Tenaya Therapeutics Announces Updates on TN-201 Gene Therapy Program for MYBPC3-associated HCM
Tenaya Therapeutics has provided updates on its TN-201 gene therapy program for MYBPC3-associated hypertrophic cardiomyopathy (HCM). The company has completed dosing of the first three patients in Cohort 1 of the MyPEAK-1 clinical trial at the 3E13 vg/kg dose, with no unexpected events or toxicities observed. An independent Data and Safety Monitoring Board (DSMB) has recommended proceeding with dose escalation to 6E13 vg/kg for Cohort 2, which is now enrolling.
Tenaya has implemented protocol changes, including adding a baseline biopsy, expanding eligibility criteria, and increasing the potential number of patients in the dose expansion portion. The company plans to report initial data from Cohort 1 in December 2024, focusing on safety, tolerability, and biomarker analyses.
Additionally, Tenaya presented data on the disease burden for children and adolescents with MYBPC3-associated HCM, highlighting the high cumulative lifetime risk of severe events and the need for new genetic medicines.
Tenaya Therapeutics ha fornito aggiornamenti sul programma di terapia genica TN-201 per l'ipertrofia cardiomiopatica associata a MYBPC3 (HCM). L'azienda ha completato la somministrazione ai primi tre pazienti nel Coorte 1 del trial clinico MyPEAK-1 con la dose di 3E13 vg/kg, senza eventi inaspettati o tossicità osservati. Un Comitato Indipendente di Monitoraggio dei Dati e della Sicurezza (DSMB) ha raccomandato di procedere con l'aumento della dose a 6E13 vg/kg per il Coorte 2, che è attualmente in fase di arruolamento.
Tenaya ha implementato modifiche al protocollo, tra cui l'aggiunta di una biopsia baseline, l'espansione dei criteri di idoneità e l'aumento del numero potenziale di pazienti nella parte di espansione della dose. L'azienda prevede di riportare dati iniziali dal Coorte 1 a dicembre 2024, concentrandosi sulla sicurezza, tollerabilità e analisi dei biomarcatori.
Inoltre, Tenaya ha presentato dati sul carico della malattia per bambini e adolescenti con HCM associata a MYBPC3, evidenziando l'elevato rischio cumulativo di eventi gravi nel corso della vita e la necessità di nuovi farmaci genetici.
Tenaya Therapeutics ha proporcionado actualizaciones sobre su programa de terapia génica TN-201 para la cardiomiopatía hipertrofia asociada a MYBPC3 (HCM). La compañía ha completado la dosificación de los primeros tres pacientes en el Cohorte 1 del ensayo clínico MyPEAK-1 con la dosis de 3E13 vg/kg, sin eventos inesperados ni toxicidades observadas. Un Comité Independiente de Monitoreo de Datos y Seguridad (DSMB) ha recomendado proceder con la escalada de la dosis a 6E13 vg/kg para el Cohorte 2, que ya está reclutando.
Tenaya ha implementado cambios en el protocolo, incluyendo la adición de una biopsia basal, la ampliación de los criterios de elegibilidad y el aumento del número potencial de pacientes en la parte de expansión de dosis. La compañía planea informar datos iniciales del Cohorte 1 en diciembre de 2024, centrándose en la seguridad, tolerabilidad y análisis de biomarcadores.
Además, Tenaya presentó datos sobre la carga de la enfermedad para niños y adolescentes con HCM asociada a MYBPC3, destacando el alto riesgo acumulativo de eventos severos a lo largo de la vida y la necesidad de nuevos medicamentos genéticos.
Tenaya Therapeutics는 MYBPC3 관련 비대 심근병증(HCM)을 위한 TN-201 유전자 요법 프로그램의 업데이트를 제공했습니다. 이 회사는 MyPEAK-1 임상 시험의 Cohort 1에서 3E13 vg/kg 용량으로 첫 세 환자의 투여를 완료했으며, 예상치 못한 사건이나 독성은 관찰되지 않았습니다. 독립 데이터 및 안전 모니터링 위원회(DSMB)는 Cohort 2를 위한 6E13 vg/kg 용량 증가를 진행할 것을 권장했습니다. 현재 해당 코호트는 모집 중입니다.
Tenaya는 기본 생검 추가, 자격 기준 확대, 용량 증가 부분에서의 환자 수 잠재적 증대 등 프로토콜 변경을 구현했습니다. 이 회사는 2024년 12월에 Cohort 1의 초기 데이터를 보고할 계획이며, 안전성, 내약성 및 바이오마커 분석에 초점을 맞출 것입니다.
또한 Tenaya는 MYBPC3 관련 HCM을 가진 아동 및 청소년의 질병 부담에 대한 데이터를 발표하며 심각한 사건의 누적 생애 위험이 높고 새로운 유전 약물의 필요성을 강조했습니다.
