Alzheimer Disease Type 2

Dose-dependent increase in neuroprotective APOE2 expression in all participants with ongoing durability at 12 months Consistent reductions across CSF tau biomarkers and tau PET in majority of participants LX1001 well tolerated across all dose cohorts with no reports of amyloid-related imaging abnormalities (ARIA) Company to host webcast today at 7:00 AM ET NEW YORK, Oct. 30, 2024 (GLOBE NEWSWIRE) -- Lexeo Therapeutics, Inc. (Nasdaq: LXEO), a clinical stage genetic medicine company dedicated to pioneering treatments for genetically defined cardiovascular diseases and APOE4-associated Alzheimer’s disease, today announced positive interim results from the Phase 1/2 study of LX1001 (NCT03634007) for the treatment of APOE4-associated Alzheimer’s disease (AD). Treatment with LX1001 led to dose-dependent increases in APOE2 protein expression and improvements in AD-associated tau biomarkers, measures which have been closely correlated with cognitive outcomes. LX1001 also demonstrated a favorable safety profile with no reports of ARIA1. The data were presented today in a late-breaking oral presentation at the Clinical Trials on Alzheimer’s Disease (CTAD) conference in Madrid, Spain and expand the body of evidence on LX1001 as a potential therapy for the more progressive course of Alzheimer’s seen in APOE4 homozygotes. “APOE4 homozygotes are approximately 15 times more likely to develop Alzheimer’s disease than the general population, have faster disease progression, and have an increased risk of ARIA with currently available therapies that can cause serious complications,” said Dr. Kim Johnson, Division Chief, Memory Disorders at the Department of Neurology of Duke University School of Medicine and a principal investigator in the Phase 1/2 study. “Today’s results suggest the potential of LX1001, which based on available data is well tolerated without reports of ARIA. The study also resulted in notable reductions in tau biomarkers, which suggest a possible effect on Alzheimer’s disease pathology.” LX1001 is an AAVrh10-based gene therapy candidate designed to deliver the protective APOE2 allele into the central nervous system of APOE4 homozygous patients, who have two copies of the toxic APOE4 allele. APOE2 is associated with a significantly lower risk of Alzheimer’s onset and slower disease progression. In the Phase 1/2 study, which completed enrollment in Q4 2023, fifteen patients with mild cognitive impairment (MCI) or mild or moderate AD were dosed with LX1001 in four dose-ascending cohorts. The study’s primary objective was to assess safety and tolerability, with secondary outcomes including cerebrospinal fluid (CSF) APOE2 protein expression and change in tau and amyloid biomarkers. “In light of the rapid progression of Alzheimer’s disease in this population, these data highlight the therapeutic potential of delivering APOE2, which can impact multiple mechanisms of Alzheimer’s disease upstream of any specific pathway and thereby meaningfully alter the devastating course of this complex disease,” said Dr. Sandi See Tai, Chief Development Officer of Lexeo Therapeutics. “These data are highly encouraging and provide clinical evidence of the unique and targeted mechanism of LX1001 to potentially treat Alzheimer’s disease.” The interim Phase 1/2 data include follow-up through 12-months for dose Cohorts 1 through 3 and follow-up through 6-months for dose Cohort 4, demonstrating: CSF APOE2 protein expression in all participants, with dose- and time-dependent increases in expression and durability out to 12 monthsStabilization of amyloid pathology in the majority of participants, with minimal change from baseline in Aß42/40 ratio and amyloid PETConsistent reductions across CSF tau biomarkers including CSF T-tau, P-tau181, P-tau2172 and P-tau2312, in over two thirds of participants relative to baseline and natural historyReductions at 6 months in global tau PET3 SUVR in 5 of 6 participants and in regional SUVR in a majority of participants across all brain regionsParticipants with moderate AD (n=4) generally demonstrated the most improvement across various biomarker endpointsFour SAEs were reported, with three deemed unrelated to treatment and one event of mild-moderate sensorineural hearing loss assessed as possibly related to treatment with repeat audiometry pending. The Company has initiated engagement with FDA on these data and expects to provide an update on regulatory interactions and further LX1001 development plans in 2025. Conference Call InformationLexeo will host a webcast today at 7:00 AM ET to review these data and next steps for the program. To register for and access the conference call and webcast presentation, please visit https://ir.lexeotx.com/news-events/events. The webcast