plakophilin-2

RIDGE is Largest Natural History Study Conducted with More Than 175 Participants Enrolled to Date with Arrhythmogenic Right Ventricular Cardiomyopathy Due to Mutations in the PKP2 Gene Patients Experience High Burden of Arrhythmias and Severe Disease Progression Despite Standard-of-Care Treatments Large Majority of PKP2-associated ARVC Patients Appear Eligible for TN-401 Gene Therapy Based on Low Rates of Preexisting Immunity to AAV9 Antibodies SAN DIEGO, April 24, 2025 (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 interim data from its ongoing RIDGE (NCT06311708) natural history and seroprevalence study of adults with arrhythmogenic right ventricular cardiomyopathy (ARVC) caused by mutations in the Plakophilin 2 (PKP2) gene will be presented at the Heart Rhythm Society’s annual Heart Rhythm meeting taking place in San Diego, CA from April 24-27, 2025. RIDGE is the largest non-interventional natural history and seroprevalence study of adults with PKP2-associated ARVC to date and was designed to collect and assess participants’ clinical characteristics and medical history, as well as to test for preexisting neutralizing antibodies to AAV9. 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. Tenaya is developing TN-401 gene therapy as a potential treatment for PKP2-associated ARVC (also known as arrhythmogenic cardiomyopathy, or ACM). 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. “Interim data from the RIDGE observational study bring into focus what we’ve long understood about PKP2-associated ARVC – the current treatment approaches such as ablation or prescribed medications are insufficient to address the high burden of arrhythmias or alter the progression of disease, placing patients at increased risk for life-threatening ventricular tachycardias,” said Hugh Calkins, M.D., Catherine Ellen Poindexter Professor of Cardiology and Director, Johns Hopkins Hospital ARVD Program and an investigator for the RIDGE study. “I am encouraged by the potential of disease-modifying treatment approaches, such as TN-401 gene therapy, which is intended to alter the course of disease by delivering a functional PKP2 gene to the heart.” The RIDGE study has enrolled more than 175 patients at approximately 20 clinical sites in the U.S., UK, France, Germany, Italy and Sweden. As of the February 2025 cut off, clinical data from 144 adults with PKP2-associated ARVC were analyzed. Key findings being shared at Heart Rhythm 2025 include: Adults with PKP2-associated ARVC experience a high burden of arrhythmias despite treatments with standard of care medications including beta blockers and anti-arrhythmic medications such as flecainide, as well as surgical interventions such as ablation and implantable cardioverter-defibrillator (ICD) placement. 83 percent (95 of 115) of participants with available Holter data had a premature ventricular contraction (PVC) count of 500 PVCs/day or greater, a threshold linked with increased risk of life-threatening ventricular arrhythmias. 49 percent (56 of 115) of participants for whom Holter monitoring data was available had a history of ventricular tachycardia Current treatments appeared to do little to halt or prevent progressive structural changes to the heart that occur as a result of PKP2 mutations. Study participants show evidence of progressive structural changes that occur as a result of PKP2 mutations, in which the instability and disintegration of cellular structures in the desmosome results in fibrofatty scar tissue 60 percent of patients with MRI data available showed disease progression, as indicated by measures of right and left ventricular function, and heart tissue health Electrocardiogram results affirmed that a majority of patients had T-wave inversions (an indicator of ventricular strain or myocardial injury). Both QRS prolongation, which can indicate a delay in electrical conduction, and terminal active duration (TAD) were not present in a majority of participants, potentially indicating that changes in fibrofatty replacement and conduction system develop more slowly than arrhythmia symptoms. 93 percent of patients show AAV9 neutralizing antibody titers ≤1:40 A large majority of participants in the RIDGE study meet key eligibility criteria for participation in Tenaya’s ongoing Phase 1b RIDGE-1 clinical trial of TN-401 gene therapy 83 percent (95 of 115) of participants with available Holter data had a premature ventricular contraction (PVC) count of 500 PVCs/day or greater, a threshold linked with increased risk of life-threatening ventricular arrhythmias. 