Tenaya Therapeutics, Inc.
For the period ended Dec 31, 2025. Filed Mar 11, 2026.
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FY2025 · Filed Mar 11, 2026
TNYA$0.36+14.0%Stored close · as of Nov 6, 2026
What changed in Management’s Discussion and Analysis?
Read the current filingPrevious report: 10-K
Period ended 2024-12-31; filed 2025-03-10.
0000950170-25-036329
Item 7. Management’s Discussion and Analysis of Financial Condition and Results of OperationsCurrent report: 10-K
Period ended 2025-12-31; filed 2026-03-11.
0001193125-26-102252
Item 7. Management’s Discussion and Analysis of Financial Condition and Results of OperationsThe baseline is this issuer’s latest earlier reporting period of the same form that was filed before the current report. A previous 10-Q is a different quarter, not a year-over-year comparison. Amendments are excluded.
Compared 102 previous paragraphs and 114 current paragraphs.
65 unchanged; 24 reworded; 24 added; 13 removed; 0 previous and 1 current paragraphs rearranged.
Tables are not compared: 3 previous and 3 current tables excluded. Dates, whitespace, punctuation and numbering changes are ignored; changes to financial figures remain significant.
A changed paragraph is not evidence that risk increased or decreased. An unchanged paragraph does not establish that risk stayed the same.
Added paragraphs (24)
Current report
Early on in our company history, we invested in differentiated capabilities to enable modality-agnostic target identification and validation, anchored in human genetics and the use of human disease models. To support our initial focus on gene therapy candidates, we also internalized expertise in capsid engineering, novel promoter constructs and manufacturing anchored on the use of AAVs as the method of delivery to the heart. That proprietary expertise has directly informed the discovery, design, optimization and production of our pipeline.
Current report
We are primarily focused on advancing of our clinical-stage gene therapy candidates, TN-201 for MYBPC3-associated HCM, and TN-401 for PKP2-associated ARVC. Each candidate is currently in Phase 1b/2 trials to establish the safety profile of two different doses in adults with disease due to pathogenic/likely pathogenic mutations. We anticipate that data generated to date and over the course of 2026 will support our pursuit of regulatory alignment on late-stage development for our gene therapy product candidates. A third internally discovered clinical-stage candidate, TN-301, is a highly specific small molecule inhibitor of HDAC6 with potentially broad utility in HFpEF and other cardiac, metabolic, muscular and pulmonary diseases, including but not limited to genetic DCM, DMD and PAH.
Current report
For programs arising out of our modality agnostic drug discovery platform that address relatively rare conditions our strategy is to develop, manufacture, and commercialize at least some of these programs on our own, although we may selectively consider partnerships to access technology, accelerate our progress, or improve our global reach to patients. For example, in March 2026, we entered into a multi-target research collaboration with Alnylam, to identify and validate novel gene targets for the potential treatment of cardiovascular disease. Importantly, this agreement takes advantage of our modality agnostic discovery know-how and provides reimbursement for research efforts. Where our discovery efforts lead to product candidates intended for relatively prevalent indications our strategy is to out-license or partner such programs.
Current report
In November 2025, we presented interim data from MyPEAK-1 at the AHA's Scientific Sessions 2025, with simultaneous publication in Cardiovascular Research. Interim data presented included safety, biopsy and efficacy results for the three patients enrolled in Cohort 1 with follow-up ranging from Week 52-78, and safety and available assessments for the patients in Cohort 2 who have post-dose assessments ranging from Week 12-26 as of the July 2025 data cut off. Patient 5 was lost to further follow-up after week 12. TN-201 was generally well tolerated across both dose cohorts and no dose-limiting toxicities were observed. Reversible, asymptomatic liver enzyme elevations (Grade 1-3) were the most common treatment-related AEs reported. There were two treatment-related AEs classified as serious either due to inpatient administration of steroids or extended monitoring; a Grade 2 transaminase elevation that responded to steroids and a Grade 1 elevation of complement factors that resolved without additional intervention. Adjustments 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.
Current report
DNA and RNA analyses of cardiac biopsy samples from all three patients in Cohort 1 showed evidence of sustained presence of TN-201 DNA in the heart and increasing mRNA expression over time. The first patient in Cohort 2 with serial biopsy data (Patient 6) had a greater than 2-fold increase in cardiac transduction and RNA expression at Week 12 relative to the average for these measures observed across Cohort 1 patients. MyBP-C protein levels across Cohort 1 increased over time by an average of 4% from the first biopsy taken to 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.
Current report
All patients with greater than 26 weeks of follow-up demonstrated improvement in at least one parameter of disease, across biomarkers, hypertrophy and heart failure symptoms. Cardiac troponin I, a predictive risk factor of adverse cardiac outcomes such as ventricular arrhythmias, sudden cardiac death, and progression to end-stage heart failure, declined by as much as 74% from baseline, to normal or near-normal levels in all Cohort 1 patients. NT-proBNP, a biomarker of cardiac muscle strain, improved or remained stable in two of three Cohort 1 patients. All three patients in Cohort 1 showed evidence of significant improvement in one or more measures of hypertrophy at Week 52, with notable reductions in LVPWT of between 21% and 39%. Greater LVPWT is an independent risk factor for reduced long-term survival after septal myectomy. Two out of three Cohort 1 patients saw reductions from baseline in LVMI of between 12% and 22% at Week 52. In the first Cohort 2 patient for whom Week 26 data were available (Patient 4), cardiac troponin I remained within the normal range and NT-proBNP remained stable,. LVPWT and LVMI also remained stable at Week 26. NYHA 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 were NYHA Class I (asymptomatic) as of the data cutoff date. Longer-term follow-up for all patients is required to further inform our understanding of TN-201’s potential as a treatment for MYBPC3-associated HCM.
