Pegipanermin (; developmental code names and proposed brand names DN-TNF, INB-03, LIVNate, Quellor XENP345, XPro1595) is a tumor necrosis factor ñ (TNFñ) inhibitor which is under development for the treatment of Alzheimer's disease, mild cognitive impairment, major depressive disorder, and other indications. It is described as having potential anti-inflammatory effects. It is administered by subcutaneous injection.
The drug is a protein and PEGylated variant of TNFñ that does not bind to the tumor necrosis factor receptors (TNF receptors) but instead binds to and forms heterotrimers with TNFñ and prevents TNFñ from activating the TNF receptors. However, pegipanermin is said to be selective for blocking TNFñ activation of the tumor necrosis factor receptor 1 (TNFR1) but not of the tumor necrosis factor receptor 2 (TNFR2). Whereas the non-selective TNFñ inhibitor etanercept suppressed hippocampal neurogenesis, learning, and memory in animals, pegipanermin did not do so, yet still inhibited neuroinflammation. Pegipanermin crosses the bloodâÂÂbrain barrier into the central nervous system.
As of October 2024, pegipanermin is in phase 2 clinical trials for Alzheimer's disease, mild cognitive impairment, and major depressive disorder. It is in the preclinical stage of development for HER2-positive breast cancer. No recent development has been reported for other neurodegenerative disorders, non-alcoholic steatohepatitis, or solid tumors. Development was discontinued for Parkinson's disease and COVID-19 respiratory infections.