Wave Life Sciences Inc. (NASDAQ: WVE) stock declined by 3.42% in the after-hours session. Wave Life Sciences is a clinical-stage genetic medicine firm dedicated to developing life-changing solutions for patients suffering from life-threatening disorders.
What is happening?
WVE released the first proof-of-concept preclinical evidence in alpha-1 antitrypsin deficiency for their ADAR (adenosine deaminases acting on RNA)-mediated RNA editing (“ADAR editing”) program (AATD). At one timepoint, up to 40% editing of human SERPINA1 Z-allele mRNA in the liver was seen, resulting in a therapeutically significant rise in circulating functional wild-type AAT protein. Wave’s unique transgenic mouse model, which possesses both the human SERPINA1 Z-allele and human ADAR that is expressed similarly to human cells, was used in this first in vivo investigation.
Wave’s AATD program, the first one to make use of its ADAR editing modality, corrects a single base mutation in mRNA generated from the SERPINA1 Z allele using GalNAc-conjugated oligonucleotides. ADAR editing is a quick and easy way to treat AATD by decreasing the accumulation of mutated, misfolded alpha-1 antitrypsin protein (Z-AAT) while increasing total circulating levels of the wild-type protein (M-AAT), potentially addressing both the lung and liver symptoms of the disease while minimizing the problem of permanent off-target DNA changes. Wave is starting with homozygous “ZZ” individuals, who have the highest risk of disease, and where RNA editing might produce in a heterozygous “MZ” phenotype, which would have a far reduced risk of illness.
Wave’s initial in vivo proof-of-concept research had the following objectives:
- Accomplish SERPINA1 Z allele mRNA editing in the liver at levels close to the MZ phenotype
- Reestablish human M-AAT protein in serum.
- Demonstrate the restored human M-AAT protein’s functioning.
Wave is now doing preclinical research for its AATD program, with more data on durability and dosage response anticipated in the second half of 2021. Wave’s proprietary mouse model, which exhibits human ADAR and is crossed with illness-specific mice models, is also being used to test ADAR editing drugs for additional disease targets.
On June 2, 2021, these proof-of-concept preclinical findings will be presented at the Jefferies Virtual Healthcare Conference.