Wave Life Sciences Ltd. (Nasdaq: WVE), a clinical-stage genetic
medicines company committed to delivering life-changing treatments
for people battling devastating diseases, and GSK plc (LSE/NYSE:
GSK) today announced a strategic collaboration to advance
oligonucleotide therapeutics, including Wave’s preclinical RNA
editing program targeting alpha-1 antitrypsin deficiency (AATD),
WVE-006. The discovery collaboration has an initial four-year
research term. It combines GSK’s unique insights from human
genetics, as well as its global development and commercial
capabilities, with Wave’s proprietary discovery and drug
development platform, PRISM™.
Oligonucleotides are short strands of DNA or RNA that can
reduce, restore, or modulate RNA through several different
mechanisms. The unique capability of oligonucleotides to address a
wide range of genomic targets in multiple therapeutic areas is
enabling new opportunities to treat a range of human diseases,
including diseases where no medicines currently exist or that have
historically been difficult to treat with small molecules or
biologics.
Wave’s PRISM platform is the only oligonucleotide platform
offering three RNA-targeting modalities (editing, splicing, and
silencing, including siRNA and antisense). Importantly, these
modalities incorporate novel chemistry, including PN backbone
chemistry and control of stereochemistry, to optimize the
pharmacological properties of therapeutic oligonucleotides.
The collaboration includes two main components. The first is a
discovery collaboration which enables GSK to advance up to eight
programs and Wave to advance up to three programs, leveraging
Wave’s PRISM platform and GSK’s expertise in genetics and genomics.
In addition to these programs, GSK receives the exclusive global
license for Wave’s preclinical program for AATD called WVE-006,
which uses Wave’s proprietary “AIMer” technology (A-to-I(G) RNA
editing). AATD is an inherited genetic disease that affects both
the lungs and liver with limited treatment options. Wave’s WVE-006
is a first-in-class RNA editing therapeutic that is designed to
address both liver and lung manifestations of the disease.
Paul Bolno, MD, MBA, President and Chief Executive
Officer, Wave Life Sciences, said: “For the past decade,
Wave has been building a unique oligonucleotide platform that
combines novel chemistry with the means to optimally address
disease biology through multiple therapeutic modalities. In 2022,
we started to deliver on the promise of our platform with the first
data showing translation in the clinic for our next-generation
stereopure PN-chemistry containing candidates. Now with our GSK
collaboration, we are excited to leverage their expertise in
genetics to continue building a differentiated oligonucleotide
pipeline, with a focus on our best-in-class RNA editing and
upregulation capability. Additionally, GSK is the ideal partner for
our WVE-006 program, due to their longstanding history and global
reach in respiratory diseases. The collaboration meaningfully
extends our cash runway into 2025 and offers the potential for
significant future milestones, providing new resources to deliver
life-changing medicines to patients.”
Tony Wood, President and Chief Scientific Officer, GSK,
said: “Oligonucleotide therapeutics are becoming a
mainstream modality, and this collaboration will enable us to use
our leading position in human genetics and genomics to advance
novel oligonucleotide therapies. Pairing GSK's genetic expertise
with the best-in-class PRISM™ platform enables us to
accelerate drug discovery for newly-identified targets, by matching
target to modality. The addition of WVE-006 complements more
advanced, clinical-phase oligonucleotides in our pipeline,
including bepirovirsen for chronic hepatitis B and GSK4532990 for
non-alcoholic steatohepatitis (NASH).”
Bepirovirsen, an investigational antisense oligonucleotide for
the potential treatment of chronic hepatitis B infection, is now
entering Phase III trials, and GSK4532990, a siRNA oligonucleotide,
is progressing to Phase II for NASH. WVE-006 brings a third
oligonucleotide into GSK’s portfolio that has the potential to be a
first-in-class AATD treatment for both lung and liver disease and
is a well-understood genetic target, contributing to GSK’s pipeline
that is now more than 70% genetically validated.
The companies expect to pursue targets across multiple disease
areas, given preclinical data indicating Wave oligonucleotides can
distribute to various tissues and cells without complex delivery
vehicles.
Terms of the CollaborationUnder the terms of
the agreement, Wave will receive an upfront payment of $170
million, which includes a cash payment of $120 million and a $50
million equity investment.
For the WVE-006 program, 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 tiered
sales royalties. Development and commercialization responsibilities
will transfer to GSK after Wave completes the first-in-patient
study.
