oral protein-complex 1 (OXPHOS) inhibitor
200-800 mg QD, phase I, cancer/IPF
from metformin
J. Pharmacol. Exp. Ther.
ImmunoMet Therapeutics
The ImmunoMet OXPHOS modulator (PC1 inhibitor), IM156, is a derivative of the long-used biguanide diabetes drug, metformin, that appears to have activity in lung fibrosis models. The therapeutic hypothesis for IPF is that myofibroblasts play an essential role in extracellular matrix remodeling and fibrogenesis that lead to loss of pulmonary function. A complex process of metabolic reprogramming is critical to the myofibroblast phenotype and disruption of myofibroblast metabolic pathways may have anti-fibrotic effects. A phase I dose escalation study was completed in cancer patients and there are plans to conduct a Ph. II study in IPF.