Core Insights - The conference call is focused on the interim clinical data from the MyPEAK-1 Phase Ib/IIa trial of TN-201 for MYBPC3-associated hypertrophic cardiomyopathy (HCM) [2] - The data was presented at the American Heart Association's scientific sessions, highlighting advancements in HCM care [2] Company Overview - Tenaya Therapeutics is led by CEO Faraz Ali and Chief Medical Officer Dr. Whit Tingley, who are participating in the conference call to discuss the clinical trial data [3]

Tenaya Therapeutics Conference Call Summary Company Overview - **Company**: Tenaya Therapeutics (NasdaqGS:TNYA) - **Focus**: Gene therapy programs, specifically TN-201 for myBPC3-associated hypertrophic cardiomyopathy (HCM) Key Industry Insights - **Condition**: myBPC3-associated HCM is the most common genetic form of hypertrophic cardiomyopathy, affecting approximately 120,000 individuals in the U.S. alone [doc id='14'][doc id='30'] - **Unmet Need**: There are no approved therapies targeting the underlying genetic cause of this condition, particularly for the non-obstructive form, which accounts for 70% of myBPC3 cases [doc id='15'] Core Points from the Call - **Clinical Trial Update**: The interim data from the MyPeak-1 phase 1b/2a clinical trial of TN-201 was presented at the American Heart Association's scientific sessions [doc id='2'][doc id='5'] - **Data Presentation**: Dr. Melinda Tsai presented promising interim data, highlighting the significant unmet need in HCM care [doc id='5'] - **Dosing and Safety**: TN-201 has been well tolerated at both tested doses (3E13 and 6E13 vector genome per kilogram), with no dose-limiting toxicities reported [doc id='19] - **Biopsy Results**: Increased myBPC3 protein levels were observed in all patients, indicating a dose-responsive manner [doc id='8'] - **Clinical Activity**: Early signs of clinical activity were noted, with multiple measures of disease moving towards normalization [doc id='8'][doc id='27'] Regulatory and Development Updates - **FDA Interaction**: The FDA requested protocol amendments to minimize site-to-site variability, leading to a clinical hold on patient enrollment [doc id='10'][doc id='11'] - **Safety Monitoring**: The independent Data Safety Monitoring Board endorsed the continuation of the trial prior to the FDA's request [doc id='10'] - **Immunosuppression Protocol**: Adjustments were made to the immunosuppressive regimen to optimize patient safety and reduce steroid use without increasing adverse events [doc id='12'][doc id='21'] Clinical Data Highlights - **Patient Cohorts**: Six patients from cohorts one and two were analyzed, all exhibiting severe disease and requiring cardiac defibrillator devices [doc id='17'] - **Biomarker Improvements**: Cardiac troponin levels improved by as much as 74%, indicating reduced cardiac injury [doc id='23'] - **Hypertrophy Measures**: Significant reductions in left ventricular mass index (LVMI) and left ventricular posterior wall thickness were observed, with reductions ranging from 12-39% [doc id='25'][doc id='34] - **New York Heart Association Class**: All patients improved to class one, indicating no limitations from symptoms by one year post-treatment [doc id='26'] Future Outlook - **Next Steps**: Continued monitoring of clinical data maturation and resumption of dosing after protocol changes are implemented [doc id='9'][doc id='44'] - **Pivotal Studies**: Plans to engage with regulators for potential late-stage development in adults and pediatric patients are anticipated in 2026 [doc id='43'] Additional Considerations - **Comparative Analysis**: The severity of cohort one patients is significantly higher than those in peer studies, emphasizing the need for genetic intervention [doc id='31'] - **Protocol Consistency**: The FDA's focus on protocol uniformity is seen as a positive step towards ensuring patient safety across studies [doc id='61'] This summary encapsulates the key points discussed during the Tenaya Therapeutics conference call, highlighting the company's advancements in gene therapy for hypertrophic cardiomyopathy and the ongoing regulatory considerations.

Scaling new heights in the fight against heart disease November 10, 2025 Forward-looking statement This presentation contains forward-looking statements within the meaning of Section 27A of the Securities Act and Section 21E of the Securities Exchange Act of 1934, as amended, that are based on our management's beliefs and assumptions and on information currently available to our management. Forward-looking statements are inherently subject to risks and uncertainties, some of which cannot be predicted or qua ...

