Wave Secures Initial Clinical RNA Editing Achievement in Rare Genetic Disorders

Wave Secures Initial Clinical RNA Editing Achievement in Rare Genetic Disorders

Wave Secures Initial Clinical RNA Editing Achievement in Rare Genetic Disorders

Founded in 2012 and going public on the Nasdaq in 2015, the US-based RNA biotech Wave Life Sciences recently announced a clinical trial that boosted its stock by 70%. This development is advantageous for GSK, which is set to take over the development of Wave’s treatment for alpha-1 antitrypsin deficiency (AATD), known as WVE-006, once the current trial concludes.

On the very same day, Takeda declared its decision to sever ties with Wave, as they opted not to pursue the further development of Wave’s Huntington’s disease treatment. This was a notable announcement despite promising phase 1b/2a results for the Huntington’s therapy (WVE-003) disclosed earlier in the summer. Wave has amassed approximately 0 million from their collaboration with Takeda since it began in 2018, and is now in search of new partners for this project.

Additionally, Wave shared favorable phase 2 data regarding its candidate for Duchenne muscular dystrophy, WVE-N531, earlier this year and is also working on therapies addressing obesity and other metabolic disorders.

Groundbreaking RNA Editing

AATD is a rare genetic disorder that may lead to lung or liver diseases appearing between 20 and 50 years of age. This complex condition affects an estimated 1.1 million individuals globally, with significant variability in mutations and the severity of alpha-1 antitrypsin deficiency among patients.

WVE-006 aims to address both lung and liver diseases linked to AATD. It is a GalNAc-conjugated, A-to-I RNA editing oligonucleotide (known as AIMer), delivered through subcutaneous injection.

The two participants in the ongoing RestorAATion-2 trial possess the Pi*ZZ AATD mutation, which leads to faulty mRNA and AATD symptoms.

After administering a single 200mg dose of WVE-006, researchers noted a restoration in wild-type alpha-1 antitrypsin protein levels (M-AAT) to those seen in healthy individuals with one copy of the mutation.

At the 57-day mark, plasma AAT levels reached around 11 micromolar, with average wild-type AAT levels exceeding 60% in both participants.

Progressing with Promise

“Securing the first successful therapeutic RNA editing in humans represents an important achievement for our company, our collaboration with GSK, and the broader field of oligonucleotides,” commented Paul Bolno, the President and CEO of Wave Life Sciences, in a statement.

“The degree of mRNA editing we are witnessing from a single dose has surpassed our expectations, and we anticipate that M-AAT levels will continue to rise with repeat dosing, as indicated by our preclinical studies. Coupled with WVE-006’s durability and the convenience of subcutaneous delivery, we believe it has a best-in-class profile compared to other editors and within the larger AATD arena.”

WVE-006 has been well tolerated among participants in both this trial and one involving healthy volunteers, with all reported side effects being mild to moderate. Wave plans to unveil further study outcomes next year.

Should GSK proceed with the development post-trial according to plan, Wave may stand to receive as much as 5 million in milestone payments along with tiered royalties in the near future.