Tenaya Therapeutics Doses First Patient in RIDGE™-1 Phase 1b Clinical Trial of TN-401 for the Treatment of PKP2-Associated Arrhythmogenic Right Ventricular Cardiomyopathy
Tenaya Therapeutics (NASDAQ: TNYA) has dosed the first patient in its RIDGE-1 Phase 1b clinical trial of TN-401, a gene therapy treatment for PKP2-Associated Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC). The trial, currently enrolling at six U.S. centers, will assess safety and efficacy of a one-time intravenous infusion in up to fifteen adults with PKP2-associated ARVC. TN-401 uses AAV9 capsid to deliver functional PKP2 genes to heart cells, aiming to address the underlying cause of the disease. Initial clinical data is expected in 2025. The first dose being tested is 3E13 vg/kg, which showed near maximal efficacy in preclinical studies.
Tenaya Therapeutics (NASDAQ: TNYA) ha somministrato il primo paziente nel suo studio clinico RIDGE-1 di Fase 1b per TN-401, un trattamento genico per la cardiomiopatia aritmogena ventricolare destra associata a PKP2 (ARVC). Lo studio, attualmente in fase di arruolamento in sei centri negli Stati Uniti, valuterà la sicurezza e l'efficacia di un'infusione endovenosa unica in fino a quindici adulti con ARVC associata a PKP2. TN-401 utilizza il capsid AAV9 per fornire geni PKP2 funzionali alle cellule cardiache, mirando a affrontare la causa sottostante della malattia. I dati clinici iniziali sono attesi nel 2025. La prima dose in fase di test è di 3E13 vg/kg, che ha mostrato un'efficacia quasi massima negli studi preclinici.
Tenaya Therapeutics (NASDAQ: TNYA) ha dosificado al primer paciente en su ensayo clínico RIDGE-1 de la Fase 1b de TN-401, un tratamiento de terapia génica para la cardiomiopatía arritmogénica del ventrículo derecho asociada a PKP2 (ARVC). El estudio, que actualmente está reclutando en seis centros de EE. UU., evaluará la seguridad y eficacia de una infusión intravenosa única en hasta quince adultos con ARVC asociada a PKP2. TN-401 utiliza un capsídeo AAV9 para entregar genes PKP2 funcionales a las células del corazón, con el objetivo de abordar la causa subyacente de la enfermedad. Se esperan datos clínicos iniciales en 2025. La primera dosis que se está probando es de 3E13 vg/kg, que mostró una eficacia casi máxima en estudios preclínicos.
테나야 치료학(Tenaya Therapeutics) (NASDAQ: TNYA)가 TN-401의 RIDGE-1 1상 b 임상 시험에서 첫 번째 환자에게 투약했습니다. TN-401은 PKP2 관련 심실 비대증(ARVC)을 치료하기 위한 유전자 요법입니다. 현재 미국 내 6개 센터에서 참가자를 모집 중인 이 임상 시험은 PKP2 관련 ARVC를 가진 최대 15명의 성인에게 단일 정맥 주입의 안전성과 유효성을 평가할 예정입니다. TN-401은 AAV9 캡시드를 사용하여 심장 세포에 기능적인 PKP2 유전자를 전달하여 질병의 근본 원인을 해결하는 것을 목표로 합니다. 초기 임상 데이터는 2025년에 예상됩니다. 테스트 중인 첫 번째 용량은 3E13 vg/kg로, 전임상 연구에서 거의 최대의 유효성을 보였습니다.
Tenaya Therapeutics (NASDAQ: TNYA) a administré la première dose à un patient dans son essai clinique RIDGE-1 de phase 1b de TN-401, un traitement par thérapie génique pour la cardiomyopathie arythmogène du ventricule droit associée au PKP2 (ARVC). L'essai, qui recrute actuellement dans six centres aux États-Unis, évaluera la sécurité et l'efficacité d'une infusion intraveineuse unique chez jusqu'à quinze adultes atteints d'ARVC associée au PKP2. TN-401 utilise une capside AAV9 pour délivrer des gènes PKP2 fonctionnels aux cellules cardiaques, visant à traiter la cause sous-jacente de la maladie. Les premières données cliniques sont attendues en 2025. La première dose en cours d'évaluation est de 3E13 vg/kg, qui a montré une efficacité quasi maximale lors des études précliniques.
