Specificity Screening Drug Development Tool for Biotherapeutic Safety

ABSTRACT Off-target safety problems are the single leading cause of preclinical drug failures. As a result, specificity profiling has become an FDA requirement for monoclonal antibodies (MAbs) as well as other emerging biotherapeutic categories such as CAR-T cell therapy. Current methods for profiling the specificity of biotherapeutics, primarily tissue cross-reactivity studies (TCR) and spotted protein arrays, are poorly predictive of cross-reactivity against the native human proteome, have low sensitivity, and are difficult to interpret. A novel approach for specificity profiling is needed to better predict off-target binding of MAbs and de-risk biotherapeutic discovery programs. Integral Molecular is the industry leader in membrane protein antibody discovery and characterization. As a result of previous SBIR funding, we developed a new technology for specificity profiling and deorphaning, the Membrane Proteome Array (MPA). The MPA represents 93% of the human extracellular proteome expressed in their native conformation in live cells. Recently, the MPA was the first technology accepted into the FDA’s ISTAND pilot program for drug development tools (DDT). Development of the MPA would have a large impact on the clinical pipelines of nearly every biopharmaceutical company and has significant commercial potential.