TN-201 Well Tolerated at 3E13 vg/kg Dose AAV9 Capsid Demonstrated Robust Delivery of TN-201 Transgene to Heart Muscle Cells Resulting in Increasing RNA Expression and an Increase in Protein Levels Observed at One Year Circulating Biomarkers and Other Clinical Measures Mostly Remained Stable or Improved from Baseline Tenaya Management to Host a Webcast Conference Call Today at 8:00 a.m. ET SOUTH SAN FRANCISCO, Calif., Dec. 17, 2024 (GLOBE NEWSWIRE) — Tenaya Therapeutics, Inc. (NASDAQ: TNYA), a clinical-stage biotechnology company with a mission to discover, develop and deliver potentially curative therapies that address the underlying causes of heart disease, today reported encouraging early data from the first cohort of patients in the MyPEAK-1 clinical trial of TN-201 gene therapy. TN-201 is being developed for the potential treatment of MYBPC3-associated hypertrophic cardiomyopathy (HCM), a condition caused by insufficient levels of myosin-binding protein C (MyBP-C). Preliminary data from three patients in the first dose cohort of 3E13 vg/kg (Cohort 1) showed that TN-201 was generally well tolerated, with readily detectable vector DNA in the heart, evidence of transgene RNA expression, and increasing TN-201 mRNA and MyBP-C protein levels over time. Circulating biomarkers of cardiac muscle strain and injury remained largely stable, and other clinical markers of disease showed stability or directional improvement in the first two individuals dosed, though longer-term data are needed to characterize TN-201’s activity. Tenaya will continue to follow these first three patients with additional data readouts from Cohort 1 and the higher dose Cohort 2 anticipated in 2025. “The initial patients enrolled in the MyPEAK-1 Phase 1b/2 clinical study are like many we see in our clinic: relatively young adults whose HCM is keeping them from having an adequate quality of life, including being able to perform activities of daily living and whose disease is progressing in spite of treatment interventions, putting them at significant risk of dire complications,” said Milind Desai, M.D., M.B.A, Haslam Family Endowed Chair in Cardiovascular Medicine, Vice Chair, Heart Vascular Thoracic Institute, Director of the Hypertrophic Cardiomyopathy Center and at the Cleveland Clinic, and an investigator for the MyPeak-1 Phase 1b/2 clinical trial. “The goal of gene therapy is to halt or even reverse the steady decline in MYBPC3-associated HCM by addressing the underlying genetic cause of disease. Initial data from this first-in-human clinical trial of TN-201 demonstrate tolerability and early evidence of protein expression support additional investigation to build on these findings.” “TN-201’s emerging safety profile, excellent uptake into cardiomyocytes, and evidence of transgene RNA and protein expression provide important de-risking of the program as we proceed with enrollment of the higher dose cohort,” said Whit Tingley, M.D., Ph.D., Tenaya’s Chief Medical Officer. “In addition, we have observed encouraging early hints of disease stability and improvement among certain clinical measures of disease, offering further reason to believe in TN-201’s promise. Longer-term follow up for all patients in the lower dose cohort and results from the higher dose cohort will further inform our understanding of TN-201 gene therapy’s potential in MYBPC3-associated HCM.” Interim Phase 1b/2 MyPEAK-1 ResultsData reported today focus on changes over time in the first three patients to receive TN-201 gene therapy. Patients were dosed sequentially with TN-201 via a one-time intravenous infusion of a 3E13 vg/kg dose. Patients enrolled in Cohort 1 were required to be symptomatic adults with MYBPC3-associated nonobstructive HCM at sufficiently high risk of sudden cardiac death to warrant an implantable cardiac defibrillator device (ICD). An assessment of Patient 1 at Week 52, Patient 2 at Week 40 and safety data for Patient 3 at 12 weeks are included in this first readout. All three had objectively severe disease at the time of enrollment with mild-to moderate heart failure symptoms that limited the activities of daily living as measured by New York Heart association (NYHA) classification. TN-201 was generally well tolerated with a manageable safety profile. No cardiac toxicities, complement activation-associated adverse effects, or thrombotic microangiopathy (TMA)-related events were observed.All three patients experienced isolated elevations in liver enzymes associated with TN-201 treatment. These were not associated with other signs or symptoms of liver damage and were well managed with the administration of corticosteroids, per protocol. Liver enzyme elevations are a known