Jimmy Weterings
Vice President & Head of Oligonucleotide Therapeutics Bonito Bioscience
Seminars
Wednesday 19th August 2026
Workshop C: CNS siRNA Chemistry & Conjugation Architecture: Duplex Design, 2 Modifications & Delivery Constructs
1:00 pm
This workshop explores the structural engineering challenges unique to CNS siRNA programs, where duplex chemistry, 2 modifications, phosphorothioate content, and conjugation strategy collectively determine intracellular delivery and translational feasibility. Discussions of complex multi-component constructs incorporating linkers and antibodies and introducing additional PK, DAR, and manufacturability considerations.
Highlights Include:
- Is there an optimal duplex architecture for CNS exposure and sustained knockdown?
- How should DAR be optimized in CNS shuttle systems?
- Discussion will examine whether single- versus multi-payload conjugation improves exposure or increases structural complexity and manufacturing risk
- Where and when should linker cleavage occur for effective intracellular release?
- How does premature cleavage versus delayed release affects systemic sink and CNS bioavailability?
Thursday 20th August 2026
Roundtable Discussion: Conjugation vs Intrinsic Chemistry – Is Targeted CNS Delivery Worth the Structural Complexity?
5:00 pm
- Evaluating whether receptor-mediated conjugation strategies provide a translational advantage over intrinsic chemistry optimization, given the absence of a validated receptor–ligand specific to CNS
- Examining the structural and operational complexity introduced by antibody–oligonucleotide constructs and the requirement for highly efficient delivery at low systemic doses to avoid toxicity risk
- Debating whether emerging alternatives or intrinsic chemistry tuning remains the more scalable and practical strategy for CNS programs
Thursday 20th August 2026
Pannel Discussion: Beyond Transferrin Receptors Unlocking Safer & More Specific CNS Oligo Delivery for the Next Generation of BBB Shuttles
10:30 am
- Reassessing the limitations of TfR1-mediated delivery including broad peripheral expression, systemic sink effects, tolerability concerns, and limited cell-type specificity and evaluating whether alternative receptors such as CD98, IGF1R, peptide ligands and LNP-enabled formats can deliver improved CNS selectivity
- Examining emerging BBB access strategies, including receptor alternatives and physical modulation approaches such as antibody-mediated opening or focused ultrasound, while balancing enhanced penetration against the biological risks of barrier disruption
Thursday 20th August 2026
Panel Discussion: Scaling CNS Oligonucleotides into Larger Indications & What It Means for Delivery, Manufacturing & Competition
8:30 am
- Assessing whether intrathecal administration is operationally viable for high prevalence CNS populations given procedural burden, treatment infrastructure, and long-term dosing frequency, and whether certain disorders are inherently better suited to intrathecal versus systemic BBB shuttle-based delivery approaches
- Evaluating whether systemic brain shuttle platforms can achieve therapeutically meaningful CNS exposure particularly as programs move from rare to common disease settings
- Examining how expansion into larger indications reshapes manufacturing and competitive dynamics, including oligonucleotide drug substance capacity, cost of goods at commercial scale, multi-vendor CMC complexity for antibody or ligand conjugates, raw material supply constraints for shuttles, and whether manufacturing readiness will ultimately accelerate or hinder competition in the CNS oligo space
Thursday 20th August 2026
Chair’s Closing Remarks
5:30 pm
