Author: encoded.tw

SOUTH SAN FRANCISCO, Calif. – Encoded Therapeutics, Inc. (“Encoded”), a clinical stage biotechnology company developing precision genetic medicines for severe neurological disorders, today will present an expanded dataset from the ongoing POLARIS Phase 1/2 trials of ETX101, its investigational AAV9 based gene regulation therapy designed as a one time, disease modifying treatment for SCN1A+ Dravet syndrome. The update includes additional patients, early data from the top dose level (DL4), and longer term outcomes that further define the emerging clinical profile of ETX101 in children aged 6 months to 7 years. These results will be featured in an oral presentation during the Presidential Symposium (Wednesday, May 13, 2:28-2:39 p.m. ET) at the 29th Annual Meeting of the American Society of Gene & Cell Therapy (ASGCT).

Treatment with a single dose of ETX101 resulted in a robust and dose-dependent antiseizure effect, with durability through 52 weeks of observation. Clinically meaningful improvements in adaptive behavior were reported across the full age range tested. Notably, children treated before age 2 rapidly diverged from the developmental stagnation expected from natural history, with cognitive trajectories generally consistent with neurotypical development.

“Parents of children with Dravet syndrome live with the fear of every seizure and the heartbreak of watching development stall,” said Mary Anne Meskis, CEO of the Dravet Syndrome Foundation. “To see the early and robust seizure reductions paired with meaningful developmental gains is profoundly encouraging. Families have been waiting for therapies that don’t just manage symptoms but give their children a chance to keep learning and growing.”

ASGCT Oral Presentation Highlights

All analyses reflect data through the April 10, 2026, data cutoff.

Seizure Reduction:

• From Week 5 through Week 52, durable, dose-dependent antiseizure effects were observed with approximately a 76% median monthly countable seizure frequency (MCSF) reduction at DL3 (n=3) – during a developmental window typically associated with increasing seizure burden despite treatment with standard-of-care antiseizure medicines.
• Early data from DL4 demonstrated continued dose-dependent antiseizure activity, with the strongest response observed in patients who did not receive sirolimus (n=4), consistent with molecular and animal data showing that sirolimus dampens the therapeutic signal by reducing protein expression. No differences in safety outcomes were observed between patients that received sirolimus and those who did not.

Neurodevelopmental Improvements:

• Patients who reached 52 weeks of observation (n=9) demonstrated improvements in multiple domains of adaptive behavior based on the caregiver interview-based Vineland Adaptive Behavior Scales (VABS 3). The most notable gains were observed in receptive and expressive communication and motor function, with meaningful progress also observed in self care and social interaction.
• In patients treated before age 2, progressive gains in cognition were evident as early as Week 16 (n=11) and continued through Week 52 (n=4), as measured by the Bayley Scales of Infant and Toddler Development (Bayley 4). These data show that these young patients rapidly diverged from the stagnation seen in the ENVISION natural history study, with trajectories generally consistent with neurotypical development over the 52-week observation period.

“Watching these young children not only achieve durable seizure reduction but also show early evidence of neurodevelopmental rescue is truly remarkable,” said Sal Rico, M.D., Ph.D., Chief Medical Officer of Encoded. “These data reinforce our belief that ETX101 has the potential to change the course of the disease and future outlook for the Dravet community.”

To date, ETX101 has shown a favorable safety profile and has been well-tolerated across all four dose levels, with no treatment- or procedure-related serious adverse events. The most common treatment-related adverse events were transaminase elevations (a known AAV class effect), which were clinically asymptomatic and resolved in all participants.

About the POLARIS Clinical Development Program

The POLARIS program is a comprehensive clinical investigation of ETX101 in children and adolescents with SCN1A+ Dravet syndrome, comprising multiple Phase 1-3 clinical trials. The first phase of POLARIS includes three ongoing open-label, Phase 1/2 dose-escalation, multicenter trials (ENDEAVOR Part 1 (US), EXPEDITION (UK), and WAYFINDER (Australia)) in infants and young children aged 6 months to 7 years. ENDEAVOR Part 1B, an expansion study in the US, is actively enrolling children and adolescents aged 4 to 18 years. These studies are evaluating the safety and preliminary efficacy of ETX101 in children and adolescents with Dravet syndrome due to variants in the SCN1A gene. The pivotal ENDEAVOR Part 2 study is also ongoing, evaluating seizure and neurodevelopmental outcomes in young children aged 6 months to 4 years.

About ETX101

ETX101 is an investigational AAV9-based gene regulation therapy designed to increase the expression of the SCN1A gene to restore sodium channel function in inhibitory interneurons. By targeting the root mechanism, ETX101 has the potential to treat the full spectrum of Dravet syndrome symptoms, including seizures, communication and cognitive impairment, behavioral issues, and motor dysfunction. The therapy is administered via a single intracerebroventricular (ICV) injection and is designed for long-term benefit. ETX101 has received Breakthrough Therapy, Regenerative Medicine Advanced Therapy, Fast Track, Rare Pediatric Disease, and Orphan Drug designations from the FDA. It also was selected for the FDA’s CMC Development and Readiness Pilot (CDRP) Program and received Orphan designation from the European Medicines Agency (EMA).

About Encoded Therapeutics

Encoded Therapeutics is a clinical-stage biotechnology company developing one-time precision genetic medicines for severe monogenic and common neurological disorders. The company’s vector engineering platform enables highly targeted and cell-type-selective control of gene expression in the brain and peripheral nervous system, allowing potent and precise modulation of disease-relevant genes to address underlying disease biology. Encoded’s end to end innovation engine-spanning discovery, development, and in house GMP manufacturing-creates a streamlined path to advance a diversified pipeline of one time treatments across a broad range of neurological conditions. Encoded is driven by a mission to meaningfully improve the lives of patients and families affected by devastating neurological disorders. For more information, please visit www.encoded.com.

