|BEIGENE, LTD. filed this Form 8-K on 01/07/2019|
Fc RI - + Nivolumab Pembrolizumab CD8 + T cell CD4 + T cell - Fc RI Macrophage Monocyte MDSC Dendritic cell + Tislelizumab Antibody - Dependent Cellular Phagocytosis Based on FcγR Binding Tislelizumab has minimal FcγRI binding thus abrogating ADCP activity Tislelizumab’s Lack of FcγR Binding Is Designed to Prevent Macrophage - Mediated T - Cell Clearance We believe the different FcγR design may have meaningful differences in the clinic T cell Macrophage Nivo surrogate 0 200 400 600 800 1000 1200 1400 1600 6 11 16 21 26 Mean Tumor Volume (mm 3 ± SEM) Treatment Days Vehicle BGB-A317 10mg/kg Nivolumab 10mg/kg Pembrolizumab 10mg/kg * P<0.05 Dosed Weekly Tislelizumab 10mg/kg Tislelizumab Differential Preclinical Efficacy in in vivo mouse tumor model ▪ Tislelizumab was specifically engineered to minimize binding to Fc γ R on macrophages, thereby abrogating antibody - dependent cellular phagocytosis (ADCP), a potential mechanism of T - cell clearance ▪ Hypothesis supported by literature: Dahan et al. reported that Fc γ R engagement compromises the anti - tumor activity of anti - PD - 1 Abs; Arlauckas et al. showed in a mouse model that anti - PD - 1 Abs could be transferred from PD - 1+ T cells to macrophages in FcγR - dependent manner Fc γ RI=Fc gamma receptor - 1, MDSC=myeloid - derived suppressor cell; Source: Dahan et al., Cancer Cell, 2015; Arlauckas et al., Sci. Transl. Med., 2017 38
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