side effect associated with AAV-based gene therapies. One patient experienced asymptomatic and mild (Grade 1) enzyme elevation that was designated as an SAE due to the administration of a corticosteroid bolus in the hospital setting. On-study adverse events were primarily mild, transient or reversible. The majority of observed side effects were typical of those observed with use of adeno-associated viral vector (AAV)-based gene therapies or immunosuppressive (IS) regimens. Two serious adverse events (SAEs) occurred that were not related to TN-201. Patients 1 and 2 have successfully tapered off immunosuppressives and all three patients remain on study. TN-201 achieved robust transduction into cardiomyocytes and measurable transgene RNA expression. TN-201 RNA expression and levels of MyBP-C protein increased over time.Cardiac biopsy samples were collected for analysis at Week 8 for Patients 1 and 2 and Week 52 for Patient 1 to confirm and characterize transduction of TN-201 DNA in the heart, the presence of TN-201 transgene mRNA, and changes in MyBP-C protein. Baseline biopsies have been added to the MyPEAK-1 protocol, beginning with Patient 3 to provide further insights into the changes in MyBP-C protein levels over time. At Week 8, Patients 1 and 2 achieved evidence of robust cardiac transduction at levels that were above those that were effective in preclinical knockout mouse models of disease and perform favorably to published levels for other clinical-stage AAV gene therapy agents for genetic cardiomyopathies.At Week 8, Patients 1 and 2 achieved TN-201-derived mRNA at levels similar to those of other clinical-stage cardiac gene therapies, though lower than those observed in preclinical studies. TN-201 mRNA expression increased by 50% at the Week 52 biopsy for Patient 1, offering early evidence of anticipated durability of expression.Total levels of MyBP-C protein were quantified and demonstrated a 3% increase from Weeks 8 to 52 in Patient 1. This increase, combined with the increase observed in TN-201 mRNA expression suggest that TN-201 gene therapy is successfully being transcribed and expressed after reaching target cells. As TN-201 generated MyBP-C and endogenous MyBP-C are indistinguishable via assay, baseline biopsies will further elucidate protein level changes. Clinical measures of HCM mostly remained stable or improved from baseline. Circulating biomarkers of heart muscle strain (measured via NT-proBNP) remained stable overall. Cardiac troponin I, a biomarker of heart muscle injury, normalized in Patient 2.Improvement or stabilization from baseline was observed in some clinical endpoints, including improvements in NYHA classification for Patients 1 and 2, while other measures were not yet available, interpretable or were mixed.The overall clinical picture is anticipated to become clearer with time, more follow-up, and more patients. “Taken together, the TN-201 data reported today are in line with our overall expectations at this early juncture in the study. The high levels of cardiac transduction and early evidence of increasing transgene expression support our confidence in TN-201’s potential at this early stage. We look forward to building on these results over time,” said Faraz Ali, Tenaya’s Chief Executive Officer. “We deeply appreciate the support we are receiving from the larger community of HCM clinicians and affected families, and we are especially grateful to our study investigators and to the first three patients in Cohort 1 without whom the promise and potential of TN-201 could not be explored.” Investor and Analyst Conference Call and Live WebcastTenaya management will host a conference call and webcast today beginning at 8:00 am. ET/5:00 AM PT to discuss the initial MyPEAK-1 results.  Investors and analysts may access the call here. A live webcast of the conference call, including an accompanying slide presentation, will be available on the Investors section of Tenaya’s website. A replay of the webcast, and accompanying slides, will be available on the Tenaya website for approximately 90 days following the call. About the MyPEAK-1 Phase 1b/2 Clinical TrialThe MyPEAK-1 Phase 1b/2 clinical trial (Clinicaltrials.gov ID: NCT05836259) is an ongoing, multi-center, open-label, dose-escalating study designed to assess the safety, tolerability and clinical efficacy of a one-time intravenous infusion of TN-201 gene replacement therapy. The trial is enrolling symptomatic (New York Heart Association Class II or III) adults who have been diagnosed with MYBPC3-associated HCM. MyPEAK-1 is testing doses of 3E13 vg/kg and 6E13 vg/kg in two cohorts of three patients each. MyPEAK-1 may enroll up to 24 MYBPC3-associated HCM adults with either nonobstructive or obstructive forms of HCM in planned dose expansion cohorts. To learn more about gene therapy for HCM and participation in the MyPEAK-1 study, please visit HCMStudies.com. About MYBPC3-Associated Hypertrophic Cardiomyopathy Variants in the Myosin Binding Protein C3 (MYBPC3) gene are the most common genetic cause of hypertrophic cardiomyopathy (HCM), accounting for approximately 20% of the overall HCM population, or 120,000 patients, in the United States alone.