Off-Target Screening of Biotherapeutics

Building a picture of a biotherapeutic’s off-target liability through cross-reactivity screening helps reduce risk through providing a more informed safety assessment. This will save you considerable time and resources by identifying potential clinical risks earlier on. Through off-target screening, Retrogenix Cell Microarray Technology is the only platform which assesses off-targets against both plasma membrane and secreted proteins that are expressed in human cells. Our highly specific screen typically reports one or two confirmed interactions, rather than hundreds of erroneous results, saving months of validation work and unnecessary investigation. Additionally, we are able to offer follow-up hit validation after results have been delivered, typically with materials already available from the end of the main study. Our data is globally accepted in regulatory submissions, with a greater than 95% success rate.

Off-Target Profiling Cell Microarray Technology
Discover high quality, exploitable drug targets and mechanisms of action as well as screening for potential off-targets.

Target Deconvolution Target Deconvolution
Accelerate phenotypic drug discovery through target deconvolution of phenotypic molecules.

Receptor Identification Receptor Identification
Uncover receptors for proteins, viruses, and more complex ligands such as whole cells.

CAR Cell Specificity Screening CAR Cell Specificity Screening
Safely utilize a patient’s own immune system by precisely recognizing specific tumors.

 

Data from our biotherapeutic off-target screening have been used extensively in regulatory BLA and IND submissions, where high confidence in the specificity of a novel biotherapeutic is required.

Screen for cross-reactivity of:

  • Antibodies (monospecific, bispecific and multispecific)
  • ADCs
  • ScFvs, Fabs or antibody derivatives
  • Whole CAR cells
  • Peptides
  • Protein ligands
  • Labelled small molecules

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Off-Target Screening

  • The only platform for assessing 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 and explain reduced bioavailability due to off-target binding
  • Can inform pre-clinical tox model selection, reducing animal testing
  • Prioritizes drug leads or avoid off-target activities in next-generation molecules

Graphic image showing the binding of a test article to an overexpressed human protein in HEK293 cells using the Retrogenix Cell Microarray.

Graphic images showing the binding of a test article to an overexpressed human protein in HEK293 cells using the Retrogenix Cell Microarray. Image on the right shows the fluorescence that shows binding.

Graphic images showing the binding of a test article to an overexpressed human protein in HEK293 cells using the Retrogenix Cell Microarray for off-target screening. Binding will typically be assessed via fluorescence (right image).

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Low False Positive Rate

Our highly specific off-target screening assays typically reports one or two confirmed interactions, rather than hundreds of erroneous results that can often be seen with protein microarrays. This saves months of validation work following cross-reactivity screening and avoids unnecessary investigations that could stall progress with regulatory submissions.

 

Using Screen Results to Support Regulatory Submissions

  • Cross-reactivity data were accepted globally. IND or BLA submissions have been made to: US FDA, EMA and other European regulators, PMDA (Japan) & NMPA (China)
  • A third of submissions that included our cross-reactivity results relied solely on these data for specificity assessment, with no further tissue cross-reactivity (TCR) studies performed in 38% of cases
  • 95% of submissions using our off-target screening data have been approved to date, with a further 5% still in the submissions pipeline

More details on the use of IND-enabling specificity data can be found in our regulatory submissions survey results.

See The Results

 

Frequently Asked Questions (FAQs) for Off-Target Screening