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Contacts

Investors/Business Development
Jennifer Gorzelany
communications@encoded.com

Media
Lori Rosen
lori@redhousecomms.com

SOUTH SAN FRANCISCO, Calif. – Encoded Therapeutics Inc. (“Encoded”), a clinical-stage biotechnology company developing precision genetic medicines for severe neurological disorders, today will present new preclinical data across two posters at the 29th Annual Meeting of the American Society of Gene & Cell Therapy (ASGCT). The presentations expand the growing body of evidence supporting the company’s vector engineering platform, which is designed to achieve cell-type-selective regulation of disease relevant genes across neurological disorders and to enable differentiated, one time genetic medicines. Posters will be available 5:00-6:30 p.m. ET in the Poster Hall.

“The data we’re presenting at ASGCT further demonstrate how our vector engineering platform can be tuned to achieve the level of cellular precision required to address the diverse biological challenges of neurological disorders,” said Stephanie Tagliatela, Co-founder and Chief Scientific Officer of Encoded. “From highly selective nociceptor targeting in the peripheral nervous system to broad neuronal transduction and UBE3A unsilencing in the CNS, these findings reinforce the potential for one time genetic medicines that directly address the underlying mechanisms of disease. Our goal is to build therapies that are both biologically precise and clinically meaningful, and these new data move us closer to that vision.”

NociPro: A Novel Modality Agnostic Promoter Platform for Precise Cellular Targeting of Nociceptor Sensory Neurons in Gene Therapy for Chronic Pain (Poster #1312):

The poster highlights NociPro-a regulatory element derived from human genomic sequences that enables potent and selective targeting of pain sensing nociceptive neurons. Developed using Encoded’s precision vector engineering platform, NociPro is a core component of ETX301, the company’s vectorized miRNA candidate targeting SCN9A (miRNA^hSCN9A) to treat post amputation neuroma pain.

In new preclinical studies across mouse, human iPSC derived neurons, and non-human primates (NHPs), NociPro drove robust and selective transgene expression in pain-sensing dorsal root ganglion (DRG) nociceptors, with activity comparable to ubiquitous and pan neuronal benchmark promoters. Across species, NociPro demonstrated highly selective DRG restricted activity, with no detectable expression in the CNS. When coupled with miRNA^hSCN9A, NociPro achieved Na_V1.7 protein reduction comparable to a ubiquitous benchmark promoter in NHPs, while demonstrating improved tolerability.

Building on prior work that demonstrated robust, gene selective knockdown of SCN9A (Na_V1.7) using an engineered vectorized miRNA, these findings underscore the potential of NociPro to enhance the precision and therapeutic index of gene therapies for chronic pain.

Neuronal Transduction and UBE3A Unsilencing for the Treatment of Angelman Syndrome (Poster #1468):

The poster features preclinical proof of concept data for a one time, intravenously delivered vectorized miRNA gene therapy designed to unsilence the UBE3A gene. By pairing an optimized miRNA candidate with an externally-developed blood brain barrier-crossing AAV variant, the approach achieved widespread miRNA expression across disease relevant brain regions in NHPs.

Corresponding target engagement included a 57% increase in UBE3A expression and a 24% increase in UBE3A protein levels across disease-relevant brain regions, including cortex, hippocampus, and thalamus. This therapy was well tolerated in a 60 day study with no adverse findings. These results highlight the potential for a non invasive, durable therapeutic approach that addresses the underlying cause of Angelman syndrome.

About Encoded Therapeutics

Encoded Therapeutics is a clinical-stage biotechnology company developing one-time precision genetic medicines for severe monogenic and common neurological disorders. The company’s vector engineering platform enables highly targeted and cell-type-selective control of gene expression in the brain and peripheral nervous system, allowing potent and precise modulation of disease-relevant genes to address underlying disease biology. Encoded’s end to end innovation engine-spanning discovery, development, and in house GMP manufacturing-creates a streamlined path to advance a diversified pipeline of one time treatments across a broad range of neurological conditions. Encoded is driven by a mission to meaningfully improve the lives of patients and families affected by devastating neurological disorders. For more information, please visit www.encoded.com.

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Contacts

Investors/Business Development
Jennifer Gorzelany
communications@encoded.com

Media
Lori Rosen
lori@redhousecomms.com

SOUTH SAN FRANCISCO, Calif. – Encoded Therapeutics, Inc. (“Encoded”), a clinical-stage biotechnology company developing precision genetic medicines for severe neurological disorders, today announced that the first patient has been dosed in the pivotal ENDEAVOR Part 2 study of ETX101 for Dravet syndrome, marking an important transition into late-stage clinical development for the program. Encoded has also initiated dosing in the ENDEAVOR Part 1B expansion study in patients aged 4 to 18 years, extending evaluation of ETX101 across a broader patient population.

In addition, ETX101 has been selected for the FDA’s Chemistry, Manufacturing, and Controls Development and Readiness Pilot (CDRP) Program, supporting alignment of manufacturing readiness with accelerated clinical development. The company also announced advancement of its pipeline, with the nomination of ETX301 as a development candidate for post-amputation neuroma pain and an Investigational New Drug (IND) application planned for 2027.

ETX101 in Dravet Syndrome

ETX101, which has received Breakthrough Therapy designation from the FDA, is advancing as a potential disease-modifying therapy for SCN1A+ Dravet syndrome, with dosing now underway in the pivotal ENDEAVOR Part 2 study. This milestone builds on encouraging data from earlier clinical experience.

ETX101 is an AAV9 based, cell selective gene regulation therapy designed to durably restore SCN1A expression and directly target the underlying cause of the disease. Part of the POLARIS program, ENDEAVOR Part 2 is evaluating seizure and neurodevelopmental outcomes in 30 infants and young children aged 6 months to 4 years, with enrollment expected to be completed by the end of 2026 and initial data anticipated by the end of 2027. The study is being conducted across multiple centers of excellence in the US, UK, and Australia.

Encoded has also dosed the first patient in ENDEAVOR Part 1B, an open-label expansion study assessing safety and preliminary efficacy in older children and adolescents aged 4 to 18 years. This study is designed to extend the evaluation of ETX101 across a broader patient population. Initial data from Part 1B is expected in the fourth quarter of 2026.

