Wave Life Sciences Highlights Therapeutic Potential for

WVE-006 is probably the most superior candidate for AATD designed to revive useful wild-type AAT protein and scale back Z-AAT protein aggregation with potential for illness modification in each lung and liver phenotypes

IND-enabling actions for WVE-006 are underway and Wave expects to submit scientific trial purposes for WVE-006 in 2023

Wave can be pioneering new therapeutic purposes for RNA modifying, together with activating gene pathways and upregulating gene expression

CAMBRIDGE, Mass., Sept. 28, 2022 (GLOBE NEWSWIRE) — Wave Life Sciences Ltd. (Nasdaq: WVE), a clinical-stage genetic medicines firm dedicated to delivering life-changing therapies for folks battling devastating ailments, right this moment hosted a digital occasion, “Towards the Clinic: Spotlight on RNA Editing for AATD,” highlighting its WVE-006 program, which is Wave’s preclinical A-to-I RNA base modifying oligonucleotide (“AIMer”) candidate for the remedy of alpha-1 antitrypsin deficiency (AATD). The occasion featured a presentation from an AATD scientific professional, D. Kyle Hogarth, MD, FCCP, Professor of Medicine within the Section of Pulmonary and Critical Care Medicine on the University of Chicago. The firm additionally outlined future therapeutic purposes of its main RNA modifying functionality, together with modulating protein interactions in addition to addressing ailments outdoors the liver. A replay of the occasion and slide presentation can be found right here.

“Wave continues to lead the genetic medicines field in advancing therapeutic RNA editing toward the clinic with our WVE-006 AIMer program and we expect to submit clinical trial applications for our first-in-human study in 2023. WVE-006 is distinct from other approaches in development for AATD, as it offers the opportunity to treat the root genetic cause of the disease and restore functional, wild-type protein that remains under physiological regulation. This would be a holistic solution and applicable to those with lung disease, liver disease, or both,” stated Paul Bolno, MD, MBA, President and Chief Executive Officer of Wave Life Sciences. “Additionally, the opportunity for AIMers is much broader than restoring or correcting protein function in genetic diseases, as we demonstrated today with our preclinical data supporting the use of AIMers to modulate protein-protein interactions and upregulate gene expression. RNA editing is emerging as a distinct class of therapeutics with potential to address disease biology in novel and innovative ways and reach patients suffering from an array of diseases, including neurological disorders, as well as renal, cardiometabolic, or immunologic diseases. We are proud to be pioneers in this new area of genetic medicine and to have a best-in-class RNA editing capability with our AIMers.”

Highlights from right this moment’s occasion, “Towards the Clinic: Spotlight on RNA Editing for AATD,” are under.

Best-in-Class Potential of WVE-006 for AATD
WVE-006 is a first-in-class, GalNAc-conjugated RNA modifying candidate and probably the most superior program at present in improvement utilizing an oligonucleotide to harness an endogenous enzyme for modifying. WVE-006 is designed to right the only G-to-A base mutation in mRNA coded by the SERPINA1 Z allele, thereby enabling useful, wild-type M-AAT protein to be produced.

Data for WVE-006 highlighted right this moment embody:

• At 13 weeks in an AATD mouse mannequin (NSG-PiZ), remedy with WVE-006 resulted in roughly 50% RNA modifying of SERPINA1 transcript. Additionally on this similar preclinical research:
  • AAT protein ranges in mice dosed with WVE-006 had been roughly 7-fold higher than PBS-administered controls and nicely above the established protecting threshold of 11 uM.
  • WVE-006 led to restoration of roughly 50% wild-type M-AAT protein in serum.
  • WVE-006 led to a 3-fold enhance in neutrophil elastase inhibition exercise, indicating the restored M-AAT protein was useful.
• An earlier lead (pre-optimization) AIMer lowered Z-AAT aggregates and irritation in mouse livers (mouse mannequin: huADARxSA1).
• Wave’s AATD AIMers are extremely particular in vitro and in vivo primarily based on transcriptome-wide analyses.

WVE-006 Advancing Toward the Clinic
IND-enabling actions for WVE-006 are underway and Wave expects to submit scientific trial purposes (CTAs) for WVE-006 in 2023.

In addition, Wave introduced right this moment preliminary plans for the anticipated first-in-human research of WVE-006. This Phase 1/2 research would consider security, pharmacokinetics, and related biomarkers, together with serum AAT. The research, which might use Wave’s adaptive design method, is anticipated to first enroll wholesome volunteers to determine dose, adopted by cohort growth with Pi*ZZ sufferers to judge goal engagement primarily based on change in serum AAT ranges.

Future Applications of AIMers
Wave is advancing analysis utilizing AIMers for purposes past correction of G-to-A driver mutations and right this moment highlighted preclinical information supporting the usage of AIMers to activate gene pathways and upregulate gene expression. These purposes would considerably broaden the universe of targets addressable with AIMers, together with ailments with giant affected person populations. Highlights from the presentation embody:

• GalNAc-AIMers can disrupt KEAP1 protein/NRF2 protein interactions, thereby enabling NRF2 downstream gene upregulation within the liver of mice.
• GalNAc-AIMers can edit RNA motifs to revive or upregulate gene expression within the liver of mice.

Wave can be advancing analysis utilizing AIMers past hepatocytes and utilizing free uptake as an alternative of GalNAc conjugation. Preclinical in vivo information helps the power to edit with systemic supply in a number of tissues, together with coronary heart, kidney, lung, spleen, liver, white adipose tissue, and brown adipose tissue. Wave has additionally generated in vivo information demonstrating substantial and sturdy modifying and supporting administration of AIMers with intrathecal or intracerebroventricular supply in central nervous system tissues.

