To study the safety of novel peptide, RLS-0071 in healthy human volunteers. RLS-0071 is a 15 amino acid peptide that both inhibits humoral inflammation by blocking classical pathway complement activation and cellular inflammation by blocking the neutrophil effectors myeloperoxidase (MPO) and neutrophil extracellular traps (NETs).

RLS-0071 is being developed to treat neonatal hypoxic-ischemic encephalopathy (HIE) - in animal models of HIE RLS-0071 demonstrates neuroprotection with decreased brain infarction size, decreased neuronal death and improved long-term cognitive outcome (PMID: 34591905).

RLS-0071 was administered to healthy adult volunteers in both single ascending doses (SAD) and multiple ascending doses (MAD). Fifty-six were enrolled; forty-two were dosed with RLS-0071 across seven dosing cohorts in a 6:2 ratio of active:placebo. The maximum single dose tested was 120 mg/kg IV and the maximum multiple dose tested was 40 mg/kg IV every eight hours x 9 doses.

There were no deaths, SAEs, infusion-related reactions (IRRs), or treatment-related AEs. There were no changes in individual safety laboratory parameters (hematology, chemistry, and urinalysis), vital signs, or ECGs. No TEAEs were identified. No drug-antibodies were found in MAD subjects and 3 positive samples in SAD subjects were consistent with false-positives. No autoantibodies were detected. Biomarker data and target engagement assays demonstrated time-limited dose responses for humoral and cellular-based inflammatory effectors with return to baseline.   

RLS-0071 demonstrated excellent safety profiles in healthy human volunteers.  Pharmacodynamic testing confirmed target engagement and biomarker changes consistent with known mechanisms of action for this dual-targeting anti-inflammatory peptide. In light of confirmed RLS-0071 based neuroprotection in animal models of HIE and its now confirmed excellent safety profile in healthy human volunteers, this peptide appears safe and should be considered for human studies as an intervention to decrease neurological injury from HIE.