presentation includes slides with further analysis of the LX1001 interim data. The on-demand webcast presentation may be accessed under the News & Events tab in the Investors section of the Company’s website, and a replay will be available following the presentation. About LX1001LX1001 is an AAVrh10-based gene therapy candidate for the treatment of APOE4-homozygous Alzheimer’s disease. Individuals homozygous for APOE4, an allele of the gene APOE, are approximately 15 times more likely to develop Alzheimer’s disease than the general population, and it is estimated that there are approximately 900,000 APOE4 homozygous patients with Alzheimer’s disease in the United States. Conversely, individuals homozygous for the APOE allele APOE2 are 40% less likely to develop Alzheimer’s disease than the general population. LX1001 is designed to express the protective APOE2 gene in the central nervous system of APOE4 homozygous patients, potentially slowing or halting the progression of Alzheimer’s disease. LX1001 has been granted Fast Track designation by the FDA. About Lexeo Therapeutics Lexeo Therapeutics is a New York City-based, clinical stage genetic medicine company dedicated to transforming healthcare by applying pioneering science to fundamentally change how genetically defined cardiovascular diseases and APOE4-associated Alzheimer’s disease are treated. Using a stepwise development approach, Lexeo is leveraging early proof-of-concept functional and biomarker data to advance a pipeline of cardiovascular and APOE4-associated Alzheimer’s disease programs. Cautionary Note Regarding Forward-Looking StatementsCertain statements in this press release may constitute “forward-looking statements” within the meaning of the federal securities laws, including, but not limited to, our expectations and plans regarding our current product candidates and programs, including statements regarding the potential benefits and safety of LX1001 for the treatment of Alzheimer’s disease and the timing for receipt and announcement of data from its clinical trials, and the timing and likelihood of potential regulatory approval. 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 global macroeconomic conditions and related volatility; 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 Quarterly Report on Form 10-Q for the quarterly period 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. 1 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. 2 CSF P-tau217 and P-tau231 collected only in Cohorts 2, 3 and 4; all Cohort 4 samples, including 6 month and 12 month, pending analysis3 Tau PET performed only in Cohorts 3 and 4; Cohort 4 12-mth visits pending analysis Media:Media@lexeotx.com Investors:Carlo Tanzi, Ph.D.ctanzi@kendallir.com

Late-breaking oral presentation to highlight safety and efficacy of LX1001 across four dose cohortsNEW YORK, Oct. 22, 2024 (GLOBE NEWSWIRE) -- Lexeo Therapeutics, Inc. (Nasdaq: LXEO), a clinical stage genetic medicine company dedicated to pioneering treatments for genetically defined cardiovascular diseases and APOE4-associated Alzheimer’s disease, today announced that interim data from the ongoing Phase 1/2 trial (NCT03634007) of LX1001 have been selected as a late-breaking oral presentation at the Clinical Trials on Alzheimer’s Disease (CTAD) conference taking place October 29 - November 1, 2024, in Madrid, Spain. The presentation will include new safety and biomarker data from four dose cohorts of LX1001, an AAVrh10-based gene therapy candidate designed to deliver the protective APOE2 gene into the central nervous systems of APOE4 homozygotes with Alzheimer’s disease. “APOE4-associated Alzheimer’s disease is a devastating, genetically distinct condition and despite recent therapeutic advances, patients with this genetic profile have limited effective treatment options,” said Dr. Sandi See Tai, Chief Development Officer of Lexeo Therapeutics. “We look forward to presenting new data from the first clinical trial seeking to address the underlying genetic cause of APOE4-associated Alzheimer’s disease with a targeted approach.” The Phase 1/2 clinical trial is an open-label, dose-ranging study evaluating the safety and tolerability of LX1001 in fifteen patients with Alzheimer’s disease and two copies of the APOE4 allele (APOE4 homozygous patients). Study enrollment was completed in Q4 2023. The presentation will review safety as well as multiple measures of efficacy, including protein expression and tau and amyloid biomarkers. 