NASDAQ: TNYA

We are primarily focused on advancing our clinical-stage gene therapy candidates, TN-201, for MYBPC3-associated hypertrophic cardiomyopathy (HCM), and TN-401, for PKP2-associated arrhythmogenic right ventricular cardiomyopathy (ARVC). Each candidate is currently in Phase 1b/2 clinical testing to establish the safety and efficacy profile of two different doses. We anticipate that data generated to date and over the course of 2026 will support pursuit of regulatory alignment on late-stage development for TN-201 and TN-401. A third clinical-stage candidate discovered utilizing our targeted drug discovery capabilities is TN-301, a highly specific small molecule inhibitor of histone deacetylase 6 (HDAC6) with a unique multi-modal mechanism of action that has potentially broad utility in prevalent conditions such as heart failure with preserved ejection fraction (HFpEF), as well as other cardiac, metabolic, muscular and pulmonary diseases, including but not limited to genetic dilated cardiomyopathy (DCM), Duchenne muscular dystrophy (DMD) and pulmonary arterial hypertension (PAH).

We were founded with a long-term goal of building a fully integrated biopharmaceutical company focused on discovering, developing and ultimately commercializing first-/best-in-class precision medicines for heart disease. Early on in our company history, we invested in differentiated capabilities to enable modality agnostic target identification and validation and product candidate optimization efforts anchored in human genetics and the use of human disease models. These highly productive platform drug discovery capabilities directly contributed to the development of our three clinical-stage programs, as well as to several earlier-stage pipeline. To support our initial focus on gene therapy candidates, we have internalized expertise in capsid engineering, promoters and regulatory elements and manufacturing science anchored on the use of adeno-associated viruses (AAVs) as the method of delivery to the heart. That in-depth genetic medicines expertise has directly informed the design, optimization and production of our lead gene therapy candidates, TN-201 and TN-401.

Our extensive cardiac genetic medicines capabilities make us a potential partner of choice for academic researchers and industry partners alike. In March 2026, we entered into a multi-target research collaboration with Alnylam Pharmaceuticals, Inc. (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.

For programs addressing relatively rare conditions – for example, our gene therapies for genetic cardiomyopathies – 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. Where our discovery efforts lead to product candidates intended for relatively prevalent indications our strategy is to out-license or partner such programs.

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Our Product Pipeline

We are advancing a diverse pipeline of product candidates intended to target the underlying causes of rare and highly prevalent forms of heart disease.

Each of our most advanced product candidates, TN-201, TN-401, and TN-301, emerged from an initial examination of the genetic underpinnings of heart conditions and has progressed to clinical stage with the support of our proprietary internal capabilities.

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TN-201 gene therapy for HCM caused by variants in the MYBPC3 gene: TN-201 is our AAV9-based gene therapy being developed to treat the underlying cause of MYBPC3-associated HCM by delivering a working MYBPC3 gene to specific cells of the heart via a single infusion. MYBPC3 mutations are the most common genetic cause of HCM, accounting for approximately 20% of the overall HCM population or more than 120,000 people in the U.S. alone. Patients may experience serious complications such as shortness of breath, fainting and palpitations, significant impairment in overall quality of life, heart failure, and sudden cardiac death. We are currently conducting the Phase 1b/2 MyPEAKTM-1 clinical trial in symptomatic adults diagnosed with MYBPC3-associated HCM, for which we presented one year or greater safety, biopsy and efficacy results for the three patients enrolled in Cohort 1 and initial safety and available biopsy data for patients in Cohort 2 at the American Heart Association’s (AHA) Scientific Sessions 2025 in November 2025, with simultaneous publication in Cardiovascular Research. We plan to present longer-term Cohort 1 and interim Cohort 2 data in the first half of 2026, followed by two-year Cohort 1 data and one-year Cohort 2 data in the second half of the year. We also intend to pursue alignment with regulatory authorities on pivotal trial plans for TN-201. TN-201 has received Fast Track, Orphan Drug and Rare Pediatric Disease Designation from the FDA and also received orphan medicinal product designation from the European Commission (EC).

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TN-401 gene therapy for ARVC caused by variants in the PKP2 gene: TN-401 is our AAV9-based gene therapy being developed for the treatment of ARVC due to disease-causing variants in the PKP2 gene. PKP2 mutations are the most common genetic cause of ARVC, also known as arrhythmogenic cardiomyopathy (ACM), a condition characterized by arrhythmias, palpitations, lightheadedness, dizziness and fainting that typically strikes before age 40. The prevalence of PKP2-associated ARVC is estimated at more than 70,000 people in the U.S. alone, though it frequently goes undiagnosed as sudden cardiac death is the first sign of disease in nearly one quarter of known cases. We are currently conducting RIDGETM-1, our Phase 1b/2 clinical trial evaluating TN-401 in adult patients with PKP2-

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associated ARVC, for which we presented initial safety, biopsy and arrhythmia results for three patients enrolled in Cohort 1. 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. TN-401 has received Fast Track and Orphan Drug designation from the FDA and orphan medicinal product designation from the EC.

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TN-301 small molecule HDAC6 inhibitor for the potential treatment of HFpEF and other cardiac, muscular or metabolic conditions: We initially discovered the cardioprotective qualities of selective HDAC6 inhibition in a genetic model of DCM. In subsequent preclinical studies, TN-301 was also shown to reverse many of the signs and symptoms of HFpEF, with evidence of improvements in cardiac function, glucose tolerance, inflammation and fibrosis. We completed Phase 1 clinical testing of TN-301 in healthy volunteers, observing an acceptable safety profile, suitability for once-daily dosing, and dose-dependent target engagement. 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 with seeking opportunities to partner TN-301, we plan to selectively explore its utility in rare and orphan indications in which it may be possible to demonstrate proof-of-activity in a well-defined patient population. Using the mechanistic insights gained from our preclinical studies of TN-301, we have identified additional indications where TN-301’s distinct activity has the potential to address the underlying pathophysiology of disease. Among the most promising of these is the potential for TN-301 to target the mechanisms that drive DMD, a severe disease involving muscle fibrosis and atrophy for which the leading cause of death is cardiomyopathy. In preclinical studies, TN-301 improved muscle function in the mouse mdx in vivo model of the disease and addressed key drivers of cardiomyopathy in relevant human cell-based models of DMD, while minimizing off-target toxicities associated with an approved pan-HDAC6 treatment for DMD.

While our resources are firmly focused on our lead product candidates, we have multiple early-stage programs progressing through preclinical development using various therapeutic approaches, including cellular regeneration, gene addition, gene editing and gene silencing to address rare and/or prevalent heart diseases. Today, our pipeline consists of programs to which we have exclusive worldwide rights and that have emerged from our internal efforts, with select product candidates originating based on intellectual property licensed from academic institutions.

Our Integrated Capabilities

Our distinct suite of integrated capabilities broadly enable modality agnostic target identification and validation, design of AAV-based genetic medicines and in-house manufacturing to support our efforts to discover and develop disease-modifying treatments focused on heart disease. Our interrelated capabilities include the use of human-induced Pluripotent Stem Cell (iPSC)-derived and engineered heart tissue disease models, machine learning and phenotypic screening and capsid engineering and novel promoter constructs, all of which are intended to enable the discovery, design, delivery and development of therapeutics that are best suited to a given cardiovascular condition. For manufacturing, our early strategy was to have complete ownership of process development and analytical development for our gene therapy product candidates. This strategy supported our ability to produce the clinical trial material needed for our current Phase 1b/2 clinical trials of TN-201 and TN-401, as well as the development of the know-how and capabilities necessary to manage our late-stage drug manufacturing requirements.

Collaboration Agreements

We seek to enter into collaborations pursuant to which we can use our platform to benefit patients with cardiovascular diseases, or that we believe will contribute to our ability to develop and ultimately commercialize our clinical-stage product candidates and to advance our preclinical programs.

Alnylam

In March 2026, we entered into a collaboration agreement with Alnylam, pursuant to which both parties agreed to a research collaboration to discover and validate novel gene targets for the potential treatment of cardiovascular disease.

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Together, both parties will nominate an aggregate of 15 targets, align on which targets to move forward into the collaboration and then collaborate for a period of twenty-four (24) months (which may be extended for completion of the work) during which the parties will conduct in vitro and in vivo validation activities under a mutually agreed research plan and budget. Each party will be solely responsible for its own costs incurred to conduct its activities under the research plan, except that Alnylam will reimburse us for full-time employees and out-of-pocket costs and expenses incurred by us in accordance with the agreed-upon research budget. After completion of the validation activities, Alnylam will be solely responsible, at its own expense, for all development, manufacture, regulatory and commercialization activities for any products directed to a collaboration target.

Under the terms of the collaboration agreement, we granted Alnylam an exclusive, worldwide license, with the right to sublicense, under our relevant intellectual property rights and know-how related to the collaboration targets, to evaluate and utilize such collaboration targets and to research, develop, manufacture and commercialize any product directed to such collaboration targets. During the twenty-four (24)-month period following the completion of the validation activities, Alnylam will have the right to evaluate each collaboration target to determine whether to further develop products directed to such collaboration target. In the event Alnylam fails to commence a non-human primate pharmacodynamic study for any target nominated by us prior to the end of such evaluation period, then such target will be deemed a terminated collaboration target, the collaboration agreement will expire for such target, and the license we granted to Alnylam with respect to such target will be terminated. During the term of the collaboration agreement, except in connection with the conduct of validation activities under the research plan, we are not permitted to conduct any research or development activities with respect to certain collaboration targets or any therapeutic products designed to be directed to such targets for as long as the target remains a collaboration target.

Pursuant to the terms of the collaboration agreement, Alnylam will pay us an upfront payment of up to $10.0 million within thirty (30) days after Alnylam’s receipt of an invoice from us. The upfront fee is subject to $500,000 reductions for up to eight targets we nominate that do not meet certain agreed-upon standards and that the joint steering committee chooses not to advance. We are also eligible to receive up to an aggregate of $1.13 billion in development, regulatory and sales-based milestones related to products directed to targets we nominate.

For targets we nominate for which Alnylam has commenced a non-human primate pharmacodynamic study prior to the end of the aforementioned evaluation period, the collaboration agreement will continue on a target-by-target basis through the date on which no more payment obligations remain. For targets nominated by Alnylam, the collaboration agreement will continue through the completion of the validation activities performed by us. Either party may terminate the collaboration agreement for the other party’s uncured material breach or insolvency, subject to specified notice and cure periods. Alnylam may unilaterally terminate the collaboration agreement in its entirety, for any or no reason, subject to a specified notice period.

The collaboration agreement contains, among other provisions, customary representations and warranties by the parties, intellectual property protection covenants, certain indemnification rights in favor of each party and customary confidentiality provisions.

The foregoing description of the collaboration agreement with Alnylam does not purport to be complete and is qualified in its entirety by the full text of such agreement, a copy of which the Company intends to file as an exhibit to its Quarterly Report on Form 10-Q for the quarter ending March 31, 2026.

Overview of Heart Disease

Heart disease is the leading cause of death in the world, representing an estimated 32% of all global fatalities. The heart is a complex organ due to its biological structure as well as its tightly regulated and coordinated electrophysiological and biomechanical properties. Heart disease comes in many forms, affects individuals at many ages, and is a result of many factors. In each case, the underlying cause could be genetic or due to normal aging or due to environmental factors. Our initial research and development focus has been on the genetics associated with conditions affecting the heart muscle, also known as cardiomyopathies, specifically HCM and ARVC, each of which can lead to serious comorbidities such as sudden cardiac arrest or heart failure.

Historically, treatments for heart disease have been aimed at broadly addressing symptoms of highly prevalent conditions and the development of novel treatments has been stymied by the need for lengthy studies primarily focused on survival and hospitalization outcomes. Such studies required enrolling large, heterogeneous patient populations in an effort to achieve statistically significant signals of efficacy. Consequently, innovation in heart

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disease drug development has lagged in comparison to therapeutic areas such as oncology and rare diseases where more targeted approaches have achieved clinical and regulatory success.

Growing Momentum for Precision Approaches

In the past several years, increasing clinical and regulatory validation for more targeted approaches have emerged for precision approaches to heart disease and AAV-based gene therapies. These include FDA draft guidance supporting smaller clinical studies that emphasize the use of clinically meaningful endpoints of “feel and function” and a small but growing number of examples of clinical success and regulatory approvals for disease-modifying treatments geared toward targeted disease populations, including in genetic cardiomyopathies, that have followed similar development and regulatory paths.

A combination of increasing insights into the genetic causes of heart disease and recognition of the importance of genetic testing support the discovery, development and commercial opportunities for precision medicines that target the underlying genetic cause of heart conditions. More than 250 genetically defined disorders are now known where the primary source of morbidity and mortality involves the heart, providing numerous potentially druggable targets for characterization. Updated clinical practice guidelines from the American College of Cardiology, American Heart Association and European Society of Cardiology recommending genetic testing and family counseling, and the push for mandatory screening of young athletes, are all leading to improved access to genetic testing, patient diagnosis and disease management. At the same time, the field of gene therapy drug development has matured. The safety and efficacy of genetic medicines, and AAV9-based gene therapies in particular, continues to grow with multiple new regulatory approvals in recent years resulting in thousands of patients dosed worldwide.

We believe with the evolving understanding of heart disease, and the genetic underpinnings of disease in particular, there are significant opportunities where our proprietary capabilities and singular focus will enable us to benefit from and support the evolution towards more precise diagnosis, drug development, and treatment for heart disease.

Evolving Regulatory Pathway for Gene Therapy

The regulatory pathway for gene therapy is evolving toward a more efficient, science-driven approach that is beginning to bridge the gap between innovative drug development and patient access to medicines that address the unmet need for rare disease conditions. A study by the Association for Regenerative Medicine found that gene therapies for rare disease have a 2 to 3.5-fold higher likelihood of achieving regulatory approval as compared to other modalities. This report is bolstered by multiple emerging FDA policies and practices intended to help streamline the development of gene therapies and mitigate safety and tolerability concerns that can delay development timelines. In just the past year, several developments impacting U.S. regulatory consideration of genetic medicines for rare diseases have emerged or been reaffirmed:

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Alignment with multiple gene therapy sponsors on pivotal trial and accelerated approval pathways indicating a willingness to consider surrogate markers of efficacy and expedited regulatory review.

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The FDA’s issuance of important guidance, including expedited programs for regenerative medicines and the regenerative medicine advanced therapy (RMAT) designation, the issuance of advice on study design, endpoints and analysis for rare and pediatric cell and gene therapies, and the recent adoption of Rare Disease Evidence Principles which facilitates the approval of medicines for rare diseases with very small patient populations in which a known genetic defect is a known driver of disease, among others.

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Congress’s reauthorization of the Rare Disease Priority Review Voucher Program is another important step that provides stability for the rare disease community, stimulates investment in pediatric rare disease and allows sponsors to expedite the FDA review process, reducing the time to market for new treatments. This reauthorization further strengthens the opportunity for TN-201 as a treatment for pediatric patients suffering from MYBPC3-associated HCM.

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For Tenaya, we believe these actions collectively reflect a commitment to facilitating the development and approval of cell and gene therapy products for rare conditions and balancing safety and rigorous standards with accelerating access to innovative medicines for patients.

Our Strategy

Our long-term goal is to become a leading, fully integrated biotechnology company delivering next-generation therapies that address the underlying causes of heart disease. We are taking advantage of an expanded understanding of heart biology and advances in the science of genetics and disease models to discover, develop, manufacture and ultimately commercialize a deep and diverse pipeline of novel heart disease therapies. The key components of our strategy to achieve these goals are:

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Focus on heart disease. Heart disease remains a leading cause of death globally, and the unmet medical need remains high. We see significant opportunity to address this sizable market with our dedicated strategy. The heart is a complex organ to target, in part due to the tightly regulated and coordinated electrophysiological and biomechanical properties that can complicate delivery of effective therapies and necessitates a deep understanding of heart biology. Our laser focus leads to insights that underpin our foundational and differentiated capabilities to address challenges that have historically presented barriers to the successful development of novel therapies for the heart.

