Glutathione transferase omega-1 (GSTO1-1) helps drive inflammatory disorders and cancers by activating the NLRP3 inflammasome and promoting production of pro-inflammatory interleukin-1b. Numerous small molecules have been generated to inhibit the enzyme, but none has progressed to clinical trials, mostly because of off-target activity or poor pharmacokinetics.

Researchers at Calluna Pharma AS, Agiana Pharmaceuticals AS and Roskilde University have developed the first humanized IgG4 antibody that inhibits S100A4, which is a calcium-binding protein that helps drive fibrotic inflammatory diseases.

For 75 years, the standard tools for autoimmune disease have consisted of steroids, cytotoxics and broad biologics that tamp down the entire immune system. They can help, but they are rarely curative. “They’re blunt instruments,” Regcell Inc. CEO Mike McCullar told BioWorld. “They can’t distinguish good immune cells and bad immune cells,” which is why many carry black-box warnings and must be taken for years, sometimes for life.

In idiopathic pulmonary fibrosis, the lung tissue thickens and stiffens through proliferation of fibroblasts and invasion by inflammatory cells. One of the drivers of these processes is the enzyme autotaxin, which produces the signaling molecule lysophosphatidic acid. Several inhibitors of autotaxin have been reported, which show varying degrees of clinical potential.

Anti-inflammatory compounds can alleviate many acute and chronic diseases, including autoimmune, cardiovascular and neurodegenerative disorders. However, many such compounds increase risk of numerous adverse events because they inhibit not only cyclooxygenase-2 (COX-2), which induces pathological inflammation, but also COX-1, which is important for renal and gastrointestinal function.