Abstract: TH-PO0252
XTL6001: A Novel Triple MasR/GCGR/GLP-1 Receptor Agonist for Hyperuricemic Nephropathy
Session Information
- CKD: Mechanisms of Injury and Fibrosis - 1
October 22, 2026 | Location: Exhibit Hall A, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: CKD (Non-Dialysis)
- 2203 CKD (Non-Dialysis): Mechanisms
Authors
- Wang, Xiangling, Shaanxi Micot Pharmaceutical Technology Co., Ltd, Xi'an, China
- Zhou, Hong, Shaanxi Micot Pharmaceutical Technology Co., Ltd, Xi'an, China
- Liu, Yongzhen, Shaanxi Micot Pharmaceutical Technology Co., Ltd, Xi'an, China
- Wang, Ying, Shaanxi Micot Pharmaceutical Technology Co., Ltd, Xi'an, China
- Zhang, Ying, Shaanxi Micot Pharmaceutical Technology Co., Ltd, Xi'an, China
- Wang, Linyuan, Shaanxi Micot Pharmaceutical Technology Co., Ltd, Xi'an, China
- Wang, Xiaodong, Shaanxi Micot Pharmaceutical Technology Co., Ltd, Xi'an, China
- Jiao, Wenjuan, Shaanxi Micot Pharmaceutical Technology Co., Ltd, Xi'an, China
- Song, Lanlan, Shaanxi Micot Pharmaceutical Technology Co., Ltd, Xi'an, China
- Wang, Bing, Shaanxi Micot Pharmaceutical Technology Co., Ltd, Xi'an, China
Background
Although observational studies link hyperuricemia to CKD progression,RCTs have not consistently proven that urate-lowering therapy slows renal decline.We developed XTL6001,a novel triple MasR/GCGR/GLP-1R agonist,designed to lower uric acid,reduce proteinuria,and preserve renal function.Here,we show that XTL6001 significantly improves hyperuricemic nephropathy in rodent models,and present First-In-Human data exploring its uric acid–handling mechanism in humans.
Methods
Chronic kidney disease (CKD) with proteinuria and hyperuricemia was induced in rats and mice by oral administration of adenine combined with potassium oxonate.Animals were treated subcutaneously with XTL6001 twice weekly for four weeks.Plasma and urine biochemical parameters were subsequently analyzed.In a first-in-human study(NCT07205432),the preliminary urate-lowering mechanism of XTL6001 was investigated by measuring serum uric acid levels and uric acid clearance in healthy participants during the multiple-ascending dose(MAD) phase.
Results
In rodent models of hyperuricemic nephropathy,XTL6001(4 weeks,SC,biweekly) dose-dependently lowered serum uric acid(SUA). In rats,SUA reduction reached 57% at 6 mg/kg(P<0.05),near normalization,comparable to benzbromarone.Urinary protein was reduced by 68%(not significant).In mice,SUA reduction reached 42% at 12 mg/kg(P<0.001),superior to benzbromarone and comparable to allopurinol.XTL6001 also significantly improved serum creatinine and urea in mice(P<0.01~0.001)and reduced urinary protein by up to 80%(P<0.001).No significant adverse effects were observed.The lowest effective doses were 6 mg/kg (rats) and 12 mg/kg(mice).In FIH study,15 healthy subjects(12 active,3 placebo),weekly XTL6001(75–300 mg)reduced mean serum uric acid(SUA) by 20.0% on Day 22 and 14.3% on Day 29,with a sustained 10.6% reduction at 4 weeks post treatment.Placebo SUA reduction was ≤5.4%.XTL6001 increased uric acid clearance by 12.37% from baseline,representing a 40.27 percentage-point difference versus placebo,demonstrating a significant uricosuric effect.Higher BMI subjects showed greater SUA reduction.These data indicate that XTL6001 enhances renal uric acid excretion.
Conclusion
These findings indicated XTL6001 offers a multidimensional therapeutic solution for patients with CKD/DKD complicated by proteinuria and hyperuricemia by integrating renal protection and metabolic regulation.Thus,XTL6001 warrant further clinical assessment.
Funding
- Commercial Support – Shanghai Xitaili Biomedicine Technology co., Ltd.