LXEO Lexeo Therapeutics Inc

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Interim Phase 1/2 Clinical Data of LX1001 for the Treatment of APOE4-associated Alzheimer’s DiseaseOctober 30, 2024 1 Exhibit 99.2

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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 anticipated benefits of LX1001 for the treatment of APOE4-associated Alzheimer’s disease, the timing for receipt and announcement of data from its clinical trials and the likelihood of receiving regulatory approvals. 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 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 Annual Report on Form 10-K for the year ended December 31, 2023, filed with the SEC on March 11, 2024, Quarterly Report on Form 10-Q for the quarter ended June 30, 2024, filed with the SEC on August 12, 2024, 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.

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Advancing Genetic Medicines in Larger-Rare and Prevalent Patient Populations Clinical: Discovery Preclinical Phase 1/2 Phase 2/3 Preclinical: Cardiovascular Indication: LX1001 LX1020 LX1021 Programs: Alzheimer’s: APOE4 homozygotes APOE4-Associated Alzheimer’s Disease FA(1) Cardiomyopathy PKP2-ACM(2) FXN PKP2 APOE2+ Gene of Interest: LX2006 LX2020 APOE2+ Christchurch(4) APOE2+ Alzheimer’s: APOE4 homozygotes Alzheimer’s: APOE4 homozygotes APOE4- (1) Friedreich’s ataxia. (2) Plakophilin 2 Arrhythmogenic Cardiomyopathy. (3) Desmoplakin. (4) Christchurch Modified APOE2 gene. CX43 LX2021 DSP(3) Cardiomyopathy Hypertrophic Cardiomyopathy TNNI3 LX2022 Today’s Focus Wholly-owned pipeline with franchises in two core therapeutic areas of high unmet need

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APOE 4/4 Homozygotes: A Distinct, Genetically Defined Alzheimer’s Disease Population APOE4/4 homozygotes exhibit earlier symptom onset, a distinct sequence of biomarker changes, and a faster rate of cognitive decline(3,4) ~2% of population Nearly all APOE4 homozygotes will develop Alzheimer’s symptoms within 49-81 years of age(3) Individuals with two copies of the APOE4 allele carry a ~15x increased risk of developing Alzheimer’s Disease(1) ~15% of Alzheimer’s cases are APOE4/4 homozygotes Belloy, M. E., Napolioni, V. & Greicius, M. D. A quarter century of APOE and Alzheimer’s disease: progress to date and the path forward. Neuron. 2019; 101, 820–838 Alzheimer’s Association: Alzheimer’s Disease Facts & Figures, 2024 | Yamazaki Y, et al. Nature Neurology Review, 2019. Vol 15, p501 Fortea, J. et al. APOE4 homozygozity represents a distinct genetic form of Alzheimer’s disease. Nature Medicine. 2024; 30, 1284–1291. doi: 10.1038/s41591-024-02931-w. Martins, C.A.R. et al. APOE alleles predict the rate of cognitive decline in Alzheimer disease: a nonlinear model. Neurology. 2005; 65(12):1888-93. doi: 10.1212/01.wnl.0000188871.74093.12. PMID: 16380608. are APOE4/4 homozygotes(2) ~900K APOE4/4 AD patients in US(2) population with high incidence rate, expected to increase with aging population No suitable treatment options for E4/E4s; anti-amyloid therapies carry increased ARIA risk & reduced efficacy for this population

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APOE4 Is A Known Driver of Alzheimer’s Risk, Affecting Multiple Pathways Neuroinflammation Tau aggregation Mitochondrial dysfunctional Aß deposition/clearance Synaptic deficits Neurotoxicity APOE4 APOE4 drives Alzheimer’s disease pathogenesis Associated with toxicity to neurons Accelerates amyloid deposition/slows clearance Accelerates propagation of tau tangles and tau-mediated neurodegeneration Linked to synaptic defects and mitochondrial dysfunction Activates microglia, adding to CNS inflammation Contributes to breakdown of BBB Associated with dysregulation and reduction of cerebral blood flow Adapted from Yu J, et al. Annual Reviews of Neuroscience, 2014.

