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