Tenaya Therapeutics Announces Publication of TN-401 Gene Therapy Preclinical Data in Nature Communications Medicine
18 Marzo 2024 - 1:30PM
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 the publication of its
preclinical research related to its gene therapy candidate, TN-401,
in the current issue of Nature Communications 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)
gene mutations. PKP2 mutations are the most common genetic cause of
ARVC, also known as arrhythmogenic cardiomyopathy (ACM), and result
in a loss of key proteins needed to maintain the structural
integrity and cell-to-cell electrical signaling of heart muscle
cells. TN-401 is designed to deliver a functional PKP2 gene to
heart cells where it works to restore normal protein levels in
order to halt or even reverse disease after a single dose.
“Following a single infusion of our AAV9-based PKP2 gene therapy
in a severe knock-out mouse model of the disease, PKP2 protein
levels were restored. This led to dose-dependent improvements in
right ventricular dilation and ejection fraction, reductions in
arrhythmia frequency and severity, and prevention of adverse
fibrotic remodeling, with near-maximal efficacy achieved at the
3E13 vg/kg dose.” said Tim Hoey, Ph.D., Chief Scientific Officer of
Tenaya.
“ARVC can have a devastating effect on patients’ lives, putting
them at risk of life-threatening arrhythmias and placing
limitations on their quality of life,” said Whit Tingley, M.D.,
Ph.D., Chief Medical Officer of Tenaya. “These promising
preclinical results show the potential of TN-401 to prevent, halt
or even reverse the steady progression of PKP2-associated ARVC by
addressing the underlying genetic cause, and offer hope to
patients. We look forward to commencing dosing of TN-401 in
patients with PKP2-associated ARVC in our 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
multi-center, open-label study to assess the safety, tolerability
and clinical efficacy of a one-time intravenous infusion of TN-401.
Tenaya is currently also conducting the RIDGE™ global
non-interventional natural history and serotype study of
PKP2-associated ARVC. Both studies are being conducted at leading
centers for ARVC care.
Key FindingsThe paper, titled “AAV9:PKP2
improves heart function and survival in a Pkp2-deficient mouse
model of arrhythmogenic right ventricular cardiomyopathy,”
describes results from preclinical studies in a Pkp2-deficient
mouse model to understand gene therapy’s impact in both prevention
mode before disease onset and in treatment mode after disease
onset. A single dose of Tenaya’s AAV9:PKP2 gene therapy:
- Restored normal levels of PKP2 protein expression,
- Led to a highly coordinated and durable correction in
structural genes encoding desmosome, sarcomere and calcium handling
proteins with a role in maintaining cellular integrity and
function,
- Reduced the frequency and severity of arrhythmias,
- Demonstrated durable efficacy in preventing disease
development,
- Slowed or reversed disease progression after onset,
- Prevented fibrotic remodeling, and
- Improved long-term survival.
Tenaya selected AAV9 as the vector for delivery for TN-401 based
on its extensive clinical and commercial safety record in thousands
of patients globally and its demonstrated ability in clinical
studies to broadly distribute in all regions of the human heart and
to more robustly express the PKP2 gene in cardiomyocytes as
compared to other vectors.
About PKP2-Associated
ARVCMutations in the desmosome gene PKP2 are the most
frequent cause of ARVC, with greater than 40% of those diagnosed
estimated to carry pathogenic PKP2 mutations. In the U.S.
prevalence of PKP2-associated ARVC is estimated at more than
70,000, though the condition is frequently undiagnosed; in nearly
one in four cases, sudden cardiac death is the first sign of
disease.
Mutations of the PKP2 gene result 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
adverse remodeling and irregular heart rhythms. A progressive
disease, ARVC is typically diagnosed before age 40 and symptoms may
include arrhythmias, palpitations, lightheadedness, dizziness and
fainting and sudden cardiac arrest. 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 and the RIDGE Clinical
ProgramTN-401 is an investigational AAV9-based gene
therapy being developed for the treatment of ARVC due to mutations
in the PKP2 gene. Tenaya has received clearance from the FDA to
initiate its first-in-human 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 TherapeuticsTenaya 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. Leveraging
integrated proprietary core capabilities enabling target
identification and validation, design of AAV-based genetic
medicines and in-house manufacturing the company is advancing a
pipeline of novel therapies with diverse treatment modalities for
rare genetic cardiovascular disorders and more prevalent heart
conditions. Tenaya’s most advanced candidates include TN-201, a
gene therapy for MYBPC3-associated hypertrophic cardiomyopathy
(HCM), TN-401, a gene therapy for PKP2-associated arrhythmogenic
right ventricular cardiomyopathy (ARVC), and TN-301, a small
molecule HDAC6 inhibitor being initially developed for heart
failure with preserved ejection fraction (HFpEF). Tenaya also has
multiple early-stage programs progressing through preclinical
development. For more information,
visit www.tenayatherapeutics.com.
Forward Looking StatementsThis 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,” “promising,” “potential,” “look
forward,” “plan,” 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 TN-401 as a treatment for PKP2-associated
ARVC and the plan for initiation of patient dosing in RIDGE-1. 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 potential failure of TN-401 to demonstrate safety and/or
efficacy in clinical testing; unexpected concerns that may arise as
a result of the occurrence of adverse safety events or additional
data analyses of clinical trials evaluating TN-401; the 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 approvals, for any of its product
candidates; 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 business
and 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.
Contacts
Michelle CorralVice President, Investor Relations and Corporate
CommunicationsTenaya TherapeuticsIR@TenayaThera.com
InvestorsAnneMarie FieldsStern
IRAnneMarie.Fields@SternIR.com
MediaWendy RyanTen Bridge
Communicationswendy@tenbridgecommunications.com
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