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Develop disease-modifying therapies. We are focused on developing disease-modifying and potentially life-saving novel therapies that target the underlying causes of heart disease. We are particularly interested in areas where there is no current standard-of-care or where we believe the nature and the magnitude of the effect of our therapies will be significant relative to existing standards-of-care. For example, we believe our AAV-based gene therapy candidates for genetically defined conditions have the potential to be curative after a single dose.

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Target defined sub-populations of patients most likely to respond to our therapies. We seek to focus on patient populations where the genetic cause of the disease is well-established, including genetic cardiomyopathies and other monogenic disorders. We also seek to use different strategies to sub-segment larger heart failure populations through the use of genetics or biomarkers to improve selection of patients with attributes that are more suited to the specific mechanism of action of a given product candidate. We believe this strategy can accelerate clinical development, reduce overall development costs, and improve the probability of clinical and regulatory success.

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Internalize and integrate core capabilities to support our innovation. Powering our drug discovery engine are genetic insights into cardiac biology, coupled with a suite of core capabilities centered on modality agnostic target discovery and validation and design, production and delivery know-how for AAV-based genetic medicines. We believe the integration of our know-how and innovations in these areas will allow us to generate scientific insights more rapidly and improve the probability of technical and regulatory success of our product candidates.

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Advance a deep and diverse pipeline of therapies. The diversity of our programs illustrates the ambition of our vision and the versatility and depth of our scientific approach. Our pipeline includes therapeutics for both rare and prevalent heart diseases across multiple treatment modalities. Our most advanced rare disease programs include two AAV-based gene therapy candidates in early clinical development: TN-201, our product candidate for MYBPC3-associated HCM and TN-401, our product candidate for PKP2-associated ARVC. TN-301, a small molecule inhibitor of HDAC6 intended to address HFpEF has successfully completed a Phase 1 clinical trial. We are also working on several other early-stage programs, including gene editing and cardiac regeneration, that we believe will add to our future pipeline opportunities.

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Seek partnerships that can expand our reach and accelerate our efforts. We believe our focus on heart disease and extensive platform and core capabilities make us a potential partner of choice for academics and larger companies alike who wish to access deep expertise in next-generation therapies for heart disease. We also strategically evaluate collaborations and partnerships with biopharmaceutical companies that may have more robust and complimentary capabilities and resources to accelerate the development and maximize the availability and potential of our product candidates, particularly for more prevalent indications and/or specific modalities.

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Become a fully integrated biopharmaceutical company with commercial capabilities. We aim to discover, develop, manufacture, and eventually commercialize therapies, with an initial focus on those therapies for rare disease populations that could be launched and marketed by a relatively small, specialized salesforce.

Our Clinical-Stage Gene Therapy Programs

Gene therapy is a way of treating or preventing diseases or medical conditions caused by genetic mutations. Our initial programs target loss-of-function mutations that affect a given gene’s ability to make a protein resulting in a pathogenic protein deficiency. Gene therapy compensates for the mutated gene by delivering a working gene to target cells in order to restore healthy function and thereby address the underlying cause of a disease.

We utilize AAVs, and specifically AAV9, to deliver the therapeutic working gene to target cells of the heart muscle. AAVs are naturally occurring viruses that are not known to cause diseases in people and are the most common viral vectors used in gene therapy. Viral DNA is removed and the resulting viral shell, or capsid, is loaded with a working gene and regulatory elements to ensure preferential delivery to target tissues and successful transfer of the gene into cells, known as transduction. AAV9 is the most widely studied and clinically validated capsid and has been proven to transduce human cardiomyocytes.

TN-201: Gene Therapy for MYBPC3-associated HCM

We are developing TN-201, an investigational AAV-based gene therapy for MYBPC3-associated HCM, a condition caused by insufficient levels of myosin-binding protein C (MyBP-C). MYBPC3 genetic mutations are the most common cause of familial HCM. These mutations and the associated deficiency in MyBP-C protein, result in dysregulation of the heart’s contractile mechanism which in turn causes the heart walls of affected individuals to become significantly thickened, leading to fibrosis, abnormal heart rhythms, cardiac dysfunction, heart failure, and increased risk of sudden cardiac death. There are currently no approved therapies that address the underlying cause of MYBPC3-associated HCM.

Overview of HCM

HCM is a condition in which the heart walls become thickened (hypertrophy) due to excess contraction, resulting in a reduced ability of the left ventricle (LV) to relax and fill (diastole) and pump (systole) blood effectively with each heartbeat. HCM is a chronic, progressive disease associated with significant impairment to patients’ overall quality of life, as well as an elevated risk of sudden cardiac death. Symptoms include chest pain, shortness of breath (dyspnea), fainting (syncope), fatigue and palpitations. As the disease progresses, patients may suffer premature death due to end-stage heart failure or malignant ventricular arrhythmia (VA) sometimes leading to sudden cardiac death or stroke. Disease onset can occur at any age, with HCM most frequently emerging in adults in their mid-40s. When HCM emerges in children and young adults, the disease course is typically more aggressive and prognosis is worse than that observed in older patients. HCM is the leading cause of sudden cardiac death in young adults.

HCM is estimated to affect one in every 500 people, approximating more than 600,000 people in the U.S. A majority of HCM patients are currently undiagnosed, with diagnosis typically starting with the onset of symptoms, family screening, or the discovery of an abnormal electrocardiogram (ECG) pattern. A clinical diagnosis of HCM in adults is defined as a left ventricular wall thickening of greater than 15mm. Patients with HCM can present with either the obstructive form (oHCM) or the nonobstructive form (nHCM) of the disease. Both forms of the disease involve significant LV hypertrophy; however, in oHCM, the thickening of the LV wall is such that the LV outflow tract (LVOT) narrows and “obstructs” the proper flow of blood to the rest of the body. Nonobstructive HCM is more frequently characterized by diastolic dysfunction resulting in increased LV filling pressures that leads to chest pain and dyspnea. The genetic causes of HCM may be diverse, but approximately 60% of patients with HCM have clearly identifiable familial disease with an autosomal dominant pattern of inheritance. Mutations in the MYBPC3 gene are estimated to represent approximately 20% of the overall HCM population and to affect approximately 120,000 patients in the U.S. MYBPC3 gene mutations may result in either form of HCM. In contrast to the general HCM population in which oHCM makes up approximately two-thirds of diagnoses, a majority of MYBPC3-associated HCM patients have the nonobstructive form of the disease, with one study involving a series of more than 1,000 patients finding that 69% of patients with MYBPC3 mutations had nHCM, while 31% presented with LVOT characteristic of oHCM.

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HCM patients who are heterozygous for MYBPC3 gene mutations are typically diagnosed earlier in life as compared to genotype-negative HCM patients and have more severe disease associated with increases in arrhythmia, sudden cardiac death and cardiovascular mortality. Those diagnosed with MYBPC3-associated HCM before the age of eighteen represent a sizeable severe population subject to more rapid disease progression and a markedly greater cumulative disease burden compared to those with adult-onset. Infants with homozygous MYBPC3 gene mutations represent a rare, but particularly severe patient group. With high risk of death and no available treatment options to address the underlying genetic mutation, the only option for those born with homozygous MYBPC3 gene mutations is a heart transplant, typically within the first year of life.

The MYBPC3 gene encodes the MyBP-C protein, which forms a key component of the cardiac sarcomere, the fundamental contractile unit of the cardiomyocyte. MyBP-C protein is central to regulation of both contraction and relaxation of the cardiac muscle. Reduced MyBP-C protein levels associated with heterozygous mutations in the MYBPC3 gene result in increased activity of the myosin contractile machinery, which over time leads to LV muscle thickening, known as hypertrophy, excess deposition of extracellular matrix in the cardiac muscle, known as fibrosis, and disorganized muscle cells. As a result, the LV wall stiffens, and the chamber is reduced in size, decreasing the heart’s ability to pump. The contractile strength of the muscle declines in some cases, resulting in LV systolic dysfunction, which ultimately can necessitate advanced therapies, such as an LV assist device (LVAD) or transplantation, in the most severely affected patients. Fibrosis and muscle cell disarray may also lead to arrhythmias in some patients, including life-threatening VA and atrial fibrillation, which can lead to stroke.

Approximately 90% of MYBPC3 gene mutations result are truncating. Analysis of the hearts of patients who carry truncating mutations of the MYBPC3 gene show on average approximately 40% lower levels of functional MyBP-C protein compared to unaffected hearts. In the most severe cases in which both copies of the gene are affected, there is a complete lack of functional MyBP-C protein expression. We believe these findings support the idea that mutations of the MYBPC3 gene cause human disease through haploinsufficiency and the hypothesis that gene replacement may address the underlying cause of disease by increasing the levels of functional MyBP-C protein.

The current goal of HCM treatment is to relieve symptoms and prevent sudden cardiac death in people at high risk. In current guideline-directed care, patients are typically prescribed one or more symptomatic therapies, including beta-blockers, calcium channel blockers and antiarrhythmics. These therapies do not address the underlying genetic cause of HCM and do not appear to affect disease progression. No randomized clinical trials have assessed these therapies specifically in HCM. The standards of care are slightly different for patients with oHCM versus nHCM, but the unmet need is high in both forms of the disease. Cardioverter-defibrillators may be implanted for patients at high risk for malignant arrhythmias and sudden death. For a subset of oHCM patients with severe and disabling disease, invasive interventions, such as myectomy and septal ablation in which portions of the enlarged septum are removed, may be appropriate. For patients with severe nHCM implantation of an LVAD or a heart transplant may be the only options.

In recent years, a class of agents known as cardiac myosin inhibitors have emerged as potential treatments for HCM. Two of these agents, mavacamten and aficamten, are approved for the treatment of adults with oHCM. However, there are currently no therapies approved specifically for adult and pediatric HCM patients with MYBPC3 gene mutations, or for those with nonobstructive disease.

Our Solution

We believe TN-201 has the potential to address the underlying biological basis of disease in adult and pediatric HCM patients with MYBPC3 gene mutations. Based on our early clinical data, TN-201 gene therapy has the potential to achieve robust expression of the MYBPC3 gene and to slow or even reverse the course of MYBPC3-associated HCM, including LV hypertrophy. By increasing MyBP-C expression, TN-201 may improve heart functional capacity, stabilize or reverse disease symptoms, reduce the need for invasive treatments and improve survival. As with other AAV-based gene therapies, benefits are expected to be durable and a one-time dose may be sufficient to halt or even reverse disease. TN-201 has received Orphan Drug, Fast Track and Rare Pediatric Disease Designations from the FDA and orphan medicinal product designation from the EC.

The MyPEAK-1 Phase 1b/2 Clinical Trial of TN-201

MyPEAK-1 is a multi-center, open-label clinical trial designed to assess the safety, tolerability and efficacy of a one-time intravenous infusion of TN-201. The trial may enroll up to thirty symptomatic (New York Heart

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Association (NYHA) class II or III) adults (ages 18-75) with low titers of pre-existing AAV9 neutralizing antibodies who have been diagnosed with MYBPC3-associated HCM. Endpoints for the trial include safety and tolerability, pharmacokinetics (PK) (as measured by transgene, mRNA expression and MyBP-C protein level changes via cardiac biopsies), pharmacodynamic (PD) (as measured by imaging and plasma biomarkers), exercise capacity (as measured by a six-minute walk test and cardiopulmonary exercise testing (CPET)) and patient-reported outcomes (as measured by a Kansas City Cardiomyopathy Questionnaire). These assessments are taken at regular intervals during the first year of the study. Patients enrolled in MyPEAK-1 are monitored for an additional four years to gather long-term safety and efficacy data. The trial includes a preventative immunosuppressive regimen at the time of dosing, close safety monitoring, and the gradual tapering of immunosuppressive medications. Two dose levels of TN-201 are being assessed in the trial, 3E13 vg/kg (Cohort 1) and 6E13 vg/kg (Cohort 2). These doses associated with near-maximal efficacy in preclinical studies of a homozygous knock-out model. As per protocol, review by the independent data safety monitoring board (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.

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 had 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 adverse events (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.

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.

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 left ventricular posterior wall thickness (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 left ventricular mass index (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.

Following proactive correspondence with the FDA relating to future development plans for TN-201 the FDA placed MyPEAK-1 on clinical hold requesting an amendment to the protocol primarily to standardize activities related to patient monitoring and management of the immunosuppression regimen across trial sites. We worked swiftly and collaboratively with the FDA to resolve the clinical hold and received notification from the FDA within less than six weeks that the clinical hold was removed and we do not expect this action to have impacted data milestones or development timelines for TN-201.

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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.

Noninterventional Studies in Support of TN-201's Clinical Development

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 the 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.

Preclinical Evidence Supporting TN-201 Clinical Development

In preclinical studies, we systemically administered a mouse surrogate of TN-201 (AAV:mMybpc3 or mTN-201) in two-week-old Mybpc3 knockout (KO) mice. The Mybpc3 KO model develops marked LV hypertrophy, poor cardiac function, and dilation at two weeks of age, comparable to HCM patients with truncating or null mutations. Due to the severe phenotype of the Mybpc3 KO mice and the lack of any MyBP-C protein, this is considered a demanding model to demonstrate efficacy particularly for modeling heterozygous patients, who lack only 35% to 40% of normal sarcomeric MyBP-C protein. Treatment with mTN-201 improved LV hypertrophy and cardiac function compared to their pre-treatment baseline levels, indicating partial reversal of the disease and dramatically extended lifespan. Treated mice exhibited an absolute improvement of ejection fraction (EF) of more than 20% versus untreated controls that eventually increases to more than 30% at 13 months, the last echocardiography measurement. EF and LV hypertrophy (LV mass normalized to body weight) improvements did not diminish over time, suggesting that a single systemic dose may be sufficient for a durable reversal of MYBPC3-associated HCM. Additionally, we observed improvements in LV diameter and ECG measurements. There is also a clear survival benefit with no deaths due to heart failure in the mTN-201 arm and 100% mortality in the untreated control arm out to 20 months following dosing.

In addition, a dose-response relationship has been demonstrated with mTN-201. Weight-based doses, 1E13 vg/kg, 3E13 vg/kg and 1E14 vg/kg, all produced significant improvements in EF, LV hypertrophy, and measures of electrophysiological function (QT interval) at eight months post-injection in the Mybpc3 KO HCM mouse model. The 1E13 vg/kg dose had the lowest levels of efficacy, while the 3E13 vg/kg had high improvement with a mean decrease of hypertrophy of more 5.3 mg/g LV Mass (± 1.3) and a mean improvement of EF of 26% (± 3.7), similar to the 1E14 vg/kg dose, suggesting a plateau in the dose-response curve.

During optimization of our MYBPC3 gene therapies, we discovered a cardiomyocyte-specific promoter, TNP-CM1, with improved performance attributes as compared to the standard cardiac troponin T (cTnT) promoter. In vitro and in vivo analyses confirmed that TNP-CM1 significantly increased expression of the MYBPC3 gene compared to what can be achieved with the standard cTnT promoter.

TN-401: Gene Therapy for PKP2-associated ARVC

We are developing TN-401, an investigational AAV-based gene therapy for the potential treatment of ARVC, also known as arrhythmogenic cardiomyopathy or ACM, caused by mutations to the PKP2 gene. Such mutations are estimated to affect more than 70,000 patients in the U.S. PKP2 mutations result in insufficient expression of a protein needed for the proper functioning of desmosome, a complex that maintains physical connections and electrical signaling between heart muscle cells. As the desmosome structure is impaired, cardiac muscle cells are progressively replaced by fibrofatty tissue and electrical pulses in the heart become unstable, resulting in adverse remodeling and irregular heart rhythms. TN-401 is designed to deliver a working PKP2 gene into heart muscle cells using an AAV9 capsid where the functional PKP2 gene produces the missing protein, restoring function and reversing or slowing progression of disease by addressing the genetic mutation most frequently underlying ARVC.

