Author: encoded.tw

SOUTH SAN FRANCISCO, Calif. – Encoded Therapeutics Inc., a clinical-stage genetic medicines company, today announced upcoming presentations of interim clinical data from its ongoing POLARIS Phase 1/2 open-label trials evaluating ETX101 in children with SCN1A+ Dravet syndrome. The data will be featured at the American Epilepsy Society Annual Meeting, taking place December 5-9, 2025, in Atlanta, Georgia.

Dravet syndrome is a severe developmental and epileptic encephalopathy with onset in infancy, followed by a devastating period of escalating, treatment-resistant seizures and neurodevelopmental stagnation despite current medications. ETX101, an AAV9-based gene regulation therapy, was designed to target the root cause of Dravet syndrome by durably restoring SCN1A expression. The presentations will highlight interim safety data and early efficacy data from a single administration of ETX101, including seizure frequency through a 7-month observation period and outcomes on standardized neurodevelopmental assessments – the caregiver interview-based Vineland Adaptive Behavior Scales (VABS-3) and the clinician-administered Bayley Scales of Infant and Toddler Development (Bayley-4).

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., University of California, San Francisco, Principal Investigator on the ENDEAVOR study.

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 an AAV9-based gene regulation therapy in development to treat SCN1A+ Dravet syndrome. ETX101 is designed to target the underlying cause of Dravet syndrome by increasing SCN1A expression in GABAergic inhibitory neurons with a single administration. By addressing this root mechanism, ETX101 has the potential to treat the full spectrum of Dravet symptoms, including seizures, communication and cognitive impairment, behavioral issues, and motor dysfunction. ETX101 has received Regenerative Medicine Advanced Therapy, Fast Track, Rare Pediatric, and Orphan Drug Designations from the U.S. Food and Drug Administration, as well as Orphan Designation from the European Medicines Agency.

About the POLARIS Studies: ENDEAVOR (United States), EXPEDITION (United Kingdom), and WAYFINDER (Australia)

The POLARIS program is a comprehensive clinical investigation of ETX101 in infants and young children (6 months to <7 years of age) with SCN1A+ Dravet syndrome, comprising multiple clinical trials. The first phase of POLARIS comprises three Phase 1/2 open-label, dose-escalation, multi-center trials. The primary objective of the studies is to assess the safety and tolerability of ETX101. Secondary objectives are to evaluate the gene therapy’s efficacy 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 selectively 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 pioneer transformative therapies that 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., a clinical-stage biotechnology company developing genetic medicines for severe neurological disorders, today announced preclinical data demonstrating that its AAV9 microRNA (miRNA) gene therapy candidate achieved robust knockdown of SCN9A (Na_V1.7), a key mediator of pain signaling, in non-human primates (NHPs). The levels of target engagement in NHPs exceeded therapeutic thresholds observed in an established rodent pain model. Together, these findings support the potential of Encoded’s candidate as a one-time, non-opioid gene therapy for intractable chronic pain.

The candidate, developed through Encoded’s vector engineering platform, is designed to selectively and durably knock down SCN9A (Na_V1.7), a voltage-gated sodium channel that is well-established as a key mediator of pain sensitivity. Despite its validation, achieving both selective inhibition of Na_V1.7 and sufficient access to dorsal root ganglia (DRG) neurons remains a significant challenge. Encoded’s program leverages intrathecal delivery of clinically-validated AAV9 to enable selective knockdown of SCN9A in DRG sensory neurons, while limiting systemic biodistribution and potential off-target safety effects in organs such as the brain, heart, and liver.

“Chronic pain remains a highly prevalent and underserved neurological condition globally, with current treatments often offering limited relief, significant side effects, and a risk of dependency,” said Stephanie Tagliatela, Chief Scientific Officer of Encoded Therapeutics. “Our approach is uniquely designed to knock down a well-validated mediator of pain signaling, SCN9A (Na_V1.7), through intrathecal delivery of low-dose AAV9 to DRG neurons. By integrating validated biology, optimized delivery, and translational insights from our clinical-stage ETX101 program, we see the potential for our candidate to emerge as a one-time, non-opioid therapy capable of transforming care for people living with chronic pain.”

