Wave Life Sciences宣布正在进行的1b/2a期恢复-2研究200毫克单剂量和多剂量以及400毫克单剂量队列的数据，该研究评估WVE-006作为AATD的治疗方法

Achieved durable production of serum AAT protein at levels associated with a lower risk of AATD liver and lung diseases following repeat 200 mg doses of WVE-006 (11.9 µM total AAT, 7.2 µM M-AAT) 

First-ever demonstration of therapeutically restored physiological serum AAT production in a Pi*ZZ individual during a non-drug related acute phase response (20.6 µM total AAT, 10.3 µM M-AAT)

Single dose of 400 mg achieved 12.8 µM total AAT and 5.3 µM M-AAT; ongoing 400 mg multidose cohort has potential to deliver further increases in serum AAT

Data from 200 mg and 400 mg cohorts support monthly or less frequent subcutaneous dosing; 400 mg monthly multidose cohort data expected in 1Q 2026

WVE-006 continues to be well tolerated with a favorable safety profile to date

Wave to host investor conference call and webcast at 8:30 a.m. ET today

CAMBRIDGE, Mass., Sept. 03, 2025 (GLOBE NEWSWIRE) -- Wave Life Sciences Ltd. (NASDAQ:WVE), a clinical-stage biotechnology company focused on unlocking the broad potential of RNA medicines to transform human health, today 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 (AATD). WVE-006 is a GalNAc-conjugated, subcutaneously delivered A-to-I RNA editing oligonucleotide (AIMer) developed with Wave's best-in-class oligonucleotide chemistry platform.

Approximately 200,000 people in the US and Europe living with AATD are homozygous for the Z mutation (Pi*ZZ) in the SERPINA1 gene, which can lead to severe lung disease, liver disease, or both. Pi*ZZ individuals make only mutant Z-AAT protein, which gets trapped in the liver, and their ability to produce protective levels of AAT protein during an acute phase response is compromised, thus leaving the lungs vulnerable to damage. WVE-006 is designed to address both lung and liver manifestations of AATD by correcting the Z mutation in SERPINA1 mRNA, thereby converting Z-AAT to wild-type M-AAT without altering the endogenous transcriptional regulation of the SERPINA1 gene.

The data reported today include RestorAATion-2 cohort 1 (200 mg, n=8), 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 (400 mg, n=8). Circulating M-AAT, Z-AAT, and total (M + Z) AAT protein in the serum were measured by highly selective and sensitive LC-MS/MS assays (LLOQ: 0.096 µM (M), 0.029 µM (Z)) and reported as mean maximums.

Production of M-AAT protein indicates WVE-006 led to RNA editing in all treated participants, with durable production of serum AAT at levels associated with a lower risk of liver and lung disease following repeat 200 mg doses.

In the 200 mg multidose cohort, total AAT reached therapeutically relevant levels of 11.9 micromolar (µM). Wild-type M-AAT increased from below the level of quantitation at baseline to 7.2 µM, which was significantly increased from levels achieved during the single dose portion of the cohort (4.8 µM; p=0.012). 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 >50% 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.

Notably, following a single 200 mg dose of WVE-006, a total AAT level of 20.6 µM, including a M-AAT level of 10.3 µM, was observed in one individual during an acute phase response due to a kidney stone. These data demonstrate that treatment with WVE-006 enables endogenous regulation and dynamic increased secretion of AAT protein during an acute phase response as indicated by a concurrent C-reactive protein elevation.

In the 200 mg single dose cohort, total AAT reached 12.9 µM, M-AAT increased to 4.8µM, and Z protein decreased by 47.3%. Excluding the individual with an acute phase response, total AAT reached 11.8 µM, M-AAT increased to 4.0 µM, and Z protein decreased by 48.8%.

A single 400 mg dose of WVE-006 resulted in achievement of total AAT of 12.8 µM and M-AAT of 5.3 µM. Circulating serum M-AAT levels reached 47.2% of total AAT and Z-AAT decreased by 49% versus baseline. Data from both the 200 mg and 400 mg (single dose only) cohorts support a monthly or less frequent subcutaneous dosing regimen. 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.

WVE-006 continues to be well tolerated with a favorable safety profile to date. All adverse events (AEs) were mild to moderate in intensity, and there were no SAEs or discontinuations.

GSK has the exclusive global license for WVE-006. Development and commercialization responsibilities will transfer to GSK after Wave completes the RestorAATion-2 study. In total, Wave is eligible for up to $525 million in milestones, as well as tiered royalties on net sales, for WVE-006.

Behind WVE-006, Wave is continuing to advance a wholly owned pipeline of RNA editing candidates which utilize its proprietary chemistry in a variety of hepatic and extrahepatic tissues. The company plans to share new preclinical data from these programs at Research Day in the fall of 2025 and to initiate clinical development of additional RNA editing programs in 2026.