Current report
We expect to present longer-term Cohort 1 and interim Cohort 2 data in the first half of 2026. In the second half of 2026, one-year Cohort 2 data and two-year Cohort 1 data from MyPEAK-1 are anticipated. We also intend to pursue alignment with regulatory authorities on pivotal trial plans for TN-201.
Current report
Despite advances in the treatment of the obstructive HCM in recent years with the approval of cardiac myosin inhibitors, there are no approved treatments for those with the non-obstructive form of disease or those diagnosed before the age of 18. Recognizing the urgent medical need among pediatric patients, we initiated MyClimb, a retrospective and prospective natural history study of pediatric patients to characterize the outcomes, burden of illness, risk factors, quality of life, and biomarkers associated with disease progression in pediatric patients. MyClimb complements existing disease registries focused primarily on adult patient HCM populations and may support and expedite the development of TN-201 in the pediatric patient population. MyClimb completed enrollment of more than 200 individuals, and is believed to be the largest study of pediatric individuals with MYBPC3-associated HCM ever conducted. Initial data indicated that 93% of participants had the nonobstructive HCM phenotype, for which there are currently no approved treatment options and that genotype was a significant predictor of risk. The data also revealed that LVMI may serve as a surrogate marker for poor long-term outcomes and as an appropriate marker to evaluate the early effectiveness of TN-201’s potential in a future pivotal trial.
Current report
The FDA has granted TN-201 Fast Track, Orphan Drug and Rare Pediatric Drug Designations. TN-201 has also received orphan medicinal product designation from the EC.
Current report
RIDGETM-1 is our Phase 1b/2 multi-center, open-label clinical trial, designed to assess the safety, tolerability and efficacy of a one-time intravenous infusion of TN-401. Enrollment and dosing in both the 3E13 vg/kg dose (Cohort 1) and 6E13 vg/kg dose (Cohort 2) cohorts are complete. In January 2026, the DSMB for RIDGE-1 reviewed all available data from Cohort 1 and Cohort 2, determined that TN-401 had an acceptable safety profile and endorsed proceeding into expansion cohorts at either dose level, per protocol. We are enrolling additional patients in RIDGE-1 to inform dose selection for late-stage clinical trials.
Current report
In December 2025, we presented interim data from RIDGE-1, including safety, biopsy and arrhythmia results as of the October 2025 data cut off for three patients enrolled in Cohort 1, with follow-up ranging from Week 20 to Week 40. TN-401 was generally well tolerated and no dose-limiting toxicities were observed. AEs were generally mild, asymptomatic and manageable and a majority of the AEs were deemed unrelated to TN-401. Among the AEs related to TN-401, there was a Grade 1 incidence of elevated troponin levels categorized as a serious AE due to inpatient monitoring. There were no incidents of thrombotic microangiopathy or cardiotoxicities observed and no arrhythmias associated with TN-401 occurred. Additionally, no Cohort 1 patients had experienced an ICD shock post-treatment and all had tapered off prophylactic immunosuppressive medicines.
Current report
Serial biopsies taken at baseline and Week 8 post dose for Patients 1 and 2 provided consistent evidence of TN-401 transduction and expression. At Week 8, TN-401 robust mRNA expression was observed across all three patients. Post-treatment protein levels of PKP2 increased significantly in Patients 1 and 2 by a mean of 10% from baseline to Week 8 as measured by liquid chromatography–mass spectrometry normalized to myosin heavy chain, a motor protein in the sarcomere found exclusively in cardiomyocytes. Change in PKP2 protein levels for Patient 3 appeared slightly lower than baseline despite having the highest levels of TN-401 mRNA expression across Cohort 1. This confounding result for PKP2 protein level falls within the standard deviation of these methods and may be due to the inherent variability in sampling biopsies. A second post-dose biopsy will be collected and analyzed from Week 52 per protocol for all patients.
Current report
All three patients in Cohort 1 had severe electrical instability with a history of VAs and had undergone a catheter ablation procedure, an elective procedure to reduce ventricular tachycardia recurrence. At baseline, each Cohort 1 patient met the enrollment criteria of greater than 500 premature ventricular contractions per 24 hours as measured over a seven-day monitoring period prior to dosing. Two of three patients experienced significant and clinically meaningful improvements in electrical instability, as measured by seven-day ambulatory monitoring of PVCs following dosing. Patient 1 experienced a decrease in PVCs by 46% as of their most recent (Week 40) visit, while Patient 2 experienced a decrease in PVCs of 89% as of their most recent (Week 32) visit. Non-sustained ventricular tachycardia (NSVT) burden was eliminated or stable six months after treatment with TN-401. Patient 1 had a low NSVT count at baseline, which remained low at their most recent visit (Week 40). Patient 2 also had a substantial NSVT burden of 78 counts per 24-hour period at baseline that dropped to zero and remained stable by Week 32. Meaningful changes in PVCs or NSVTs were not expected nor observed for Patient 3 as of the data cut off, which was less than six months following treatment with TN-401. Other potential measures of clinical response including QRS duration, T wave inversions, heart function and NYHA class were in the normal range or remained stable for all three Cohort 1 patients during the post-dose follow-up period. We expect to present one-year Cohort 1 data and initial Cohort 2 data in the first half of 2026, with interim Cohort 2 results anticipated in the second half of the year. We also intend to pursue alignment with regulatory authorities on pivotal trial plans for TN-401.
Current report
To support our development efforts for TN-401, we have initiated RIDGE a global noninterventional study to collect treatment history and seroprevalence to AAV9 antibodies data among ARVC patients who carry pathogenic or likely pathogenic PKP2 gene mutations. Interim data from RIDGE, believed to be the largest natural history study of adults with PKP2-associated ARVC, was presented at HRS’s annual meeting in April 2025. Adults with PKP2-associated ARVC experience a high burden of arrhythmias despite treatments with anti-arrhythmic medications, beta blockers and the anti-arrhythmic flecainide, as well as surgical interventions such as ablation and ICD placement. Further, current treatments appeared to do little to halt or prevent progressive structural changes to the heart that occur as a result of PKP2 mutations. A large majority of adults with PKP2-associated ARVC would be eligible to participate in RIDGE-1 based on low levels of pre-existing antibodies to AAV9.
