Abstract: TH-PO1295
Izicopan, a Second-Generation Oral C5a Receptor 1 (C5aR1) Antagonist, Demonstrates Promising Therapeutic Potential in Kidney Disease Models
Session Information
- Late-Breaking Research Posters
October 22, 2026 | Location: Exhibit Hall A, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Acute Kidney Injury
- 103 AKI: Mechanisms
Authors
- Liu, Rui, InflaRx Pharmaceuticals Inc., Ann Arbor, Michigan, United States
- Chen, Ophelia, InflaRx Pharmaceuticals Inc., Ann Arbor, Michigan, United States
- Xu, Zhongli, InflaRx GmbH, Jena, Thuringia, Germany
- Phuapradit, Wantanee, InflaRx Pharmaceuticals Inc., Ann Arbor, Michigan, United States
- Pei, Yazhong, InflaRx Pharmaceuticals Inc., Ann Arbor, Michigan, United States
- Habel, Maria, InflaRx GmbH, Jena, Thuringia, Germany
- Guo, Renfeng, InflaRx Pharmaceuticals Inc., Ann Arbor, Michigan, United States
Background
Izicopan is a next-generation small-molecule C5aR1 antagonist developed to provide improved pharmacologic properties compared with avacopan, the first-in-class oral C5aR1 inhibitor. Izicopan achieves therapeutic exposure within days in humans, compared with weeks for avacopan, and demonstrates improved metabolic stability without evidence of time-dependent CYP3A4 inhibition. Together, these properties support a differentiated pharmacokinetic profile with potentially reduced drug–drug interaction liability.
Methods
C5a–C5aR1 signaling promotes neutrophil activation and recruitment and contributes to inflammatory kidney injury across diverse disease settings, including immune complex–mediated disease, ischemia–reperfusion injury (IRI), and unilateral ureteral obstruction (UUO). In the immune complex assay, levels of the neutrophil activation marker CD11b were measured using flow cytometry. In the IRI and UUO models, changes in whole blood cell counts (WBC), renal function indicators including creatinine (CREA) and blood urea nitrogen (BUN) were evaluated, and histopathological investigation were performed on kidney tissue samples.
Results
In human whole blood, izicopan effectively suppressed immune complex–mediated neutrophil activation. In hamster models of IRI and UUO-induced nephropathy, oral izicopan significantly attenuated renal injury. In the IRI model, izicopan reduced plasma CREA and BUN levels (p < 0.05) and improved kidney histopathology compared with vehicle controls. In the UUO model, izicopan maintained CREA levels comparable to sham controls and significantly improved total histological scores, including reductions in infarction, tubular dilation, plugging, and necrosis (p < 0.001).
Conclusion
Across complementary in vitro and in vivo models of renal injury, izicopan demonstrated robust inhibition of C5aR1-mediated inflammatory responses and renal protection, supporting its potential as a therapeutic candidate for complement-driven kidney diseases.
Funding
- Commercial Support – InfaRx