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]

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 March 31, 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 (St ...

Exhibit 99.1 Interim Data from Low Dose Cohort in MyPEAKTM-1 Clinical Trial of TN-201 Showed Encouraging Safety Profile, Transduction and Expression, Plus Improvements in Hypertrophy and NYHA Classification RIDGE Natural History and Seroprevalence Study Highlights Significant Disease Burden and Unmet Need Among Adults with PKP2-associated ARVC Data Readouts for TN-201 and TN-401 Clinical Programs On Track for the Second Half of 2025 Cash Runway Extended into Second Half of 2026 SOUTH SAN FRANCISCO, Calif., ...

Core Insights - Tenaya Therapeutics reported positive interim data from the MyPEAK-1 clinical trial for TN-201, indicating a favorable safety profile and improvements in hypertrophy and NYHA classification [1][4] - The RIDGE study highlighted a significant disease burden among adults with PKP2-associated ARVC, emphasizing the unmet need for effective treatments [1][8] - The company has extended its cash runway into the second half of 2026, supported by recent funding and cost containment measures [1][9] Clinical Programs - **TN-201**: - Interim data from the MyPEAK-1 trial showed TN-201 was well tolerated at a dose of 3E13 vg/kg, with robust DNA transduction and RNA expression [4] - All three patients in the initial cohort achieved NYHA Class I post-treatment, with two showing improvements in hypertrophy measures [4] - Initial data from Cohort 2 is expected in the second half of 2025 [4] - **TN-401**: - Enrollment for the RIDGE-1 trial is on track, with initial data anticipated in the second half of 2025 [8] - The RIDGE study revealed over 80% of participants experienced significant arrhythmias, indicating a high unmet need for TN-401 [8] Financial Highlights - For Q1 2025, Tenaya reported a net loss of $26.9 million, or $0.24 per share, an improvement from a net loss of $32.2 million, or $0.40 per share in Q1 2024 [9][14] - Research and development expenses decreased to $21.1 million from $25.1 million year-over-year [7][14] - Cash, cash equivalents, and marketable securities totaled $88.2 million as of March 31, 2025, with additional net proceeds of approximately $48.8 million from a public offering [7][16] Business Updates - The company implemented a restructuring plan to focus financial resources on clinical execution, which is expected to significantly reduce cash expenses [8][9] - Tenaya received an $8.0 million clinical grant from the California Institute for Regenerative Medicine to support the TN-401 trial [8]

Core Insights - Tenaya Therapeutics announced interim data from the RIDGE study, the largest natural history study of adults with arrhythmogenic right ventricular cardiomyopathy (ARVC) due to PKP2 gene mutations, highlighting the high burden of arrhythmias and severe disease progression despite standard treatments [1][3][4] Group 1: Study Overview - The RIDGE study has enrolled over 175 patients across approximately 20 clinical sites in the U.S., UK, France, Germany, Italy, and Sweden, focusing on clinical characteristics and medical history of PKP2-associated ARVC patients [3][4] - Interim data from 144 adults with PKP2-associated ARVC were analyzed as of February 2025 [3] Group 2: Key Findings - 83% of participants with Holter data had a premature ventricular contraction (PVC) count of 500 PVCs/day or greater, indicating a higher risk of life-threatening ventricular arrhythmias [4] - 49% of participants with available Holter monitoring data had a history of ventricular tachycardia [4] - 60% of patients with MRI data showed disease progression, as indicated by measures of right and left ventricular function and heart tissue health [4] - Electrocardiogram results indicated that a majority of patients had T-wave inversions, suggesting ventricular strain or myocardial injury [4][5] Group 3: Treatment Insights - Current treatment approaches, including medications and surgical interventions, have proven insufficient in addressing the high burden of arrhythmias and disease progression in PKP2-associated ARVC patients [3][4] - Tenaya is developing TN-401 gene therapy, which aims to deliver a functional PKP2 gene to heart muscle cells using an adeno-associated virus serotype 9 (AAV9) [2][10] Group 4: Future Directions - Enrollment is ongoing for Tenaya's Phase 1b clinical trial, RIDGE-1, to assess the safety, tolerability, and activity of a one-time dose of TN-401, with initial safety and biopsy data expected in the second half of 2025 [6][11] - The RIDGE study is expected to serve as a control arm for assessing the efficacy of TN-401 gene therapy in PKP2-associated ARVC [7]

