2854-LB: Efficacy and Safety of CU01-1001 in Patients with Diabetic Kidney Disease: Significant Reduction in Urine Albumin–to–Creatinine Ratio (uACR)

Introduction and Objective: Diabetic kidney disease (DKD), one of the leading causes of chronic kidney disease (CKD), is associated with increased oxidative stress and the accumulation of advanced glycation end-product. CU01-1001, dimethyl fumarate (DMF) is being developed as a potential therapeutic agent for DKD. In preclinical models, DMF attenuated renal fibrosis via the Nrf2-mediated inhibition of TGF-b/Smad3 signaling in an antioxidant response element independent manner, suggesting its potential protective effects against kidney damage. In this study, we evaluated the efficacy and safety of CU01-1001 in patients with DKD. Methods: In this randomized, double-blind phase 2b trial, 241 adults with DKD (uACR 100 to 1000mg/g; eGFR 25 to 75 ml/min/1.73m2) were randomized to CU01-1001 240mg, CU01-1001 360mg or placebo for 24 weeks. The primary endpoint was percent change from baseline in uACR at Week 24. Results: The baseline mean uACR was 269.34mg/g with CU01-1001 240mg, 235.95mg/g with CU01-1001 360mg, and 244.87 mg/g with placebo. Compared with placebo, CU01-1001 demonstrated a significant reduction in uACR of -21.45% (95% CI: -37.95, -0.57, p=0.0448) with CU0-1001 240mg and -22.21% (95% CI: -38.09, -2.26, p=0.0313) with CU01-1001 360mg. The baseline mean eGFR was 54.01 mL/min/1.73 m² with CU01-1001 240mg, 54.46 mL/min/1.73 m² with CU01-1001 360mg, and 57.24 mL/min/1.73 m² with placebo. After 24 weeks of treatment, eGFR remained stable without further decline. One predictable serious adverse event, Herpes zoster oticus, was reported with CU01-1001. No unexpected adverse events were observed during the trial. Conclusion: CU01-1001 significantly reduced uACR at week 24 compared with placebo and demonstrated a favorable safety profile. Importantly, albuminuria reduction was achieved while maintaining stable eGFR. These findings provide a clinical rationale for the advancement into a Phase 3 trial in patients with DKD. ClinicalTrials.gov Number, NCT05718375 Disclosure K. Won: None. J. Moon: None. J. Jeon: None. P. Kim: Employee; Current; Curacle. J. Park: Employee; Current; Curacle Co., Ltd. S. Yuo: Consultant; Current; Curacle Co., Ltd. Y. Kwon: Board Member; Current; Curacle Co., Ltd.