Managing Director NewGround Pharmaceutical Consulting
This 30-minute talk is structured to be part of a suggested symposium titled “Advancements in translational PK/PD approaches towards novel biologic modalities”. Talks proposed within this symposium are carefully stitched to ensure that each talk details a ‘novel view / approach / meta-analysis with case examples’ rather than just a general overview on the topic.
This talk titled “Rational FIH dose selection of AAV mediated gene therapy based on allometric principles”, will introduce a novel concept of gene efficiency factor (GEF) to describe the efficiency of the gene transfer system and describe and apply the concept of GEF in AAV mediated in vivo gene transfer systems.
In vivo gene therapy delivers genetic material into target organs or tissues, and it has enormous potential in treating diseases caused by defective genes. Among vectors used in in vivo gene therapy,recombinant adeno-associated virus (AAV) vectors are most favored due to their non-pathogenicity, broad tissue tropism, and the ability to produce continuous transgene expression primarily in the forms of episomal circular genomes in transduced tissues. We explore the utility of allometric scaling to translate novel concept, GEF across species using AAV-mediated in vivo factor IX (FIX) gene therapy for hemophilia B and to demonstrate the use of GEF in predicting efficacious AAV vector doses in humans. We show for the first time that an allometric relationship exists for GEF of AAV-mediated in vivo gene therapy. Furthermore, we demonstrate the feasibility of using the allometric relationship of GEF to select efficacious first-in- human doses of virus-mediated in vivo gene therapy. Based on our findings, allometry of GEF can be used to translate biological efficiency from animal studies to clinical studies and provide a rational basis of setting first-in-human doses for new virus-mediated in vivo gene therapy products.
Learning Objectives:
Upon complettion, the participant will be able to appreciate the key challenges, mitigation strategies, and translational considerations for prediction of FIH doses for gene therapy
Upon complettion, the participant will be able to gain basic understanding of the novel concept “Gene Efficiency Factor” in describing the efficiency of gene transfer system
Upon complettion, the participant will be able to gain the basic understnading of the potential utility of the Gene Efficiency Factor in assiting the FIH dose selection of gene therapy
