TSHA-113 significantly reduced tau mRNA and
protein levels in mouse models of human tauopathies via cerebral
spinal fluid (CSF) delivery supporting further preclinical
development
TSHA-105 significantly reduced plasma citrate
levels, normalized EEG brain activity, and reduced the number of
seizures and seizure susceptibility in SLC13A5 knockout mice
TSHA-106 increased UBE3A expression through
shRNA-mediated knockdown of UBE3A-ATS in in vitro cell lines across
26 distinct shRNA candidates for the treatment of Angelman
disease
TSHA-112 generated significant reductions in
GYS1 protein, abnormal glycogen accumulation and polyglucosan
bodies in the APBD knockout mouse model
TSHA-111-LAFORIN and TSHA-111-MALIN achieved
effective knockdown of GYS1 expression and insoluble glycogen and
decreased Lafora body formation in laforin and malin mouse
models
TSHA-110 caused a dose-dependent reduction of
GM2 accumulation at 20 weeks in GM2A knockout mice
Positive proof-of-concept data for gene therapy
candidates in SCL13A5 deficiency, APBD, Lafora disease and GM2 AB
variant support advancement into clinical testing
Expect to submit IND/CTA for one of the
following programs by the end of 2021: SLC13A5 deficiency, APBD,
Lafora disease or GM2 AB variant
Taysha’s virtual Research and Development Day
in June 2021 will highlight progress across R&D pipeline
Taysha Gene Therapies, Inc. (Nasdaq: TSHA), a patient-centric,
pivotal-stage gene therapy company focused on developing and
commercializing AAV-based gene therapies for the treatment of
monogenic diseases of the central nervous system (CNS) in both rare
and large patient populations, today announced new data for
multiple preclinical programs and a planned R&D Day, which will
be held in June 2021.
“Collectively, these new preclinical data highlight Taysha’s
next wave of novel gene therapies that have the potential to impact
meaningful patient populations. The promising data underscore our
ability to rapidly and reproducibly investigate disease biology,
design innovative gene therapies and efficiently advance the
development of these drug candidates,” said RA Session II,
President, Founder and Chief Executive Officer of Taysha. “Among
the compelling new data, for the first time, we have shown that
TSHA-113, an AAV9 gene therapy that utilizes AAV-mediated gene
silencing, reduced tau expression in mouse models of human
tauopathies. The potential implications of these data are far
reaching, and we intend to further evaluate TSHA-113 in additional
preclinical studies. The totality of the preclinical data presented
today support the fundamental elements of our scientific approach
of coupling validated technology with novel targeted payload design
while utilizing a proven HEK293 suspension manufacturing process.
We believe our deep pipeline and innovative scientific engine hold
tremendous potential, and we are poised to continue delivering
meaningful value to patients with monogenic CNS diseases.”
“Today’s data demonstrate the breadth, depth and velocity of our
development engine as a sustainable pivotal-stage gene therapy
company. There are no approved disease modifying therapies for any
of the programs in our portfolio and we are encouraged by the
results of our gene therapy approach of vectorized RNA and gene
replacement therapies across our portfolio,” said Suyash Prasad,
MBBS, M.SC., MRCP, MRCPCH, FFPM, Chief Medical Officer and Head of
Research and Development of Taysha. “We are very excited to further
develop TSHA-113 in tauopathies, including Alzheimer’s disease,
MAPT-associated frontotemporal dementia and progressive
supranuclear palsy, based on the significant reduction in tau
expression demonstrated in transgenic mouse models of human
tauopathies. In addition, to date, we have advanced five programs
into IND/CTA-enabling studies, including TSHA-105 in SLC13A5
deficiency, TSHA-111-LAFORIN in Lafora disease, TSHA-111-MALIN in
Lafora disease, TSHA-112 in APBD and TSHA-119 in GM2 AB variant. We
intend to file an IND/CTA for one of these five named programs by
the end of 2021. By mid-year, we intend to select a development
candidate for Angelman syndrome and obtain interim expression and
safety data from confirmatory non-human primate studies by
year-end. We remain on track to report Phase 1/2 biomarker data for
TSHA-101 in GM2 gangliosidosis in the second half of this year and
to provide a clinical and regulatory update for TSHA-120 in giant
axonal neuropathy by year-end. Finally, in the second half of the
year, we continue to expect dosing of the first patient with CLN1
disease in a Phase 1/2 trial for TSHA-118 under an already open
IND, filing an IND/CTA for TSHA-102 in Rett syndrome and TSHA-104
in SURF1-associated Leigh syndrome, and filing an IND for TSHA-101
in GM2 gangliosidosis in the U.S. These anticipated clinical and
regulatory milestones are expected to be followed by the initiation
of Phase 1/2 clinical trials for each of these indications. We look
forward to providing additional updates at our R&D Day in
June.”
