Wave Life Sciences Announces New Data for Advanced RNA Editing Capability Across Multiple … | Your money

Sustainable ADAR edition in vivo in preclinical models including CNS tissue with at least four month edition

Optimization of chemistry results in a fourfold increase compared to the PBS control in the restoration of AAT proteins in vivo in preclinical (or more than 15 micromolar)

CAMBRIDGE, Mass., September 28, 2021 (GLOBE NEWSWIRE) – Wave Life Sciences Ltd. (Nasdaq: WVE), a clinical-stage genetic drug company committed to providing life-changing treatments for people with devastating diseases, today presented new data for its RNA editing ability mediated by ADAR (ADAR edition), including new preclinical edition data on several tissues, as well as an update on its program for discovering alpha-1 antitrypsin deficiency (AATD) during the search for Webcast Company 2021 analysts and investors. The webcast also included updates on the company’s PRISM ™ platform and early results from applying the ADAR edition to neurology targets.

“Our presentations today represent strong and meaningful contributions to the rapidly evolving field of RNA editing, where we are at the forefront of defining both new levels of editing, as well as tissues and cell types suitable for this approach, ”said Chandra Vargeese, PhD, chief technology officer of Wave Life Sciences. “The application of PRISM to RNA editing means that there is potential for therapeutic applications going 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 significant and to increase the overall percentage of wild-type M-AAT protein. secreted.

A summary of the RNA editing presentations is below. A replay of the analyst and investor research webcast is available on the Wave Investor Relations website.

State-of-the-art RNA editing capability using endogenous ADAR

Wave’s RNA-editing ability exploits widely expressed endogenous ADAR enzymes to achieve highly specific RNA A-to-I (G) editing using stereopure oligonucleotides, called “AIMers”, without having need lipid nanoparticles (LNP) or viral vectors, and without altering the genome.Wave is developing short and fully chemically modified AIMers with and without GalNAc conjugation, with the aim 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 sustained editing of UGP2 mRNA for up to at least four months in several regions of the CNS in a mouse model with human ADAR. Wave applies ADAR editing to several therapeutic targets in the CNS, including MECP2, seeking to correct a nonsense mutation and potentially restore a 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 part of the mouse eye one month after the single intravitreal injection New tissue and cell types: Wave-shared ACTB RNA editing in non-human primates (PNH) in using systemic delivery, including to kidneys, liver, lungs and heart, as well as ACTB editing in several types of immune cells in vitro, including CD4 + T cells, CD8 + T cells and others .

ADAR Edition Offers Promising Therapeutic Approach for Alpha-1 Antitrypsin Deficiency (AATD)

Wave’s AATD program, its first experimental ADAR editing program, uses AIMers to potentially correct for the single base mutation in mRNA encoded by the SERPINA1 Z allele. ADAR editing may provide an ideal approach to treat AATD by increasing circulating levels of functional alpha-1 antitrypsin protein (M-AAT) and by reducing the aggregation of mutant proteins in the liver, thereby potentially attacking the pulmonary and hepatic manifestations of the disease. shared new in vivo data demonstrating a sustainable restoration of M-AAT protein in the liver of mice transgenic with human SERPINA1 and human ADAR after initial doses of a SERPINA1 AIMer conjugated to GalNAc. Serum concentrations of human AAT protein remained at least three times higher than the PBS control for 30 days after the last dose with the SERPINA1 AIMer.Wave also shared data demonstrating progress in improving the activity of editing and restoration of proteins after optimization of PRISM chemistry. These AIMers obtained an average editing of approximately 50% of SERPINA1 mRNA in vivo. In addition, through chemical optimization, Wave demonstrated in vivo a four-fold increase over the PBS control in restoring the AAT protein in serum (or greater than 15 micromolar), which is an improvement over the the tripling achieved with the initial Wave AIMers. Approximately 85% of circulating AAT was confirmed to be M-AAT in transgenic mice treated with human SERPINA1 and human ADAR. The ADAR edition of Wave appears very specific with nominal off-target edits observed after transcriptome analysis, and there were no viewer edits observed in the SERPINA1 transcript. Ongoing and planned preclinical studies are evaluating durability, dose response, pharmacokinetics and pharmacodynamics. Wave also plans to evaluate the reduction in Z-AAT aggregates in the liver and changes in liver pathology in its transgenic mouse model. Wave expects to have an AATD development candidate in 2022.

About PRISM ™ PRISM ™ is Wave Life Sciences’ proprietary drug discovery and development platform for targeting genetically defined diseases with stereopure oligonucleotides across multiple therapeutic modalities, including silencing, splicing and editing. PRISM combines the company’s unique ability to construct stereopure oligonucleotides with an in-depth understanding of how the interplay between oligonucleotide sequence, backbone chemistry and stereochemistry influences key pharmacological properties. By exploring these interactions through iterative analysis of in vitro and in vivo results and predictive modeling based on machine learning, the company continues to define design principles that are deployed in programs to rapidly develop and manufacture candidates. clinics responding to predefined product profiles.

About Wave Life Sciences Wave Life Sciences (Nasdaq: WVE) is a clinical-stage genetic drug company committed to providing life-changing treatments for people with devastating diseases. Wave aspires to develop world-leading drugs in multiple therapeutic modalities using PRISM ™, the Company’s proprietary drug discovery and development platform that enables the precise design, optimization and production of stereopure oligonucleotides. Driven by a strong sense of urgency, the Wave team targets a wide range of genetically defined diseases so that patients and families can achieve a better future. For more information, visit www.wavelifesciences.com and follow Wave on Twitter @WaveLifeSci.

Forward-looking statements This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, as amended, including, without limitation, our understanding of the application of PRISM to RNA publishing and therapeutic benefits expected from RNA editing capabilities using endogenous ADAR; our beliefs about the lessons learned from our first generation clinical programs and early chemistry; our understanding of AIMers and their expected capabilities; the therapeutic benefits expected from our ADAR editing program for AATD; the expected timeline for our development candidate AATD; and the potential benefits of PRISM, including our stereopure oligonucleotides. The words “can”, “represent”, “expect”, “plan”, “objective”, “achieve”, “demonstrate”, “represent”, “predict”, “appear”, “,, “Target” and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. All forward-looking statements contained in this press release are based on the current expectations and beliefs of management and are subject to a number of risks, uncertainties and important factors that may cause actual events or results to occur. differ materially from those expressed or implied by any forward-looking statement. the statements contained in this press release and actual results may differ materially from those indicated in these forward-looking statements due to these risks, uncertainties and important factors, including, without limitation, the risks and uncertainties described in the section entitled “Factors”. risk ”in Wave’s most recent annual report on Form 10-K filed with the Securities and Exchange Commission (SEC), as amended, and in other documents filed by Wave with the SEC from time to time. other. Wave does not undertake to update the information contained in this press release to reflect events or circumstances occurring subsequently.

Investor contact: Kate Rausch 617-949-4827 [email protected]

Media contact: Alicia Suter 617-949-4817 [email protected]

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