Current report
We are also advancing TN-301, a highly specific HDAC6 inhibitor that has potential utility in HFpEF and other cardiac, metabolic and muscular diseases. TN-301 was initially discovered and validated as having cardioprotective qualities in preclinical studies of a rapidly worsening mouse model of BAG3 mutant DCM. HDAC6 is a cytoplasmic enzyme known to regulate diverse cellular processes. Based on TN-301’s multi-modal mechanism of action, that includes reductions in inflammation, oxidative stress, fibrosis, and metabolic dysregulation, as well as improvements in autophagy, protein quality control, mitochondrial metabolism, and lipid metabolism, TN-301 may be well suited to the treatment of HFpEF, as well as other cardiac, metabolic, muscular and pulmonary disorders where there is strong alignment between TN-301’s mechanism and the pathophysiology of disease.
Current report
Based on our observations of TN-301’s mechanism and evidence of efficacy for an approved pan-HDAC agent, we are also exploring the development of TN-301 for DMD, a condition caused by genetic mutations in thedystrophin gene, leading to absence of functional dystrophin protein in the heart and skeletal muscle. The muscle pathologies that underlie muscle wasting in the absence of dystrophin include inflammation, fibrosis, altered regeneration, mitochondrial dysfunction and disrupted autophagic flux – all processes that can be improved by HDAC6 inhibition.
Current report
At the MDA Clinical & Scientific Congress 2026, we presented results from preclinical studies comparing TN-301 with the FDA-approved pan HDAC inhibitor, givinostat, in a well-established mouse model of DMD, and in human iPSC-derived cardiomyocytes from DMD patients. After five weeks of once-daily oral dosing, TN-301 showed a statistically significant increase in forelimb grip strength inmdx mice at both 3 mg/kg and 30 mg/kg compared to vehicle with both doses of TN-301 achieving WT levels of grip strength after five weeks. Further, TN-301 demonstrated greater efficacy at both doses compared to the 10 mg/kg dose of givinostat, which corresponds to the clinically relevant dose used in DMD patients. Notably, the effects of TN-301 at both doses approached those observed with the 30 mg/kg dose of givinostat, a level that is not tolerated in humans.
Current report
In engineered heart tissues derived from human DMD-induced iPSCs, TN-301 corrected calcium handling abnormalities, a key driver of DMD cardiomyopathy, including beat-to-beat fluctuations in calcium amplitude. In contrast, givinostat exacerbated calcium handling irregularities. In an experiment of DMD patient-derived iPSC cardiomyocytes designed to measure oxygen consumption and mitochondrial stress, both known contributors to DMD cardiomyopathy, TN-301 corrected basal and maximal respiration whereas givinostat worsened both measures. Taken together, these data support advancement of TN-301 as a potential DMD therapy with benefits for both skeletal and cardiac muscle and reduced liabilities compared to pan-HDAC inhibitors.
Current report
Consistent with our strategy, we believe that TN-301’s late-stage development and commercialization in large indications such as HFpEF would best be led by a strategic pharmaceutical partner with global resources to explore the full potential of the molecule. In parallel, we plan to explore indications in which it may be possible to demonstrate proof-of-activity in smaller, well-defined patient populations. Based on our preclinical observations, initial indications of interest include DMD, other muscular dystrophies, genetic DCM and PAH.
Current report
a decrease of $6.1 million in clinical trial related costs primarily driven by a decrease in clinical support costs, including regulatory consulting fees and lower employee-related costs driven by workforce reductions initiated in March 2025 and May 2024 (together, the Workforce Reductions);
Current report
a decrease of $5.7 million in manufacturing costs due to lower employee-related costs driven by the Workforce Reductions, as well as reduced spending on supplies, materials, and facility maintenance; and
Current report
decreases of $4.4 million in research costs and $1.9 million in other research and development costs due to lower employee-related costs driven by the Workforce Reductions.
Current report
On August 6, 2024, we entered into a Loan Agreement with Silicon Valley Bank (SVB). As of December 31, 2025, all of the term loan commitments expired under the Loan Agreement and no term loans were outstanding. The Loan Agreement provides that an additional loan of $20.0 million may be available at SVB’s discretion, subject to specified conditions.
Current report
On August 10, 2022, we entered into a sales agreement (the Sales Agreement) with Leerink Partners LLC to establish an “at-the-market” (ATM) offering defined in Rule 415 under the Securities Act. Pursuant to the Sales Agreement, we are permitted to offer and sell, from time to time, shares of our common stock having a maximum aggregate offering price of up to $75.0 million. In January 2025, we sold 822,566 shares of our common stock under the ATM offering for net proceeds of $0.9 million, after deducting commissions and offering costs of $0.3 million. As of December 31, 2025, we may issue and sell up to approximately $69.8 million of common stock under the ATM offering.
Removed paragraphs (13)
Previous report
We are advancing a deep and diverse pipeline of disease-modifying targeted therapies that includes both gene therapies and small molecules discovered internally and developed using our extensive core capabilities to address rare or highly prevalent forms of heart disease. All of our programs are currently being assessed in clinical trials or are in the preclinical stage; we do not have any products approved for sale and have not generated any revenue to date.
Previous report
Our lead investigational product candidates are TN-201, a gene therapy for MYBPC3-associated hypertrophic cardiomyopathy (HCM), TN-401, a gene therapy for PKP2-associated arrhythmogenic right ventricular cardiomyopathy (ARVC), and TN-301, a small molecule for heart failure with HFpEF.
