Alderley Park, Cheshire, U.K. Infex Therapeutics, a leading anti-infectives specialist, announces that the first patient has been dosed in a Phase IIa clinical trial for RESP-X, a new anti-virulence therapy to treat Pseudomonas aeruginosa (Pa) infections in non-cystic fibrosis bronchiectasis (NCFB) patients. Pa is a critical factor in this chronic and debilitating respiratory disease leading to recurring severe episodes of life-threatening infection, for which there are currently no approved preventative treatments.

The Phase IIa trial is a 12 patient, single centre, double-blind, placebo-controlled, dose-ranging study to evaluate the safety, initial efficacy and determine the optimal dosing of RESP-X ahead of a wider Phase IIb efficacy study. The study is taking  place at the NIHR Clinical Research Facility in Liverpool University NHS Foundation Trust and will assess two doses of RESP-X at 6mg/kg and 10mg/kg.

RESP-X is a first-in-class anti-virulence antibody targeting chronic Pa bacterial infections in respiratory diseases. RESP-X is initially being developed as a long-term treatment to reduce disease flares/exacerbations in NCFB patients colonised with Pa, a chronic and debilitating respiratory disease. Colonisation with Pa increases the severity of NCFB, leading to recurring episodes of debilitating and life-threatening infection called exacerbations. There are currently up to six million NCFB patients in major global markets, of which up to 30% have chronic Pa colonisation. Despite its prevalence and severity. Despite its prevalence and severity, there are currently no licensed treatments for the prevention or reduction of infective exacerbations due to Pa colonisation in NCFB patients.  There is also potential to expand the development of RESP-X into cystic fibrosis and COPD in addition to acute settings such as hospital and ventilator-acquired pneumonia and blood stream infections due to Pa.

Dr Peter Jackson, Executive Director of Infex Therapeutics, said: “The start of the phase IIa study for RESP-X in NCFB patients is an important milestone for Infex, which will provide valuable insights on dosing as well as early signs of efficacy in patients ahead of a larger phase II study. RESP-X is a promising new treatment option for NCFB patients colonised with Pa, a chronic and debilitating disease that impacts millions of patients around the world for which there are currently no approved preventative treatment options. The Phase I data demonstrated an excellent safety and pharmacokinetics profile and I look forward to progressing RESP-X through phase II.

About RESP-X

In-licensed from Japanese pharma company Shionogi, RESP-X is a novel humanised monoclonal antibody designed to help the body tackle Pa infections, a hard-to-treat, drug-resistant pathogen recognised by the WHO as a critical threat to human health.

RESP-X does not kill the bacteria directly but deactivates a critical virulence mechanism, enabling the patient’s own immune system to more efficiently fight the infection. It blocks Pa exotoxin delivery by the Pa type III secretion system (T3SS). The T3SS is a critical mechanism by which Pa causes organ injury, evades the immune system and gains a foothold in humans. By blocking this virulence system RESP-X downgrades the ability of Pa to attack human tissues and restores the ability of immune cells to control Pa.

NCFB is a disease defined by an irreversible and progressive dilatation of bronchi due to chronic bronchial inflammation. It is characterised by periods of stable disease, with flare-ups, known as “exacerbations”, that increase in frequency and severity over the patient’s lifetime. There are at least eight million NCFB patients in major markets, of which around 30% have chronic Pa colonisation. In the UK, the British Lung Foundation estimates there are in excess of 30,000 NCFB patients.

NCFB exacerbations are closely associated with acute bacterial infections, with Pa being one of the leading causes. In most severe cases, patients have multiple exacerbations per year, resulting in high hospitalisation and mortality rates. As the disease progresses there are serious economic impacts for patients and healthcare systems.