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Wave Life Sciences and GSK Enter Collaboration to Discover and Oligonucleotides for Novel Genetic Targets

December 14, 2022

Wave Life Sciences and GSK entered a strategic collaboration to advance oligonucleotide therapeutics, including Wave’s preclinical RNA editing program targeting alpha-1 antitrypsin deficiency, WVE-006.

Photo: Paul Bolno, president and CEO of Wave Life Sciences

The discovery collaboration has an initial four-year research term and combines GSK’s human genetics insights, 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). 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, which is designed to correct mutations in an RNA transcript, thereby avoiding permanent changes to the genome that occur with DNA-targeting approaches.

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 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.

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.

“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,” said Paul Bolno, president and CEO of Wave Life Sciences. “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.”

Under 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 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 and pursuing targets across multiple disease areas, given preclinical data indicating Wave oligonucleotides can distribute to various tissues and cells without complex delivery vehicles.

“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,” said Tony Wood, president and chief scientific officer at GSK.  “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.”

Author: Rare Daily Staff

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