Pipeline and Programs - Tenaya Therapeutics has 3 clinical-stage programs focused on heart disease[9] - TN-201, a gene therapy for MYBPC3-associated HCM, is in Phase 1b/2 clinical trials with data readouts expected in Q4 2025[10, 12] - TN-401, a gene therapy for PKP2-associated ARVC, is in Phase 1b clinical trials with initial data including safety and biopsy results expected in 2025[10, 94] - TN-301, a small molecule HDAC6 inhibitor for HFpEF, has completed Phase 1 trials and is seeking a partner for further development[10, 99, 104] TN-201 for MYBPC3-associated HCM - MYBPC3-associated HCM affects an estimated 120,000 people in the U S alone[22] - Interim Cohort 1 data for TN-201 showed the therapy was well-tolerated at 3E13 vg/kg dose, with no cardiotoxicities and manageable liver enzyme elevations[17, 40] - All three patients in Cohort 1 improved from NYHA class II/III to NYHA class I, and elevated troponin levels dropped by 60% in two patients into normal ranges[19] - TN-201 DNA in cardiac biopsy surpassed preclinical efficacy threshold and compares favorably to peer, with long-term stability achieved[42] - TN-201 RNA expression increased by as much as 13-fold from week 8 to Week 52[46] TN-401 for PKP2-associated ARVC - PKP2-associated ARVC is estimated to affect over 70,000 people in the U S [75] - Preclinical studies showed that a single 3E13 vg/kg dose of TN-401 in a KO mouse model reversed hallmarks of the disease and extended survival[91] - RIDGE natural history study shows that over 80% of ARVC patients continue to experience high PVC count despite standard of care treatments[87]

Summary of Tenaya Therapeutics (TNYA) FY Conference Call Company Overview - **Company**: Tenaya Therapeutics (TNYA) - **Founded**: 2016 - **Mission**: Focus on therapies for heart disease, including both rare genetic forms and prevalent forms [3][4] Pipeline and Clinical Development - **Clinical Stage Assets**: Three clinical stage assets currently in development [4] - **Gene Therapies**: Focus on gene therapies for genetic causes of cardiomyopathy and a small molecule for HFpEF [4] - **Clinical Sites**: Over 40 clinical sites active in seven countries for patient recruitment [4] Gene Therapy Programs TN-201 for MYBPC3 Positive Hypertrophic Cardiomyopathy - **Target Disease**: Leading genetic cause of hypertrophic cardiomyopathy, affecting approximately 120,000 patients in the US [15] - **Mechanism**: Addresses deficiency of myBPC3 protein, leading to heart thickening and potential heart failure [16][17] - **Natural History Study**: MyCLIMB study with over 220 children enrolled to characterize disease progression [20][21] - **Phase 1b Study**: Completed dosing of high dose cohort; initial results show improvement in heart function [25][27] - **Upcoming Data**: Full cohort data expected in Q4 2025, with focus on safety and efficacy [37] TN-401 for PKP2-Related Arrhythmogenic Right Ventricular Cardiomyopathy - **Target Disease**: Accounts for about 40% of arrhythmogenic right ventricular cardiomyopathy cases, approximately 70,000 patients in the US [44] - **Mechanism**: Aims to add a copy of the human gene to improve desmosome function and reduce arrhythmia burden [46] - **Biopsy Data**: Expected in Q4 2025, focusing on vector copy number, RNA, and protein levels [50][51] Safety and Efficacy - **AAV9 Vector**: Selected for its extensive safety database and effectiveness in cardiac applications [5][6] - **Safety Record**: No significant safety issues reported in ongoing trials; adverse events consistent with other gene therapies [13][14] - **Patient Outcomes**: Initial data shows symptomatic improvement in patients treated with TN-201 [25][27] Small Molecule Program TN-301 - **Status**: Completed first-in-human study with 72 patients; well tolerated with no dose-limiting toxicities [55] - **Future Plans**: Exploring opportunities to advance the program, focusing on HFpEF and potentially severe rare diseases [56] Key Takeaways - **Market Opportunity**: Both TN-201 and TN-401 target large orphan conditions with significant unmet medical needs [44][46] - **Data Releases**: Important data updates expected in Q4 2025 for both gene therapy programs, which could influence future clinical development strategies [37][50]

