MyPEAK-1 Data Presented During Late-Breaking Session at AHA Scientific Sessions 2025 with Simultaneous Publication in Cardiovascular Research TN-201 Has Been Generally Well Tolerated at Both Doses Longer-term Follow Up of Cohort 1 Patients Showed Consistent, Deeper, and Durable Improvement in Measures of Hypertrophy Initial Cohort 2 Data Demonstrated Early Dose Responsive Increases in TN-201 Transduction and MyBP-C Protein Expression Tenaya Management to Host Webcast Call for Analysts and Investors on Monday, November 10 at 8:00 a.m. EST NEW ORLEANS and SOUTH SAN FRANCISCO, Calif., Nov. 08, 2025 (GLOBE NEWSWIRE) — Tenaya Therapeutics, Inc. (NASDAQ: TNYA) announced that new interim safety and efficacy data from the company’s MyPEAK™-1 Phase 1b/2a clinical trial of TN-201 were presented today during the Late-Breaking Science: Main Event session at the American Heart Association’s (AHA) Scientific Sessions 2025 by Milind Desai, M.D., MBA, director of the Hypertrophic Cardiomyopathy Center at Cleveland Clinic and vice chair of Cleveland Clinic’s Heart, Vascular & Thoracic Institute. These data, which included longer-term follow-up results for three patients dosed with TN-201 gene therapy at a dose of 3E13vg/kg (Cohort 1) and initial results for three patients who received TN-201 at a dose of 6E13 vg/kg (Cohort 2) were simultaneously published in Cardiovascular Research. 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). Single administration of TN-201 gene therapy was generally well-tolerated at both the 3E13 vg/kg and 6E13 vg/kg dose levels and immunogenicity was well managed through monitoring and individualized tapering of immunosuppressives. TN-201 achieved robust transduction and durable expression with early dose-dependent increase in both transduction and MyBP-C protein expression. Among Cohort 1 patients for whom there was greater than one year of follow up, decreases in circulating biomarkers and reductions in measures of left ventricular hypertrophy deepened over time. “These initial results are promising for a patient population that too often live with difficult, even dangerous, symptoms,” said Dr. Desai, an investigator for the MyPeak-1 Phase 1b/2a clinical trial. “In the past decade, we’ve made great progress in understanding and treating hypertrophic cardiomyopathy, and as our understanding of the genetic underpinnings of HCM increases, research into gene therapies such as TN-201 offer the opportunity to further advance and improve patient care.” “Results of TN-201 treatment are in line with our expectations for this stage of trial, with a manageable safety profile and dose-dependent MyBP-C protein level increases over time. In particular, the durable changes in multiple parameters of disease – biomarkers, hypertrophy and heart failure symptoms – all moving with directional consistency toward normalization after a single dose are an encouraging early signal of TN-201’s activity,” said Whit Tingley, M.D., Ph.D., Tenaya’s Chief Medical Officer. “We look forward to building on these data with continued long-term follow-up of Cohort 1 and the maturation of early results for Cohort 2, which will inform our plans for TN-201’s late-stage development.” Interim results from the MyPEAK-1 Phase 1b/2a Clinical TrialData reported today includes safety, biopsy and leading indicators of efficacy for the three patients enrolled in Cohort 1 with follow-up ranging from Week 52-78, and safety for the three patients in Cohort 2, Week 12 biopsy for Patient 6 and Week 26 assessments for Patient 4 as of the July 2025 data cut off. Patient 5 was lost to further follow-up after week 12. All patients other than Patient 5 have completed every visit and remain on study. All patients enrolled in MyPEAK-1 had serious burden of disease at baseline. All six had objectively severe nonobstructive HCM with levels of hypertrophy significantly above average for people with HCMAll six were at sufficiently high risk of sudden cardiac death to warrant an implantable cardiac defibrillator (ICD) deviceAll experienced mild-to-moderate symptoms of heart failure that interfered in activities of daily living (New York Heart Association, or NYHA, Class II-III)Four of the six have previously undergone surgical myectomy Safety data for all six patients in Cohorts 1 and 2 showed that TN-201 