– Data from multiple ongoing clinical studies
of STK-001 show reductions in convulsive seizure frequency and
improvements in cognition and behavior in children and adolescents
with Dravet syndrome –
– Data support the potential for STK-001 to be
the first disease-modifying treatment for Dravet syndrome –
– New pharmacokinetic (PK) modeling of clinical
data from ongoing studies demonstrate that higher STK-001 drug
exposures in brain correlate with greater reductions in seizure
frequency –
Stoke Therapeutics, Inc. (Nasdaq: STOK), a biotechnology company
dedicated to addressing the underlying cause of severe diseases by
upregulating protein expression with RNA-based medicines, today
announced highlights from presentations related to the ongoing
clinical development of STK-001, the first potential new medicine
to treat the underlying cause of Dravet syndrome. Four posters from
the Company’s work in Dravet syndrome are being presented at the
International Epilepsy Congress (IEC) 2023, September 2-6, in
Dublin, Ireland. Data from the recently announced analysis of
results from the ongoing Phase 1/2a studies (MONARCH & ADMIRAL)
and the SWALLOWTAIL open-label extension study are being presented
in a scientific forum for the first time. In addition, a new
pharmacokinetic (PK) analysis of 61 patients treated in STK-001
clinical trials is being presented for the first time, and
demonstrates a correlation between higher STK-001 drug exposure in
brain and greater reductions in seizure frequency over time.
Dravet syndrome is a severe and progressive genetic epilepsy
characterized by frequent, prolonged and refractory seizures
beginning within the first year of life. The disease is classified
as a developmental and epileptic encephalopathy due to the
developmental delays and cognitive impairment associated with the
disease.
“The data from ongoing studies of STK-001 provide the first
evidence of a disease modifying medicine for Dravet syndrome,” said
Helen Cross, MB ChB, Ph.D., Professor, The Prince of Wales’s Chair
of Childhood Epilepsy and Director of University College London
Great Ormond Street Institute of Child Health, Honorary Consultant
in Paediatric Neurology, and the ADMIRAL study lead investigator.
“The primary goal of these studies is to assess safety and
tolerability as well as to inform dose selection for future
studies. Importantly, within these data we can now see a
differentiated pattern of response emerging among the 11 patients
treated with an initial two or three doses of 70mg. Additionally,
data from the open-label extension study that is evaluating ongoing
dosing at lower levels showed, for the first time, improvements in
multiple measures of cognition and behavior among patients who have
been highly refractory to standard anti-seizure medicines.”
The potential of STK-001, a proprietary antisense
oligonucleotide (ASO), to be the first disease-modifying medicine
for Dravet syndrome is supported by multiple presentations of
clinical and other data at IEC.
- MONARCH and ADMIRAL Interim Analyses: Single and multiple doses
of STK-001 up to 70mg were generally well tolerated. Patients
treated with 2 or 3 initial doses of 70mg experienced substantial
and sustained reductions in convulsive seizure frequency with
median reductions of 80% (n=6) at 3 months and 89% (n=3) at 6
months after last dose, compared to baseline.
- SWALLOWTAIL open label extension (OLE): Safety findings among
patients, who are continuing to be dosed with STK-001, were
consistent with the findings from MONARCH and ADMIRAL with the
exception of a greater incidence of CSF protein elevation. Durable
reductions in convulsive seizure frequency were observed throughout
the course of treatment in SWALLOWTAIL. Additionally, data
indicated substantial improvements from baseline through 12 months
of continued STK-001 dosing in multiple assessments of cognition
and behavior.
- BUTTERFLY (natural history study): Small but significant
improvements in receptive communication were observed at Month 12;
however, little to no change was observed across other measures of
cognition and behavior. Data from this study will inform future
Dravet syndrome studies.
- PK Model for STK-001: A relationship between STK-001 brain
exposure and convulsive seizure frequency was evaluated based on
patients treated in the two ongoing Phase 1/2a studies (MONARCH and
ADMIRAL) and the SWALLOWTAIL OLE study in children and adolescents
with Dravet syndrome. The exposure-seizure relationship showed a
significant negative trend based on simulated brain Cavg (R=-0.23,
P<0.001) demonstrating that higher STK-001 brain exposure leads
to greater reductions in convulsive seizure frequency. This PK
model is anticipated to help identify an optimal dosing regimen for
a Phase 3 study.
“Our clinical findings to date show that patients treated with
STK-001 experienced substantial and sustained reductions in
seizures and importantly, improvements in cognition and behavior,”
said Barry Ticho, M.D., Ph.D., Chief Medical Officer of Stoke
Therapeutics. “The new data from our pharmacokinetic model provide
additional confidence in the observed effects of STK-001 and
provide helpful information as we design the pivotal program for
STK-001. We look forward to sharing additional data in the first
quarter of 2024 that are anticipated to provide greater clarity on
dose and dose regimen, and to updating the Dravet community on our
Phase 3 plans in the first half of 2024.”
Details of the Company’s four presentations can be found in the
table below. All presentations are available for download on the
Stoke Therapeutics website under the Investors & News tab.