“Promising open-label data from the initial Phase 1/2 studies generated significant interest from the Dravet community, and dosing the first patients at the University of California, San Francisco in the pivotal and expansion studies is an important step forward for families affected by this disease,” said Adam Numis, M.D., Associate Professor of Neurology and Pediatrics at UCSF, and Principal Investigator for the ENDEAVOR studies. “This therapy is designed to target SCN1A and address the underlying genetic cause of disease. Evaluating this approach across infants, children, and adolescents reflects our dedicated effort to understand its potential to meaningfully alter disease trajectory in the broader patient population.”

ETX101 Selected for FDA CDRP Program

ETX101 has been selected for the FDA’s CDRP Program, which is designed to ensure that Chemistry, Manufacturing, and Controls (CMC) development keeps pace with clinical progress, particularly for therapies addressing serious unmet need. Participation in this selective program facilitates deeper engagement with the FDA to support Encoded’s manufacturing strategy as the program advances.

ETX301 in Post-Amputation Neuroma Pain

Encoded has nominated ETX301, an investigational AAV9 based vectorized microRNA (miRNA), as a development candidate for post-amputation neuroma pain, with an IND submission planned for 2027. ETX301 is designed to selectively and durably knock down SCN9A (Na_V1.7), a key mediator of pain signaling. The therapy is designed to target dorsal root ganglia (DRG) nociceptive neurons, with the goal of achieving durable analgesia while limiting potential off-target effects.

Painful neuromas following limb amputation represent a well-defined, localized neuropathic pain condition driven by aberrant peripheral nerve signaling, with evidence of increased Na_V1.7 expression in affected tissues. ETX301 will initially be evaluated in patients with lower limb amputations, a population with a high burden of chronic pain and substantial impact on function and quality of life. Post-amputation neuroma pain affects an estimated 100,000 patients in the US, with approximately 5,000 new cases annually.

Encoded’s preclinical studies support the therapeutic potential of this approach, including durable Na_V1.7 knockdown in non-human primates and sustained analgesic effects in rodent models of neuropathic pain.

“By targeting a key mediator of pain signaling, ETX301 has the potential to address conditions associated with severe and persistent pain in a fundamentally new way,” said Stephanie Tagliatela, Chief Scientific Officer of Encoded. “With an IND planned for 2027, we’re advancing a program grounded in strong preclinical data and enabled by the same platform and translational framework as ETX101.”

About ETX101

ETX101 is an investigational AAV9-based gene regulation therapy designed to increase the expression of the SCN1A gene to restore sodium channel function in inhibitory interneurons. By targeting the root mechanism, ETX101 has the potential to treat the full spectrum of Dravet syndrome symptoms, including seizures, communication and cognitive impairment, behavioral issues, and motor dysfunction. The therapy is administered via a single intracerebroventricular (ICV) injection and is designed for long-term benefit. ETX101 has received Breakthrough Therapy, Regenerative Medicine Advanced Therapy, Fast Track, Rare Pediatric Disease, and Orphan Drug designations from the FDA, was selected for the FDA’s CMC Development and Readiness Pilot (CDRP) Program and received Orphan designation from the European Medicines Agency (EMA).

About ETX301

ETX301 is an investigational AAV9-based vectorized microRNA (miRNA) therapy designed to selectively and durably knock down SCN9A (Na_V1.7), a key mediator of pain signaling, in nociceptors. The therapy is designed for administration via a single intrathecal (IT) injection and is intended to deliver long-term benefit. ETX301 is currently in development for the treatment of chronic neuropathic pain caused by lower limb post-amputation neuroma, with an Investigational New Drug (IND) application anticipated in 2027. This initial indication is supported by the localized and well-characterized biology of painful neuromas, including evidence of upregulated Na_V1.7 expression in affected tissues. By targeting a key mediator of pain signaling, ETX301 has the potential to address severe, intractable chronic pain across multiple settings.

About Encoded Therapeutics

Encoded Therapeutics is a clinical-stage biotechnology company developing one-time precision genetic medicines for severe monogenic and common neurological disorders. The company’s vector engineering platform enables highly targeted and cell-type-selective control of gene expression in the brain and peripheral nervous system, allowing potent and precise modulation of disease-relevant genes to address underlying disease biology. Encoded’s end to end innovation engine-spanning discovery, development, and in house GMP manufacturing-creates a streamlined path to advance a diversified pipeline of one time treatments across a broad range of neurological conditions. Encoded is driven by a mission to meaningfully improve the lives of patients and families affected by devastating neurological disorders. For more information, please visit www.encoded.com.

View source version on businesswire.com: https://www.businesswire.com/news/home/20260506415018/en/

Contacts

Investors/Business Development
Jennifer Gorzelany
communications@encoded.com

Media
Lori Rosen
lori@redhousecomms.com

SOUTH SAN FRANCISCO, Calif. – Encoded Therapeutics Inc., a clinical-stage genetic medicines company, today announced its participation in the 29^th Annual Meeting of the American Society of Gene & Cell Therapy (ASGCT), taking place May 11-15, 2026, in Boston, Massachusetts. Encoded will present three abstracts, including one oral presentation in the Presidential Symposium and two scientific posters, demonstrating the breadth of its vector engineering platform across severe neurological disorders.

The Presidential Symposium oral presentation will focus on ETX101, Encoded’s precision gene-regulation therapy being developed as a one-time treatment for patients with SCN1A+ Dravet syndrome. ETX101 is designed to increase SCN1A expression selectively within GABAergic inhibitory neurons, offering the potential for disease modification.

The poster presentations will include preclinical data on Encoded’s novel regulatory element, NociPro, which targets pain-sensing nociceptive neurons for the treatment of chronic pain conditions, and an intravenously delivered vectorized miRNA approach designed to unsilence UBE3A for the treatment of Angelman syndrome.

“We are incredibly proud to present our latest POLARIS data at this prestigious ASGCT platform, showcasing ETX101’s potential to improve seizure control and fundamentally rescue learning and cognitive development in children living with Dravet syndrome,” said Sal Rico, M.D., Ph.D., Chief Medical Officer of Encoded. “Together with our poster presentations, these findings underscore our vector engineering approach and its potential to deliver precision one time genetic medicines for neurological disorders.”