Previous report
In December 2024, we announced early but encouraging initial interim safety and biopsy data from Cohort 1 of MyPEAK-1. TN-201 administered at the starting dose of 3×1013 vg/kg was generally well-tolerated among the first three patients enrolled in the clinical trial. Among the first two patients for whom Week 8 biopsy results were available, TN-201 achieved readily detectable vector DNA in the heart and evidence of transgene RNA expression. Serial biopsies at Week 8 and Week 52 for Patient 1 demonstrated increasing TN-201 mRNA and MyBP-C protein levels over time. Circulating biomarkers of cardiac muscle strain and injury remained largely stable, and certain clinical markers of disease showed stability or directional improvement in the first two individuals dosed, while other measures were not yet available, interpretable or were mixed. We plan to present additional follow-up data from Cohort 1 during the first half of 2025 and initial Cohort 2 data, along with an update on Cohort 1 patients, in the second half of 2025.
Previous report
To support our development efforts for TN-201 we are conducting two noninterventional studies: a study evaluating seroprevalence to AAV9 antibodies among adults with MYBPC3-associated HCM, and MyClimb, a prospective and retrospective global natural history study focused on pediatric patients with MYBPC3 mutation-associated cardiomyopathy. The seroprevalence study has completed enrollment. Initial data from the study indicated that antibodies to AAV9 in the majority of participants were below the eligibility threshold that would allow for participation in MyPEAK-1. The MyClimb natural history study is following patient medical history to characterize the outcomes, burden of illness, risk factors, quality of life, and biomarkers associated with disease progression in pediatric patients. MyClimb complements existing disease registries focused primarily on adult patient HCM populations and may support and expedite the development of TN-201 in the pediatric patient population. We plan to present data from MyClimb in the second half of 2025. In July 2024, we received rare pediatric disease designation from the FDA for TN-201 in MYBPC3-associated HCM. TN-201 has also been granted orphan drug designation from the FDA, orphan medicinal product designation from the European Commission (EC), and Fast Track Designation from the FDA.
Previous report
TN-301 is our small molecule inhibitor of HDAC6, initially being developed for the potential treatment of HFpEF. HFpEF is characterized by a stiffening of the heart muscle resulting in an inability for the left ventricle to relax and fill with oxygenated blood sufficient to meet the body’s needs. There are several cellular processes thought to underlie the pathophysiology of HFpEF, including increases in fibrosis and inflammation and defects in metabolism. Although HFpEF accounts for approximately half of all heart failures, there are few proven treatment options.
Previous report
We have established a distinct suite of integrated capabilities, including the use of human-induced pluripotent stem cell-derived cardiomyocyte disease models, machine learning and phenotypic screening, gene editing, AAV capsid engineering and novel promoter constructs, which support our efforts to discover and develop disease-modifying treatments focused on heart disease and continue to build on these proprietary capabilities with the aim of increasing the safety and efficacy of our product candidates and accelerating early-stage discovery and preclinical optimization across modalities.
Previous report
We have also internalized and integrated both current cGMP and non-GMP AAV manufacturing capabilities to support our emerging portfolio of gene therapy and cellular regeneration product candidates. Our GMMC, a cGMP facility, is strategically located near our research labs and Manufacturing Technology Development Center, a non-GMP facility, in the San Francisco Bay Area to enable smooth scale-up of production to support our clinical studies and utilizes a modular, scalable design to produce AAV-based gene therapies under cGMP standards. We utilized our GMMC to produce drug product for our first-in-human clinical trials for both TN-201 and TN-401. Building on our manufacturing capabilities, we have also presented data on manufacturing innovations intended to reduce the overall cost of goods by increasing productivity and scalability.
Previous report
a decrease of $6.7 million in manufacturing costs reflecting lower employee-related costs driven by our workforce reduction plan initiated in May 2024 (the Workforce Reduction), lower costs of supplies and materials and lower facility management fees;
Previous report
a decrease of $5.7 million in research costs as there were no IND-enabling activities; partially offset by
Previous report
an increase of $2.6 million in clinical trial related costs for TN-201 and TN-401
Previous report
On August 6, 2024, we entered into a Loan Agreement with SVB. As of December 31, 2024, under the Loan Agreement, we have the right to draw down $22.5 million at our discretion, up to an additional $2.5 million upon the satisfaction of a clinical milestone orthe receipt of specified proceeds from equity financings and other qualified funding, and up to an additional $20.0 million that may be available at SVB’s discretion, subject to specified conditions.
Previous report
On August 10, 2022, we entered into a sales agreement (the Sales Agreement) with Leerink Partners LLC (formerly SVB Securities LLC). Pursuant to the Sales Agreement, we may sell from time to time up to an aggregate of $75.0 million of our common stock through an “at-the-market” (ATM) offering defined in Rule 415 under the Securities Act. The $75.0 million of common stock that may be offered, issued and sold under the Sales Agreement is included in the $300.0 million of securities that may be offered, issued and sold by us under our registration statement on Form S-3 (File No. 333-266741). As of the date of the filing of this Annual Report on Form 10-K, we sold an aggregate of 1,358,333 shares of our common stock under this program for aggregate gross proceeds of $5.2 million, resulting in $69.8 million of shares of our common stock remaining for future sale under this program. On
Previous report
March 3, 2025, we suspended and terminated the prospectus related to our common stock issuable pursuant to the Sales Agreement. As a result, we will not make any sales of our securities pursuant to the Sales Agreement unless and until a new prospectus, prospectus supplement or a new registration statement is filed.
Reworded paragraphs (24)
Previous wording
We are a clinical-stage biotechnology company focused on discovering, developing and delivering potentially curative therapies that address the underlying drivers of heart disease. Our vision is to change the treatment paradigm for heart disease, and in doing so improve and extend the lives of millions of patients.
Current wording
We are a clinical-stage biotechnology company focused on discovering, developing and delivering potentially curative therapies that address the underlying drivers of heart disease. Heart disease remains a leading cause of death in the world. We believe the emerging insights into the genetic causes of cardiovascular conditions and increased recognition for precision medicine approaches has created an opportunity to change the treatment paradigm for heart disease, and in doing so improve and extend the lives of patients.
