Amos Baruch, Chin Wong, Leslie W Chinn, Anjali Vaze, Junichiro Sonoda, Thomas Gelzleichter, Shan Chen, Nicholas Lewin-Koh, Linda Morrow, Suresh Dheerendra, Richard Boismenu, Johnny Gutierrez, Eric Wakshull, Maria E Wilson, Puneet S Arora
Fibroblast growth factor 21 (FGF21) controls metabolic organ homeostasis and eating/drinking behavior via FGF receptor 1/Klothoβ (FGFR1/KLB) complexes expressed in adipocytes, pancreatic acinar cells, and the nervous system in mice. Chronic administration of recombinant FGF21 or engineered variants improves metabolic health in rodents, nonhuman primates, and humans; however, the rapid turnover of these molecules limits therapeutic utility. Here we show that the bispecific anti-FGFR1/KLB agonist antibody BFKB8488A induced marked weight loss in obese cynomolgus monkeys while elevating serum adiponectin and the adipose expression of FGFR1 target genes, demonstrating its action as an FGF21 mimetic...
November 17, 2020: Proceedings of the National Academy of Sciences of the United States of America