Wave Life Sciences Ltd. (Nasdaq: WVE), a clinical-stage RNA
medicines company committed to delivering life-changing treatments
for people battling devastating diseases, today announced the
submission of its first clinical trial application (CTA) for
WVE-006 in alpha-1 antitrypsin deficiency (AATD). WVE-006 is a
first-in-class, GalNAc-conjugated RNA editing oligonucleotide
(“AIMer”) and is designed to correct the single base mutation in
messenger RNA (mRNA) coded by the SERPINA1 Z allele, thereby
enabling restoration and circulation of functional, wild-type
alpha-1 antitrypsin (M-AAT) protein. The WVE-006 clinical program
will be highlighted in Wave’s virtual “R&D Day” on September
28, 2023 at 10:00 a.m. ET, among other programs.
“With the submission of the first CTA for WVE-006, we have
officially initiated clinical development of the industry’s
first-ever RNA editing therapeutic candidate,” said Anne Marie
Li-Kwai-Cheung, Chief Development Officer at Wave Life Sciences.
“We designed WVE-006 to correct the most common underlying genetic
mutation that causes AATD, providing an innovative therapeutic
option for individuals with lung disease, liver disease or both.
Indeed, our preclinical data support this profile, with mouse
models showing restored AAT protein well above 11 micromolar, as
well as improvement in several markers of liver disease and
inhibition of neutrophil elastase. As a GalNAc-RNA editing
oligonucleotide, WVE-006 is reversible and re-dosable, with
potential for infrequent subcutaneous dosing. WVE-006 is highly
specific with no evidence of bystander editing and, by virtue of
the mechanism of action, no permanent changes to the genome that
occur with DNA-targeting approaches. For these reasons, we believe
WVE-006 has potential to revolutionize how AATD is treated.”
The current clinical development plan for WVE-006 includes
healthy volunteers as well as individuals with AATD who have the
homozygous PiZZ mutation, and is designed to provide an efficient
path to proof-of-mechanism as measured by restoration of M-AAT
protein in serum. Wave expects to initiate dosing in healthy
volunteers in the fourth quarter of 2023 and deliver
proof-of-mechanism data in individuals with AATD in 2024.
“WVE-006 is on a path to potentially deliver the first-ever
proof-of-mechanism clinical data for an RNA editing therapeutic.
Positive data would be a pivotal milestone for people living with
AATD and would unlock the potential of RNA editing more broadly.
Additionally, WVE-006 is a foundational component of our
collaboration with GSK and carries with it meaningful milestone and
royalty payments, including near-term clinical milestones,” said
Paul Bolno, MD, MBA, President and Chief Executive Officer of Wave
Life Sciences. “RNA editing is a promising new therapeutic
modality, capable of accessing untapped areas of disease biology.
We are incredibly proud to be pioneers leading the way forward in
RNA editing, and we plan to share more updates on AATD and other
RNA editing programs during our R&D Day later this month.”
Earlier this year, Wave commenced its strategic collaboration
with GSK to advance transformative RNA medicines using Wave’s
multimodal RNA platform, including WVE-006. Wave received $170
million in upfront cash and equity and is also receiving research
funding. Wave is eligible for up to $3.3 billion in potential
milestone payments, including near-term preclinical and clinical
milestones, as well as royalties, for WVE-006 and GSK’s eight
collaboration programs. For WVE-006, Wave is eligible to receive up
to $225 million in development and launch milestone payments, and
up to $300 million in sales-related milestone payments, as well as
double-digit tiered royalties as a percentage of net sales up to
the high teens.
Wave expects that its cash and cash equivalents will be
sufficient to fund operations into 2025. Wave does not include
future milestones or other contingent payments in its cash
runway.
Wave Virtual R&D Day A link to register for
the event is available here. A live webcast of the event can be
accessed by visiting “Investor Events” on the investor relations
section of the Wave Life Sciences website:
https://ir.wavelifesciences.com/events-and-presentations. Following
the live event, an archived version of the webcast will be
available on the Wave Life Sciences website.
About WVE-006 and AATDWVE-006 is a
clinical-stage GalNAc-conjugated investigational RNA editing
oligonucleotide for the treatment of alpha-1 antitrypsin deficiency
(AATD). AATD is an inherited genetic disorder that is commonly
caused by a G-to-A point mutation (“Z allele”) in the SERPINA1
gene. This mutation leads to lung disease due to a lack of
wild-type alpha-1 antitrypsin (M-AAT) function in lungs, and it
leads to liver disease due to aggregation of misfolded Z-AAT
protein in hepatocytes. There are approximately 200,000 patients in
the United States and Europe who have Z mutations on both alleles,
known as the PiZZ genotype. Augmentation therapy via delivery of
AAT protein is currently the only treatment option for AATD lung
disease and requires weekly intravenous infusions. There are
currently no treatments for AATD liver disease, other than liver
transplantation.
About AIMersA-to-I(G) RNA editing
oligonucleotides (“AIMers”) are designed to edit specific sites on
an RNA transcript, thereby avoiding permanent changes to the genome
that occur with DNA-targeting approaches. Rather than using an
exogenous editing enzyme, AIMers recruit proteins that exist in the
body, called ADAR enzymes, which naturally edit certain adenine (A)
bases to inosine (I). Because I is read as G (guanine) by the
cellular translational machinery, sequence-directed editing with
ADAR has the potential to revert transcripts with single G-to-A
point mutations that cause genetic diseases. This approach
redirects a natural system for therapeutic purposes, enables
simplified delivery without viral particles or liposomes, and
avoids the risk of irreversible off-target effects of DNA-targeting
approaches. AIMers are short in length, fully chemically modified,
and use novel chemistry, including proprietary PN backbone
modifications and chiral control, that make them distinct from
other ADAR-mediated editing approaches.
About Wave Life SciencesWave Life Sciences
(Nasdaq: WVE) is a clinical-stage RNA medicines company committed
to delivering life-changing treatments for people battling
devastating diseases. Wave aspires to develop best-in-class
medicines across multiple therapeutic modalities using PRISM, the
company’s proprietary discovery and drug development platform that
enables the precise design, optimization, and production of
stereopure oligonucleotides. Driven by a resolute sense of urgency,
the Wave team is targeting a broad range of genetically defined
diseases so that patients and families may realize a brighter
future. To find out more, please
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 expectations for our
GalNAc-conjugated RNA editing oligonucleotides (AIMers), including
WVE-006, and the anticipated therapeutic benefits thereof,
including the potential of WVE-006 to treat AATD; the anticipated
timing to initiate dosing in the first-in-human clinical program
with WVE-006, and the associated delivery of AAT protein
restoration data from AATD patients treated with WVE-006; the
future performance and results of our clinical programs; our
expectations for delivering proof-of-mechanism clinical data for an
RNA editing therapeutic; 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; our
expectations regarding the ability of our AIMers to address
diseases of many different tissues and cell types; the potential
benefits of our AIMers compared with other RNA base editing
approaches; and the potential achievement of milestones under our
collaborations and receipt of cash payments therefor. 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 circumstances.
Investor Contact:Kate Rausch+1
617-949-4827krausch@wavelifesci.com
Media Contact:Alicia Suter+1
617-949-4817asuter@wavelifesci.com
AATD Community Contact:Chelley Casey+1
617-949-2900ccasey@wavelifesci.com
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