Off-Target Screening of Biotherapeutics

Biotherapeutics cross-reactivity

Toxicity that is due to off-target binding to either cell surface or secreted proteins is a leading cause of failure in drug development. Retrogenix’s Cell Microarray screening can provide an understanding of the off-target binding potential of novel biologic drug leads during discovery and early development. Building a picture of the ‘toxic liability’ of a candidate drug helps reduce risk through more informed safety assessment and can save considerable time and resources by allowing bad drugs to fail earlier. Retrogenix’s off target screening data has been used in regulatory submissions for clinical studies where high confidence in the specificity of a novel biotherapeutic is required.

 

Retrogenix off target profiling:

  • Is the only platform for assessing for off-targets against both plasma membrane and secreted proteins that are expressed in human cells
  • Provides supporting information for IND regulatory submissions, including submissions to the US FDA, EMA and China FDA
  • Is highly specific with very low numbers of false positives/negatives
  • Is used in addition to, or in place of, tissue cross reactivity (TCR) and immunohistochemistry studies
  • 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

Low false positive rate

Our highly specific screen typically reports one or two confirmed interactions rather than 100s of erroneous results that can often be seen with protein microarrays. This saves months of validation work and avoids unnecessary investigations that could stall progress with regulatory submissions.

Please contact us to discuss an off-target project.

Screen for off-targets of:

  • Antibodies & bispecifics
  • ADCs
  • ScFvs, Fabs or antibody derivatives
  • whole CAR T cells
  • Peptides
  • Protein ligands
  • Labelled small molecules

Correcting specificity in an antibody therapeutic

A recent publication describes how an anti-PD1 antibody, which caused the unique side-effect of capillary hemangioma in early phase clinical studies, was screened using Retrogenix technology and found to bind to off-target receptors that are biologically relevant to the formation of hemangioma. Subsequent molecular remodelling of the antibody not only eradicated the in vitro off-target binding but also led to increased potency in PD1/PD-L1 blockade…

Read the case study

Identifying a monoclonal antibody off-target

A single monoclonal test antibody – developed against a key GPCR target – was provided by the study sponsors along with an isotype-matched negative control antibody for screening…

Read the case study

Talk to us about a project
Pfizer
The University of Sheffield
Aveo Oncology - The Human Response
Theraclone Sciences
BioInvent
AstraZeneca
Bluebird Bio
glycotope_logo
The Center for Infectious Disease Research
Compugen Logo
The University of Copenhagen
Lund University
MedImmune
NIH - National Institutes of Health
The University of Pennsylvania
Scripps Florida - The Scripps Research Institute
Peptinnovate Ltd - Unlocking Nature's Potential
Capella Bioscience Logo
Sanofi Logo
Everything was perfect and we are definitely looking forward to collaborate with Retrogenix again.
Head of Medicinal Chemistry, Sanofi