Toxicity due to cross-reactivity – or “off-target” binding – involving either cell surface or secreted proteins is a serious cause for concern in drug development. Furthermore, demonstrating on-target specificity is a necessary hurdle in the race for regulatory approval for a novel biotherapeutic.
Retrogenix’s Cell Microarray screening provides an understanding of the off-target profile of a biologic candidate during discovery and early development. Building a picture of a biotherapeutic’s ‘toxic liability’ through cross-reactivity screening helps reduce risk through more informed safety assessment and can save considerable time and resources by allowing bad drugs to fail earlier. Retrogenix’s cross-reactivity screening data have been used extensively in regulatory IND and BLA submissions, where high confidence in the specificity of a novel biotherapeutic is required.
Where Retrogenix results have been used in regulatory submissions:
- Cross-reactivity data were accepted globally. IND or BLA submissions have been made to: US FDA, EMA (Europe), PMDA (Japan) & NMPA (China)
- Over a third of submissions that included Retrogenix’s cross reactivity results relied solely on these data for specificity assessment, with no tissue cross-reactivity (TCR) studies performed in 38% of cases
- 90% of submissions using Retrogenix data have been approved to date.
More details on the use of Retrogenix’s IND-enabling specificity data can be found in our regulatory submissions survey results.
Retrogenix off target profiling:
- The only platform for assessing for off-targets against both plasma membrane and secreted proteins that are expressed in human cells
- Highly specific with very low numbers of false positives/negatives
- Can predict/explain reduced bioavailability due to off-target binding
- Can inform pre-clinical tox model selection, reducing animal testing
- Helps prioritise drug leads or avoid off-target activities in next-generation of molecules