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

• 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