P136 Immunogenicity Risk Assessment Using Pre-clinical Tools For Biotherapeutics

Pu Shi , Takeda Pharmaceuticals International Co., Cambridge, MA
Christopher Gemski , Takeda Pharmaceuticals International Co., Cambridge, MA
Li Zhou , Takeda Pharmaceuticals International Co., Cambridge, MA
Jing-Tao Wu , Takeda Pharmaceuticals International Co., Cambridge, MA
Cindy Xia , Takeda Pharmaceuticals International Co., Cambridge, MA
Immunogenicity of biotherapeutics triggers the responses of anti-drug antibodies (ADAs), significantly affecting pharmacokinetic, pharmacodynamic, efficacy and safety profiles of the drug. TBOS DMPK has established new in-house capability to evaluate the immunogenicity risk of biotherapeutics using both in silico and in vitro cell-based approaches at pre-clinical settings. The new immunogenicity risk assessment strategy can be applied at early and late discovery stages to support lead selection and optimization.

The in silico immunogenicity algorithm has high-throughput capacity to screen hundreds of clones based on their amino acid sequences, and identify and rank order the ones with low immunogenicity prediction scores according to the containing T cell epitopes. The in vitro human PBMC-based assays can be utilized to further assess the immune reactions caused by the molecules with the detection of CD4 T cell responses and also can be used to examine potential changes in immunogenicity property due to the changes of formulation, expression system and other factors at developmental stage. This new capability may help us at Takeda identify and select the biologic molecules with the lowest possibility to trigger anti-drug antibody response and achieve better efficacy and safety profiles.