(1) MYBPC3-associated HCM is a severe and progressive condition affecting adults, teens, children and infants. Mutations of the MYBPC3 gene result in insufficient expression of a protein, called MyBP-C, needed to regulate heart contraction. The heart becomes hypercontractile and the left ventricle thickens, resulting in symptoms such as chest pain, shortness of breath, palpitations and fainting. Patients whose disease is caused by MYBPC3 mutations are more likely than those with non-genetic forms of HCM to experience earlier disease onset and have high rates of serious outcomes, including heart failure symptoms, arrhythmias, stroke and sudden cardiac arrest or death.(2) There are currently no approved therapeutics that address the underlying genetic cause of HCM. About TN-201TN-201 is an adeno-associated virus serotype 9 (AAV9)-based gene therapy designed to deliver a working MYBPC3 gene to heart muscle cells via a single intravenous infusion, increasing MyBP-C protein levels to address the underlying cause of MYBPC3-associated HCM with the aim of halting or even reversing disease after a single dose. The U.S. Food and Drug Administration has granted TN-201 Fast Track, Orphan Drug and Rare Pediatric Drug Designations. TN-201 has also received orphan medicinal product designation from the European Commission. About Tenaya TherapeuticsTenaya Therapeutics is a clinical-stage biotechnology company committed to a bold mission: to discover, develop and deliver potentially curative therapies that address the underlying drivers of heart disease. Tenaya employs a suite of integrated internal capabilities, including modality agnostic target validation, capsid engineering and manufacturing, to generate a portfolio of genetic medicines aimed at the treatment of both rare genetic disorders and more prevalent heart conditions. Tenaya’s pipeline includes TN-201, a gene therapy for MYBPC3-associated hypertrophic cardiomyopathy (HCM), TN-401, a gene therapy for PKP2-associated arrhythmogenic right ventricular cardiomyopathy (ARVC), TN-301, a small molecule HDAC6 inhibitor intended for heart failure with preserved ejection fraction (HFpEF), and multiple early-stage programs in preclinical development. For more information, visit www.tenayatherapeutics.com. (1) Sedaghat-Hemedani, et al., Clinical Research Cardiology, 2017(2) Ho, et al., Circulation 2018 Forward Looking Statements This press release contains forward-looking statements as that term is defined in Section 27A of the Securities Act of 1933 and Section 21E of the Securities Exchange Act of 1934. Statements in this press release that are not purely historical are forward-looking statements. Words such as “will,” “anticipated,” “believe,” “look forward,” “potential,” and similar expressions are intended to identify forward-looking statements. Such forward-looking statements include, among other things, the planned timing to report additional data from MyPEAK-1; the clinical, therapeutic and commercial potential of, and expectations regarding TN-201; the value of additional MyPEAK-1 data to inform the potential of TN-201; the inferences regarding MyBP-C protein and mRNA expression; statements regarding the continued development TN-201 and TN-201 clinical outcomes, which may materially change as patient enrollment continues or more patient data become available; and statements made by Tenaya’s Chief Medical Officer and Chief Executive Officer and investigator for MyPEAK-1. The forward-looking statements contained herein are based upon Tenaya’s current expectations and involve assumptions that may never materialize or may prove to be incorrect. These forward-looking statements are neither promises nor guarantees and are subject to a variety of risks and uncertainties, including but not limited to: availability of MyPEAK-1 data at the referenced time; the timing and progress of MyPEAK-1; the potential failure of TN-201 to demonstrate safety and/or efficacy in clinical testing; the potential for any MyPEAK-1 clinical trial results to differ from preclinical, interim, preliminary or expected results; Tenaya’s ability to enroll and maintain patients in clinical trials, including MyPEAK-1; risks associated