Preclinical Results

• NHP studies demonstrated 69% knockdown of SCN9A expression in lumbar DRG following a single dose of 1.5E13 vector genomes (vg)/animal, with minimal biodistribution in the brain, heart, and liver.

• In rats, consistent analgesic effects were observed in a well-established spared nerve injury model of chronic pain through 8 weeks post-dosing, with as little as 40% Scn9a knockdown sufficient to induce a durable analgesic response.

• Treatment was well-tolerated with no dose-limiting or treatment-related adverse findings across species.

These results establish a strong translational foundation for selective Na_V1.7 knockdown delivered with a validated AAV capsid, supporting potential broad application of gene therapy to a highly prevalent neurological disorder.

Poster Presentation Details

European Society of Gene & Cell Therapy 32^nd Annual Congress, October 7 – 10, 2025, in Seville, Spain

Title: Non-opioid AAV9-miRNA Gene Therapy to Silence SCN9A Achieves Durable Pain Control and Target Engagement in Non-human Primates

Session Date & Time: October 9, 14:00 – 15:30 CEST

Presenter: Chao Tai, PhD, Senior Scientist, Encoded Therapeutics

Poster Number: 252

Location: Seville Exhibition and Conference Centre, Fibes 2

19^th Annual Pain Therapeutics Summit, October 13 – 14, 2025, in San Diego, CA

Title: Non-opioid AAV9-miRNA Gene Therapy to Silence SCN9A Achieves Durable Pain Control and Target Engagement in Non-human Primates

Session Dates: October 13 – 14

Presenter: Sheila Sears, PhD, Associate Director, Translational Research, Encoded Therapeutics

Location: DoubleTree by Hilton – Mission Valley, Great Room

About Intractable Chronic Pain

Intractable chronic pain is defined by persistent, severe discomfort that resists conventional treatments and profoundly disrupts quality of life. It affects millions of people worldwide, yet current therapies-including opioids-often provide limited relief and are associated with significant side effects and risk of dependency. Despite its widespread impact, there remains a lack of therapies that target the underlying mechanisms of chronic pain. This underscores an urgent need for innovative, safe, and effective approaches to address this persistent and debilitating condition.

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. ETX101, our lead program, is designed to address the underlying cause of Dravet syndrome by selectively upregulating SCN1A and is currently in Phase 1/2 clinical trials. Building on this foundation, we are advancing additional programs to selectively modulate highly 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 pioneer transformative therapies that 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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Jennifer Gorzelany

communications@encoded.com

650-515-9695

SOUTH SAN FRANCISCO, Calif. – Encoded Therapeutics Inc., a clinical-stage biotechnology company developing genetic medicines for severe neurological disorders, today announced the U.S. Food and Drug Administration (FDA) has granted Regenerative Medicine Advanced Therapy (RMAT) designation to ETX101 following review of preliminary seizure data from patients treated in its ongoing Phase 1/2 program. ETX101 is an AAV9-based gene regulation therapy designed to increase SCN1A expression in GABAergic inhibitory neurons for the treatment of SCN1A+ Dravet syndrome. ETX101 has Fast Track, Rare Pediatric, and Orphan Drug Designations from FDA and Orphan Designation from EMA.

Additionally, the company reported that its North Carolina GMP manufacturing facility has initiated production of ETX101 to support pivotal trials expected in 1H26.

“The FDA’s decision to grant RMAT designation highlights the promising clinical efficacy and safety profile we have observed to date,” said Kartik Ramamoorthi, PhD, Chief Executive Officer of Encoded Therapeutics. “This milestone, together with the transition to in-house GMP manufacturing, underscores both the clinical potential of ETX101 and our readiness to efficiently advance the program through development. We look forward to sharing interim efficacy data from POLARIS later this year.”

