Category: Press Releases

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.

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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., 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 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. (“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.

View source version on businesswire.com: https://www.businesswire.com/news/home/20260512678351/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 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.

View source version on businesswire.com: https://www.businesswire.com/news/home/20260513482347/en/

Contacts

Investors/Business Development
Jennifer Gorzelany
communications@encoded.com

Media
Lori Rosen
lori@redhousecomms.com

SOUTH SAN FRANCISCO, Calif. – Encoded Therapeutics today announced the upcoming presentation of initial data from the ENVISION prospective natural history study of children with SCN1A+ Dravet syndrome, a rare developmental and epileptic encephalopathy, at the American Epilepsy Society 2021 Annual Meeting, taking place in Chicago from December 3-7, 2021. Additionally, Encoded will present on its ongoing DRAVET ENGAGE initiative, which aims to capture the Dravet syndrome patient community’s experiences and perspectives, and a summary of molecular diagnostic and phenotypic findings in people with SCN1A+ Dravet syndrome identified through genetic testing.

Title: ENVISION: An International, Prospective Natural History Study in Young Children With SCN1A+ Dravet Syndrome

Abstract number: 2.222

Date: Sunday, December 5th

Platform presentation details: #B.07 | 10-10:15 a.m. CT | W475, Level 4

Poster session details: 12-2 p.m. CT | Hall F1, Level 3

Presenting author: Andreas Brunklaus, M.D., Consultant Pediatric Neurologist at the Royal Hospital for Children, Glasgow, United Kingdom

Title: A Patient-Oriented Approach to Integrating Families’ Experiences in Clinical Trials Design and Clinical Care for Dravet Syndrome

Abstract number: 3.073

Date/time: Monday, December 6th | 12-1:45 p.m. CT

Location: Hall F1, Level 3

Presenting author: Emma James, Ph.D., M.F.P.M. (Hon), VP, Medical & Patient Affairs at Encoded Therapeutics

Title: Molecular Diagnostic and Phenotypic Findings in Individuals With SCN1A-Related Disease Identified Through a Sponsored, No-Charge Epilepsy Genetic Testing Program

Abstract number: 3.351

Date/time: Monday, December 6th | 12-1:45 p.m. CT

Location: Hall F1, Level 3

Co-presenting author: Jennifer Gorzelany, Head of Strategy at Encoded Therapeutics

About ETX101

Encoded is developing ETX101 as a potential one-time, disease-modifying gene regulation therapy targeting the underlying cause of SCN1A+ Dravet syndrome in hopes of addressing the full range of disease manifestations. In ETX101, a cell-selective regulatory element and a transgene coding for an engineered transcription factor are delivered in a clinically validated adeno-associated virus (AAV) capsid to upregulate, or increase, the expression of the endogenous SCN1A gene in the brain. This approach is expected to increase production of Na_V1.1 protein and density of sodium channels in target neurons, leading to restored function. ETX101 has been granted Orphan Drug Designation and Rare Pediatric Disease Designation by the U.S. Food and Drug Administration. Encoded anticipates treating the first participant in the ENDEAVOR interventional trial in 2022.

About the ENVISION Natural History Study

ENVISION is an ongoing observational study of infants and children with SCN1A+ Dravet syndrome. This prospective natural history study is designed to further define the seizure, neurodevelopmental, motor and behavioral manifestations of SCN1A+ Dravet syndrome in children aged 6 to 60 months with SCN1A mutations. The study will examine these characteristics over two years using standardized assessments and will also explore the impact of the disease on parents/caregivers and healthcare resource utilization. These findings will help identify appropriate scales and endpoints to assess ETX101 safety and efficacy in clinical trials. For more information about ENVISION (NCT04537832), visit clinicaltrials.gov and search for “Encoded Therapeutics”.