Tenaya Therapeutics (NASDAQ: TNYA) hat den ersten Patienten in seiner RIDGE-1 Phase 1b-Studie mit TN-401 dosiert, einer Gentherapie zur Behandlung der PKP2-assoziierten arrythmogenen rechtsventrikulären Kardiomyopathie (ARVC). Die Studie, die derzeit an sechs US-Zentren rekrutiert, wird die Sicherheit und Wirksamkeit einer einmaligen intravenösen Infusion bei bis zu fünfzehn Erwachsenen mit PKP2-assoziierter ARVC bewerten. TN-401 verwendet die AAV9-Kapsel, um funktionale PKP2-Gene in Herzmuskelzellen zu übertragen, mit dem Ziel, die zugrunde liegende Ursache der Krankheit anzugehen. Erste klinische Daten werden für 2025 erwartet. Die erste getestete Dosis beträgt 3E13 vg/kg, die in präklinischen Studien nahezu maximale Wirksamkeit zeigte.
- Successful initiation of Phase 1b clinical trial with first patient dosed
- Preclinical studies showed promising results with disease progression reversal
- Trial already enrolling at six centers with potential expansion
- Non-interventional study ongoing at 20 clinical sites across multiple countries
- Initial clinical data won't be available until 2025
- initial enrollment of only fifteen patients
- Sequential dosing requirement for first three patients may slow trial progress
Insights
The initiation of TN-401's Phase 1b trial marks a significant milestone in addressing PKP2-associated ARVC, a serious cardiac condition. The trial's design shows promising potential with several key strengths:
- The selected dose of 3E13 vg/kg demonstrated near-maximal efficacy in preclinical studies
- The AAV9 viral vector has a proven safety record and showed superior performance in preclinical testing
- The trial spans multiple centers and includes comprehensive safety monitoring
The preclinical data is particularly encouraging, showing normalization of heart rhythms and disease reversal. The multi-center approach across 6 U.S. sites, supported by a parallel natural history study across 20 international locations, provides a robust framework for data collection. However, investors should note that initial data won't be available until 2025 and as with all early-stage gene therapy trials, success is not guaranteed.
This development positions Tenaya strategically in the gene therapy space for cardiac diseases. The addressable market for ARVC treatments represents a significant opportunity, as PKP2 mutations are the most common genetic cause of this condition. The company's approach of combining the clinical trial with a natural history study strengthens their market position and data collection capabilities.
The trial's design targeting patients with ICDs and increased arrhythmia risk creates a well-defined patient population, potentially streamlining the path to market. If successful, TN-401 could establish Tenaya as a leader in cardiac gene therapy, a relatively untapped market segment. The extensive international clinical site network also suggests strong potential for global commercialization.
TN-401 AAV9-based Gene Therapy Designed to Deliver Fully Functional PKP2 Gene with the Aim of Increasing Protein Levels to Address Underlying Disease
RIDGE-1 Currently Enrolling at Six Centers; Observational Natural History and Seroprevalence Study of PKP2-associated ARVC Adults Continues Enrollment at 20 Clinical Sites in the U.S., UK and Europe
Initial Clinical Data for RIDGE-1 Anticipated in 2025
SOUTH SAN FRANCISCO, Calif., Nov. 25, 2024 (GLOBE NEWSWIRE) -- Tenaya Therapeutics, Inc. (NASDAQ: TNYA), a clinical-stage biotechnology company with a mission to discover, develop and deliver potentially curative therapies that address the underlying causes of heart disease, today announced that the first patient has been dosed with TN-401 gene therapy in the RIDGE-1 Phase 1b clinical trial at the University of California, San Francisco. Tenaya currently anticipates sharing initial data from the RIDGE-1 trial in 2025.