Presentation Details

Oral Presentation: Safety and Efficacy of ETX101, an Investigational AAV9-based Gene Therapy for SCN1A+ Dravet Syndrome: Interim Results from the POLARIS Phase 1/2 Clinical Trials
Session: General Session: Presidential Symposium
Location: Exhibit Hall B1 (Exhibit Level)
Date and Time: Wednesday, May 13, 2026; 2:26 PM – 2:37 PM ET

Poster Presentation: NociPro: A Novel Modality-Agnostic Promoter Platform for Precise Cellular Targeting of Nociceptor Sensory Neurons in Gene Therapy for Chronic Pain
Abstract Number: 1312
Location: Poster Hall
Date and Time: Tuesday, May 12, 2026; 5:00 PM – 6:30 PM ET

Poster Presentation: An Experimental Intravenous AAV-miRNA-based Approach Achieves Broad Neuronal Transduction and UBE3A Unsilencing for the Treatment of Angelman Syndrome
Abstract Number: 1468
Location: Poster Hall
Date and Time: Tuesday, May 12, 2026; 5:00 PM – 6:30 PM ET

About Encoded Therapeutics

Encoded Therapeutics is a clinical-stage biotechnology company developing one-time precision genetic medicines for severe monogenic and common neurological disorders. The company’s vector engineering platform enables highly targeted and cell-type-selective control of gene expression in the brain and peripheral nervous system, allowing potent and precise modulation of disease-relevant genes to address underlying disease biology. Encoded’s end to end innovation engine-spanning discovery, development, and in house GMP manufacturing-creates a streamlined path to advance a diversified pipeline of one time treatments across a broad range of neurological conditions. Encoded is driven by a mission to meaningfully improve the lives of patients and families affected by devastating neurological disorders. For more information, please visit www.encoded.com.

View source version on businesswire.com: https://www.businesswire.com/news/home/20260427756983/en/

Contacts

Investors/Business Development
Jennifer Gorzelany
communications@encoded.com

Media
Lori Rosen
lori@redhousecomms.com

SOUTH SAN FRANCISCO, Calif. – Encoded Therapeutics, Inc. (“Encoded”), a clinical-stage biotechnology company developing precision genetic medicines for severe neurological disorders, today announced the successful completion of its Initial Comprehensive Multidisciplinary Regenerative Medicine Advanced Therapy (RMAT) meeting with the U.S. Food and Drug Administration (FDA), and alignment on the pivotal study design supporting the company’s planned BLA submission for ETX101, an AAV9-based gene regulation therapy designed as a one-time, disease-modifying treatment for SCN1A+ Dravet syndrome.

Key meeting outcomes included:

• Confirmation of the pivotal study design; ENDEAVOR Part 2 will evaluate a single administration of ETX101 over 52 weeks compared with a sham delayed-treatment control in 30 infants and young children aged 6 months to <4 years with SCN1A+ Dravet syndrome. The primary endpoint is reduction in monthly countable seizure frequency (MCSF), with a key secondary endpoint assessing improvement in cognition as measured by the Bayley Scales of Infant and Toddler Development, Fourth Edition (Bayley-4).
• Alignment on expansion of Phase 1/2 open label study; ENDEAVOR Part 1B will evaluate ETX101 in older participants aged 4 years to <18 years with SCN1A+ Dravet syndrome (n=5). The primary objective is to assess safety and tolerability. Secondary objectives are to evaluate preliminary efficacy, including reduction in MCSF and impact on neurodevelopment relative to baseline and natural history controls.

“Our alignment with the FDA on the pivotal study design marks an important step toward regulatory approval of ETX101 for children with Dravet syndrome,” said Sal Rico, M.D., Ph.D., Chief Medical Officer of Encoded. “This study design provides a rigorous and efficient path to evaluate ETX101 in the youngest population where we have the greatest opportunity to demonstrate a rapid and transformative benefit, while the ENDEAVOR Part 1B study enables the assessment of disease-modifying potential of ETX101 across the entire population of older children and adolescents with Dravet syndrome.”

Dr. Rico added, “We are proud to also announce that initiation of both ENDEAVOR Part 1B and Part 2 is already underway, demonstrating our ability to rapidly translate regulatory feedback into clinical execution. We expect patient dosing in both studies to begin in 2Q26, marking another meaningful advance in our ETX101 program and continuing our work on behalf of the Dravet community.”

In parallel with this progress, ETX101 clinical data will be presented in the Presidential Symposium at the 2026 ASGCT Annual Meeting taking place in Boston, May 11 – 15, 2026. This recognition underscores the strength of the emerging clinical data and the potential for ETX101 to meaningfully impact the course of disease in children with Dravet syndrome.

For ENDEAVOR Part 1B, initial data is expected in the fourth quarter of 2026. For ENDEAVOR Part 2, the Company plans to complete enrollment by the end of 2026 with initial data expected by the end of 2027.

Clinical Data from the POLARIS Phase 1/2 Study Support the Pivotal Study Design

In December 2025, Encoded reported positive interim data from the POLARIS Phase 1/2 program, showing significant and durable seizure reductions and neurodevelopmental gains in participants treated with ETX101. These data support the potential for ETX101 to rescue disease stagnation in young children, and together with the favorable safety profile observed to date, informed the design of the pivotal study.

ENDEAVOR Part 2 Study Design

The pivotal study is a randomized, double-blind, sham delayed-treatment controlled trial in 30 patients with SCN1A+ Dravet syndrome aged 6 months to <4 years. Participants will receive a single intracerebroventricular administration of ETX101. The primary endpoint of the study is percent change from baseline in MCSF at 52 weeks in patients receiving ETX101 compared with patients undergoing a sham procedure. The key secondary endpoint is change from baseline in the Bayley-4 Cognitive subdomain raw score. Additional endpoints include safety and improvements in behavior and cognition as measured by the Vineland Adaptive Behavior Scales, Third Edition (Vineland-3). ENDEAVOR Part 2 will be conducted in the United States, United Kingdom and Australia.