TSHA-113 for Tauopathies
Taysha is developing tau-specific microRNA (miRNA) shuttles
designed to target tau mRNA for all six isoforms found in the human
brain and/or mouse brain. TSHA-113 is an AAV9 capsid that packages
these miRNA shuttles and is delivered in the CSF for the treatment
of tauopathies.
- In transgenic mouse models carrying human tau, TSHA-113
significantly reduced tau mRNA and protein levels, while
demonstrating widespread expression in neurons and glia
- Together with previous in vitro findings, these data further
validate selective reduction of tau mRNA and protein levels and
warrant further preclinical development
- An estimated 6.2 million Americans and 7.8 million Europeans
are living with Alzheimer's disease
- There are an estimated 13,000 patients in the U.S. and Europe
affected by MAPT-associated frontotemporal dementia, progressive
supranuclear palsy and corticobasal degeneration, which represent a
significant commercial opportunity
TSHA-105 for SLC13A5 deficiency
TSHA-105 is a recombinant self-complementary AAV9 vector that
expresses the human SLC13A5 protein under the control of a
ubiquitous promoter. The drug candidate is being developed for the
treatment of SLC13A5 deficiency.
- In SLC13A5 knockout mice, treatment with TSHA-105 resulted in a
significant, sustainable decrease of plasma citrate levels up to
three months post-injection compared to age-matched, wildtype
controls
- TSHA-105 normalized electroencephalogram (EEG) brain activity,
reduced the number of seizures, and reduced seizure susceptibility
compared to vehicle-treated controls
- The company has advanced TSHA-105 into IND/CTA-enabling
studies
- There are an estimated 1,900 patients with SLC13A5 deficiency
in the United States and in Europe
TSHA-106 for Angelman syndrome
TSHA-106 is an intrathecally delivered AAV9 viral vector
designed for shRNA-mediated knockdown of UBE3A-ATS, the antisense
transcript governing the expression of UBE3A through the paternal
allele.
- In vitro testing in a neuroblast cell line demonstrated
consistent knockdown of UBE3A-ATS and a subsequent increase in
UBE3A expression across 26 distinct shRNA candidates
- Selection of development candidate expected by mid-year
- Interim expression and safety data from confirmatory non-human
primate (NHP) studies expected by the end of 2021
- There are an estimated 55,000 patients with Angelman syndrome
in the United States and in Europe
TSHA-112 for Adult Polyglucosan Body
Disease (APBD)
TSHA-112 is an intrathecally delivered AAV9 viral vector
designed for miRNA-mediated knockdown of the GYS1 gene to treat
APBD.
- In preclinical studies, miRNA knockdown of GYS1 induced
significant reductions in GYS1 mRNA, GYS1 protein, abnormal
glycogen accumulation, and polyglucosan bodies throughout the brain
in an APBD knockout mouse model
- TSHA-112 decreased neuroinflammatory markers across three
distinct mouse models
- The company has advanced TSHA-112 into IND/CTA-enabling
studies
- There are an estimated 10,000 patients with APBD in the United
States and in Europe
TSHA-111-LAFORIN for EPM2A and
TSHA-111-MALIN for EPM2B for Lafora disease
TSHA-111-LAFORIN and TSHA-111-MALIN are intrathecally delivered
AAV9 viral vectors designed for miRNA-mediated knockdown of the
GYS1 gene to treat Lafora disease.