was generally well tolerated at both the 3E13 vg/kg and 6E13 vg/kg doses. No dose-limiting toxicities were observed and all patients have tapered off immunosuppressive medicines. Reversible, asymptomatic liver enzyme elevations (Grade 1-3) were the most common treatment-related adverse events (AEs) reportedThere were no signs of cardiotoxicities, including no declines in left ventricular ejection fraction, clinical myocarditis or ventricular arrhythmiasThere were two treatment-related AEs classified as serious due to inpatient treatment or monitoring: a Cohort 1 patient with Grade 2 transaminase elevation that responded to steroids and a Cohort 2 patient with Grade 1 elevation of complement factors that resolved without additional interventionAdjustments to monitoring and immunosuppression during Cohort 1 resulted in faster tapers and lower cumulative corticosteroid doses in Cohort 2, despite the higher TN-201 dose MyBP-C protein levels increased over time, with early evidence of a substantial increase commensurate with higher dose in Cohort 2. TN-201 DNA transduction and TN-201 mRNA expression following similar dose response. Tenaya reported that TN-201 transduction and TN-201 mRNA expression were robust. All three patients in Cohort 1 demonstrated sustained presence of TN-201 DNA in the heart and mRNA expression that increased over time, supporting the observed increases in MyBP-C level changes.In Cohort 1 patients, protein levels increased by an average of 4% from the first biopsy taken to Week 52. In Patient 3, the first patient for whom baseline biopsies were available, MyBP-C protein was shown to increase by 5% at Week 52.The first evaluable patient in Cohort 2 (Patient 6) demonstrated a clear dose response, and early MyBP-C expression increased by 14% after only 12 weeks post-dose. Of note, Patient 6 had a greater than 2-fold increase in transduction and expression at Week 12 relative to the averages for these measures observed across Cohort 1. Multiple parameters, including biomarkers, hypertrophy, heart failure symptoms, associated with increased risks of complications or reduced survival, have improved among a majority of patients with greater than 26 weeks of follow-up. Cardiac Troponin I levels declined significantly (48%-74%) to normal or near-normal levels in all Cohort 1 patients. Cardiac troponin I is a predictive risk factor of cardiac AEs such as ventricular arrhythmias, sudden cardiac death, and progression to end-stage heart failure.(1)NT-proBNP, a biomarker of cardiac muscle strain, improved or remained stable in two of three Cohort 1 patientsCardiac Troponin I remained within the normal range and NT-proBNP remained stable for Patient 4 from Cohort 2 at their 26-Week assessmentAll three patients in Cohort 1 now have evidence of significant improvement in one or more measures of hypertrophy at Week 52, including notable reductions in left ventricular posterior wall thickness (LVPWT) of between 21% and 39%. LVPWT for Patient 4 in Cohort 2 was stable at Week 26. Greater LVPWT is an independent risk factor for reduced long-term survival after septal myectomy.(2)Two out of three Cohort 1 patients saw reductions in overall left ventricular mass index (LVMI) of between 12% and 22% at Week 52. LVMI for Patient 4 in Cohort 2 was stable at Week 26NYHA classification, a measure of the impact of heart failure symptoms on activities of daily living, improved in all patients by at least one class by Week 26, and all Cohort 1 patients are now NYHA Class I (asymptomatic). While the interim results from MyPEAK-1 are promising, longer-term follow-up for all patients is required to further inform Tenaya’s understanding of TN-201’s potential as a treatment for MYBPC3-associated HCM. Tenaya plans to periodically report additional results from longer-term follow-up. These interim data were presented during the “Forgotten No More: The Current Belle of the Ball? Breakthrough Evolutions in Hypertrophic Cardiomyopathy” Late-Breaking Science: Main Event session during AHA 2025 and were published simultaneously in an article titled “First-in-human study of AAV9:MYBPC3 gene replacement therapy (TN-201) in hypertrophic cardiomyopathy: Initial safety, pharmacodynamic, and imaging results from MyPEAK-1” in Cardiovascular Research. Conference Call and WebcastTenaya management will host a conference call on Monday, November 10, 2025, at 8:00 a.m. ET/5:00 a.m. PT to discuss the TN-201 data presented and published today and the status of the MyPEAK-1 clinical trial.  