ENDEAVOR Part 1B Study Design

Part 1B is an open-label expansion of ENDEAVOR Part 1 to evaluate ETX101 in older children and adolescents aged 4 years to <18 years with SCN1A+ Dravet syndrome. The primary objective of the study is to assess the safety and tolerability of ETX101. Secondary objectives are to evaluate preliminary efficacy of ETX101 by assessing the percent change from baseline in MCSF, as well as the impact on the neurodevelopmental symptoms of Dravet syndrome, including cognition, communication, and motor function. ENDEAVOR Part 1B will be conducted in the United States.

About ETX101

ETX101 is an investigational AAV9-based gene regulation therapy designed to increase the expression of the SCN1A gene to restore sodium channel function in inhibitory interneurons. By targeting the root mechanism, ETX101 has the potential to treat the full spectrum of Dravet syndrome symptoms, including seizures, communication and cognitive impairment, behavioral issues, and motor dysfunction. The therapy is administered via a single intracerebroventricular (ICV) injection and is designed for long-term benefit. ETX101 has received Breakthrough Therapy, Regenerative Medicine Advanced Therapy, Fast Track, Rare Pediatric Disease, and Orphan Drug designations from the FDA, as well as Orphan designation from the European Medicines Agency (EMA).

About Encoded Therapeutics

Encoded Therapeutics is a clinical-stage biotechnology company developing precision genetic medicines to transform the lives of patients with severe neurological disorders. The company’s vector engineering platform enables potent and cell-type-selective regulation of gene expression, allowing for targeted modulation of disease-relevant genes. Encoded is advancing a pipeline of programs across genetic epilepsies and other neurological disorders with significant unmet need. With integrated discovery, development, and manufacturing capabilities, Encoded is positioned to efficiently move programs from concept through the clinic. Encoded is driven by a mission to meaningfully improve the lives of patients and families affected by devastating neurological disorders. For more information, please visit www.encoded.com.

View source version on businesswire.com: https://www.businesswire.com/news/home/20260325295907/en/

Contacts

Investors/Business Development
Jennifer Gorzelany
communications@encoded.com

Media
Lori Rosen
lori@redhousecomms.com

SOUTH SAN FRANCISCO, Calif. – Encoded Therapeutics, Inc. (“Encoded”), a clinical-stage biotechnology company developing precision genetic medicines for severe neurological disorders, today announced that the U.S. Food and Drug Administration (FDA) has granted Breakthrough Therapy Designation to ETX101 for the treatment of SCN1A+ Dravet syndrome. This designation is in addition to Regenerative Medicine Advanced Therapy (RMAT), Fast Track, Orphan Drug, and Rare Pediatric Disease Designations, all previously granted by the FDA.

“Breakthrough Therapy Designation reflects the FDA’s recognition of both the urgent need for disease-modifying Dravet syndrome treatments and the potential of ETX101 as a meaningful treatment option for this devastating disease,” said Salvador Rico, M.D., Ph.D., Chief Medical Officer of Encoded. “Data from the ongoing Phase 1/2 studies showed durable reduction of seizures and improvements in neurodevelopment following a one-time administration. We are grateful to the FDA for recognizing the potential of ETX101 and look forward to continued collaboration to bring a meaningful new treatment option to the Dravet syndrome community as soon as possible.”

Breakthrough Therapy Designation is a process designed to expedite development and review of investigational therapies that are intended to treat a serious or life-threatening condition and for which preliminary clinical evidence indicates the therapy may demonstrate substantial improvement over available therapies on one or more clinically significant endpoints. The designation provides Encoded with more frequent and intensive FDA guidance, including the involvement of senior reviewers, as well as eligibility for rolling and priority review of the marketing application.

About Dravet Syndrome

Dravet syndrome is a severe genetic developmental and epileptic encephalopathy that begins in infancy and is most commonly caused by loss-of-function variants in the SCN1A gene. The disorder is characterized by frequent, prolonged seizures that are often resistant to treatment, as well as significant cognitive, behavioral, and motor impairments. Individuals with Dravet syndrome face a lifelong disease burden and an increased risk of premature mortality. Current treatment options are largely symptomatic and do not address the underlying genetic cause of the disease. More information about Dravet syndrome can be found at www.dravetfoundation.org.

About ETX101

ETX101 is an investigational AAV9-based gene regulation therapy designed to increase the expression of the SCN1A gene to restore sodium channel function in inhibitory interneurons. By addressing this root mechanism, ETX101 has the potential to treat the full spectrum of Dravet syndrome symptoms, including seizures, communication and cognitive impairment, behavioral issues, and motor dysfunction. The therapy is administered via a single intracerebroventricular (ICV) injection and is designed for long-term benefit. ETX101 has received Breakthrough Therapy, Regenerative Medicine Advanced Therapy, Fast Track, Rare Pediatric Disease, and Orphan Drug Designations from the FDA, as well as Orphan Designation from the European Medicines Agency (EMA).

About Encoded Therapeutics

Encoded Therapeutics is a clinical-stage biotechnology company developing precision genetic medicines to transform the lives of patients with severe neurological disorders. The company’s vector engineering platform enables potent and cell-type-selective regulation of gene expression, allowing for targeted modulation of disease-relevant genes. Encoded is advancing a pipeline of programs across genetic epilepsies and other neurological disorders with significant unmet need. With integrated discovery, development, and manufacturing capabilities, Encoded is positioned to efficiently move programs from concept through the clinic. Encoded is driven by a mission to meaningfully improve the lives of patients and families affected by devastating neurological disorders. For more information, please visit www.encoded.com.

