This service is designed for investors, VCs and licensees who require an independent view on the quality of the pre-clinical data package of a small molecule asset prior to investing or licensing.
It is also designed for licensors to evaluate their data packages prior to licensing, and for organisations reviewing their internal portfolio to determine how resources should be allocated.
Where a clinical candidate has been identified, the XenoGesis team will put together a detailed data package for review.
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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.
The XenoGesis team can work with you to put together data packages for hit/lead compounds and for lead optimisation programmes.
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Hit Identification / Lead Identification / Lead Optimisation Programmes
Typically, a data package for review will cover a broad range of compounds in less depth than a clinical candidate.
- Molecular weight
- Hepatocyte/microsome stability
- Kinetic solubility for a selection of compounds
A further more detailed package covering one or two lead compounds would include:
- In vivo PK in one or two pre-clinical species
- Plasma protein binding & permeability
- Some preliminary in vivo pharmacology
- An understanding of the intended clinical use (indication, dose route) or target candidate profile
The data would be reviewed to explore the trends between in vitro and in vivo data and their relationship with potency and the physicochemical properties. The aim would be to identify the deficiencies in the lead compound(s) and, the likelihood that these could be addressed during a lead optimisation campaign. A proposal for a screening cascade to achieve this would be suggested.
In general, we will assume all data provided is accurate. However, we can perform an in-depth review of raw data and reports if required.