AAV-miRNA targeting UBE3A-ATS(Encoded)

ORLANDO, Fla.--( BUSINESS WIRE )--Encoded Therapeutics Inc., a clinical-stage biotechnology company developing genetic medicines for severe central nervous system (CNS) disorders, announced today that it will present new preclinical data on ETX201, an AAV9-based vectorized miRNA approach designed to reduce the expression of the UBE3A-ATS and unsilence paternal UBE3A expression for the treatment of Angelman syndrome. At the Foundation for Angelman Syndrome Therapeutics (FAST) 17 th Annual Global Science Summit in Orlando, FL, Encoded will present data showing that ETX201 was well tolerated in non-human primates (NHPs) with broad expression across multiple brain regions following a single intracerebroventricular administration. ETX201 miRNA transcript was also detectable in the cerebrospinal fluid. Knockdown of the UBE3A antisense transcript (UBE3A-ATS) was observed, in addition to widespread paternal UBE3A upregulation across the cortex and hippocampus -- critical, disease-relevant brain regions important for learning, memory, and cognitive functioning. “ Our approach restores expression of the UBE3A gene by unsilencing the paternal allele and represents an important step towards addressing the underlying cause of Angelman syndrome with a potentially durable, one-time therapy,” said Stephanie Tagliatela, co-founder and Chief Scientific Officer of Encoded. “ These data validate our vectorized miRNA technology and provide strong rationale for exploring its application for common CNS diseases.” FAST Global Science Summit Presentation Details: Title: ETX201: An experimental vectorized miRNA-based approach for the treatment of Angelman syndrome Presenter: Sirika Pillay, Ph.D., Director of Molecular and Cellular Pharmacology, Encoded Therapeutics Date & Time: Saturday, November 9, at 9:50-10:10 a.m. ET About Angelman Syndrome Angelman syndrome is a severe and lifelong neurodevelopmental disorder that is estimated to affect approximately 1 in 12,000 to 1 in 20,000 people globally. It is caused by loss of function in the maternally inherited copy of the UBE3A gene, which plays a critical role in the development and function of the nervous system. As a result of this deficiency, individuals with Angelman syndrome experience a range of challenges, including cognitive impairment, developmental delays, lack of speech, movement disorders (such as ataxia and tremors), seizures, as well as sleeping and feeding problems. While affected individuals typically have a normal lifespan, they are unable to live independently; they require substantial support throughout their lives, relying on caregivers and family for assistance with daily activities. Despite its significant impact, there are currently no approved therapies specifically designed to treat Angelman syndrome. About ETX201 ETX201 is a vectorized microRNA (miRNA) designed to unsilence the paternal copy of UBE3A , which is naturally silenced in neurons by the UBE3A antisense transcript (UBE3A-ATS). ETX201 expresses a miRNA that targets the UBE3A-ATS to knock down its expression and is delivered using a clinically-validated adeno-associated virus serotype 9 (AAV9) vector. This potential one-time treatment approach aims to consistently and durably restore UBE3A expression and address the spectrum of symptoms associated with Angelman syndrome by targeting the underlying cause of the disease. 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 rare and common CNS conditions. 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 .