RMAT designation

RMAT is an expedited program to facilitate development and review of regenerative medicine therapies that are intended to treat, modify, reverse, or cure a serious or life-threatening disease. The RMAT designation provides Encoded with early, close and frequent interactions with the FDA, organizational commitments from senior managers and other opportunities to expedite review of ETX101.

Clinical program

The POLARIS clinical development plan comprises a suite of ongoing open-label, dose-escalation clinical trials of ETX101 in infants and young children (6 months to <7 years of age) with SCN1A+ Dravet syndrome across the US, UK and Australia (ENDEAVOR Part 1, EXPEDITION, and WAYFINDER, respectively). These studies are assessing safety, tolerability, and preliminary efficacy of ETX101. Enrollment in the dose-escalation studies is expected to complete in 4Q25.

GMP manufacturing facility

Encoded’s state-of-the art GMP facility in North Carolina was completed in 1Q25. Designed to support the production of multiple gene therapies, the facility enhances Encoded’s strategic capabilities from early process development through commercial GMP manufacturing. By bringing key CMC activities in-house, Encoded ensures greater control over product quality and has the opportunity to accelerate development timelines and commercial readiness.

About Encoded Therapeutics

Encoded Therapeutics is a clinical-stage genetic medicines company developing potentially one-time, disease-modifying therapies for severe neurological disorders. Our proprietary vector engineering technologies combine novel regulatory elements and payloads within AAV vectors to unlock innovative solutions for intractable conditions. Our lead clinical candidate, ETX101 for Dravet syndrome, is designed to target the underlying cause of the disorder through selective upregulation of SCN1A for potentially long-lasting benefit. Encoded’s pipeline also includes a development-stage vectorized miRNA-based gene therapy designed to restore expression of UBE3A in individuals with Angelman syndrome. In parallel, we are advancing potentially best-in-class programs for common neurological conditions, including chronic pain and Alzheimer’s disease / tauopathies. Harnessing our proprietary technology platform, GMP manufacturing capabilities, and clinical and regulatory expertise, we can efficiently advance programs from discovery through clinical development. Encoded is committed to pioneering breakthrough treatments for neurological disorders. For more information, please visit www.encoded.com.

About Encoded’s ETX101 Clinical Development Program POLARIS

POLARIS is a suite of clinical studies including ENDEAVOR Part 1 (US) and Part 2 (Global), EXPEDITION (UK) and WAYFINDER (Australia), to assess the safety and efficacy of ETX101 in infants and young children with SCN1A+ Dravet syndrome. 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 completed natural history study (ENVISION), the largest prospective, longitudinal natural history study of Dravet patients to date.

About ETX101

ETX101 is 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, and to restore function. By targeting the underlying mechanism of disease, ETX101 has the potential to address the full range of symptoms associated with Dravet syndrome. ETX101 is an investigational product and its clinical efficacy and safety have not yet been established.

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 drug-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 become clinically evident by the second or third year of a child’s life. More information about Dravet syndrome can be found at www.dravetfoundation.org.

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Jennifer Gorzelany

communications@encoded.com

650-515-9695

SOUTH SAN FRANCISCO, Calif. – Encoded Therapeutics Inc., a clinical-stage biotechnology company developing genetic medicines for severe central nervous system (CNS) disorders, today announced three presentations that underscore the strength of the Company’s vector engineering platform and demonstrate continued progress of the ETX201 in Angelman syndrome (AS), chronic pain and Alzheimer’s disease / tauopathies programs. The presentations will be made at the 28^th Annual Meeting of the American Society of Gene & Cell Therapy (ASGCT) in New Orleans, LA, May 13 – 17, 2025.