Tenaya Therapeutics a fourni des mises à jour sur son programme de thérapie génique TN-201 pour la cardiomyopathie hypertrophique associée à MYBPC3 (HCM). La société a terminé l'administration aux trois premiers patients de la Cohorte 1 de l'
Tenaya a mis en œuvre des modifications du protocole, notamment l'ajout d'une biopsie de base, l'élargissement des critères d'éligibilité et l'augmentation du nombre potentiel de patients dans la partie d'expansion de dose. La société prévoit de publier des données initiales de la Cohorte 1 en décembre 2024, en se concentrant sur la sécurité, la tolérabilité et les analyses des biomarqueurs.
De plus, Tenaya a présenté des données sur la charge de la maladie pour les enfants et les adolescents atteints de HCM associée à MYBPC3, soulignant le risque cumulatif élevé d'événements graves et la nécessité de nouveaux médicaments génétiques.
Tenaya Therapeutics hat Updates zu seinem TN-201-Gentherapieprogramm für die mit MYBPC3 assoziierte hypertrophe Kardiomyopathie (HCM) bereitgestellt. Das Unternehmen hat die Dosierung der ersten drei Patienten in Kohorte 1 der MyPEAK-1-Studie mit einer Dosis von 3E13 vg/kg abgeschlossen, ohne unerwartete Ereignisse oder Toxizitäten zu beobachten. Ein unabhängiges Daten- und Sicherheitsüberwachungsgremium (DSMB) hat empfohlen, die Dosis für Kohorte 2 auf 6E13 vg/kg zu erhöhen, welches nun rekrutiert.
Tenaya hat Protokolländerungen umgesetzt, darunter die Hinzufügung einer Baseline-Biopsie, die Erweiterung der Eignungskriterien und die Erhöhung der potenziellen Anzahl an Patienten im Teil zur Dosissteigerung. Das Unternehmen plant, erste Daten aus Kohorte 1 im Dezember 2024 zu berichten, wobei der Fokus auf Sicherheit, Verträglichkeit und Biomarkeranalysen liegt.
Darüber hinaus präsentierte Tenaya Daten zur Krankheitslast für Kinder und Jugendliche mit MYBPC3-assoziierter HCM, die das hohe kumulative Lebensrisiko schwerer Ereignisse und den Bedarf an neuen genetischen Medikamenten hervorhebt.
- Completion of Cohort 1 dosing with no unexpected events or toxicities
- DSMB recommendation to proceed with dose escalation
- Expansion of eligibility criteria to include more HCM patients
- Increase in potential patient enrollment for dose expansion portion
- Planned initial data report from Cohort 1 in December 2024
- None.
Insights
The update on Tenaya Therapeutics' TN-201 gene therapy program for MYBPC3-associated HCM is promising. Key points:
- Safety profile at 3E13 vg/kg dose appears appropriate, allowing dose escalation to 6E13 vg/kg
- Expanded eligibility criteria to include obstructive HCM patients and those without ICDs
- Increased study size from 9 to 24 patients in dose expansion phase
- Added baseline biopsy and more flexible timing for post-dose biopsies
These changes suggest confidence in the therapy's safety and potential efficacy. The December 2024 data readout will be crucial, focusing on safety, cardiac biopsy analysis and biomarker changes. Long-term, TN-201 could significantly impact MYBPC3-HCM treatment, especially given the high morbidity rates in pediatric patients by age 40. However, it's still early-stage and efficacy data is pending.
Independent Data Safety and Monitoring Board Endorsed Dose Escalation and Broadening of Eligibility Criteria; Cohort 2 Now Enrolling
Initial Data from Cohort 1 to be Reported in December 2024
Highlights Recently Presented Insights on Pediatric MYBPC3-associated HCM Disease Burden
SOUTH SAN FRANCISCO, Calif., Oct. 17, 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 shared updates related to its ongoing Phase 1b/2 MyPEAK-1 clinical trial of TN-201. TN-201 is being developed for the potential treatment of MYBPC3-associated hypertrophic cardiomyopathy (HCM), a condition caused by insufficient levels of myosin-binding protein C (MyBP-C). TN-201 gene replacement therapy is designed to increase protein levels of MyBP-C to slow or even reverse the course of disease by delivering a functional copy of the MYBPC3 gene to heart muscle cells.
“The MyPEAK-1 study of TN-201 is primarily intended to establish the safety profile of TN-201 gene therapy, and we are pleased to report that TN-201 has an appropriate tolerability profile at the 3E13 vg/kg dose without unexpected adverse reactions,” said Whit Tingley, M.D., Ph.D., Tenaya’s Chief Medical Officer. “The DSMB’s recommendation to proceed with dose escalation and endorsement to expand eligibility criteria are further positive early indicators for TN-201’s safety profile and enable Tenaya to explore the utility of TN-201 in different populations. We’ve implemented adjustments to the protocol, including the addition of a biopsy at baseline, broadening eligibility to include obstructive HCM patients and increasing the size of the overall MyPEAK-1 study.”