About Dravet Syndrome

Dravet syndrome is a severe, lifelong disorder of the central nervous system that occurs in approximately 1 in 16,000 births worldwide, with the majority of cases resulting from loss-of-function mutations in the SCN1A gene. This rare developmental and epileptic encephalopathy equally affects people of both sexes and all races, manifesting in a wide array of symptoms. Frequent, prolonged and difficult-to-treat seizures typically begin in the first year of life of a previously healthy baby. Additional symptoms, such as cognitive delays, sleep abnormalities, motor impairment and behavioral difficulties, compound the effects of the disease when they appear, often in the second or third year of a child’s life. More information about Dravet syndrome can be found at www.dravetfoundation.org.

About Encoded Therapeutics

Encoded Therapeutics is creating one-time, disease-modifying gene therapies for pediatric central nervous system (CNS) disorders with its cell-selective targeting and regulation platform. The Encoded approach offers unprecedented gene specificity and cell selectivity to unlock novel opportunities by targeting a range of disease mechanisms. Encoded’s technology is compatible with any delivery system to control where and when therapeutic transgenes are expressed, thereby shaping the functionality of target cells and holding broader therapeutic potential beyond CNS disorders. For more information, please visit www.encoded.com, and follow us on LinkedIn, Twitter @EncodedTx and YouTube.

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Lynnea Olivarez

lolivarez@encoded.com

956-330-1917

SOUTH SAN FRANCISCO, Calif. – Encoded Therapeutics today announced initial findings from its ENVISION natural history study of children living with SCN1A+ Dravet syndrome, a rare developmental and epileptic encephalopathy. Along with a substantial seizure burden, preliminary findings suggest the trajectory and timing by which children with Dravet syndrome deviate from neurotypical peers, showing that these children experience early and substantial delay in adaptive functioning, communication and socialization, worsening with age. These data and others from 46 study participants are being presented this weekend in Chicago at the American Epilepsy Society (AES) 2021 Annual Meeting.

“The primary goal of ENVISION is to elucidate Dravet syndrome progression during a critical period of child development by further defining the full range and evolution of disease manifestations, as well as their impact on young children and families living with this disease,” said Andreas Brunklaus, M.D., Consultant Pediatric Neurologist at the Royal Hospital for Children in Glasgow, United Kingdom. Dr. Brunklaus is a leading Dravet syndrome expert and presenting author of the ENVISION study data at the AES 2021 Annual Meeting. “ENVISION is generating a comprehensive contemporary dataset that evidences the profound neurodevelopmental stagnation in young children with Dravet syndrome. We hope that data over time will enable the community to refine our understanding of Dravet syndrome pathophysiology, paving the way for potential new disease-modifying medicines to be administered at a time point in young children’s lives that could change the course of disease as we know it.”

One of the key findings to date is that, regardless of SCN1A variant type, there was global evidence of developmental stagnation as young as two years of age across domains of communication, language, socialization, and motor and adaptive functioning compared with neurotypical peers. Researchers also observed that seizure frequency continues to increase with age, despite the use of multiple and newer antiseizure medications.

“We have heard directly from families in the Dravet syndrome community that seizures and communication significantly impact quality of life, and that preservation of neurodevelopment is a key outcome sought from a gene therapy,” said Salvador Rico, M.D., Chief Medical Officer at Encoded. “These preliminary ENVISION data reinforce the ongoing impact that Dravet syndrome has on the lives of people and their families, and the need for a therapy that addresses the underlying cause of disease to positively affect both seizure and neurocognitive symptoms. Though we will gain further insights through longitudinal data as ENVISION advances, we believe that early administration of a potential one-time disease-modifying therapy such as ETX101 could yield the maximum benefit.”

“We are thankful to the children and families participating in ENVISION and to all the experts and health professionals involved in the study for their ongoing contributions that are critically important to understand the progression of Dravet syndrome,” Dr. Rico continued.

Encoded will share additional learnings from its ongoing DRAVET ENGAGE initiative, which aims to capture the Dravet syndrome patient community’s experiences and perspectives, in a separate presentation at the AES 2021 Annual Meeting. For a full list of Encoded’s presentations, click here. All abstracts are available on the AES website.

