UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 FORM 10-K (Mark One) ☒ ANNUAL REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the fiscal year ended December 31, 2024 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) (State or other jurisdict ...

Exhibit 99.1 Tenaya Therapeutics Reports Fourth Quarter and Full Year 2024 Financial Results and Provides Business Update Dosing Initiated in Cohort 2 of the MyPEAK™-1 Phase 1b/2 Clinical Trial of TN-201 for Treatment of MYBPC3-Associated Hypertrophic Cardiomyopathy TN-201 – Gene Therapy for MYBPC3-Associated Hypertrophic Cardiomyopathy • In December 2024, Tenaya reported promising early data from the first cohort of patients in the MyPEAK-1 Phase 1b/2 clinical trial of TN-201 gene therapy. o Preliminary da ...

Dosing Initiated in Cohort 2 of the MyPEAK™-1 Phase 1b/2 Clinical Trial of TN-201 for Treatment of MYBPC3-Associated Hypertrophic Cardiomyopathy MyPEAK-1 Cohort 1 Data Accepted for Late-Breaker Presentation at the American College of Cardiology Meeting Initial Data from RIDGE™-1 Phase 1b Clinical Trial of TN-401 for PKP2-Associated Arrhythmogenic Right Ventricular Cardiomyopathy Expected in 2H25 Recent $48.9 Million Financing Extends Cash Runway into mid-2026 SOUTH SAN FRANCISCO, Calif., March 10, 2025 (GLO ...

Core Viewpoint - Tenaya Therapeutics, Inc. has announced a public offering of 75,000,000 units, aiming to raise approximately $52.5 million to support its clinical development and general corporate purposes [1][2]. Group 1: Offering Details - The offering consists of 75,000,000 units priced at $0.70 per unit, each unit includes one share of common stock and two types of warrants [3]. - The warrants include a Series A Warrant for one share at an exercise price of $0.80, and a Series B Warrant for half a share at an exercise price of $0.70, both immediately exercisable [3]. - The offering is expected to close around March 5, 2025, pending customary closing conditions [4]. Group 2: Use of Proceeds - The net proceeds from the offering will be utilized for the ongoing and planned development of clinical and early-stage product candidates, particularly TN-201 and TN-401, along with working capital and other general corporate purposes [2]. Group 3: Company Overview - Tenaya Therapeutics is a clinical-stage biotechnology company focused on developing potentially curative therapies for heart disease, employing integrated capabilities for genetic medicine development [8]. - The company's pipeline includes TN-201 for MYBPC3-associated hypertrophic cardiomyopathy, TN-401 for PKP2-associated arrhythmogenic right ventricular cardiomyopathy, and TN-301, a small molecule HDAC6 inhibitor for heart failure with preserved ejection fraction [8].

Company Overview - Tenaya Therapeutics, Inc. is a clinical-stage biotechnology company focused on discovering, developing, and delivering potentially curative therapies for heart disease [5] - 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 [5] Proposed Offering - Tenaya intends to offer and sell units consisting of common stock and Series A and Series B warrants, which allow the purchase of common stock [1] - The offering may also include pre-funded units with pre-funded warrants at a purchase price of $0.001 per share, which will be immediately exercisable and will not expire [1] - The offering is subject to market conditions, and there is no assurance regarding its completion or the actual size and terms [1] Management and Regulatory Aspects - Leerink Partners and Piper Sandler are acting as joint bookrunning managers for the proposed offering [2] - The offering is being conducted under a Registration Statement on Form S-3, previously filed and declared effective by the SEC [2] Pipeline and Product Development - Tenaya's pipeline includes several gene therapies: TN-201 for MYBPC3-associated hypertrophic cardiomyopathy, TN-401 for PKP2-associated arrhythmogenic right ventricular cardiomyopathy, and TN-301, a small molecule HDAC6 inhibitor for heart failure with preserved ejection fraction [5] - The company also has multiple early-stage programs in preclinical development [5]

