Taysha Gene Therapies Presents Preclinical Data on TSHA-102 for Rett Syndrome Demonstrating Cellular Regulation of MeCP2 Expression in Key Mouse Models at the American Society of Gene and Cell Therapy 26th Annual Meeting
May 19 2023 - 8:00AM
Taysha Gene Therapies, Inc. (Nasdaq: TSHA), a clinical-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), today presents preclinical data from
neonatal mouse models on TSHA-102 for Rett syndrome, including new
data in wild-type mice, at the American Society of Gene and Cell
Therapy (ASGCT) 26th Annual Meeting. TSHA-102 utilizes a miniMECP2
gene and a novel miRNA-Responsive Auto-Regulatory Element (miRARE)
technology designed to regulate cellular MECP2 expression. In a
Taysha-sponsored study, the safety and efficacy of TSHA-102 were
explored in both neonatal wild-type and Mecp2–/Y knockout mice,
respectively. Preclinical in-life data on early intervention of
TSHA-102 in neonatal mice suggest miRARE enables the expression of
the MeCP2 protein in deficient CNS cells while preventing toxic
overexpression within cells expressing normal levels of MeCP2.
“These encouraging new preclinical data in wild-type mice
indicate that TSHA-102, engineered with our miRARE technology,
avoided overexpression of MeCP2 within cells already expressing
MeCP2, while maintaining normal survival, neurobehavioral function
and overall health,” said Sukumar Nagendran, M.D., President, and
Head of R&D. “These new data augment previous findings in the
Mecp2–/Y knockout mouse model, suggesting that THSA-102 regulated
expression of MECP2 in both normal and MECP2 deficient cells, which
is critical given that Rett syndrome represents such a challenging
case for human gene therapy because the therapeutic window for
MECP2 transgene expression is narrow. Either MECP2 deficiency or
duplication can lead to serious neurodevelopmental disease. We
believe these new data from neonatal wild-type mice support the
potential of miRARE to enable the optimal amount of MeCP2. This
would be critical to modulating the cellular expression of MeCP2 in
an appropriate, clinically relevant manner, given the mosaic
pattern of MECP2 silencing characteristic of female patients with
Rett syndrome.”
Sarah Sinnett, Ph.D., University of Texas Southwestern Medical
Center, Co-Inventor of miRARE technology, added, “TSHA-102 pairs a
therapeutic gene with miRARE, all within a single vector genome.
The miRARE technology was designed to mitigate the risk of MeCP2
overexpression through a post-transcriptional feedback repression
mechanism. We are pleased that miRARE permitted efficacy in
Mecp2–/Y mice without compromising safety in wild-type mice.
Importantly, these findings could translate into clinical benefits
for treating patients with Rett syndrome.”
Preclinical data in neonatal wild-type mice suggest
miRARE suppressed toxic overexpression after early intervention
with TSHA-102:
- In wild-type mice treated with TSHA-102, new data showed no
deleterious impact on survival, neurobehavioral functions and
overall health, suggesting miRARE regulated expression of MeCP2
with the below results from the study:
- No toxicity relative to vehicle treatment
- No reduction in survival over 36-weeks
- No treatment effect on Bird Score (a measure of Rett
syndrome-like behaviors and pathologies) analysis relative to
vehicle treatment
- No impact on overall growth over
the course of the study
This builds on prior preclinical data in
neonatal Mecp2–/Y
knockout mice showing miRARE regulated
MECP2 expression levels in deficient CNS
cells with early intervention of TSHA-102:
- In Mecp2–/Y knockout mice (mouse model recapitulating
developmental, physiological, and behavioral features of human Rett
syndrome) treated with TSHA-102 with the below results from the
study:
- 47% survived the 36-week study vs a median survival of 8.1
weeks with vehicle‐treated knockout mice, representing a
significant (p<0.0001) >4-fold extension of their
lifespan
- Restoration of normal and faster-than-normal growth
- Aggregate Bird Score was significantly improved at several time
points, with a significant delay in the onset of severe Rett
syndrome-like phenotypes, including the delayed average age of
onset for severe clasping from approximately 7 to 21 weeks and
severely abnormal gait from approximately 8 to 20 weeks
TSHA-102 is a self-complementary
intrathecally delivered AAV9 investigational gene transfer therapy
in clinical evaluation for Rett syndrome, a rare genetic
neurodevelopmental disorder caused by mutations in the X-linked
MECP2 gene. TSHA-102 is currently being evaluated in the Phase 1/2
REVEAL trial in adult patients with Rett syndrome. The dosing of
the first adult patient with TSHA-102 is expected in Q2 2023, with
initial available clinical data, primarily on safety, anticipated
thereafter in Q2 2023. TSHA-102 has received Orphan Drug and Rare
Pediatric Disease designations from the U.S. Food and Drug
Administration (FDA) and has been granted Orphan Drug designation
from the European Commission for the treatment of Rett
syndrome.
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. Together, we leverage our fully integrated platform 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,” “plans,” 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 TSHA-102, 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, 2022, 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.
Company Contact:Hayleigh Collins Director, Head
of Corporate CommunicationsTaysha Gene Therapies,
Inc.hcollins@tayshagtx.com
Media Contact:Carolyn HawleyCanale
Communicationscarolyn.hawley@canalecomm.com
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