Late Breaking Abstract - Exciting phase 1 data on RESP-X, a novel monoclonal antibody targeting a key virulence mechanism of Pseudomonas aeruginosa, with potential as a treatment to reduce exacerbations in non-CF bronchiectasis

<bold>Introduction:</bold> <italic>Pseudomonas aeruginosa</italic> colonisation increases exacerbations & mortality in patients with non-cystic fibrosis bronchiectasis (NCFB). Current therapy has limited efficacy, & accompanying compliance & side effect issues. RESP-X is a novel monoclonal antibody targeting the type III secretion system of <italic>P. aeruginosa</italic>, a key virulence mechanism contributing to tissue damage & immune system evasion. We present first in human phase 1 data on RESP-X which was in licensed to INFEX Therapeutics after early development at Shionogi. <bold>Methods:</bold> A single ascending dose phase 1 study in healthy volunteers was carried out at the Liverpool University Hospitals clinical research facility. Four cohorts of 8 healthy volunteers (6 active, 2 placebo in each group) received single doses of RESP-X intravenously at 1mg/kg, 3 mg/kg, 6 mg/kg and 10 mg/kg. Primary outcomes were safety & pharmacokinetics, with exploratory endpoints looking for anti-drug antibodies & assessing anti-cytotoxicity effect of serum samples following IV dosing <bold>Results:</bold> There were no significant drug-related adverse effects at any of the dose levels. Half-life was >30 days. No significant anti-drug antibodies were detected. RESP-X maintains inhibition of <italic>P. aeruginosa</italic>-mediated cytotoxicity ex vivo. Long half-life supports Ph2 patient dosing at 3 month intervals <bold>Conclusion:</bold> RESP-X is safe with a long half-life & has potential as a treatment for patients with NCFB who are colonised with <italic>P. aeruginosa</italic> to reduce frequency & severity of exacerbations, & may facilitate eradication.