The webcast conference call, including an accompanying slide presentation, can be accessed from the Investor section on the “Events and Presentations” page of the Tenaya website at www.tenayatherapeutics.com. About the MyPEAK-1 Phase 1b/2a Clinical TrialThe MyPEAK-1 Phase 1b/2 clinical trial (Clinicaltrials.gov ID: NCT05836259) is a multi-center, open-label, dose-escalating (3E13 vg/kg and 6E13 vg/kg) study of symptomatic adults (up to 24) who have been diagnosed with MYBPC3-associated HCM. MyPEAK-1 is designed to assess the safety, tolerability and clinical efficacy of a one-time intravenous infusion of TN-201 gene replacement therapy. MyPEAK-1 has tested doses of 3E13 vg/kg and 6E13 vg/kg in two cohorts of three patients each. On July 30, 2025, Tenaya reported that the trial’s independent Data Safety Monitoring Board (DSMB) concluded that TN-201 had an acceptable safety profile to allow enrollment of expansion cohorts at either the 3E13 vg/kg (Cohort 1) or 6E13 vg/kg (Cohort 2) dose levels. On November 7, 2025, Tenaya announced the FDA placed MyPEAK-1 on a clinical hold. Tenaya is working with the FDA to address the agency’s concerns through an amendment to the trial protocol. To learn more about gene therapy for HCM and participation in the MyPEAK-1 study, please visit HCMStudies.com. About MYBPC3-Associated Hypertrophic Cardiomyopathy (HCM)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. 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. 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 address the underlying cause of MYBPC3-associated hypertrophic cardiomyopathy (HCM) by delivering a working MYBPC3 gene to heart muscle cells via a single intravenous infusion and thereby increasing insufficient MyBP-C protein levels 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’s pipeline includes clinical-stage candidates TN-201, a gene therapy for MYBPC3-associated hypertrophic cardiomyopathy (HCM) and TN-401, a gene therapy for PKP2-associated arrhythmogenic right ventricular cardiomyopathy (ARVC). Tenaya has employed a suite of integrated internal capabilities, including modality agnostic target validation, capsid engineering and manufacturing, to generate a portfolio of novel medicines based on genetic insights, including TN-301, a clinical-stage small molecule HDAC6 inhibitor for the potential treatment of heart failure and related cardio/muscular disease, and multiple early-stage programs in preclinical development aimed at the treatment of both rare genetic disorders and more prevalent heart conditions. For more information, visit www.tenayatherapeutics.com.       (1)   Kubo, et al, Journal Am Coll Cardiol, 2013      (2)   Schaff, et al, JACC Heart Failure, 2022 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 “promising,” “opportunity,” “expectations,” “encouraging,” “look forward,” “will,” “potential,” 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-201 as a treatment for MYBPC3-associated HCM; the potential for additional MyPEAK-1 data to inform plans for TN-201’s late stage development; statements regarding the continued development of TN-201, clinical hold, anticipated timelines, TN-201 clinical outcomes and risk/benefit profile, which may materially change as more patient data become available and statements made by Tenaya’s Chief Medical Officer and the 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: the expected timing and outcome of Tenaya’s regulatory interactions related to the clinical hold on MyPEAK-1; the timing and availability of MyPEAK-1 data; the potential 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; the potential for the FDA and/or other regulatory agencies to conclude at any time that TN-201 may not have an appropriate risk/benefit profile; 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 June 30, 2025, 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. Tenaya ContactsMichelle CorralVP, Corporate Communications and Investor RelationsIR@tenayathera.com InvestorsAnne-Marie FieldsPrecision AQannemarie.fields@precisionaq.com MediaWendy RyanTen Bridge Communicationswendy@tenbridgecommunications.com

