Principal Scientist Stoke Therapeutics Bedford, Massachusetts
STK-001 is a chemically synthesized antisense oligonucleotide that is being developed by Stoke Therapeutics for the treatment of Dravet syndrome in children of age 2 to 18 years. STK-001 is administered intrathecally and is being investigated in Phase 1/2 and Open Label Extension studies in US and UK. To assess the potential immunogenicity response due to ADA generation induced by STK-001 administration in NHP and Human, we developed reliable and sensitive ELISA methods for detection and titration of STK-001 ADA. STK-001 derived immunogen was administered in rabbits to generate positive control (PC). Following affinity purification of PC, an ELISA method was developed to determine minimum required dilution (MRD), sensitivity, cut point, and drug tolerance in serum from NHP and Human. The immunogenicity assays were validated per current industry practice and regulatory guidelines and successfully used to support sample testing in repeat dose toxicity studies in NHP and ongoing clinical studies.
Learning Objectives:
Development and validation of ADA assay for ASO, STK-001
Generation of ADA positive control
Evaluation of MRD, sensitivity, cut point, and drug tolerance
