Encoded Shows Therapeutic Promise of miRNA-based Approach for Angelman Syndrome at FAST Summit

Encoded Therapeutics Inc., a biotechnology company in the clinical-stage, is innovating genetic medicines for severe central nervous system (CNS) disorders. Recently, this company revealed preclinical data on their product ETX201, an AAV9-based vectorized miRNA method aimed at decreasing the expression of the UBE3A-ATS and reactivating the paternal UBE3A gene to treat Angelman syndrome.

During the Foundation for Angelman Syndrome Therapeutics (FAST) 17th Annual Global Science Summit in Orlando, FL, Encoded presented significant findings. The data indicated that ETX201 was well tolerated in non-human primates (NHPs) and showed broad distribution across multiple brain areas after a single intracerebroventricular administration. Furthermore, the ETX201 miRNA transcript was present in cerebrospinal fluid, demonstrating knockdown of the UBE3A antisense transcript (UBE3A-ATS) and significant upregulation of paternal UBE3A across the cortex and hippocampus. These brain regions are essential for learning, memory, and cognitive functions.

Stephanie Tagliatela, co-founder and Chief Scientific Officer of Encoded, expressed that their method restores UBE3A gene expression by unsilencing the paternal allele. This approach represents a crucial step towards addressing the root cause of Angelman syndrome with a potentially long-lasting, one-time therapy. She further stated that the presented data validate their vectorized miRNA technology and offer a solid rationale for its application to other CNS diseases.

Angelman syndrome is a severe, lifelong neurodevelopmental disorder, affecting an estimated 1 in 12,000 to 1 in 20,000 individuals worldwide. This condition arises from the loss of function in the maternally inherited UBE3A gene, which is vital for nervous system development and function. Due to this gene's deficiency, individuals with Angelman syndrome face various challenges, including cognitive impairment, developmental delays, lack of speech, movement disorders (such as ataxia and tremors), seizures, and issues with sleeping and feeding. Despite having a normal lifespan, those affected cannot live independently and require significant support throughout their lives. Presently, no approved therapies specifically address Angelman syndrome.

ETX201 represents an innovative vectorized microRNA (miRNA) designed to unsilence the silenced paternal copy of UBE3A in neurons by targeting the UBE3A antisense transcript (UBE3A-ATS). This product uses a clinically-validated adeno-associated virus serotype 9 (AAV9) vector to deliver miRNA that reduces UBE3A-ATS expression. This potential one-time treatment aims for sustained UBE3A expression and addresses the symptoms of Angelman syndrome by tackling the disease's underlying cause.

Encoded Therapeutics is a genetic medicines company focused on developing potentially disease-modifying therapies for severe CNS disorders. Their proprietary vector engineering approach combines new regulatory elements and payloads with AAV vectors to create innovative solutions for difficult CNS conditions. Their leading clinical program, ETX101 for Dravet syndrome, targets the disorder's root cause to enable selective upregulation of SCN1A for long-lasting benefits. Additionally, Encoded is progressing a pipeline of programs to address unmet needs in rare and common CNS conditions. Utilizing their proprietary technology platform, they efficiently advance programs from discovery to clinical development. Encoded is dedicated to pioneering breakthrough treatments for CNS disorders.