Chinook Therapeutics, Inc. announced a free communication presentation on CHK-336 presented at the 60th ERA Congress being held virtually and live in Milan, Italy. CHK-336 is an oral small molecule LDHA inhibitor with liver-targeted tissue distribution in development for the treatment of patients with primary hyperoxaluria (PH) and other kidney stone disorders driven by endogenous overproduction of oxalate. The phase 1 single-center trial was designed to evaluate the safety, tolerability, pharmacokinetic profile of CHK-336 in 104 healthy volunteers in randomized, placebo-controlled, double-blinded, single-ascending dose (SAD) and multiple-ascending dose (MAD) settings.

In addition, Chinook's research and discovery efforts are focused on building a pipeline of precision medicines for rare, severe chronic kidney diseases with defined genetic and molecular drivers. Chinook is leveraging insights from kidney single cell RNA sequencing and large CKD patient cohorts that have been comprehensively panomically phenotyped, with retained biosamples and prospective clinical follow-up, to discover and develop therapeutic candidates with mechanisms of action targeted against key kidney disease pathways. 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.