Chinook Therapeutics Presents Data from CHK-336 Phase 1 Trial in Healthy Volunteers and New Insights into the Role of Failed Repair in Chronic Kidney Disease at the 60th European Renal Association (ERA) Congress - Seite 2

Key highlights from the presentation include the following:

• CHK-336 was generally well tolerated in HVs who received single doses up to 500 mg and multiple doses (14 days) up to 60 mg.
  • There were no dose-related trends in adverse events, vital signs or EKG findings.
  • The most common treatment emergent adverse event was headache in six subjects receiving CHK-336 (8.8%) and no placebo subjects, with no dose-related trend.
    
• There was one serious adverse event (SAE) of anaphylaxis that occurred in a single HV following the first dose in the 125 mg MAD group. The SAE had a rapid onset within one hour following the first dose and rapidly resolved after treatment with an antihistamine, without requiring epinephrine administration. The HV had clinically significant elevations in serum tryptase levels during the event, confirming anaphylaxis. This SAE resulted in voluntary pausing of the trial to enable further investigation.
  
• PK was well characterized with dose proportional exposures, a plasma half-life consistent with once daily oral dosing and no exposure accumulation following repeat dosing.
  
• The successful utilization of a novel ¹³C₂-glycolate tracer in the trial establishes proof-of-mechanism for CHK-336 as an orally administered small molecule inhibitor of hepatic LDH. CHK-336 effectively blocked conversion of the ¹³C₂-glycolate tracer to ¹³C₂-oxalate with maximal inhibition observed following a single dose of CHK-336 at 60-125 mg.
  

Accumulation of Maladaptive Tubular Epithelial Cells (TECs) is Ubiquitous in Chronic Kidney Diseases and Represents a Common Initiating Mechanism of Disease Progression

Disease-associated maladaptive TECs have been described in rodent models and are characterized by a failed repair phenotype that contributes to tubulointerstitial inflammation and fibrosis. This study explores the significance of maladaptive TECs in the NURTuRE chronic kidney disease (CKD) cohort by integrating clinical, histological, transcriptomic and proteomic data from blood and urine to gain insights into mechanisms of CKD progression. The NURTuRE consortium biobank comprises patient samples from a broad range of CKD diagnoses and kidney functional states with rich clinical data from over 3,500 subjects.