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APOE2 is Protective Across Multiple Pathways; Increasing the Ratio of APOE2/4 Can Dilute APOE4 Toxicity and Express APOE2 Protectivity Martins, C.A.R. et al. APOE alleles predict the rate of cognitive decline in Alzheimer disease: a nonlinear model. Neurology. 2005; 65(12):1888-93. doi: 10.1212/01.wnl.0000188871.74093.12. PMID: 16380608. Raulin, AC. et al. ApoE in Alzheimer’s disease: pathophysiology and therapeutic strategies. Mol Neurodegeneration 17, 72 (2022). https://doi.org/10.1186/s13024-022-00574-4 Shi, Y. et al. ApoE4 markedly exacerbates tau-mediated neurodegeneration in a mouse model of tauopathy. Nature. 2017;549(7673):523-527. doi: 10.1038/nature24016.  Clifford, J.R. et al. Hypothetical Model of Dynamic Biomarkers of the Alzheimer’s pathological cascade. The Lancet Neurology, 2010; Volume 9 Issue 1, 119-128. Rawat, P. et al. Phosphorylated Tau in Alzheimer's Disease and Other Tauopathies. Int J Mol Sci. 2022;23(21):12841. doi: 10.3390/ijms232112841. PMID: 36361631; PMCID: PMC9654278. APOE-Targeting Interventional Treatment APOE2 can dilute APOE4: The dilutive effect in APOE2/4 vs. APOE4/4 AD genotypes demonstrates a strong case for therapeutic promise; APOE2/4 heterozygotes have lower risk of onset and slower disease progression(1) Increasing evidence that APOE2 suppresses Aß toxicity and tau pathology later in disease course (2,3) Introduction of APOE2 following AD diagnosis will address ‘downstream’ Tau pathology(4) Reduce Tau-mediated injury & degeneration for the most clinically meaningful impact on function & memory(5) Early Accumulation of Amyloid Burden Accumulation of Tau Burden Neuro-degeneration Brain Atrophy Underlying E4/E4 Genetics Disease Diagnosed Presymptomatic AD MCI AD with Dementia Memory & Clinical Function

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Unique Approach to Targeting Underlying Genetics of APOE4/E4 Alzheimer’s Disease LX1001 Mechanism of Action: Gene therapy delivering protective APOE2 transgene to the CNS of APOE4 homozygotes Phase 1/2 First & only clinical-stage gene therapy candidate targeting genetics of APOE4/4 AD Differentiated single-dose treatment Clinically validated AAVrh.10 capsid, utilized in multiple human studies and large animal proof-of-concept studies Ubiquitous promoter CAG APOE2 gene Poly-A Rabbit β-globin polyA LX1001 Construct APOE2 cDNA (full length gene) AAVrh10.hAPOE2

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LX1001 Phase 1/2 Trial in APOE4 Homozygotes Key Inclusion Criteria: ≥50 yr APOE4 homozygotes Mild cognitive impairment (MCI) to moderate dementia with biomarkers (amyloid PET and CSF) consistent with Alzheimer’s disease Cohort 1 n=5 Cohort 2 n=4 Cohort 3 n=3 1.4x1010 vg/ml CSF 5.7x1012 Total VGs 4.4x1010 vg/ml CSF 1.8x1013 Total VGs 1.4x1011 vg/ml CSF 5.7x1013 Total VGs Primary Endpoint: Safety Secondary Endpoint: APOE2 CSF protein expression Other Secondary Endpoints: CSF biomarkers: Aß42/Aß40 ratio, T Tau and P Tau Amyloid and tau PET scans Cognitive testing Endpoints Trial Design: 52-Week Follow-up Key Features: 52-week, dose-ranging, open-label trial with 5-yr long-term follow-up Vector: AAVrh10 Route of Administration: C1-C2 (between cervical vertebrae 1 and 2) or intracisternal injection Immune Suppression: corticosteroids prior to treatment & tapering post dosing Vector genomes measured using ddPCR. Assumes average CSF in patient of 408.7 ml. Cohort 4 n=3 12-mo. data available for Cohorts 1-3; 6-mo. data for Cohort 4 1.4x1014 Total VGs Study Status (as of July 26th data cut) Study Summary Enrolled (N= 15) Cohort 1 (n = 5) Cohort 3 (n = 3) Cohort 4 (n = 3) Cohort 2 (n = 4) Discontinued (n = 0) Discontinued (n = 0) Discontinued (n = 0) Completed (n = 4)** Completed (n = 4) Completed (n = 3)§ Completed (n = 0) Discontinued* (n = 1) *Withdrawal by Participant (no 6- and 12-month follow-up) **One completed by remote visit; 12mo visit without CSF/imaging §One completed M12 visit but lumbar puncture and PET scans not completed

