Lexeo Therapeutics, Inc. · NASDAQ:LXEO
Lexeo Therapeutics — Investor Presentation (January 2025)
24 slides from Lexeo Therapeutics's investor presentation, Jan 13, 2025
Slide 1: Lexeo Therapeutics Corporate Overview
Lexeo Therapeutics Corporate Overview January 13, 2025
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: Lexeo: Advancing Cardiac Genetic Medicines In Diseases with High Unmet Need
Lexeo: Advancing Cardiac Genetic Medicines In Diseases with High Unmet Need Leveraging gene therapy to address devastating cardiac diseases with no existing disease-modifying treatments Potential best-in-class treatment of PKP2-ACM; ~60K patients in US with no disease-modifying treatment available I
Slide 4: Favorable Landscape for Cardiac Genetic Medicines Continues to Mature
Favorable Landscape for Cardiac Genetic Medicines Continues to Mature Evolving Regulatory Environment: Continued shift towards surrogate endpoints may circumvent need for larger cardiovascular outcome trials to achieve accelerated approval Improved Delivery Platforms: Improvements in modern AAV deli
Slide 5: Our Pipeline: Focused on Diseases with Significant Unmet Need and Clear Mechanisms
Our Pipeline: Focused on Diseases with Significant Unmet Need and Clear Mechanisms Clinical: Discovery Preclinical Phase 1/2 Phase 2/3 Preclinical: Indication: Programs: FA(1) Cardiomyopathy PKP2-ACM(2) FXN PKP2 Gene: LX2006 LX2020 (1) Friedreich ataxia. (2) Plakophilin 2 Arrhythmogenic Cardiomyopat
Slide 6: Cardiac Tropism of AAVrh10 May Allow Lower Dosing for Cardiac Gene Therapy
Cardiac Tropism of AAVrh10 May Allow Lower Dosing for Cardiac Gene Therapy AAVrh10 cardiac tropism may allow for lower doses compared to other vector serotypes while achieving targeted transgene biodistribution Observed ~1.5x to 2.0x greater biodistribution in the heart compared to AAV9 in multiple
Slide 7: LX2006 (FA Cardiomyopathy)
——S LEXEO / i LX2006 (FA Cardiomyopathy) a ‘A
Slide 8: FA is a rare, devastating and progressive disorder caused by loss of function mutations
FA is a rare, devastating and progressive disorder caused by loss of function mutations in the FXN gene (GAA repeat expansion) With a typical age of onset between 10 and 15 years, people with FA experience a combination of neurological and cardiac manifestations, with ~80% developing cardiomyopathy(
Slide 9: LX2006 Has the Potential to Treat the Root Cause of FA Cardiomyopathy
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
Slide 10: Elevated LVMI Predicts Mortality in FA and is Not Expected to Significantly Decrease Without Intervention
Elevated LVMI Predicts Mortality in FA and is Not Expected to Significantly Decrease Without Intervention Increases in LVMI Independently Predict Mortality in Friedreich Ataxia (FA) Natural history study showed a 19% higher risk of death per 10g/m2 (HR 1.19; 95% CI)(1) HR, Hazard Ratio; CI, Confiden
Slide 11: Dysfunction in Heart Muscle Cells Can Lead to Concentric Hypertrophy
Dysfunction in Heart Muscle Cells Can Lead to Concentric Hypertrophy and Poorer Outcomes in Multiple Cardiomyopathies Normal LVMI Normal LV Wall Thickness Normal hs-Troponin I LVMI LV Wall Thickness Hs-Troponin I Disease Progression Normal Heart Concentric Hypertrophy Measurements of Hypertrop
Slide 12: LX2006 Evaluated in Parallel SUNRISE-FA and Weill Cornell Trials
LX2006 is Being Evaluated in Parallel Lexeo-Sponsored SUNRISE-FA and Weill Cornell Investigator Initiated Trial 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 & O
