Slide 1: Interim Clinical Data from the Phase 1/2 HEROIC-PKP2 Trial of LX2020
Interim Clinical Data from the Phase 1/2 HEROIC-PKP2 Trial of LX2020 for Arrhythmogenic Cardiomyopathy Caused by Mutations in the PKP2 Gene January 12, 2026 Exhibit 99.2
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, statements regarding Lexeo’s expectations and plans regarding its current product candidates and programs, including statements regardi
Slide 3: Preliminary Results Demonstrate Increased PKP2 Expression and Potential to Reduce Arrhythmia Burden
Preliminary Results Demonstrate Increased PKP2 Expression and Potential for LX2020 to Reduce Severe Arrhythmia Burden Mean decrease in non-sustained ventricular tachycardia (NSVT) of 20% across all participants at latest visit (n=8) and 22% at high dose (n=5); key arrhythmia measure correlated with
Slide 4: 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 of Disease ACM, arrhythmogenic cardiomyopathy; ARVD/C, arrhythmogenic right ventricular dysplasia/cardiomyopathy; ICD implantable cardioverter defibrillator; SDC sudde
Slide 5: 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 Potentially driven by calcium instability; may be improved with flecainide that blocks cardiac fast sodium channels1,2 PVC sp
Slide 6: PVCs May Trigger Ventricular Tachycardia; Measures Are Related But Driven by Different Mechanisms
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 7: Sustained VT Risk is Predicted by Increased PVC Burden and Non-Sustained VT Events
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 8: 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 Cardiac-specific promoter Promoter PKP2 gene Poly-A Rabbit β-globin polyA LX2020 Construct AAVrh.10hPKP2 PKP2-ACM LX2020 Mechanism Absence of PKP2 r
Slide 9: 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 10: Baseline Characteristics Consistent with PKP2 Arrhythmogenic Cardiomyopathy
Baseline Characteristics Consistent with PKP2 Arrhythmogenic Cardiomyopathy; More Advanced Disease Observed in High-Dose Cohorts Characteristic Statistic Low-Dose Cohort 1 2.0x1013 vg/kg, N=3 High Dose Cohorts 2 and 3 6.0x1013 vg/kg, N=7 Age, years Mean (SD) Min, Max 28 (6) 22, 34 38 (6.4) 28, 44 Ye
Slide 11: Baseline Characteristics by Participant, with More Advanced Disease in High-Dose Cohorts
Baseline Characteristics Consistent with PKP2 Arrhythmogenic Cardiomyopathy, with More Advanced Disease in High-Dose Cohorts Cohort 1 (2.0x1013 vg/kg) Cohort 2 (6.0x1013 vg/kg) Cohort 3 (6.0x1013 vg/kg) Characteristic Participant 1 Participant 2 Participant 3 Participant 4 Participant 5 Participant
Slide 12: Treatment with LX2020 Has Been Well Tolerated to Date
Treatment with LX2020 Has Been Well Tolerated to Date LX2020 generally well tolerated across ten participants dosed No clinically significant complement activation Elevations in liver function tests (LFT) observed in five participants at the high-dose, treated successfully with modified immunosuppre
Slide 13: LX2020 Transduction and Transcription Observed in All Participants
LX2020 Transduction and Transcription Observed in All Participants Post-Dose Levels1 Vector Copies / Diploid Genome LX2020 not detected in pre-dose VCN or mRNA samples as expected. Participant 3 elected not to undergo a post-treatment biopsy. Participant 1 VCN not performed due to insufficient remai
Slide 14: Increased PKP2 Protein Observed Across Most Participants
Increased PKP2 Protein Observed Across Most Participants % Increase PKP2 (Western Blot, GAPDH Normalized) PKP2 expression increased across participants with greater mean response at high dose Fibrofatty tissue (characteristic of ACM) may have impacted biopsy samples from participants 4 and 5; other
Slide 15: Appropriate Localization of PKP2 With Other Key Proteins at the Intercalated Disc
Appropriate Localization of PKP2 With Other Key Proteins at the Intercalated Disc Pre-Dose Following LX2020 administration, PKP2 protein colocalizes with Cx43 (a gap junction protein) and Ncad (a desmosomal adhesion protein) within cardiac intercalated discs Plakophilin–2 (PKP2) Connexin 43 (Cx43) N
Slide 16: Improvements Observed Across Clinical Parameters at Latest Visit
Improvements Observed Across Clinical Parameters at Latest Visit; PVCs and NSVT Reduced or Stable in Majority of Participants Cohort Part. # Latest Visit (months) ∆ PVC / 24H Baseline LV ∆ NSVT/7d Baseline LV ∆ RVEF2 Baseline LV ∆ PGIC Scale3 Baseline LV Cohort 1 (2E13 vg/kg) #1 (M) 12 861
Slide 17: Clinically Meaningful Reductions in Arrhythmia Burden Over Time
Clinically Meaningful Reductions in Arrhythmia Burden Over Time Mean PVC Change: PVCs and NSVT reduced or stabilized in majority of participants with >6 months of follow up -14% mean improvement in PVCs and -22% mean improvement in NSVT at latest visit in high-dose cohort 4 of 5 high-dose participan
Slide 18: Participants Stable Across Other Clinical Measures
Participants Stable Across Other Clinical Measures QRS Duration QRS duration stable across participants; majority start and remain within normal range Milliseconds (ms) Upper Limit of Normal1 (1) Wagner, G. S., et al. J Am Coll Cardiol, 2009. T-Wave Inversion T-wave inversion stable across participa
Slide 19: Summary of Results and Next Steps for LX2020
Summary of Results and Next Steps for LX2020 LX2020 generally well tolerated across 10 participants dosed Biopsies demonstrate robust LX2020 transduction and increased PKP2 expression at 3 months post treatment, with dose-dependent increases: Mean vector copy number of 1.5 at low dose (n=1) and 3.3
Slide 20: Lexeo Thanks the Arrhythmogenic Cardiomyopathy Community
Lexeo Thanks the Arrhythmogenic Cardiomyopathy Community Individuals and families impacted by genetically mediated cardiovascular diseases are at the center of our mission Lexeo is grateful to the study participants, caregivers, investigators and other members of the ACM community who have helped us
Slide 21: Thank you
therapeutics Thank you