Previous wording
TN-201 is our potential first-in-class and best-in-class gene therapy for adults and children with HCM due to MYBPC3 gene mutations. These mutations result in a deficiency of myosin binding protein, which in turn can cause the heart walls of affected individuals to become significantly thickened, leading to fibrosis, abnormal heart rhythms, cardiac dysfunction, heart failure and death. HCM is a chronic, progressive condition and those diagnosed with the disease often experience significant impairment in overall quality of life and may be at higher risk for serious complications and co-morbidities. TN-201 utilizes a recombinant adeno-associated virus serotype 9 (AAV9) capsid and is designed to deliver a working MYBPC3 gene to specific cells of the heart in order to produce cardiac myosin binding protein and thereby potentially slow or even reverse the course of MYBPC3-associated HCM following a single infusion.
Current wording
TN-201 is our investigational gene therapy for individuals with HCM due to MYBPC3 gene mutations. These mutations result in a deficiency of MyBP-C, which in turn can cause the heart walls of affected individuals to become significantly thickened, leading to fibrosis, abnormal heart rhythms, cardiac dysfunction, heart failure and death. HCM is a chronic, progressive condition and those diagnosed with the disease often experience significant impairment in overall quality of life and may be at higher risk for serious complications and co-morbidities. TN-201 utilizes a recombinant AAV9 capsid and is designed to deliver a working MYBPC3 gene to specific cells of the heart in order to produce MyBP-C and thereby potentially slow or even reverse the course of MYBPC3-associated HCM following a single infusion.
Previous wording
MyPEAKTM-1 is our Phase 1b/2 multi-center, open-label clinical trial, designed to assess the safety, tolerability and efficacy of a one-time intravenous infusion of TN-201. We have completed Cohort 1 dosing at the 3x1013 vg/kg dose in the MyPEAK-1 trial with no unexpected events or toxicities associated with TN-201 observed. Following review of safety data from the first three MyPEAK-1 patients by an independent DSMB, the DSMB recommended that we proceed with the planned escalation to the 6x1013 vg/kg dose, per protocol. We have dosed two patients in the sentinel phase of Cohort 2 at the 6x1013 vg/kg dose and anticipate completing enrollment of Cohort 2 in the first half of 2025.
Current wording
MyPEAKTM-1 is our Phase 1b/2 multi-center, open-label clinical trial, designed to assess the safety, tolerability and efficacy of a one-time intravenous infusion of TN-201. Enrollment and dosing in both the 3E13 vg/kg dose (Cohort 1) and 6E13 vg/kg dose (Cohort 2) cohorts are complete. A per protocol review by the DSMB of all available data from the first six patients dosed determined that TN-201 had an acceptable safety profile to proceed with dosing expansion cohorts at either dose level. We are enrolling additional patients in MyPEAK-1 to further characterize dose response and inform dose selection for late-stage clinical trials.
Previous wording
TN-401 is our potential best-in-class AAV9-based gene therapy for the treatment of ARVC due to disease-causing variants in the PKP2 gene. ARVC, also known as arrhythmogenic cardiomyopathy, or ACM, is a chronic, progressive disease characterized by frequent, severe, and potentially life-threatening ventricular arrhythmias. The disease is associated with adverse heart remodeling, fibrosis, cardiac dysfunction, significant impairment to patients’ overall quality of life, as well as an elevated risk of sudden cardiac death. PKP2 mutations are the most common genetic cause of ARVC and result in insufficient expression of a protein needed for proper functioning of the desmosomal complex that maintains physical connections and electrical signaling between heart muscle cells. TN-401 utilizes a recombinant AAV9 capsid and is designed to deliver a working PKP2 gene to specific cells of the heart in order to produce plakophilin protein and thereby potentially slow or even reverse the course of PKP2-associated ARVC following a single infusion.
Current wording
TN-401 is our AAV9-based gene therapy for the treatment of ARVC due to disease-causing variants in the PKP2 gene. ARVC, also known as ACM, is a chronic, progressive disease characterized by frequent, severe, and potentially life-threatening ventricular arrhythmias. The disease is associated with adverse heart remodeling, fibrosis, cardiac dysfunction, significant impairment to patients’ overall quality of life, as well as an elevated risk of sudden cardiac death. PKP2 mutations are the most common genetic cause of ARVC and result in insufficient expression of a protein needed for proper functioning of the desmosomal complex that maintains physical connections and electrical signaling between heart muscle cells. TN-401 utilizes a recombinant AAV9 capsid and is designed to deliver a working PKP2 gene to specific cells of the heart in order to produce plakophilin protein and thereby potentially slow or even reverse the course of PKP2-associated ARVC following a single infusion.
Previous wording
We have dosed two patients in RIDGETM-1, our Phase 1b multi-center, open-label clinical trial, designed to assess the safety, tolerability and efficacy of a one-time intravenous infusion of TN-401. We have activated multiple clinical trial sites at leading cardiology centers in the U.S. with ARVC expertise and intend to expand enrollment of RIDGE-1 to the United Kingdom following receipt of approval from the United Kingdom Medicines and Healthcare Products Regulatory Agency (MHRA), Research Ethics Committee and Health Research Authority for our TN-401 Clinical Trial Authorization in 2024. We expect to complete enrollment of the first cohort of patients at the 3×1013 vg/kg in the first half of 2025. An independent safety review will then inform plans for dose escalation to 6×1013 vg/kg, as needed, and/or enrollment of additional patients in the first cohort. Initial clinical data from the first cohort of patients is expected in the second half of 2025. In February 2025, we were awarded a Clinical Grant (Clin2) of $8.0 million from the CIRM. Proceeds from the grant will help fund clinical trial costs for our ongoing Phase 1b RIDGE-1 clinical trial of TN-401 gene therapy.