Title
Presenter
Date
Utilization of a Pharmacokinetic (PK)
Model for STK-001, an antisense oligonucleotide (ASO), in Patients
with Dravet Syndrome (DS) To Predict Pharmacologically Active Doses
in Clinic
Meena, Ph.D., Senior Vice President of
Translational DMPK and Clinical Pharmacology at Stoke
Therapeutics
Sunday, Sept. 3
9:00 AM ET (2:00 PM BST)
Location: Digital Poster
Presentation - Station B
Poster Number: P913
MONARCH and ADMIRAL Interim Analyses:
Ongoing Open-label, Phase 1/2a Studies in US and UK Investigating
Safety and Drug Exposure of STK-001, an Antisense Oligonucleotide
(ASO), in Children and Adolescents with Dravet Syndrome (DS)
Helen Cross, MB ChB, Ph.D., Professor, The
Prince of Wales’s Chair of Childhood Epilepsy and Head of the
Developmental Neuroscience Programme at University College London
Great Ormond Street Institute of Child Health, Honorary Consultant
in Paediatric Neurology, President of the International League
Against Epilepsy
Tuesday, Sept. 5
8:00 AM ET (1:00 PM BST)
Location: Poster Hall
Poster Number: P287
SWALLOWTAIL: An Open-Label Extension (OLE)
Study for Children and Adolescents with Dravet Syndrome (DS) who
Previously Participated in a Study of Antisense Oligonucleotide
(ASO) STK-001
M. Scott Perry, M.D., Head of
Neurosciences and Director of the Genetic Epilepsy Clinic at the
Jane and John Justin Neurosciences Center of Cook Children’s
Medical Center
Tuesday, Sept. 5
8:00 AM ET (1:00 PM BST)
Location: Poster Hall
Poster Number: P286
Twelve-month Analysis of BUTTERFLY: An
Observational Study to Investigate Cognition and Other Non-seizure
Comorbidities in Children and Adolescents with Dravet Syndrome
(DS)
Elaine Wirrell, M.D., Director of
Pediatric Epilepsy at Mayo Clinic, Director of the Child and
Adolescent Neurology Residency Training Program at Mayo Clinic
Tuesday, Sept. 5
2:00 PM ET (7:00 PM BST)
Location: Digital Poster
Presentation - Station A
Poster Number: P169
About Dravet Syndrome Dravet syndrome is a severe and
progressive genetic epilepsy characterized by frequent, prolonged
and refractory seizures, beginning within the first year of life.
Dravet syndrome is difficult to treat and has a poor long-term
prognosis. Complications of the disease often contribute to a poor
quality of life for patients and their caregivers. The effects of
the disease go beyond seizures and often include intellectual
disability, developmental delays, movement and balance issues,
language and speech disturbances, and sleep abnormalities. The
disease is classified as a developmental and epileptic
encephalopathy due to the developmental delays and cognitive
impairment associated with the disease. Compared with the general
epilepsy population, people living with Dravet syndrome have a
higher risk of sudden unexpected death in epilepsy, or SUDEP. There
are no approved disease-modifying therapies for people living with
Dravet syndrome. One out of 16,000 babies are born with Dravet
syndrome, which is not concentrated in a particular geographic area
or ethnic group.
About STK-001 STK-001 is an investigational new medicine
for the treatment of Dravet syndrome currently being evaluated in
ongoing clinical trials. Stoke believes that STK-001, a proprietary
antisense oligonucleotide (ASO), has the potential to be the first
disease-modifying therapy to address the genetic cause of Dravet
syndrome. STK-001 is designed to upregulate NaV1.1 protein
expression by leveraging the non-mutant (wild-type) copy of the
SCN1A gene to restore physiological NaV1.1 levels, thereby reducing
both occurrence of seizures and significant non-seizure
comorbidities. STK-001 has been granted orphan drug designation by
the FDA and the EMA, and rare pediatric disease designation by the
FDA as a potential new treatment for Dravet syndrome.
About the Phase 1/2a MONARCH Study (United States) The
MONARCH study is a Phase 1/2a open-label study of children and
adolescents ages 2 to 18 who have an established diagnosis of
Dravet syndrome and have evidence of a genetic mutation in the
SCN1A gene. The primary objectives for the study are to assess the
safety and tolerability of STK-001, as well as to determine the
pharmacokinetics in plasma and exposure in cerebrospinal fluid. A
secondary objective is to assess the efficacy as an adjunctive
antiepileptic treatment with respect to the percentage change from
baseline in convulsive seizure frequency. Stoke also intends to
measure non-seizure aspects of the disease, such as quality of
life, as secondary endpoints. Additional information about the
MONARCH study can be found at https://www.monarchstudy.com/.
Patients who participated in the MONARCH study and meet study
entry criteria are eligible to continue treatment in SWALLOWTAIL,
an open-label extension (OLE) study designed to evaluate the
long-term safety and tolerability of repeat doses of STK-001. We
expect that SWALLOWTAIL will also provide valuable information on
the preliminary effects of STK-001 on seizures along with
non-seizure aspects of the disease, such as quality of life and
cognition.
