RLS-0071, a dual-targeting anti-inflammatory peptide - biomarker findings from a first in human clinical trial

Abstract Background RLS-0071 is a novel 15 amino acid peptide dual-targeting anti-inflammatory inhibitor of complement and neutrophil effectors. inhibits classical pathway activation at C1 blocks the enzymatic activity myeloperoxidase that leads to generation hypochlorous induces NETosis. This being developed for treatment neonatal hypoxic ischemic encephalopathy (HIE) neutrophilic pulmonary diseases. Methods was first in human clinical trial healthy volunteers assess safety pharmacokinetics single multiple ascending doses RLS-0071. Results were not associated with any clinically significant changes parameters, laboratory test results or ECG measurements. Adverse events similar between active drug placebo groups. The pharmacokinetic profile demonstrated dose proportionality two-compartment kinetics rapid tissue distribution. Exploratory biomarker target engagement assays dependent inhibition binding. Discussion/Conclusion shown be safe well-tolerated all tested distribution both myeloperoxidase. findings are supportive further development evaluation conditions such as HIE acute Trial registration ClinicalTrials.gov Identifier: NCT05298787 March 28, 2022. Retrospectively registered.