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Target occupancy biomarker assay development using a conformation-selective antibody against small-molecule-bound TNF
Elizabeth S Hickford1, James O'Connell1, Alison Maloney1
1Early Solutions, UCB Biopharma UK, 208 Bath Road, Slough, SL1 3WE, UK.
Bioanalysis
|April 7, 2023
Summary
New assays measure target occupancy for TNF inhibitors, aiding autoimmune disorder drug development. This biomarker supports the advancement of novel small-molecule treatments targeting TNF.
Area of Science:
- Immunology
- Pharmacology
- Biomarker Development
Background:
- Tumor Necrosis Factor (TNF) is a key target in autoimmune disorders.
- Small-molecule inhibitors offer a novel therapeutic approach for these conditions.
- Measuring drug target engagement is crucial for therapeutic development.
Purpose of the Study:
- To develop and validate assays for measuring TNF target occupancy.
- To support the clinical progression of small-molecule TNF inhibitors.
Main Methods:
- Development of Enzyme-Linked Immunosorbent Assays (ELISAs) for bound and total TNF.
- Utilized electrochemiluminescence immunoassay for simultaneous measurement.
- Validated assays using stimulated blood and plasma samples.
Main Results:
- TNF occupancy directly correlated with inhibitor concentration in plasma.
- Validated electrochemiluminescence method for clinical use.
- Demonstrated feasibility of measuring a target occupancy biomarker.
Conclusions:
- Novel assays enable measurement of TNF target occupancy.
- This biomarker supports the development of small-molecule TNF inhibitors.
- Facilitated the progression of first-in-class TNF-targeting drugs.