Gene Therapy Development - The company is focused on developing gene therapies for heart diseases, with lead candidates TN-201 for MYBPC3-associated hypertrophic cardiomyopathy (HCM) and TN-401 for PKP2-associated arrhythmogenic right ventricular cardiomyopathy (ARVC) currently in clinical testing stages [96][106]. - TN-201 has shown an average increase of 4% in MyBP-C protein levels from the first biopsy to Week 52 in Cohort 1, with a 14% increase observed in the first evaluable patient of Cohort 2 after 12 weeks [101]. - Cardiac Troponin I levels declined by as much as 74% from baseline to normal or near-normal levels in all Cohort 1 patients, indicating significant improvement in cardiac function [102]. - The FDA has granted Fast Track, Orphan Drug, and Rare Pediatric Drug Designations for TN-201, which also received orphan medicinal product designation from the European Commission [105]. - TN-401 has also received Orphan Drug and Fast Track designations from the FDA, along with orphan medicinal product designation from the European Commission [110]. - The independent data safety monitoring board (DSMB) endorsed the safety profile of TN-201, allowing for expansion cohorts to proceed in the MyPEAK-1 trial [98]. - The company aims to advance its lead gene therapy product candidates, TN-201 and TN-401, and transition into late-stage clinical development [142]. Financial Performance - Research and development expenses decreased to $15.4 million for the three months ended September 30, 2025, down from $20.4 million in 2024, representing a 25% decline [121]. - General and administrative expenses were $5.6 million for the three months ended September 30, 2025, compared to $6.4 million in 2024, a decrease of 12% [124]. - Net loss for the three months ended September 30, 2025, was $20.3 million, an improvement from a net loss of $25.6 million in the same period of 2024, reflecting a 21% reduction [126]. - For the nine months ended September 30, 2025, total research and development expenses were $53.8 million, down from $68.1 million in 2024, a decrease of 21% [129]. - Interest income for the nine months ended September 30, 2025, was $2.1 million, compared to $3.9 million in 2024, a decline of 46% [131]. - The company had cash, cash equivalents, and investments totaling $56.3 million as of September 30, 2025, with an accumulated deficit of $584.8 million [134]. - The net loss for the nine months ended September 30, 2025 was $70.4 million, compared to a net loss of $87.3 million for the same period in 2024 [144][145]. - Net cash used in operating activities for the nine months ended September 30, 2025 was $54.3 million, compared to $72.1 million for the same period in 2024, indicating a reduction in cash outflow [144][145]. - The company reported a net cash provided by investing activities of $56.2 million for the nine months ended September 30, 2025, primarily from marketable securities [146]. - Net cash provided by financing activities for the nine months ended September 30, 2025 was $50.2 million, mainly from a follow-on offering [148]. Grants and Funding - The company received a Clinical Grant of $8.0 million from the California Institute for Regenerative Medicine to support the ongoing Phase 1b RIDGE-1 clinical trial of TN-401 [108]. - The company was awarded an $8 million grant from CIRM in February 2025 to support the RIDGE-1 project, contingent on achieving certain clinical milestones [135]. - The company completed a follow-on offering on March 5, 2025, raising approximately $48.8 million in net proceeds [137]. - As of September 30, 2025, the company had the right to draw down $10.0 million under a Loan Agreement with Silicon Valley Bank [136]. - The company recognized $1.5 million in connection with the CIRM grant for the nine months ended September 30, 2025 [135]. Operational Plans - The company maintains complete ownership of process development and quality control for its gene therapy candidates, producing all necessary clinical trial material at its cGMP-certified facility [116]. - The company plans to establish commercial-scale manufacturing capabilities and expand operational, financial, and information systems to support future product development [142]. - The company expects to continue incurring operating losses and will require substantial additional funding to complete the development and commercialization of its product candidates [140]. Market Position and Challenges - The company remains classified as an emerging growth company and a smaller reporting company, with annual revenue below $100 million [153][155]. - The company may face challenges in raising additional funds due to global economic conditions and market volatility [141]. - The company has not engaged in any off-balance sheet arrangements since inception [150].