View source version on businesswire.com: https://www.businesswire.com/news/home/20260112051311/en/

Investors/Business Development

Jennifer Gorzelany

communications@encoded.com

Media

Lori Rosen

lori@redhousecomms.com

SOUTH SAN FRANCISCO, Calif. – Encoded Therapeutics Inc. (“Encoded”), a clinical-stage biotechnology company developing genetic medicines for severe neurological disorders, today provided an update on the significant progress made during 2025 with its Dravet syndrome candidate, ETX101, including an overview of the positive interim Phase 1/2 clinical results announced last month, establishment of GMP manufacturing capabilities to support its pipeline of gene therapies, and progress across its overall pipeline.

“Last year marked a period of significant execution for Encoded, including meaningful progress across our pipeline and manufacturing capabilities. Data that were recently presented at the American Epilepsy Society Annual Meeting underscore the potential clinical impact of ETX101 for people with Dravet syndrome. With our highly experienced team and an operational GMP manufacturing facility we are well-positioned to initiate a pivotal trial of ETX101 in 2026,” said Kartik Ramamoorthi, Ph.D., Chief Executive Officer of Encoded Therapeutics. “We are excited about multiple near-term catalysts in the year ahead and are focused on executing our vision to deliver transformative gene therapies to patients.”

Progress Across Dravet Syndrome Program

The Company’s clinical development of ETX101 reached a strategic inflection point, marked by significant progress across the following clinical and manufacturing milestones:

• ETX101 demonstrated dose-dependent and sustained reductions in monthly countable seizure frequency. Progressive and clinically meaningful gains were observed in multiple measures of neurodevelopment across initial dose levels, supporting the potential for ETX101 to prevent neurodevelopmental stagnation with early intervention.

• Attained Regenerative Medicine Advanced Therapy (RMAT) designation for ETX101 following review of preliminary clinical data from POLARIS Phase 1/2 studies.

• Launched a fully operational GMP manufacturing facility, successfully producing clinical material to supply the pivotal study while establishing a foundation that is readily scalable to support future commercial demand. The facility’s integrated CMC and GMP production capabilities enable tight control over quality and timelines that de-risk supply and preserve economic flexibility.

• Strengthened clinical leadership team with the addition of Joseph Sullivan, M.D., as Vice President of Clinical Development.

Progress Across Preclinical Pipeline

Preclinical programs further advanced toward clinical development with robust proof-of-concept data in non-human primates (NHPs) presented at key scientific meetings:

• Chronic pain: Durable knockdown of SCN9A (Na_V1.7) following one-time intrathecal lumbar administration of AAV9-based miRNA candidate presented at the European Society of Gene & Cell Therapy Annual Congress. Level of target engagement observed in NHPs exceeded the threshold for pain relief established in rodent chronic pain models.

• Angelman syndrome: Strong safety and target engagement data with unsilencing of UBE3A across disease relevant brain regions for AAV9-based candidate ETX201 presented at the American Society of Gene & Cell Therapy (ASGCT) Annual Meeting, and for IV-delivered novel capsid candidate at the Foundation for Angelman Therapeutics (FAST) Global Science Summit.

• Tauopathies: Potent and robust knockdown of MAPT (tau) with AAV9 candidates presented at the ASGCT Annual Meeting.

2026 Anticipated Milestones

The Company expects important milestones in 2026 to reflect ongoing program progress related to:

• Interim efficacy results from the highest dose level of the POLARIS clinical program;

• Initiation of ETX101 pivotal study; and

• Additional progress across the early-stage pipeline, including nomination of a development candidate for chronic pain.

J.P. Morgan Healthcare Conference Presentation Details

Dr. Ramamoorthi will present a corporate overview and 2026 outlook on Monday, January 12, 2026, starting at 5:30 p.m. PT at The Westin St. Francis Hotel (Golden Gate Room, 32^nd Floor).

About ETX101

ETX101 is a potential one-time, disease-modifying AAV9-based gene regulation therapy for SCN1A+ Dravet syndrome. ETX101 is designed to target the underlying cause of Dravet syndrome by increasing SCN1A expression in GABAergic inhibitory neurons. By addressing this root mechanism, ETX101 has the potential to treat the full spectrum of Dravet syndrome symptoms, including seizures, communication and cognitive impairment, behavioral issues, and motor dysfunction. ETX101 has received Regenerative Medicine Advanced Therapy, Fast Track, Rare Pediatric Disease, and Orphan Drug Designations from the FDA, as well as Orphan Designation from the EMA.

About the POLARIS Program

POLARIS is a comprehensive clinical investigation of ETX101 in children with SCN1A+ Dravet syndrome, comprising multiple Phase 1-3 clinical trials. The first phase of POLARIS comprises three open-label, Phase 1/2 dose-escalation, multi-center trials (ENDEAVOR Part 1 (US), EXPEDITION (UK), and WAYFINDER (Australia)) in infants and young children 6 months to <7 years of age. The primary objective of the studies is to assess the safety and tolerability of ETX101. Secondary objectives are to evaluate the preliminary efficacy of ETX101 by assessing the percent change from baseline in monthly countable seizure frequency (MCSF), as well as the impact on the neurodevelopmental symptoms of Dravet syndrome, including cognition, communication, and motor function.

About Encoded Therapeutics

Encoded Therapeutics is a clinical-stage genetic medicines company developing one-time therapies for severe neurological disorders. Our vector engineering platform enables highly selective, potent, and durable gene modulation. The lead program, ETX101, is designed to address the underlying cause of Dravet syndrome by durably upregulating SCN1A and is currently in Phase 1/2 clinical trials. Building on this foundation, we are advancing programs to modulate validated genetic targets in chronic pain, Angelman syndrome, and Alzheimer’s disease/tauopathies. With integrated discovery, development, and manufacturing capabilities, we are positioned to efficiently move programs from concept through the clinic. We are driven by a mission to meaningfully improve the lives of patients and families affected by devastating neurological disorders. For more information, please visit www.encoded.com.

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Jennifer Gorzelany

communications@encoded.com

Media

Lori Rosen

lori@redhousecomms.com

SOUTH SAN FRANCISCO, Calif. – Encoded Therapeutics Inc., a clinical-stage biotechnology company developing genetic medicines for severe neurological disorders, today announced that Kartik Ramamoorthi, Ph.D., Chief Executive Officer, will present at the 44^th Annual J.P. Morgan Healthcare Conference on Monday, January 12, 2026 at 5:30 p.m. PT in San Francisco, California.