About ETX101

Encoded is developing ETX101 as a potential one-time, disease-modifying gene regulation therapy targeting the underlying cause of SCN1A+ Dravet syndrome, in hopes of addressing the full range of disease manifestations. In ETX101, a cell-selective regulatory element and a transgene coding for an engineered transcription factor are delivered in a clinically validated adeno-associated virus (AAV) capsid to upregulate, or increase, the expression of the endogenous SCN1A gene in the brain. This approach is expected to increase production of Na_V1.1 protein and density of sodium channels in target neurons, leading to restored function. ETX101 has been granted Orphan Drug Designation and Rare Pediatric Disease Designation by the U.S. Food and Drug Administration. Encoded anticipates treating the first participant in the ENDEAVOR interventional trial in 2022.

About the ENVISION Natural History Study

ENVISION is an ongoing observational study of infants and children with SCN1A+ Dravet syndrome. This prospective natural history study is designed to further define the seizure, neurodevelopmental, motor and behavioral manifestations of SCN1A+ Dravet syndrome in children aged 6 to 60 months with SCN1A mutations. The study will examine these characteristics over two years using standardized assessments and will also explore the impact of the disease on parents/caregivers and healthcare resource utilization. These findings will help identify appropriate scales and endpoints to assess ETX101 safety and efficacy in clinical trials. For more information about ENVISION (NCT04537832), visit clinicaltrials.gov and search for “Encoded Therapeutics”.

About Dravet Syndrome

Dravet syndrome is a severe, lifelong disorder of the central nervous system that occurs in approximately 1 in 16,000 births worldwide, with the majority of cases resulting from loss-of-function mutations in the SCN1A gene. This rare developmental and epileptic encephalopathy equally affects people of both sexes and all races, manifesting in a wide array of symptoms. Frequent, prolonged and difficult-to-treat seizures typically begin in the first year of life of a previously healthy baby. Additional symptoms, such as cognitive delays, sleep abnormalities, motor impairment and behavioral difficulties, compound the effects of the disease when they appear, often in the second or third year of a child’s life. More information about Dravet syndrome can be found at www.dravetfoundation.org.

About Encoded Therapeutics

Encoded Therapeutics is creating one-time, disease-modifying gene therapies for pediatric central nervous system (CNS) disorders with its cell-selective targeting and regulation platform. The Encoded approach offers unprecedented gene specificity and cell selectivity to unlock novel opportunities by targeting a range of disease mechanisms. Encoded’s technology is compatible with any delivery system to control where and when therapeutic transgenes are expressed, thereby shaping the functionality of target cells and holding broader therapeutic potential beyond CNS disorders. For more information, please visit www.encoded.com, and follow us on LinkedIn, Twitter @EncodedTx and YouTube.

View source version on businesswire.com: https://www.businesswire.com/news/home/20211203005088/en/

Lynnea Olivarez

lolivarez@encoded.com

956-330-1917

SOUTH SAN FRANCISCO, Calif. – Encoded Therapeutics announced nonclinical data being presented today at the American Society for Cell and Gene Therapy 25^th Annual Meeting showing how its proprietary human genomic regulatory element (RE) engineering platform has been used to develop cell-selective expression vectors for targeted gene therapy. The company efficiently discovered a spectrum of sequence-encoded genetic elements, including enhancers, promoters and UTR elements, that drive selective expression profiles in mice. These REs function within the size constraints and episomal architecture of adeno-associated viruses (AAVs) and are compatible with multiple capsids and gene delivery systems.

“By combining human genomic regulatory elements to customize expression profiles and minimize off-target effects, we aim to improve the safety and efficacy of gene therapies for a broad range of monogenic and non-monogenic diseases in the future,” said Encoded CEO Kartik Ramamoorthi, Ph.D. “Our regulatory elements engineering approach increases cell-selective expression, reducing toxicity concerns in tissues like the liver. The data we’re sharing today at ASGCT are exemplary of the Encoded platform’s ability to achieve appropriately targeted transgene expression across many other central nervous system (CNS) cell types, like dorsal root ganglia (DRG) neurons, as well as non-CNS cell types .”