with the process of discovering, developing and commercializing drugs that are safe and effective for use as human therapeutics and operating as an early stage company; Tenaya’s continuing compliance with applicable legal and regulatory requirements; Tenaya’s ability to raise any additional funding it will need to continue to pursue its product development plans; Tenaya’s reliance on third parties; Tenaya’s manufacturing, commercialization and marketing capabilities and strategy; the loss of key scientific or management personnel; competition in the industry in which Tenaya operates; Tenaya’s ability to obtain and maintain intellectual property protection for its product candidates; general economic and market conditions; and other risks. Information regarding the foregoing and additional risks may be found in the section titled “Risk Factors” in Tenaya’s Quarterly Report on Form 10-Q for the fiscal quarter ended September 30, 2024 and other documents that Tenaya files from time to time with the Securities and Exchange Commission. These forward-looking statements are made as of the date of this press release, and Tenaya assumes no obligation to update or revise any forward-looking statements, whether as a result of new information, future events or otherwise, except as required by law. ContactMichelle CorralVP, Corporate Communications and Investor RelationsIR@tenayathera.com InvestorsAnne-Marie FieldsPrecision AQ (formerly Stern Investor Relations)annemarie.fields@precisionaq.com Media Wendy Ryan Ten Bridge Communications wendy@tenbridgecommunications.com

TN-401 AAV9-based Gene Therapy Designed to Deliver Fully Functional PKP2 Gene with the Aim of Increasing Protein Levels to Address Underlying Disease RIDGE-1 Currently Enrolling at Six Centers; Observational Natural History and Seroprevalence Study of PKP2-associated ARVC Adults Continues Enrollment at 20 Clinical Sites in the U.S., UK and Europe Initial Clinical Data for RIDGE-1 Anticipated in 2025 SOUTH SAN FRANCISCO, Calif., Nov. 25, 2024 (GLOBE NEWSWIRE) — Tenaya Therapeutics, Inc. (NASDAQ: TNYA), a clinical-stage biotechnology company with a mission to discover, develop and deliver potentially curative therapies that address the underlying causes of heart disease, today announced that the first patient has been dosed with TN-401 gene therapy in the RIDGE-1 Phase 1b clinical trial at the University of California, San Francisco. Tenaya currently anticipates sharing initial data from the RIDGE-1 trial in 2025. TN-401 is being developed for the treatment of arrhythmogenic right ventricular cardiomyopathy (ARVC, also known as arrhythmogenic cardiomyopathy or ACM) caused by mutations in the plakophilin-2 (PKP2) gene. PKP2 gene mutations result in insufficient levels of critical proteins needed to maintain the structural integrity and cell-to-cell signaling of heart muscle cells. TN-401 gene replacement therapy is designed to deliver a functional PKP2 gene into heart muscle cells using an adeno associated virus serotype 9 (AAV9) capsid. In preclinical studies, the new, healthy PKP2 gene was successfully integrated into heart cells where it produced the missing protein to slow or even reverse the course of disease. Compared to untreated in vivo knock-out models, TN-401 normalized heart rhythms, reversed disease progression and extended survival following a single dose. “People living with ARVC frequently experience dangerous arrhythmias and are at risk for developing heart failure, cardiac arrest and sudden death. To minimize their risk, ARVC patients live with significant activity restrictions, take chronic medications, and require interventions that together negatively impact their quality of life but don’t address the underlying problem of a defective gene,” said Vasanth Vedantham, M.D., Ph.D., Professor of Medicine, Cardiac Electrophysiologist, Director of Cardiovascular Genetics at the University of California, San Francisco and an investigator for the RIDGE-1 Phase 1b clinical trial. “PKP2 genetic mutations are the most common single gene cause of ARVC and unlike existing treatments for ARVC, TN-401 gene therapy seeks to directly address the underlying cause of disease by delivering a fully functional copy of PKP2 to the heart.” The RIDGE-1 Phase 1b clinical trial is a multi-center, open-label, dose escalation study being conducted in the U.S. and UK. RIDGE-1 will assess the safety, tolerability and preliminary clinical efficacy of a one-time intravenous infusion of TN-401. The trial will seek to enroll up to fifteen adults who have been diagnosed with PKP2-associated ARVC, have an implantable cardioverter defibrillator (ICD) and are at increased risk for arrhythmias