Largest Noninterventional Natural History Study of People Under 18 with MYBPC3-associated HCM with More than 200 Participants 93% of MyClimb Participants had the Nonobstructive Form of HCM for Which There Are No Approved Therapeutics Genotypic Status Identified as a Significant Predictor of Risk and Left Ventricular Mass Index May Serve as a Surrogate Marker for Poor Long-Term Outcomes SOUTH SAN FRANCISCO, Calif., Aug. 31, 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 the presentation of interim data from its ongoing MyClimb™ (ClinicalTrials.gov ID: NCT05112237) natural history study of pediatric participants with MYBPC3-associated hypertrophic cardiomyopathy (HCM) at the European Society of Cardiology Congress (ESC). “The interim data from MyClimb presented at ESC highlight the distinct risks of complications, heightened severity and rapid rate of disease progression experienced by pediatric patients with MYBPC3-associated HCM,” said Georgia Brugada, M.D., Pediatric Cardiologist, Head of Arrhythmias Unit, and Medical Consultant at SJD Barcelona Children’s Hospital and an investigator for the MyClimb study. “The data emerging from MyClimb underscore the urgent need for disease-modifying approaches to the treatment of children with MYBPC3-associated HCM, as well as the importance of genetic diagnosis, genetic counseling and close monitoring in this population.” “Data obtained from MyClimb offer actionable information for predicting those severe MYBPC3-associated HCM pediatric patients who may be at higher risk of death or severe complications, such as life-threatening ventricular arrhythmias, cardiovascular-related hospitalizations, heart failure, sudden cardiac arrest, and/or heart transplant,” said Whit Tingley, M.D., Ph.D., Tenaya’s Chief Medical Officer. “Among the new observations, we believe certain genetic profiles or higher left ventricular mass index can identify those children who are at substantially greater risk of serious potential complications, relatively rapid progression and poor long-term outcomes. These new insights into predictive risk factors can inform clinicians’ thinking on risk stratification and interventions and offer important clues for endpoints and eligibility criteria as we consider advancing genetic medicines such as TN-201 gene therapy in clinical trials for pediatric patients where there is high unmet need.” MyClimb is believed to be the largest natural history study of those under 18 diagnosed with MYBPC3-associated HCM. As of the July 2025 cutoff for this interim readout, 213 MYBPC3-associated HCM individuals diagnosed before the age of 18 were analyzed, with retrospective data for 173 and prospective data for 42 participants available. Participants were enrolled from 27 centers across the U.S., Canada, Spain and the UK. Key findings from MyClimb shared at ESC 2025 include: 93% of participants were classified as having the nonobstructive HCM phenotype, for which there are currently no approved treatment options.Participants were stratified based on three genetic inheritance patterns, revealing distinct risk profiles. Among the Homozygous group (also referred to as biallelic; those born with two pathogenic or likely pathogenic truncating variants in MYBPC3), nearly all died or required heart transplant before age one.Compound Heterozygous participants (with one pathogenic or likely pathogenic truncating variant and one missense variant in MYBPC3) had a median age of diagnosis of 2.9 years of age and experienced severe cardiomyopathy with significant arrythmia burden and high prevalence of heart-failure related hospitalization (63%), transplant or death (27%).Heterozygous children (with one pathogenic or likely pathogenic variant in MYBPC3) had a median age of diagnosis of 6.5 years of age. Among these, 27% experienced heart failure-related hospitalizations and 13% had arrhythmia-related symptoms. Initial modeling suggests Left Ventricular Mass Index (LVMI) was found to be a significant predictor of risk in compound heterozygous and heterozygous groups, with every 10-unit (g/m2) increase associated with a 10% higher hazard of a serious event. These findings indicate LVMI may serve as an appropriate surrogate marker to evaluate the early effectiveness of gene therapy in potential future pivotal studies. The