Discovery and development of SIM0709, a novel bi-specific antibody targeting TL1A and IL23p19 for the treatment of IBD and beyond 4676

Abstract Description Despite recent advances in the treatment of IBD, patients still suffer from suboptimal efficacy and are eagering for more effective treatment options. Translational scRNAseq data from IBD patients reveal potential synergistic function of TL1A and IL-23 pathways indicating better treatment efficacy might be achieved with dual pathway blockade. SIM0709 is a novel humanized half-life extended bi-specific antibody simultaneously targeting human TL1A and IL23p19. In vitro, SIM0709 demonstrated superior functional activities under various functional assays on both TL1A and IL23 axes compared to that of benchmark anti-TL1A mAb RG6631 and Guselkumab, respectively. SIM0709 also exhibited superior dual pathway blockade synergy in vitro in inhibiting Th17 differentiation and in vivo in both anti-CD40 induced colitis model and a cytokine-induced acute gut inflammation model. Further analysis on ileum and colon tissues confirmed relived intestinal inflammation after SIM0709 treatment with significantly reduced inflammatory cytokines/chemokines and improved histological scores compared to either of the anti-TL1A or anti-IL23p19 monotherapies. High solubility of SIM709 also supports patient-friendly formulation suitable for subcutaneous administration. Taken together, these data support the further development of SIM0709 as a potential FIC therapeutic agent for the treatment of IBD with expected first-in-human study in H1 2026. Topic Categories Therapeutic Approaches to Autoimmunity (THER)