49 percent (56 of 115) of participants for whom Holter monitoring data was available had a history of ventricular tachycardia 60 percent of patients with MRI data available showed disease progression, as indicated by measures of right and left ventricular function, and heart tissue health Enrollment is also underway in Tenaya’s Phase 1b clinical trial, known as RIDGE™-1, to assess the safety, tolerability and activity of a one-time dose of TN-401. Tenaya plans to report safety and biopsy data from the first cohort of RIDGE-1 patients in the second half of 2025. “The RIDGE natural history study provides a rich source of data detailing the disease characteristics and burden for adults with ARVC. We extend our heartfelt gratitude to the patients and investigators involved in this important study. Their continued support has been instrumental in achieving the progress we've made thus far,” said Whit Tingley, M.D., Ph.D., Tenaya’s Chief Medical Officer. “As the largest collection of prospective and retrospective patient demographic and medical history data, RIDGE is expected to serve as a control arm to assess activity and efficacy of the interventional TN-401 study in determining meaningful clinical and surrogate endpoints for measuring gene therapy’s efficacy in the PKP2-associated ARVC indication, as well as serving as an important means of engaging with patients and clinical sites as we enroll our Phase 1b trial of TN-401.” The interim data from RIDGE will be presented at Heart Rhythm 2025 on April 26, 2025 by Dr. Calkins during the Basic Translational Science session in a poster titled “Determining Eligibility for RIDGE™-1, a Phase 1b Interventional Study to Evaluate Safety and Efficacy of TN-401 Gene Therapy in Adults with Plakophilin-2 (PKP2)-Associated Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC): Interim Results of an Observational Study to Assess Seroprevalence to Adeno-Associated Virus Serotype 9 (AAV9)”. 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 Therapy and the RIDGE-1 Clinical TrialTN-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. TN-401 has received Orphan Drug and Fast Track Designations from the U.S. Food and Drug Administration. Tenaya is conducting the RIDGE-1 Phase 1b clinical trial of TN-401 in patients with PKP2-associated ARVC. 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. RIDGE-1 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 PVC count during screening. To learn more about gene therapy for ARVC and participation in the RIDGE-1 study, please visit ARVCstudies.com or ClinicalTrials.gov (NCT06228924). 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 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 “potential,” “expected,” “plans, “will,” 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; expectation’s regarding the RIDGE data in support of determining meaningful clinical and surrogate endpoints for measuring gene therapy’s efficacy in the PKP2-associated ARVC indication; the planned timing to report initial data from RIDGE-1 and RIDGE; 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 potential failure of TN-401 to demonstrate safety and/or efficacy in clinical testing; actions and decisions of regulatory agencies; the timing and progress of RIDGE-1; availability of RIDGE-1 and RIDGE 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

Additional alignment with FDA on LX2006 planned pivotal study including protein expression co-primary endpoint: based on improvements in LVMI across participants with abnormal LVMI at baseline, frataxin expression to be evaluated for any increase from baseline rather than numerical threshold Interim update from cohort 1 of LX2020 HEROIC-PKP2 Phase 1/2 trial: observed 71% and 115% increases in PKP2 protein expression in first two post-treatment biopsies; first participant evaluated 6-months after dosing experienced 67% reduction in premature ventricular contractions (PVCs) Completed enrollment of cohort 2 of LX2020 HEROIC-PKP2 Phase 1/2 trial; interim clinical data update expected in second half of 2025 LX2020 has been generally well tolerated with no treatment-related serious adverse events to date Cash, cash equivalents and investments of $128.5 million expected to provide operational runway into 2027 NEW YORK, March 24, 2025 (GLOBE NEWSWIRE) -- Lexeo Therapeutics, Inc. (Nasdaq: LXEO), a clinical stage genetic medicine company dedicated to pioneering novel treatments for cardiovascular diseases, today provided business updates across its portfolio and reported fourth quarter and full year 2024 financial results. “We are pleased to share further regulatory clarity for LX2006 for the treatment of Friedreich ataxia (FA) cardiomyopathy, and we appreciate the continued partnership from the FDA on an accelerated approval pathway to support adults and children living with this devastating condition,” said R. Nolan Townsend, Chief Executive Officer of Lexeo Therapeutics. “We are also encouraged by the favorable safety profile and early data observed in participants dosed with LX2020 to date. We look forward to sharing additional clinical updates later in 2025 now that the second cohort of the LX2020 HEROIC-PKP2 Phase 1/2 trial in arrhythmogenic cardiomyopathy is fully enrolled.” Business and Program UpdatesLX2006 for the Treatment of FA Cardiomyopathy: Regulatory Update: Further alignment on elements of the accelerated development pathway following a Type B RMAT meeting with the U.S. Food and Drug Administration (FDA): Frataxin expression to be evaluated for any increase from baseline rather than numerical threshold, based on improvements to date in LVMI across participants with abnormal LVMI