poster, titled “Interim results from MyClimb, a natural history study of pediatric MYBPC3-associated hypertrophic cardiomyopathy (HCM)” is being presented as a moderated e-poster by Dr. Brugada at ESC 2025 today during the Pediatric cardiomyopathy session and is available in the “Our Science” section of Tenaya’s website. About MyClimb and Pediatric MYBPC3-Associated HCMMyClimb is a retrospective and prospective natural history study of MYBPC3-associated HCM participants diagnosed before the age of 18. The study was initiated in 2021 to characterize the association between genotype, structural, and functional cardiac measures over time. To date, MyClimb has enrolled more than 200 individuals at 29 sites worldwide and is believed to be the largest study of pediatric individuals with MYBPC3-associated HCM ever conducted. Mutations in MYBPC3, the gene that encodes cardiac myosin-binding protein C, are among the most common genetic causes of HCM. MYBPC3-associated pediatric-onset HCM is estimated to comprise ~17% of all MYBPC3-driven HCM cases, with 2% of patients presenting in infancy. In the U.S. alone, there are an estimated 3,000 children with the condition and 13,000 individuals who were diagnosed before the age of 18 and are now adults. Current treatment options for children with MYBPC3-associated HCM are limited and while interventions such as implantable cardio defibrillators and heart transplant may be lifesaving, they are also highly invasive, frequently associated with considerable complication rates and do not address the underlying cause of disease. About TN-201 Gene TherapyTN-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. The MyBP-C protein plays a crucial role in regulating the heart’s contractility. Encouraging initial data from the first three patients to receive TN-201 at the 3E13 vg/kg dose level (Cohort 1) were presented at the American College of Cardiology meeting Tenaya intends to report longer-term follow-up data from Cohort 1 and initial data from Cohort 2 in the fourth quarter of 2025. 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’s pipeline includes clinical-stage candidates TN-201, a gene therapy for MYBPC3-associated hypertrophic cardiomyopathy (HCM) and TN-401, a gene therapy for PKP2-associated arrhythmogenic right ventricular cardiomyopathy (ARVC). Tenaya has employed a suite of integrated internal capabilities, including modality agnostic target validation, capsid engineering and manufacturing, to generate a portfolio of novel medicines based on genetic insights, including TN-301, a clinical-stage small molecule HDAC6 inhibitor for the potential treatment of heart failure and related cardio/muscular disease, and multiple early-stage programs in preclinical development aimed at the treatment of both rare genetic disorders and more prevalent heart conditions. 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 “believe,” “may,” 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-201; the potential for MyClimb data to help decipher endpoints and eligibility criteria for TN-201 in clinical trials for pediatric patients; the planned timing to report interim results from MyClimb; 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-201 to demonstrate safety and/or efficacy in clinical testing; actions and decisions of regulatory agencies; availability of MyClimb results at the referenced time; 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 Contact Michelle CorralVP, Corporate Communications and Investor RelationsTenaya TherapeuticsIR@TenayaThera.com InvestorsAnne-Marie FieldsPrecision AQ annmarie.fields@precisionaq.com MediaWendy RyanTen Bridge Communicationswendy@tenbridgecommunications.com

