P001 Obefazimod upregulates miR-124 and downregulates the expression of some cytokines in blood and rectal biopsies of patients with moderate-to-severe ulcerative colitis

Abstract Background The oral small molecule obefazimod (ABX464) has demonstrated efficacy and safety in patients with moderate-to-severe ulcerative colitis (UC) a randomized, placebo-controlled, 8-week phase 2b induction study1. We examined the effects of on miR-124 cytokines levels blood (baseline, weeks 4 8) rectal biopsies week these patients. Methods Absolute quantification (QuantaSoft Pro) copy number was performed by using droplet digital PCR technology 644 biopsy samples 1104 whole from receiving (25mg, 50mg or 100mg once daily) placebo. A total 15 (IL1b, IL13, IL17, IL6, IL10, IL23, MCP-1, IL34, CXCL-12, IL22, LIF, TGFb, GM-CSF, IFNg TNFa) were immunohistochemistry (IHC) 208 biopsies. For each cytokine, antibodies tested for chromogenic IHC detection paraffin tissue sections; repeatability reproducibility tests conducted to validate protocols robust signal. signal digitized quantified Halo® image analysis software. IL17 also measured an ELLA immunoassay (Bio-Techne). Results three doses significantly upregulated at 1 (A) 8 (B), (C) (from p<0.001 p<0.0001 vs. placeb reduced 1, p<0.01 placebo). validated out cytokines: INFg. Compared baseline levels, treatment down-regulated expression (at all doses, p<0.05 p<0.001), IL23 (p<0.01 50mg, 100 mg), INFg (p<0.001 50 mg). Within treated subjects, clinical responders showed higher reduction IL-17A IL-23 than non-clinical (reduction MMS ≥2 points ≥30% + decrease bleeding subscore ≥1 absolute ≤1 point). No significant change observed CXCL-12. Conclusion UC is associated increase colorectal tissue. References 1. Vermeire S, et al. ABX464 (obefazimod) moderate severe active colitis: randomised, placebo controlled trial 48 extension. Lancet Gastroenterology & Hepatology. 2022. https://doi.org/10.1016/S2468-1253(22)00233-3