at baselineInclusion of pediatric cohorts, both adolescents and children, in planned pivotal studyUse of prospective natural history data as external control in planned pivotal studyFinal dose selection and remaining elements of registrational trial alignment expected in 2025 In light of these regulatory updates and anticipated timelines for assay validation, the Company expects to measure frataxin protein expression using liquid chromatography mass spectrometry (LCMS) in the planned registrational trial. Mid-Year Clinical Update Expected to Include: Safety and tolerability data for all participants dosed across both the SUNRISE-FA and Weill Cornell clinical trials (at least 16 participants, including 6 participants with abnormal LVMI at baseline)Pre- and post-treatment cardiac frataxin protein expression measured via LCMS for all four participants at the highest dose (1.2x1012 vg/kg, Cohort 3)Clinical biomarker data, including left ventricular mass index (LVMI), left ventricular wall thickness and high-sensitivity troponin I, for participants with >6-months of follow upFunctional and patient-reported outcome data for participants with >6-months of follow up Safety: LX2006 continues to be generally well tolerated with no new treatment-related serious adverse events to report LX2020 for the Treatment of PKP2-ACM: Cohort 1 Interim Update: Post-treatment cardiac biopsies from two participants in cohort 1 showed increases in PKP2 protein expression from baseline; the third cohort 1 participant elected not to undergo a post-treatment biopsy Observed increases in exogenous mRNA and 71% and 115% increases in PKP2 protein levels from baselineFirst participant evaluated 6-months post treatment experienced 67% reduction in PVCs from baseline (from 861 to 284) and resolution of non-specific intraventricular block (normalization of QRS duration) Enrollment Update: Completed enrollment of cohort 2 of LX2020 HEROIC-PKP2 (n=3), interim clinical data update expected in second half of 2025Safety: LX2020 has been generally well tolerated with no treatment-related serious adverse events to date across both dose cohortsRegulatory Update: In March 2025 the European Commission granted orphan medicinal product designation for LX2020 for the treatment of PKP2-ACM Fourth Quarter and Full Year Financial Results Cash Position: As of December 31, 2024, cash, cash equivalents, and investments were $128.5 million, which Lexeo believes will be sufficient to fund operations into 2027.R&D Expenses: R&D expenses were $18.4 million for the three months ended December 31, 2024, compared to $8.2 million for the three months ended December 31, 2023. R&D expenses were $74.1 million for the year ended December 31, 2024, compared to $53.1 million for the year ended December 31, 2023.G&A Expenses: G&A expenses were $9.0 million for the three months ended December 31, 2024, compared to $6.8 million for the three months ended December 31, 2023. G&A expenses were $31.7 million for the year ended December 31, 2024, compared to $15.4 million for the year ended December 31, 2023.Net Loss: Net loss was $25.9 million or $0.78 per share (basic and diluted) for the three months ended December 31, 2024, compared to $14.2 million or $0.86 per share (basic and diluted) for the three months ended December 31, 2023. Net loss was $98.3 million or $3.09 per share (basic and diluted) for the year ended December 31, 2024, compared to $66.4 million or $12.40 per share (basic and diluted) for the year ended December 31, 2023. About Lexeo TherapeuticsLexeo Therapeutics is a New York City-based, clinical stage genetic medicine company dedicated to reshaping heart health by applying pioneering science to fundamentally change how cardiovascular diseases are treated. The Company is advancing a portfolio of therapeutic candidates that take aim at the underlying genetic causes of conditions, including LX2006 for the treatment of Friedreich ataxia (FA) cardiomyopathy, LX2020 for the treatment of plakophilin-2 (PKP2) arrhythmogenic cardiomyopathy, and other devastating diseases with high unmet need. 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 and the timing for receipt and announcement of data from its clinical trials, the timing and likelihood of potential regulatory approval, and 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 September 30, 2024, filed with the SEC on November 13, 2024, and subsequent future filings Lexeo may make with the SEC. Additional information will also be set forth in Lexeo’s Annual Report on Form 10-K for the year ended December 31, 2024. 