ION464 (Ionis Pharmaceuticals)

ION464 (IONIS-KEAP1-LRx) is an investigational antisense oligonucleotide (ASO) developed by Ionis Pharmaceuticals that targets the mRNA of Kelch-like ECH-associated protein 1 (KEAP1). KEAP1 is a primary negative regulator of the transcription factor NRF2 (Nuclear factor erythroid 2-related factor 2), which orchestrates the cellular antioxidant and anti-inflammatory response. By binding to KEAP1 mRNA and inducing its degradation, ION464 reduces KEAP1 protein levels, allowing NRF2 to stabilize, accumulate, and translocate to the nucleus. This activation of the NRF2 pathway induces the expression of a broad range of cytoprotective genes, aiming to mitigate oxidative stress and inflammation. The drug utilizes Ionis' Ligand-Conjugated Antisense (LRx) technology, specifically GalNAc-conjugation, to enhance delivery to the liver, where it promotes systemic NRF2 activation. It is primarily being evaluated for the treatment of chronic kidney disease (CKD) and Alport syndrome.

Other names

KEAP1 antisense oligonucleotideKEAP-1 antisense oligonucleotideKEAP 1 antisense oligonucleotide