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At Baseline, Cohorts 1 and 3 Include Patients with More Advanced Disease Baseline Characteristics Cohort 1 (n=5*) Cohort 2 (n=4) Cohort 3 (n=3) Cohort 4 (n=3) Total (n=15) Demographics Age, years, mean (SD) 63.8 (5.5) 64.3 (2.2) 63.7 (12.2) 70.7 (3.5) 65.3 (6.4) Sex – Female, n (%) 5 (100) 4 (100) 2 (66.7) 1 (33.3) 12 (80) Race – White, n (%) 5 (100) 4 (100) 3 (100) 3 (100) 15 (100) Ethnicity – Hispanic or Latino, n (%) 0 1 (25) 0 0 1 (6.7) AD Diagnosis by Physician Assessment MCI, n (%) 1 (20) 4 (100) 1 (33.3) 1 (33.3) 7 (46.7) Mild dementia, n (%) 0 0 0 2 (66.7) 2 (13.3) Moderate dementia, n (%) 4 (80) 0 2 (66.7) 0 6 (40) Cognitive Scales MMSE Mean (SD) Median (Min-Max) 14.8 (8.9) 13.0 (4-27) 27.0 (2.7) 28.0 (23-29) 15.3 (2.9) 17.0 (12-17) 25.3 (3.2) 24.0 (23-29) 20.3 (7.8) 23.0 (4-29) MMSE Groups, n (%) <20 >20 to <26 >27 3 (60) 1 (20) 1 (20) 0 1 (25) 3 (75) 3 (100) 0 0 0 2 (66.7) 1 (33.3) 6 (40) 4 (26.7) 5 (33.0) CDR-SB Mean Score (SD) Median Score (Min-Max) 8.10 (4.3) 10.0 (2.5-12.0) 2.00 (1.4) 2.0 (1.0-3.0) 5.17 (2.5) 4.0 (3.5-8) 2.50 (1.3) 3.00 (1.0-3.5) 5.20 (3.8) 3.50 (1.0-12.0) ADAS-Cog 13 Mean Score (SD) Median Score (Min-Max) 36.4 (16.1) 46.0 (16.0-50.0) 15.2 (14.7) 9.5 (5.0-37) 33.7 (5.6) 34.7 (27.7-38.7) 24.8 (12.2) 31.7 (10.7-32.0) 27.9 (15.0) 31.7 (5.0-50.0) PET Imaging Amyloid PET SUVR, mean (SD) Centiloids, mean (SD) 1.5 (NA) 175.5 (120.9) 1.34 (0.39) 59.3 (55.4) 1.69 (0.19) 126.0 (37.6) 1.66 (0.12) 120.3 (21.1) 1.54 (0.29) 110.58 (65.7) Tau PET SUVR, mean (SD) NA NA 2.09 (0.18) 1.62 (0.36) 1.85 (0.36) MMSE 30-point scale Lower score= Greater impairment CDR-SB 0-18 scale ADAS-Cog 13 0-85 scale Higher score= Greater impairment *Post-treatment data unavailable for two patients with moderate dementia in Cohort 1

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LX1001 Was Well Tolerated Across All Four Dose Cohorts Treatment with LX1001 was  well-tolerated across all 4 dose cohorts No reports of ARIA(1) Transient CSF pleocytosis (>5cells/μL), predominantly lymphocytic, was observed in 12 participants, with no significant adverse events associated Four SAE’s: Three unrelated to treatment: diverticulitis, pneumothorax, skin ulcer One event possibly related: mild-moderate sensorineural hearing loss Cognitive measures indicated no safety signal with no clear pattern of change observed in this study. Significant change not expected given sample size and measurement variability. Average change from baseline across all patients with 12-months of follow up: MMSE -1.2 (n=9) ADAS-Cog13 7.1 (n=8) CDR-SB 1.8 (n=6) Safety Findings Amyloid-related imaging abnormalities (ARIA) refer to MRI findings observed in patients receiving anti-amyloid therapies for Alzheimer’s disease. ARIA is most commonly observed as brain swelling, and/or microhemorrhages, and has a higher incidence in patients who are APOE4 allele carriers.