About Encoded Therapeutics

Encoded Therapeutics is a clinical-stage genetic medicines company developing one-time therapies for severe neurological disorders. Our vector engineering platform enables highly selective, potent, and durable gene modulation. The lead program, ETX101, is designed to address the underlying cause of Dravet syndrome by durably upregulating SCN1A and is currently in Phase 1/2 clinical trials. Building on this foundation, we are advancing programs to modulate validated genetic targets in chronic pain, Angelman syndrome, and Alzheimer’s disease/tauopathies. With integrated discovery, development, and manufacturing capabilities, we are positioned to efficiently move programs from concept through the clinic. We are driven by a mission to meaningfully improve the lives of patients and families affected by devastating neurological conditions. For more information, please visit www.encoded.com.

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Investors/Business Development

Jennifer Gorzelany

communications@encoded.com

Media

Lori Rosen

lori@redhousecomms.com

SOUTH SAN FRANCISCO, Calif. – Encoded Therapeutics Inc. (“Encoded”), a clinical-stage biotechnology company developing genetic medicines for severe neurological disorders, today announced the appointment of Dr. Joseph Sullivan M.D., as Vice President of Clinical Development. In this role, Dr. Sullivan will be responsible for leading all clinical development activities at Encoded and will report directly to the Company’s Chief Medical Officer, Sal Rico, M.D., Ph.D.

“Joe’s unparalleled expertise in Dravet syndrome and his track record of driving some of the most important recent advancements in epilepsy treatment make him an invaluable addition to our clinical team. Having collaborated closely with him for several years, I have witnessed first-hand his academic rigor, clinical excellence, and deep empathy for the patient community,” said Dr. Rico. “His decision to join Encoded is a powerful endorsement of our science and clinical progress, and together, we are poised to accelerate the development of ETX101 for the patients and families impacted by this disorder.”

Dr. Sullivan joins Encoded after two decades at the University of California, San Francisco (UCSF), where he directed the Pediatric Epilepsy Center of Excellence and served as Professor of Neurology and Pediatrics. Under his leadership, UCSF became an internationally recognized center for rare pediatric epilepsies and a sought after site for clinical trials. He has held leadership roles with the Epilepsy Foundation of Northern California and the Dravet Syndrome Foundation and is board certified in child neurology and epilepsy.

“I am excited to begin a new chapter in my career at Encoded and to support its mission of developing one-time gene therapies that have the potential to transform the lives of people living with devastating neurological diseases such as Dravet syndrome,” said Dr. Sullivan. “Throughout my career, I have been driven by the opportunity to deliver breakthrough treatments, and the science at Encoded represents a remarkable step forward. I look forward to partnering with this talented team to advance our programs into later-stage development and bring these therapies closer to the patients who urgently need them.”

About Encoded Therapeutics

Encoded Therapeutics is a clinical-stage genetic medicines company developing one-time therapies for severe neurological disorders. Our vector engineering platform enables highly selective, potent, and durable gene modulation. The lead program, ETX101, is designed to address the underlying cause of Dravet syndrome by durably upregulating SCN1A and is currently in Phase 1/2 clinical trials. Building on this foundation, we are advancing programs to modulate validated genetic targets in chronic pain, Angelman syndrome, and Alzheimer’s disease/tauopathies. With integrated discovery, development, and manufacturing capabilities, we are positioned to efficiently move programs from concept through the clinic. We are driven by a mission to meaningfully improve the lives of patients and families affected by devastating neurological disorders. For more information, please visit www.encoded.com.

View source version on businesswire.com: https://www.businesswire.com/news/home/20251216682441/en/

Investors/Business Development

Jennifer Gorzelany

communications@encoded.com

Media

Lori Rosen

lori@redhousecomms.com

SOUTH SAN FRANCISCO, Calif. – Encoded Therapeutics Inc., a clinical-stage biotechnology company developing genetic medicines for severe neurological disorders, today announced positive interim results from its ongoing POLARIS clinical development program evaluating ETX101 in children with SCN1A+ Dravet syndrome. The data will be featured in an oral presentation at the American Epilepsy Society (AES) Annual Meeting today and again tomorrow in a poster session.

The POLARIS program includes three ongoing open-label, dose-escalation trials of ETX101 in the US (ENDEAVOR Part 1), UK (EXPEDITION), and Australia (WAYFINDER). POLARIS is evaluating the safety and preliminary efficacy of ETX101 in children 6 months to 7 years of age with Dravet syndrome due to variants in the SCN1A gene. ETX101 is administered via a single intracerebroventricular injection into the cerebrospinal fluid (CSF). Across these studies, 19 participants received ETX101 at one of four dose levels: 5.0E11 (n=3), 1.9E12 (n=4), 3.3E12 (n=3), or 6.6E12 vg/mL CSF (n=9). Interim results are reported with a data cutoff of November 10, 2025, including safety data from all four dose levels and efficacy data for the first three dose levels.

ETX101 demonstrated dose-dependent and sustained reductions in monthly countable seizure frequency (MCSF) in drug-resistant participants during a worsening period typically associated with increasing seizure burden. Progressive and clinically meaningful neurodevelopmental gains were observed in both the caregiver interview-based Vineland Adaptive Behavior Scales (VABS-3) and the clinician-administered Bayley Scales of Infant and Toddler Development (Bayley-4) through 52 weeks of observation. In children treated before 2 years of age, substantial acceleration in cognitive skill acquisition was evident by 16 weeks, supporting the potential for ETX101 to prevent neurodevelopmental stagnation with early intervention. To date, ETX101 has been well-tolerated, with no treatment-related serious adverse events reported through the fourth and highest dose level.

“These results point to the possibility of a one-time treatment that not only reduces seizures, but also addresses the profound neurodevelopmental stagnation that affects the ability of children with Dravet syndrome to communicate, learn, and function independently,” said Joseph Sullivan, M.D., Professor of Neurology & Pediatrics, University of California, San Francisco, and Principal Investigator on the ENDEAVOR study. “These early signals of developmental rescue in our youngest patients offer real hope for families facing the challenges of living with this disease.”

