Director Stoke Therapeutics, Inc. Bedford, Massachusetts
Antisense Oligonucleotides (ASOs) are nucleic acid therapeutic modalities with potential to address diseases that have been challenging to treat with small molecules or biologics. Out of the currently 10 approved ASOs, only two target neurodegenerative diseases. Targeting Central Nervous System (CNS) diseases with ASO requires unique considerations for bioanalysis and pharmacokinetic (PK) modelling. In this talk, a case study will be presented discussing the LC-MS and Hybridization based immunoassays for STK-001, an ASO that is currently being evaluated in Phase 1/2 and Open-label extension studies for treatment of Dravet Syndrome, a severe and progressive genetic epilepsy. The decision-making process for selection of bioanalytical methods to support PK modelling efforts for STK-001 will be described. Finally, a PK model for STK-001 developed using data from cynomolgus monkeys following intrathecal dosing of STK-001 will be discussed to demonstrate the role of PK modelling in prediction of PK in humans for CNS diseases.
Learning Objectives:
Upon completion, participants will be able to discuss challenges associated with bioanalysis of antisense-oligonucleotides (ASOs) targeting CNS diseases.
Participants will be able to understand the decision-making process for selection of bioanalytical methods to support PK-modelling efforts for ASOs targeting CNS diseases.
Gain knowledge regarding the role of PK modelling in prediction of human PK for ASOs targeting CNS diseases.