GSK and Wave Life Sciences collaborate to discover and develop oligonucleotide therapeutics

By Rachel Arthur

- Last updated on GMT


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GSK and genetic medicines company, Wave Life Sciences, have announced a strategic collaboration to advance oligonucleotide therapeutics across multiple disease areas.

The partnership will include Cambridge, Massachusetts-headquartered Wave’s preclinical RNA editing program targeting alpha-1 antitrypsin deficiency (AATD), WVE-006.

The discovery collaboration has an initial four-year research term with the option to extend for a further three years: combining GSK’s insights from human genetics and its global development and commercial capabilities with Wave’s proprietary discovery and drug development platform, called PRISM..

Oligonucleotide potential

Oligonucleotides are short strands of DNA or RNA that can reduce, restore, or modulate RNA through several different mechanisms.

GSK eyes up the capability of oligonucleotides to address a wide range of genomic targets in multiple therapeutic areas, 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 porgress up to three programs, leveraging Wave’s PRISM platform and GSK’s expertise in genetics and genomics.

In addition, 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.

Terms of the deal

Under the collaboration, GSK will pay Wave $170m upfront, covering a cash payment of $120m and a $50m equity investment.

For the WVE-006 program, Wave is eligible to receive up to $225m in development and launch milestone payments and up to $300m in sales-related ones, 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 program, Wave will be eligible to receive up to $130-$175m in development and launch milestones and $200m in sales-related targets, along with tiered sales royalties.

Wave will lead all preclinical research for the jointly run program, up to investigational new drug (IND) enabling studies. 

'Differentiated pipeline'

Tony Wood, 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 other oligonucleotides in GSK’s pipeline. 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.

Paul Bolno, CEO of 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.”

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.

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