This workshop will explore how teams approach potency, sequence selection, and dosing considerations when advancing antisense oligonucleotides for CNS applications. Given the long tissue half-life and dosing requirements often associated with CNS delivery, early discovery decisions can have important implications for clinical strategy, safety, and manufacturability. The session will focus on how different organizations define and balance potency, tolerability, and feasibility, and whether there are emerging best practices in early screening and candidate selection that support successful translation.

Highlights Include:

• Discussion around how teams define and interpret sufficient knockdown in vitro and in vivo, and how this informs progression decisions
• Exploring challenges in identifying accessible and functionally relevant transcript regions
• Examining how potency influences dose levels, delivery strategy, and overall development considerations in CNS settings
• Considering how sequence-dependent off-target effects are evaluated and incorporated into early decision-making
• Reflecting on whether there are opportunities to evolve screening paradigms and selection criteria to better support downstream success