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 two upcoming healthcare conferences, showcasing its commitment to advancing its innovative therapies [1][2] Company Overview - Tenaya Therapeutics aims to discover, develop, and deliver therapies targeting the underlying causes of heart disease [3] - The company utilizes integrated capabilities such as target validation, capsid engineering, and manufacturing to create genetic medicines [3] - Tenaya's pipeline includes: - TN-201: Gene therapy for MYBPC3-associated hypertrophic cardiomyopathy (HCM) - TN-401: Gene therapy for PKP2-associated arrhythmogenic right ventricular cardiomyopathy (ARVC) - TN-301: Small molecule HDAC6 inhibitor for heart failure with preserved ejection fraction (HFpEF) - Multiple early-stage programs in preclinical development [3]

Core Insights - Tenaya Therapeutics has received an $8.0 million CLIN2 grant from the California Institute for Regenerative Medicine (CIRM) to support the ongoing Phase 1b RIDGE-1 clinical trial of TN-401 gene therapy for PKP2-associated arrhythmogenic right ventricular cardiomyopathy (ARVC) [2][4] - The RIDGE-1 trial aims to evaluate the safety, tolerability, and preliminary clinical efficacy of TN-401, which is designed to deliver a functional PKP2 gene to heart muscle cells [3][4] - Initial data from the RIDGE-1 trial is expected in the second half of 2025 [1][4] Company Overview - Tenaya Therapeutics is a clinical-stage biotechnology company focused on developing potentially curative therapies for heart disease [12] - The company is advancing a portfolio of genetic medicines, including TN-401 for PKP2-associated ARVC and TN-201 for MYBPC3-associated hypertrophic cardiomyopathy [12] Clinical Trial Details - The RIDGE-1 clinical trial is an open-label, dose-escalation study enrolling symptomatic adults diagnosed with PKP2-associated ARVC [3][4] - TN-401 utilizes an adeno-associated virus serotype 9 (AAV9) vector for gene delivery, which has a strong safety record and targets heart muscle cells effectively [7][9] Disease Background - PKP2 mutations are the most common genetic cause of ARVC, affecting approximately 70,000 people in the U.S. [5][6] - Current treatments for ARVC do not address the underlying genetic cause, highlighting the potential significance of TN-401 as a novel therapeutic approach [6][9] Funding and Support - CIRM has been instrumental in funding regenerative medicine research, having provided billions since its establishment in 2004 [10][11] - The grant awarded to Tenaya Therapeutics is part of CIRM's efforts to accelerate the development of transformative treatments for serious medical conditions [4][10]

Core Insights - Tenaya Therapeutics is advancing its gene therapy programs, TN-201 and TN-401, targeting cardiomyopathies, with significant milestones expected in 2025 [1][2][3] Program Updates - **TN-201**: A gene therapy for MYBPC3-associated hypertrophic cardiomyopathy (HCM) is currently in the MyPEAK-1 Phase 1b/2 clinical trial. Additional data from Cohort 1 is anticipated in the first half of 2025, including safety assessments and biopsy results from the first three patients dosed [3][6] - **TN-401**: A gene therapy for PKP2-associated arrhythmogenic right ventricular cardiomyopathy (ARVC) is in the RIDGE-1 Phase 1b clinical trial. Initial clinical data from the first cohort is expected in the second half of 2025 [3][7] Clinical Trial Details - The MyPEAK-1 trial for TN-201 has shown promising initial results, with the first two patients demonstrating detectable vector DNA and transgene RNA expression. The trial is expanding to include adults with obstructive forms of HCM [3][4] - The RIDGE-1 trial for TN-401 has enrolled over 100 participants, with initial seroprevalence data indicating low antibody levels to AAV9, which is crucial for eligibility [10] Strategic Priorities - Tenaya plans to enhance its capabilities in drug discovery and genetic medicine delivery, focusing on both rare genetic disorders and prevalent heart conditions in 2025 [5][8] - The company aims to complete enrollment for both Cohort 1 of RIDGE-1 and Cohort 2 of MyPEAK-1 in the first half of 2025, with data presentations planned for the second half of the year [3][10] Market Context - MYBPC3 mutations are the most common genetic cause of HCM, affecting approximately 120,000 patients in the U.S. alone, while PKP2 mutations are linked to over 70,000 ARVC cases [6][7] - Both TN-201 and TN-401 have received Fast Track and Orphan Drug Designations from the FDA, indicating their potential significance in treating these conditions [6][7]

