Wave Life Sciences Announces New Data for Leading RNA Editing Capability Across Multiple Tissues and Provides Update on AATD Program During Analyst and Investor Research Webcast

Durable ADAR editing in vivo in preclinical models, including in CNS tissues with editing out to at least four months

Chemistry optimization yields a four-fold increase over PBS control in AAT protein restoration in vivo preclinically (or more than 15 micromolar)

CAMBRIDGE, Mass., Sept. 28, 2021 (GLOBE NEWSWIRE) -- Wave Life Sciences Ltd. (Nasdaq: WVE), a clinical-stage genetic medicines company committed to delivering life-changing treatments for people battling devastating diseases, today presented new data for its ADAR-mediated RNA editing capability (ADAR editing), including new preclinical editing data across multiple tissues, as well as an update on its discovery-stage alpha-1 antitrypsin deficiency (AATD) program during the company’s 2021 Analyst and Investor Research Webcast. The webcast also included updates on the company’s PRISM platform and initial results from the application of ADAR editing to neurology targets.

“Our presentations today represent robust and meaningful contributions to the rapidly advancing field of RNA editing, where we are at the forefront defining both new levels of editing, as well as the tissues and cell types amenable to this approach,” said Chandra Vargeese, PhD, Chief Technology Officer of Wave Life Sciences. “The application of PRISM to RNA editing means that there is the potential for therapeutic applications extending beyond the restoration of protein function, such as upregulation of protein expression, modification of protein function by altering post-translational modifications or protein-protein interactions, or alteration of protein stability. Additionally, with our AATD program, we have shown an ability in preclinical experiments to drive alpha-1 antitrypsin protein significantly above levels that are potentially therapeutically meaningful and increase the overall percentage of secreted wild-type M-AAT protein.”

A summary of the RNA editing presentations is below. A replay of the Analyst and Investor Research Webcast is available on Wave’s Investor Relations website.

Leading RNA Editing Capability Using Endogenous ADAR

• Wave’s RNA editing capability leverages widely expressed endogenous ADAR enzymes to achieve highly specific A-to-I (G) RNA editing using stereopure oligonucleotides, called “AIMers,” without the need for lipid nanoparticles (LNPs) or viral vectors, and without altering the genome.
• Wave is developing short, fully-chemically modified AIMers with and without GalNAc conjugation, with the objective of achieving productive editing in the liver, central nervous system (CNS), and other tissues.
• CNS: Wave presented new in vivo data that demonstrated potent editing (up to 65%) and durable editing of UGP2 mRNA out to at least four months in multiple regions of the CNS in a mouse model with human ADAR.
  • Wave is applying ADAR editing to multiple therapeutic targets in the CNS, including MECP2, seeking to correct a nonsense mutation and potentially restore functional protein in Rett Syndrome.
  • Additionally, in vitro data were presented demonstrating the potential to target protein-protein interactions and upregulate downstream gene expression with AIMers.
• Ophthalmology: Wave also presented preclinical data demonstrating up to 50% editing of UGP2 mRNA in the posterior of the eye of mice at one-month post-single intravitreal injection.
• New tissue and cell types: Wave shared ACTB RNA editing in non-human primates (NHPs) using systemic administration, including in the kidneys, liver, lungs and heart, as well as editing of ACTB in multiple immune cell types in vitro, including CD4+ T-cells, CD8+ T-cells, and others.