Using Encoded’s genomic medicine platform, researchers applied both expression-based functional screening and computational modeling to simultaneously test thousands of genomic elements in vivo. They uncovered sequence elements that selectively decrease liver expression while maintaining CNS expression in mice. Additionally, the research team constructed predictive models to rapidly and iteratively continue to improve the discovery rate and distribution of activity profiles, resulting in further reduction of liver expression in mice, with unchanged expression in the brain.

Click here for the abstract of Encoded’s ASGCT presentation, “Optimized Human Regulatory Sequences Achieve Targeted Expression in CNS and Decreased Liver Expression in Mice.”

About Encoded Therapeutics

Encoded Therapeutics is creating one-time, disease-modifying gene therapies for pediatric central nervous system (CNS) disorders with its cell-selective targeting and regulation platform. The Encoded approach offers unprecedented gene specificity and cell selectivity to unlock novel opportunities by targeting a range of disease mechanisms. Encoded’s technology is compatible with any delivery system to control where and when therapeutic transgenes are expressed, thereby shaping the functionality of target cells and holding broader therapeutic potential beyond CNS disorders. For more information, please visit www.encoded.com, and follow us on LinkedIn, Twitter @EncodedTx and YouTube.

View source version on businesswire.com: https://www.businesswire.com/news/home/20220518005469/en/

Lynnea Olivarez

lolivarez@encoded.com

956-330-1917

SOUTH SAN FRANCISCO, Calif. – Encoded Therapeutics announced today the presentation of non-human primate (NHP) validation of the company’s technology to drive desired gene and protein expression patterns at the American Society of Gene and Cell Therapy (ASGCT) 26^th Annual Meeting. An important challenge of developing gene therapy in many central nervous system (CNS) disorders is the toxicity concern associated with high transgene expression in the dorsal root ganglion (DRG). By incorporating a DRG de-targeting regulatory element (RE) derived from Encoded’s research platform into a CNS-targeted gene therapy construct, the company achieved a significant reduction in DRG protein expression to endogenous baseline. This resulted in a greater than 10-fold selective reduction in DRG transcriptional activity without impacting brain expression.

“Off-target expression in the DRG and other organs has created limitations on gene therapy efficacy optimization,” said Encoded CEO Kartik Ramamoorthi, Ph.D. “In addition to de-targeting the DRG and other organ systems, we believe that Encoded REs have the potential to drive high levels of cell-type selectivity, potency and specificity, irrespective of the gene modulation approach at hand. We’re incorporating this technology into our pipeline to unlock novel indications, and we hope to have an even greater impact for people living with CNS diseases by collaborating with other gene therapy developers in the future.”

Encoded tested over 10,000 REs in vivo with its high-throughput NGS-based platform to screen for human genomic sequences that can modulate transgene expression and produce a more highly targeted gene therapy expression profile in mice. The research team analyzed top candidates in NHPs, showing successful translation to higher species while still achieving precise expression in the CNS.

Click here for the abstract of Encoded’s 2023 ASGCT presentation, “High Throughput Discovery of Optimized Human Genomic Regulatory Elements That Selectively Decrease Off-Target Expression in Dorsal Root Ganglion in Mice and Non-Human Primates” (Abstract No. 1481).

About Encoded Therapeutics

Encoded Therapeutics is creating one-time, disease-modifying gene therapies for pediatric central nervous system (CNS) disorders with its cell-selective targeting and regulation platform. The Encoded approach offers potentially unprecedented gene specificity and cell selectivity to unlock novel opportunities by targeting a range of disease mechanisms. Encoded’s technology is compatible with any delivery system to control where and when therapeutic transgenes are expressed, thereby shaping the functionality of target cells and holding broader therapeutic potential beyond CNS disorders. For more information, please visit www.encoded.com.