Financial Performance - Tenaya reported a net loss of $20.3 million, or $0.12 loss per share, for Q3 2025, compared to a net loss of $25.6 million, or $0.30 per share, in Q3 2024[10]. - For the three months ended September 30, 2025, total operating expenses were $20,936,000, a decrease from $26,711,000 in the same period of 2024, representing a reduction of approximately 21.6%[16]. - The net loss for the three months ended September 30, 2025, was $20,275,000, compared to a net loss of $25,634,000 for the same period in 2024, indicating an improvement of about 20.5%[16]. - The company reported a net loss per share of $0.12 for the three months ended September 30, 2025, compared to a net loss per share of $0.30 for the same period in 2024[16]. - Interest income for the three months ended September 30, 2025, was $658,000, compared to $1,080,000 for the same period in 2024, showing a decrease of approximately 39.0%[16]. - Total other income, net, for the three months ended September 30, 2025, was $661,000, down from $1,077,000 in the same period of 2024, reflecting a decline of about 38.7%[16]. Expenses - Research and Development (R&D) expenses were $15.4 million for Q3 2025, down from $20.4 million in the same period of 2024[10]. - General & Administrative (G&A) expenses decreased to $5.6 million in Q3 2025 from $6.4 million in Q3 2024[10]. - Research and development expenses for the nine months ended September 30, 2025, totaled $53,809,000, down from $68,054,000 in 2024, reflecting a decrease of approximately 21%[16]. Cash and Assets - As of September 30, 2025, Tenaya had cash, cash equivalents, and investments totaling $56.3 million, expected to support operations into the second half of 2026[10]. - Cash, cash equivalents, and marketable securities as of September 30, 2025, were $56,312,000, a decrease from $61,446,000 as of December 31, 2024[18]. - Total assets decreased to $104,980,000 as of September 30, 2025, down from $119,940,000 as of December 31, 2024, representing a decline of approximately 12.5%[18]. - Total liabilities decreased to $22,112,000 as of September 30, 2025, from $27,086,000 as of December 31, 2024, indicating a reduction of about 18.4%[18]. Clinical Trials and Research - The MyPEAK-1 trial for TN-201 gene therapy showed robust transduction and durable expression with dose-dependent increases in MyBP-C protein[4]. - Tenaya completed dosing in Cohort 2 of the RIDGE-1 trial for TN-401, with three patients enrolled at a dose of 6E13 vg/kg[5]. - A seroprevalence study indicated that nearly 95% of MYBPC3-associated HCM patients had low or absent pre-existing immunity to AAV9, meeting eligibility criteria for the MyPEAK-1 trial[6]. - The independent Data Safety Monitoring Board (DSMB) for the MyPEAK-1 trial confirmed an acceptable safety profile for TN-201, allowing for enrollment in dose expansion cohorts[6]. - Interim data from the MyClimb study indicated that 93% of pediatric participants had the nonobstructive HCM phenotype, with no approved treatment options available[6]. - Tenaya's ongoing clinical trials and research initiatives are focused on transformative treatments for serious genetic cardiomyopathies[3].

Core Insights - Tenaya Therapeutics announced significant advancements in its gene therapy programs, TN-201 and TN-401, aimed at treating serious genetic cardiomyopathies, with positive recommendations from Data Safety Monitoring Boards for both products [2][3]. Business and Program Updates - TN-201, a gene therapy for MYBPC3-associated hypertrophic cardiomyopathy (HCM), showed robust transduction and durable expression, with a dose-dependent increase in MyBP-C protein. Cohort 1 patients exhibited decreases in circulating biomarkers and reductions in left ventricular hypertrophy over time [3]. - The MyPEAK-1 trial for TN-201 is currently on clinical hold, with the company working with the FDA to resolve the issue and resume dosing [4]. - TN-401, targeting PKP2-associated arrhythmogenic right ventricular cardiomyopathy (ARVC), has completed dosing in Cohort 2 of the RIDGE-1 trial, with initial safety and biopsy data expected to be shared by year-end 2025 [5][6]. Research and Development Updates - A seroprevalence study indicated that nearly 95% of MYBPC3-associated HCM patients had low pre-existing immunity to AAV9, suggesting a favorable patient eligibility for the MyPEAK-1 trial [7]. - The MyClimb study, focusing on pediatric patients with MYBPC3-associated HCM, revealed that 93% of participants had the nonobstructive HCM phenotype, highlighting the need for treatment options [7]. - Tenaya presented new preclinical data on cardiac function improvement in a pig model of ischemic heart failure, achieved through a proprietary in vivo reprogramming cocktail [7]. Financial Highlights - As of September 30, 2025, Tenaya reported cash, cash equivalents, and marketable securities totaling $56.3 million, sufficient to support operations into the second half of 2026 [12]. - Research and Development (R&D) expenses for Q3 2025 were $15.4 million, down from $20.4 million in Q3 2024. General and Administrative (G&A) expenses also decreased to $5.6 million from $6.4 million in the same period [12][16]. - The net loss for Q3 2025 was $20.3 million, or $0.12 per share, compared to a net loss of $25.6 million, or $0.30 per share, in Q3 2024 [12][16].

