TN-401 AAV9-based gene therapy in development to treat the root cause of PKP2-related arrhythmogenic right ventricular cardiomyopathy (ARVC)

PKP2 gene replacement therapy normalized heart rhythm, reversed disease progression and extended survival in a critically ill mouse model

Tenaya Expects First Patient Dosing in Phase 1b RIDGE™-1 Clinical Trial of TN-401
Second half of 2024

SOUTH SAN FRANCISCO, Calif., March 18, 2024 (Globe Newswire) — Tenaya Therapeutics, Inc. (NASDAQ: TNYA) is committed to discovering, developing and delivering potentially curative therapies that address underlying problems. A clinical-stage biotechnology company with a mission to The company, which researches the causes of heart disease, today announced that it has published preclinical research related to its gene therapy candidate TN-401 in its latest issue. nature communication medicine.

TN-401 is an adeno-associated virus serotype 9 (AAV9)-based gene therapy being developed for the treatment of arrhythmogenic right ventricular cardiomyopathy (ARVC) caused by: Plakophilin-2 (PKP2) Genetic mutation. PKP2 Mutations are the most common genetic cause of ARVC, also known as arrhythmogenic cardiomyopathy (ACM), and are essential for maintaining the structural integrity of heart muscle cells and electrical signaling between cells. causes loss of protein. TN-401 is designed to provide functional functionality. PKP2 It transfers this gene to heart cells and works to restore normal protein levels, stopping or even reversing the disease after a single dose.

“After one injection of our AAV9-based drug; PKP2 Gene therapy in a severe knockout mouse model of the disease restored PKP2 protein levels. This led to dose-dependent improvements in right ventricular dilatation and ejection fraction, reduced arrhythmia frequency and severity, and prevention of deleterious fibrotic remodeling, with near-maximal efficacy at a dose of 3E13 vg/kg. sexuality has been achieved. ” said Dr. Tim Hoey, Chief Scientific Officer at Tenaya.

“ARVC can have a devastating impact on a patient’s life, putting them at risk for life-threatening arrhythmias and limiting their quality of life,” said Whit Tingley, MD, Tenaya’s chief medical officer. I am. “These promising preclinical results demonstrate that TN-401 has the potential to prevent, halt, or even reverse the steady progression of the disease.” PKP2-Related to ARVC by addressing the underlying genetic causes and bringing hope to patients. We look forward to beginning treatment with TN-401 in the following patients: PKP2– Research related to ARVC was conducted in the Phase 1b RIDGE-1 clinical trial in the second half of this year. ”

Tenaya’s RIDGE-1 Phase 1b clinical trial of TN-401 is a multicenter, open-label study to evaluate the safety, tolerability, and clinical efficacy of a single intravenous infusion of TN-401. Tenaya is also currently conducting RIDGE™ global non-intrusive natural history and serotyping studies. PKP2-Related ARVC. Both studies are being conducted at major centers for ARVC care.

Main findings
A paper entitled “”AAV9:PKP2 improves cardiac function and survival in a Pkp2-deficient mouse model of arrhythmogenic right ventricular cardiomyopathy,” We will discuss the results of preclinical studies. PKP2– Deficient mouse models to understand the impact of gene therapy in both a preventive mode before disease onset and a therapeutic mode after disease onset. Tenaya’s single dose of his AAV9:PKP2 gene therapy:

• restores normal levels of PKP2 protein expression,
• leading to highly regulated and permanent modifications of structural genes encoding desmosomes, sarcomeres, and calcium-handling proteins that are responsible for maintaining cell integrity and function,
• The frequency and severity of arrhythmias were reduced.
• It has been proven to have a lasting effect on preventing the onset of disease.
• slowing or reversing the progression of the disease after onset,
• prevents fibrotic remodeling,
• Improved long-term survival.

