions (PVCs) may trigger ventricular tachycardia (VT); measures are related but driven by potentially different mechanisms (1) Cerrone et al. Nature Comm, 2017. (2) Kim et al. Circulation, 2019. (3) Sato P. et al. Circulation Research, 2009. (4) Oxford E.M et al. Circula
Slide 24: Sustained VT risk is predicted by increased PVC burden and non-sustained VT
In people with ACM, sustained VT risk is predicted by increased PVC burden and by non-sustained VT events PVC burden in ACM decreases initially after diagnosis but persists long term1 Initial drop driven by lifestyle change (exercise modification) and medication PVCs remain elevated (>500/24h) and v
Slide 25: Lexeo's role in advancing PKP2-ACM research
Phase I/II Trial Lexeo’s role in advancing PKP2-ACM research Retrospective EMR Review and Prospective Observational Natural History Study Objective: Assess the safety and efficacy of LX2020 in individuals with PKP2-ACM Dose: 2.0E13 vg/kg (Cohort 1), 6.0E13 vg/kg (Cohorts 2, 3) Key Endpoints: PKP2 ex
Slide 26: LX2020 is being evaluated in an ongoing phase 1/2 study (HEROIC-PKP2)
LX2020 is being evaluated in an ongoing phase 1/2 study (HEROIC-PKP2); enrollment completed in Q4 2025 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 LX2020 in i
Slide 27: Interim results demonstrate increased PKP2 expression and potential to reduce arrhythmia burden
Interim results demonstrate increased PKP2 expression and potential for LX2020 to reduce severe arrhythmia burden n=3 n=8 n=5 n=5 n=2 n=3 n=3 n=8 n=5 n=5 n=2 n=3 Mean change in PKP2 expression from baseline (western blot) Mean PVC change PVCs reduced or stabilized in majority of participants with >6
Slide 28: Preclinical Programs
Preclinical Programs
Slide 29: Lexeo is also advancing two preclinical cardiac gene therapy programs
Lexeo is also advancing two preclinical cardiac gene therapy programs +2026 research collaboration with Johnson & Johnson exploring novel routes of administration for cardiac AAV gene therapy to maximize safety and efficacy LX2021 High unmet need characterized by extensive fibrosis, high arrhythmic
Slide 30: Lexeo – a leader in cardiac gene therapy
Lexeo – a leader in cardiac gene therapy Leader in cardiac genetic medicine addressing high unmet need and clear market opportunity Catalyst rich 2026 with multiple key milestones expected across two clinical stage programs Differentiated AAVrh10 capsid and innovative Sf9 baculovirus manufacturing p
Slide 31: Thank You
‘therapeutics Thank You
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