“While early, the emerging clinical impact of ETX101 underscores its potential as a one-time, disease-modifying medicine for Dravet syndrome,” said Kartik Ramamoorthi, Ph.D., Chief Executive Officer of Encoded Therapeutics. “We’re incredibly grateful to the study participants and their families, clinicians, and advocacy partners whose commitment and collaboration have made this progress possible. We look forward to presenting efficacy data from the fourth and final dose level as we seek to advance ETX101 toward a pivotal clinical trial in 2026.”

Safety: Well-Tolerated Across all Dose Levels

To date, ETX101 has shown a favorable safety profile and has been well-tolerated across all four dose levels with no treatment-related serious adverse events (n=19). The most common treatment-related adverse events were expected transaminase elevations (a known AAV class effect), which were clinically asymptomatic and resolved in all participants.

Efficacy: Seizure Reduction

Substantial antiseizure effects were observed through 7 months at the third dose level (n=3), with a 78% median reduction in MCSF in drug-resistant participants already receiving the best available antiseizure medications. These reductions occurred during a worsening period typically associated with increasing seizure burden in young children with Dravet syndrome.

Efficacy: Neurodevelopmental Improvements

Neurodevelopmental improvements were observed across all three initial dose levels, supporting the disease-modifying potential of ETX101.

• On VABS-3, four participants across dose levels 1 and 2 have reached 52 weeks of follow-up, all of whom showed meaningful positive divergence from untreated children in the ENVISION natural history study. The most notable improvements were in receptive and expressive communication and motor function, with significant progress also seen in self-care and social interaction.
• On Bayley-4, four out of five participants treated before 2 years of age showed substantial acceleration of cognitive skill acquisition as early as 16 weeks, with progressive gains through 52 weeks of observation. The rate of cognitive development in these participants treated with ETX101 represents an important deviation from the developmental slowing and eventual plateauing observed in the ENVISION natural history study, supporting the potential of ETX101 to prevent neurodevelopmental stagnation with early intervention.

Presentation Details

“POLARIS Phase 1/2 Program Interim Safety and Preliminary Efficacy Results of ETX101, a One-Time Gene Regulation Therapy, in Young Children with Dravet Syndrome” will be presented by Joseph Sullivan, M.D.

Oral Session: Platform session B.02

Date & Time: Friday, December 5, 2025, 12:45-1:00 pm ET

Location: Georgia World Congress Center Room B313

Poster Session: Poster #1.308

Date & Time: Saturday, December 6, 2025, 12:00-6:00 pm ET (Poster displayed); 12:00-2:00 pm ET (Author present)

Location: Georgia World Congress Center Exhibit Hall B2

About Dravet Syndrome

Dravet syndrome is a severe, lifelong developmental and epileptic encephalopathy (DEE) that begins in infancy. Most cases are caused by variants in the SCN1A gene, resulting in reduced Na_V1.1 protein in the brain. Seizures typically begin within the first year of life and are frequent, prolonged, and difficult to control, even with treatment. As the disease progresses, people experience cognitive and developmental delays, motor and balance difficulties, sleep disturbances, and behavioral challenges. Dravet syndrome carries a high risk of SUDEP (Sudden Unexpected Death in Epilepsy), with up to 1 in 5 children dying before adulthood. Dravet syndrome affects approximately 35,000 people in the United States, United Kingdom, EU4 and Japan. Currently, there are no approved disease-modifying therapies for Dravet syndrome, leaving a significant and urgent unmet need for patients and families. More information about Dravet syndrome can be found at www.dravetfoundation.org.

About ETX101

ETX101 is a potential one-time, disease-modifying AAV9-based gene regulation therapy for SCN1A+ Dravet syndrome. ETX101 is designed to target the underlying cause of Dravet syndrome by increasing SCN1A expression in GABAergic inhibitory neurons. By addressing this root mechanism, ETX101 has the potential to treat the full spectrum of Dravet syndrome symptoms, including seizures, communication and cognitive impairment, behavioral issues, and motor dysfunction. ETX101 has received Regenerative Medicine Advanced Therapy, Fast Track, Rare Pediatric Disease, and Orphan Drug Designations from the FDA, as well as Orphan Designation from the EMA.

About the POLARIS Program

The POLARIS program is a comprehensive clinical investigation of ETX101 in children with SCN1A+ Dravet syndrome, comprising multiple Phase 1-3 clinical trials. The first phase of POLARIS comprises three open-label, Phase 1/2 dose-escalation, multi-center trials (ENDEAVOR (US), EXPEDITION (UK), and WAYFINDER (Australia)) in infants and young children 6 months to 7 years of age. The primary objective of the studies is to assess the safety and tolerability of ETX101. Secondary objectives are to evaluate the preliminary efficacy of ETX101 by assessing the percent change from baseline in monthly countable seizure frequency (MCSF), as well as the impact on the neurodevelopmental symptoms of Dravet syndrome, including cognition, communication, and motor function.

About Encoded Therapeutics

Encoded Therapeutics is a clinical-stage genetic medicines company developing one-time therapies for severe neurological disorders. Our vector engineering platform enables highly selective, potent, and durable gene modulation. The lead program, ETX101, is designed to address the underlying cause of Dravet syndrome by durably upregulating SCN1A and is currently in Phase 1/2 clinical trials. Building on this foundation, we are advancing programs to modulate validated genetic targets in chronic pain, Angelman syndrome, and Alzheimer’s disease/tauopathies. With integrated discovery, development, and manufacturing capabilities, we are positioned to efficiently move programs from concept through the clinic. We are driven by a mission to meaningfully improve the lives of patients and families affected by devastating neurological conditions. For more information, please visit www.encoded.com.

View source version on businesswire.com: https://www.businesswire.com/news/home/20251205992024/en/

Investors/Business Development

Jennifer Gorzelany

communications@encoded.com

Media

Lori Rosen

lori@redhousecomms.com