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Overview of ARVC

ARVC is a chronic, progressive disease with an estimated prevalence in the general population of approximately 1:1000 to 1:5000. It occurs when the structure and electrical signals of cardiomyocytes are disrupted, resulting in irregular heart rhythms and a gradual replacement of heart muscle cells with fatty deposits and fibrotic tissue which can lead to heart failure over time.

Patients with ARVC are typically diagnosed between the ages of 20 and 40 and most commonly present with symptoms related to VAs, particularly abnormally high heart rates known as ventricular tachycardia and premature ventricular contractions (PVCs). These dangerous rhythm abnormalities place patients at increased risk for sudden cardiac arrest or sudden cardiac death. ARVC is a common cause of sudden cardiac arrest in young people, and it is estimated that in up to 23% of cases, the first sign of disease is sudden cardiac death. To reduce the risk of sudden cardiac death, patients with ARVC are typically discouraged from competitive or endurance sports activities and physical exercise may be limited. ARVC patients may also grapple with additional symptoms, including palpitations, lightheadedness, dizziness, and fainting.

Mutations in the PKP2 gene are the most common genetic cause of ARVC, with more than 40% of ARVC patients carrying pathogenic variants. PKP2 protein is an integral component of cell adhesion protein complexes known as desmosomes which connect adjacent cardiomyocytes in the heart. Desmosomes are responsible for maintaining the heart tissue integrity and for stabilizing channels called gap junctions that allow for cellular communication among heart cells, which in turn is important to proper synchronization of cardiomyocyte contractions across the myocardium contributing to each heartbeat. When the PKP2 gene is mutated, reduction of PKP2 protein disrupts structure and function of desmosomes and gap junctions. As a result of these disruptions, cardiomyocytes become more sensitive to the normal mechanical stress of the beating heart, leading to progressive cell loss, inflammation, scar formation, and fat deposition, illustrating the crucial role the PKP2 protein plays in maintaining the structural and functional integrity of heart tissue.

Mutations in the PKP2 gene are commonly heterozygous and inherited in an autosomal dominant fashion, i.e., a mutation in one allele is sufficient to cause the disease. On average, these mutations lead to a reduction of wild-type protein level of about 50%. We believe these findings support the idea that mutations of the PKP2 gene cause human disease through haploinsufficiency and support the hypothesis that gene replacement may address the underlying cause of disease by increasing the levels of functional PKP2 protein.

Following a diagnosis, ARVC patients are typically implanted with an implantable cardioverter defibrillator (ICD) to prevent sudden cardiac arrest by resetting arrhythmias. ICD implantation is currently the only proven effective treatment for preventing sudden cardiac arrest and death in ARVC patients, but ICDs are also associated with complications, including inappropriate interventions. Patients may progress to catheter ablation procedures which have a high rate of recurrent VA and have not been shown to reduce risk of sudden cardiac death or improve survival. ARVC treatment options may also include beta blockers and other anti-arrhythmic or heart failure medications, intended to reduce VAs. However, studies comparing the efficacy of such treatments have not been conducted. Despite the availability of these treatments, clinical heart failure has been documented in up to 40% of ARVC patients and there remains no approved therapies that address the underlying genetic causes of the disease.

Our Solution

TN-401 is our AAV-based gene replacement therapy designed to deliver a fully functional copy of the human PKP2 gene to the hearts of ARVC patients carrying PKP2 mutations. We believe that delivery of a working PKP2 gene to cardiomyocytes represents a promising treatment that can address the underlying genetic cause of this disease. As the disease is most often caused by haploinsufficiency, expression of a functional PKP2 gene to increase PKP2 protein levels in cardiomyocytes is expected to restore proper structure and function of the desmosome. This in turn has the potential to slow and even reverse the progression of disease in patients. The PKP2 gene will be delivered using AAV9 capsid with well-established tropism for the heart and expression of the PKP2 protein will be selective to the heart through use of a cardiomyocyte-specific promoter. TN-401 has received Fast Track and Orphan Drug Designations from the FDA and orphan medicinal product designation from the EC.

The RIDGE-1 Phase 1b/2 Clinical Trial of TN-401

RIDGE-1 is our multi-center, open-label clinical trial designed to assess the safety, tolerability and efficacy of a one-time intravenous infusion of TN-401. The trial permits dosing up to 15 symptomatic (NYHA class I, II or III)

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adults (ages 18-65) with low titers of AAV9 neutralizing antibodies who have been diagnosed with PKP2-associated ARVC and have an ICD. The primary endpoints for the trial include safety and tolerability, PK (as measured by transgene, mRNA and protein expression via cardiac biopsies at 8 weeks and 52 weeks) and PD (as measured by changes in daily PVCs and non-sustained ventricular tachycardia).

Additional endpoints include changes in premature ventricular contractions, frequency of ventricular tachycardia, frequency of ICD shocks or pacing, imaging biomarkers by echo evaluating structural/hemodynamic changes, plasma biomarkers and patient-reported outcomes. The trial will include a preventative immunosuppressive regimen and close safety monitoring, as well as a 5-year follow-up on safety and efficacy. We are evaluating two dose levels of TN-401 in the trial, 3E13 vg/kg (Cohort 1), a dose associated with near-maximal efficacy in preclinical studies, and 6E13 vg/kg (Cohort 2). 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 further characterize dose response and inform dose selection for late-stage clinical trials.

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.

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.

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. 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.

In February 2025, we were awarded a Clinical Grant (Clin2) of $8.0 million from the California Institute for Regenerative Medicine (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 RIDGE-1, which is being conducted at multiple clinical trial sites with ARVC expertise at leading cardiology centers in the U.S. and United Kingdom.

Noninterventional Studies in Support of TN-401's Clinical Development

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

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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 Heart Rhythm Society’s (HRS) 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

Preclinical Evidence Supporting TN-401 Clinical Development Plan

Our preclinical efficacy studies employed a Pkp2 cardiac conditional knockout (Pkp2-cKO) mouse model that simulates key aspects of ARVC including dilation of the right ventricle (RV) and LV, decline in LV heart function, severe ventricular arrhythmia, and early mortality.

In preclinical studies, we systemically administered either TN-401 or a mouse surrogate (referred to interchangeably as a “PKP2 gene therapy”) in Pkp2-cKO mice across a range of dose levels from 1E13 vg/kg to 1E14 vg/kg and observed near maximal efficacy in the mouse model at 3E13 vg/kg. The severity and rapid progression of this disease model, combined with the homozygous gene KO and near complete loss of PKP2 protein in cardiac tissue, resulted in 100% mortality within 4-6 weeks post induction of KO. Whether administered prior to or following disease onset, PKP2 gene therapy demonstrated prevention or attenuation and/or reversal of disease progression, ultimately culminating in improved survival in both modes of treatment. These improvements in disease state were accompanied by restoration of desmosomes and gap junctions at the molecular and cellular level. PKP2 gene therapy was well tolerated in preclinical studies compliant with Good Laboratory Practice (GLP).

Specifically, when administered prior to disease onset, PKP2 gene therapy prevented all ARVC disease characteristics in Pkp2-cKO mice including RV enlargement, LVEF decline, ventricular arrhythmias, and adverse fibrotic remodeling. Even when administered after disease onset in this rapidly progressing model, PKP2 gene therapy attenuated LVEF decline with an average 15% (+/- 5.6%) increase in absolute EF versus the vehicle-treated group and attenuated worsening of VA event frequency and severity. Administration of PKP2 gene therapy also supported a near-complete reversal of RV enlargement leading to a restoration of the wild-type level. The beneficial effects of PKP2 gene therapy have been shown to be dose dependent and durable following a single dose. Survival was also improved in a dose-dependent manner and the effect was sustained for the duration of the study; PKP2 gene therapy extended median lifespan from 4.7 weeks to ≥ 50 weeks, regardless of preventative or post-onset dosing.

Our Clinical-Stage Small Molecule Program

TN-301: HDAC6 Inhibitor Program with Potential Utility in HFpEF and Other Cardiac, Metabolic, Muscular and Pulmonary Diseases

While much of our research, development and manufacturing focus is on cardiac conditions for which genetic medicines such as gene therapy or gene editing can address the underlying cause of disease, our proprietary target discovery and validation capabilities allow us to pursue modality-agnostic drug discovery efforts. These capabilities led to the discovery of cardio-protective properties of HDAC6 inhibition, which in turn led to the development of TN-301, a highly selective small molecule inhibitor of HDAC6 with broad utility in HFpEF and other cardiac, metabolic, muscular and pulmonary diseases.

Initial preclinical testing of our HDAC6 inhibitors in a severely progressive murine model of BAG3-associated DCM demonstrated protection against dilation and stabilization of ejection fraction. Subsequent preclinical testing in multiple HFpEF mouse models then demonstrated improvements in cardiac structure and function, including reversal of LV hypertrophy and diastolic dysfunction. More recently, following the approval of a pan-HDAC inhibitor to slow progression in Duchenne muscular dystrophy, we conducted preclinical comparative studies intended to explore the potential for TN-301 to delay or reverse both skeletal muscle pathology and cardiomyopathy in DMD.

Our work has confirmed that HDAC6 inhibition exerts its benefits on the heart and other organs in the body through a 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,

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and lipid metabolism. These preclinical results and mechanistic insights encourage us to believe that TN-301 and our portfolio of HDAC6 inhibitor molecules 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.

Phase 1 Clinical Trial of TN-301 in Healthy Participants

Following extensive preclinical work to characterize TN-301’s mechanism, we completed a randomized (3:1), double-blind, placebo-controlled Phase 1 clinical trial to assess the safety and tolerability of escalating oral doses of TN-301 in healthy adult participants. Secondary objectives of the clinical trial included assessment of PK and PD measures.

We shared positive data from our Phase 1 clinical trial of TN-301 in healthy participants at the 2023 Heart Failure Society of America (HFSA) Annual Scientific Meeting. The Phase 1 trial enrolled participants in two stages. In Stage 1, participants received single ascending doses (SAD) (1mg – 700mg) and in Stage 2, participants received multiple ascending doses (MAD) (25mg, 100mg and 300mg once daily for 14 days).

TN-301 was generally well tolerated across the broad range of doses studied. Most adverse events were gastro-intestinal related, occurred with similar frequency in the placebo group and did not increase as doses of TN-301 increased. No thrombocytopenia or QT prolongation risk was observed as has been reported from clinical experience with pan-HDAC inhibition (e.g., givinostat).

PK results showed dose-proportional increases in plasma exposure in the SAD and MAD stages of the study with a half-life supportive of once-daily dosing. Increasing TN-301 doses and exposures in both stages of the clinical trial also resulted in corresponding increases in PD effect. Unlike other HDAC enzymes which are found in the cell nucleus, HDAC6 is localized to the cell cytoplasm where it interacts with multiple proteins to coordinate cellular processes. One of the main substrates of HDAC6 inhibition is tubulin. In the Phase 1 clinical trial, acetylated tubulin was evaluated in circulating cells in order to measure target engagement in a robust and reproducible manner. Inhibition of HDAC6 resulted in an increase in acetylated tubulin over baseline. There were no corresponding changes in histone acetylation with TN-301, underscoring the selectivity of TN-301 for HDAC6 and potentially reducing the risk of off target effects observed with less selective HDAC6 inhibitors or pan-HDAC inhibition.

Based on the safety profile, robust target engagement and pharmacokinetics observed in our Phase 1 clinical trial in healthy volunteers, we believe TN-301 is ready for advancement into clinical studies in patients, with HFpEF and DMD being among the most promising potential indications identified to date.

Clinical Potential for TN-301 in HFpEF

Overview of HFpEF

HFpEF is generally defined as heart failure with an EF greater than or equal to 50%. In patients with HFpEF, the LV is stiffened and does not adequately relax, and increased pressure is needed for the ventricle to properly fill. As a result, blood begins to build up inside the left atrium of the heart and eventually swells into the lungs, veins and tissues of the body. HFpEF is a progressive disease in many patients. Symptoms initially include fatigue, shortness of breath, and edema, resulting in reduced physical activity. Over time, this results in a substantial limitation in activities and impact on quality of life, and patients are at risk of premature death.

Patients with HFpEF represent approximately half of all heart failure patients, with prevalence of the disease anticipated to increase by more than 45% by 2030. The increase in HFpEF prevalence is at least in part due to the high overlap of this condition with diabetes and obesity which are also on the rise in the U.S. and globally. At least half of all hospital admissions for heart failure are related to HFpEF and approximately 24% of the HFpEF population is considered to have NYHA Class III or Class IV disease, representing a disease burden that markedly impacts quality of life and limits physical activity. Among patients hospitalized for HFpEF, readmission for heart failure and mortality rates over a five-year period are as high as 40% and 75%, respectively. Historically, HFpEF patients have been prescribed therapies for heart failure with reduced ejection fraction, including diuretics, beta-blockers, and ACE inhibitors, despite limited data demonstrating efficacy or improved outcomes. While recent advances in treatment have been made with the approval of new classes of medications such as the sodium glucose cotransporter 2 (SGLT2) inhibitors and glucagon-like peptide 1 (GLP-1) receptor agonists, HFpEF remains one of the greatest unmet needs in cardiovascular medicine.

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Key aspects of HFpEF disease biology include oxidative stress and inflammation, cardiac fibrosis, cardiac hypertrophy and cardiac stiffness, which all result in diastolic dysfunction, and decreased ability of the heart to fill its chambers during contraction. Defects in glucose tolerance and insulin sensitivity and overall defective metabolism have also been proposed to play a role in HFpEF onset and progression due to high overlap between patients with HFpEF population and those suffering from diabetes and obesity.

Our Solution

Based on our observations of TN-301’s mechanism, we believe TN-301 has the potential to target converging mechanisms that drive HFpEF disease progression, with the potential to slow down or even reverse the symptoms.

Preclinical Evidence Supporting TN-301 Clinical Development in HFpEF

Preclinical studies of TYA-018, a structurally similar and functionally equivalent compound to TN-301, in a relevant murine model that recapitulates systemic and cardiovascular features of HFpEF in humans demonstrated reversal of LV wall thickness, LV mass, LV end diastolic pressure and LV relaxation and filling. Treatment with TYA-018 also resulted in a trend of decreased lung weight, indicative of improvement in pulmonary congestion consistent with the reduction of filling pressure. In addition, we observed an improvement in glucose tolerance, suggesting that treatment with a selective HDAC6 inhibitor may have a positive impact on glucose metabolism, as well as reductions of key biomarkers of inflammation, fibrosis, and cardiac damage. The data overall confirmed that the multi-modal mechanism of action of selective HDAC6 inhibitors, such as TN-301 may address many of the hallmarks of HFpEF.

We also conducted a comparison study of TYA-018, with empagliflozin, an SGLT2 inhibitor approved for HFpEF. TYA-018 reduced LV mass and diastolic pressure and improved diastolic function and glucose tolerance with comparable efficacy to empagliflozin. TYA-018 co-administered with empagliflozin demonstrated additive benefit compared to either agent alone improving several measures of heart function. In the study, empagliflozin achieved efficacy as anticipated based on the data generated in HFpEF patients from large clinical trials, which provides strong validation of our mouse model and suggests that preclinical results may translate to the clinic.

Taken together, these data support the potential for a selective HDAC6 inhibitor such as TN-301 to be used either alone or in combination with SGLT2 inhibitors, as a treatment for patients with HFpEF.

Future Clinical Development of TN-301 in HFpEF

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.

Clinical Potential for TN-301 in DMD

Based on our observations of TN-301’s mechanism and evidence of efficacy for an approved pan-HDAC agent, we are exploring the development of TN-301 for DMD, a condition caused by genetic mutations in the dystrophin 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. Further, DMD-related cardiomyopathy, which develops as healthy heart tissue becomes fibrotic, is the leading cause of death among patients. Based on TN-301’s cardioprotective profile, we believe it may offer differentiated benefit in slowing DMD cardiomyopathy’s progression.

