Wave Life Sciences Announces Approval of First Clinical Trial Application for RestorAATion-2 Trial of WVE-006 in Individuals with Alpha-1 Antitrypsin Deficiency (AATD)

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Wave Life Sciences announced the approval of its first clinical trial application for the RestorAATion-2 trial of WVE-006 in individuals with Alpha-1 Antitrypsin Deficiency (AATD). WVE-006, a first-in-class RNA editing oligonucleotide, aims to correct disease-causing RNA mutations in AATD patients. The company is on track to deliver proof-of-mechanism data in 2024, showcasing the potential of RNA editing technology in treating genetic diseases like AATD. Wave Life Sciences continues to advance its RNA editing pipeline with a focus on GalNAc-hepatic and extra-hepatic targets, utilizing its proprietary 'edit-verse' platform for target identification and development.

Positive

• Approval of the first clinical trial application for WVE-006 marks a significant milestone in advancing RNA editing technology for treating AATD.

• WVE-006 has the potential to correct disease-causing RNA mutations in AATD patients, offering a promising therapeutic option for individuals with AATD liver disease, lung disease, or both.

• The company's progress in dose escalation in healthy volunteers demonstrates the translation of safety and pharmacokinetics of WVE-006 in humans, setting the stage for clinical efficacy evaluation.

• The collaboration with GSK for the global licensing of WVE-006 highlights the strong commercial potential of Wave Life Sciences' RNA editing pipeline.

Negative

• Transfer of development and commercialization responsibilities to GSK after the completion of the RestorAATion-2 study may impact Wave Life Sciences' control over WVE-006's future direction.

• The reliance on proof-of-mechanism data expected in 2024 for WVE-006's efficacy may pose a risk if the results do not meet expectations.

Medical Research Analyst

Wave Life Sciences' advancement into Phase 1b/2a trials for WVE-006 represents a pivotal development for investors monitoring the progress of RNA editing technologies. RNA editing oligonucleotides like WVE-006 aim to correct genetic mutations at the RNA level, a novel approach which could potentially offer significant advantages over traditional DNA-based therapies. The specific targeting of the Pi*ZZ mutation associated with Alpha-1 antitrypsin deficiency (AATD) indicates a precision medicine strategy that could lead to a more effective treatment for this genetic disorder. The absence of lipid nanoparticle (LNP) delivery systems in WVE-006 could also mean a better safety profile as LNPs have been known to cause immune reactions in some cases. If the upcoming proof-of-mechanism data align with preclinical expectations, this could have a positive impact on investor confidence, particularly as Wave Life Sciences has positioned itself to rapidly transition development and commercialization responsibilities to GSK, a pharmaceutical giant, after study completion. This strategic partnership could potentially accelerate the timeline to market and reduce development costs for Wave Life Sciences.

Market Research Analyst

Investors should note the strategic positioning of Wave Life Sciences in the RNA editing sector. With the approval of their CTA for WVE-006, the company is not solely advancing a new therapy but also reinforcing its 'edit-verse' platform. This proprietary technology underpins their RNA editing pipeline and may offer long-term value creation opportunities across a range of disorders. The mention of leveraging genetic datasets and deep learning models indicates a commitment to cutting-edge research that could keep Wave Life Sciences at the forefront of RNA medicine. Furthermore, the exclusive licensing agreement with GSK for WVE-006 underscores the market potential perceived by industry leaders. Investors might find the prospect of early-stage assets with such licensing agreements attractive, as they can de-risk investment and signal the asset's commercial viability. The clear paths to proof-of-concept and the use of accessible biomarkers are also critical points that suggest an efficient and potentially expedited regulatory and development process, potentially improving the speed to market and reducing costs.

Biotech Industry Analyst

From an industry perspective, the progression of WVE-006 into Phase 1b/2a trials is indicative of broader trends within biotech focused on RNA therapies. As such, the development of alpha-1 antitrypsin deficiency (AATD) treatments is a microcosm of the sector's push towards targeted genetic therapies. The absence of LNP delivery systems in this candidate pivots away from a more commonly used delivery method in RNA therapeutics, which may be a response to recent industry concerns regarding safety and tolerability. This trial approval is representative of the innovation within the RNA space and for investors, it could signify a potential edge over competitors in this niche market. The company’s use of GalNAc conjugation for subcutaneous delivery is also a notable aspect, as it represents a potentially more patient-friendly administration route compared to intravenous alternatives. The likely implications for the market are an increase in competitive pressure on peers to innovate similarly and an affirmation of investor interest in precision medicine platforms.

Proof-of-mechanism data for WVE-006 in individuals with AATD remain on track for 2024

CAMBRIDGE, Mass., April 30, 2024 (GLOBE NEWSWIRE) -- Wave Life Sciences Ltd. (Nasdaq: WVE), a clinical-stage biotechnology company focused on unlocking the broad potential of RNA medicines to transform human health, today announced the approval of its first clinical trial application (CTA) for its RestorAATion-2 clinical trial of WVE-006, the company’s first-in-class RNA editing oligonucleotide, which is being developed for the treatment of alpha-1 antitrypsin deficiency (AATD). WVE-006 is GalNAc-conjugated and subcutaneously administered; it does not use a lipid nanoparticle (LNP) delivery system.