Current wording
In February 2025, we were awarded a Clinical Grant (Clin2) of $8.0 million from CIRM, a state of California Agency that funds regenerative medicine, stem cell, and gene therapy research. Proceeds from the grant will help fund clinical trial costs for our ongoing Phase 1b/2 RIDGE-1 clinical trial of TN-401 gene therapy. RIDGE-1 is being conducted at multiple clinical trial sites with ARVC expertise at leading cardiology centers in the U.S. and United Kingdom.
Previous wording
In support of our development efforts for TN-401, we initiated RIDGE, a global noninterventional study to collect natural history and seroprevalence to AAV9 antibodies data among ARVC patients who carry pathogenic or likely pathogenic PKP2 gene mutations. Initial data from RIDGE indicated that antibodies to AAV9 in a majority of participants were below the eligibility threshold that would allow for participation in RIDGE-1. We plan to present additional data from RIDGE in the first half of 2025. TN-401 has received orphan drug designation from the FDA and orphan medicinal product designation from the EC, as well as Fast Track Designation from the FDA.
Current wording
TN-401 has received Orphan Drug and Fast Track designation from the FDA and orphan medicinal product designation from the EC.
Previous wording
We shared positive data from our Phase 1 clinical trial of TN-301 in healthy participants at the 2023 Heart Failure Society of America Annual Scientific Meeting. TN-301 was generally well tolerated across the broad range of doses studied. Pharmacokinetic results showed overall dose proportionality with a half-life supportive of once-daily dosing. Increasing doses and exposures with TN-301 correlated with increased pharmacodynamic effects. There were no changes in histone acetylation with TN-301 underscoring the selectivity of TN-301 for HDAC6 and potentially reducing the risk of off target effects. In preclinical studies, selective HDAC6 inhibition has been shown to have comparable efficacy to empagliflozin, a sodium-glucose cotransporter-2 (SGLT2) inhibitor which is approved for the treatment of HFpEF and co-administration of our HDAC6 inhibition with a SGLT2 inhibitor in a HFpEF model demonstrated additive benefit. Taken together, these data support continued development of TN-301 as a potential treatment for patients with HFpEF. We believe late-stage clinical development of TN-301 is best suited for development by or with a well-resourced partner.
Current wording
We shared positive data from our Phase 1 clinical trial of TN-301 in healthy participants at the 2023 Heart Failure Society of America Annual Scientific Meeting. TN-301 was generally well tolerated across the broad range of doses studied. Pharmacokinetic results showed overall dose proportionality with a half-life supportive of once-daily dosing. Increasing doses and exposures with TN-301 correlated with increased pharmacodynamic effects. There were no changes in histone acetylation with TN-301 underscoring the selectivity of TN-301 for HDAC6 and potentially reducing the risk of off target effects. Extensivein vitro andin vivo studies have also shown that TN-301 addresses diverse pathological processes with direct and systemic benefits in models of HFpEF. In comparative studies, selective HDAC6 inhibition as a single agent has been shown to have similar efficacy to empagliflozin, an SGLT2 inhibitor which is approved for the treatment of HFpEF and co-administration of our HDAC6 inhibition with a SGLT2 inhibitor in a HFpEF mouse model demonstrated additive benefit. Taken together, these data support continued development of TN-301 as a potential treatment for patients with HFpEF and other severe diseases - including those outside of cardiology- in which inflammation, fibrosis and metabolic dysregulation may be implicated.
Previous wording
In addition to our lead product candidates, we have multiple early-stage programs progressing through preclinical development using various therapeutic approaches, including gene addition, gene editing, gene silencing, and cellular regeneration to address other forms of rare and/or prevalent heart disease.
Current wording
In addition to our clinical-stage candidates, we have multiple early-stage programs using various therapeutic approaches, including gene addition, gene editing, gene silencing, and cellular regeneration to address other forms of rare and/or prevalent forms of heart disease. We do not have any products approve for sale and have not generated any revenue to date.
Previous wording
The process of conducting the necessary research to advance through the clinical stages and ultimately obtain regulatory approval is costly and time-consuming, and the successful development of our product candidates is highly uncertain. As a result, we cannot reasonably estimate or know the nature, timing or estimated costs of the efforts that will be necessary to complete the development of, and obtain regulatory approval for, or when and to what extent we will generate revenue from the commercialization and sale of any of our product candidates. The level of our research and development expenses over the next twelve months will be subject to operational decisions made following data generated from our MyPEAK-1 and RIDGE-1 clinical trials.
Current wording
The process of conducting the necessary research to advance through the clinical stages and ultimately obtain regulatory approval is costly and time-consuming, and the successful development of our product candidates is highly uncertain. As a result, we cannot reasonably estimate or know the nature, timing or estimated costs of the efforts that will be necessary to complete the development of, and obtain regulatory approval for, or when and to what extent we will generate revenue from the commercialization and sale of any of our product candidates. The level of our research and development expenses over the next twelve months will be subject to operational decisions made following data generated from our MyPEAK-1 and RIDGE-1 clinical trials and our ability to achieve regulatory alignment on our pivotal trial plans for our TN-201 and TN-401 programs.
Previous wording
Research and development expenses were $86.7 million and $98.0 million for the years ended December 31, 2024 and 2023, respectively. The decrease of $11.3 million, or 12%, was primarily due to:
Current wording
Research and development expenses were $68.6 million and $86.7 million for the years ended December 31, 2025 and 2024, respectively. The decrease of $18.1 million, or 21%, was primarily due to:
Previous wording
We will continue to incur legal, accounting, insurance and other expenses in operating our business as a public company, including costs associated with regulatory and compliance activities. As with our research and development, the level of our general and administrative expenses over the next twelve months will be subject to operational decisions made following data generated from our MyPEAK-1 and RIDGE-1 clinical trials.
