Encoded Therapeutics Presents Preclinical Data Across its Gene Therapy Portfolio at the 27th Annual Meeting of the American Society of Gene & Cell Therapy (ASGCT)
2024年5月7日 - 8:02PM
ビジネスワイヤ(英語)
- Four presentations highlight expansion of the company’s CNS
pipeline and vector engineering platform
- Preclinical data presented supports potential to advance
programs in Angelman Syndrome and Lennox-Gastaut Syndrome
- Proof-of-concept data demonstrating knock-down of neuropathic
pain (SCN9A) and Alzheimer’s disease (MAPT) targets showcase
advancements in the company’s vector engineering platform
Encoded Therapeutics Inc., a biotechnology company developing
genetic medicines for severe central nervous system (CNS)
disorders, today highlights oral and poster presentations on the
Company’s preclinical gene therapy programs and vector engineering
platform at the 27th ASGCT Annual Meeting being held May 7 – 11,
2024 in Baltimore, MD.
“We are thrilled to share multiple advancements across our
portfolio of precision genetic medicines, showcasing substantial
progress across various fronts. These data underscore our
platform’s potential to deliver precision therapies for a range of
CNS diseases,” said Stephanie Tagliatela, Chief Scientific Officer
at Encoded. “Alongside clinical advancement of our lead program,
ETX101 for SCN1A+ Dravet syndrome, we are poised to nominate
multiple programs to development in 2025, marking yet another
significant milestone.”
Oral Presentation
Title: GABA Selective AAV-mediated Gene Therapy Provides
Durable Seizure Protection in Multiple Refractory Epilepsy
Models (Abstract #19) Session: AAV Vectors - Preclinical and
Proof-of-Concept: Therapy Focus Date & Time: Tuesday, May 7,
1:45–2:00 p.m. ET Location: Ballroom 2
Epilepsy affects approximately 1% of the population, with nearly
one third of cases failing to respond to first- and second-line
treatments. Encoded’s vector engineering platform has enabled the
development of GABA-selective AAV-mediated gene therapies designed
to potentiate GABAergic neurotransmission and modulate the circuit
dysfunction underlying refractory epilepsies. Our lead candidate
reduced seizure incidence and severity in two biologically distinct
seizure assays with no adverse impact on body weight, motor
function or locomotion. Furthermore, the top candidate is
well-tolerated in non-human primates (NHP) even at high doses.
These data support further development of our candidate gene
therapy for the treatment for refractory epilepsies.
Poster Presentations
Title: Advancing Gene Therapy for STXBP1-related Disorders
Through Targeted Vector Engineering: Efficacy and Safety Results in
Mice and Non-Human Primates (Abstract #508) Date & Time:
Wednesday, May 8, 5:30–7:00 p.m. ET Location: Exhibit Hall
STXBP1-related disorders (STXBP1-RD) result from
loss-of-function variants in STXBP1, causing severe developmental
delay and treatment-resistant epilepsy. Encoded has engineered AAV9
vectors that drive potent expression within CNS tissue while
reducing off-target expression in dorsal root ganglia (DRG) and
non-neuronal tissues. These engineered AAV9-STXBP1 vectors achieved
robust, dose-dependent improvements in seizure, cognitive, and
motor phenotypes in Stxbp1+/- mice, with no observed dose-limiting
toxicity. In NHPs, the engineered vectors showed strong CNS
expression and were well-tolerated. Furthermore, the inclusion of a
DRG de-targeting element reduced expression within the DRG and
spinal cord by >10-fold, ameliorating microscopic DRG-related
findings. These findings establish proof-of-concept for an
AAV9-based gene therapy for STXBP1-RD and support the use of
modular regulatory element engineering to drive desired expression
profiles within the CNS.
Title: A Vectorized miRNA-based Approach to Unsilence UBE3A
in Angelman Syndrome (Abstract #1125) Date & Time:
Thursday, May 9, 5:30–7:00 p.m. ET Location: Exhibit Hall
Angelman syndrome (AS) is a severe neurodevelopmental disorder
characterized by intellectual disability, ataxia, and seizures. AS
is caused by loss-of-function of the maternally-inherited UBE3A
gene. Unsilencing of the paternal copy of UBE3A has the potential
address the underlying cause of the disease while mitigating the
risk of UBE3A overexpression-related toxicity. We demonstrated that
an AAV-based miRNA vector was capable of upregulating paternal
UBE3A and correcting multiple phenotypes in the AS mouse model.
Encoded’s lead miRNA candidate was well-tolerated in NHPs and
demonstrated potent unsilencing of paternal UBE3A in critical brain
regions. Collectively, these data support further development an
AAV-based miRNA treatment approach for Angelman Syndrome.
Title: Identification of Potent and Selective AAV-miRNA
Candidates to Knockdown Non-Monogenic Neurological Targets SCN9A
(Pain) and MAPT (Tauopathies) (Abstract #1601) Date & Time:
Friday, May 10, 5:30–7:00 p.m. ET Location: Exhibit Hall
Encoded's innovative AAV-mediated miRNA platform offers a
promising strategy for long-term knockdown of target genes in the
central and peripheral nervous systems. We identified potent and
target-specific miRNA candidates to effectively knock down two
clinically relevant, non-monogenic neuronal targets: SCN9A and
MAPT. SCN9A encodes the NaV1.7 sodium channel, which is associated
with pain sensation, while MAPT encodes the microtubule protein,
Tau, which is implicated in Alzheimer's disease neuropathology.
Encoded's miRNA candidates demonstrated potent, dose-dependent, and
selective knockdown of SCN9A in human iPSC sensory neurons and in
mouse dorsal root ganglion sensory neurons, establishing
proof-of-concept for miRNA-based inhibition of NaV1.7. Similarly,
MAPT candidates significantly reduced Tau protein levels in vitro
and in vivo. These findings support advancement of SCN9A and MAPT
candidates to NHP studies and showcase the potential of vectorized
miRNA knockdown as a promising treatment avenue for various
neurological disorders.
About Encoded Therapeutics
Encoded Therapeutics is a clinical-stage genetic medicines
company developing potentially disease-modifying therapies to
improve the lives of people with severe CNS disorders. Our
proprietary vector engineering approach combines novel regulatory
elements and payloads with AAV vectors to unlock innovative
solutions for debilitating, intractable CNS conditions. At the
forefront is our flagship clinical program, ETX101 for Dravet
syndrome, which targets the underlying cause of the disorder to
enable highly selective upregulation of SCN1A for potentially
long-lasting benefit. In parallel, we are advancing a pipeline of
potentially best-in-class programs to address significant unmet
needs across both monogenic and prevalent CNS conditions. For more
information, please visit www.encoded.com.
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Jennifer Gorzelany communications@encoded.com 650-515-9695