Tenaya has an extensive clinical and commercial safety record in thousands of patients worldwide and a demonstrated ability in clinical studies to be widely distributed and more strongly expressed in all regions of the human heart. Based on this, we selected AAV9 as the delivery vector for TN-401. PKP2 Cardiomyocyte genes compared to other vectors.

about PKP2-Related ARVC
Mutations in desmosomal genes PKP2 It is the most common cause of ARVC, and it is estimated that more than 40% of people diagnosed carry the pathogenic virus. PKP2 mutation. In the United States, PKP2– Although it is estimated that there are more than 70,000 associated ARVCs, this condition is often undiagnosed. In nearly one in four cases, sudden cardiac death is the first sign of the disease.

mutation of PKP2 Genetic influences result in insufficient expression of proteins required for the proper functioning of the desmosomal complex, which maintains the physical connections and electrical signaling between cardiomyocytes. Degradation of the desmosomal structure causes cardiomyocytes to be replaced by fibroadipose tissue, which destabilizes electrical pulses within the heart, resulting in harmful remodeling and irregular heart rhythms. Her ARVC, a progressive disease, is usually diagnosed before age 40, and symptoms can include arrhythmia, palpitations, lightheadedness, dizziness, fainting, and sudden cardiac arrest. Current treatments include antiarrhythmic drugs, implantable cardioverter defibrillators (ICDs), and ablative procedures, but these do not address the underlying genetic causes of the disease.

About TN-401 gene therapy and the RIDGE clinical program
TN-401 is an investigational AAV9-based gene therapy being developed for the treatment of ARVC caused by genetic mutations. PKP2 gene. Tenaya has received permission from the FDA to begin her first-in-human RIDGE-1 Phase 1b clinical trial of TN-401 in patients with: PKP2-Related ARVC. To support the clinical development of TN-401, the company is currently enrolled in the RIDGE global non-interventional study to collect natural history and AAV9 antibody (seroprevalence) data for ARVC patients. PKP2 Gene mutations. TN-401 has received Orphan Drug and Fast Track designation from the FDA.

About Tenaya Therapeutics
Tenaya Therapeutics is a clinical-stage biotechnology company on a bold mission to discover, develop and deliver potentially curative therapies that address the root causes of heart disease. The company leverages its integrated, unique core capabilities that enable target identification and validation, AAV-based genetic medicine design, and in-house manufacturing to address rare inherited cardiovascular diseases and more common heart diseases. The company is promoting a pipeline of new treatments with a variety of treatments. Tenaya’s most advanced candidates include the gene therapy drug TN-201. MYBPC3– Associated hypertrophic cardiomyopathy (HCM), TN-401, gene therapy PKP2TN-301, a small molecule HDAC6 inhibitor originally developed for arrhythmia-associated right ventricular cardiomyopathy (ARVC) and heart failure with preserved ejection fraction (HFpEF). Tenaya also has multiple early-stage programs in preclinical development. For more information, please visit www.tenayatherapeutics.com.

Forward-looking statements
This press release contains forward-looking statements as 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,” “commits,” “may,” “looks forward to,” “plans” and similar expressions are intended to identify forward-looking statements. Masu. Such forward-looking statements include, among other things, the clinical, therapeutic and commercial potential of TN-401 as a treatment. PKP2-Related ARVC and patient initiation plans in RIDGE-1. The forward-looking statements contained herein are based on Tenaya’s current expectations and involve assumptions that may never materialize or prove to be inaccurate. These forward-looking statements are not promises or guarantees and are subject to various risks and uncertainties, including, but not limited to: unanticipated concerns that may arise as a result of the occurrence of adverse safety events or additional data analysis from clinical trials evaluating TN-401; timing and progress of the RIDGE-1 clinical trial; the timing, scope and likelihood of regulatory filings and approvals for TN-401; 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 ability to develop, initiate or complete preclinical studies and clinical trials and obtain approval for its product candidates; Tenaya will continue to comply with applicable legal and regulatory requirements. Tenaya’s ability to obtain additional financing needed to continue advancing its business and product development plans; Tenaya relies on third parties. Tenaya’s manufacturing, commercialization and marketing capabilities and strategies; loss of key scientific or administrative personnel; competition in the industries 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 these and additional risks is contained in the section entitled “Risk Factors” in Tenaya’s filings with the Securities and Exchange Commission from time to time. These forward-looking statements are made as of the date of this press release and, except as required by law, Tenaya does not believe that future forward-looking statements, whether as a result of new information, future events or otherwise, will We undertake no obligation to update or revise any forward-looking statements.

contact address

Michelle Corral
Vice President of Investor Relations and Corporate Communications
Tenaya Therapeutics
IR@TenayaThera.com

Investor
Annmarie Fields
Stern IR
AnneMarie.Fields@SternIR.com

media
wendy ryan
tenbridge communications
wendy@tenbridgeecommunications.com