Investigation of monoclonal antibody CSX-1004 for fentanyl overdose.

ABSTRACT: The opioid crisis in the United States is primarily driven by the highly potent synthetic opioid fentanyl leading to >70,000 overdose deaths annually; thus, new therapies for fentanyl overdose are urgently needed. Here, we present the first clinic-ready, fully human monoclonal antibody CSX-1004 with picomolar affinity for fentanyl and related analogs. In mice CSX-1004 reverses fentanyl antinociception and the intractable respiratory depression caused by the ultrapotent opioid carfentanil. Moreover, toxicokinetic evaluation in a repeat-dose rat study and human tissue cross-reactivity study reveals a favorable pharmacokinetic profile of CSX-1004 with no safety-related issues. Using a highly translational non-human primate (NHP) model of respiratory depression, we demonstrate CSX-1004-mediate

SUBMITTER: Bremer PT 

PROVIDER: S-EPMC10698161 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature