Greta Garrido Hidalgo

The therapeutic window of RNAi is defined by the intricate balance between potent silencing and off-target effects, driven by advances in chemical modifications, novel conjugate strategies, and a deeper understanding of RNAi pharmacology. This roundtable convenes experts pioneering these chemical and biological innovations to define the principles for building better, safer RNAi therapeutics by discussing:

• How are novel phosphorothioate patterns, 2’-modifications, and scaffold designs being used to actively direct biodistribution, improve cellular uptake, and facilitate endosomal escape
• Comparing the advantages, limitations, and unique pharmacological profiles of emerging delivery vehicles.
• Integrating predictive tools for immunogenicity and off-target effects early in candidate selection.

• Showcasing early preclinical evidence of tumor-selective siRNA activity with minimized off-target effects through aptamer-based targeting
• Introducing the Antibody-Oligonucleotide Conjugate (AOC) platform and proof-ofconcept studies validating precision tumor delivery
• Presenting data from lead candidate selection and in-depth characterization to demonstrate potency and durability
• Exploring future opportunities to integrate Sebastian BioPharma’s RNAi platforms with checkpoint inhibitors and precision medicine strategies to expand patient benefit