Enrollment and dosing in SWALLOWTAIL are ongoing.
About the Phase 1/2a ADMIRAL Study (United Kingdom) The
ADMIRAL study is a Phase 1/2a open-label study of children and
adolescents ages 2 to <18 who have an established diagnosis of
Dravet syndrome and have evidence of a genetic mutation in the
SCN1A gene. The primary objectives for the study are to assess the
safety and tolerability of multiple doses of STK-001, as well as to
determine the pharmacokinetics in plasma and exposure in
cerebrospinal fluid. A secondary objective is to assess the effect
of multiple doses of STK-001 as an adjunctive antiepileptic
treatment with respect to the percentage change from baseline in
convulsive seizure frequency. Stoke also intends to measure
non-seizure aspects of the disease, such as overall clinical status
and quality of life, as secondary endpoints.
Patients who participated in the ADMIRAL study and meet study
entry criteria are eligible to continue treatment in LONGWING, an
open-label extension (OLE) study designed to evaluate the long-term
safety and tolerability of repeat doses of STK-001. We expect that
LONGWING will also provide valuable information on the preliminary
effects of STK-001 on seizures along with non-seizure aspects of
the disease, such as quality of life and cognition.
Enrollment and dosing in LONGWING are ongoing.
About TANGO TANGO (Targeted Augmentation of Nuclear Gene
Output) is Stoke’s proprietary research platform. Stoke’s initial
application for this technology are diseases in which one copy of a
gene functions normally and the other is mutated, also called
haploinsufficiencies. In these cases, the mutated gene does not
produce its share of protein, resulting in disease. Using the TANGO
approach and a deep understanding of RNA science, Stoke researchers
design antisense oligonucleotides (ASOs) that bind to pre-mRNA and
help the functional (or wild-type) genes produce more protein.
TANGO aims to restore missing proteins by increasing – or stoking –
protein output from healthy genes, thus compensating for the mutant
copy of the gene.
About Stoke Therapeutics Stoke Therapeutics (Nasdaq:
STOK), is a biotechnology company dedicated to addressing the
underlying cause of severe diseases by upregulating protein
expression with RNA-based medicines. Using Stoke’s proprietary
TANGO (Targeted Augmentation of Nuclear Gene Output) approach,
Stoke is developing antisense oligonucleotides (ASOs) to
selectively restore protein levels. Stoke’s first compound,
STK-001, is in clinical testing for the treatment of Dravet
syndrome, a severe and progressive genetic epilepsy. Dravet
syndrome is one of many diseases caused by a haploinsufficiency, in
which a loss of ~50% of normal protein levels leads to disease.
Stoke is pursuing the development of STK-002 for the treatment of
autosomal dominant optic atrophy (ADOA), the most common inherited
optic nerve disorder. Stoke’s initial focus is haploinsufficiencies
and diseases of the central nervous system and the eye, although
proof of concept has been demonstrated in other organs, tissues,
and systems, supporting its belief in the broad potential for its
proprietary approach. Stoke is headquartered in Bedford,
Massachusetts with offices in Cambridge, Massachusetts. For more
information, visit https://www.stoketherapeutics.com/ or follow
Stoke on X @StokeTx.
Cautionary Note Regarding Forward-Looking Statements This
press release contains forward-looking statements within the
meaning of the “safe harbor” provisions of the Private Securities
Litigation Reform Act of 1995, including, but not limited to the
ability of STK-001 to treat the underlying causes of Dravet
syndrome and reduce seizures or show improvements in non-seizure
comorbidities at the indicated dosing levels or at all, and the
timing and expected progress of clinical trials, data readouts and
presentations. Statements including words such as “plan,” “will,”
“continue,” “expect,” or “ongoing” and statements in the future
tense are forward-looking statements. These forward-looking
statements involve risks and uncertainties, as well as assumptions,
which, if they prove incorrect or do not fully materialize, could
cause our results to differ materially from those expressed or
implied by such forward-looking statements, including, but not
limited to, risks and uncertainties related to: the Company’s
ability to advance, obtain regulatory approval of and ultimately
commercialize its product candidates; the timing and results of
preclinical and clinical trials; the risk that positive results in
a clinical trial may not be replicated in subsequent trials or
successes in early stage clinical trials may not be predictive of
results in later stage trials and preliminary interim data readouts
of ongoing trials may show results that change when such trials are
completed; the Company’s ability to fund development activities and
achieve development goals; the Company’s ability to protect its
intellectual property; and other risks and uncertainties described
under the heading “Risk Factors” in the Company’s Annual Report on
Form 10-K for the year ended December 31, 2022, its quarterly
reports on Form 10-Q, and the other documents the Company files
from time to time with the Securities and Exchange Commission.
These forward-looking statements speak only as of the date of this
press release, and the Company undertakes no obligation to revise
or update any forward-looking statements to reflect events or
circumstances after the date hereof.
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Stoke Media & Investor Contacts: Dawn Kalmar Chief
Communications Officer dkalmar@stoketherapeutics.com
781-303-8302
Eric Rojas Vice President, Investor Relations
IR@stoketherapeutics.com 617-312-2754
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