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APOE2 Protein Expressed in CSF in All Participants, with Dose- and Time-Dependent Increase in Expression and Durability to 12 Months APOE2 (fmol/µl) – Mean APOE4 (fmol/µl) – Mean APOE 2:4 Ratio (%) – Mean Cohort 1 Cohort 2 Cohort 3 Cohort 4 Cohort 3 Outlier Cohort 3 Outlier Screening Day 1 Month 3 Month 6 Month 12 Cohort 1 n=5 n=5 n=2 n=2 n=1 Cohort 2 n=4 n=3 n=4 n=4 n=4 Cohort 3* n=2 n=2 n=2 n=2 n=2 Cohort 4 n=3 n=3 n=3 n=3 NA *excludes Cohort 3 outlier

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LX1001 Stabilized Amyloid Progression in Majority of Participants at Last Follow-Up CSF Aß42/40 Amyloid PET – SUVR Majority of patients with minimal change from baseline Change from Baseline (Ratio) Mean Change from Baseline (SUVR) At 12 months or last follow up, patients remained similar to baseline, suggesting stabilization of Aß pathology Cohort 1 Cohort 2 Cohort 3 Cohort 4* No Change No Change MCI or MILD MOD Baseline Cognition by MMSE: Cohort 1 Cohort 2 Cohort 3 Cohort 4* * * *Indicates results as of 6-month visit. Each bar represents absolute change from baseline per participant at 12 months, or last follow up if 12-month follow-up unavailable. Note: protocol deviation, amyloid PET not performed in two subjects in Cohort 1. 12-Month 12-Month

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LX1001 Reduced CSF T-Tau & P-Tau181 in 9 of 13 Patients at Last Follow-Up CSF T-Tau CSF P-Tau181 Note: Assay variability within +/- 6% PBO = Placebo, LEC = Lecanemab. *Indicates results as of 6-month visit. Each bar represents absolute change from baseline per participant at 12 months, or last follow up if 12-month follow-up unavailable. Source: Iwatsubo, T., Irizarry, M., Van Dyck, C., Sabbagh, M., Bateman, R.J., Cohen, S. (2022) Clarity AD: A Phase 3 Placebo-Controlled, Double-Blind, Parallel-Group, 18-month Study Evaluating Lecanemab in Early Alzheimer's Disease. Powerpoint, Clinical Trials on Alzhiemer’s Disease (CTAD). Dotted lines reflect mean results from separate study of lecanemab versus placebo, and are used to show mean change from baseline data for participants in that study, which included all APOE genotypes and only patients with MCI and mild AD. Lecanemab was not studied in the Phase 1/2 study of LX1001. Cohort 1 Cohort 2 Cohort 3 Cohort 4* MCI or MILD MOD Baseline Cognition by MMSE: * Cohort 1 Cohort 2 Cohort 3 Cohort 4* * Change from Baseline (pg/mL) Change from Baseline (pg/mL) PBO (LEC) LEC PBO (LEC) LEC 12-Mo Mean Change: PBO (LEC): +12% | LEC: -6% LX1001 moderate patients mean change (last visit): -16% (n=4) 12-Mo Mean Change: PBO (LEC): +10% | LEC: -15% LX1001 moderate patients mean change (last visit): -20% (n=4) Improvement Improvement 12-Month 12-Month

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LX1001 Reduced P-Tau217 & P-Tau231 In 4 of 6 Patients at Last Follow-Up CSF P-Tau231 (12 month) Note: Assay variability within +/- 6% *Indicates results as of 6-month visit. Each bar represents absolute change from baseline per participant at 12 months, or last follow up if 12-month follow-up unavailable. AD Natural History (NHx) progression represents natural history for CSF P-tau217 over 12 months per Ashton NJ, et al. Diagnostic Accuracy of a Plasma Phosphorylated Tau 217 Immunoassay for Alzheimer Disease Pathology. JAMA Neurol. 2024 Mar 1;81(3):255-263. Sample includes 70% E4 carriers with MCI/mild dementia. Cohort 3 Cohort 2 * MCI or MILD MOD Baseline Cognition by MMSE: Change from Baseline (pg/mL) Change from Baseline (pg/mL) CSF P-Tau217 (12 month) AD NHx Progression Improvement Cohort 3 Cohort 2 * Measure not collected in Cohort 1; Cohort 4 samples pending analysis Improvement

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LX1001 Reduced Tau Burden via Global SUVR (PET); Highly Correlated Predictor of Cognitive Outcomes Driven by Alzheimer’s Disease(1) Tau PET – Global SUVR Note: APOE4/4 NHx progression represents natural history for tau PET in E4 homozygotes over 12 months per ADNI database, converted from centiloids; Malpetti. M. et al. Tau Beats Amyloid in Predicting Brain Atrophy in Alzheimer Disease: Implications for Prognosis and Clinical Trials. J Nucl Med. (2022) Cohort 3 Cohort 4 Reduced intensity in Tau PET SUVR from a single patient in Cohort 3 over 12 months Baseline M12 0.0 Tau PET SUVR 4.0 Cohort 4 not yet available 12-Month Improvement APOE4/E4 NHx Progression Mean CFB (SUVR) Measure not collected in Cohorts 1 or 2; Cohort 4 12mth pending analysis 6-Month Mean Change from Baseline (SUVR) Cohort 3 outlier with highest APOE2 expression; 12-mth PET not performed