Overview of DMD

DMD is a severe, progressive, and ultimately fatal genetic disorder estimated to impact 15,000 individuals in the U.S. and over 300,000 globally. DMD predominantly affects males as a result of mutations in the dystrophin gene located on the X chromosome. The absence of functional dystrophin, a structural protein essential for maintaining the stability and integrity of muscle cell membranes, results in progressive muscle weakness and degeneration. Muscle fibers become structurally unstable and susceptible to contraction-induced damage, leading to repeated cycles of degeneration and regeneration. These recurrent injury cycles trigger a sustained inflammatory response and over time, the progressive replacement of healthy muscle tissue with fibrotic and adipose tissue leads to worsening muscle weakness and loss of function.

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As the disease progresses, degeneration extends beyond skeletal muscle to involve the cardiac muscle, frequently culminating in heart failure. DMD-related cardiomyopathy is the most common cause of mortality, with most individuals with DMD succumbing to cardiac or respiratory failure between 20 and 30 years of age.

There are presently eight FDA-approved therapeutics for DMD, including a targeted gene therapy aimed at restoring dystrophin and four exon-skipping antisense oligonucleotides which target specific gene mutations to produce shortened, functional dystrophin proteins. Each of these require genetic testing and their efficacy is limited to specific mutations. Two corticosteroid therapies are intended to reduce inflammatory damage, improve muscle strength and slow progression, but are subject to traditional steroid side effects. Givinostat is an oral pan-HDAC inhibitor that has been shown to reduce inflammation and slow muscle loss. While offering the advantage of being appropriate for children over six regardless of genetic variant, givinostat has dose-limiting toxicities such as thrombocytopenia, QT prolongation risk, and gastrointestinal issues. Despite the advances in treatment for DMD, there are no approved therapies that address both the muscle atrophy associated with DMD and DMD cardiomyopathy.

Our Solution

We believe TN-301 has the potential to target converging mechanisms that drive DMD disease progression, slowing the degeneration of both skeletal and cardiac muscle.

Preclinical studies have demonstrated that selective HDAC6 inhibition enhances tubulin acetylation, leading to stabilization of the microtubule network and improved structural integrity of muscle fibers resulting in significant increases in muscle strength and function. In dystrophin-deficient models, HDAC6 inhibition was observed to reduce fibrotic remodeling, leading to an overall improvement in muscle morphology and function. HDAC6 inhibition may also exert indirect anti-inflammatory effects by modulating gene expression networks across muscle fibers, fibroblasts, and immune cells, further limiting secondary damage and supporting regeneration. By stabilizing the cytoskeleton, enhancing autophagy, and reducing fibrosis and inflammation, selective HDAC6 inhibitors address multiple pathogenic pathways implicated in disease progression.

We believe TN-301 may offer dosing and compliance advantages to currently approved treatments. As a once-daily small molecule with an orthogonal mechanism, HDAC6 inhibition may add benefit to existing dystrophin-replacement or anti-inflammatory steroidal regimens, which are administered by infusion or injection.

Preclinical Studies in DMD

At the Muscular Dystrophy Association (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 in mdx mice at both 3 mg/kg and 30 mg/kg compared to vehicle with both doses of TN-301 achieving wildtype (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.

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.

Future Clinical Development of TN-301 in DMD and Other Cardiac, Metabolic and Muscular Diseases

In parallel with seeking opportunities to partner TN-301 for late-stage development and commercialization in large indications such as HFpEF, we plan to explore indications in which it may be possible to demonstrate

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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.

Our Integrated Capabilities

Foundational to our modality-agnostic research and drug discovery efforts are our proprietary integrated capabilities that include disease models, capsid engineering, promoters and regulatory elements, drug delivery and manufacturing. These differentiated capabilities collectively support discovery of novel targets, in vitro optimization and lead validation, in vivo lead characterization, and efficient development, engineering and production of product candidates that, if approved, could address the high unmet need of patients with heart diseases.

Leveraging our extensive in-house capabilities, we are able to take a differentiated and competitively advantageous approach to target identification and validation and preclinical characterization of each of our prospective candidates, which we believe provides us with deeper insights, shortened product development cycles, reduced scientific risks and improved probability of technical and regulatory success for our product candidates relative to others. For example, with regard to our gene therapy candidates, the application of our capsid engineering and promoter design and delivery expertise may enable us to overcome the limitations faced by prior cardiac gene therapy approaches by enabling more precise delivery and more robust gene expression while lowering the risk of off-target effects. Each of our core internal capabilities is described in more detail below:

Disease Models

We have internalized the ability to create and integrate proprietary in vitro and in vivo models within our research organization, which allows us to simulate human heart disease phenotypes. This combination of human in vitro and rodent in vivo models creates significant value to the organization, as singular models of human heart disease may not be adequate to assess the efficacy or safety of novel therapies. Our disease modeling capabilities serve to facilitate the discovery of new leads and to characterize the activity of existing leads as we move through preclinical development.

In Vitro: For our in vitro human iPSC-cardiomyocyte (iPSC-CM) disease models, we use multiple methods to induce phenotypes within cell lines that simulate human diseases and then use these models for high throughput target identification and drug discovery. We have developed our own high-throughput imaging analysis technologies to characterize the impact of drug leads directly on cardiomyocytes and cardiac fibroblasts. Taken together, our advancements in disease modeling, including our practice of characterizing targets using three-dimensional human engineered heart tissues, our ability to produce human iPSC-CMs reliably and at an increasing scale, and our combination of immunostaining, high-resolution imaging and application of machine learning algorithms to support high-throughput phenotypic screening, enhance our ability to both identify and characterize potential product candidates early in the discovery process.

In Vivo: We have to date established approximately 20 rodent heart disease models in pursuit of our early pipeline. Our rodent models represent both in-licensed and novel genetically modified lines, as well as surgically or pharmacologically induced models. Over time, we have developed important insights into the advantages and limitations of specific models and have learned how to optimize experimental design to maximize learnings and de-risk program advancement. This insight influences our preclinical drug development strategies and our discussions with regulatory agencies.

Capsid Engineering

We believe selection of the right capsid for optimal delivery and safety of genetic medicines can make a profound difference in patient safety, therapeutic efficacy, manufacturing productivity and cost of goods. As part of our early product design efforts, we tested AAV9, which has clinically established safety profile and cardiac tropism and proven manufacturability, alongside several other capsids for tropism to cardiomyocytes and for resulting mRNA and protein expression, and in our hands AAV9 proved to be superior to other available capsids. This work contributed to the selection of AAV9 for use with TN-201 and TN-401 and also contributed to the foundations of our novel capsid engineering efforts.

Our goal is to discover, design, and develop novel cardiac-tropic AAV capsids with superior attributes to AAV9 in order to enable more precise targeting of heart cells and to improve the safety profile of future product candidates by reducing tropism for other organs, particularly the liver. We also believe that using capsids that more

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specifically target one cell type over another may help lower cost of goods for such candidates by lowering doses while increasing efficacy. To achieve our goals related to capsid engineering, we have established in-house AAV capsid engineering capabilities and have designed and screened over one billion variants from diverse, proprietary libraries to discover, design, and develop novel capsids to support our programs.

Our approach includes the use of diverse screening methods across a variety of in vitro, in vivo, and in silico systems to enable our ability to identify novel capsids, followed by the application of specific criteria for the selection of novel capsids, including improved tropism for the heart compared to other organs, with a particular interest in de-targeting the liver; improved transduction of specific heart cell types; lower susceptibility to neutralizing antibodies; and comparable manufacturing in both HEK293- and Sf9/rBV-based manufacturing systems. We then evaluate these novel capsids to identify ones that can outperform the relevant parental capsids, which may vary depending on the intended use.

Through these efforts, we have discovered proprietary capsids with superior performance over parental variants across multiple species. These next-generation capsids have improved tropism for the heart compared to other organs and even for specific cells within the heart; improved expression within the heart cells; and lower susceptibility to neutralizing antibodies. We have identified novel capsids capable of equivalent or superior transduction in the heart, liver detargeting and evasion of preexisting neutralizing antibodies as compared to AAV9. We have also generated data that demonstrate that certain of these capsids have a greater ability to improve heart function compared to the same dose of AAV9 in specific disease models.

Overall, these data provide important proof of concept of the potential utility of capsid engineering. We believe our capsid engineering efforts will be critical in supporting the successful clinical development of future product candidates and enabling those product candidates, if approved, to reach more patients.

Promoters and Regulatory Elements

We have created novel promoters and regulatory elements that support our gene therapy and cellular regeneration programs by controlling the expression of genes within the cells. We use these innovations, which are essential to the success of gene therapy, to help ensure more precise and more robust expression of therapeutic payloads in the different cell types of the heart as compared to what can be achieved with currently available methods. We believe our innovations can support successful clinical development in part by improving the efficacy and safety profile of our product candidates. For example, we have developed cardiac-specific promoters that enable more selective and robust expression in the heart as compared to other organs. Specifically, during optimization of TN-201, we developed a cardiomyocyte-specific promoter, TNP-CM1, with improved performance attributes and a shorter length as compared to the standard cTnT promoter. In vitro and in vivo analyses confirmed that TNP-CM1 significantly increased expression of the MYBPC3 gene compared to what can be achieved with the standard cTnT promoter. In addition, in a mouse model we observed 1000-fold selectivity of expression in cardiac tissue relative to other tissues, including skeletal muscle, brain and liver. This shorter, yet effective promoter enabled packaging of full-length MYBPC3 DNA despite the limited capacity of AAV.

Drug Delivery

Delivery of drugs to the heart is widely considered to be an important challenge to successful translation of cardiac gene therapy and regenerative medicines into approved products. In an effort to maximize the success of programs within our diverse pipeline, we have actively explored different routes of administration, as well as different infusion- or injection-based catheters to support more targeted delivery and more efficient uptake of therapies based on viral vectors. For our gene therapy product candidates, including TN-201 and TN-401, we generally need broad distribution across the heart tissue that is best suited to infusion-based approaches. Other programs, such as our TN-101 therapy designed to convert resident fibroblasts into working myocardial cells in the setting of post-ischemic heart failure, require more precise delivery into the heart tissue directly around the scar area of the LV. Thus TN-101 is more suited to injection-based approaches. We believe our drug delivery approaches may widen the therapeutic index of certain product candidates by reducing the dose required for a therapeutic benefit.

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Manufacturing

Our early strategy was to have complete ownership of our process development, analytical development, manufacturing and quality control (QC) for our gene therapy programs. Maintaining internalized manufacturing for these programs increased our understanding of the attributes of our drug substance and drug product, enabled continuous process improvement, consistency (quality and productivity) and supported the manufacturing requirements for our gene therapy programs in clinical development. The resulting innovation and insights are expected to apply not only for rare populations, but also for more prevalent indications, and allow us to be a partner of choice in AAV-based genetic medicines manufacturing. Overall, the internalization of manufacturing efforts provided us with the know-how and capabilities necessary to manage our late-stage drug manufacturing requirements. Today, we rely on a combination of internal manufacturing capabilities and external contract development manufacturing organizations (CDMOs) for our manufacturing requirements and intend to continue to utilize this strategy as our programs progress through various stages of clinical development and future commercialization, if approved.

Competition

The biotechnology and pharmaceutical industries are characterized by rapidly advancing technologies, intense competition and a strong emphasis on intellectual property. We believe our scientific know-how, core internal capabilities and experience provides us with competitive advantages. However, we face substantial competition from many different sources, including large and specialty pharmaceutical companies and biotechnology companies, academic research institutions and governmental agencies, and public and private research institutions. Any product candidate we develop and commercialize will have to compete with existing therapies, as well as therapies currently in development or that may be developed in the future.

Due to the depth and diversity of our pipeline, we may face competition from a variety of companies, including:

TN-201: We believe the principal competition for TN-201 will be programs that address the underlying genetic cause of MYBPC3-associated HCM. Based on publicly available data, we don’t believe any such treatments have received approval from a regulatory agency or reached clinical development. Notwithstanding, we may face competition from treatments for both nHCM and oHCM, including Bristol Myers Squibb’s myosin inhibitor Camzyos and Cytokinetics’ Myqorzo. There are also several other programs at the regulatory review stage or in clinical development for HCM, including Edgewise Therapeutics’ EDG-7500, Lexicon Pharmaceutical's sotagliflozin and Imbria Pharmaceutical's ninerafaxstat.

TN-301: We believe that the principal competition for TN-301 in HFpEF includes agents approved in the U.S. and/or Europe for the treatment of HFpEF, including Novartis’ Entresto and Eli Lilly and Boehringer Ingleheim’s SGLT2 inhibitor, Jardiance and Astra Zeneca’s SGLT2 inhibitor, Farxiga. While there are no approved HDAC6 inhibitors for cardiovascular indications, HFpEF clinical development is an area of robust investment and multiple additional agents for the treatment of HFpEF are in clinical development, including Eli Lilly and Company’s Tirzepatide. We believe that the principal approved in-class competition for TN-301 in DMD is Italfarmaco's Duvyzat. Alternative approved treatments include branded steroids such as Catalyst Pharmaceuticals and Santhera Pharmaceutical's Agamree and PTC Therapeutics' Emflaza, gene therapies such as Sarepta Therapeutics' Elevidys and exon skippers such as Sarepta Therapeutics' Exondys 51 and NS Pharma's Viltepso. There are other potential treatments in development for DMD including Capricor Therapeutics' and NS Pharma's cardiosphere-derived cell therapy, Deramiocel, Edgewise Therapeutics' myosin inhibitor, Sevasemten, and Avidity Bioscience's exon skipper, AOC-1044, and multiple gene therapies and other therapies.

TN-401: We believe the principal competition for TN-401 will be programs that address the underlying genetic cause of PKP2-associated ARVC. Based on publicly available data, we don’t believe any such treatments have received approval from a regulatory agency. However, there are several programs in clinical development for treating the underlying cause of PKP2-associated ARVC, including Rocket Pharmaceutical’s RP-A601 and Lexeo Therapeutics’ LX2020. We may also face competition from therapies and medical devices directed to treat the symptoms of ARVC.

For information regarding the risks related to competition, see “Risk Factors—Risks Related to the Discovery Development, Manufacturing and Commercialization of Our Product Candidates.”

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Intellectual Property

Our success depends in part on our ability to obtain and maintain intellectual property protection for our product candidates, technology, manufacturing processes and know-how, to operate without infringing, misappropriating or otherwise violating the intellectual property or other proprietary rights of others and to prevent others from infringing, misappropriating or otherwise violating our intellectual property or other proprietary rights. To protect our intellectual property rights, we primarily rely on patent and trade secret laws, confidentiality procedures, and agreements, including employee disclosure and invention assignment agreements. Our policy is to seek to protect our proprietary position by, among other methods, pursuing patent applications in the U.S., European Union (EU) and other select jurisdictions related to our proprietary technology, inventions, improvements and product candidates that are important to our business. Our patent portfolio is intended to cover our product candidates and components thereof, their methods of use and processes for their manufacture, medical devices and systems for their administration, our proprietary reagents and assays and any other inventions that are commercially important to our business.

Each of our lead product candidates is covered by at least one or more issued U.S. patents, which are described below. We also have numerous pending patent applications, and will continue to file new patent applications, in the U.S., the EU and other select countries covering our lead product candidates, as well as our early-stage programs in preclinical development. Beyond these issued patents and pending patent applications, our owned and exclusively licensed patent portfolio also covers various aspects of our core capabilities, including our gene delivery expression cassettes and vectors, recombinant capsid proteins, gene editing technology and manufacturing processes.

