Presentation Description: A study where a mouse Fc-fusion of a human ligand, cross-reactive in mouse, showed PK liability in mice when dosed IV at 0.5, 1, and 10 mg/kg. PK profiles showed clear differences between samples analyzed with a generic IgG2A assay, and specific assay to quantify active species. Generic assay results exhibit large distribution volumes and sustained drug concentrations up-to Day 21 with ~12-day half-life. Specific assay concentrations differentiate from the generic assay at concentrations below 10-30 ug/mL and profiles show rapid clearance at lower doses. The low drug concentrations likely contributed to the lack of activity observed in vivo studies at the lower doses.
Identify drug development challenges with development of fusion proteins/novel formats particularly in regards to assays to measure drug concentrations in biological matrices
Determine the impact of assessing in vivo stability of fusion proteins and its affect on in vivo PK and efficacy
Identify the relationship between in vivo PK and in vivo efficacy