as determined by premature ventricular contraction count during screening. The first dose of TN-401 being assessed in the RIDGE-1 clinical trial is 3E13 vg/kg, a dose that was associated with near maximal efficacy in preclinical studies. The first three patients will be dosed on a sequential basis. Once three patients have been dosed at the 3E13 vg/kg level, a panel of independent safety reviewers will advise on plans to dose escalate and/or expand enrollment of the initial cohort dosing in parallel. “Initiation of this first-in-human study of TN-401 is a significant milestone for Tenaya and we are grateful for the ongoing support received from our trial sites, advocacy organizations, patients and families in our efforts to advance a novel gene replacement therapy for PKP2-associated ARVC,” said Whit Tingley, M.D., Ph.D., Tenaya’s Chief Medical Officer. “We believe TN-401 has best-in-class potential due to its differentiated construct, which utilizes an AAV9 capsid to deliver a fully functioning PKP2 gene directly to heart cells. We selected AAV9 capsid due to its extensive track record and in preclinical studies it outperformed other capsids and TN-401 restored PKP2 levels in a knockout model, leading to reductions in arrhythmia frequency and severity, and halted disease progression.” The RIDGE-1 clinical trial is currently enrolling patients at six leading U.S. centers specializing in ARVC care. To learn more about gene therapy for ARVC and participation in the RIDGE-1 study, please visit ARVCstudies.com or ClinicalTrials.gov (NCT06228924). In 2022, Tenaya initiated a non-interventional global natural history and seroprevalence study of adults with PKP2-assocated ARVC (NCT06311708). The RIDGE study continues to enroll participants at more than 20 clinical sites in the U.S., UK, France, Germany, Italy and Sweden. About PKP2-Associated ARVCPlakophilin-2 (PKP2) mutations are the most common genetic cause of arrhythmogenic right ventricular cardiomyopathy (ARVC, also known as arrhythmogenic cardiomyopathy or ACM), estimated to represent approximately 40 percent of the overall ARVC population. The prevalence of PKP2-associated ARVC is estimated at more than 70,000 people in the U.S. alone. In PKP2-associated ARVC, mutations of the PKP2 gene results in insufficient expression of a protein needed for the proper functioning of the desmosomal complex that maintains physical connections and electrical signaling between heart muscle cells. As the desmosome structure degrades, cardiac muscle cells are replaced by fibrofatty tissue and electrical pulses in the heart become unstable, resulting in irregular heart rhythms. ARVC symptoms include arrhythmias, palpitations, lightheadedness, dizziness and fainting. It is typically diagnosed before age 40, and sudden cardiac arrest due to life-threatening ventricular arrhythmias is frequently the first manifestation of disease. Current treatments include anti-arrhythmic medications, implantable cardioverter-defibrillators (ICDs) and ablation procedures, which do not address the underlying genetic cause of disease. About TN-401 Gene TherapyTN-401 is an investigational AAV9-based gene therapy being developed for the treatment of ARVC due to mutations in the PKP2 gene. AAV9 was selected as the vector for delivery of Tenaya’s PKP2 gene therapy based on its extensive clinical and commercial safety record and demonstrated ability to target heart muscle cells. In preclinical studies, Tenaya has shown that a single dose of TN-401 restored healthy levels of PKP2 protein, normalized heart rhythms, improved right and left ventricular size and function and extended survival. Tenaya is conducting the RIDGE-1 Phase 1b clinical trial of TN-401 in patients with PKP2-associated ARVC. To support TN-401’s clinical development, the company is currently enrolling the RIDGE global non-interventional study to collect natural history and AAV9 antibody (seroprevalence) data among ARVC patients carrying PKP2 gene mutations. TN-401 has received Orphan Drug and Fast Track Designations from the FDA. About Tenaya TherapeuticsTenaya Therapeutics is a clinical-stage biotechnology company committed to a bold mission: to discover, develop and deliver potentially curative therapies that address the underlying drivers of heart disease. Tenaya employs a suite of integrated internal capabilities, including modality agnostic target validation, capsid engineering and manufacturing, to generate a portfolio of genetic medicines aimed at the treatment of both rare genetic disorders and more prevalent heart conditions. Tenaya’s pipeline includes TN-201, a gene therapy for MYBPC3-associated hypertrophic cardiomyopathy (HCM), TN-401, a gene