TN-401 is being developed for the treatment of arrhythmogenic right ventricular cardiomyopathy (ARVC, also known as arrhythmogenic cardiomyopathy or ACM) caused by mutations in the plakophilin-2 (PKP2) gene. PKP2 gene mutations result in insufficient levels of critical proteins needed to maintain the structural integrity and cell-to-cell signaling of heart muscle cells. TN-401 gene replacement therapy is designed to deliver a functional PKP2 gene into heart muscle cells using an adeno associated virus serotype 9 (AAV9) capsid. In preclinical studies, the new, healthy PKP2 gene was successfully integrated into heart cells where it produced the missing protein to slow or even reverse the course of disease. Compared to untreated in vivo knock-out models, TN-401 normalized heart rhythms, reversed disease progression and extended survival following a single dose.
“People living with ARVC frequently experience dangerous arrhythmias and are at risk for developing heart failure, cardiac arrest and sudden death. To minimize their risk, ARVC patients live with significant activity restrictions, take chronic medications, and require interventions that together negatively impact their quality of life but don’t address the underlying problem of a defective gene,” said Vasanth Vedantham, M.D., Ph.D., Professor of Medicine, Cardiac Electrophysiologist, Director of Cardiovascular Genetics at the University of California, San Francisco and an investigator for the RIDGE-1 Phase 1b clinical trial. “PKP2 genetic mutations are the most common single gene cause of ARVC and unlike existing treatments for ARVC, TN-401 gene therapy seeks to directly address the underlying cause of disease by delivering a fully functional copy of PKP2 to the heart.”
The RIDGE-1 Phase 1b clinical trial is a multi-center, open-label, dose escalation study being conducted in the U.S. and UK. RIDGE-1 will assess the safety, tolerability and preliminary clinical efficacy of a one-time intravenous infusion of TN-401. The trial will seek to enroll up to fifteen adults who have been diagnosed with PKP2-associated ARVC, have an implantable cardioverter defibrillator (ICD) and are at increased risk for arrhythmias as determined by premature ventricular contraction count during screening.
The first dose of TN-401 being assessed in the RIDGE-1 clinical trial is 3E13 vg/kg, a dose that was associated with near maximal efficacy in preclinical studies. The first three patients will be dosed on a sequential basis. Once three patients have been dosed at the 3E13 vg/kg level, a panel of independent safety reviewers will advise on plans to dose escalate and/or expand enrollment of the initial cohort dosing in parallel.
“Initiation of this first-in-human study of TN-401 is a significant milestone for Tenaya and we are grateful for the ongoing support received from our trial sites, advocacy organizations, patients and families in our efforts to advance a novel gene replacement therapy for PKP2-associated ARVC,” said Whit Tingley, M.D., Ph.D., Tenaya’s Chief Medical Officer. “We believe TN-401 has best-in-class potential due to its differentiated construct, which utilizes an AAV9 capsid to deliver a fully functioning PKP2 gene directly to heart cells. We selected AAV9 capsid due to its extensive track record and in preclinical studies it outperformed other capsids and TN-401 restored PKP2 levels in a knockout model, leading to reductions in arrhythmia frequency and severity, and halted disease progression.”
The RIDGE-1 clinical trial is currently enrolling patients at six leading U.S. centers specializing in ARVC care. To learn more about gene therapy for ARVC and participation in the RIDGE-1 study, please visit ARVCstudies.com or ClinicalTrials.gov (NCT06228924). In 2022, Tenaya initiated a non-interventional global natural history and seroprevalence study of adults with PKP2-assocated ARVC (NCT06311708). The RIDGE study continues to enroll participants at more than 20 clinical sites in the U.S., UK, France, Germany, Italy and Sweden.
About PKP2-Associated ARVC
Plakophilin-2 (PKP2) mutations are the most common genetic cause of arrhythmogenic right ventricular cardiomyopathy (ARVC, also known as arrhythmogenic cardiomyopathy or ACM), estimated to represent approximately 40 percent of the overall ARVC population. The prevalence of PKP2-associated ARVC is estimated at more than 70,000 people in the U.S. alone.
In PKP2-associated ARVC, mutations of the PKP2 gene results in insufficient expression of a protein needed for the proper functioning of the desmosomal complex that maintains physical connections and electrical signaling between heart muscle cells. As the desmosome structure degrades, cardiac muscle cells are replaced by fibrofatty tissue and electrical pulses in the heart become unstable, resulting in irregular heart rhythms. ARVC symptoms include arrhythmias, palpitations, lightheadedness, dizziness and fainting. It is typically diagnosed before age 40, and sudden cardiac arrest due to life-threatening ventricular arrhythmias is frequently the first manifestation of disease. Current treatments include anti-arrhythmic medications, implantable cardioverter-defibrillators (ICDs) and ablation procedures, which do not address the underlying genetic cause of disease.