TN-201: With regard to TN-201, we own four issued U.S. patents covering a recombinant adeno-associated virus (rAAV) virion whose vector genome encodes MYBPC3and methods of using the same for treating cardiomyopathy, one pending non-provisional U.S. patent application, four issued foreign patents in Eurasia, Malaysia, and South Africa, and 24 pending foreign patent applications. The pending foreign patent applications are in a number of jurisdictions, including Australia, Brazil, Canada, China, European Patent Office, Israel, India, Japan, Republic of Korea, Mexico, New Zealand, Saudi Arabia, Singapore, South Africa, and United Arab Emirates. Any U.S. or foreign patents issued from the pending patent applications are expected to expire in 2041, assuming payment of all appropriate maintenance, renewal, annuity or other governmental fees, and without taking potential patent term extensions or adjustments into account. The issued U.S. patents and pending U.S. non-provisional patent applications are directed to various aspects of TN-201, including MYBPC3 gene expression cassettes, rAAV vectors, rAAV viral genomes and methods of using such compositions for therapeutic indications.

TN-301: With regard to TN-301, we own three issued U.S. patents, one pending non-provisional U.S. patent application and two issued foreign patents in Mexico, Japan, and Saudi Arabia and twenty-seven pending foreign patent applications covering TN-301 and various analogs. The pending foreign applications are in a number of jurisdictions, including Australia, Brazil, Canada, China, Eurasia, Europe, Hong Kong, India, Israel, Japan, South Korea, New Zealand, and South Africa. Any U.S. or foreign patents issued from these pending patent applications are expected to expire in 2040, assuming payment of all appropriate maintenance, renewal, annuity or other governmental fees, and without taking potential patent term extensions or adjustments into account. We also own four patent families that cover methods of treatment of various diseases and disorders with TN-301 and its analogs, with one issued U.S. patent, two pending non-provisional U.S. patent applications, one pending PCT application, one pending U.S. provisional patent application, and fifteen foreign patent applications in multiple jurisdictions including Australia, Canada, China, Europe, Hong Kong, Israel, Japan, Mexico, New Zealand, Singapore, South Africa, and Taiwan. Any U.S. or foreign patents issued from the pending applications are expected to expire between 2042 and 2046, assuming payment of all appropriate maintenance, renewal, annuity or other governmental fees, and without taking potential patent term extensions or adjustments into account. We also own one patent family that covers additional HDAC6i compounds, with one pending non-provisional U.S. patent application, one issued foreign patent in Japan, and two pending foreign patent applications in Europe and Canada. Any U.S. or foreign patents issued from these pending patent applications are expected to expire in 2040, assuming payment of all appropriate maintenance, renewal, annuity or other governmental fees, and without taking potential patent term extensions or adjustments into account.

TN-401: With regard to TN-401, we own one issued U.S. patent, three pending U.S. non-provisional patent applications, three issued foreign patents in Japan, South Africa, and Eurasia, and 24 pending foreign patent applications, related to proprietary PKP2 gene expression vectors and methods of use. The pending foreign patent

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applications are in a number of jurisdictions, including Australia, Brazil, Canada, China, Europe, Israel, India, Japan, Republic of Korea, Mexico, New Zealand, Saudi Arabia, Singapore, South Africa, and United Arab Emirates. Any U.S. or foreign patents issued from the pending patent applications are expected to expire in 2041, assuming payment of all appropriate maintenance, renewal, annuity or other governmental fees and without taking potential patent term extensions or adjustments into account. We own one pending U.S. non-provisional patent application and five foreign patent applications in multiple jurisdictions, including Argentina, Europe, Hong Kong, Japan, and Taiwan, related to PKP2 therapeutic treatment methods. Any U.S. or foreign patents issued from the pending patent applications are expected to expire in 2043, assuming payment of all appropriate maintenance, renewal, annuity or other governmental fees, and without taking potential patent term extensions or adjustments into account.

Trade Secrets

In addition to our reliance on patent protection for our technology and product candidates, we also rely on trade secret protection of our confidential information and know-how relating to our proprietary technology, product platforms and product candidates. Through development of internal manufacturing capabilities for AAV-based gene vectors, we have secured proprietary know-how and trade secrets related to our most-advanced programs as well as vector technologies widely applicable to potential AAV therapies. However, trade secrets can be difficult to protect. We seek to protect our trade secrets, proprietary technology and processes, in part, by entering into confidentiality and invention assignment agreements with our employees, consultants, scientific advisors, contractors and other third parties. We also seek to preserve the integrity and confidentiality of our data and trade secrets by maintaining physical security of our premises and physical and electronic security of our information technology systems.

For information regarding the risks related to our intellectual property, see “Risk Factors—Risks Related to Our Intellectual Property.”

Manufacturing

We rely on a combination of internal manufacturing capabilities and external CDMOs for the manufacture of the drug substance and/or drug product of our portfolio programs and intend to continue to utilize this strategy as our programs progress through various stages of clinical development and future commercialization, if approved.

AAV Manufacturing

We fully integrated and internalized AAV manufacturing capabilities to support product candidates emerging from our discovery efforts that utilize AAV for delivery. Simultaneously, we established a Quality Management System to oversee our GxP operations, including Current Good Manufacturing Practices (cGMP), GLP and Good Clinical Practice (GCP).

Our Manufacturing Technology Development Center, or MTDC, includes a Vector Core, upstream and downstream process development labs, as well as assay development and QC capabilities, and is co-located with our research labs in the San Francisco Bay Area. The MTDC does non-GMP work using both the sf9-baculovirus and HEK293 systems and operates at the shake flask, 50L, and 200L scales to support all non-clinical studies, including IND-enabling efficacy, pharmacology, toxicology, and biodistribution, as well as process and analytical work appropriate for later stages of development and approval for our lead gene therapy programs. We also utilize the MTDC to support our work on novel technologies intended to improve the scalability, yield and attributes of AAV manufactured products, including improvements in upstream and downstream processes and novel cell lines; we believe this work has the potential to contribute to our existing clinical-stage and/or future potential gene therapy programs.

In 2021 we established our Genetic Medicines Manufacturing Center, or GMMC, at a time when CDMO capacity was limited and the industry was experiencing quality issues with the available CDMOs. When fully operational, our GMMC can operate at the 200L and 1000L scales to support clinical development activities from first-in-human clinical trials through to late-stage development, and potentially initial commercialization, should regulatory approval be obtained. We successfully utilized the GMMC to produce sufficient drug product to support the current planned dosing for both MyPEAK-1 and RIDGE-1. However, in 2025, due to the available inventory of TN-201 and TN-401 and to support our cost containment initiatives, we decided to decommission the GMMC facility. We will evaluate recommissioning it based on clinical program requirements, or alternatively, will initiate the transfer of our AAV manufacturing process to a CDMO at the appropriate time.

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In addition to our internal manufacturing capabilities, we have also negotiated and entered into master service agreements with multiple CDMOs to provide additional AAV manufacturing and filling capacity, storage, stability program management, and associated risk mitigation. Additionally, we will rely on third parties for certain manufacturing of ancillary materials and release assays, for which we have already secured or intend to secure dual-sourced capacity. To support outsourced manufacturing activities across our gene therapy portfolio, we employ a technical operations staff with the requisite expertise to facilitate technology transfer to and oversight of our CDMOs.

Small Molecule Manufacturing

We rely on various third parties for our cGMP small molecule manufacturing. This external network consists of well-established and reputable CDMOs for our chemistry, manufacturing and control development that have good regulatory standing, suitable manufacturing capacities and capabilities. We will continue to expand this network as appropriate to meet future manufacturing needs for TN-301 and other small molecule product candidates, should such programs advance in the clinic, to regulatory approval and subsequent commercialization.

We source raw materials that are used to manufacture our drug substance from multiple third-party suppliers across the globe. Where appropriate, we stock sufficient quantities of these materials and provide them to our CDMOs so they can manufacture adequate drug substance quantities per our requirements. We also rely on third parties to source materials such as excipients, components and reagents, which are required to manufacture our drug substance and finished drug product.

Government Regulation

Government authorities in the U.S. at the federal, state and local level and in other countries regulate, among other things, the research, development, testing, manufacture, QC, approval, labeling, packaging, storage, record-keeping, promotion, advertising, distribution, post-approval monitoring and reporting, marketing and export and import of biologic and small molecule therapeutic products. Generally, before a new therapeutic product can be marketed, considerable data demonstrating a biologic candidate’s quality, safety, purity and potency, or a small molecule candidate’s quality, safety and efficacy, must be obtained, organized into a format specific for each regulatory authority, submitted for review and approved by the regulatory authority. For biologic candidates, potency is similar to efficacy and is interpreted to mean the specific ability or capacity of the product, as indicated by appropriate laboratory tests or by adequately controlled clinical data obtained through the administration of the product in the manner intended, to effect a given result.

U.S. Biologic and Small Molecule Drug Product Development

In the U.S., the FDA regulates small molecule and biologic therapeutic products under the Food, Drug and Cosmetic Act (FDCA) and the Public Health Service Act (PHSA). Biopharmaceuticals, including both small molecule and biologic products, also are subject to other federal, state and local statutes and regulations. The process of obtaining regulatory approvals and the subsequent compliance with appropriate federal, state, local and foreign statutes and regulations require the expenditure of substantial time and financial resources.

Biologics must be licensed by the FDA through a biologics license application (BLA), and small molecule products must be approved by the FDA through a new drug application (NDA), before they may be legally marketed in the U.S. The process generally involves the following:

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Completion of extensive preclinical studies in accordance with applicable regulations, including studies conducted in accordance with GLP requirements;

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Submission to the FDA of an IND, which must become effective before human clinical trials may begin, and alignment with the FDA on clinical trial design;

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Approval by an independent institutional review board (IRB), or ethics committee at each clinical trial site before each trial may be initiated;

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Performance of adequate and well-controlled human clinical trials in accordance with applicable IND regulations, GCP requirements and other clinical trial-related regulations to establish the safety and potency or efficacy of the investigational product for each proposed indication;

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Submission to the FDA of a BLA or NDA;

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A determination by the FDA within 60 days of its receipt of a BLA or NDA to accept the filing for review;

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Satisfactory completion of a FDA pre-approval inspection of the manufacturing facility or facilities where biologic or small molecule product will be produced to assess compliance with cGMP requirements to assure that the facilities, methods and controls are adequate to preserve the biologic’s identity, strength, purity, potency, and QCs, or the small molecule product’s identity, chemistry, and QCs;

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Potential FDA audit of the preclinical study and/or clinical trial sites that generated the data in support of the BLA or NDA;

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Satisfactory completion of other studies required by the FDA, including immunogenicity, carcinogenicity, genotoxicity, and stability studies;

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FDA review and approval of the BLA or NDA, including consideration of the views of any FDA advisory committee, prior to any commercial marketing or sale of the biologic or small molecule therapeutic in the United States; and

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Compliance with any post-approval requirements, including the potential requirement to implement risk evaluation and mitigation strategies (REMS), and the potential requirement to conduct post-approval studies.

The data required to support a BLA or NDA are generated in two distinct developmental stages: preclinical and clinical. The preclinical and clinical testing and approval process requires substantial time, effort and financial resources, and we cannot be certain that any approvals for any future product candidates will be granted on a timely basis, or at all.

Preclinical Studies and IND

Preclinical studies include laboratory evaluation of product biochemistry, formulation and stability, as well as in vitro and animal studies to assess the potential for toxicity and to establish a rationale for therapeutic use for supporting subsequent clinical testing. The conduct of preclinical studies is subject to federal regulations and requirements, including GLP regulations for safety/toxicology studies. An IND sponsor must submit the results of the preclinical tests, together with manufacturing information, analytical data, any available clinical data or literature and a proposed clinical protocol, among other things, to the FDA as part of an IND. An IND is a request for authorization from the FDA to administer an investigational product to humans and must become effective before human clinical trials may begin. Some long-term preclinical testing, such as animal tests of reproductive adverse events and carcinogenicity, may continue after the IND is submitted. An IND automatically becomes effective 30 days after receipt by the FDA, unless before that time the FDA raises concerns or questions related to one or more proposed clinical trials and places the trial on clinical hold. In such a case, the IND sponsor and the FDA must resolve any outstanding concerns before the clinical trial can begin. As a result, submission of an IND may not result in the FDA allowing clinical trials to commence.

Clinical Trials

The clinical stage of development involves the administration of the investigational product to healthy volunteers or patients under the supervision of qualified investigators, generally physicians not employed by or under the trial sponsor’s control, in accordance with GCP requirements, which include the requirement that all research subjects provide their informed consent for their participation in any clinical trial. Clinical trials are conducted under protocols detailing, among other things, the objectives of the clinical trial, dosing procedures, subject selection and exclusion criteria and the parameters to be used to monitor subject safety and assess efficacy. Each protocol, and any subsequent amendments to the protocol, must be submitted to the FDA as part of the IND. Furthermore, each clinical trial must be reviewed and approved by an IRB for each institution at which the clinical trial will be conducted to ensure that the risks to individuals participating in the clinical trials are minimized and are reasonable in relation to anticipated benefits. The IRB also approves the informed consent form that must be provided to each clinical trial subject or his or her legal representative and must monitor the clinical trial until

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completed. There also are requirements governing the reporting of ongoing clinical trials and completed clinical trial results to public registries.

A sponsor who wishes to conduct a clinical trial outside of the United States may, but need not, obtain FDA authorization to conduct the clinical trial under an IND. If a foreign clinical trial is not conducted under an IND, the sponsor may submit data from the clinical trial to the FDA in support of a BLA or NDA. The FDA will accept a well-designed and well-conducted foreign clinical trial not conducted under an IND if the trial was conducted in accordance with GCP requirements and the FDA is able to validate the data through an onsite inspection if deemed necessary.

Clinical trials in the United States generally are conducted in three sequential phases, known as Phase 1, Phase 2 and Phase 3, and may overlap.

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Phase 1 clinical trials generally involve a small number of healthy volunteers or disease-affected patients who are initially exposed to a single dose and then multiple doses of the product candidate. The primary purpose of these clinical trials is to assess the metabolism, pharmacologic action, tolerability and safety of the drug.

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Phase 2 clinical trials involve studies in disease-affected patients to determine the dose required to produce the desired benefits. At the same time, safety and further pharmacokinetic and pharmacodynamic information is collected, possible adverse effects and safety risks are identified and a preliminary evaluation of efficacy is conducted.

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Phase 3 clinical trials generally involve a large number of patients at multiple sites and are designed to provide the data necessary to demonstrate the effectiveness of the product for its intended use, its safety in use and to establish the overall benefit/risk relationship of the product and provide an adequate basis for product approval. These trials may include comparisons with placebo and/or other comparator treatments. The duration of treatment is often extended to mimic the actual use of a product during marketing.

Post-approval trials, sometimes referred to as Phase 4 clinical trials, may be conducted after initial marketing approval. These trials are used to gain additional experience from the treatment of patients in the intended therapeutic indication. In certain instances, the FDA may mandate the performance of Phase 4 clinical trials as a condition of approval of a BLA or NDA.

Progress reports detailing the results of the clinical trials, among other information, must be submitted at least annually to the FDA and written IND safety reports must be submitted to the FDA and the investigators for serious and unexpected adverse events, findings from other trials suggesting a significant risk to humans exposed to the investigational product, findings from animal or in vitro testing that suggest a significant risk for human subjects and any clinically important increase in the rate of a serious suspected adverse reaction over that listed in the protocol or investigator brochure.

Phase 1, Phase 2 and Phase 3 clinical trials may not be completed successfully within any specified period, if at all. The FDA or the sponsor may suspend or terminate a clinical trial at any time on various grounds, including a finding that the research subjects or patients are being exposed to an unacceptable health risk or non-compliance with GCP requirements. Similarly, an IRB can suspend or terminate approval of a clinical trial at its institution if the clinical trial is not being conducted in accordance with the IRB’s requirements or if the investigational product has been associated with unexpected serious harm to patients. Additionally, some clinical trials are overseen by an independent group of qualified experts organized by the clinical trial sponsor, known as a data safety monitoring board or committee. This group provides authorization for whether a trial may move forward at designated check-points based on access to certain data from the trial. Concurrent with clinical trials, companies usually complete additional animal studies and also must develop additional information about the biochemical and physical characteristics of the investigational product as well as finalize a process for manufacturing the product in commercial quantities in accordance with cGMP requirements. The manufacturing process must be capable of consistently producing quality batches of the product and, among other things, companies must develop methods for testing the identity, strength, quality and purity of the final product. Additionally, appropriate packaging must be selected and tested and stability studies must be conducted to demonstrate that the product candidates do not undergo unacceptable deterioration over their shelf life.

