Wave Life soars on positive early data for WVE-006

US RNA medicines biotech Wave Life Sciences (Nasdaq: WVE) yesterday announced positive proof-of-mechanism data from the ongoing Phase Ib/IIa RestorAATion-2 study of WVE-006 in alpha-1 antitrypsin deficiency (AATD), with the news sending the firm’s shares rocketing 71% to $11.24.

WVE-006 is a GalNAc-conjugated, subcutaneously delivered, A-to-I RNA editing oligonucleotide (AIMer) that was developed with Wave’s best-in-class oligonucleotide chemistry platform. 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 (200 mg) in RestorAATion-2 and include the first two patients with “ZZ” AATD (Pi*ZZ AATD) to reach day 57. Individuals with Pi*ZZ AATD do not naturally produce wild-type alpha-1 antitrypsin (M-AAT) 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.