Where a clinical candidate has been identified, the XenoGesis team will put together a detailed data package for review.
Typically, a data package for review would include the following:
- Pharmacokinetic data in pre-clinical species
- In vitro ADME (stability in hepatocytes/microsomes/plasma, plasma protein binding, blood:plasma ratio)
- Physiochemical properties (lipophilicity, permeability, ionisation, solubility)
- Pharmacology (in vitro & in vivo)
- Chemical structure
- Intended clinical application (primary indication & dose route)
The data package would be reviewed in the context of predicting likely human PK and dose.
The relationship between in vivo and in vitro data in the pre-clinical species would be explored using Physiologically Based Pharmacokinetic (PBPK) modelling using GastroPlusTM.
Once a suitable model that describes the pre-clinical data has been identified, this will be used to predict human PK. The human PK model will then be integrated with a PK/PD hypothesis; if sufficient data is available a PK/PD model will be used to predict an efficacious dose regime and an initial assessment of drug-drug interaction risk.
A review of the data package in the context of predicting human PK and dose. A summary of potential ADME liabilities and any recommendations for future work to address these.
Under this service we assume all data provided is accurate. As the quality of data packages varies, XenoGesis can perform an in-depth review of raw data and reports if required.