therapy for PKP2-associated arrhythmogenic right ventricular cardiomyopathy (ARVC), TN-301, a small molecule HDAC6 inhibitor intended for heart failure with preserved ejection fraction (HFpEF), and multiple early-stage programs in preclinical development. For more information, visit www.tenayatherapeutics.com. Forward Looking StatementsThis press release contains forward-looking statements as that term is defined in Section 27A of the Securities Act of 1933 and Section 21E of the Securities Exchange Act of 1934. Statements in this press release that are not purely historical are forward-looking statements. Words such as “anticipates,” “will,” “believe” and similar expressions are intended to identify forward-looking statements. Such forward-looking statements include, among other things, the clinical, therapeutic and commercial potential of, and expectations regarding TN-401; the planned timing to report initial data from RIDGE-1 and related focus of the data readout; and statements made by Tenaya’s Chief Medical Officer. The forward-looking statements contained herein are based upon Tenaya’s current expectations and involve assumptions that may never materialize or may prove to be incorrect. These forward-looking statements are neither promises nor guarantees and are subject to a variety of risks and uncertainties, including but not limited to: the timing and progress of RIDGE-1; the potential failure of TN-401 to demonstrate safety and/or efficacy in clinical testing; availability of RIDGE-1 data at the referenced time; the potential for any RIDGE-1 clinical trial results to differ from preclinical, interim, preliminary, topline or expected results; risks associated with the process of discovering, developing and commercializing drugs that are safe and effective for use as human therapeutics and operating as an early stage company; Tenaya’s continuing compliance with applicable legal and regulatory requirements; Tenaya’s ability to raise any additional funding it will need to continue to pursue its product development plans; Tenaya’s reliance on third parties; Tenaya’s manufacturing, commercialization and marketing capabilities and strategy; the loss of key scientific or management personnel; competition in the industry in which Tenaya operates; Tenaya’s ability to obtain and maintain intellectual property protection for its product candidates; general economic and market conditions; and other risks. Information regarding the foregoing and additional risks may be found in the section entitled “Risk Factors” in documents that Tenaya files from time to time with the Securities and Exchange Commission. These forward-looking statements are made as of the date of this press release, and Tenaya assumes no obligation to update or revise any forward-looking statements, whether as a result of new information, future events or otherwise, except as required by law.Tenaya ContactsMichelle CorralVP, Corporate Communications and Investor RelationsIR@tenayathera.com InvestorsAnne-Marie FieldsPrecision AQ annemarie.fields@precisionaq.com MediaWendy RyanTen Bridge Communicationswendy@tenbridgecommunications.com

TN-401 AAV9-Based Gene Therapy Being Developed to Treat the Underlying Cause of PKP2-associated Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC) PKP2 Gene Replacement Therapy Normalized Heart Rhythms, Reversed Disease Progression and Extended Survival in a Severe Mouse Model of Disease Tenaya Anticipates Dosing First Patient in Phase 1b RIDGE™-1 Clinical Trial of TN-401 in Second Half of 2024 SOUTH SAN FRANCISCO, Calif., March 18, 2024 (GLOBE NEWSWIRE) — Tenaya Therapeutics, Inc. (NASDAQ: TNYA), a clinical-stage biotechnology company with a mission to discover, develop and deliver potentially curative therapies that address the underlying causes of heart disease, today announced the publication of its preclinical research related to its gene therapy candidate, TN-401, in the current issue of Nature Communications Medicine. TN-401 is an adeno-associated virus serotype 9 (AAV9)-based gene therapy being developed for the treatment of arrhythmogenic right ventricular cardiomyopathy (ARVC) caused by Plakophilin-2 (PKP2) gene mutations. PKP2 mutations are the most common genetic cause of ARVC, also known as arrhythmogenic cardiomyopathy (ACM), and result in a loss of key proteins needed to maintain the structural integrity and cell-to-cell electrical signaling of heart muscle cells. TN-401 is designed to deliver a functional PKP2 gene to heart cells where it works to restore normal protein levels in order to halt or even reverse disease after a single dose. “Following a single infusion of our AAV9-based PKP2 gene therapy in a severe