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NDA and BLA Review Process

Following completion of the clinical trials, data is analyzed to assess whether the investigational product is safe and effective for the proposed indicated use or uses. The results of preclinical studies and clinical trials are then submitted to the FDA as part of a BLA for a biologic product or an NDA for a small molecule drug product, along with proposed labeling, biochemistry and manufacturing information to ensure product quality, identity, purity and other relevant data. In short, the BLA or NDA is a request for approval to market the biologic or drug product for one or more specified indications and must contain proof of safety, purity and potency for a biologic, or safety and efficacy for a small molecule drug product. The application may include both negative and ambiguous results of preclinical studies and clinical trials, as well as positive findings. Data may come from company-sponsored clinical trials intended to test the safety and efficacy of a product’s use or from a number of alternative sources, including studies initiated by investigators. To support marketing approval, the data submitted must be sufficient in quality and quantity to establish the safety and efficacy of the investigational product to the satisfaction of the FDA. FDA approval of a BLA or NDA must be obtained before the product may be marketed in the United States.

Under the Prescription Drug User Fee Act (PDUFA), as amended, each BLA or NDA must be accompanied by a user fee. FDA adjusts the PDUFA user fees on an annual basis. According to the FDA’s FY 2026 fee schedule, effective through September 30, 2026, the user fee for an application requiring clinical data, such as a BLA or NDA, is approximately $4.68 million. PDUFA also imposes an annual program fee for each marketed human prescription drug product ($442,213 in 2026) and an annual establishment fee on facilities used to manufacture prescription biologics or small molecular drug products. Fee waivers or reductions are available in certain circumstances, including a waiver of the application fee for the first application filed by a small business. Additionally, no user fees are assessed on BLAs or NDA for products designated as orphan drugs, unless the product also includes a non-orphan indication.

The FDA reviews all submitted BLAs and NDAs before it accepts them for filing and may request additional information rather than accepting the BLA or NDA for filing. The FDA must make a decision on accepting a BLA or NDA for filing within 60 days of receipt. Once the submission is accepted for filing, the FDA begins an in-depth review of the BLA or NDA. Under the goals and policies agreed to by the FDA under PDUFA, the FDA has ten months, from the filing date, in which to complete its initial review of an original BLA or NDA and respond to the applicant, and six months from the filing date of an original BLA or NDA designated for priority review. The FDA does not always meet its PDUFA goal dates for standard and priority BLAs or NDAs, and the review process is often extended by FDA requests for additional information or clarification.

Before approving a BLA or NDA, the FDA will conduct a pre-approval inspection of the manufacturing facilities for the new product to determine whether they comply with cGMP requirements. The FDA will not approve the product unless it determines that the manufacturing processes and facilities are in compliance with cGMP requirements and adequate to assure consistent production of the product within required specifications. The FDA also may audit data from clinical trials to ensure compliance with GCP requirements. Additionally, the FDA may refer applications for novel drug products or drug products which present difficult questions of safety or efficacy to an advisory committee, typically a panel that includes physicians and other experts, for review, evaluation and a recommendation as to whether the application should be approved and under what conditions, if any. The FDA is not bound by recommendations of an advisory committee, but it considers such recommendations when making decisions on approval. The FDA likely will reanalyze the clinical trial data, which could result in extensive discussions between the FDA and the applicant during the review process. After the FDA evaluates a BLA or NDA, it will issue an approval letter or a Complete Response Letter. An approval letter authorizes commercial marketing of the drug product with specific prescribing information for specific indications. A Complete Response Letter indicates that the review cycle of the application is complete and the application will not be approved in its present form. A Complete Response Letter usually describes all of the specific deficiencies in the BLA or NDA identified by the FDA. The Complete Response Letter may require additional clinical data, additional pivotal Phase 3 clinical trial(s) and/ or other significant and time-consuming requirements related to clinical trials, preclinical studies or manufacturing. If a Complete Response Letter is issued, the applicant may either resubmit the BLA or NDA, addressing all of the deficiencies identified in the letter, or withdraw the application. Even if such data and information are submitted, the FDA may decide that the BLA or NDA does not satisfy the criteria for approval. Data obtained from clinical trials are not always conclusive and the FDA may interpret data differently than we interpret the same data.

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Orphan Drugs

Under the Orphan Drug Act, the FDA may grant orphan designation to a drug product intended to treat a rare disease or condition, which is generally a disease or condition that affects fewer than 200,000 individuals in the United States, or more than 200,000 individuals in the United States and for which there is no reasonable expectation that the cost of developing and making the product available in the United States for this type of disease or condition will be recovered from sales of the product.

For biologic or small molecule drug products, an orphan drug designation must be requested before submitting a BLA or NDA. After the FDA grants orphan drug designation, the identity of the therapeutic agent and its potential orphan use are disclosed publicly by the FDA. Orphan drug designation does not convey any advantage in or shorten the duration of the regulatory review and approval process.

If a product that has orphan designation subsequently receives the first FDA approval for the disease or condition for which it has such designation, the product is entitled to orphan drug exclusivity, which means that the FDA may not approve any other applications to market the same drug for the same indication for seven years from the date of such approval, except in limited circumstances, such as a showing of clinical superiority to the product with orphan exclusivity by means of greater effectiveness, greater safety or providing a major contribution to patient care or in instances of drug supply issues. However, competitors may receive approval of either a different product for the same indication or the same product for a different indication but that could be used off-label in the orphan indication. Orphan drug exclusivity also could block the approval of one of our products for seven years if a competitor obtains approval before we do for the same product, as defined by the FDA, for the same indication we are seeking approval, or if a product candidate is determined to be contained within the scope of the competitor’s product for the same indication or disease. If one of our products designated as an orphan drug receives marketing approval for an indication broader than the indication for which it is designated, it may not be entitled to orphan drug exclusivity. Orphan drug status in the European Union has similar, but not identical, requirements and benefits.

In Catalyst Pharms., Inc. v. Becerra, 14 F.4th 1299 (11th Cir. 2021), the court disagreed with the FDA’s longstanding position that the orphan drug exclusivity only applies to the approved use or indication within an eligible disease. On January 24, 2023, the FDA published a notice in the Federal Register to clarify that while the agency complies with the court’s order in Catalyst, the FDA intends to continue to apply its longstanding interpretation of the regulations to matters outside of the scope of the Catalyst order. The Consolidated Appropriations Act of 2026, signed into law in February 2026, codified this longstanding FDA interpretation of the Orphan Drug Act, allowing the FDA to approve multiple versions of the same orphan drug for different subindications and subpopulations.

In June 2024, the U.S. Supreme Court overruled the Chevron doctrine, which gives deference to regulatory agencies’ statutory interpretations in litigation against federal government agencies, such as the FDA, where the law is ambiguous. This landmark Supreme Court decision may invite more stakeholders to bring lawsuits against the FDA and other federal agencies to challenge longstanding decisions and policies, including the FDA’s statutory interpretations of market exclusivities and the “substantial evidence” requirements for drug approvals, which could undermine the FDA's authority and lead to uncertainties in the industry. Further, changes in the leadership of the FDA and other federal agencies under the current administration may lead to new policies and regulatory changes that can impact our clinical development programs and timelines. For example, the FDA has proposed a new process under RDEP to facilitate the approval of drugs to treat rare diseases with very small patient populations with significant unmet medical need and with a known genetic defect that is the major driver of the pathophysiology. We may engage with the FDA for candidates that qualify for this new process, which permits substantial evidence of effectiveness based upon one adequate and well-controlled study with confirmatory evidence.

Expedited Development and Review Programs

The FDA has a fast-track program that is intended to expedite or facilitate the process for reviewing new drug products that meet certain criteria. Specifically, new drug products are eligible for fast-track designation if they are intended to treat a serious or life-threatening condition and preclinical or clinical data demonstrate the potential to address unmet medical needs for the condition. Fast track designation applies to both the product and the specific indication for which it is being studied. The sponsor can request the FDA to designate the product for fast-track status any time before receiving a BLA or NDA approval, but ideally no later than the pre-BLA or pre-NDA meeting.

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Any product submitted to the FDA for marketing, including under a fast-track program, may be eligible for other types of FDA programs intended to expedite development and review, such as priority review, RMAT designation, and accelerated approval. Any product is eligible for priority review if it treats a serious or life-threatening condition and, if approved, would provide a significant improvement in safety and effectiveness compared to available therapies.

A product may also be eligible for accelerated approval, if it treats a serious or life-threatening condition and generally provides a meaningful advantage over available therapies. In addition, it must demonstrate an effect on a surrogate endpoint that is reasonably likely to predict clinical benefit or on a clinical endpoint that can be measured earlier than irreversible morbidity or mortality (IMM), which is reasonably likely to predict an effect on IMM or other clinical benefit. As a condition of approval, the FDA may require that a sponsor of a drug product receiving accelerated approval perform adequate and well-controlled post-marketing clinical trials. If the FDA concludes that a biologic or small molecule drug product shown to be potent or effective for the proposed indication can be safely used only if distribution or use is restricted, it may require such post-marketing restrictions as it deems necessary to assure safe use of the product. In some cases, FDA may limit the scope of the indication.

Additionally, a drug product may be eligible for designation as a breakthrough therapy if the product is intended, alone or in combination with one or more other drug products, to treat a serious or life-threatening condition and preliminary clinical evidence indicates that the product may demonstrate substantial improvement over currently approved therapies on one or more clinically significant endpoints. The benefits of breakthrough therapy designation include the same benefits as fast-track designation, plus intensive guidance from the FDA to ensure an efficient drug development program. Fast track designation, priority review, accelerated approval and breakthrough therapy designation do not change the standards for approval but may expedite the development or approval process. Depending on other factors that impact clinical trial timelines and development, such as our ability to identify and onboard clinical sites and rates of study participant enrollment and drop-out, we may not realize all the benefits of these expedited or accelerated review programs. For accelerated approval, the FDA has the authority to specify conditions for post approval study requirements and can withdraw a product on an expedited basis for noncompliance with post-approval requirements.

Abbreviated Licensure Pathway of Biological Products as Biosimilars or Interchangeable Biosimilars

The Patient Protection and Affordable Care Act (Affordable Care Act or ACA), signed into law in 2010, includes the Biologics Price Competition and Innovation Act of 2009 (BPCIA), which created an abbreviated approval pathway for biological products shown to be highly similar to an FDA-licensed reference biological product. The BPCIA attempts to minimize duplicative testing and thereby lower development costs and increase patient access to affordable treatments. An application for licensure of a biosimilar product must include information demonstrating biosimilarity based upon the following, unless the FDA determines otherwise:

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Analytical studies demonstrating that the proposed biosimilar product is highly similar to the approved product notwithstanding minor differences in clinically inactive components;

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Animal studies (including the assessment of toxicity); and

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A clinical trial or trials (including the assessment of immunogenicity and pharmacokinetic or pharmacodynamic) sufficient to demonstrate safety, purity and potency in one or more conditions for which the reference product is licensed and intended to be used.

In addition, an application must include information demonstrating that:

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The proposed biosimilar product and reference product utilize the same mechanism of action for the condition(s) of use prescribed, recommended or suggested in the proposed labeling, but only to the extent the mechanism(s) of action are known for the reference product;

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The condition or conditions of use prescribed, recommended or suggested in the labeling for the proposed biosimilar product have been previously approved for the reference product;

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The route of administration, the dosage form and the strength of the proposed biosimilar product are the same as those for the reference product; and

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The facility in which the biological product is manufactured, processed, packed or held meets standards designed to assure that the biological product continues to be safe, pure and potent.

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Biosimilarity means that the biological product is highly similar to the reference product notwithstanding minor differences in clinically inactive components, and that there are no clinically meaningful differences between the biological product and the reference product in terms of the safety, purity and potency of the product. In addition, the law provides for a designation of “interchangeability” between the reference and biosimilar products, whereby the biosimilar may be substituted for the reference product without the intervention of the healthcare provider who prescribed the reference product. The higher standard of interchangeability must be demonstrated by information sufficient to show that:

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The proposed product is biosimilar to the reference product;

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The proposed product is expected to produce the same clinical result as the reference product in any given patient; and

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For a product that is administered more than once to an individual, the risk to the patient in terms of safety or diminished efficacy of alternating or switching between the biosimilar and the reference product is no greater than the risk of using the reference product without such alternation or switch.

FDA approval is required before a biosimilar may be marketed in the United States. However, complexities associated with the large and intricate structures of biological products and the process by which such products are manufactured pose significant hurdles to the FDA’s implementation of the law that are still being worked out by the FDA. For example, the FDA has discretion over the kind and amount of scientific evidence—laboratory, preclinical and/or clinical—required to demonstrate biosimilarity to a licensed biological product.

The FDA intends to consider the totality of the evidence provided by a sponsor to support a demonstration of biosimilarity and recommends that sponsors use a stepwise approach in the development of their biosimilar products. Biosimilar product applications thus may not be required to duplicate the entirety of preclinical and clinical testing used to establish the underlying safety and effectiveness of the reference product. However, the FDA may refuse to approve a biosimilar application if there is insufficient information to show that the active ingredients are the same or to demonstrate that any impurities or differences in active ingredients do not affect the safety, purity or potency of the biosimilar product. In addition, as with BLAs, biosimilar product applications will not be approved unless the product is manufactured in facilities designed to assure and preserve the biological product’s safety, purity and potency.

The submission of a biosimilar application does not guarantee that the FDA will accept the application for filing and review, as the FDA may refuse to accept applications that it finds are insufficiently complete. The FDA will treat a biosimilar application or supplement as incomplete if, among other reasons, any applicable user fees assessed under the Biosimilar User Fee Act of 2012 have not been paid. In addition, the FDA may accept an application for filing but deny approval on the basis that the sponsor has not demonstrated biosimilarity, in which case the sponsor may choose to conduct further analytical, preclinical or clinical studies and submit a BLA for licensure as a new biological product.

The timing of final FDA approval of a biosimilar for commercial distribution depends on a variety of factors, including whether the manufacturer of the branded product is entitled to one or more statutory exclusivity periods, during which time the FDA is prohibited from approving any products that are biosimilar to the branded product. The FDA cannot approve a biosimilar application for twelve years from the date of first licensure of the reference product.

Additionally, a biosimilar product sponsor may not submit an application for four years from the date of first licensure of the reference product. A reference product may also be entitled to exclusivity under other statutory provisions. For example, a reference product designated for a rare disease or condition (an orphan drug) may be entitled to seven years of exclusivity, in which case no product that is biosimilar to the reference product may be approved until either the end of the twelve-year period provided under the biosimilarity statute or the end of the seven-year orphan drug exclusivity period, whichever occurs later. In certain circumstances, a regulatory exclusivity period can extend beyond the life of a patent, and thus block biosimilarity applications from being approved on or after the patent expiration date. In addition, the FDA may under certain circumstances extend the exclusivity period for the reference product by an additional six months if the FDA requests, and the manufacturer undertakes, studies on the effect of its product in children, a so-called pediatric extension.

The first biological product determined to be interchangeable with a branded product for any condition of use is also entitled to a period of exclusivity, during which time the FDA may not determine that another product is

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interchangeable with the reference product for any condition of use. This exclusivity period extends until the earlier of: one year after the first commercial marketing of the first interchangeable product; 18 months after resolution of a patent infringement suit against the applicant that submitted the application for the first interchangeable product, based on a final court decision regarding all of the patents in the litigation or dismissal of the litigation with or without prejudice; 42 months after approval of the first interchangeable product, if a patent infringement suit against the applicant that submitted the application for the first interchangeable product is still ongoing; or 18 months after approval of the first interchangeable product if the applicant that submitted the application for the first interchangeable product has not been sued.

