Maze Therapeutics has shared positive outcomes from the randomised Phase I study of the oral SLC6A19 inhibitor, MZE782, for treating phenylketonuria (PKU) and chronic kidney disease (CKD).
The placebo-controlled, double-blind trial, which involved 112 healthy adult volunteers, is aimed at assessing single ascending doses (SAD) and multiple ascending doses (MAD) of the therapy.
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It included 56, 40, and 16 subjects in the SAD, MAD, and the food effect cohorts, respectively.
Each SAD and MAD cohort included eight subjects who were randomised in a 6:2 ratio.
The single doses ranged from 30mg to 960mg while multiple doses were administered once or twice a day over a week, ranging from 120mg to 720mg.
In addition, the impact of a high-fat meal and a low-fat meal on the therapy’s absorption was evaluated.
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By GlobalDataThe primary goals of the trial focused on the safety and tolerability of SAD and MAD doses of the therapy while the secondary and exploratory objectives included assessing the impact of food, pharmacokinetic (PK) analysis, and pharmacodynamic (PD) evaluations of the therapy’s target interaction.
This included the measurement of urinary excretion levels of phenylalanine (Phe) and glutamine (Gln), which serve as indicative biomarkers for the inhibition of SLC6A19 and the management of the disease.
In addition, the study measured the estimated glomerular filtration rate (eGFR) to estimate kidney function.
Results were positive, with MZE782 showing good tolerance across all dosage levels. It exhibited a consistent absorption pattern, reaching a maximum concentration in six hours and having a half-life of 11 hours.
In terms of PD, MZE782 increased the urinary excretion of phenylalanine (Phe) and glutamine (Gln) across the MAD and SAD cohorts.
The study also observed an initial decrease in the estimated glomerular filtration rate (eGFR), a measure of kidney function. The eGFR reduction was reversed after the dosing period ended at day 11.
Maze Therapeutics chief medical officer and research and development president Harold Bernstein said: “The rapid and profound increase in urinary phenylalanine excretion confirms SLC6A19 inhibition in healthy individuals that we anticipate will translate to meaningful reductions in plasma phenylalanine levels in patients with PKU, based on the biology of this transporter.”
In February 2025, Maze dosed the first subject in the Phase II HORIZON study to evaluate MZE829 in treating subjects with APOL1 kidney disease (AKD).