knock-out mouse model of the disease, PKP2 protein levels were restored. This led to dose-dependent improvements in right ventricular dilation and ejection fraction, reductions in arrhythmia frequency and severity, and prevention of adverse fibrotic remodeling, with near-maximal efficacy achieved at the 3E13 vg/kg dose.” said Tim Hoey, Ph.D., Chief Scientific Officer of Tenaya. “ARVC can have a devastating effect on patients’ lives, putting them at risk of life-threatening arrhythmias and placing limitations on their quality of life,” said Whit Tingley, M.D., Ph.D., Chief Medical Officer of Tenaya. “These promising preclinical results show the potential of TN-401 to prevent, halt or even reverse the steady progression of PKP2-associated ARVC by addressing the underlying genetic cause, and offer hope to patients. We look forward to commencing dosing of TN-401 in patients with PKP2-associated ARVC in our Phase 1b RIDGE-1 clinical trial in the second half of this year.” Tenaya’s RIDGE-1 Phase 1b clinical trial of TN-401 is a multi-center, open-label study to assess the safety, tolerability and clinical efficacy of a one-time intravenous infusion of TN-401. Tenaya is currently also conducting the RIDGE™ global non-interventional natural history and serotype study of PKP2-associated ARVC. Both studies are being conducted at leading centers for ARVC care. Key FindingsThe paper, titled “AAV9:PKP2 improves heart function and survival in a Pkp2-deficient mouse model of arrhythmogenic right ventricular cardiomyopathy,” describes results from preclinical studies in a Pkp2-deficient mouse model to understand gene therapy’s impact in both prevention mode before disease onset and in treatment mode after disease onset. A single dose of Tenaya’s AAV9:PKP2 gene therapy: Restored normal levels of PKP2 protein expression,Led to a highly coordinated and durable correction in structural genes encoding desmosome, sarcomere and calcium handling proteins with a role in maintaining cellular integrity and function,Reduced the frequency and severity of arrhythmias,Demonstrated durable efficacy in preventing disease development,Slowed or reversed disease progression after onset,Prevented fibrotic remodeling, andImproved long-term survival. Tenaya selected AAV9 as the vector for delivery for TN-401 based on its extensive clinical and commercial safety record in thousands of patients globally and its demonstrated ability in clinical studies to broadly distribute in all regions of the human heart and to more robustly express the PKP2 gene in cardiomyocytes as compared to other vectors. About PKP2-Associated ARVCMutations in the desmosome gene PKP2 are the most frequent cause of ARVC, with greater than 40% of those diagnosed estimated to carry pathogenic PKP2 mutations. In the U.S. prevalence of PKP2-associated ARVC is estimated at more than 70,000, though the condition is frequently undiagnosed; in nearly one in four cases, sudden cardiac death is the first sign of disease. Mutations of the PKP2 gene result in insufficient expression of a protein needed for the proper functioning of the desmosomal complex that maintains physical connections and electrical signaling between heart muscle cells. As the desmosome structure degrades, cardiac muscle cells are replaced by fibrofatty tissue and electrical pulses in the heart become unstable, resulting in adverse remodeling and irregular heart rhythms. A progressive disease, ARVC is typically diagnosed before age 40 and symptoms may include arrhythmias, palpitations, lightheadedness, dizziness and fainting and sudden cardiac arrest. Current treatments include anti-arrhythmic medications, implantable cardioverter-defibrillators (ICDs) and ablation procedures, which do not address the underlying genetic cause of disease. About TN-401 Gene Therapy and the RIDGE Clinical ProgramTN-401 is an investigational AAV9-based gene therapy being developed for the treatment of ARVC due to mutations in the PKP2 gene. Tenaya has received clearance from the FDA to initiate its first-in-human RIDGE-1 Phase 1b clinical trial of TN-401 in patients with PKP2-associated ARVC. To support TN-401’s clinical development, the company is currently enrolling the RIDGE global non-interventional study to collect natural history and AAV9 antibody (seroprevalence) data among ARVC patients carrying PKP2 gene mutations. TN-401 has received Orphan Drug and Fast Track Designations from the FDA. About Tenaya TherapeuticsTenaya Therapeutics is a clinical-stage biotechnology company committed to a bold mission: to discover, develop and deliver potentially curative therapies that address the underlying drivers of heart disease. Leveraging integrated proprietary