Abbreviated NDA Pathway for Generic Drug Products

The Drug Price Competition and Patent Term Restoration Act of 1984, commonly known as “the Hatch-Waxman Act,” established abbreviated FDA approval procedures for drugs that are shown to be bioequivalent to drugs previously approved by the FDA through its NDA process, which are commonly referred to as the “innovator” or “reference” drugs. Approval to market and to distribute these bioequivalent drugs is obtained by filing an abbreviated NDA (ANDA) with the FDA. An ANDA is a comprehensive submission that contains, among other things, data and information pertaining to the active pharmaceutical ingredients (API), drug product formulation, specifications, stability, analytical methods, manufacturing process validation data, QC procedures and bioequivalence. Rather than demonstrating safety and effectiveness, an ANDA applicant must demonstrate that its product is bioequivalent to an approved reference drug. In certain situations, an applicant may submit an ANDA for a product with a strength or dosage form that differs from a reference drug based upon FDA approval of an ANDA Suitability Petition. The FDA will approve an ANDA Suitability Petition if it finds that the product does not raise questions of safety and efficacy requiring new clinical data. ANDAs generally cannot be submitted for products that are not bioequivalent to the referenced drug or that are labeled for a use that is not approved for the reference drug. Applicants seeking to market such products can submit an NDA under Section 505(b)(2) of the FDCA with supportive data from clinical trials.

Post-Approval Requirements

Following approval of a new product, the manufacturer and the approved product are subject to continuing regulation by the FDA, including, among other things, monitoring and record-keeping requirements, requirements to report adverse experiences and comply with promotion and advertising requirements, which include restrictions on promoting drugs for unapproved uses or patient populations, known as “off-label use,” and limitations on industry-sponsored scientific and educational activities. Although physicians may prescribe legally available drugs for off-label uses, manufacturers may not market or promote such uses. Prescription drug promotional materials must be submitted to the FDA in conjunction with their first use. Further, if there are any modifications to the drug product, including changes in indications, labeling or manufacturing processes or facilities, the applicant may be required to submit and obtain FDA approval of a new application or supplement, which may require the development of additional data or preclinical studies and clinical trials.

The FDA may also place other conditions on approvals including the requirement for REMS, to assure the safe use of the product. A REMS could include medication guides, physician communication plans or elements to assure safe use, such as restricted distribution methods, patient registries and other risk minimization tools. Any of these limitations on approval or marketing could restrict the commercial promotion, distribution, prescription or dispensing of products. Product approvals may be withdrawn for non-compliance with regulatory standards or if problems occur following initial marketing.

The FDA may withdraw approval if compliance with regulatory requirements and standards is not maintained or if problems occur after the product reaches the market. Later discovery of previously unknown problems with a product, including adverse events of unanticipated severity or frequency, or with manufacturing processes, or failure to comply with regulatory requirements, may result in revisions to the approved labeling to add new safety information; imposition of post-market studies or clinical studies to assess new safety risks or imposition of distribution restrictions or other restrictions under a REMS program. Other potential consequences include, among other things:

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Restrictions on the marketing or manufacturing of the product, complete withdrawal of the product from the market, or product recalls;

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Warning letters, or holds on post-approval clinical studies;

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Refusal of the FDA to approve pending applications or supplements to approved applications;

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Applications, or suspension or revocation of product license approvals;

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Product seizure or detention, or refusal to permit the import or export of products; or

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Injunctions or the imposition of civil or criminal penalties.

The FDA strictly regulates marketing, labeling, advertising and promotion of products that are placed on the market. Drugs and biologics may be promoted only for the approved indications and in accordance with the provisions of the approved label. The FDA and other agencies actively enforce the laws and regulations prohibiting the promotion of off-label uses, and a company that is found to have improperly promoted off-label uses may be subject to significant liability.

FDA Regulation of Combination Biologic-Medical Device Products

Certain products may be comprised of components, such as biologic components and device components, that would normally be regulated under different types of regulatory authorities and frequently by different Centers at the FDA. These products are known as combination products. Under the FDCA and its implementing regulations, the FDA is charged with assigning a Center with primary jurisdiction, or a lead Center, for review of a combination product. The designation of a lead Center generally eliminates the need to receive approvals from more than one FDA component for combination products, although it does not preclude consultations by the lead Center with other components of the FDA. The determination of which Center will be the lead Center is based on the “primary mode of action” of the combination product. Thus, if the primary mode of action of a biologic-device combination product candidate is attributable to the biologic product candidate, the FDA Center responsible for premarket review of the drug product would have primary jurisdiction for the combination product. The FDA has also established an Office of Combination Products to address issues surrounding combination products and provide more certainty to the regulatory review process. That Office serves as a focal point for combination product issues for agency reviewers and industry. It is also responsible for developing guidance and regulations to clarify the regulation of combination products, and for assignment of the FDA Center that has primary jurisdiction for review of combination products where the jurisdiction is unclear or in dispute.

A combination product with a biologic product candidate as the primary mode of action generally would be reviewed and approved pursuant to the biologic approval processes under the FDCA. In reviewing the BLA application for such a product, however, FDA reviewers in the Center for Biologics Evaluation and Research (CBER) could consult with their counterparts in the device center to ensure that the device component of the combination product meet applicable requirements regarding safety, effectiveness, durability and performance. In addition, under FDA regulations, combination products are subject to cGMP requirements applicable to both biologics and devices, including the Quality System Regulations (QSR) applicable to medical devices. Further, in February 2024, the FDA issued a final rule replacing the QSR with the Quality Management System Regulation (QMSR) which incorporates by reference the quality management system requirements of ISO 13485:2016. The FDA has stated that the standards contained in ISO 13485:216 are substantially similar to those set forth in the existing QSR. This final rule went into effect on February 2, 2026.

We may develop one or more of our biologic product candidates in combination with a novel delivery medical device. Regulatory review of such combination product candidate will increase the timing, cost, and the complexity of the FDA review and approval process, and subject us to additional regulations and exposure to liability. Pending discussion with the FDA, if the medical device is considered a significant risk device under the FDA’s Investigational Device Exemption (IDE) regulations, then we may be required to comply with the IDE regulations for clinical studies in addition to the IND regulations and may be required to submit both an IDE and an IND before commencing clinical testing of the combination product. We cannot provide any assurance regarding how FDA will regulate our combination product, or if we will be successful in obtaining approval for any combination product.

510(k) clearance process

To obtain 510(k) clearance, a pre-market notification is submitted to the FDA demonstrating that the proposed device is substantially equivalent to a previously cleared 510(k) device or a device that was in commercial distribution before May 28, 1976, for which the FDA has not yet required the submission of a Premarket Approval Application (PMA). The FDA’s 510(k) clearance process may take three to twelve months from the date the

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application is submitted and filed with the FDA, but may take longer if FDA requests additional information, among other reasons. In some cases, the FDA may require clinical data to support substantial equivalence. In reviewing a pre-market notification submission, the FDA may request additional information, which may significantly prolong the review process. Notwithstanding compliance with all these requirements, clearance is never assured.

After a device receives 510(k) clearance, any subsequent modification of the device that could significantly affect its safety or effectiveness, or that would constitute a major change in its intended use, will require a new 510(k) clearance or require a PMA. In addition, the FDA may make substantial changes to industry requirements, including which devices are eligible for 510(k) clearance, which may significantly affect the process.

De novo classification process

If a new medical device does not qualify for the 510(k) premarket notification process because no predicate device to which it is substantially equivalent can be identified, the device is automatically classified into Class III. The Food and Drug Administration Modernization Act of 1997 established a different route to market for low to moderate risk medical devices that are automatically placed into Class III due to the absence of a predicate device, called the “Request for Evaluation of Automatic Class III Designation,” or the de novo classification process. This process allows a manufacturer whose novel device is automatically classified into Class III to request down-classification of its medical device into Class I or Class II on the basis that the device presents low or moderate risk, rather than requiring the submission and approval of a PMA. If the manufacturer seeks reclassification into Class II, the manufacturer must include a draft proposal for special controls that are necessary to provide a reasonable assurance of the safety and effectiveness of the medical device. The FDA may reject the reclassification petition if it identifies a legally marketed predicate device that would be appropriate for a 510(k) or determines that the device is not low to moderate risk and requires PMA or that general controls would be inadequate to control the risks and special controls cannot be developed. Obtaining FDA marketing authorization, de novo down-classification, or approval for medical devices is expensive and uncertain, and may take several years, and generally requires significant scientific and clinical data.

PMA approval process

The PMA process, including the gathering of clinical and nonclinical data and the submission to and review by the FDA, can take several years or longer. The applicant must prepare and provide the FDA with reasonable assurance of the device’s safety and effectiveness, including information about the device and its components regarding, among other things, device design, manufacturing, and labeling. PMA applications are subject to an application fee. In addition, PMAs for medical devices must generally include the results from extensive preclinical and adequate and well-controlled clinical trials to establish the safety and effectiveness of the device for each indication for which FDA approval is sought. As part of the PMA review, the FDA will typically inspect the manufacturer’s facilities for compliance with the QMSR, which imposes extensive testing, control, documentation, and other Quality Assurance and GMP requirements.

Other U.S. Regulatory Matters

Manufacturing, sales, promotion and other activities following product approval are also subject to regulation by numerous regulatory authorities in the United States in addition to the FDA, including the Centers for Medicare & Medicaid Services (CMS), other divisions of the Department of Health and Human Services (HHS), the Department of Justice, the Drug Enforcement Administration, the Consumer Product Safety Commission, the Federal Trade Commission, the Occupational Safety & Health Administration, the Environmental Protection Agency, and state and local governments.

For example, in the United States, sales, marketing and scientific and educational programs must also comply with state and federal fraud and abuse laws. These laws include the federal Anti-Kickback Statute, which makes it illegal for any person, including a prescription drug manufacturer (or a party acting on its behalf), to knowingly and willfully solicit, receive, offer or pay any remuneration that is intended to induce or reward referrals, including the purchase, recommendation, order or prescription of a particular drug, for which payment may be made under a federal healthcare program, such as Medicare or Medicaid. Violations of this law are punishable by up to five years in prison, criminal fines, administrative civil money penalties and exclusion from participation in federal healthcare programs. Moreover, the ACA provides that the government may assert that a claim including items or services

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resulting from a violation of the federal Anti-Kickback Statute constitutes a false or fraudulent claim for purposes of the False Claims Act.

Pricing and rebate programs must comply with the Medicaid rebate requirements of the U.S. Omnibus Budget Reconciliation Act of 1990 and more recent requirements in the ACA. If products are made available to authorized users of the Federal Supply Schedule of the General Services Administration, additional laws and requirements apply. Products must meet applicable child-resistant packaging requirements under the U.S. Poison Prevention Packaging Act. Manufacturing, sales, promotion and other activities also are potentially subject to federal and state consumer protection and unfair competition laws.

The distribution of biologic and pharmaceutical products is subject to additional requirements and regulations, including extensive record-keeping, licensing, storage and security requirements intended to prevent the unauthorized sale of pharmaceutical products.

The failure to comply with any of these laws or regulatory requirements subjects firms to possible legal or regulatory action, including fines, penalties, injunctions, requests for recall, and exclusion from participating in government programs. Any action against us for violation of these laws, even if we successfully defend against it, could cause us to incur significant legal expenses and divert our management’s attention from the operation of our business. Changes in regulations, statutes or the interpretation of existing regulations could impact our business and increase our exposure to additional liabilities. For more information, see “Risk Factors— Risks Related to Regulatory Approval and Other Legal Compliance Matters.”

U.S. Data Privacy and Security Laws

In the United States, a broad variety of laws, rules, regulations and standards relating to privacy, data protection and security may apply to our activities, such as state data breach notification laws, state personal data privacy laws (for example, the California Consumer Privacy Act of 2018, as amended by the California Privacy Rights Act (CCPA)), state health information privacy laws, and federal and state consumer protection laws. The CCPA requires covered businesses that process personal information of California residents to disclose their data collection, use, sharing and retention practices, provides California residents with data privacy rights (including the ability to opt out of certain disclosures of personal information including for certain advertising purposes), imposes operational requirements for covered businesses, provides for significant civil penalties for violations as well as a private right of action for certain data breaches and statutory damages. Aspects of the CCPA and its interpretation and enforcement remain uncertain. Although there are limited exemptions for clinical trial data under the CCPA, the CCPA and other similar laws could impact our business activities, depending on their interpretation. Other states have enacted laws similar to the CCPA, and other state legislatures are currently considering, and may pass, their own comprehensive data privacy and security laws, with potentially greater penalties and more rigorous compliance requirements, and laws in all 50 states require businesses, in certain cases, to provide notice to customers whose personal data has been disclosed as a result of a data breach. We will continue to monitor and assess the impact of these state laws, which may impose substantial penalties for violations, impose significant costs for investigation and compliance, allow private class-action litigation and carry significant potential liability for our business. For more information, see “Risk Factors— Risks Related to Regulatory Approval and Other Legal Compliance Matters.” We are subject to stringent laws, rules, regulations, policies, industry standards and contractual obligations regarding data privacy and security and may be subject to additional laws and regulations in jurisdictions into which we expand. Many of these laws and regulations are subject to change and reinterpretation and could result in claims, changes to our business practices, monetary penalties, increased cost of operations or other harm to our business.

U.S. Patent-Term Restoration and Marketing Exclusivity

Depending upon the timing, duration and specifics of FDA approval of any future product candidates, some of our U.S. patents may be eligible for limited patent term extension under the Hatch-Waxman Act. The Hatch-Waxman Act permits restoration of the patent term of up to five years as compensation for patent term lost during product development and FDA regulatory review process. Patent-term restoration, however, cannot extend the remaining term of a patent beyond a total of 14 years from the product’s approval date. The patent-term restoration period is generally one-half the time between the effective date of an IND and the submission date of a BLA or NDA plus the time between the submission date of a BLA or NDA and the approval of that application, except that the review period is reduced by any time during which the applicant failed to exercise due diligence. Only one patent applicable to an approved drug is eligible for the extension and the application for the extension must be

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submitted prior to the expiration of the patent. The United States Patent and Trademark Office (USPTO), in consultation with the FDA, reviews and approves the application for any patent term extension or restoration. In the future, we may apply for restoration of patent term for our currently owned or licensed patents to add patent life beyond its current expiration date, depending on the expected length of the clinical trials and other factors involved in the filing of the relevant BLA or NDA. However, there can be no assurance that our pending patent applications will issue or that we will benefit from any patent term extension or favorable adjustments to the terms of any patents we may own or in-license in the future.

Market exclusivity provisions under the FDCA also can delay the submission or the approval of certain applications. A reference biological product is granted twelve years of data exclusivity from the time of first licensure of the product, and the FDA will not accept an application for a biosimilar or interchangeable product based on the reference biological product until four years after the date of first licensure of the reference product. “First licensure” typically means the initial date the particular product at issue was licensed in the United States. Date of first licensure does not include the date of licensure of (and a new period of exclusivity is not available for) a biological product if the licensure is for a supplement for the biological product or for a subsequent application by the same sponsor or manufacturer of the biological product (or licensor, predecessor in interest or other related entity) for a change (not including a modification to the structure of the biological product) that results in a new indication, route of administration, dosing schedule, dosage form, delivery system, delivery device or strength or for a modification to the structure of the biological product that does not result in a change in safety, purity or potency. Therefore, one must determine whether a new product includes a modification to the structure of a previously licensed product that results in a change in safety, purity or potency to assess whether the licensure of the new product is a first licensure that triggers its own period of exclusivity. Whether a subsequent application, if approved, warrants exclusivity as the “first licensure” of a biological product is determined on a case-by-case basis with data submitted by the sponsor.

