Wave Life Sciences and GSK Announce Collaboration to Drive Discovery and Development of Oligonucleotide Therapeutics Focusing on Novel Genetic Targets
Wave receives upfront payment of
Collaboration brings together Wave’s PRISM™ oligonucleotide platform and GSK’s expertise in genetics and genomics
GSK to advance up to eight preclinical programs
Additionally, GSK receives exclusive global license to Wave’s preclinical, potential first-in-class RNA editing program, WVE-006, to treat alpha-1 antitrypsin deficiency, a disease that impacts the lungs and liver
Wave to advance up to three preclinical programs for targets informed by GSK’s novel insights
Wave to host investor conference call and webcast at
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.
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 Collaboration
Under the terms of the agreement, Wave will receive an upfront payment of
For the WVE-006 program, Wave is eligible to receive up to
For each of GSK’s eight collaboration programs, Wave will be eligible to receive up to
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 Webcast
Wave management will host an investor conference call today at
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
Oligonucleotide 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.
Wave’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 Deficiency
Alpha-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
WVE-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.
This 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
Source: Wave Life Sciences USA, Inc.