Wave Life Sciences Ltd. announced the initiation of dosing in healthy volunteers in the RestorAATion clinical trial program, which is investigating WVE-006 as a potential treatment for alpha-1 antitrypsin deficiency (AATD). WVE-006 is a first-in-class, GalNAc-conjugated RNA editing oligonucleotide (AIMer). It is designed to restore circulation of healthy, wild-type alpha-1 antitrypsin (M-AAT) protein and reduce dysfunctional Z-AAT protein, thereby potentially addressing AATD-related lung disease, liver disease, or both.

The RestorAATion clinical program includes healthy volunteers (RestorAATion-1) as well as individuals with AATD who have the homozygous PiZZ mutation (RestorAATion-2) and is designed to provide an efficient path to proof-of-mechanism as measured by restoration of M-AAT protein in serum. Wave expects to deliver proof-of-mechanism data in individuals with AATD in 2024. With initiation of dosing in RestorAATion, Wave has achieved its first WVE-006 milestone in its collaboration with GSK, resulting in a $20 million payment to Wave.

For WVE-006, Wave is eligible to receive up to $505 million in additional development, launch, and sales-related milestone payments, as well as tiered royalties on net sales, from GSK. Development and commercialization responsibilities will transfer to GSK after Wave completes the RestorAATion-2 study. Beyond WVE-006, Wave is advancing a pipeline of wholly owned RNA editing therapeutics designed to either correct or upregulate mRNA across a range of high impact 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. At its R&D Day in September 2023, Wave shared in vivo and in vitro proof-of-concept data on several undisclosed targets, achieving at least 2-fold mRNA upregulation in liver and kidney targets and more than 60% mRNA correction in liver and lung targets.