For each of GSK’s eight collaboration programs, Wave will be
eligible to receive up to $130-$175 million in development and
launch milestones and $200 million in sales-related milestones,
along with tiered sales royalties. Wave will lead all preclinical
research for GSK and Wave programs up to investigational new drug
(IND) enabling studies. GSK collaboration programs will transfer to
GSK for IND-enabling studies, clinical development, and
commercialization. The collaboration includes an option to extend
the research term for up to three additional years, expanding the
number of programs available to both parties.
The equity investment and collaboration agreement will complete
at the same time and are conditional upon customary conditions
including regulatory review by the appropriate regulatory agencies
under the Hart-Scott-Rodino Act.
Investor Conference Call and WebcastWave
management will host an investor conference call today at 8:30 a.m.
ET to discuss the strategic collaboration announcement. The webcast
of the conference call and corresponding slide presentation may be
accessed by visiting “Events” on the investor relations section of
the Wave Life Sciences corporate website:
ir.wavelifesciences.com/events-and-presentations.
Analysts planning to participate during the Q&A portion of
the live call can join the conference call at the audio
conferencing link available here. Once registered, participants
will receive the dial-in information. Following the live event, an
archived version of the webcast will be available on the Wave Life
Sciences website.
About OligonucleotidesOligonucleotide
mechanisms that can reduce, increase or modify RNA include
silencing (oligonucleotides that promote degradation of the target
RNA, including antisense and siRNA); splicing (oligonucleotides
that involve binding to the target RNA and modulating its function
by promoting exon skipping); and ADAR-mediated RNA editing
(oligonucleotides that edit adenosines in target RNAs to correct
RNA or modulate protein function or production). GSK's investments
in genetics have revealed that a significant number of genetic
associations point to proteins where modulation of RNA function
and/or expression would likely be the most effective mechanism for
therapeutic intervention versus more traditional small molecules
and biologic-based therapeutics. Oligonucleotide therapeutics
represent a modality that addresses this gap by regulating target
expression rather than function.
About AIMersWave’s AIMers are designed to
correct mutations in 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
normal 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 Alpha-1 Antitrypsin DeficiencyAlpha-1
antitrypsin deficiency (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 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 the only treatment option for AATD lung disease and
requires weekly intravenous infusions. There are no treatments for
AATD liver disease, other than liver transplantation.
About WVE-006WVE-006 is a PN chemistry-modified
GalNAc-conjugated investigational development candidate for the
treatment of alpha-1 antitrypsin deficiency (AATD), designed to
correct the mutant SERPINA1 Z allele transcript to address both
liver and lung manifestations of disease. WVE-006 is a potential
first-in-class RNA editing candidate (AIMer) and the most advanced
program currently in development using an oligonucleotide to
harness an endogenous enzyme for editing. Wave expects to submit
clinical trial applications for WVE-006 in 2023.
About Wave Life SciencesWave Life Sciences
(Nasdaq: WVE) is a clinical-stage genetic 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 StatementsThis press release
contains forward-looking statements within the meaning of the
Private Securities Litigation Reform Act of 1995, as amended,
including, without limitation, statements regarding the
collaboration and license agreement between Wave and GSK, including
anticipated payments, as well as the discovery, development,
manufacture and commercialization of potential oligonucleotide
therapeutics under the agreement, and Wave’s strategy and business
plans. 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, including, without
limitation, risks and uncertainties related to Wave’s ability to
successfully advance multiple potential programs simultaneously;
the delay of any current or planned clinical trials or the other
development activities for WVE-006; the effectiveness of PRISM,
including our novel PN backbone chemistry modifications; the
effectiveness of our novel ADAR-mediated RNA editing platform
capability and our AIMers; our dependence on third parties,
including contract research organizations, contract manufacturing
organizations, collaborators and partners; our ability to obtain,
maintain and protect our intellectual property; competition from
others developing therapies for similar indications; and the
severity and duration of the COVID-19 pandemic and variants
thereof, and its negative impact on the conduct of, and the timing
of enrollment, completion and reporting with respect to our
clinical trials. These and other risks and uncertainties are
described in greater detail in the section entitled “Risk Factors”
in Wave’s Annual Report on Form 10-K for the year ended December
31, 2021, as filed with the Securities and Exchange Commission
(SEC) on March 3, 2022, and other filings that Wave may make with
the SEC from time to time. Any forward-looking statements contained
in this press release represent Wave’s views only as of the date
hereof and should not be relied upon as representing its views as
of any subsequent date. Wave explicitly disclaims any obligation to
update any forward-looking statements.
Investor Contact:Kate
Rausch617-949-4827InvestorRelations@wavelifesci.com
Media Contact:Alicia
Suter617-949-4817asuter@wavelifesci.com
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