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:Media@lexeotx.com Investor Response:Carlo Tanzi, Ph.D.ctanzi@kendallir.com Lexeo Therapeutics, Inc.Selected Financial Information(in thousands, except share and per share amounts) Statements of Operations Three Months Ended December 31, Year Ended December 31, 2024 2023 2024 2023 (unaudited) (unaudited) Operating expenses Research and development$18,366 $8,210 $74,091 $53,130 General and administrative 9,016 6,764 31,675 15,383 Total operating expenses 27,382 14,974 105,766 68,513 Operating loss (27,382) (14,974) (105,766) (68,513)Other income and expense Loss on fair value adjustment to convertible SAFE Note - (258) - (530)Other income (expense), net - (8) (9) (13)Interest expense (30) (51) (137) (205)Interest income 1,465 1,103 7,556 2,867 Accretion of discount on investments 23 - 23 - Total other income and expense 1,458 786 7,433 2,119 Loss from operations before income taxes (25,924) (14,188) (98,333) (66,394)Income taxes - - - - Net loss$(25,924) $(14,188) $(98,333) $(66,394)Net loss per common share, basic and diluted$(0.78) $(0.86) $(3.09) $(12.40)Weighted average number of shares outstanding used in computation of net loss per common share, basic and diluted 33,076,094 16,438,237 31,787,491 5,354,368 Balance Sheet Data December 31, December 31, 2024 2023 Cash, cash equivalents, and investments $128,530 $121,466 Total assets 146,942 139,807 Total liabilities 30,100 26,272 Total stockholders' equity 116,842 113,535

Funding will Support Ongoing RIDGE™-1 Clinical Trial of TN-401 Gene Therapy for the Potential Treatment of PKP2-Associated Arrhythmogenic Right Ventricular Cardiomyopathy Initial Data from RIDGE-1 Phase 1b Clinical Trial Expected in 2H25 SOUTH SAN FRANCISCO, Calif., Feb. 03, 2025 (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 California Institute for Regenerative Medicine (CIRM), a state of California Agency that funds regenerative medicine, stem cell, and gene therapy research, has awarded Tenaya Therapeutics an $8.0 million CLIN2 grant. Proceeds from the grant will help fund clinical trial costs for Tenaya’s ongoing Phase 1b RIDGE-1 clinical trial of TN-401 gene therapy. 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 address the underlying cause of disease by delivering a functional PKP2 gene into heart muscle cells using an adeno associated virus serotype 9 (AAV9) capsid. The RIDGE-1 clinical trial will assess the safety, tolerability and preliminary clinical efficacy of a one-time intravenous infusion of TN-401. The open-label, dose-escalation study is currently enrolling symptomatic adults who have been diagnosed with PKP2-associated ARVC. "We are honored to be awarded this substantial grant and gratified to continue our collaboration with CIRM, whose efforts to accelerate world-class science and deliver transformative regenerative medicine treatments are making a profound impact on the advancement of novel treatments for serious conditions," said Faraz Ali, Chief Executive Officer of Tenaya Therapeutics. "Funds from this grant will support our ongoing RIDGE-1 clinical trial of TN-401, a potential best-in-class gene therapy for the treatment of PKP2-associated ARVC, a severe, progressive disease affecting an estimated 70,000 people in the U.S. RIDGE-1 is actively enrolling patients at leading centers, and we look forward to sharing initial data from the low-dose cohort in the second half of this year." To learn more about gene therapy for ARVC and participation in the RIDGE-1 study, please visit ARVCstudies.com or ClinicalTrials.gov (NCT06228924). Tenaya is also conducting a global natural history and seroprevalence study of adults with PKP2-assocated ARVC (NCT06311708). About PKP2-Associated ARVCPlakophilin-2 (PKP2) mutations are the most common genetic cause of arrhythmogenic right ventricular cardiomyopathy (ARVC), 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 the California Institute for Regenerative Medicine (CIRM) CIRM is a funding agency established by Californians to accelerate regenerative medicine research to deliver treatments for patients with unmet medical needs. Established in 2004 through the passage of Proposition 71, CIRM was initially funded with $3 billion from the state of California to support ongoing research, and in 2020, was funded again with another $5.5 billion through Proposition 14 to continue the Agency’s important work. CIRM has provided billions in funding to support stem cell, genetic research, and development programs in its portfolio. Through the Agency’s research, infrastructure, and education programs, CIRM aims to transform the field of regenerative medicine, stimulate economic growth, and improve the lives of diverse communities throughout the state. For more information go to cirm.ca.gov. 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 “expected,” “will,” “potential,” “estimated,” “look forward” and similar expressions are intended to identify forward-looking statements. Such forward-looking statements include, among other things, the planned timing to report initial data from RIDGE-1, the clinical, therapeutic and commercial potential of, and expectations regarding TN-401; clinical development plans for TN-401; targeted populations for PKP2-associated ARVC clinical trials and treatments; and statements made by Tenaya’s Chief Executive 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; our estimates of the number of patients who suffer from PKP2-associated ARVC; 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 the development of TN-401; 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 TN-401; 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