- In preclinical studies, TSHA-111-LAFORIN and TSHA-111-MALIN
achieved effective knockdown of GYS1 expression and insoluble
glycogen in the Lafora disease laforin and malin mouse models,
respectively
- Both product candidates decreased Lafora body formation within
the brain in their respective mouse models
- The company has advanced TSHA-111-LAFORIN and TSHA-111-MALIN
into IND/CTA-enabling studies
- There are an estimated 700 patients with Lafora disease in the
United States and in Europe
TSHA-119 for GM2 AB variant
TSHA-119 is a self-complementary AAV9 vector designed to deliver
a functional copy of the GM2A gene to treat GM2 AB variant.
- In preclinical studies, TSHA-110 caused a significant,
dose-dependent reduction of GM2 accumulation at 20 weeks in mice
that were dosed intrathecally at postnatal day 1 or at 6 weeks of
age
- Long-term follow up studies, which include bi-monthly
behavioral, as well as biochemical and histological analyses, are
currently ongoing
- The company has advanced TSHA-112 into IND/CTA-enabling
studies
- There are approximately 200 patients with GM2 AB variant in the
United States and in Europe
About Taysha Gene Therapies
Taysha Gene Therapies (Nasdaq: TSHA) is on a mission to
eradicate monogenic CNS disease. With a singular focus on
developing curative medicines, we aim to rapidly translate our
treatments from bench to bedside. We have combined our team’s
proven experience in gene therapy drug development and
commercialization with the world-class UT Southwestern Gene Therapy
Program to build an extensive, AAV gene therapy pipeline focused on
both rare and large-market indications. Together, we leverage our
fully integrated platform—an engine for potential new cures—with a
goal of dramatically improving patients’ lives. More information is
available at www.tayshagtx.com.
Forward-Looking Statements
This press release contains forward-looking statements within
the meaning of the Private Securities Litigation Reform Act of
1995. Words such as “anticipates,” “believes,” “expects,”
“intends,” “projects,” and “future” or similar expressions are
intended to identify forward-looking statements. Forward-looking
statements include statements concerning the potential of our
product candidates, including our preclinical product candidates,
to positively impact quality of life and alter the course of
disease in the patients we seek to treat, our research, development
and regulatory plans for our product candidates, the potential for
these product candidates to receive regulatory approval from the
FDA or equivalent foreign regulatory agencies, and whether, if
approved, these product candidates will be successfully distributed
and marketed, and the potential market opportunity for these
product candidates. Forward-looking statements are based on
management’s current expectations and are subject to various risks
and uncertainties that could cause actual results to differ
materially and adversely from those expressed or implied by such
forward-looking statements. Accordingly, these forward-looking
statements do not constitute guarantees of future performance, and
you are cautioned not to place undue reliance on these
forward-looking statements. Risks regarding our business are
described in detail in our Securities and Exchange Commission
(“SEC”) filings, including in our Annual Report on Form 10-K for
the full-year ended December 31, 2020, which is available on the
SEC’s website at www.sec.gov. Additional information will be made
available in other filings that we make from time to time with the
SEC. Such risks may be amplified by the impacts of the COVID-19
pandemic. These forward-looking statements speak only as of the
date hereof, and we disclaim any obligation to update these
statements except as may be required by law.
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version on businesswire.com: https://www.businesswire.com/news/home/20210414005278/en/
Company Contact: Kimberly Lee, D.O. SVP, Corporate
Communications and Investor Relations Taysha Gene Therapies
klee@tayshagtx.com Media Contact: Carolyn Hawley Canale
Communications carolyn.hawley@canalecomm.com
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