Core Insights - Tenaya Therapeutics presented new interim safety and efficacy data for TN-201 during the AHA Scientific Sessions 2025, indicating promising results for patients with MYBPC3-associated hypertrophic cardiomyopathy (HCM) [1][3][7] Group 1: Clinical Trial Overview - The MyPEAK-1 Phase 1b/2a clinical trial is assessing the safety and efficacy of TN-201, a gene therapy for HCM, with two cohorts receiving different doses [9] - Cohort 1 patients showed consistent improvements in hypertrophy measures over a follow-up period of 52 to 78 weeks, while initial data from Cohort 2 indicated early dose-responsive increases in TN-201 transduction and MyBP-C protein expression [1][4][5] Group 2: Safety and Tolerability - TN-201 was generally well tolerated at both tested doses (3E13 vg/kg and 6E13 vg/kg), with no dose-limiting toxicities observed [2][6] - The most common treatment-related adverse events were reversible, asymptomatic liver enzyme elevations, with no signs of cardiotoxicities reported [6][12] Group 3: Efficacy Results - Significant reductions in cardiac biomarkers were observed, with Cardiac Troponin I levels declining by 48% to 74% in Cohort 1 patients, indicating improved cardiac health [6][5] - All patients in Cohort 1 experienced notable reductions in left ventricular posterior wall thickness (LVPWT) by 21% to 39% and improvements in NYHA classification, with all now classified as NYHA Class I [6][5][4] Group 4: Future Plans and Regulatory Status - Tenaya plans to continue long-term follow-up of patients and periodically report additional results to inform the late-stage development of TN-201 [6][8] - The FDA has placed the MyPEAK-1 trial on clinical hold, and Tenaya is working to address the agency's concerns [9][12]

Core Insights - Tenaya Therapeutics is set to present interim safety and efficacy results from the MyPEAK-1 Phase 1b/2a clinical trial for TN-201, a gene therapy targeting MYBPC3-associated hypertrophic cardiomyopathy, at the AHA 2025 Scientific Sessions [1][2] - The company will also showcase results from a preclinical study on cellular reprogramming gene therapy in a pig model of ischemic heart failure [1][2] Company Overview - Tenaya Therapeutics is a clinical-stage biotechnology company focused on developing potentially curative therapies for heart disease [4] - The company's pipeline includes TN-201 for MYBPC3-associated hypertrophic cardiomyopathy and TN-401 for PKP2-associated arrhythmogenic right ventricular cardiomyopathy [4][5] - Tenaya employs integrated capabilities such as target validation and capsid engineering to develop novel medicines based on genetic insights [5] Upcoming Events - The AHA presentation will occur on November 8, 2025, featuring Dr. Milind Y Desai as the presenting author [2] - A second presentation on cellular reprogramming will take place on November 9, 2025, led by Kathy Ivey [2] - Tenaya management will host a conference call on November 10, 2025, to discuss the TN-201 data presented at the AHA sessions [3]

