Wave Life Sciences Ltd. announced the approval of its first clinical trial application (CTA) for its RestorAATion-2 clinical trial of WVE-006, the company?s first-in-class RNA editing oligonucleotide, which is being developed for the treatment of alpha-1 antitrypsin deficiency (AATD). WVE-006 is GalNAc-conjugated and subcutaneously administered; it does not use a lipid nanoparticle (LNP) delivery system. RestorAATion-2 is a Phase 1b/2a open label study designed to evaluate the safety, tolerability, pharmacodynamics (PD) and pharmacokinetics (PK) of WVE-006 in individuals with AATD who have the homozygous Pi*ZZ mutation.

The trial includes both single ascending dose (SAD) and multiple ascending dose (MAD) portions. The company remains on track to deliver proof-of-mechanism data, as measured by restoration of M-AAT protein in serum, in 2024. 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 addition to WVE-006, Wave continues to advance its wholly owned RNA editing pipeline across a range of high-impact GalNAc-hepatic and extra-hepatic targets. The company?s discovery and development efforts in RNA editing are powered by its proprietary ?edit-verse,?

which leverages genetic datasets and deep learning models to identify new RNA editing targets and edit sites. These targets leverage easily accessible biomarkers, offer efficient paths to proof-of-concept in humans, and represent meaningful commercial opportunities. WVE-006 is a first-in-class, GalNAc-conjugated and subcutaneously administered RNA editing oligonucleotide designed to correct the single base mutation in messenger RNA (mRNA) coded by the SERPINA1 Z allele, thereby enabling restoration and circulation of functional M-AAT protein.

In preclinical studies, WVE-006 demonstrated potent and durable editing of SERPINA1 Z transcript in mice, restoration of AAT protein up to 30 micromolar, and improvement in several markers of liver disease. WVE-006 is also highly specific with no evidence of bystander editing. Together, these data demonstrate the potential of WVE-006 to address AATD-related liver disease, lung disease, or both.