Keynote lecture by KateTx Chief Scientific
Officer and Scientific Co-founder Sharif Tabebordbar, Ph.D.,
features non-human primate data demonstrating best-in-class
potential of KT809, a novel muscle and heart-targeted,
liver de-targeted development candidate for Duchenne muscular
dystrophy
Additional preclinical data highlight
company's lead candidate in facioscapulohumeral muscular
dystrophy
SAN
DIEGO, May 9, 2024 /PRNewswire/ -- Kate
Therapeutics Inc. ("KateTx"), a next-generation gene therapy
company, will present detailed preclinical efficacy and safety
results on its pipeline and platform at the American Society of
Gene and Cell Therapy (ASGCT) 2024 Annual Meeting being held
May 7-11, 2024, in Baltimore, MD and virtually. The results
support the best-in-class potential of KateTx's newest generation
of skeletal muscle- and heart-targeted, liver de-targeted
engineered MyoAAV capsids and gene regulation technology to treat
Duchenne muscular dystrophy (DMD), facioscapulohumeral muscular
dystrophy (FSHD), and other devastating genetic skeletal muscle and
heart diseases.
KateTx debuted less than a year ago with a $51 million Series A round co-led by Westlake
Village BioPartners and Versant Ventures and an exclusive license
of KT430 to Astellas Pharmaceuticals for the treatment of X-linked
myotubular myopathy. Since that time, the company has used its
DELIVER platform to identify a proprietary class of muscle- and
heart-targeted, liver de-targeted "MyoAAV-LD" capsids with improved
potency and selectivity in non-human primates (NHPs) and selected
KT809 as a development candidate to treat DMD. This product
incorporates MyoAAV-LD 6.1, which is a sixth generation internally
generated and fully owned capsid, as well as a proprietary
regulatory element developed to express the transgene in both
skeletal muscle and heart in primates. KateTx remains on track to
select development candidates for additional muscle and cardiac
programs in the near term. In addition, Astellas has formally
advanced KT430 into IND enablement.
"KateTx has made significant advances over the past 12 months,"
said Kevin Forrest, Ph.D.,
co-founder, president and CEO of KateTx. "These ASGCT presentations
are a meaningful milestone for the company and demonstrate the
potential of our medicines to be the preferred therapies in both
DMD and FSHD. We look forward to advancing these differentiated
products to patients as quickly as possible."
Key advances in next-generation DMD gene therapy
KateTx will present data on its Duchenne muscular dystrophy
(DMD) development candidate showing markedly higher and more
uniform expression at lower doses than competing gene therapies in
NHPs. KateTx CSO and scientific co-founder, Sharif Tabebordbar,
Ph.D., will give a keynote lecture presenting these data at the
meeting as recipient of the 2024 Outstanding Investigator Award for
contributions to the field of gene therapy. Dr. Tabebordbar's
plenary lecture will take place on Friday,
May 10, 2024, at 11:40 AM
ET.
"First-generation gene therapies for DMD use very high doses of
naturally occurring capsids that primarily target the liver, and
promoters that are more active in skeletal muscle than heart in
primates," said Dr. Tabebordbar. "By leveraging our novel capsid
and gene regulation technologies, we have developed a DMD gene
therapy candidate that potently, uniformly, and selectively
expresses high levels of microdystrophin in both skeletal muscle
and heart, which are the major affected organs in the disease,
while avoiding off-target tissues like the liver."
In NHPs, KateTx's product expressed high levels of
microdystrophin uniformly in skeletal and cardiac muscles at a dose
three times lower than a surrogate version of an FDA-approved DMD
gene therapy. In contrast, microdystrophin expression from the
surrogate was barely detectable in skeletal muscles and heart of
NHPs at the clinical dose of 1.33E+14 vg/kg. High and uniform
levels of microdystrophin protein expression across muscle fibers
are required to protect muscles against injury and death in DMD and
are important factors affecting DMD gene therapy durability.
Furthermore, KateTx's DMD development candidate resulted in 27
times lower vector genomes per nucleus in the liver compared with
animals injected with the surrogate. Collectively, these findings
support the potential for superior improvements in skeletal muscle
strength, cardiac function (largely responsible for mortality in
DMD), and safety.
Strong preclinical data for the FSHD program
KateTx will also present new preclinical data from its program
in facioscapulohumeral muscular dystrophy (FSHD), which is a common
muscular dystrophy that results from toxic expression in skeletal
muscle of a protein called DUX4. KateTx's results show the
potential to give a one-time gene therapy that potently suppresses
DUX4 whenever it is expressed in skeletal muscles.
In vitro, the company's MyoAAV-LD mediated RNAi gene
therapy candidate showed potent knockdown of DUX4 in FSHD patient
myotubes with no off-target effects. In mice, the therapy reduced
DUX4 target gene expression and led to dose-dependent improvements
in muscle function and ultimately protected animals from severe
impairment in treadmill time to exhaustion at a low dose.
"Both DMD and FSHD are challenging diseases – they require
delivery of therapeutic cargoes to a substantial tissue mass, and
expression of significant amounts of protein uniformly and durably
across skeletal muscle fibers and cardiomyocytes in the case of
DMD, and effective inhibition of toxic DUX4 expression in skeletal
muscle in the case of FSHD," said Katherine
A. High, M.D., Visiting Professor at Rockefeller University, Professor Emerita of
Pediatrics at the Perelman School of Medicine at the University of Pennsylvania, and member of the
KateTx Scientific Advisory Board. "The clinical evaluation of these
novel bioengineered capsids is in my judgment one of the most
exciting near-term developments in our field and I look forward to
these programs moving into clinical development."
A list of KateTx's presentations and posters at ASGCT is
available on the company's website at
https://www.katetherapeutics.com/publications/. Abstracts can be
found at https://annualmeeting.asgct.org/abstracts.
About DMD
Duchenne muscular dystrophy (DMD) is a fatal genetic disorder
and the most common form of muscular dystrophy. The disease is
characterized by progressive weakness and degeneration of muscle,
leading to loss of ambulation, cardiomyopathy, ventilatory
compromise, and death due to cardiopulmonary causes by early
adulthood. DMD affects about 1 in 3,500-5,000 live male births, and
about 20,000 children are diagnosed globally each year.
About FSHD
Facioscapulohumeral muscular dystrophy (FSHD) is a heritable
muscle disorder affecting approximately 40,000 people in
the United States. Onset of FSHD
is commonly 15-30 years of age, with weakness affecting the face,
shoulders and upper arms, lower legs, and hips. Upper extremity
weakness is often most pronounced, but many patients will have
significant difficulty walking, and about 20% will require a
wheelchair. There are no approved medicines for FSHD.
About Kate Therapeutics
Kate Therapeutics (KateTx) is a patient-focused biotechnology
company developing adeno-associated virus (AAV)-based gene
therapies to treat genetically defined muscle and heart diseases.
The company is applying novel technology platforms that directly
address the key limitations of current gene therapies, including
tissue-specific delivery and gene regulation. These breakthroughs
have the potential to improve the efficacy and safety of gene
therapies and enable the pursuit of a broader set of targets that
are otherwise difficult to drug with current technologies. For more
information, please visit KateTx's website at
https://www.katetherapeutics.com/.
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