Nucleic acid drugs continue to deliver on their promise to become a third therapeutic modality, in addition to small molecules and biologics. Several antisense oligonucleotide drugs have been on the market for some time, while the first RNAi approval was granted in 2018. Despite the common “nucleic acid” component, the mechanisms of action and non-specific effects differ for each of these drug types.

ICH guidelines have established clear expectations for the control strategy for synthetically manufactured medicines. Oligonucleotides fall into the synthetic category and yet their manufacture and control are very different compared to small molecules. In this short course we will look at the requirements for a control strategy combining starting material control, process understanding and final drug substance specifications and methods. With a common understanding in mind we will discuss how to apply the control principles to therapeutic oligonucleotides from early development to registration.

Conjugated modalities such as antibody-drug conjugates (ADCs), oligonucleotide conjugates, and peptide-drug conjugates are revolutionizing precision medicine. However, their success relies on smart linker strategies that ensure stability, controlled payload release, and manufacturability. This intensive 2-hour course will explore the latest innovations in linker chemistry, site-specific conjugation, formulation and delivery considerations, and scalable manufacturing approaches. Participants will gain practical insights into optimizing linker design for enhanced efficacy, reduced toxicity, and regulatory compliance.