Since the first approval in 1998, 15 oligonucleotide therapies have been approved to date. The well-established relationship between plasma and tissue concentrations, along with the availability of measurable biomarkers, has enabled the widespread application of modeling and simulation to support the development of antisense oligonucleotides (ASOs). However, modeling ASOs also presents unique challenges, including nonlinear tissue distribution across clinically relevant dose ranges and complexities associated with different routes of administration. The speaker will provide an overview of ASOs, highlighting its general properties and key absorption, distribution, metabolism, and excretion (ADME) and pharmacodynamic (PD) characteristics in contrast to other therapeutic modalities, feature case studies highlighting general modeling approaches applied at various stages of ASO development. The speaker will also discuss strategies used to overcome key challenges, demonstrating how modeling and simulation can inform decision-making and optimize development in this rapidly evolving field.