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LX1001 Reduced Tau Burden via Regional SUVR (PET), Indicating Reduction of Tau Propagation and Slowing of Disease Progression Tau PET – Regional SUVR 6-Month (n=6) Medial Temporal Temporal Parietal Cingulate Frontal Occipital 12-Month (n=2) Improvement Improvement C4 not yet available Cohort 3 outlier (with highest APOE2 expression) demonstrated the greatest reduction in Tau PET at 6-months; 12-month PET data not collected for this patient Mean Change from Baseline (SUVR) Mean CFB (SUVR) Cohort 3 (MOD) Cohort 4

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LX1001 Phase 1/2 Key Takeaways Confidential Safety Well-tolerated across all cohorts No reports of ARIA Four SAEs, one possibly treatment related Efficacy APOE2 expressed in CSF of all participants, with dose-and time-dependent increase in E2:E4 expression Stabilization of amyloid pathology Consistent reduction in key tau biomarkers Greatest effect observed in patients with moderate dementia 1 2 Ph. 1/2 results confirm therapeutic potential of APOE2 for APOE4 homozygotes

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Regulatory Precedent for Biomarker-Based Approvals in Alzheimer’s and Gene Therapy Accelerated approval based on reduction in amyloid plaques as seen in amyloid-PET scans Regulatory precedent: accelerated approval of two Alzheimer’s therapies to date Ioannou, K. et al. Tau PET positivity predicts clinically relevant cognitive decline driven by Alzheimer’s disease compared to comorbid cases; proof of concept in the ADNI study. Mol Psychiatry. 2024; doi: 10.1038/s41380-024-02672-9. Malpetti M. et al. Tau Beats Amyloid in Predicting Brain Atrophy in Alzheimer Disease: Implications for Prognosis and Clinical Trials. J Nucl Med. 2022;63(6):830-832. doi: 10.2967/jnumed.121.263694. PMID: 35649659; PMCID: PMC9157718. Significant unmet need in APOE4/4 Alzheimer’s, and particularly in moderate AD patients Stated interest from CBER to leverage accelerated approval in neurologic diseases where traditional endpoints could take more time to measure Growing acceptance of tau as a predictor of cognitive decline Scientific literature confirms tau pathology is closely correlated with Alzheimer’s disease progression and cognitive decline(1) Studies suggest tau PET is a more sensitive marker than amyloid-beta for Alzheimer’s disease and is a clear predictor of cognitive decline(2)

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LX1001 Offers Encouraging Clinical Data with Potential Path to Accelerated Approval Meaningful impact across hallmark Alzheimer’s biomarkers Consistent reduction in Tau biomarkers that are highly correlative to progression & cognition Patient population with worse prognosis and no suitable alternatives Stabilization of amyloid pathology; indicative of disease slowing Effect on biomarkers comparable to approved therapies, without ARIA Comparable or better effect vs. anti-amyloid therapies in key tau biomarkers, particularly in patients with moderate disease Meaningful improvement vs. APOE/AD progression based on natural history 1 2 3 No ARIA events demonstrating favorable safety profile for APOE4 homozygotes Increased Flexibility for biomarker-based accelerated approvals from FDA (Alzheimer’s) and CBER (neurodegenerative conditions) Significant Unmet Need for safe and effective treatment for APOE4 homozygotes despite approved therapies

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Q&A 20

v3.24.3

Document And Entity Information	Oct. 30, 2024
Cover [Abstract]
Document Type	8-K
Amendment Flag	false
Document Period End Date	Oct. 30, 2024
Entity Registrant Name	Lexeo Therapeutics, Inc.
Entity Central Index Key	0001907108
Entity Emerging Growth Company	true
Entity File Number	001-41855
Entity Incorporation, State or Country Code	DE
Entity Tax Identification Number	85-4012572
Entity Address, Address Line One	345 Park Avenue South, Floor 6
Entity Address, City or Town	New York
Entity Address, State or Province	NY
Entity Address, Postal Zip Code	10010
City Area Code	212
Local Phone Number	547-9879
Entity Information, Former Legal or Registered Name	N/A
Written Communications	false
Soliciting Material	false
Pre-commencement Tender Offer	false
Pre-commencement Issuer Tender Offer	false
Entity Ex Transition Period	false
Title of 12(b) Security	Common Stock, $0.0001 par value per share
Trading Symbol	LXEO
Security Exchange Name	NASDAQ

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