12-month data will be presented for all patients in Cohorts 1-3, and 6-month data for Cohort 4. Oral presentation details: Title: Safety and Preliminary Efficacy of AAV Gene Therapy (LX1001) in Patients with APOE4 Homozygote Alzheimer’s Disease – Interim Data from a Phase 1/2, Open-Label, 52-Week, Multicenter Study, Abstract #486Date/Time: Wednesday, October 30, at 10:50AM, CET (5:50AM ET) About LX1001LX1001 is an AAVrh10-based gene therapy candidate for the treatment of APOE4-homozygous Alzheimer’s disease. Individuals homozygous for APOE4, an allele of the gene APOE, are approximately 15 times more likely to develop Alzheimer’s disease than the general population, and it is estimated that there are approximately 900,000 APOE4 homozygous patients with Alzheimer’s disease in the United States. Conversely, individuals homozygous for the APOE allele APOE2 are 40% less likely to develop Alzheimer’s disease than the general population. LX1001 is designed to express the protective APOE2 gene in the central nervous system of APOE4 homozygous patients, potentially slowing or halting the progression of Alzheimer’s disease. LX1001 has been granted Fast Track designation by the FDA. About Lexeo Therapeutics Lexeo Therapeutics is a New York City-based, clinical stage genetic medicine company dedicated to transforming healthcare by applying pioneering science to fundamentally change how genetically defined cardiovascular diseases and APOE4-associated Alzheimer’s disease are treated. Using a stepwise development approach, Lexeo is leveraging early proof-of-concept functional and biomarker data to advance a pipeline of cardiovascular and APOE4-associated Alzheimer’s disease programs. Cautionary Note Regarding Forward-Looking StatementsCertain statements in this press release may constitute “forward-looking statements” within the meaning of the federal securities laws, including, but not limited to, our expectations and plans regarding our current product candidates and programs, including statements regarding the potential benefits of LX1001 for the treatment of Alzheimer’s disease and the timing for receipt and announcement of data from its clinical trials, and the timing and likelihood of potential regulatory approval. 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 global macroeconomic conditions and related volatility; 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 Quarterly Report on Form 10-Q for the quarterly period 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. Media:Media@lexeotx.com Investors:Carlo Tanzi, Ph.D.ctanzi@kendallir.com

Announced positive interim data from Phase 1/2 studies in Friedreich ataxia (FA) cardiomyopathy, which showed LX2006 was well tolerated with no treatment-related serious adverse events and demonstrated evidence of sustained and consistent treatment effect across multiple cardiac measures Recently initiated formal engagements with FDA on surrogate endpoints for LX2006 registrational study; expects to provide update by end of year Phase 1/2 clinical trial of LX2020 (HEROIC-PKP2) currently recruiting patients; data update from Cohort 1 on track for 2H 2024 Cash and cash equivalents of $175.0 million expected to provide operational runway into 2027 NEW YORK, Aug. 12, 2024 (GLOBE NEWSWIRE) -- Lexeo Therapeutics, Inc. (Nasdaq: LXEO), a clinical stage genetic medicine company dedicated to pioneering treatments for genetically defined cardiovascular diseases and APOE4-associated Alzheimer’s disease, today reported second quarter 2024 financial results and provided operational highlights. “We were proud to present the recent interim data of LX2006 for the treatment of FA cardiomyopathy, the first ever to show promise of treating this rare and fatal condition,” said R. Nolan Townsend, Chief Executive Officer of Lexeo Therapeutics. “Based on the favorable evidence to date, we have initiated engagements with FDA on surrogate endpoints for a registrational study so we can work to bring this potentially transformative gene therapy to patients as quickly as possible.” Business and Program Updates LX2006 for the Treatment of FA Cardiomyopathy: In July 2024, Lexeo announced positive interim data of LX2006 across both the Lexeo SUNRISE-FA Phase 1/2 clinical trial (NCT05445323) and the Weill Cornell Medicine investigator-initiated Phase 1A trial (NCT05302271). Safety and Tolerability: Interim safety results showed LX2006 was well tolerated with no treatment-related serious adverse events in either study.Efficacy and Protein Expression: Sustained and consistent improvements were observed across multiple cardiac biomarkers associated with outcomes in FA cardiomyopathy, and increased frataxin protein levels were observed in all SUNRISE-FA participants post-treatment.Regulatory Plans: In light of the evidence of treatment effect with improvements across multiple cardiac measures, Lexeo recently initiated formal engagements with FDA to discuss surrogate endpoints for a future registrational study and expects to provide an update on ongoing regulatory