Core Insights - Tenaya Therapeutics announced promising interim data from the MyPEAK-1 Phase 1b/2 clinical trial of TN-201, a gene therapy for MYBPC3-associated hypertrophic cardiomyopathy (HCM), presented at the 2025 American College of Cardiology Scientific Sessions [1][2][3] Group 1: Clinical Trial Data - TN-201 was well tolerated at a dose of 3E13 vg/kg, with treatment-emergent adverse events primarily mild and manageable [2][3] - All three patients in Cohort 1, who had severe disease at baseline, achieved NYHA Class I, indicating no limitations on physical activity [3] - Serial biopsies showed sustained presence of TN-201 DNA in the heart and robust RNA expression, increasing up to 13-fold from Week 8 to Week 52 post-dose [2][3] - 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 [2][3] - Cardiac troponin levels decreased by more than 60% in two patients, returning to normal or near normal [2][3] Group 2: Future Expectations - Enrollment for Cohort 2 is expected to be completed in the first half of 2025, with initial data to be reported in the second half of 2025 [1][2][7] - The company anticipates sharing additional data from Cohort 1 and initial safety and biopsy data from Cohort 2 later this year [3][7] - Tenaya has updated its cash guidance into the second half of 2026, positioning itself to achieve important clinical data milestones for both TN-201 and TN-401 gene therapy programs [3] Group 3: Disease Context - MYBPC3-associated HCM is a severe condition affecting approximately 120,000 patients in the U.S., with no approved therapeutics addressing its underlying genetic cause [11][12] - Patients with MYBPC3 mutations are at higher risk for serious complications, including heart failure and sudden cardiac death, particularly if diagnosed before age 40 [10][11]

Core Insights - Tenaya Therapeutics announced promising interim data from the MyPEAK-1 Phase 1b/2 clinical trial of TN-201, a gene therapy for MYBPC3-associated hypertrophic cardiomyopathy (HCM), presented at the 2025 American College of Cardiology Scientific Sessions [1][2][3] Group 1: Clinical Trial Data - TN-201 was well tolerated at a dose of 3E13 vg/kg, with treatment-emergent adverse events primarily mild and manageable [2][3] - All three patients in Cohort 1, who had severe disease at baseline, achieved NYHA Class I, indicating no limitations on physical activity [3][4] - Serial biopsies showed sustained presence of TN-201 DNA in the heart and robust RNA expression, increasing up to 13-fold from Week 8 to Week 52 post-dose [2][3] - 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 [2][3] - Cardiac troponin levels decreased by more than 60% in two patients, returning to normal or near normal [2][3] Group 2: Future Expectations - Enrollment for Cohort 2 is expected to be completed in the first half of 2025, with initial data to be reported in the second half of 2025 [1][2][8] - The company anticipates sharing additional data from Cohort 1 and initial safety and biopsy data from Cohort 2 later this year [3][8] - Tenaya has updated its cash guidance into the second half of 2026, positioning itself to achieve important clinical data milestones for both TN-201 and TN-401 gene therapy programs [3][4] Group 3: Background on MYBPC3-Associated HCM - MYBPC3 mutations are the most common genetic cause of HCM, affecting approximately 120,000 patients in the U.S. alone [12][13] - Patients with MYBPC3-associated HCM are at higher risk for serious outcomes, including heart failure and sudden cardiac death, with younger patients experiencing more rapid disease progression [11][12]