Wave Life Sciences Ltd. (NASDAQ: WVE) announced updated results from its RestorAATion-2 trial of WVE-006, an investigational RNA editing treatment for alpha-1 antitrypsin deficiency (AATD). The company reported that the treatment achieved what it characterized as an MZ-like phenotype across both biweekly and monthly dosing schedules.

In the 200 mg biweekly dosing cohort, WVE-006 generated wild-type M-AAT comprising 64% of total AAT and reduced harmful Z-AAT by 71%, with total AAT levels reaching 11.9 µM. The 400 mg monthly dosing regimen produced similar results with 13.6 µM total AAT. The company stated that editing effects were sustained for at least three months following the last dose.

The ongoing Phase 1b/2a trial includes three dose cohorts with eight participants each. Data showed dose-dependent reductions in circulating Z-AAT protein from baseline, reaching 70.5% reduction in the 200 mg biweekly cohort after seven doses and 67.7% reduction in the 400 mg monthly cohort after four doses.

The trial also documented three instances of dynamic AAT production during acute phase responses. Two participants in the 400 mg multidose cohort showed AAT increases of 57.8% and 59.8% during mild upper respiratory infections.

Wave reported that WVE-006 was generally well tolerated with no serious adverse events or liver toxicities. All adverse events were characterized as mild to moderate in intensity.

The company expects to receive regulatory feedback on a potential accelerated approval pathway in mid-2026 and plans to share data from the 600 mg monthly multidose cohort in the second half of 2026.

AATD is a genetic disorder that affects lung and liver function. The only currently approved treatment is weekly intravenous plasma-derived augmentation therapy, which addresses only lung manifestations of the disease.