Summary of Tenaya Therapeutics FY Conference Call Industry Overview - The conference focused on the cardiac gene therapy industry, highlighting both advancements and setbacks in the field. [1] - There is a supportive regulatory environment for gene therapy, particularly in areas of high unmet medical need, alongside a growing momentum for precision medicine. [1] Company Insights Tenaya Therapeutics - Tenaya Therapeutics is advancing gene therapy for BAG3 dilated cardiomyopathy, targeting heart failure in younger patients. [4] - The company is utilizing a novel cardiotropic AAV capsid designed to transduce nearly 100% of cardiac cells at a significantly lower dose compared to conventional capsids. [17] - An Investigational New Drug (IND) application is expected to be filed later this quarter, with clinical results anticipated in early next year. [5] AskBio - AskBio is focusing on gene therapy for both common and rare diseases, with lead programs in Parkinson's disease and heart failure currently in Phase II trials. [7] - The company emphasizes the importance of local delivery methods to minimize doses and avoid immunosuppression. [31] - AskBio's global Phase II trial for congestive heart failure will involve over 80 patients, supported by Bayer's expertise. [25] Lexeo Therapeutics - Lexeo Therapeutics is developing gene therapies for rare cardiac diseases, including Friedreich's ataxia and arrhythmogenic cardiomyopathy. [9] - The company is utilizing non-invasive methods to measure therapeutic benefits, including cardiac MRI and various biomarkers. [10] - Lexeo is preparing for pivotal studies and aims to demonstrate clinical efficacy through established endpoints. [12] Key Points and Arguments - **Safety and Efficacy**: The panelists discussed the importance of low dosing in gene therapy to mitigate safety risks, with a consensus that lower doses correlate with fewer adverse events. [29][41] - **Regulatory Environment**: There is optimism regarding the FDA's flexibility in approving gene therapies, especially for rare diseases, with a focus on demonstrating clear clinical benefits. [69] - **Commercialization Challenges**: The need for successful commercial launches in gene therapy was emphasized, with a call for companies to prepare for market uptake and pricing strategies. [44][56] - **Manufacturing Improvements**: Advances in manufacturing processes are expected to lower costs and improve yields, making gene therapies more commercially viable. [52][55] Additional Important Insights - The discussion highlighted the evolving landscape of gene therapy, with a shift towards precision medicine in cardiovascular treatments, similar to trends seen in oncology. [58] - The panelists expressed confidence in the future of gene therapy, citing recent clinical successes and the potential for new products to emerge from ongoing research. [66] - The importance of patient selection and trial design was noted, as these factors significantly impact the success of clinical trials and the overall perception of gene therapy safety. [42] This summary encapsulates the key discussions and insights from the Tenaya Therapeutics FY Conference Call, providing a comprehensive overview of the current state and future outlook of the cardiac gene therapy industry.

Summary of Tenaya Therapeutics Conference Call (October 14, 2025) Company Overview - **Company**: Tenaya Therapeutics (NasdaqGS:TNYA) - **Focus**: Genetic medicine, specifically gene therapies for cardiomyopathies Key Assets - **TN-201**: Targets MYBPC3-positive hypertrophic cardiomyopathy (HCM) patients - **TN-401**: Targets PKP2-positive arrhythmogenic right ventricular cardiomyopathy (ARVC) patients - Both therapies utilize AAV9-based vectors and are currently in clinical trials [3][4][5] Core Points and Arguments TN-201 (HCM) - **Mechanism**: AAV9 vector delivering a full-length MYBPC3 gene with a cardiomyocyte-specific promoter [4] - **Unique Selling Proposition**: Addresses the underlying genetic cause of HCM, particularly for non-obstructive forms, which represent 70% of the patient population [9][10] - **Market Context**: Current therapies like Camzyos are not approved for non-obstructive HCM, highlighting a significant unmet need [10] - **Clinical Data**: Positive interim data from the MyPeak-1 study showed safety and tolerability, with two out of three patients experiencing significant improvements in cardiac biomarkers [14][15][18] - **Durability of Effect**: All patients in the first dose cohort reached New York Heart Association Class I, indicating no disease impact on daily living [18] TN-401 (ARVC) - **Mechanism**: AAV9 vector delivering a full-length PKP2 gene [29] - **Unmet Need**: ARVC is a severe condition with no approved therapies addressing its genetic cause, leading to high morbidity and mortality [30] - **Preclinical Data**: Demonstrated prevention of arrhythmia and cardiac remodeling in severe preclinical models [32] - **Clinical Trial**: Ongoing Phase 1b trial (RIDGE-1) with expected data release in Q4 2025 [33] Additional Important Insights - **Safety Database**: AAV9 has the largest safety database among AAV vectors, enhancing confidence in its use [6] - **Innovative Engineering**: The company has developed unique promoters and molecular designs to optimize gene delivery [4][5] - **Data Presentation**: Upcoming data at the AHA conference is highly anticipated, with a focus on safety and efficacy [22][20] - **Comparison with Peers**: The company is mindful of how its data compares with other gene therapy programs, emphasizing the importance of robust protein measurement methods [35][36] Conclusion - **Future Outlook**: Tenaya Therapeutics is positioned to address significant unmet needs in cardiomyopathy with its innovative gene therapies, backed by promising clinical data and a strong safety profile [13][20]