B15-05 Pegtarazimod (RLS-0071) Reduces Inflammatory Biomarkers in Hospitalized Participants With Acute Exacerbation of Chronic Obstructive Pulmonary Disease (AE-COPD)

Abstract Rationale AE-COPD is a major cause of hospital admission and mortality contributing to long-term decline in lung function, physical capacity, and quality of life. Pegtarazimod is dual-acting, anti-inflammatory peptide that inhibits the classical pathway of complement and neutrophil inflammatory effectors myeloperoxidase (MPO) and neutrophil elastase (NE). A Phase 2 study to evaluate the safety and tolerability of pegtarazimod in the treatment of adults with AE-COPD was conducted and exploratory biomarker results are reported. Methods The study was a randomized, double-blind, placebo-controlled trial in hospitalized participants with AE-COPD to evaluate the safety, tolerability and preliminary efficacy of RLS-0071 compared to placebo (ClinicalTrials.gov study #NCT06175065). Eligible participants were randomized 1:1 to receive either pegtarazimod or placebo. Dosing regimen was 10mg/kg drug given IV, 3 times a day for at least 3 days and up to 5 days. Participants were followed for efficacy and safety for 30 and 60 days after the final dose. Changes in plasma chemokines (MIP-1b, MCP-1, CXCL-5, CCL22), cytokine (IL-8 and IL1-ra) and neutrophil biomarker (neutrophil elastase and MPO) levels were evaluated. Results A total of 21 patients were enrolled with 11 receiving placebo and 10 receiving study drug. Pegtarazimod was well tolerated. Compared to placebo group, patients receiving pegtarazimod showed a reduction in neutrophil proinflammatory cytokine (IL-8), upregulation of anti-inflammatory IL-RA and reduction in macrophage chemokines (MIP-1b, MCP-1, CXCL-5, CCL22). For participants with high neutrophil-to-lymphocyte ratios, indicative of strongly neutrophil driven AE-COPD event, levels of neutrophil inflammatory mediators MPO and NE were reduced for pegtarazimod compared to placebo. Conclusions The data from this clinical trial demonstrated that pegtarazimod was safe and well tolerated in AE-COPD patients. Compared to patients receiving placebo, improvements in inflammatory biomarkers were observed, consistent with pegtarazimod mechanisms of action as well as consistent with results from prior animal model studies and a human inhaled LPS challenge study. An abstract reporting pegtarazimod’s effect on clinical outcomes in these patients will also be presented. This abstract is funded by: ReAlta Life Sciences