Current wording
We will continue to incur legal, accounting, insurance and other expenses in operating our business as a public company, including costs associated with regulatory and compliance activities. As with our research and development, the level of our general and administrative expenses over the next twelve months will be subject to operational decisions made following data generated from our MyPEAK-1 and RIDGE-1 clinical trials and our ability to achieve regulatory alignment on our pivotal trial plans for our TN-201 and TN-401 programs.
Previous wording
General and administrative expenses were $29.2 million and $33.2 million for the years ended December 31, 2024 and 2023, respectively. The decrease of $3.9 million, or 12%, was primarily due to decreases in employee-related costs driven by the Workforce Reduction and lower professional fees.
Current wording
General and administrative expenses were $24.7 million and $29.2 million for the years ended December 31, 2025 and 2024, respectively. The decrease of $4.5 million, or 15%, was primarily due to decreases in employee-related costs driven by the Workforce Reductions and lower professional fees.
Previous wording
Interest income primarily consists of interest earned on our cash, cash equivalents and investment balances. Interest income was $4.7 million and $7.1 million for the years ended December 31, 2024 and 2023, respectively. The year-over-year decrease of $2.3 million was primarily due to lower cash, cash equivalents and investment balances.
Current wording
Interest income primarily consists of interest earned on our cash, cash equivalents and investment balances. Interest income was $2.7 million and $4.7 million for the years ended December 31, 2025 and 2024, respectively. The year-over-year decrease of $2.1 million was primarily due to lower cash, cash equivalents and investment balances.
Previous wording
Net loss for the year ended December 31, 2024, was $111.1 million, compared to a net loss of $124.1 million for the year ended December 31, 2023.
Current wording
Net loss for the year ended December 31, 2025, was $90.6 million, compared to a net loss of $111.1 million for the year ended December 31, 2024.
Previous wording
Since our inception, we have not generated any revenue and we have incurred significant net losses and negative cash flows from operations. From our inception through December 31, 2024, we have funded our operations primarily from the sale and issuance of our equity securities. As of December 31, 2024, we had cash, cash equivalents and investments in marketable securities of $61.4 million and an accumulated deficit of $514.4 million.
Current wording
Since our inception, we have not generated any revenue and we have incurred significant net losses and negative cash flows from operations. From our inception through December 31, 2025, we have funded our operations primarily from the sale and issuance of our equity securities. As of December 31, 2025, we had cash, cash equivalents and investments in marketable securities of $100.5 million and an accumulated deficit of $605.0 million.
Previous wording
In February 2025, we announced we were awarded an $8 million grant from the CIRM to support RIDGE-1, our Phase 1b clinical trial of TN-401 gene therapy for the potential treatment of PKP2-associated ARVC. The award is payable to us upon achievement of milestones to be determined by CIRM in collaboration with us. Additionally, if CIRM determines, in its sole discretion, that we have not complied with the terms and conditions of the grant, CIRM may suspend or permanently cease disbursements. Funds received under this grant may only be used for allowable project costs specifically identified with the CIRM-funded project. Such costs can include, but are not limited to, salary for personnel, itemized supplies, consultants, and itemized clinical study costs. Under the terms of the grant, we will co-fund the research project with CIRM and the amount of our co-funding requirement is predetermined as a part of the award. We expect to begin receiving funds from the grant beginning in the first half of 2025.
Current wording
In February 2025, we announced we were awarded an $8 million grant from the CIRM to support RIDGE-1. The award is payable to us upon achievement of certain clinical milestones. Additionally, if CIRM determines, in its sole discretion, that we have not complied with the terms and conditions of the grant, CIRM may suspend or permanently cease disbursements. Funds received under this grant may only be used for allowable project costs specifically identified with the CIRM-funded project. Such costs can include, but are not limited to, salary for personnel, itemized supplies, consultants, and itemized clinical study costs. Under the terms of the grant, we will co-fund the research project with CIRM and the amount of our co-funding requirement is predetermined as a part of the award. For the year ended December 31, 2025, we recognized $2.5 million as a reduction of research and development expenses in connection with the grant.
Previous wording
On March 5, 2025, we completed an underwritten offering of 75,000,000 units, priced at a public offering price of $0.70 per unit, with each unit consisting of one share of our common stock, a warrant to purchase one share of our common stock at an exercise price of $0.80 per share, which will be immediately exercisable and will expire five years from the date of issuance (a Series A Warrant) and a warrant to purchase one-half of a share of our common stock at an exercise price of $0.70 per share, which will be immediately exercisable and expire on June 30, 2026 (a Series B Warrant), under our registration statement on Form S-3 (File No. 333-266741). We received net proceeds of approximately $48.9 million, after deducting underwriting discounts and commissions of approximately $3.2 million and other offering expenses of approximately $0.5 million.
Current wording
On March 5, 2025, we completed an underwritten offering of 75,000,000 units, priced at a public offering price of $0.70 per unit, with each unit consisting of one share of our common stock, a warrant to purchase one share of our common stock at an exercise price of $0.80 per share, which are immediately exercisable and expire five years from the date of issuance (a Series A Warrant) and a warrant to purchase one-half of a share of our common stock at an exercise price of $0.70 per share, which are immediately exercisable and expire on June 30, 2026 (a Series B Warrant), under our registration statement on Form S-3 (File No. 333-266741). We received net proceeds of approximately $48.9 million, after deducting underwriting discounts and commissions of approximately $3.2 million and other offering expenses of approximately $0.5 million.
Previous wording
continue to advance our lead gene therapy product candidates, TN-201 and TN-401;
Current wording
continue to advance our lead product candidates, TN-201, TN-401 and TN-301;
Previous wording
Based on our current operating plan, we believe that our existing cash, cash equivalents and investments in marketable securities, along with the $22.5 million of funds available under our Loan Agreement with SVB, will be sufficient to meet our working capital and capital expenditure needs through at least the next twelve months following the date of this Annual Report on Form 10-K.
Current wording
Based on our current operating plan, we believe that our existing cash, cash equivalents and investments in marketable securities, will be sufficient to meet our working capital and capital expenditure needs through at least the next twelve months following the date of this Annual Report on Form 10-K.