TN-201 Has Been Well Tolerated at 3E13 vg/kg Dose New Biopsy Data Reaffirm Robust Transduction and RNA Expression with TN-201; RNA and Protein Levels Increase Over Time All Cohort 1 Patients with Severe Disease at Baseline Achieved NYHA Class I Two of Three Patients Experienced Improvements in One or More Measures of Hypertrophy Expects to Complete Enrollment of Cohort 2 in 1H25 and to Report Initial Data in 2H25 SOUTH SAN FRANCISCO, Calif., March 31, 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, announced that interim data from the first three patients enrolled in the company’s MyPEAK-1 Phase 1b/2 clinical trial of TN-201 were highlighted in a Late-Breaker presentation at the 2025 American College of Cardiology Scientific Sessions (ACC.25). TN-201 is being developed for the potential treatment of Myosin Binding Protein C3 MYBPC3-associated hypertrophic cardiomyopathy (HCM), a condition caused by insufficient levels of myosin-binding protein C (MyBP-C). “TN-201 is the first gene therapy to be tested in HCM patients whose disease is caused by mutations to the MYBPC3 gene. For patients with this mutation, their disease is often more aggressive in its progression and they are at higher risk of serious – sometimes fatal – complications,” said Milind Desai, M.D., M.B.A, Haslam Family Endowed Chair in Cardiovascular Medicine, Vice Chair of Education in the Heart Vascular Thoracic Institute, Director of the Hypertrophic Cardiomyopathy Center at Cleveland Clinic, and an investigator for the MyPEAK-1 Phase 1b/2 clinical trial. “I look forward to continuing to study and evaluate this to see if this patient population is one that could be treated with gene therapy, as we have seen with other diseases.”  “TN-201’s emerging safety profile at the 3E13 vg/kg dose, combined with biopsy results showing robust transduction, encouraging expression in the heart and suggestions of clinical improvement or stability are positive early signals of TN-201’s clinical impact,” said Whit Tingley, M.D., PhD., Tenaya’s Chief Medical Officer. “These data reinforce our optimism about TN-201’s potential to transform the treatment landscape for MYBPC3-associated HCM patients by addressing the underlying cause of their disease. We look forward to reporting additional data from Cohort 1 and getting our first look at the higher dose cohort later this year. We are profoundly grateful to the HCM community for their support of this work, and particularly to all those participating in the MyPEAK-1 clinical trial.” Interim data presented at ACC.25 include results from serial biopsies and assessments of Patient 1 and 2 at Week 52 and Patient 3 at Week 26, analyzing changes over time in the first three patients to receive a one-time infusion of TN-201 gene therapy (Cohort 1). TN-201 was generally well tolerated at 3E13 vg/kg, and treatment-emergent adverse events (AEs) were primarily mild, manageable and/or reversible.Serial biopsies taken at two timepoints for all three patients demonstrated sustained presence of TN-201 DNA in the heart (0.8 to 1.4 vg/dg) and robust TN-201 RNA expression ( >1.25×105 copies per microgram of RNA) that increased as much as 13-fold from Week 8 to Week 52 post-dose.MyBP-C protein levels increased from 56 to 59% and from 62 to 64% of normal between Week 8 and Week 52 for Patients 1 and 2, respectively. 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. Patient 3 was the first patient on study to receive a baseline biopsy, which is expected to offer insight into the total change in protein levels following TN-201 treatment. The post-dose biopsy sample from Patient 3 was not evaluable; a second post dose biopsy is planned later this year and will be reported in a future data readout. Cardiac troponin, a biomarker of myocardial injury, was elevated in Cohort 1 patients at baseline and decreased by more than 60% in two patients, whose levels are now normal or near normal. NT-proBNP, a biomarker of cardiac strain, increased and remained elevated while patients were on immunosuppression, but returned to baseline as immunosuppressive drugs were discontinued.Key measures of hypertrophy, or enlargement of the heart, improved in two patients while other assessments remained stable. Left ventricular posterior wall thickness, which was elevated at baseline, decreased in two patients by up to 40% into the normal range for healthy individuals. In one patient, left ventricular mass (LVMI) improved by 10%. Additional measures of hypertrophy and diastolic function remained stable.All three patients in Cohort 1 had objectively severe disease at the time of enrollment with mild-to moderate heart failure symptoms (New York Heart Association (NYHA) classification II or III) that interfered in activities of daily living. All three have now achieved NYHA Class I, defined as having no limitations on physical activity. “We are excited by these promising early data from Dose Cohort 1 and the