Encoded Therapeutics Shares Preclinical Data at ASGCT 27th Annual Meeting

Encoded Therapeutics Inc., a biotechnology firm focused on developing genetic medicines for severe central nervous system (CNS) disorders, has recently shared significant advancements in its preclinical gene therapy programs and vector engineering platform at the 27th ASGCT Annual Meeting held in Baltimore, MD. The presentations highlight potential treatments for conditions such as Angelman Syndrome, Lennox-Gastaut Syndrome, neuropathic pain, and Alzheimer’s disease.

Stephanie Tagliatela, Chief Scientific Officer at Encoded, emphasized the substantial progress in their portfolio of precision genetic medicines, underscoring the platform’s potential to deliver targeted therapies for various CNS diseases. Tagliatela also mentioned the clinical advancement of ETX101 for SCN1A+ Dravet syndrome, with plans to nominate several programs for development by 2025.

One of the key oral presentations, titled "GABA Selective AAV-mediated Gene Therapy Provides Durable Seizure Protection in Multiple Refractory Epilepsy Models," showcased the development of gene therapies aimed at enhancing GABAergic neurotransmission to address circuit dysfunction in refractory epilepsies. The leading candidate demonstrated a significant reduction in seizure incidence and severity in two different seizure models without adverse effects on body weight, motor function, or locomotion. Moreover, high-dose tolerance was confirmed in non-human primates, supporting further development for treating refractory epilepsies.

In addition to the oral presentation, several poster presentations highlighted other promising developments. One presentation, "Advancing Gene Therapy for STXBP1-related Disorders Through Targeted Vector Engineering," revealed efficacy and safety results in both mice and non-human primates for gene therapies targeting STXBP1-related disorders (STXBP1-RD). The engineered AAV9 vectors demonstrated strong CNS expression and tolerance, with significant improvements in seizure, cognitive, and motor phenotypes in Stxbp1+/- mice. The inclusion of a dorsal root ganglia (DRG) de-targeting element successfully reduced off-target expression, reinforcing the potential of AAV9-based gene therapies for STXBP1-RD.

Another poster, "A Vectorized miRNA-based Approach to Unsilence UBE3A in Angelman Syndrome," detailed efforts to upregulate the paternal UBE3A gene using an AAV-based miRNA vector, addressing the loss-of-function issue in Angelman Syndrome (AS). The lead miRNA candidate showed promising results in the AS mouse model, correcting multiple phenotypes and demonstrating tolerance in non-human primates, suggesting further development of this approach for AS treatment.

The final highlighted poster, "Identification of Potent and Selective AAV-miRNA Candidates to Knockdown Non-Monogenic Neurological Targets SCN9A (Pain) and MAPT (Tauopathies)," focused on the potential for long-term knockdown of genes associated with neuropathic pain and Alzheimer’s disease using an AAV-mediated miRNA platform. Potent miRNA candidates were identified to selectively target and reduce SCN9A and MAPT gene expression in various models, supporting the advancement of these candidates to preclinical studies in non-human primates.

Encoded Therapeutics leverages a proprietary vector engineering approach combining novel regulatory elements and payloads with AAV vectors to develop innovative treatments for debilitating CNS conditions. The company's flagship program, ETX101 for Dravet syndrome, aims for selective upregulation of SCN1A, offering potentially long-lasting benefits. Alongside ETX101, Encoded is advancing a pipeline of promising programs addressing both monogenic and prevalent CNS disorders, striving to meet significant unmet medical needs.