Wave Life Sciences宣布WVE-006在RestorAATion-2试验中取得积极进展

CAMBRIDGE, Mass.,May 18, 2026(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 updated data from the ongoing RestorAATion-2 trial of WVE-006, its investigational, GalNAc-conjugated, subcutaneously delivered RNA editing oligonucleotide (AIMer) for alpha-1 antitrypsin deficiency (AATD). These data further affirm WVE-006’s potential as a novel therapeutic addressing both lung and liver AATD by generating healthy, wild-type M-AAT, reducing harmful Z-AAT, and restoring the ability to dynamically produce functional AAT protein when needed.

Individuals with Pi*ZZ AATD cannot produce healthy, wild-type M-AAT, have unhealthy, mutant Z-AAT aggregates in liver, and cannot dynamically increase AAT, a protein responsible for protecting lungs against ongoing damage. Heterozygous Pi*MZ individuals have low risk of lung or liver disease and circulating M-AAT levels ranging from 57% to 71% of total (mean=64%), based on analysis of natural history study samples measured with the same assay used in RestorAATion-2.

The only approved treatment for AATD is weekly intravenous plasma-derived augmentation therapy, which only addresses lung manifestations and may leave individuals living with AATD at risk if AAT protein levels fall too low during an acute phase response. There are no approved therapies for AATD liver disease.

"We have now seen consistent results across multiple cohorts that reaffirm WVE-006’s potential to protect the liver by reducing the toxic Z-AAT protein, while simultaneously enabling a dynamic response capable of protecting the lung, especially during acute infections. RNA editing with WVE-006 offers distinct advantages compared to other treatment types. Our approach avoids delivery via lipid nanoparticles (LNPs), which have been associated with liver inflammation and dose-limiting toxicities. It also avoids the consequences associated with DNA base editing, including bystander edits, indels, and other off-target editing — permanent mutations in the human genome with unpredictable effects on gene expression,” saidChristopher Wright, MD, PhD, Chief Medical Officer atWave Life Sciences. “Based on these data, we believe WVE-006 may offer a new standard of care that treats both lung and liver disease with convenient, infrequent subcutaneous dosing. We look forward to engaging with the FDA on our next phase of development.”

Updated RestorAATion-2 clinical data
RestorAATion-2 is an ongoing open-label Phase 1b/2a trial with three dose cohorts (each n=8), with single and multidose portions. In the multidose portions, individuals receive multiple doses of WVE-006 (200 mg biweekly, 400 mg monthly, 600 mg monthly), over 12 weeks, followed by 12 weeks of follow-up. As of the data cutoff, data is available for the 200 mg (single and multidose), 400 mg (single and multidose), and 600 mg (single dose) cohorts. Circulating M-AAT, Z-AAT, and total (M + Z) AAT protein in the serum were measured by LC-MS/MS assays and reported as mean maximums.

Reductions in Z-AAT protein: In Pi*ZZ individuals, Z-AAT aggregates in the liver, where it can result in progressive liver disease. Treatment with WVE-006 led to robust, dose-dependent reductions of circulating, mutant Z-AAT from baseline following a single dose of WVE-006, reaching 47.3% (200 mg), 49.7% (400 mg), and 59.1% (600 mg). There were further reductions in Z-AAT with multiple doses of WVE-006, reaching 70.5% in the 200 mg biweekly dose cohort (seven doses). Reduction of Z-AAT was similar when extending the dosing interval, reaching 67.7% in the 400 mg monthly dose cohort (four doses).

Restoration of wild-type M-AAT protein: Individuals with Pi*ZZ AATD cannot produce wild-type M-AAT, the protein responsible for protecting the lungs against ongoing damage. Treatment with WVE-006 led to robust, dose-dependent restoration of wild-type M-AAT protein (canonical M-AAT) as a percentage of total circulating AAT following single doses of WVE-006, reaching 44.4% (200 mg), 48.0% (400 mg), and 52.3% (600 mg). In each single dose cohort, total AAT reached therapeutically relevant levels (200 mg: 12.9 µM; 400 mg: 14.0 µM; 600 mg: 13.0 µM). In the 200 mg multidose cohort, total AAT was 11.9 µM and M-AAT levels reached 64.4% of total AAT, in line with heterozygous MZ individuals with low risk of disease. A similar robust response was also observed when extending the dose interval to monthly (400 mg multidose cohort), where M-AAT levels reached 58.7% of total AAT. Total AAT in the 400 mg multidose cohort reached 13.6 µM.

Restoration of dynamic AAT protein: Notably, following treatment with WVE-006, three instances of dynamic and rapid production of AAT protein due to acute phase responses were observed across RestorAATion-2 as indicated by concurrent C-reactive protein (CRP) and AAT elevation. As previously reported, in the 200 mg single dose cohort, one individual produced a significant increase in total AAT (20.6 µM) following an acute phase response related to a kidney stone. In the 400 mg multidose cohort, there were two additional instances of significant increases in AAT (57.8% and 59.8% versus pre-event) following acute phase responses to mild upper respiratory infection (common cold). Additionally, across all available RestorAATion-2 data to date, CRP increases are strongly correlated with increases in AAT (r=0.73, p<0.001, n=19).

Convenient dosing and strong safety: Data support monthly subcutaneous dosing, with editing sustained at least three months following the last dose in both the 200 mg and 400 mg multidose cohorts. 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 clinically meaningful liver function test elevations.

D. Kyle Hogarth, MD, FCCP, Professor of Medicine, Director of theAlpha One Antitrypsin Deficiency Clinical Resource Center, Director of Bronchoscopy at theUniversity of Chicago Medicine, commented: “This data represents another important development in the management of Alpha One. Being able to have the patient safely make their own M protein while decreasing their Z protein levels through a reversible approach that avoids permanent genomic modifications, and, importantly, restores dynamic AAT production to protect patients during acute phase response, is a major step forward for the Alpha One patient community.”

Pavel Strnad, MD, Professor of Translational Gastroenterology and Senior Physician at the University Hospital Aachen,Department of Medicine III, commented: "AATD-associated liver disease is underdiagnosed, and individuals with the Pi*ZZ genotype are at risk for liver manifestations of disease including progressive fibrosis and cirrhosis, so it is essential that emerging therapies for AATD protect not only the lung but also the liver. The notable reductions in Z-AAT observed after treatment with WVE-006 suggest the potential to meaningfully reduce the toxic protein burden and reinforce the promise of RNA editing as a differentiated approach capable of delivering more complete care for people living with alpha-1. Beyond alpha-1, by correcting rather than silencing, these data demonstrate RNA editing’s potential as an entirely new class of precision medicines to treat a range of genetic liver diseases."

Data from the RestorAATion-2 clinical trial were also highlighted earlier today at theAmerican Thoracic Society (ATS) International Conferencein an oral presentation byKenneth R. Chapman, MsC, MD, FRCPC, FACP, FERS, Department of Medicine, University ofToronto.