Aim(s):
- To compile a 'gold standard' data set of PK, Immunogenicity and Phys Chem properties for Biologics (primarily antibodies) based on information in the public domain, in the first instance. 'Gold standard' dataset defined as one which allows the direct comparison of different studies and contains a minimum set of required parameters.
- Beyond this, would like to model PK from primary sequence.
Contributors:
Vincent Dubois (MedImmune), Dave Fairman (GSK), Anna Gaulton (EMBL-EBI), Theresa Goletz (EMD Serono), Boris Grinshpun (EMD Serono), Anne Hersey (EMBL-EBI), Tushar Jain (Adimab), Andrew Leach (EMBL-EBI), Chris Lloyd (MedImmune), Yves Fomekong Nanfack (EMD Serono), Friedrich Rippmann (Merck)
Value proposition and use:
>Need well curated, more diverse (different animal models, different Abs, etc.) and evolving data on reference molecules - this is already available internally but to a lesser extent.
>Use the dataset to improve the likelihood of developing new predictive models
>Use the dataset for better standardisation; allowing for robust comparison, cross referencing, identifying outliers and further analyses.
>Use the dataset to link early screening data to later (endpoint) data.
Scope:
>Initial focus is on mAbs
>Include information on ADCs (this needs to be contextualised in the database)
>Other IgG-like molecules to be included based on absence of technical limitations
Approach:
>Collate PK on 10 priority marketed Ab drugs which are know to have high quality published data and check whether this meets the above definition.
>Propose 'data quality' tiers into which data from published molecules can be placed.
>Collate PK and other data from additional Ab molecules and fit these into proposed 'quality tiers'
>Once we identify T3 data - can we use internal data to move this to T1 or T2?
>Once we have identified molecules in each Tier can we characterise these from a biophysical perspective and see whether there are correlations between PK and early data
Further needs:
-Discussion on sources of data e.g. Jain et al., (2017) publication, FDA drug approval packages
-Discussion on technicalities of database build, setup, etc. bearing in mind future inclusion of data from other biologic drug modalities beyond standard mAbs