[5] The company was founded in 1989 as Isis Pharmaceuticals by Stanley T. Crooke, a former head of research of GlaxoSmithKline, with the goal of commercializing antisense therapy.

[16] Clinical trials of antisense therapeutics by all the companies in the early 2000s were also plagued by lack of efficacy and immune reactions to drug candidates.

[18] In 2007, Isis and Alnylam Pharmaceuticals, which focuses on RNA interference, formed a 50/50 joint venture, Regulus Therapeutics, to apply their intellectual property and knowledge around oligomer biotherapeutics to micro-RNA targets.

[25] It had been discovered in a collaboration between Adrian Krainer at Cold Spring Harbor Laboratory and Ionis (then Isis)[26][27][17][28] and preclinical work was done at University of Massachusetts.

[32] In December 2024, Ionis Pharmaceuticals secured FDA approval for Tryngolza (olezarsen), a treatment for familial chylomicronemia syndrome (FCS), a rare and life-threatening genetic condition that prevents the body from properly breaking down fats.

The approval was based on late-stage trial data showing that Tryngolza effectively reduced triglyceride levels and was generally well-tolerated.

[35] Patients receiving the therapy were also less likely to experience pancreatitis, a severe and potentially fatal complication characterized by painful inflammation of the pancreas.