“Our vector engineering platform continues to demonstrate its potential to bring life-changing therapies to patients,” commented Chief Scientific Officer and co-founder Stephanie Tagliatela. “Specifically, in our Angelman syndrome and Alzheimer’s / tauopathies programs, new findings further validate the ability of our engineered vectors to modulate disease-relevant genes in bulk NHP CNS tissue with AAV9. In our SCN9A-targeted pain program, we have achieved robust and durable efficacy in a well-established rat model of chronic pain. These results fuel our commitment to diligently advancing these therapies towards the clinic.”

Poster Presentation Details

Title: ETX201: An AAV9-based Vectorized miRNA Therapeutic Candidate for Angelman Syndrome. Poster # 547. Presenter, Sirika Pillay, PhD

Date & Time: Tuesday, May 13, 6 – 7:30 PM CT

Location: Poster Hall I2

Title: Potent and Specific AAV9-miRNA Candidates Demonstrate Robust Reduction of Microtubule-associated Protein Tau (MAPT) in Non-Human Primates. Poster # 1440. Presenter, Veda Tatavarty, PhD

Date & Time: Wednesday, May 14, 5:30 – 7 PM CT

Location: Poster Hall I2

Title: Developing an AAV-based Gene Therapy for Chronic Pain Through Identification of Potent and Selective Artificial miRNA Candidates to Knockdown SCN9A. Poster # 1925. Presenter, Chao Tai, PhD

Date & Time: Thursday, May 15, 5:30 – 7 PM CT

Location: Poster Hall I2

About Encoded Therapeutics

Encoded Therapeutics is a clinical-stage genetic medicines company developing potentially one-time, disease-modifying therapies for severe CNS disorders. Our proprietary vector engineering technology combines novel regulatory elements and payloads with AAV vectors, unlocking innovative solutions for intractable CNS conditions. Our lead clinical-stage program, ETX101 for Dravet syndrome, targets the underlying cause of the disorder through selective upregulation of SCN1A for potentially long-lasting benefit. Encoded’s second program, ETX201, is a development-stage vectorized miRNA-based gene therapy designed to restore expression of UBE3A in individuals with Angelman syndrome. In parallel, we are advancing potentially best-in-class programs for common CNS conditions, including chronic pain and Alzheimer’s disease / tauopathies. Harnessing our proprietary technology platform and expertise, we can efficiently advance programs from discovery through clinical development. Encoded is committed to pioneering breakthrough treatments for CNS disorders. For more information, please visit www.encoded.com.

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Jennifer Gorzelany

communications@encoded.com

650-515-9695

SOUTH SAN FRANCISCO, Calif. – Encoded Therapeutics Inc., a clinical-stage biotechnology company developing genetic medicines for severe central nervous system (CNS) disorders, today announced continued progress in its lead clinical program, ETX101, and highlighted corporate achievements that advance its research pipeline and further develop infrastructure to fully integrate the Company’s gene therapy capabilities.

“In 2024, we launched our ongoing POLARIS program evaluating ETX101 in SCN1A+ Dravet syndrome. With multiple dose levels administered, we expect to share preliminary efficacy data in the second half of the year,” said Kartik Ramamoorthi, Ph.D., co-founder and Chief Executive Officer. “This rapid progress, coupled with advancement of our Angelman syndrome program, ETX201, and our broader CNS pipeline, underscores the potential for our organization to discover and develop innovative CNS therapies. Given the significant potential of our portfolio, Encoded is focusing resources on ETX101 and our established programs where we have the greatest opportunity to create near-term value. In parallel, we have made the difficult decision to reduce the size of our technology and early-stage research and development functions. I am exceptionally grateful for the team’s contributions and confident that 2025 will be a transformative year for Encoded.”

ETX101 for Dravet Syndrome, POLARIS Program

• ETX101 is an AAV9-based gene regulation therapy designed to upregulate expression of the SCN1A gene in inhibitory neurons and is the first potential one-time therapy to address the underlying genetic cause of Dravet syndrome.