core capabilities enabling target identification and validation, design of AAV-based genetic medicines and in-house manufacturing the company is advancing a pipeline of novel therapies with diverse treatment modalities for rare genetic cardiovascular disorders and more prevalent heart conditions. Tenaya’s most advanced candidates include TN-201, a gene therapy for MYBPC3-associated hypertrophic cardiomyopathy (HCM), TN-401, a gene therapy for PKP2-associated arrhythmogenic right ventricular cardiomyopathy (ARVC), and TN-301, a small molecule HDAC6 inhibitor being initially developed for heart failure with preserved ejection fraction (HFpEF). Tenaya also has multiple early-stage programs progressing through preclinical development. For more information, visit www.tenayatherapeutics.com. Forward Looking StatementsThis press release contains forward-looking statements as that term is defined in Section 27A of the Securities Act of 1933 and Section 21E of the Securities Exchange Act of 1934. Statements in this press release that are not purely historical are forward-looking statements. Words such as “anticipates,” “promising,” “potential,” “look forward,” “plan,” and similar expressions are intended to identify forward-looking statements. Such forward-looking statements include, among other things, the clinical, therapeutic and commercial potential of TN-401 as a treatment for PKP2-associated ARVC and the plan for initiation of patient dosing in RIDGE-1. The forward-looking statements contained herein are based upon Tenaya’s current expectations and involve assumptions that may never materialize or may prove to be incorrect. These forward-looking statements are neither promises nor guarantees and are subject to a variety of risks and uncertainties, including but not limited to: the potential failure of TN-401 to demonstrate safety and/or efficacy in clinical testing; unexpected concerns that may arise as a result of the occurrence of adverse safety events or additional data analyses of clinical trials evaluating TN-401; the timing and progress of the RIDGE-1 clinical trial; the timing, scope and likelihood of regulatory filings and approvals for TN-401; risks associated with the process of discovering, developing and commercializing drugs that are safe and effective for use as human therapeutics and operating as an early stage company; Tenaya’s ability to develop, initiate or complete preclinical studies and clinical trials, and obtain approvals, for any of its product candidates; Tenaya’s continuing compliance with applicable legal and regulatory requirements; Tenaya’s ability to raise any additional funding it will need to continue to pursue its business and product development plans; Tenaya’s reliance on third parties; Tenaya’s manufacturing, commercialization and marketing capabilities and strategy; the loss of key scientific or management personnel; competition in the industry in which Tenaya operates; Tenaya’s ability to obtain and maintain intellectual property protection for its product candidates; general economic and market conditions; and other risks. Information regarding the foregoing and additional risks may be found in the section entitled “Risk Factors” in documents that Tenaya files from time to time with the Securities and Exchange Commission. These forward-looking statements are made as of the date of this press release, and Tenaya assumes no obligation to update or revise any forward-looking statements, whether as a result of new information, future events or otherwise, except as required by law. Contacts Michelle CorralVice President, Investor Relations and Corporate CommunicationsTenaya TherapeuticsIR@TenayaThera.com InvestorsAnneMarie FieldsStern IRAnneMarie.Fields@SternIR.com MediaWendy RyanTen Bridge Communicationswendy@tenbridgecommunications.com 

Highly selective Small Molecule HDAC6 Inhibitor Effectively Reversed Heart Failure and Improved Diastolic Heart Function Alone or in Combination with SGLT2 Inhibitor in Murine Models of Disease SOUTH SAN FRANCISCO, Calif., Feb. 26, 2024 (GLOBE NEWSWIRE) — Tenaya Therapeutics, Inc. (NASDAQ: TNYA), […]

PKP2 Mutations Are the Leading Cause of ARVC, a Dangerous Condition Linked to Sudden Cardiac Arrest in Young People Estimated to Affect 70,000 People in the US TN-401 Preclinical Studies Demonstrated Robust Reduction of Ventricular Arrhythmias and Extended Survival in […]

SOUTH SAN FRANCISCO, Calif. and CLEVELAND, Oct. 09, 2023 (GLOBE NEWSWIRE) — Tenaya Therapeutics, Inc. (NASDAQ: TNYA), a clinical-stage biotechnology company with a mission to discover, develop and deliver potentially curative therapies that address the underlying causes of heart disease, […]