Clinical Programs & Data - Tenaya Therapeutics has 3 clinical-stage programs focused on heart disease [9] - TN-201 for MYBPC3-associated HCM plans data release including longer-term follow-up for Cohort 1 (3E13 vg/kg) and initial safety and biopsy results for Cohort 2 (6E13 vg/kg) in Q4'25 [15] - TN-401 for PKP2-associated ARVC plans data release will include initial Cohort 1 (3E13 vg/kg) data focused on safety and biopsy results in Q4'25 [16] - Interim Cohort 1 TN-201 data showed improvements in ≥ 1 measures of hypertrophy in two of three patients [17] Disease & Patient Populations - MYBPC3-associated HCM is estimated to affect 120,000 people in the U S alone [22] - Approximately 57% of identified genetic variants underlying familial HCM are MYBPC3 mutations [22] - Over 30% of genetic variants underlying childhood-onset HCM are MYBPC3 mutations [22] - PKP2-associated ARVC is estimated to affect >70,000 people in the U S [75] - In ARVC patients, >15% of heart-related deaths in patients < 35 are due to ARVC [75] - In ARVC patients, 23% of ARVC patients present with sudden cardiac death [75] - In ARVC patients, 40% of ARVC patients carry pathogenic PKP2 mutations [75] Capabilities & Milestones - Tenaya has cGMP AAV manufacturing scale achieved; 1000L clinical supply for TN-201 and TN-401 ready [115]

Core Insights - Tenaya Therapeutics, Inc. is a clinical-stage biotechnology company focused on developing potentially curative therapies for heart disease [1][3] - The company will participate in the Canaccord Genuity 45 Annual Growth Conference on August 12, 2025 [1] Company Overview - Tenaya's mission is to discover, develop, and deliver therapies that target the underlying causes of heart disease [3] - The company's pipeline includes clinical-stage candidates TN-201 for MYBPC3-associated hypertrophic cardiomyopathy and TN-401 for PKP2-associated arrhythmogenic right ventricular cardiomyopathy [3] - Tenaya employs integrated capabilities such as target validation, capsid engineering, and manufacturing to create novel medicines based on genetic insights [3] - Additional products in development include TN-301, a small molecule HDAC6 inhibitor for heart failure, and various early-stage programs targeting rare genetic disorders and common heart conditions [3]

UNITED STATES SECURITIES AND EXCHANGE COMMISSION WASHINGTON, DC 20549 FORM 10-Q (Mark One) ☒ QUARTERLY REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the quarterly period ended June 30, 2025 OR ☐ TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the transition period from ________ to _________ Commission File Number: 001-40656 TENAYA THERAPEUTICS, INC. (Exact name of registrant as specified in its charter) Delaware 81-3789973 | | ...

Exhibit 99.1 Tenaya Therapeutics Reports Second Quarter 2025 Financial Results and Provides Business Update Enrollment Complete in Cohorts 1 and 2 of MyPEAKTM-1 Phase 1b/2 Trial of TN-201 for MYBPC3- associated HCM; Positive DSMB Safety Review Enables Enrollment of Expansion Cohorts Cohort 1 of RIDGE™-1 Phase 1b Trial of TN-401 Enrolled and First PKP2-associated ARVC Patient Dosed in Cohort 2 Following DSMB Recommendation to Dose Escalate and Expand Data Readouts from Both TN-201 and TN-401 Clinical Program ...

Core Insights - Tenaya Therapeutics has completed enrollment in its gene therapy clinical trials for TN-201 and TN-401, targeting MYBPC3-associated hypertrophic cardiomyopathy (HCM) and PKP2-associated arrhythmogenic right ventricular cardiomyopathy (ARVC) respectively [1][3][4] - The company received positive recommendations from the Data Safety Monitoring Board (DSMB) for dose escalation and expansion in both trials, marking significant milestones in their development [3][4] - Data readouts for both clinical programs are anticipated in the fourth quarter of 2025, which will provide further insights into the efficacy and safety of the therapies [1][3] Clinical Development Updates - Enrollment for Cohort 1 of the MyPEAK™-1 Phase 1b/2 trial of TN-201 is complete, with three patients dosed at the 6E13 vg/kg level [4] - The DSMB for MyPEAK-1 has determined that TN-201 has an acceptable safety profile, allowing for the enrollment of additional patients in the dose expansion cohorts [4] - The RIDGE-1 Phase 1b trial for TN-401 has also completed enrollment for its first cohort, with the first PKP2-associated ARVC patient dosed following DSMB recommendations [1][4] Financial Performance - As of June 30, 2025, Tenaya reported cash, cash equivalents, and marketable securities totaling $71.7 million, sufficient to support operations into the second half of 2026 [9][14] - Research and Development (R&D) expenses for Q2 2025 were $17.4 million, a decrease from $22.6 million in Q2 2024 [9][13] - General and Administrative (G&A) expenses were $6.7 million for Q2 2025, down from $8.2 million in the same period of 2024 [9][13] Upcoming Events and Presentations - Tenaya plans to host a Virtual Key Opinion Leader event on August 19, 2025, focusing on protein expression in cardiac gene therapy [9] - An abstract regarding Tenaya's pediatric non-interventional natural history study, MyClimb, has been accepted for presentation at the European Society of Cardiology Annual Meeting [4]