• POLARIS, a global clinical program in the US, UK and Australia enrolling infants and children (6 months – 7 years of age) with SCN1A+ Dravet syndrome is ongoing; eight patients have been treated at multiple dose levels.

• As of February 12, ETX101 has been well-tolerated; no treatment-related serious adverse events have been reported at any dose level.

• Completion of additional dose levels and reporting of preliminary safety and efficacy data are planned for 2H25.

• Encoded has aligned with FDA and MHRA on the design of a sham-controlled, delayed-treatment, potentially confirmatory trial.

• ETX101 has Fast Track, Rare Pediatric, and Orphan Drug Designations from FDA and Orphan Designation from EMA.

ETX201 for Angelman Syndrome

• ETX201 is an AAV9-based vectorized microRNA (miRNA) designed to reduce the expression of the UBE3A antisense transcript (UBE3A-ATS) and unsilence paternal UBE3A expression.

• Encoded presented positive results of an NHP study at the Foundation for Angelman Syndrome Therapeutics (FAST) Global Science Summit in November. Data showed that ETX201 was well-tolerated and capable of widespread paternal UBE3A upregulation across critical, disease-relevant brain regions.

• Following guidance from FDA, IND-enabling studies have been initiated to support a potential ETX201 IND filing in 2026.

• ETX201 has the potential to be a one-time treatment approach to address the underlying cause of Angelman syndrome.

Research Pipeline

• Chronic pain candidate, an AAV9-based vectorized miRNA designed to knock down expression of SCN9A (Na_V1.7), demonstrated robust and durable correction of multiple pain phenotypes in an established rodent pain model. NHP studies are ongoing with the potential to nominate a development candidate in 2H25.

• Alzheimer’s disease candidate, an AAV9-based vectorized miRNA, demonstrated robust and durable knockdown (up to 32%) of MAPT (tau) across disease relevant brain regions in an NHP study.

• Data for both the pain and Alzheimer’s disease programs will be presented at scientific meetings in mid-2025.

Strategic Reorganization

• Encoded implemented a 29% reduction in workforce, extending cash runway through 3Q26.

• Impacted functions primarily include technology and early-stage research and development.

• Enhanced runway supports our goal of achieving key milestones, including preliminary clinical safety and efficacy for ETX101, IND/CTA for ETX201, and nomination of development candidates for our common CNS programs.

Additional Corporate Updates

• In 2024, Encoded initiated the build of a GMP facility to support the next stage of development for ETX101 and the broader portfolio; facility will be fully operational in 1Q25. Moving forward, all drug substance material for ETX101, ETX201 and pipeline programs will be manufactured in-house.

• Encoded and Prevail Therapeutics, a wholly owned subsidiary of Eli Lilly and Company, signed a collaboration agreement in May 2024 for Lilly Gene Therapy to use Encoded’s novel regulatory elements. These regulatory elements are designed to enhance or reduce transgene expression in specific tissues and organs. Encoded received an upfront payment and is eligible to receive preclinical, development, regulatory and commercial milestone payments.

About Encoded Therapeutics

Encoded Therapeutics is a clinical-stage genetic medicines company developing potentially one-time, disease-modifying therapies for severe CNS disorders. Our proprietary vector engineering technology combines novel regulatory elements and payloads with AAV vectors, unlocking innovative solutions for intractable CNS conditions. Our lead clinical-stage program, ETX101 for Dravet syndrome, targets the underlying cause of the disorder through selective upregulation of SCN1A for potentially long-lasting benefit. Encoded’s second program, ETX201, is a development-stage vectorized miRNA-based gene therapy designed to restore expression of UBE3A in individuals with Angelman syndrome. In parallel, we are advancing potentially best-in-class programs for common CNS conditions, including chronic pain and Alzheimer’s disease. Harnessing our proprietary technology platform and expertise, we can efficiently advance programs from discovery through clinical development. Encoded is committed to pioneering breakthrough treatments for CNS disorders. For more information, please visit www.encoded.com.

