Wave Life Sciences Reports Positive Data for First-Ever RNA Editing in Humans

Key Results

In the initial single-dose cohort (200 mg), two participants with Pi*ZZ AATD (who naturally lack wild-type M-AAT) showed positive outcomes by day 57:

• Plasma total AAT reached ~11 micromolar.
• Wild-type M-AAT protein made up over 60% of total AAT.

CEO Paul Bolno commented:

“The level of RNA editing with a single dose exceeded expectations, and we expect further increases with repeat dosing.”

Study Overview and Mechanism

The open-label RestorAATion-2 trial assesses safety, tolerability, and pharmacokinetics through single and multiple ascending doses. WVE-006 is a GalNAc-conjugated A-to-I RNA editing oligonucleotide (AIMer), designed to correct a mutation in the SERPINA1 Z allele. This enables production of functional M-AAT protein, improving AATD-related symptoms.

At day 15, wild-type M-AAT reached 6.9 micromolar, while total AAT increased to 10.8 micromolar, meeting levels used for AAT augmentation therapy. Additionally, increased inhibition of neutrophil elastase confirmed functional protein production.

Safety and Future Directions

Both the RestorAATion-2 and RestorAATion-1 trials reported no serious adverse events, with only mild to moderate side effects observed. Multidose data from RestorAATion-2 are expected in 2025.

Following this announcement, Wave’s stock surged 63%. Dr. Bolno highlighted:
“This milestone in RNA editing validates our platform and advances the field of oligonucleotide therapeutics.”

Wave Life Sciences will share updates on its INHBE GalNAc-siRNA obesity program on October 30. The company aims to redefine genetic therapies through RNA editing, targeting unmet medical needs with innovative treatments.

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