Core Insights - Tenaya Therapeutics reported early data from the MyPEAK-1 clinical trial of TN-201, a gene therapy for MYBPC3-associated hypertrophic cardiomyopathy (HCM), indicating that TN-201 was well tolerated and showed promising early efficacy [2][3][4] Group 1: Clinical Trial Results - Preliminary data from three patients in the first dose cohort (3E13 vg/kg) showed TN-201 was generally well tolerated, with detectable vector DNA in the heart and increasing levels of TN-201 mRNA and MyBP-C protein over time [3][6] - Circulating biomarkers of cardiac muscle strain and injury remained stable, with some clinical measures showing improvement from baseline, particularly in Patients 1 and 2 [9][10] - The MyPEAK-1 trial is designed to assess the safety, tolerability, and clinical efficacy of TN-201, with a focus on symptomatic adults diagnosed with MYBPC3-associated HCM [12] Group 2: Safety Profile - TN-201 exhibited a manageable safety profile with no observed cardiac toxicities or serious adverse events related to the treatment [6][7] - Isolated elevations in liver enzymes were noted but were well managed and not indicative of liver damage [7] - Most adverse events were mild and transient, typical of AAV-based gene therapies [7] Group 3: Future Outlook - Tenaya plans to continue monitoring the initial patients and anticipates additional data readouts from Cohort 1 and a higher dose cohort in 2025 [3][4] - The company expressed confidence in TN-201's potential based on early evidence of transgene expression and cardiac transduction [10][11] - The MyPEAK-1 trial may expand to enroll up to 24 patients with MYBPC3-associated HCM in planned dose expansion cohorts [12]

Core Insights - Tenaya Therapeutics reported early data from the MyPEAK-1 clinical trial of TN-201 gene therapy, showing it was well tolerated and demonstrated promising early efficacy in treating MYBPC3-associated hypertrophic cardiomyopathy (HCM) [2][3][4] Group 1: Clinical Trial Results - Preliminary data from three patients in the first dose cohort (3E13 vg/kg) indicated that TN-201 was generally well tolerated, with detectable vector DNA in the heart and increasing levels of TN-201 mRNA and MyBP-C protein over time [3][6] - Clinical measures of HCM mostly remained stable or showed improvement from baseline, with some patients experiencing better NYHA classification scores [10][11] - The trial is ongoing, with additional data readouts expected from Cohort 1 and a higher dose cohort anticipated in 2025 [3][4] Group 2: Safety Profile - TN-201 exhibited a manageable safety profile, with no observed cardiac toxicities or serious adverse events related to the treatment [6][7] - Isolated elevations in liver enzymes were noted, which were well managed and consistent with known side effects of AAV-based gene therapies [6][7] Group 3: Mechanism and Efficacy - TN-201 achieved robust transduction into cardiomyocytes, with measurable transgene RNA expression and a 50% increase in TN-201 mRNA levels observed at Week 52 for one patient [8][9] - Total levels of MyBP-C protein showed a 3% increase from Weeks 8 to 52, indicating successful transcription and expression of the gene therapy [9] Group 4: Future Outlook - The company expressed confidence in TN-201's potential based on the early data, with plans to continue monitoring patients and gathering more data [12] - The MyPEAK-1 trial is designed to assess the safety and efficacy of TN-201, with a focus on symptomatic adults diagnosed with MYBPC3-associated HCM [14][15]