S13-03 NAMs and immunosafety assessment of biotherapeutics

Biotherapeutics, including various immunotherapy modalities (monoand bi-specific antibodies, proteins and fusion proteins, cellular therapies), are now very well established or highly pursued approaches for the treatment of a variety of diseases, including many cancers and auto-immune / inflammatory diseases. A particularity of some biotherapeutics is the lack of pharmacologically relevant animal model for nonclinical safety assessment. In addition, it is generally accepted that animal models are not appropriate to assess immunogenicity of biotherapeutics. In that context, in silico and in vitro approaches have been and are being developed to mitigate for the lack of proper animal model and it can be envisioned that, when appropriate, nonclinical safety assessment relies solely on such approaches. This presentation will address how immune-related putative liabilities (immunogenicity, cytokine release, immunosuppression, off-target activity, on-target on-disease and/or on-target-off disease acitivty) of biologics and cell therapies (engineered effector and regulatory T cells) can be assessed using in silico and in vitro tools.