Wave Life Sciences announces data from ongoing Phase 1b/2a RestorAATion-2 study

Wave Life Sciences announced positive proof-of-mechanism data from the ongoing Phase 1b/2a RestorAATion-2 study of WVE-006 in alpha-1 antitrypsin deficiency, AATD. WVE-006 is a GalNAc-conjugated, subcutaneously delivered, A-to-I RNA editing oligonucleotide, AIMer. It is uniquely designed to address AATD-related lung disease, liver disease, or both. Today’s proof-of-mechanism data are the first-ever clinical demonstration of RNA editing in humans. These data are from the first single dose cohort in RestorAATion-2 and include the first two patients with “ZZ” AATD to reach day 57. Individuals with Pi*ZZ AATD do not naturally produce wild-type alpha-1 antitrypsin protein; therefore, the presence of M-AAT protein is confirmation of successful editing of mutant Z-AAT mRNA. Additionally, restoring 50% M-AAT would be consistent with the heterozygous “MZ” genotype with low risk of AATD lung and liver disease. WVE-006 has been well-tolerated with a favorable safety profile to date. All adverse events in RestorAATion-2, as well as in the ongoing RestorAATion-1 trial of healthy volunteers, are mild to moderate, with no Serious Adverse Events reported. The RestorAATion-2 trial is ongoing and Wave expects to share multidose data in 2025.