Wave Life Sciences Ltd. announced the submission of its first clinical trial application (CTA) for WVE-006 in alpha-1 antitrypsin deficiency (AATD). WVE-006 is a first-in-class, GalNAc-conjugated RNA editing oligonucleotide ("AIMer") and is designed to correct the single base mutation in messenger RNA (mRNA) coded by the SERPINA1 Z allele, thereby enabling restoration and circulation of functional, wild-type alpha-1 antitryps in (M-AAT) protein. The current clinical development plan for WVE-006 includes healthy volunteers as well as individuals with AATD who have the homozygous PiZZ mutation, 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 initiate dosing in healthy volunteers in the fourth quarter of 2023 and deliver proof-of-mechanism data in individuals with AATD in 2024. Earlier this year, Wave commenced its strategic collaboration with GSK to advance transformative RNA medicines using Wave?s multimodal RNA platform, including WVE-006. Wave received $170 million in upfront cash and equity and is also receiving research funding.

Wave is eligible for up to $3.3 billion in potential milestone payments, including near-term preclinical and clinical milestones, as well as royalties, for WVE-006 and GSK?s eight collaboration programs. For WVE-006, Wave is eligible to receive up to $225 million in development and launch milestone payments, and up to $300 million in sales-related milestone payments, as well as double-digit tiered royalties as a percentage of net sales up to the high teens.