“Towards the Clinic: Spotlight on RNA Editing for AATD” Presentation and Slideshow
A replay of right this moment’s webcast and the complete slideshow presentation could be accessed and downloaded by visiting “Events & Publications” on the investor relations part of the Wave Life Sciences company web site: ir.wavelifesciences.com/events-and-presentations.

About AIMers
Wave’s AIMers are designed to right mutations in an RNA transcript, thereby avoiding everlasting modifications to the genome that happen with DNA-targeting approaches. Rather than utilizing an exogenous modifying enzyme, AIMers recruit proteins that exist within the physique, referred to as ADAR enzymes, which naturally edit sure adenine (A) bases to inosine (I). Because I is learn as G (guanine) by the mobile translational equipment, sequence-directed modifying with ADAR has the potential to revert transcripts with single G-to-Some extent mutations that trigger genetic ailments. This method redirects a pure system for therapeutic functions, allows simplified supply with out viral particles or liposomes, and avoids the danger of irreversible off-target results of DNA-targeting approaches. AIMers are brief in size, absolutely chemically modified, and use novel chemistry, together with proprietary PN spine modifications and chiral management, that make them distinct from different ADAR-mediated modifying approaches.

About Alpha-1 antitrypsin deficiency (AATD)
Alpha-1 antitrypsin deficiency (AATD) is an inherited genetic dysfunction that’s generally brought on by a G-to-Some extent mutation (“Z allele”) within the SERPINA1 gene. This mutation results in lung illness on account of lack of wild-type alpha-1 antitrypsin (M-AAT) in lungs and liver illness on account of aggregation of misfolded Z-AAT protein in hepatocytes. There are roughly 200,000 sufferers within the United States and Europe who’ve Z mutations on each alleles, often known as the PiZZ genotype. Augmentation remedy is the one remedy possibility for AATD lung illness and requires weekly intravenous infusions. There are not any therapies for AATD liver illness, apart from liver transplant. The common age of analysis of AATD lung illness is 46 years and the typical age of adult-onset liver illness is 61 years.

About PRISM™
PRISM is Wave Life Sciences’ proprietary discovery and drug improvement platform that permits genetically outlined ailments to be focused with stereopure oligonucleotides throughout a number of therapeutic modalities, together with silencing, splicing, and modifying. PRISM combines the corporate’s distinctive potential to assemble stereopure oligonucleotides with a deep understanding of how the interaction amongst oligonucleotide sequence, chemistry and spine stereochemistry impacts key pharmacological properties. By exploring these interactions by iterative evaluation of in vitro and in vivo outcomes and machine learning-driven predictive modeling, the corporate continues to outline design rules which can be deployed throughout applications to quickly develop and manufacture scientific candidates that meet pre-defined product profiles.

About Wave Life Sciences
Wave Life Sciences (Nasdaq: WVE) is a clinical-stage genetic medicines firm dedicated to delivering life-changing therapies for folks battling devastating ailments. Wave aspires to develop best-in-class medicines throughout a number of therapeutic modalities utilizing PRISM, the corporate’s proprietary discovery and drug improvement platform that permits the exact design, optimization, and manufacturing of stereopure oligonucleotides. Driven by a resolute sense of urgency, the Wave crew is focusing on a broad vary of genetically outlined ailments in order that sufferers and households could notice a brighter future. To discover out extra, please go to www.wavelifesciences.com and comply with Wave on Twitter @WaveLifeSci.

Forward-Looking Statements
This press launch accommodates forward-looking statements throughout the that means of the Private Securities Litigation Reform Act of 1995, as amended, together with, with out limitation, our expectations for our GalNAc-conjugated A-to-I(G) RNA base modifying oligonucleotides (AIMers) and the anticipated therapeutic advantages thereof; our perception that WVE-006 is probably the most superior candidate for AATD designed to revive useful wild-type AAT protein and scale back Z-AAT protein aggregation; our expectations concerning the power of our AIMers to handle ailments of many alternative tissues and cell varieties; the potential advantages of our AIMers in contrast with different RNA base modifying approaches; the anticipated timing of future improvement milestones for our lead AIMer program, WVE-006; and our expectations concerning potential future purposes of our AIMERs to activate genetic pathways and upregulate gene expression. The phrases “may,” “will,” “could,” “would,” “should,” “expect,” “plan,” “anticipate,” “intend,” “believe,” “estimate,” “predict,” “project,” “potential,” “continue,” “target” and comparable expressions are supposed to establish forward-looking statements, though not all forward-looking statements comprise these figuring out phrases. Any forward-looking statements on this press launch are primarily based on administration’s present expectations and beliefs and are topic to a variety of dangers, uncertainties and essential elements which will trigger precise occasions or outcomes to vary materially from these expressed or implied by any forward-looking statements contained on this press launch and precise outcomes could differ materially from these indicated by these forward-looking statements on account of these dangers, uncertainties and essential elements, together with, with out limitation, the dangers and uncertainties described within the part entitled “Risk Factors” in Wave’s most up-to-date Annual Report on Form 10-Okay filed with the Securities and Exchange Commission (SEC), as amended, and in different filings Wave makes with the SEC once in a while. Wave undertakes no obligation to replace the data contained on this press launch to replicate subsequently occurring occasions or circumstances.

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

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