The FDCA provides a five-year period of non-patent marketing exclusivity in the United States to the first applicant to gain approval of an NDA for a new chemical entity. A drug is a new chemical entity if the FDA has not previously approved any other new drug containing the same active moiety, which is the molecule or ion responsible for the action of the drug substance. During the exclusivity period, the FDA may not accept for review an ANDA, or a 505(b)(2) NDA submitted by another company for a generic version of such drug where the applicant does not own or have a legal right of reference to all the data required for approval. However, an application may be submitted after four years if it contains a certification of patent invalidity or non-infringement with respect to one or more patents listed for the drug in the FDA’s Approved Drug Products with Therapeutic Equivalence Evaluations publication. The FDCA also provides three years of marketing exclusivity for a NDA, 505(b)(2) NDA or supplement to an existing NDA if new clinical investigations, other than bioavailability studies, that were conducted or sponsored by the applicant are deemed by the FDA to be essential to the approval of the application, for example, new indications, dosages or strengths of an existing drug. This three-year exclusivity covers only the conditions of use associated with the new clinical investigations and does not prohibit the FDA from approving ANDAs for drugs containing the original active agent. Five-year and three-year exclusivity will not delay the submission or approval of a full NDA. However, an applicant submitting a full NDA would be required to conduct or obtain a right of reference to all of the preclinical studies and adequate and well-controlled clinical trials necessary to demonstrate safety and effectiveness or generate such data themselves.

European Union Drug Development

The Clinical Trials Regulation EU No 536/2014 (the Regulation) repealed the Clinical Trials Directive No. 2001/20/EC on January 31, 2022, which harmonizes the processes for assessment and supervision of clinical trials throughout the European Union. Under the Regulation, clinical trial sponsors can use the Clinical Trials Information System (CTIS) from January 31, 2022, but are not required to use it immediately, in line with a three-year transition period. CTIS publishes certain clinical trial information on a searchable public website and supports the flow of information and interactions between clinical trial sponsors and regulatory authorities in European Union Member States, European Economic Area countries, and the EC.

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EU Drug Review and Approval

In the European Economic Area (EEA), which is comprised of the 27 Member States of the European Union (including Norway and excluding Croatia), Iceland and Liechtenstein, medicinal products can only be commercialized after obtaining a Marketing Authorization (MA). There are two types of MAs:

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The Community MA is issued by the EC through the Centralized Procedure, based on the opinion of the Committee for Medicinal Products for Human Use (CHMP), of the European Medicines Agency (EMA), and is valid throughout the entire territory of the EEA. The Centralized Procedure is mandatory for certain types of products, such as biotechnology medicinal products, orphan medicinal products, advanced-therapy medicines such as gene-therapy, somatic cell-therapy or tissue-engineered medicines and medicinal products containing a new active substance indicated for the treatment of HIV, AIDS, cancer, neurodegenerative disorders, diabetes, auto-immune and other immune dysfunctions and viral diseases. The Centralized Procedure is optional for products containing a new active substance not yet authorized in the EEA, or for products that constitute a significant therapeutic, scientific or technical innovation or for products that are in the interest of public health in the European Union.

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National MAs, which are issued by the competent authorities of the Member States of the EEA and only cover their respective territory, are available for products not falling within the mandatory scope of the Centralized Procedure. Where a product has already been authorized for marketing in a Member State of the EEA, this National MA can be recognized in another Member States through the Mutual Recognition Procedure. If the product has not received a National MA in any Member State at the time of application, it can be approved simultaneously in various Member States through the Decentralized Procedure. Under the Decentralized Procedure an identical dossier is submitted to the competent authorities of each of the Member States in which the MA is sought, one of which is selected by the applicant as the Reference Member State (RMS). The competent authority of the RMS prepares a draft assessment report, a draft summary of the product characteristics (SPC) and a draft of the labeling and package leaflet, which are sent to the other Member States (referred to as the Member States Concerned) for their approval. If the Member States Concerned raise no objections, based on a potential serious risk to public health, to the assessment, SPC, labeling or packaging proposed by the RMS, the product is subsequently granted a national MA in all the Member States (i.e., in the RMS and the Member States Concerned).

Under the above-described procedures, before granting the MA, the EMA or the competent authorities of the member states of the EEA make an assessment of the risk-benefit balance of the product on the basis of scientific criteria concerning its quality, safety and efficacy.

Foreign Data Privacy and Security Laws

Outside of the United States, we are subject to extensive legal requirements relating to privacy, data protection, security and the collection, use, transfer and other processing of personal data, and these requirements are continuing to evolve. For example, in the EU, the General Data Protection Regulation (GDPR) imposes stringent operational requirements for processors and controllers of personal data, including transparent and expanded disclosure to data subjects about how their personal data is to be used, limitations on retention of information, mandatory data breach notification requirements, and higher standards for data controllers to demonstrate that they have obtained valid consent for certain data processing activities. We are also subject to the UK GDPR, which implements the GDPR in the UK post-Brexit. Failure to comply with the GDPR or UK GDPR may result in fines up to €20,000,000 (£17.5 million in the UK) or 4% of the total worldwide annual turnover of the preceding financial year, whichever is higher, and other administrative penalties. The GDPR and UK GDPR have increased our responsibility and liability in relation to personal data that we may process, and we may be required to implement additional measures in an effort to comply with the GDPR and UK GDPR and with other laws, rules and regulations in the EEA, United Kingdom (UK) and Switzerland relating to privacy and data protection. If our efforts to comply with GDPR and UK GDPR or other applicable foreign laws, rules and regulations are not successful, or are perceived to be unsuccessful, it could adversely affect our business. For more information, see “Risk Factors—Risks Related to Regulatory Approval and Other Legal Compliance Matters.” We are subject to stringent laws, rules, regulations, policies, industry standards and contractual obligations regarding data privacy and security and may be subject to additional laws and regulations in jurisdictions into which we expand. Many of these laws and regulations

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are subject to change and reinterpretation and could result in claims, changes to our business practices, monetary penalties, increased cost of operations or other harm to our business.

Coverage and Reimbursement

Sales of our products will depend, in part, on the extent to which our products will be covered by third-party payors, such as government health programs, commercial insurance and managed healthcare organizations. In the United States, no uniform policy of coverage and reimbursement for drug products exists. Accordingly, decisions regarding the extent of coverage and amount of reimbursement to be provided for any of our products will be made on a payor-by-payor basis. As a result, the coverage determination process is often a time-consuming and costly process that will require us to provide scientific and clinical support for the use of our products to each payor separately, with no assurance that coverage and adequate reimbursement will be obtained.

The U.S. government, state legislatures, and foreign governments have shown significant interest in implementing cost containment programs to limit the growth of government-paid healthcare costs, including price-controls, restrictions on reimbursement and requirements for substitution of generic products for branded prescription drugs. For example, the ACA contains provisions that may reduce the profitability of drug products through increased rebates for drugs reimbursed by Medicaid programs, extension of Medicaid rebates to Medicaid managed care plans, mandatory discounts for certain Medicare Part D beneficiaries and annual fees based on pharmaceutical companies’ share of sales to federal health care programs. Adoption of general controls and measures, coupled with the tightening of restrictive policies in jurisdictions with existing controls and measures, could limit payments for pharmaceutical drugs.

The Medicaid Drug Rebate Program requires pharmaceutical manufacturers to enter into and have in effect a national rebate agreement with the Secretary of the Department of HHS as a condition for states to receive federal matching funds for the manufacturer’s outpatient drugs furnished to Medicaid patients. The ACA made several changes to the Medicaid Drug Rebate Program, including increasing pharmaceutical manufacturers’ rebate liability and requiring pharmaceutical manufacturers to pay rebates on Medicaid managed care utilization and enlarging the population potentially eligible for Medicaid drug benefits. The American Rescue Plan Act of 2021, beginning January 1, 2024, eliminated the statutory cap on Medicaid Drug Rebate Program rebates that manufacturers pay to state Medicaid programs. Elimination of this cap may require pharmaceutical manufacturers to pay more in rebates than it receives on the sale of products, which could have a material impact on our business. Moreover, there has been heightened governmental scrutiny over the manner in which drug manufacturers set prices for their marketed products, which has resulted in several Congressional inquiries as well as proposed and enacted federal and state legislation designed to, among other things, bring more transparency to product pricing, impose limitations on drug price increases and reform government program reimbursement methodologies for drug products. Changes in the leadership of the Department of HHS and various federal agencies under the new Trump administration may lead to new policies and regulatory changes that can increase our compliance costs and impact our operations.

The Medicare Prescription Drug, Improvement and Modernization Act of 2003 (MMA), established the Medicare Part D program to provide a voluntary prescription drug benefit to Medicare beneficiaries. Under Part D, Medicare beneficiaries may enroll in prescription drug plans offered by private entities that provide coverage of outpatient prescription drugs. Unlike Medicare Part A and B, Part D coverage is not standardized. While all Medicare drug plans must give at least a standard level of coverage set by Medicare, Part D prescription drug plan sponsors are not required to pay for all covered Part D drugs, and each drug plan can develop its own drug formulary that identifies which drugs it will cover and at what tier or level. However, Part D prescription drug formularies must include drugs within each therapeutic category and class of covered Part D drugs, though not necessarily all the drugs in each category or class. Any formulary used by a Part D prescription drug plan must be developed and reviewed by a pharmacy and therapeutic committee. Government payment for some of the costs of prescription drugs may increase demand for products for which we receive marketing approval. However, any negotiated prices for our products covered by a Part D prescription drug plan likely will be lower than the prices we might otherwise obtain. Moreover, while the MMA applies only to drug benefits for Medicare beneficiaries, private payors often follow Medicare coverage policy and payment limitations in setting their own payment rates. Any reduction in payment that results from the MMA may result in a similar reduction in payments from non-governmental payors.

For a drug product to receive federal reimbursement under the Medicaid or Medicare Part B programs, or to be sold directly to U.S. government agencies, the manufacturer must extend discounts to entities eligible to

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participate in the 340B drug pricing program. The required 340B discount on a given product is calculated based on the AMP and Medicaid rebate amounts reported by the manufacturer.

In August 2022, Congress passed the Inflation Reduction Act of 2022 (IRA), which includes prescription drug provisions that have significant implications for the pharmaceutical industry and Medicare beneficiaries, including allowing the federal government to negotiate a maximum fair price for certain high-priced single source Medicare drugs, imposing penalties and excise tax for manufacturers that fail to comply with the drug price negotiation requirements, requiring inflation rebates for all Medicare Part B and Part D drugs, with limited exceptions, if their drug prices increase faster than inflation, and redesigning Medicare Part D to reduce out-of-pocket prescription drug costs for beneficiaries, among other changes. Various stakeholders, including pharmaceutical companies and the Pharmaceutical Research and Manufacturers of America, have initiated lawsuits against the federal government asserting that the price negotiation provisions of the IRA are unconstitutional. Further, the current administration has issued executive orders focused on decreasing prescription drug prices, including directing the Secretary of HHS to establish a mechanism through which American patients can buy drugs directly from manufacturers who sell at a most-favored-nation price and directing the U.S. Trade Representative and Secretary of Commerce to take action to ensure foreign countries are not engaged in practices that purposefully and unfairly undercut market prices and drive price hikes in the U.S. In November 2025, CMS announced a voluntary initiative called the GENEROUS Model (GENErating cost Reductions fOr U.S. Medicaid Model) to introduce the option of most-favored-nation pricing to the Medicaid program, whereby a drug manufacturer may voluntarily offer supplemental rebates to participating state Medicaid programs for a manufacturer’s covered outpatient drugs. Government agreements with pharmaceutical companies and other measures that use most-favored-nation pricing targets for prescription drugs or that increase generic and biosimilar drug entry sooner than expected can have a material adverse effect on our industry, ability to set adequate pricing for new drugs to recover R&D costs, ability to attract potential investors and potential buyers in the future, or the pricing of our approved product in the U.S. and in foreign countries. The impact of such judicial challenges, legislative, executive, and administrative actions and any future healthcare measures and agency rules implemented by the new Trump administration on us and the pharmaceutical industry as a whole is unclear.

In addition, in most foreign countries, the proposed pricing for a drug must be approved before it may be lawfully marketed. The requirements governing drug pricing and reimbursement vary widely from country to country. For example, the European Union provides options for its member states to restrict the range of medicinal products for which their national health insurance systems provide reimbursement, in order to control the prices of medicinal products for human use. A member state may approve a specific price for the medicinal product, or it may instead adopt a system of direct or indirect controls on the profitability of the company placing the medicinal product in the market. There can be no assurance that any country that has price controls or reimbursement limitations for pharmaceutical products will allow favorable reimbursement and pricing arrangements for any of our products. Historically, products launched in the European Union do not follow price structures of the United States and generally, prices tend to be significantly lower.

We are unable to predict the future course of federal or state healthcare legislation in U.S. or foreign legislation directed at containing or lowering the cost of healthcare and prescription drug prices. These and any further changes in the law or regulatory framework that reduce our revenue or increase our costs could have a material and adverse effect on our business, financial condition and results of operations. For more information, see “Risk Factors—Risks Related to Regulatory Approval and Other Legal Compliance Matters.”

Human Capital Resources

As of December 31, 2025, we had 70 full-time employees. Of the full-time employees employed as of December 31, 2025, 52 engaged in research, development and technical operations. 24 of such employees hold Ph.D. or M.D. (or foreign equivalent) degrees and 10 hold other professional degrees such as a J.D. or M.B.A. None of our employees are represented by a labor union or covered under a collective bargaining agreement. We focus on employee engagement and consider our relationship with our employees to be good, in part as measured by relatively high scores from employee surveys.

Our human capital resources objectives include, as applicable, identifying, recruiting, retaining, incentivizing and integrating our existing and new employees, advisors and consultants. The principal purposes of our equity and cash incentive plans are to attract, retain and reward personnel through the granting of stock-based and cash-based compensation awards, in order to increase stockholder value and the success of our company by motivating such

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individuals to perform to the best of their abilities and achieve our objectives. In addition, we provide a variety of programs and services to help employees meet and balance their needs at work, at home and in life, including healthcare, insurance and other benefit plans. We regularly assess our benefit programs, employee engagement and turnover, recruitment initiatives, workforce diversity and other matters relevant to human capital management and review those results with our board of directors on a periodic basis.

We are an equal opportunity employer and maintain policies that prohibit unlawful discrimination based on race, color, religion, gender, sexual orientation, gender identity/expression, national origin/ancestry, age, disability, marital and veteran status. We employ a diverse workforce that, as December 31, 2025, was approximately 60% non-white and 51% women based on our employees’ voluntary self-identification. We strive to create a collaborative culture that fosters internal engagement around our company and our mission to discover, develop and deliver curative therapies that address the underlying drivers of heart disease.

Our mission is to foster and create a unique culture where belonging and empowerment are at the forefront of our community. We advocate for diverse perspectives and encourage employees to be authentic, inclusive, and respectful to each other. We discourage behaviors that do not have a positive impact on our community or support our mission to discover, develop, and deliver curative therapies that target the underlying causes of heart disease.

Corporate Information

We were incorporated in Delaware in August 2016. Our principal executive offices are located at 171 Oyster Point Boulevard, 5th Floor, South San Francisco, California 94080. Our telephone number is (650) 825-6990. We maintain a site on the worldwide web at www.tenayatherapeutics.com; however, information found on our website is not incorporated by reference into this report.

Investors and others should note that we may announce material information to the public through filings with the SEC, our website (www.tenayatherapeutics.com), press releases, public conference calls, and public webcasts. We use these channels, as well as social media, to communicate with the public about us, our product candidates and other matters. As such, investors, the media and others are encouraged to review the information disclosed through our social media and other channels listed above as such information could be deemed to be material information. Please note that this list may be updated from time to time.

We make available free of charge on or through our website our Securities and Exchange Commission (SEC) filings, including our annual report on Form 10-K, quarterly reports on Form 10-Q, current reports on Form 8-K and amendments to those reports filed or furnished pursuant to Section 13(a) or 15(d) of the Exchange Act, as soon as reasonably practicable after we electronically file such material with, or furnish it to, the SEC. The SEC maintains a site on the worldwide web that contains reports, proxy and information statements and other information regarding our filings at www.sec.gov.

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