2019 PharmSci 360
Therapeutic Antisense Oligonucleotides (ASOs) are 15 – 30 nucleotides in length designed to bind to a specific region of a messenger RNA. They can hence be used to target specific disease-related RNAs and modulate expression of the corresponding protein. This session will briefly summarize the rationale of targeting the TMPRSS6-Hepcidin Pathway for Iron regulation and then dive into the details of a clinical proof of concept for ISIS 702843, a TMPRSS6 targeting nucleic-acid based therapy. It will then mainly focus on the development of a mechanistic model that links two key biomarkers for Non-transfusion dependent thalassemia (NTDT) using Phase 1 data of ISIS 702843 and eventually discuss the application of modeling and simulation in Phase 1-Phase 2 development of this program.