View source version on businesswire.com: https://www.businesswire.com/news/home/20230519005038/en/

communications@encoded.com

SOUTH SAN FRANCISCO, Calif. – Encoded Therapeutics Inc., a biotechnology company focused on developing genetic medicines for severe central nervous system (CNS) disorders, today outlined the global development strategy for its lead gene therapy candidate, ETX101, for the treatment of SCN1A+ Dravet syndrome. Individuals with Dravet syndrome, the most common developmental and epileptic encephalopathy, experience a spectrum of clinical symptoms, including treatment-resistant seizures and neurodevelopmental stagnation. Dravet syndrome is primarily caused by loss-of-function variants in the SCN1A gene, accounting for over 85% of cases. ETX101 is an AAV9-mediated candidate gene regulation therapy designed to selectively upregulate expression of the SCN1A gene in GABAergic inhibitory interneurons and potentially address the underlying cause of the disease.

ETX101 Global Clinical Development

Encoded has received clearance for its Investigational New Drug (IND) application from the US Food and Drug Administration and approval under the Clinical Trial Approval (CTA) scheme from the Australia Therapeutic Goods Administration to initiate clinical trials of its gene therapy candidate, ETX101. The company plans to initiate ENDEAVOR, a two-part, Phase 1/2 clinical trial in US patients 6 months to <3 years of age with SCN1A+ Dravet syndrome in the first half of 2024. WAYFINDER, a Phase 1/2 trial in patients 3 to <7 years of age in Australia, will be conducted concurrently with ENDEAVOR.

“Dravet syndrome is a devastating disorder that necessitates a paradigm shift from conventional symptomatic management towards precise and targeted interventions at the genetic level. I’m hopeful that gene therapy will not just alleviate symptoms but address the root cause of Dravet syndrome, marking a potentially transformative approach in our quest to address the ongoing medical burden of families living with Dravet syndrome,” said Joseph Sullivan, M.D., Murphy Parker Endowed Professor in Pediatric Epilepsy, Professor of Neurology & Pediatrics at UCSF Pediatric Epilepsy Center of Excellence and Principal Investigator on the ENDEAVOR study.

The ENDEAVOR and WAYFINDER clinical trials are part of Encoded’s global clinical development program, POLARIS, which aims to assess safety and efficacy of ascending doses of ETX101 in infants and young children. Importantly, POLARIS will evaluate the initial effects of ETX101 on seizure burden, as well as potential long-term improvements in neurodevelopment. Furthermore, Encoded has aligned with FDA on the design of ENDEAVOR as a two-part study, which creates an opportunity to seamlessly transition to a potentially confirmatory trial following demonstration of initial safety and efficacy.

The POLARIS program is based on preceding patient-focused drug development initiatives (Dravet ENGAGE), a multipronged biomarker discovery project (ELUCIDATE) and a recently completed natural history study (ENVISION), the largest longitudinal natural history study in Dravet syndrome to date. These initiatives have informed the optimal clinical design for POLARIS and emphasize the urgent unmet need for disease-modifying therapies.

“ETX101 represents a groundbreaking advancement in the therapeutic landscape for Dravet syndrome, with potential not only for seizure management but also for addressing the broader spectrum of non-seizure manifestations. ENDEAVOR and WAYFINDER are the first step in bringing a potentially one-time, disease-modifying gene therapy to the Dravet community, and we are excited to be partnering with leading experts in the care of patients with Dravet syndrome to begin clinical trials in the US and Australia in the coming months,” said Sal Rico, M.D., Ph.D., Chief Medical Officer.

Encoded will be providing additional updates on its research pipeline, which is focused on both rare genetic and common disease programs, in addition to clinical progress with ETX101 for Dravet syndrome later in 2024.

