Friday, September 25Friday, 25 September 2026 - EST (Eastern Time, UTC-05:00

• The presentation introduces zorevunersen, an antisense oligonucleotide (ASO), designed to address the underlying genetic cause of Dravet syndrome.
• It highlights how the ASO approach aims to restore Nav1.1 protein levels, potentially improving seizure control and neurodevelopmental deficits in patients with Dravet syndrome.
• Preclinical and clinical findings on safety and efficacy of zorevunersen in Dravet syndrome are discussed

• TTX-MC138 is an antisense oligonucleotide therapeutic targeting miR-10b, a driver of metastatic disease, with preclinical studies showing successful delivery to metastatic lesions and complete regression without recurrence

• Phase 0 microdose study (NCT05908773) demonstrated drug accumulation in metastatic lesions, stability in circulation with an 18.7-hour half-life, and robust pharmacodynamic activity

• Phase 1a dose-escalation study (NCT06260774) enrolled 16 patients across four dose levels (0.8-4.8 mg/kg), met primary safety endpoints, and established a recommended Phase 2 dose with median treatment duration of four months

• 44% of patients achieved stable disease lasting ≥4 months, with one thyroid cancer patient showing reversal of rising thyroglobulin levels to undetectable during treatment

This presentation introduces Chemoenzymatic Synthesis as a next-generation solution for oligonucleotide synthesis. Unlike traditional solid-phase synthesis, Chemoenzymatic Synthesis assembles short, chemically prepared oligonucleotide fragments using enzymatic ligation under mild aqueous conditions, reducing impurities and improving yield, scalability, and cost efficiency. By optimizing fragment design, ligation parameters, and purification strategies, Chemoenzymatic Synthesis enables high-purity oligonucleotide manufacturing with enhanced reproducibility. 

• Provide an overview of the scientific and clinical rationale for targeting tau biology in Alzheimer’s disease, including how tau-lowering approaches may fit within the evolving treatment landscape.
• Describe the rationale for MAPT gene silencing with siRNA as a precision approach designed to reduce production of tau protein, with potential relevance across Alzheimer’s disease and related tauopathies.
• Highlight Arrowhead’s TRiM and CNS-SC platform approaches, including TfR1-mediated systemic delivery to the CNS and translational evidence supporting CNS delivery and target engagement.
• Review the ARO-MAPT-SC development program, including key preclinical and translational findings and the design of the ARO-MAPT-SC-1001 Phase 1/2a study.

This presentation explores next-generation siRNA manufacturing strategies that address growing industry demand for scalable, cost-effective production. By integrating enzymatic ligation and thermostable enzyme technologies, we demonstrate pathways to improve efficiency, reduce cost of goods, and enable flexible manufacturing at scale.

• Transition from conventional SPOS to hybrid enzymatic ligation for improved yield, purity, and sustainability

• Design and screening of thermostable ligases to enable high-temperature, high-efficiency ligation

• Impact of elevated temperature on impurity control, fragment selectivity, and ligation performance

• Scalable manufacturing strategies (C-to-C, C-to-P, P-to-P) to optimize cost, robustness, and process efficiency

• Explore the cutting-edge frontiers of RNA drug discovery as industry leaders discuss breakthrough technologies and strategies shaping the next generation of genetic medicines. This session will examine emerging areas of innovation, including in vivo mRNA CAR-T approaches, circRNAs, RNA editing and antisense oligonucleotide (ASO) development for CNS disorders.
• Gain insights into overcoming key challenges in stability, immunogenicity, and delivery while discovering how advances in chemical modifications, formulation science, and AI-driven design are unlocking new therapeutic possibilities across oncology, rare diseases, metabolic disorders, and beyond.