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Jennifer Gorzelany

communications@encoded.com

650-515-9695

SOUTH SAN FRANCISCO, Calif. – Encoded Therapeutics Inc., a biotechnology company developing genetic medicines for severe central nervous system (CNS) disorders, today highlights oral and poster presentations on the Company’s preclinical gene therapy programs and vector engineering platform at the 27^th ASGCT Annual Meeting being held May 7 – 11, 2024 in Baltimore, MD.

“We are thrilled to share multiple advancements across our portfolio of precision genetic medicines, showcasing substantial progress across various fronts. These data underscore our platform’s potential to deliver precision therapies for a range of CNS diseases,” said Stephanie Tagliatela, Chief Scientific Officer at Encoded. “Alongside clinical advancement of our lead program, ETX101 for SCN1A+ Dravet syndrome, we are poised to nominate multiple programs to development in 2025, marking yet another significant milestone.”

Oral Presentation

Title: GABA Selective AAV-mediated Gene Therapy Provides Durable Seizure Protection in Multiple Refractory Epilepsy Models (Abstract #19)

Session: AAV Vectors – Preclinical and Proof-of-Concept: Therapy Focus

Date & Time: Tuesday, May 7, 1:45-2:00 p.m. ET

Location: Ballroom 2

Epilepsy affects approximately 1% of the population, with nearly one third of cases failing to respond to first- and second-line treatments. Encoded’s vector engineering platform has enabled the development of GABA-selective AAV-mediated gene therapies designed to potentiate GABAergic neurotransmission and modulate the circuit dysfunction underlying refractory epilepsies. Our lead candidate reduced seizure incidence and severity in two biologically distinct seizure assays with no adverse impact on body weight, motor function or locomotion. Furthermore, the top candidate is well-tolerated in non-human primates (NHP) even at high doses. These data support further development of our candidate gene therapy for the treatment for refractory epilepsies.

Poster Presentations

Title: Advancing Gene Therapy for STXBP1-related Disorders Through Targeted Vector Engineering: Efficacy and Safety Results in Mice and Non-Human Primates (Abstract #508)

Date & Time: Wednesday, May 8, 5:30-7:00 p.m. ET

Location: Exhibit Hall

STXBP1-related disorders (STXBP1-RD) result from loss-of-function variants in STXBP1, causing severe developmental delay and treatment-resistant epilepsy. Encoded has engineered AAV9 vectors that drive potent expression within CNS tissue while reducing off-target expression in dorsal root ganglia (DRG) and non-neuronal tissues. These engineered AAV9-STXBP1 vectors achieved robust, dose-dependent improvements in seizure, cognitive, and motor phenotypes in Stxbp1^+/- mice, with no observed dose-limiting toxicity. In NHPs, the engineered vectors showed strong CNS expression and were well-tolerated. Furthermore, the inclusion of a DRG de-targeting element reduced expression within the DRG and spinal cord by >10-fold, ameliorating microscopic DRG-related findings. These findings establish proof-of-concept for an AAV9-based gene therapy for STXBP1-RD and support the use of modular regulatory element engineering to drive desired expression profiles within the CNS.

Title: A Vectorized miRNA-based Approach to Unsilence UBE3A in Angelman Syndrome (Abstract #1125)

Date & Time: Thursday, May 9, 5:30-7:00 p.m. ET

Location: Exhibit Hall

Angelman syndrome (AS) is a severe neurodevelopmental disorder characterized by intellectual disability, ataxia, and seizures. AS is caused by loss-of-function of the maternally-inherited UBE3A gene. Unsilencing of the paternal copy of UBE3A has the potential address the underlying cause of the disease while mitigating the risk of UBE3A overexpression-related toxicity. We demonstrated that an AAV-based miRNA vector was capable of upregulating paternal UBE3A and correcting multiple phenotypes in the AS mouse model. Encoded’s lead miRNA candidate was well-tolerated in NHPs and demonstrated potent unsilencing of paternal UBE3A in critical brain regions. Collectively, these data support further development an AAV-based miRNA treatment approach for Angelman Syndrome.

