Animal to human PK translation

Goal: Support selection of First-in-Human dose

Available data

• Plasma concentration measurements in mice, rat, and dog (>10 studies)
• IV and oral administration
• Efficacy and tox study data in animals allowing to assume potential concentration thresholds for efficacy and safety

Questions

• Potential non-linearities observed in animal
• What might be the source?
• Could it translate to human?
• Is the currently planned starting dose realistic?
• Are the dose strengths currently planned to be manufactured reasonable?

Approach

• Integration of all available data
• Weight-based allometric scaling to human
• Simulation based assessment of candidate dose scenarios in human

Benefit for the Client

• Refined assumption on likely human PK
• More informed dose selection
• Buy-in of stakeholders (incl. investors)
• Improved FIH study design (e.g. PK sampling times, follow-up time)