Core Insights - Tenaya Therapeutics has received positive endorsements from the Data Safety and Monitoring Boards (DSMB) for its two cardiovascular gene therapy clinical trials, MyPEAK-1 for TN-201 and RIDGE-1 for TN-401, allowing the trials to proceed as planned [1][2] MyPEAK-1 Phase 1b/2 Clinical Trial - The MyPEAK-1 trial is focused on TN-201 for MYBPC3-associated hypertrophic cardiomyopathy (HCM) and has completed enrollment in both dose cohorts [1] - The DSMB has reviewed data from the first three patients in Cohort 2 and determined that TN-201 has an acceptable safety profile, allowing for the enrollment of expansion cohorts at both 3E13 vg/kg and 6E13 vg/kg dose levels [3][4] - Initial data from Cohort 1 showed that TN-201 reached cardiomyocytes, resulting in increased MyBP-C protein levels and significant improvement in heart failure symptoms for patients [4][5] RIDGE-1 Phase 1b Clinical Trial - The RIDGE-1 trial is investigating TN-401 for PKP2-associated arrhythmogenic right ventricular cardiomyopathy (ARVC) and has also completed initial patient enrollment [6] - The DSMB has endorsed dose escalation to 6E13 vg/kg and expansion of Cohort 1, with the first patient in Cohort 2 already dosed [6][7] - Initial data from Cohort 1 is expected to focus on safety and tolerability, with results anticipated in the fourth quarter of 2025 [7] Future Expectations - Tenaya plans to report longer-term follow-up data from Cohort 1 and initial data from Cohort 2 of both trials in the fourth quarter of 2025, which will inform dose selection and pivotal study design for both pediatric and adult populations [5][7] Company Overview - Tenaya Therapeutics is a clinical-stage biotechnology company focused on developing potentially curative therapies for heart disease, with a pipeline that includes TN-201 and TN-401 [13] - TN-201 is designed to deliver a functional MYBPC3 gene to heart muscle cells, while TN-401 targets the PKP2 gene to restore healthy protein levels in ARVC [10][12] - Both therapies have received Fast Track and Orphan Drug designations from the FDA, indicating their potential significance in treating rare diseases [10][12]

Company Overview - Tenaya Therapeutics Inc. is a clinical-stage biotechnology company focused on discovering, developing, and delivering potentially curative therapies for heart disease [3] - The company employs integrated capabilities such as target validation, capsid engineering, and manufacturing to create genetic medicines for both rare genetic disorders and common heart conditions [3] Recent Developments - On May 15, 2025, Tenaya granted stock options to purchase a total of 461,000 shares of common stock to three new non-executive employees as part of their employment commencement [1] - The stock options have an exercise price of $0.4373 per share, equal to the closing price on the grant date, and will vest over four years [1][2] Product Pipeline - 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 for heart failure with preserved ejection fraction (HFpEF) - Multiple early-stage programs in preclinical development [3]

Core Insights - Tenaya Therapeutics is advancing its capabilities in genetic medicines for heart disease, presenting five abstracts at the ASGCT 2025 Annual Meeting [1][2] Group 1: Research and Development Highlights - The company is focusing on novel capsid engineering and optimization of cardiomyocyte-targeting genetic medicines, particularly through the use of adeno-associated virus (AAV) gene therapies [2][5] - A prime editing prototype demonstrated successful correction of the mutated RBM20 allele in a murine model of dilated cardiomyopathy (DCM), improving cardiac function [4] - Tenaya has developed a humanized mouse model for RBM20-mutant DCM, validating the effectiveness of cardiac editing using a dual vector prime editing approach [4] Group 2: Presentation Details - Presentations at ASGCT 2025 include advancements in capsid engineering, with high-throughput screening identifying novel capsid candidates that outperform AAV9 in cardiomyocyte targeting [5] - The company is sharing its progress on TN-501, a Cas9 gene editing candidate aimed at treating PLN-R14del-associated DCM, which showed promising preclinical results in murine models [6][11] - Tenaya has established a proprietary HEK293-based manufacturing process for AAV gene therapies, improving yield and reducing costs compared to existing options [6] Group 3: Company Overview - Tenaya Therapeutics is a clinical-stage biotechnology company dedicated to developing curative therapies for heart disease, with a pipeline that includes gene therapies for various cardiomyopathies and heart failure [9]