Taysha Gene Therapies Provides Clinical Updates for Investigational Programs TSHA-120 in Giant Axonal Neuropathy (GAN) and TSHA-102 in Rett Syndrome at R&D Day
28 Junho 2023 - 9:00AM
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), announced
new data analyses for TSHA-120 in GAN and initial clinical
observations for TSHA-102 in Rett syndrome. Taysha will host a
virtual R&D Day today at 10:00 AM ET to discuss these updates.
The webcast link can be accessed on the Events and Presentations
section of Taysha’s website.
“Late last year, the company submitted and discussed with the
FDA a subset of available evidence supporting the potential
therapeutic benefit and safety profile for TSHA-120 in patients
with GAN, an ultra-rare disease with currently no approved
treatments. FDA feedback included the need to address the
heterogeneity of disease progression in GAN and the
effort-dependent nature of MFM32 as a primary endpoint, considering
the unblinded study design,” said Sean P. Nolan, Chairman and Chief
Executive Officer of Taysha. “Given the FDA also indicated it is
open to regulatory flexibility in a controlled trial setting and
willing to consider alternative study designs, we undertook an
extensive analysis of the totality of data available to determine a
feasible regulatory path forward for TSHA-120.”
Mr. Nolan continued, “We believe the new analyses may help
support an approval pathway for TSHA-120 for the treatment of GAN.
Our newly developed disease progression model demonstrates
predictable and homogenous disease progression in classic GAN,
which in our view supports the use of natural history data as an
external control. Additionally, we identified objective functional,
electrophysiological and biological measurements that demonstrated
a clinically meaningful treatment effect, which is also accompanied
by over seven years of clinical data supporting the safety profile.
We’ve requested a formal FDA meeting to discuss these new
developments to support a potential regulatory path forward for
TSHA-120. We expect the meeting to take place in the third quarter
of this year.”
“For our TSHA-102 program in Rett syndrome, we are encouraged by
the initial clinical observations of the first adult patient
recently dosed in the REVEAL Phase 1/2 trial,” said Sukumar
Nagendran, M.D., President, and Head of R&D. “We look forward
to providing further clinical updates on the safety and efficacy
observations for the first patient early in the third quarter of
this year, following the required IDMC adjudication of the initial
clinical data. Subsequent REVEAL trial updates will be provided
quarterly, thereafter. We remain on track to submit a CTA to the UK
MHRA in pediatric patients in mid-2023 and to submit an IND
application to the FDA in the second half of 2023.”
Key R&D Day Highlights
TSHA-120: a self-complimentary intrathecally
delivered AAV9 gene therapy being evaluated in an open-label,
dose-escalation, non-randomized Phase 1/2 trial for GAN, an
ultra-rare inherited genetic neurodegenerative disorder with no
approved treatments.
- New comprehensive data analysis
enabled the development of a DPM using all available data from the
largest existing GAN natural history database; DPM demonstrates a
predictable and homogenous disease progression in classic GAN,
which supports the potential for natural history data to serve as a
suitable external control
- Given patient age and the extensive
and wide-spread damage to the central nervous system as well as a
length-dependent progression in the peripheral nervous system, a
more positive treatment impact is expected in outcomes related to
the arms compared to the legs; the longer the disease progresses,
the greater the degeneration with decreasing likelihood of
impacting the disease
- Relatively stable to improved
sensory response amplitudes observed on nerve conduction studies,
in conjunction with increased regenerative clusters on nerve
biopsy, suggest sensory nerve or neuron regeneration in a
progressive neurodegenerative disease
- Using natural history data as an external control, Bayesian
analysis demonstrated a clinically meaningful treatment effect of
TSHA-120 as measured through the slowing of disease progression
observed across multiple functional, electrophysiological and
biological measures:
- Functional endpoints:
- Modified Friedreich’s Ataxia Rating Scale (mFARS) demonstrated
a 99% probability of positive treatment effect on slowing disease
progression, with an estimated average treatment effect of
31%
- Motor Function Measure 32 (MFM32) Domain 3 (distal motor
function – hands) demonstrated a 99% probability of positive
treatment effect on slowing disease progression, with an estimated
treatment effect of 28%
- Visual Acuity, as measured by Logarithm of the Minimum Angle of
Resolution (LogMAR), demonstrated 100% probability of positive
treatment effect on slowing disease progression, with an estimated
treatment effect of 70% in the right eye and 51% in the left
eye
- Electrophysiological endpoints:
- Analysis demonstrated a
100% probability of positive treatment effect on slowing disease
progression, with an estimated treatment effect of 189% and 152%
for Ulnar Sensory Nerve Action Potential (SNAP) and median SNAP
amplitude, respectively, indicating disease improvement
- Compound Muscle Action Potential
(CMAP) demonstrated a 94% probability of positive treatment
effect on slowing disease progression, with an estimated 29%
treatment effect
- Biological
Endpoints:
- 4 out of the 5 patients that had
stabilization or improvements in SNAPs had increased regenerative
clusters on nerve biopsy
- Skin biopsy-nerve fiber density: 5
patients saw stabilization or increases in nerve fiber density of
the skin in at least one location of the proximal or distal leg at
month 12, including 3/3 in the high-dose and one in the medium-high
dose
- Over seven years of long-term clinical data support the safety
and tolerability profile of TSHA-120
- New data analysis will help inform
discussion with the FDA regarding a regulatory path forward for
TSHA-120; formal meeting with FDA expected in the third quarter of
2023
TSHA-102: a self-complementary intrathecally
delivered AAV9 gene transfer therapy being evaluated in the
first-in-human, open labeled, randomized dose escalation and
expansion REVEAL Phase 1/2 trial for Rett syndrome, a rare genetic
neurodevelopmental disorder caused by mutations in the X-linked
MECP2 gene. TSHA-102 utilizes a novel miRNA-Responsive
Auto-Regulatory Element (miRARE) platform designed to regulate
cellular MECP2 expression.
- First patient has been dosed in the REVEAL Phase 1/2 trial in
adult patients with Rett syndrome being conducted at CHU
Sainte-Justine, the Université de Montréal mother and child
university hospital centre in Montreal, Canada
- The patient was discharged from the hospital and has completed
multiple follow-up visits, per the study protocol. Additional
safety and efficacy updates on the first patient are expected in
the early third quarter of 2023, following initial review of
available safety data by the IDMC
- Second potential patient has been identified and will undergo
screening if all protocol defined criteria are met; dosing expected
to proceed pending IDMC review of available clinical data from the
first patient
- CTA submission to UK MHRA in pediatric patients anticipated in
mid-2023
- IND application submission to U.S. FDA expected in the second
half of 2023
About Taysha Gene TherapiesTaysha 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 StatementsThis 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 timing, progress and results of
our preclinical studies and clinical trials of our product
candidates, including TSHA-102 and TSHA-120, including statements
regarding the timing of initiation and completion of studies or
trials and related preparatory work and the period during which the
results of the trials will become available, the potential of our
product candidates, including TSHA-120 and 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 CollinsDirector, Head
of Corporate CommunicationsTaysha Gene Therapies,
Inc.hcollins@tayshagtx.com
Media Contact:Carolyn HawleyCanale
Communicationscarolyn.hawley@canalecomm.com
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