Lexeo Therapeutics, Inc. · NASDAQ:LXEO
Lexeo Therapeutics — Technical Presentation (April 2025)
22 slides from Lexeo Therapeutics's technical presentation, Apr 7, 2025
Slide 1: Interim Data Update of LX2006 for the Treatment of Friedreich Ataxia Cardiomyopathy
Interim Data Update of LX2006 for the Treatment of Friedreich Ataxia Cardiomyopathy April 7, 2025 Exhibit 99.1
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: Individuals with FA Typically Present with Cardiac Symptoms in Adolescence
Individuals with FA Typically Present with Cardiac Symptoms in Adolescence, and Face an Average Life Expectancy of 35-40 Years Ron and his son, Keith, who passed from FA cardiomyopathy at age 24 “There are no approved treatments for the cardiomyopathy of FA. Time is of the essence.” – Ron Bartek, Co
Slide 4: Interim Results Support LX2006 as Potential First-in-Class Treatment for FA Cardiomyopathy
Interim Results Support LX2006 as Potential First-in-Class Treatment for FA Cardiomyopathy; Expect to Initiate Registrational Study By End of 2025 or Early 2026 Cohort 3 cardiac biopsies evaluated via LCMS demonstrated dose response relative to Cohorts 1-2 with increase of 115% on average from basel
Slide 5: FA is a rare, devastating and progressive multi-system disorder
FA is a rare, devastating and progressive multi-system 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 ca
Slide 6: LX2006 Has the Potential to Treat the Root Cause of FA Cardiomyopathy
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 le
Slide 7: 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 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 &
Slide 8: Recent FDA Alignment Guides 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 cardiac MRI at 12 months Interim Phase 1/2 Results: participants with abnormal LVMI at baseline achieved a mean
Slide 9: Baseline Characteristics Consistent with Cardiac Phenotype of FA
Baseline Characteristics 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 #12 #14 #15 #16 Gender F M F F M M F M F F F F M
Slide 10: Treatment with LX2006 Has Been Generally Well Tolerated to Date
Treatment with LX2006 Has Been Generally Well Tolerated to Date No signs of complement activation or other immunogenicity 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
Slide 11: Increased Frataxin Expression Across All Participants Evaluated at 3 Months
Participant #9 Increased Frataxin Expression Across All Participants Evaluated at 3-Months Post Treatment Utilizing LCMS Post-Treatment FXN Levels Increased in All Participants – Measured by LCMS Participant #6 Participant #10 Participant #11 Cohort 1 (n=1) Cohort 2 (n=3) Cohort 3 (n=4) Participant
Slide 12: Participants with Abnormal LVMI at Baseline: Improvements in Key Clinical Parameters
Participants with Abnormal LVMI at Baseline: Improvements in Key Clinical Parameters at Latest Visit, Latest Visit Average Reduction of 27% 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
Slide 13: 5 of 6 Achieve >10% Reduction in LVMI by 12-Month or Sooner Visit
Registrational Co-Primary Endpoint LVMI % Change Participants with Abnormal LVMI at Baseline: 5 of 6 Achieve >10% Reduction in LVMI by 12-Month or Sooner Visit with Trend of Deepening Improvement Over Time Cohort 1 (n=3) Cohort 2 (n=2) Cohort 3 (n=1) Note: Participant had less elevated LVMI baseline
Slide 14: LVMI Reductions Supported by Improvements in Lateral Wall Thickness and Troponin I
Participants with Abnormal LVMI at Baseline: LVMI Reductions Supported by Improvements in Lateral Wall Thickness and High-Sensitivity Troponin I Change from Baseline (mm) Note: Participant 7 remote 6-month follow-up, biomarkers unavailable. Change in LWT for Participants with Abnormal LVMI at Baseli
Slide 15: Participants with Normal LVMI at Baseline Showed Improvement or Stabilization
Participants with Normal LVMI at Baseline Showed Improvement or Stabilization in Key Clinical Parameters at Latest Visit 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) Partic
Slide 16: All Participants: Majority Reach or Remain in Normal Range for LVMI
All Participants (n=12): Majority Reach or Remain in the Normal Range for LVMI at Latest Visit Cohort 1 (n=3) Cohort 2 (n=1) Cohort 3 (n=1) LVMI (g/m2) for All Male Participants LVMI (g/m2) for All Female Participants LVMI (g/m2) Cohort 1 (n=3) Cohort 2 (n=4) Cohort 3 (n=0) LVMI (g/m2) Note: Normal
Slide 17: All Participants: Improvements in Lateral Wall Thickness and Troponin I
All Participants (n=12): Improvements in Lateral Wall Thickness and High-Sensitivity Troponin I Observed Across Participants Regardless of Baseline LVMI Change from Baseline (mm) Note: Participant 7 remote 6-month follow-up, biomarkers unavailable. *Participant 10 not included in Hs-TNI chart due to
Slide 18: All Participants: Evidence of Functional Improvement Over Time
All Participants (n=12): Evidence of Functional Improvement Observed Across Participants Over Time Regardless of Baseline Status Change from Baseline (latest visit) Improvement Improvement Modified Friedreich’s Ataxia Rating Scale (mFARS): All Participants Kansas City Cardiomyopathy Questionnaire (K
Slide 19: Interim Data Inform Preliminary Pivotal Trial Design
Interim Data Inform Preliminary Pivotal Trial Design: Registrational Single Arm Study with External Comparator Pivotal Phase 2 Study Design to Support Accelerated Approval Pathway Dose: Anticipate 1.2E12 vg/kg (cohort 3) based on safety data from ongoing Phase 1/2 study Key Eligibility Criteria: FA-
Slide 20: Large Unmet Need Remains in FA-CM
Large Unmet Need Remains in FA-CM Across Individuals with Early Signs of Cardiac Dysfunction to Later Stage Hypertrophy Significant Market Opportunity Significant commercial opportunity to impact the leading cause of death in FA While planned pivotal study will focus on severe FA-CM, Phase 1/2 resul
Slide 21: Summary of Results and Next Steps for LX2006
Summary of Results and Next Steps for LX2006 LX2006 (AAVrh10.hFXN) has been generally well tolerated with no signs of complement activation or other immunogenicity to date All biopsies showed increase in FXN expression at 3 months post treatment; Cohort 3 biopsies achieved mean increase of 115% from
Slide 22: Thank you
therapeutics Thank you
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