Title: Identification of Potent and Selective AAV-miRNA Candidates to Knockdown Non-Monogenic Neurological Targets SCN9A (Pain) and MAPT (Tauopathies) (Abstract #1601)

Date & Time: Friday, May 10, 5:30-7:00 p.m. ET

Location: Exhibit Hall

Encoded’s innovative AAV-mediated miRNA platform offers a promising strategy for long-term knockdown of target genes in the central and peripheral nervous systems. We identified potent and target-specific miRNA candidates to effectively knock down two clinically relevant, non-monogenic neuronal targets: SCN9A and MAPT. SCN9A encodes the Na_V1.7 sodium channel, which is associated with pain sensation, while MAPT encodes the microtubule protein, Tau, which is implicated in Alzheimer’s disease neuropathology. Encoded’s miRNA candidates demonstrated potent, dose-dependent, and selective knockdown of SCN9A in human iPSC sensory neurons and in mouse dorsal root ganglion sensory neurons, establishing proof-of-concept for miRNA-based inhibition of Na_V1.7. Similarly, MAPT candidates significantly reduced Tau protein levels in vitro and in vivo. These findings support advancement of SCN9A and MAPT candidates to NHP studies and showcase the potential of vectorized miRNA knockdown as a promising treatment avenue for various neurological disorders.

About Encoded Therapeutics

Encoded Therapeutics is a clinical-stage genetic medicines company developing potentially disease-modifying therapies to improve the lives of people with severe CNS disorders. Our proprietary vector engineering approach combines novel regulatory elements and payloads with AAV vectors to unlock innovative solutions for debilitating, intractable CNS conditions. At the forefront is our flagship clinical program, ETX101 for Dravet syndrome, which targets the underlying cause of the disorder to enable highly selective upregulation of SCN1A for potentially long-lasting benefit. In parallel, we are advancing a pipeline of potentially best-in-class programs to address significant unmet needs across both monogenic and prevalent CNS conditions. For more information, please visit www.encoded.com.

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Jennifer Gorzelany

communications@encoded.com

650-515-9695

SOUTH SAN FRANCISCO, Calif. – Encoded Therapeutics Inc., a biotechnology company developing genetic medicines for severe central nervous system (CNS) disorders, today unveiled multiple pipeline programs ahead of the 27^th ASGCT Annual meeting on May 7 – 11, 2024 in Baltimore, MD. Presentations will highlight progress of preclinical programs for Angelman syndrome, Lennox-Gastaut syndrome (LGS), STXBP1-related disorders (STXBP1-RD), Alzheimer’s disease (MAPT) and neuropathic pain (SCN9A), together with innovations in the company’s vector engineering platform.

“Our ASGCT presentations showcase the depth and versatility of our vector engineering platform to develop highly specific precision therapies for CNS disorders with high unmet need,” said Stephanie Tagliatela, Chief Scientific Officer at Encoded. “Combining our novel regulatory elements and transgenes provides control of expression in target cells, potentially enabling treatment of devastating, intractable diseases. Building on our strong foundation in neuroscience, we are leveraging the experience and infrastructure established for our Dravet syndrome program, ETX101, to rapidly advance our promising pipeline of potentially best-in-class gene therapies.”

Platform Innovations

Encoded is engineering precision and selectivity into gene therapy constructs by combining highly selective and potent regulatory elements (REs) with novel transgenes to customize expression and functionality while minimizing off-target effects. These modular elements are compatible with multiple capsids and gene delivery systems.