engagements by end of 2024. LX2006 was also granted Orphan Medicinal Product designation for the treatment of Friedreich ataxia by the European Commission in July 2024. Appointment of Tim Van Hauwermeiren to Board of Directors: In July 2024, Lexeo announced the appointment of Tim Van Hauwermeiren to its Board of Directors. Mr. Van Hauwermeiren currently serves as the co-founder and CEO of argenx SE, a global immunology company focused on severe autoimmune diseases, and he brings over 20 years of life sciences business development and general management experience to Lexeo. Expected Upcoming Milestones LX2006 for the treatment of Friedreich ataxia cardiomyopathy Previously disclosed data, and one additional cardiac biopsy from Cohort 2, will be shared at a scientific conference in Fall 2024Update on ongoing regulatory engagements expected by end of 2024 LX2020 for the treatment of PKP2-ACM Interim data readout (Cohort 1) in 2H 2024 LX1001 for the treatment of APOE4-associated Alzheimer’s disease Interim Phase 1/2 data readout (all cohorts) in 2H 2024 LX2021 for the treatment of DSP cardiomyopathy Initiate IND-enabling studies in 2024 Second Quarter Financial Results Cash Position: As of June 30, 2024, cash and cash equivalents were $175.0 million, which Lexeo believes will be sufficient to fund operations into 2027.R&D Expenses: R&D expenses were $16.6 million for the three months ended June 30, 2024, compared to $11.2 million for the three months ended June 30, 2023.G&A Expenses: G&A expenses were $7.0 million for the three months ended June 30, 2024, compared to $2.7 million for the three months ended June 30, 2023.Net Loss: Net loss was $21.2 million or $0.64 per share (basic and diluted) for the three months ended June 30, 2024, compared to $13.4 million or $8.30 per share (basic and diluted) for the three months ended June 30, 2023. About Lexeo TherapeuticsLexeo Therapeutics is a New York City-based, clinical stage genetic medicine company dedicated to transforming healthcare by applying pioneering science to fundamentally change how genetically defined cardiovascular diseases and APOE4-associated Alzheimer’s disease are treated. Using a stepwise development approach, Lexeo is leveraging early proof-of-concept functional and biomarker data to advance a pipeline of cardiovascular and APOE4-associated Alzheimer’s disease programs. Cautionary Note Regarding Forward-Looking StatementsCertain statements in this press release may constitute “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, including statements regarding the potential benefits of LX2006 for the treatment of Friedreich ataxia cardiomyopathy and the timing for receipt and announcement of data from its clinical trials, the timing and likelihood of potential regulatory approval, expectations regarding the time period over which Lexeo’s capital resources will be sufficient to fund its anticipated operations and estimates regarding Lexeo’s financial condition. 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 global macroeconomic conditions and related volatility; 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 annual period ended December 31, 2023, filed with the SEC on March 11, 2024, Quarterly Report on Form 10-Q for the quarterly period ended March 31, 2024, filed with the SEC on May 9, 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. Media Response:Janine Bogris(201) 245-6838janine.bogris@inizioevoke.com Investor Response:Stephen Jasper(858) 525-2047stephen@gilmartinir.com Lexeo Therapeutics, Inc.Selected Condensed Financial Information(unaudited, in thousands, except share and per share amounts) Condensed Statements of Operations Three Months Ended June 30, Six Months Ended June 30, 2024 2023 2024 2023 Operating expenses Research and development $16,560 $11,236 $32,302 $27,674 General and administrative 6,990 2,739 14,539 5,592 Total operating expenses 23,550 13,975 46,841 33,266 Operating loss (23,550) (13,975) (46,841) (33,266)Other income and expense Other income (expense), net (1) (3) (6) (7)Interest expense (35) (53) (72) (103)Interest income 2,348 590 3,999 1,277 Total other income and expense 2,312 534 3,921 1,167 Loss from operations before income taxes (21,238) (13,441) (42,920) (32,099)Income taxes - - - - Net loss and comprehensive loss $(21,238) $(13,441) $(42,920) $(32,099)Net loss per common share, basic and diluted $(0.64) $(8.30) $(1.41) $(19.87)Weighted average number of shares outstanding used in computation of net loss per common share, basic and diluted 33,001,946 1,619,547 30,490,892 1,615,194 Condensed Balance Sheet Data June 30 December 31, 2024 2023 Cash and cash equivalents $174,981 $121,466 Total assets 192,007 139,807 Total liabilities 27,059 26,272 Total stockholders' equity 164,948 113,535