“The approval of our first CTA for the RestorAATion-2 clinical trial of WVE-006 marks an important milestone as we continue extending our leadership in RNA editing. It is also important for the alpha-1 community as WVE-006 has the potential to enable correction of the disease-causing RNA mutation and provide a single therapeutic option regardless of whether patients have AATD liver disease, lung disease or both,” said Paul Bolno, MD, MBA, President and Chief Executive Officer of Wave Life Sciences. “Our rapid progress in dose escalating healthy volunteers enabled us to demonstrate the translation of safety and pharmacokinetics of WVE-006 in humans and quickly identify a starting dose level that, based on preclinical data, is expected to engage the target in patients. With proof-of-mechanism data from RestorAATion-2 expected later this year, we look forward to the opportunity to provide clinical demonstration of RNA editing and proof-of-concept for our wholly owned pipeline of RNA editing candidates.”

RestorAATion-2 is a Phase 1b/2a open label study designed to evaluate the safety, tolerability, pharmacodynamics (PD) and pharmacokinetics (PK) of WVE-006 in individuals with AATD who have the homozygous Pi*ZZ mutation. The trial includes both single ascending dose (SAD) and multiple ascending dose (MAD) portions. The company remains on track to deliver proof-of-mechanism data, as measured by restoration of M-AAT protein in serum, in 2024.

GSK has the exclusive global license for WVE-006. Development and commercialization responsibilities will transfer to GSK after Wave completes the RestorAATion-2 study.

In addition to WVE-006, Wave continues to advance its wholly owned RNA editing pipeline across a range of high-impact GalNAc-hepatic and extra-hepatic targets. The company’s discovery and development efforts in RNA editing are powered by its proprietary “edit-verse,” which leverages genetic datasets and deep learning models to identify new RNA editing targets and edit sites. These targets leverage easily accessible biomarkers, offer efficient paths to proof-of-concept in humans, and represent meaningful commercial opportunities.

About WVE-006
WVE-006 is a first-in-class, GalNAc-conjugated and subcutaneously administered RNA editing oligonucleotide designed to correct the single base mutation in messenger RNA (mRNA) coded by the SERPINA1 Z allele, thereby enabling restoration and circulation of functional M-AAT protein. In preclinical studies, WVE-006 demonstrated potent and durable editing of SERPINA1 Z transcript in mice, restoration of AAT protein up to 30 micromolar, and improvement in several markers of liver disease. WVE-006 is also highly specific with no evidence of bystander editing. Together, these data demonstrate the potential of WVE-006 to address AATD-related liver disease, lung disease, or both.

About Wave Life Sciences
Wave Life Sciences (Nasdaq: WVE) is a biotechnology company focused on unlocking the broad potential of RNA medicines to transform human health. Wave’s RNA medicines platform, PRISM^TM, combines multiple modalities, chemistry innovation and deep insights in human genetics to deliver scientific breakthroughs that treat both rare and prevalent disorders. Its toolkit of RNA-targeting modalities includes editing, splicing, RNA interference and antisense silencing, providing Wave with unmatched capabilities for designing and sustainably delivering candidates that optimally address disease biology. Wave’s diversified pipeline includes clinical programs in Duchenne muscular dystrophy, Alpha-1 antitrypsin deficiency and Huntington’s disease, as well as a preclinical program in obesity. Driven by the calling to “Reimagine Possible”, Wave is leading the charge toward a world in which human potential is no longer hindered by the burden of disease. Wave is headquartered in Cambridge, MA. For more information on Wave’s science, pipeline and people, please visit www.wavelifesciences.com and follow Wave on X (formerly Twitter) and LinkedIn.

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, the potential of WVE-006 to treat AATD; our expectations and anticipated timing for delivering proof-of-mechanism clinical data in AATD patients treated with WVE-006; and our understanding that WVE-006 is the most advanced candidate for AATD designed to restore functional wild-type AAT protein and reduce Z-AAT protein aggregation. The words “may,” “will,” “could,” “would,” “should,” “expect,” “plan,” “anticipate,” “intend,” “believe,” “estimate,” “predict,” “project,” “potential,” “continue,” “target” and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. Any forward-looking statements in this press release are based on management's current expectations and beliefs and are subject to a number of risks, uncertainties and important factors that may cause actual events or results to differ materially from those expressed or implied by any forward-looking statements contained in this press release and actual results may differ materially from those indicated by these forward-looking statements as a result of these risks, uncertainties and important factors, including, without limitation, the risks and uncertainties described in the section entitled “Risk Factors” in Wave’s most recent Annual Report on Form 10-K filed with the Securities and Exchange Commission (SEC), as amended, and in other filings Wave makes with the SEC from time to time. Wave undertakes no obligation to update the information contained in this press release to reflect subsequently occurring events or circumstance.

Investor Contact:
Kate Rausch
+1 617-949-4827
krausch@wavelifesci.com

Media Contact:
Alicia Suter
+1 617-949-4817
asuter@wavelifesci.com

AATD Community Contact:
Chelley Casey
+1 617-949-2900
ccasey@wavelifesci.com

FAQ

What is the purpose of WVE-006 in the RestorAATion-2 trial?

WVE-006 is an RNA editing oligonucleotide designed to correct disease-causing RNA mutations in individuals with Alpha-1 Antitrypsin Deficiency (AATD) in the RestorAATion-2 trial.

What is the timeline for proof-of-mechanism data for WVE-006?

Proof-of-mechanism data for WVE-006 is expected in 2024, demonstrating the potential of RNA editing technology in treating AATD.

Who has the exclusive global license for WVE-006?

GSK holds the exclusive global license for WVE-006, with development and commercialization responsibilities transitioning to GSK post the RestorAATion-2 study completion.

What is the design of the RestorAATion-2 trial?

RestorAATion-2 is a Phase 1b/2a open label study evaluating the safety, tolerability, pharmacodynamics, and pharmacokinetics of WVE-006 in individuals with AATD who have the homozygous Pi*ZZ mutation.