“Encoded is committed to creating innovative genetic medicines that bring renewed hope and possibilities to patients living with severe CNS disorders. The initiation of clinical trials in Dravet syndrome and the advancement of our CNS pipeline strategically positions Encoded to achieve pivotal program milestones in 2024. We look forward to sharing additional company updates in the coming months,” said Kartik Ramamoorthi, Ph.D., Co-Founder and Chief Executive Officer.

About ETX101

Encoded is developing ETX101 as a potential one-time, disease-modifying gene regulation therapy targeting the underlying cause of SCN1A+ Dravet syndrome. In ETX101, a transgene encoding an engineered transcription factor under the control of a cell-selective regulatory element is delivered within a clinically-validated capsid (AAV9) to upregulate, or increase, the expression of the endogenous SCN1A gene. This approach is expected to increase production of Na_V1.1 protein sodium channels in target neurons in the brain, leading to restored function. By targeting the underlying mechanism, ETX101 has the potential to address the full range of symptoms associated with Dravet syndrome. ETX101 has been granted Orphan Drug Designation and Rare Pediatric Disease Designation by the US Food and Drug Administration and Orphan Designation by the European Medicines Agency.

About Encoded’s ETX101 Clinical Development Program POLARIS

POLARIS is built upon Encoded’s comprehensive preclinical research, and incorporates a multipronged biomarker discovery program (ELUCIDATE), patient-focused drug development initiatives (Dravet ENGAGE), and the recently completed natural history study (ENVISION), the largest prospective, longitudinal natural history study of Dravet patients to date. This foundational work has enabled optimization of POLARIS’ rigorous clinical design, beginning with ENDEAVOR and WAYFINDER, to assess the safety and efficacy of ETX101 in infants and young children with SCN1A+ Dravet syndrome.

ENDEAVOR Clinical Study (United States)

ENDEAVOR is a two-part Phase 1/2 dose escalation study of ETX101 in infants and young children aged 6 months to <3 years. In Part 1, up to two doses of ETX101 will be evaluated in 4 participants. The primary aims of the study are to evaluate the safety and tolerability of ETX101, to assess preliminary efficacy, and to contribute to therapeutic dose selection. ETX101 has received IND clearance, and ENDEAVOR Part 1 is expected to begin in the first half of 2024. Part 2 is planned following demonstration of safety and efficacy in ENDEAVOR Part 1.

WAYFINDER Clinical Study (Australia)

WAYFINDER is a Phase 1/2 dose escalation study of ETX101 in young children aged 3 to <7 years with SCN1A+ Dravet syndrome. Up to two doses of ETX101 will be evaluated in 4 participants. The primary aims of the study are to evaluate the safety and tolerability of ETX101, to assess preliminary efficacy, and to contribute to therapeutic dose selection. WAYFINDER has received TGA approval and is expected to begin in the first half of 2024.

About Dravet Syndrome

Dravet syndrome is a severe, lifelong disorder of the central nervous system that occurs in approximately 1 in 16,000 births worldwide, with the majority of cases resulting from loss-of-function variants in the SCN1A gene. This developmental and epileptic encephalopathy equally affects people of both sexes and all races, manifesting in a wide array of symptoms. Frequent, prolonged, and treatment-resistant seizures primarily begin in the first year of life of a typically developing infant. Severe cognitive and developmental stagnation, sleep abnormalities, motor impairment and behavioral difficulties usually manifest by the second or third year of a child’s life. More information about Dravet syndrome can be found at www.dravetfoundation.org.

About Encoded Therapeutics

Encoded Therapeutics is creating one-time, potentially disease-modifying gene therapies to improve the lives of people with severe CNS disorders. Our cell-selective targeting and regulation platform offers potentially unprecedented gene specificity and cell selectivity to unlock novel opportunities by targeting a range of disease mechanisms. We are overcoming key limitations of current gene therapies by incorporating platform innovations into therapeutic development and advancing potentially best-in-class programs in Dravet syndrome and additional CNS disorders. For more information, please visit www.encoded.com.

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Jennifer Gorzelany

communications@encoded.com

650-515-9695