Preclinical Development – Biomolecular
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. They represent the leading category of nucleic-acid based therapeutics that are approved across several therapeutic areas including rare and neurodegenerative diseases. This presentation will review the basic ADME/PK/PD profiles and properties of ASOs in non-clinical species and provide a comparison of the same across species. The session will also highlight the evolution of ASOs as a platform and some recent breakthroughs in target tissue delivery which have transformed the platform. Different methods for the non-clinical to clinical translation of ASOs such as allometry and PK/PD modeling will also be discussed. A case study briefly explaining the translational approaches from non-clinical species to first in human dose selection and studies will also be presented.