Chinook Therapeutics Presents Data During the ISN World Congress of Nephrology 2021 - Seite 3

Part 3 of the phase 1 study is ongoing to evaluate BION-1301 in adult IgAN patients in an open-label setting. Preliminary data from Part 3 will be presented at nephrology conferences in 2021.

With the aim to reduce patient burden with a more convenient alternative administration route, BION-1301 was further studied in a single-dose phase 1 study to determine safety and bioavailability of BION-1301 administered via IV infusion or SC injection in healthy volunteers. This was a phase 1, open-label, randomized, parallel group, safety and bioavailability study of 300 mg BION-1301 administered intravenously or subcutaneously to adult healthy volunteers in the United States.

Key highlights from the bioavailability study include the following:

• BION-1301 was well tolerated when administered by both IV and SC routes in healthy volunteers, and no injection site or infusion-related reactions were reported.
  
  
• The PK profile of BION-1301 was consistent with previous clinical studies and minimal differences in drug concentration were observed between administration routes after one week, following the absorption phase.
  
  
• After SC administration, BION-1301 absorption rate was typical of a monoclonal antibody with bioavailability of approximately 50%.
  
  
• Magnitude of pharmacodynamic responses were largely retained with SC dosing compared to IV dosing:
  
  • SC administration generated approximately 81% of the maximum free APRIL reduction;
  • SC administration generated approximately 75% of the maximum IgA reduction.
    
    
• No anti-drug antibodies (ADAs) were observed in the SC cohort
  

Data generated in this study will be used to enable SC administration of BION-1301 in ongoing and future clinical studies.

WCN21-0358: Selective ETA Antagonist Atrasentan, Rapidly Reduces Albuminuria and Downregulates Intra-renal Pro-Inflammatory and Pro-Fibrotic Transcriptional Networks in the g-ddY Mouse Model of Spontaneous IgA Nephropathy

The effect of short-term treatment of selective ETA antagonist atrasentan was investigated in gddY mice, a spontaneous and accelerated model of IgAN.

Four days of treatment with atrasentan reduced urinary albumin to creatinine ratio (UACR) from baseline by 28%, 62% and 63% at 10 mg/kg/day, 20 mg/kg/day and 30 mg/kg/day, respectively. This effect was statistically significant at the two higher doses.