Novel REs developed by Encoded include those for GABA selectivity to target expression to GABAergic (inhibitory) interneurons, utilized by the clinical-stage program ETX101 for Dravet syndrome and the preclinical program for LGS. For STXBP1-RD, regulatory element engineering has been harnessed to drive potent, neuron-specific expression in the brain, while de-targeting expression in dorsal root ganglia (DRG).

Engineered transgenes include transcription factors (eTFs) that upregulate the expression of endogenous genes as well miRNA sequences derived from Encoded’s miRNA discovery platform. A miRNA approach is utilized by the Angelman syndrome, Alzheimer’s disease and neuropathic pain programs, each of which demonstrate robust gene silencing or knockdown of their respective targets.

“The data we’re sharing at ASGCT highlights our platform’s ability to achieve precise, targeted expression of transgenes with unique functionality, addressing technical limitations that exist today. This enables us to potentially unlock first-in-class gene therapies in monogenic disorders, like Dravet and Angelman syndromes, while also advancing potentially best-in-class gene therapies into more common diseases such as LGS, Alzheimer’s disease and neuropathic pain,” said Encoded CEO Kartik Ramamoorthi, Ph.D. “This is a significant maturation of our pipeline, and future success in these indications has the potential to transform the lives of many people living with severe CNS diseases.”

ASGCT Annual Meeting Presentations

Oral Presentation Details

Title: GABA Selective AAV-mediated Gene Therapy Provides Durable Seizure Protection in Multiple Refractory Epilepsy Models (Abstract #19)

Session: AAV Vectors – Preclinical and Proof-of-Concept: Therapy Focus

Date & Time: Tuesday, May 7, 1:45-2:00 p.m. ET

Location: Ballroom 2

Poster Presentation Details

Title: Advancing Gene Therapy for STXBP1-related Disorders Through Targeted Vector Engineering: Efficacy and Safety Results in Mice and Non-Human Primates (Abstract #508)

Date & Time: Wednesday, May 8, 5:30-7:00 p.m. ET

Location: Exhibit Hall

Title: A Vectorized miRNA-based Approach to Unsilence UBE3A in Angelman Syndrome (Abstract #1125)

Date & Time: Thursday, May 9, 5:30-7:00 p.m. ET

Location: Exhibit Hall

Title: Identification of Potent and Selective AAV-miRNA Candidates to Knockdown Non-Monogenic Neurological Targets SCN9A (Pain) and MAPT (Tauopathies) (Abstract #1601)

Date & Time: Friday, May 10, 5:30-7:00 p.m. ET

Location: Exhibit Hall

Scientific Symposium Details

Title: Searching for Goldilocks – Scaling for AAV Clinical Dose Prediction

Presentation: Dose Scaling from Preclinical Models to First-In-Human (FIH) for Local CNS AAV Gene Therapies

Date & Time: Thursday, May 9, 8:00-8:25 a.m. ET

Location: Ballroom 4

Presenter: Stephanie Tagliatela

Full abstracts are available on the ASGCT meeting website.

About Encoded Therapeutics

Encoded Therapeutics is a clinical-stage genetic medicines company developing potentially disease-modifying therapies to improve the lives of people with severe CNS disorders. Our proprietary vector engineering approach combines novel regulatory elements and payloads with AAV vectors to unlock innovative solutions for debilitating, intractable CNS conditions. At the forefront is our flagship clinical program, ETX101 for Dravet syndrome, which targets the underlying cause of the disorder to enable highly selective upregulation of SCN1A for potentially long-lasting benefit. In parallel, we are advancing a pipeline of potentially best-in-class programs to address significant unmet needs across both monogenic and prevalent CNS conditions. Harnessing our proprietary technology platform and expertise, we are able to efficiently advance programs from discovery through clinical development. Encoded is committed to pioneering breakthrough treatments for CNS disorders. For more information, please visit www.encoded.com.

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Jennifer Gorzelany

communications@encoded.com

650-515-9695

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

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.

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communications@encoded.com

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.

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Lynnea Olivarez

lolivarez@encoded.com

956-330-1917