Slide 13: Q3'24 Enrollment Update Across Ongoing Clinical Trials
Q3’24 Enrollment Update Across Ongoing Clinical Trials Lexeo Sponsored SUNRISE-FA Weill Cornell Investigator Initiated Dose Cohort Participant # Cardiac Biopsy Months of Follow-up in Prior Data Update Cohort 1 (1.8x1011 vg/kg) Participant 6 12 months Cohort 2 (5.6x1011 vg/kg) Participant 9 12 mo
Slide 14: Recent FDA Alignment Guides Future Pivotal Study Inclusion Criteria and Co-Primary Endpoints
Recent FDA Alignment Guides Future Pivotal Study Inclusion Criteria and Co-Primary Endpoints to Support Accelerated Approval FDA Alignment Threshold of 10% reduction in LVMI as measured by cMRI Interim Phase 1/2 Results: All patients with abnormal LVMI at baseline achieved > 10% reduction in LVMI at
Slide 15: Participants with Abnormal LVMI at Baseline Showed Improvements in Key Clinical Parameters
Participants with Abnormal LVMI at Baseline from July 2024 Data Update Showed Improvements in Key Clinical Parameters Participant (sex) LVMI at Baseline(1) ∆ LVMI (g/m2) Baseline 12-mo ∆ LWT (cm) Baseline 12-mo ∆ Hs-TNI (pg/ml) Baseline 12-mo Participant 1 (F) Abnormal 81 66 -18.5% 1.2 1.0
Slide 16: Increased Frataxin Expression Across All Participants Evaluated to Date
Increased Frataxin Expression Across All Participants Evaluated to Date Utilizing FDA Aligned Immunohistochemistry FXN Positive Area (%) Quantified IHC (FXN % Positive Area(1)) Cohort 1 Participant 6 Cohort 2 Participant 10 Pre-Dose FXN Levels Post-Dose FXN Levels FXN, Frataxin; IHC, Immunohistochem
Slide 17: LX2020 (PKP2-ACM)
LEXEO / y (PKP2-ACM)
Slide 18: 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 19: LX2020 Delivers a Full-Length PKP2 Gene to Cardiomyocytes
LX2020 Has Potential to Treat PKP2-ACM by Delivering a Full-Length PKP2 Gene to Cardiomyocytes, Restoring the Desmosomal Complex Cardiac-specific promoter Promoter PKP2 gene Poly-A Rabbit β-globin polyA LX2020 Construct AAVrh10.hPKP2 PKP2-ACM LX2020 Mechanism Absence of PKP2 results in impairment of
Slide 20: Robust Preclinical Package Supporting Ongoing Phase 1/2 Trial
Robust Preclinical Package Supporting Ongoing Phase 1/2 Trial IND-Enabling NHP: VCN in Various Heart Regions Robust Preclinical Package Murine studies utilizing CRISPR-Cas 9 edited model recapitulating PKP2-ACM disease features NHP safety study showed no toxicity at highest evaluated dose level (1x1
Slide 21: In Preclinical Studies LX2020 Successfully Impacted All Modifiable Elements of ACM
In Preclinical Studies LX2020 Successfully Impacted All Modifiable Elements of ACM Diagnosis and Risk Calculator LX2020 Preclinical Evidence Arrhythmias Arrhythmia Burden Daily Premature Ventricular Contraction (PVC) Count Ectopic Beats (7/10 without PVC) Life-threatening Arrhythmia Events SCD, ICD
Slide 22: LX2020 Ongoing Phase 1/2 Study (HEROIC-PKP2); Cohort 1 Fully Enrolled
LX2020 is Being Evaluated in an Ongoing Phase 1/2 Study (HEROIC-PKP2); Cohort 1 Fully Enrolled 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 individua
Slide 23: Multiple Program Updates in 2025 Across Two Clinical Stage Cardiac Programs
Multiple Program Updates in 2025 Across Two Clinical Stage Cardiac Programs Clinical Stage Program Upcoming 2025 Milestones Mid 2025: LX2006 program update (Cohort 3 biopsies and longer duration cardiac biomarker data across all cohorts) Late Q1/Early Q2 2025: Interim Data Readout (Cohort 1 protein
Slide 24: Thank you
therapeutics Thank you
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