About TN-401 Gene Therapy
TN-401 is an investigational AAV9-based gene therapy being developed for the treatment of ARVC due to mutations in the PKP2 gene. AAV9 was selected as the vector for delivery of Tenaya’s PKP2 gene therapy based on its extensive clinical and commercial safety record and demonstrated ability to target heart muscle cells. In preclinical studies, Tenaya has shown that a single dose of TN-401 restored healthy levels of PKP2 protein, normalized heart rhythms, improved right and left ventricular size and function and extended survival.
Tenaya is conducting the RIDGE-1 Phase 1b clinical trial of TN-401 in patients with PKP2-associated ARVC. To support TN-401’s clinical development, the company is currently enrolling the RIDGE global non-interventional study to collect natural history and AAV9 antibody (seroprevalence) data among ARVC patients carrying PKP2 gene mutations. TN-401 has received Orphan Drug and Fast Track Designations from the FDA.
About Tenaya Therapeutics
Tenaya Therapeutics is a clinical-stage biotechnology company committed to a bold mission: to discover, develop and deliver potentially curative therapies that address the underlying drivers of heart disease. Tenaya employs a suite of integrated internal capabilities, including modality agnostic target validation, capsid engineering and manufacturing, to generate a portfolio of genetic medicines aimed at the treatment of both rare genetic disorders and more prevalent heart conditions. Tenaya’s pipeline includes TN-201, a gene therapy for MYBPC3-associated hypertrophic cardiomyopathy (HCM), TN-401, a gene therapy for PKP2-associated arrhythmogenic right ventricular cardiomyopathy (ARVC), TN-301, a small molecule HDAC6 inhibitor intended for heart failure with preserved ejection fraction (HFpEF), and multiple early-stage programs in preclinical development. For more information, visit www.tenayatherapeutics.com.
Forward Looking Statements
This press release contains forward-looking statements as that term is defined in Section 27A of the Securities Act of 1933 and Section 21E of the Securities Exchange Act of 1934. Statements in this press release that are not purely historical are forward-looking statements. Words such as “anticipates,” “will,” “believe” and similar expressions are intended to identify forward-looking statements. Such forward-looking statements include, among other things, the clinical, therapeutic and commercial potential of, and expectations regarding TN-401; the planned timing to report initial data from RIDGE-1 and related focus of the data readout; and statements made by Tenaya’s Chief Medical Officer. The forward-looking statements contained herein are based upon Tenaya’s current expectations and involve assumptions that may never materialize or may prove to be incorrect. These forward-looking statements are neither promises nor guarantees and are subject to a variety of risks and uncertainties, including but not limited to: the timing and progress of RIDGE-1; the potential failure of TN-401 to demonstrate safety and/or efficacy in clinical testing; availability of RIDGE-1 data at the referenced time; the potential for any RIDGE-1 clinical trial results to differ from preclinical, interim, preliminary, topline or expected results; risks associated with the process of discovering, developing and commercializing drugs that are safe and effective for use as human therapeutics and operating as an early stage company; Tenaya’s continuing compliance with applicable legal and regulatory requirements; Tenaya’s ability to raise any additional funding it will need to continue to pursue its product development plans; Tenaya’s reliance on third parties; Tenaya’s manufacturing, commercialization and marketing capabilities and strategy; the loss of key scientific or management personnel; competition in the industry in which Tenaya operates; Tenaya’s ability to obtain and maintain intellectual property protection for its product candidates; general economic and market conditions; and other risks. Information regarding the foregoing and additional risks may be found in the section entitled “Risk Factors” in documents that Tenaya files from time to time with the Securities and Exchange Commission. These forward-looking statements are made as of the date of this press release, and Tenaya assumes no obligation to update or revise any forward-looking statements, whether as a result of new information, future events or otherwise, except as required by law.
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FAQ
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