Lexeo Therapeutics, Inc.

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

Treg Cell-based Therapies refer to therapeutic approaches that utilize regulatory T cells (Tregs) to modulate the immune system. Innovations in cell expansion and engineering techniques have greatly enhanced the ability to isolate, expand, and deliver functional Tregs. Ex vivo expansion technologies and genetic engineering (such as CAR-Tregs) have opened up new possibilities for enhancing the stability, specificity, and effectiveness of Treg therapies. LAS VEGAS, Oct. 28, 2024 /PRNewswire/ -- DelveInsight's ' Treg Cell-based Therapies Pipeline Insight 2024 ' report provides comprehensive global coverage of available, marketed, and pipeline Treg cell-based therapies in various stages of clinical development, major pharmaceutical companies are working to advance the pipeline space and future growth potential of the Treg cell-based therapies pipeline domain. Key Takeaways from the Treg Cell-based Therapies Pipeline Report DelveInsight's Treg cell-based therapies pipeline report depicts a robust space with 50+ active players working to develop 55+ pipeline therapies for various indications. Key Treg cell-based therapies companies such as Orca Bio, Nektar Therapeutics, Quell Therapeutics, Cugene, Sangamo Therapeutics, Abata Therapeutics, HCW Biologics, GentiBio, Tr1X, PolTREG, Cellenkos, VT BIO, Miltenyi Biotec GmbH, KSQ Therapeutics, TeraImmune, Tract Therapeutics, and others are evaluating new Treg cell-based therapies to improve the treatment landscape. Promising Treg cell-based therapies in the pipeline in various stages of development include Orca-T, NKTR-358, QEL-001, CUG-252, TX200, ABA-101, HCW9302, GNTI-122, TRX-103, PTG-020, CK-0804, VT-301, TR-004, KSQ 001, TI-620, TRK 001, and others. In October 2024, Quell Therapeutics hired eXmoor Pharma to make supplies of its pipeline of novel immunosuppressive cell therapies—called CAR-Tregs—at its new cell and gene therapy facility. Quell recently teamed with fellow U.K.-based eXmoor in a strategic partnership that will see the contractor make its candidate autoimmune disease cell therapies for early-phase clinical studies. In September 2024, Abata Therapeutics announced that ABA-101, an autologous regulatory T-cell (Treg) therapy for the treatment of patients with progressive multiple sclerosis (MS), has received fast-track designation from the US FDA. In September 2024, PolTREG S.A. announced that China's National Intellectual Property Administration, PRC (CNIPA) had issued a notification to grant a patent for the intrathecal administration of the company's cellular therapies in patients with multiple sclerosis (MS). The intrathecal administration is an established method used to deliver therapy across the blood-brain barrier via injection into the subarachnoid space. In June 2024, Orca Bio announced that it had completed enrollment in the pivotal Precision-T Phase III clinical study. The primary endpoint of the Precision-T study is the rate of survival free from moderate-to-severe chronic graft versus host disease (GvHD). In March 2024, PolTREG announced that the company is planning to launch Phase II trials testing its Tregs therapy — the T-cell-based treatment PTG-007 in people with multiple sclerosis (MS). In February 2024, Cellenkos announced encouraging safety data from its innovative CK0803 neurotrophic T regulatory (Treg) cell therapy, being developed to help treat individuals with Amyotrophic Lateral Sclerosis (ALS). The company was given the green light to move ahead following a review of safety data by the Data Safety Monitoring Board (DSMB). In August 2023, BlueRock Therapeutics LP, a wholly owned, independently operated subsidiary of Bayer AG, and bit.bio, the company coding human cells for novel cures announced a collaboration and option agreement for the discovery and manufacture of iPSC-derived regulatory T cells (Tregs) for use in creating therapeutics. Request a sample and discover the recent advances in Treg cell-based therapies @ Treg Cell-based Therapies Pipeline Outlook The Treg cell-based therapies pipeline report provides detailed profiles of pipeline assets, a comparative analysis of clinical and non-clinical stage Treg cell-based therapies, inactive and dormant assets, a comprehensive assessment of driving and restraining factors, and an assessment of opportunities and risks in the Treg cell-based therapies pipeline landscape. Treg Cell-based Therapies Overview Treg cell-based therapies represent a promising frontier in immunotherapy, focusing on harnessing regulatory T cells (Tregs) to modulate the immune response in various clinical settings. Tregs play a crucial role in maintaining immune homeostasis and preventing autoimmune reactions by suppressing excessive immune responses. In the context of autoimmune diseases, these therapies aim to restore balance by expanding or enhancing Tregs to dampen inappropriate immune activity. For instance, in diseases like type 1 diabetes or multiple sclerosis, Treg cell-based treatments seek to prevent or slow disease progression by reestablishing immune tolerance. Beyond autoimmune disorders, Treg cell-based therapies are also being explored in cancer treatment. Tumors often exploit Tregs to evade immune detection, and by manipulating these cells, it's possible to enhance the anti-tumor immune response. Strategies include expanding Tregs ex vivo and reinfusing them to boost their numbers or modifying them to more effectively target tumor-associated antigens. These approaches hold the potential to improve the efficacy of existing immunotherapies and offer new avenues for treating cancers that are currently resistant to conventional treatments. Find out more about Treg cell-based therapies @ Treg Cell-based Therapies in Development A snapshot of the Treg Cell-based Therapies Pipeline Drugs mentioned in the report: Learn more about the emerging Treg cell-based therapies @ Treg Cell-based Therapies Clinical Trials Treg Cell-based Therapies Therapeutics Assessment The Treg cell-based therapies pipeline report proffers an integral view of the emerging Treg cell-based therapies segmented by stage, product type, molecule type, mechanism of action, and route of administration. Scope of the Treg Cell-based Therapies Pipeline Report Coverage: Global Therapeutic Assessment By Product Type: Mono, Combination, Mono/Combination Therapeutic Assessment By Clinical Stages: Discovery, Pre-clinical, Phase I, Phase II, Phase III Therapeutics Assessment By Route of Administration: Intravenous, Subcutaneous, Oral, Intramuscular Therapeutics Assessment By Molecule Type: Monoclonal antibody, Small molecule, Peptide Therapeutics Assessment By Mechanism of Action: Immunologic cytotoxicity, T lymphocyte replacements, Interleukin 2 replacements, Cell replacements Key Treg Cell-based Therapies Companies: Orca Bio, Nektar Therapeutics, Quell Therapeutics, Cugene, Sangamo Therapeutics, Abata Therapeutics, HCW Biologics, GentiBio, Tr1X, PolTREG, Cellenkos, VT BIO, Miltenyi Biotec GmbH, KSQ Therapeutics, TeraImmune, Tract Therapeutics, and others. Key Treg Cell-based Therapies in Pipeline: Orca-T, NKTR-358, QEL-001, CUG-252, TX200, ABA-101, HCW9302, GNTI-122, TRX-103, PTG-020, CK-0804, VT-301, TR-004, KSQ 001, TI-620, TRK 001, and others. Dive deep into rich insights for Treg cell-based therapies assessment, visit @ Treg Cell-based Therapies Therapeutics Assessment Table of Contents For further information on the Treg cell-based therapies pipeline therapeutics, reach out @ Treg Cell-based Therapies Pipeline Landscape Related Reports Type 1 Diabetes Market Type 1 Diabetes Market Insights, Epidemiology, and Market Forecast – 2032 report deliver an in-depth understanding of the disease, historical and forecasted epidemiology, as well as the market trends, market drivers, market barriers, and key type 1 diabetes companies, including Histogen , Novo Nordisk, Prevention Bio, among others. 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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