RATIONALE: Neutrophils are critical effector cells in many lung diseases. RLS-0071 is a small peptide inhibitor of first-response humoral and cellular inflammation targeting the complement system and neutrophil effectors, respectively. RLS-0071 substantially inhibits neutrophil inflammation in animal models. Protocol RLS-0071-103 (NCT05351671) was an inhaled LPS proof-of-mechanism (POM) study to demonstrate RLS-0071 translatability from animal disease models to humans.

METHODS: Healthy subjects (n=30) inhaled LPS followed by IV treatment at 0.5, 8 and 16 hours. Participants were randomized 1:1:1 into three treatment arms, saline placebo, RLS-0071 at low-dose or high-dose. Key endpoints were adverse events for safety assessment and biomarker analyses of induced sputum samples taken at baseline and then 6 and 24 hours after LPS inhalation.

RESULTS: Safety signals were similar between groups. Median fold-increases from baseline in sputum neutrophil counts at 6 and 24 hours post LPS for placebo, RLS-0071 low-dose and high-dose were 22.8, 13.4, 7.1 and 14.5, 8.2, 3.5, respectively. Neutrophil percentage and IL-1ß were lower at 24 hours in the low-dose group compared with placebo (P<0.1). Sputum neutrophil elastase change from baseline at 6 hours in the low-dose arm was inhibited compared with placebo (P=0.02) and sustained at 24 hours (P=0.02).

CONCLUSION: RLS-0071 demonstrated proof-of-mechanism in humans decreasing neutrophil-mediated inflammation in the lungs for the low-dose and high-dose arms out to 24 hours. This study informs the further clinical development of RLS-0071 for neutrophil-mediated diseases.