Tenaya completed dosing of the first three patients (Cohort 1) at the 3E13 vg/kg dose in the MyPEAK-1 trial with no unexpected events or toxicities associated with study drug observed. Safety data from Cohort 1 were reviewed by an independent Data and Safety Monitoring Board (DSMB), showing a safety and tolerability profile consistent with other AAV gene therapies at this dose. Accordingly, the DSMB recommended that Tenaya proceed with dose escalation to the 6E13 vg/kg dose (Cohort 2), per protocol. Enrollment of Cohort 2 is underway.
Tenaya has implemented several changes in the MyPEAK-1 protocol intended to support future development, including:
- Adding a baseline biopsy, increasing the total number of cardiac biopsies from two to three, and permitting more flexible timing of post-dose biopsies to help characterize TN-201 expression over time
- Expanding eligibility to include participants who do not have an implantable cardioverter defibrillator device (ICD) and to permit adults with either obstructive or nonobstructive forms of HCM to enroll
- Increasing the potential number of total patients enrolled in the dose expansion portion of the clinical trial from nine to twenty-four adults
Tenaya plans to report initial data from Cohort 1 in December of this year. This readout is expected to focus on TN-201’s safety and tolerability, analyses of cardiac biopsy, as well as changes from baseline in cardiac biomarkers. The MyPEAK-1 clinical trial is also collecting data to understand TN-201’s effect on imaging biomarkers, heart function, exercise capacity, functional status, and patient quality of life.
As part of Tenaya’s ongoing efforts to characterize the disease burden for children and adolescents with MYBPC3-associated HCM, Dr. Tingley recently presented data from a study conducted in partnership with the Sarcomeric Human Cardiomyopathy Registry (SHaRe):
- Of the nearly 1,800 MYBPC3-associated HCM individuals identified in SHaRe’s database, approximately
13% were diagnosed prior to age 18. - The cumulative lifetime risk of severe events for MYBPC3-associated pediatric patients is very high, with
50% experiencing significant morbidity by age 40. - Both adult and pediatric MYBPC3-associated HCM individuals have high rates of serious complications, such as heart failure and ventricular arrhythmias, highlighting the need for timely diagnosis, active monitoring and new genetic medicines that can have a meaningful impact on outcomes.
- These data were presented at the virtual HCM Society Scientific Sessions and are available in the Publications page of Tenaya’s website.
Tenaya also continues to characterize the pediatric MYBPC3-associated HCM population through the MyClimb natural history study (Clinicaltrials.gov ID: NCT05112237) with more than 200 children and adolescents enrolled across 29 sites in USA, Canada, Spain, and the United Kingdom.
About the MyPEAK-1 Phase 1b/2 Clinical Trial
The MyPEAK-1 Phase 1b/2 clinical trial (Clinicaltrials.gov ID: NCT05836259) is an ongoing, multi-center, open-label, dose-escalating study designed to assess the safety, tolerability and clinical efficacy of a one-time intravenous infusion of TN-201 gene replacement therapy. The trial is enrolling symptomatic (New York Heart Association Class II or III) adults who have been diagnosed with MYBPC3-associated HCM. MyPEAK-1 is testing doses of 3E13 vg/kg and 6E13 vg/kg in two cohorts of three patients each. Following DSMB assessment of safety at each dose, planned dose expansion cohorts may enroll up to 24 MYBPC3-associated HCM adults with either nonobstructive or obstructive forms of HCM.
To learn more about gene therapy for HCM and participation in the MyPEAK-1 study, please visit HCMStudies.com.
About MYBPC3-Associated Hypertrophic Cardiomyopathy Variants in the Myosin Binding Protein C3 (MYBPC3) gene are the most common genetic cause of hypertrophic cardiomyopathy (HCM), accounting for approximately
About TN-201
TN-201 is an adeno-associated virus serotype 9 (AAV9)-based gene therapy designed to deliver a working MYBPC3 gene to heart muscle cells via a single intravenous infusion, increasing MyBP-C protein levels to address the underlying cause of MYBPC3-associated HCM with the aim of halting or even reversing disease after a single dose. The U.S. Food and Drug Administration has granted TN-201 Fast Track, Orphan Drug and Rare Pediatric Drug Designations. TN-201 has also received orphan medicinal product designation from the European Commission.
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.
(1) Sedaghat-Hemedani, et al., Clinical Research Cardiology, 2017
(2) Ho, et al., Circulation 2018
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 “plans,” “will,” “expected,” 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-201; the planned timing to report initial data from MyPEAK-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 MyPEAK-1; the potential failure of TN-201 to demonstrate safety and/or efficacy in clinical testing; availability of MyPEAK-1 data at the referenced time; the potential for any MyPEAK-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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