Previous wording
In order to complete the development of our product candidates and commercialize our product candidates, if approved, we will require substantial additional funding. Until such time as we can generate significant revenue from sales of our product candidates, if ever, we expect to finance our operations through public or private equity offerings or debt financings or other capital sources, which may include strategic collaborations or other arrangements with third parties, or other sources of financing. We may not be able to raise additional capital on terms acceptable to us or at all. To the extent that we raise additional capital through the sale of equity or convertible debt securities, the ownership interest of our stockholders will be or could be diluted, and the terms of these securities may include liquidation or other preferences that adversely affect the rights of our common stockholders. Debt financing and preferred equity financing, if available, may involve agreements that include covenants limiting or restricting our ability to take specific actions, including restricting our operations and limiting our ability to incur liens, issue additional debt, pay dividends, repurchase our common stock, make certain investments or engage in merger, consolidation, licensing or asset sale transactions. If we raise funds through strategic collaborations, partnerships and other similar arrangements with third parties, we may be required to grant rights to develop and market product candidates that we would otherwise prefer to develop and market ourselves. If we are unable to raise additional capital on acceptable terms when needed, our business, results of operations, and financial condition would be adversely affected.
Current wording
In order to complete the development of our product candidates and commercialize our product candidates, if approved, we will require substantial additional funding. Until such time as we can generate significant revenue from sales of our product candidates, if ever, we expect to finance our operations through public or private equity offerings, debt financings or other capital sources, which may include strategic collaborations or other arrangements with third parties, or other sources of financing. We may not be able to raise additional capital on terms acceptable to us or at all. To the extent that we raise additional capital through the sale of equity or convertible debt securities, the ownership interest of our stockholders will be or could be diluted, and the terms of these securities may include liquidation or other preferences that adversely affect the rights of our common stockholders. Debt financing and preferred equity financing, if available, may involve agreements that include covenants limiting or restricting our ability to take specific actions, including restricting our operations and limiting our ability to incur liens, issue additional debt, pay dividends, repurchase our common stock, make certain investments or engage in merger, consolidation, licensing or asset sale transactions. If we raise funds through strategic collaborations, partnerships and other similar arrangements with third parties, we may be required to grant rights to develop and market product candidates that we would otherwise prefer to develop and market ourselves. If we are unable to raise additional capital on acceptable terms when needed, our business, results of operations, and financial condition would be adversely affected.
Previous wording
Net cash used in operating activities for the year ended December 31, 2023 was $102.1 million, which consisted primarily of a net loss of $124.1 million and a net change in operating assets and liabilities of $5.6 million, partially offset by $25.8 million in non-cash charges. The change in net operating assets and liabilities was primarily due to a decrease in operating lease liabilities of $4.1 million and a decrease in accounts payable and accrued expenses and other current liabilities of $1.0 million. Cash flows from operations are generally impacted by the timing of payments to vendors and vendor payment terms. The non-cash charges primarily consisted of stock-based compensation of $15.3 million and depreciation and amortization of $8.7 million.
Current wording
Net cash used in operating activities for the year ended December 31, 2025 was $68.3 million, which consisted primarily of a net loss of $90.6 million and a net change in operating assets and liabilities of $2.5 million, partially offset by $24.0 million in non-cash charges. The change in net operating assets and liabilities was primarily due to a decrease in operating lease liabilities of $2.8 million. Cash flows from operations are generally impacted by the timing of payments to vendors and vendor payment terms. The non-cash charges primarily consisted of stock-based compensation of $13.0 million and depreciation and amortization of $8.4 million.
Previous wording
Net cash provided by investing activities for the year ended December 31, 2023 was $48.7 million, which consisted primarily of proceeds from maturities of marketable securities of $106.6 million, partially offset by purchases of marketable securities of $56.6 million.
Current wording
Net cash provided by investing activities for the year ended December 31, 2025 was $56.1 million, which consisted primarily of proceeds from maturities of marketable securities of $45.7 million and sales of marketable securities of $11.0 million.
Previous wording
Net cash provided by financing activities for the year ended December 31, 2023 was $4.0 million, which primarily consisted of net proceeds from at-the-market sales of $3.9 million.
Current wording
Net cash provided by financing activities for the year ended December 31, 2025 was $108.4 million, which primarily consisted of net proceeds from our March 2025 and December 2025 follow-on offerings of $105.1 million.
Previous wording
We lease office space for our corporate headquarters in South San Francisco under a lease that expires in November 2027. We expect to pay rent of approximately $2.5 million during 2025 for this lease. We also lease the Union City Facility under a lease that expires in July 2031. We expect to pay rent of approximately $1.3 million in 2025 for this lease. As of December 31, 2024, undiscounted future minimum lease payments of $7.3 million and $9.6 million remain on the South San Francisco and Union City leases, respectively.
Current wording
We lease office space for our corporate headquarters in South San Francisco under a lease that expires in November 2027. We expect to pay rent of approximately $2.5 million during 2026 for this lease. We also lease a manufacturing facility in Union City under a lease that expires in July 2031. We expect to pay rent of approximately $1.4 million in 2026 for this lease. As of December 31, 2025, undiscounted future minimum lease payments of $4.8 million and $8.3 million remain on the South San Francisco and Union City leases, respectively.
Rearranged current paragraphs (1)
Current report — wording carried from elsewhere
On December 15, 2025, we completed an underwritten public offering of 50,000,000 units, priced at a public offering price of $1.20 per unit, with each unit consisting of one share of common stock and a warrant to purchase one share of common stock at an exercise price of $1.50 per share, which are immediately exercisable and expire five years from the date of issuance (December 2025 Warrant), under our registration statement on Form S-3 (File No. 333-286005). We received net proceeds of $55.8 million, after deducting underwriting discounts and commissions of $3.6 million and other offering expenses of $0.6 million.