prospects for initial data from Dose Cohort 2 later this year where two of three patients have already been dosed,” said Faraz Ali, Chief Executive Officer of Tenaya. “We are also pleased that with our recent financing, plus adjustments to our spend, we have updated our cash guidance into the second half of 2026 and are well-positioned to achieve important clinical data milestones on both the TN-201 and TN-401 gene therapy programs over the next 12 months.” The interim MyPEAK-1 data were presented today by Dr. Desai during the Clinical and Investigative Horizons session in a Late-breaker presentation talk titled, “First Report of Phase 1b/2a Study Evaluating Safety and Early Efficacy of TN-201, an Adeno-Associated Virus Serotype 9 Gene Replacement Therapy, in Adults with MYBPC3-Associated Hypertrophic Cardiomyopathy”. Tenaya researchers also presented data at ACC.25 offering new insights into the disease burden of patents with MYBPC3-associated HCM compared to other HCM populations. Results from this study, “Differences in Patient Characteristics and Burden of Disease in Adults with MYBPC3-Associated HCM (#129)”, conducted in collaboration with the Sarcomeric Human Cardiomyopathy Registry (SHaRE), analyzed outcomes for 1,637 MYBPC3-associated HCM adults by age of diagnosis. Patients with pathogenic/likely pathogenic MYBPC3 mutations were found to be at risk for serious clinical manifestations including heart failure, arrhythmias, and sudden cardiac death.Younger patients progressed more rapidly and were more likely to experience serious outcomes.Approximately 50% of adult patients diagnosed before the age of 40 experience a serious cardiac event by the age of 50. Both presentations are available on the Tenaya website. Cohorts 1 and 2 in the Ongoing MyPEAK-1 Phase 1b/2 Clinical TrialData reported today focus on changes over time in the first three patients to receive TN-201 gene therapy. All three participants presented with nonobstructive HCM having previously undergone myectomy and remained at sufficiently high risk of sudden cardiac death to warrant an implantable cardiac defibrillator device (ICD). Per protocol, all patients received immunosuppressives consisting of sirolimus and prednisone before and after dosing, which was tapered over time based on monitoring of liver and inflammatory markers. All three patients have successfully tapered off immunosuppressives and remain on study. Following dosing of the first three patients in MyPEAK-1, an independent data and safety monitoring board (DSMB) evaluated available safety data. The DSMB endorsed the broadening of eligibility criteria and enrollment of the planned high dose cohort. Accordingly, patients are now being enrolled in Cohort 2 to receive TN-201 at a dose of 6E13 vg/kg. Tenaya anticipates completion of enrollment of the first three patients in Cohort 2 in the first half of the year and plans to share initial safety and biopsy data from Cohort 2, along with additional follow-up data from Cohort 1, in the second half of this year. 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 “expects,” “potential,” “look forward,” “optimism,” “could,” “encouraging,” “planned,” “guidance” and similar expressions are intended to identify forward-looking statements. Such forward-looking statements include, among other things, the planned timing to complete enrollment and report additional data from MyPEAK-1; the clinical, therapeutic and commercial potential of, and expectations regarding TN-201 as a treatment for MYBPC3-associated HCM; 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; Tenaya’s cash guidance commitment to focusing its resources on generating clinical data for its gene therapy pipeline 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 Annual Report on Form 10-K for the fiscal year ended December 31, 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

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, today released new data for TN-301 at the 2023 Heart […]

Phase 1b Clinical Trial for TN-201 in MYBPC3-associated HCM Patients Expected to Begin Dosing in Third Quarter 2023; Data Anticipated in 2024 Data from First-in-Human Clinical Trial of TN-301 Anticipated in Second Half 2023 TN-401 IND Submission Planned in Second Half 2023 Cash Runway Extended into First Half 2025 SOUTH SAN […]