Wave Life Sciences announces update from RestorAATion-2 trial of WVE-006

Wave Life Sciences (WVE) announced positive data from the 200 mg single and multidose and 400 mg single dose cohorts of the ongoing Phase 1b/2a RestorAATion-2 study evaluating WVE-006 as a treatment for alpha-1antitrypsin deficiency. The data reported include RestorAATion-2 cohort 1, where participants received a single subcutaneous dose of WVE-006 and then received seven subcutaneous doses administered every other week under the multidose protocol, as well as the single dose portion of cohort 2. Circulating M-AAT, Z-AAT, and total AAT protein in the serum were measured by highly selective and sensitive LC-MS/MS assays and reported as mean maximums. In the 200 mg multidose cohort, total AAT reached therapeutically relevant levels of 11.9 micromolar. Wild-type M-AAT increased from below the level of quantitation at baseline to 7.2 microM, which was significantly increased from levels achieved during the single dose portion of the cohort. Further, M-AAT levels reached 64.4% of total AAT, and mutant Z-AAT protein declined from baseline by 60.3%. M-AAT levels were durable and sustained at greater than50% of total AAT for at least two months following the last dose. Increases in neutrophil elastase inhibition from baseline were confirmed with production of functional M-AAT. A single 400 mg dose of WVE-006 resulted in achievement of total AAT of 12.8 microM and M-AAT of 5.3 microM. Circulating serum M-AAT levels reached 47.2% of total AAT and Z-AAT decreased by 49% versus baseline. Dosing is ongoing in the 400 mg multidose cohort with a monthly dosing regimen, for which Wave expects to deliver data in the first quarter of 2026.