Wave Life Sciences Ltd. (NASDAQ: WVE) has announced the publication of two articles in the Nucleic Acids Research journal that support PN backbone chemistry modifications incorporation in stereopure oligonucleotides as a considerable advancement for the therapeutics oligonucleotide sector.
Wave conducting three trials ion PN chemistry
PN chemistry greatly increased potency, distribution, and persistence of action in the numerous in vivo and in vitro (animal) investigations described in the articles. In addition, the studies look at how stereopure silencing oligonucleotides for CNS illnesses and stereopure splicing oligonucleotides for neurological illnesses can be made using PN chemistry. Wave is now conducting three clinical trials for Duchenne muscular dystrophy (DMD), amyotrophic lateral sclerosis (ALS)/frontotemporal dementia (FTD), and Huntington’s disease using PN chemistry-based molecules (HD).
The publication focusing on PN chemistry for CNS silencing received a Breakthrough Article designation from the journal. The designation is given to high-impact works that address long-standing concerns in the area of nucleic acids study and/or open up new areas and mechanistic theories for inquiry.
Chief Technology Officer Chandra Varghese said, “These papers on PN chemistry – specifically phosphoryl guanidine linkages – demonstrate that we have identified an important new opportunity for optimizing therapeutic stereopure oligonucleotides. Wave was founded on the insight that chirality matters in oligonucleotides, just as it matters in small molecules.
Wave applying PN chemistry across its pipeline
Rather than ignoring stereochemistry’s structural feature, the company created the ability to manipulate it and construct single isomers, allowing it to better evaluate structure-activity connections and identify innovative chemistry changes. As a result, the company discovered the promise of PN biochemistry and applied it across its modalities and pipeline because of the underlying science.
Chief medical officer and Therapeutics Discovery and Development Michael Panzara commented, “The foundational work outlined in these publications resulted in our next generation of clinical candidates currently being dosed in three clinical trials and has been critical as we continue to build a robust research pipeline. The findings fuel our optimism for the clinical data we expect this year from the ongoing studies of WVE-N531 in DMD, WVE-004 in C9orf72-associated ALS and FTD, and WVE-003 in HD.”