B15-04 Pegtarazimod (RLS-0071) Decreases Supplemental Oxygen Need in a Phase 2 Proof-of-Concept Trial in Hospitalized Participants With Acute Exacerbation of Chronic Obstructive Pulmonary Disease (AE-COPD)

Abstract Rationale AE-COPD is a major cause of hospitalization 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 evaluating the safety and tolerability of pegtarazimod for treatment of adults with AE-COPD was conducted and clinical results are reported. Methods The study was a randomized, double-blind, placebo-controlled trial in hospitalized participants with AE-COPD to evaluate 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 as an add-on therapy to usual management. 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. Improvement in oxygen utilization assessed by change in fraction of inspired oxygen (FiO2), oxygen saturation (O2 sat), respiratory rate and ROX index were evaluated. The ROX index (Respiratory rate - OXygenation) was obtained by the calculation of SpO2/FiO2/respiratory rate (RR); this index is used to predict intubation in patients with acute hypoxic respiratory failure - higher values designate an improvement in oxygenation and work of breathing. 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 required less supplemental oxygen (decreased FiO2 levels) during hospitalization that endured out to 60 days. Patients on study drug showed increased blood oxygen saturation and ROX index compared to placebo. Consistent with pegtarazimod’s mechanism of action, when patients were stratified by high vs low neutrophil to lymphocyte ratio (NLR), with a high NLR consistent with a strongly neutrophil driven AECOPD event (NLR9), patients with NLR9 needed less supplemental oxygen, showed larger decreases in respiratory rate and greater increases in the ROX index compared to patients with a NLR9. Conclusions The data from this clinical trial demonstrated that pegtarazimod was safe and well tolerated in AE-COPD patients and showed durable improved oxygen utilization metrics compared to placebo. Additionally, pegtarazimod showed the most beneficial impact in respiratory outcomes for patients with an NLR9 in line with pegtarazimod’s mechanism of action. An abstract reporting pegtarazimod’s reduction of inflammatory biomarkers in these patients will also be presented. This abstract is funded by: ReAlta Life Sciences