As reported on PharmaBiz, Infex Therapeutics has announced encouraging results from a phase IIa clinical study of RESP‑X, an investigational monoclonal antibody being developed for patients with non‑cystic fibrosis bronchiectasis (NCFB) chronically colonised with Pseudomonas aeruginosa. The data suggest the first‑in‑class anti‑virulence therapy is safe, well tolerated, and shows early signs of clinical benefit in a population with limited treatment options.
The randomized, double‑blind, placebo‑controlled study assessed two intravenous dose levels of RESP‑X (6 mg/kg and 10 mg/kg) in NCFB patients with confirmed P. aeruginosa colonisation. Conducted at Liverpool University Hospitals NHS Foundation Trust in the UK, the trial was designed to evaluate safety, pharmacokinetics, immunogenicity, lung deposition, and exploratory efficacy outcomes.
According to Infex, all primary and secondary endpoints were met. RESP‑X demonstrated a favorable safety profile across both dose cohorts, with no severe or life‑threatening treatment‑emergent adverse events attributed to the study drug. No patients discontinued treatment due to adverse events, and reported reactions were mild to moderate and not dose dependent. Importantly, no infusion‑related reactions were observed.
Pharmacokinetic analyses showed dose‑proportional exposure and a long half‑life of approximately 29 days, supporting a quarterly dosing regimen. Drug levels in patients with bronchiectasis were consistent with those previously observed in healthy volunteers during phase I evaluation. Lung delivery was confirmed through bronchoscopy and bronchoalveolar lavage, with measurable concentrations detected in epithelial lining fluid within 48 hours of dosing. No anti‑drug antibodies were identified at any point during the study, indicating low immunogenicity.
Beyond safety and pharmacology, the trial produced promising early efficacy signals. All P. aeruginosa isolates obtained from patient sputum expressed the RESP‑X target, the PcrV protein, a key component of the pathogen’s type III secretion system. Patients colonised with P. aeruginosa experienced fewer exacerbations during the six‑month study period compared with the year prior to treatment, suggesting a potential role for RESP‑X in reducing disease flares.
Company leadership described the findings as an important development milestone. Infex executives highlighted the combination of safety, sustained exposure, full target coverage, and reduced exacerbation frequency as strong justification for advancing RESP‑X into a larger efficacy trial. The company plans to engage with regulatory authorities to define the next phase of clinical development.
RESP‑X is a humanized IgG4 monoclonal antibody in‑licensed from Shionogi and is designed to neutralize P. aeruginosa virulence rather than directly kill the pathogen. By targeting the PcrV protein, RESP‑X interferes with bacterial mechanisms responsible for tissue damage and immune evasion, offering a novel approach that may reduce selective pressure for antimicrobial resistance.
NCFB is a chronic respiratory condition marked by irreversible airway dilation and recurrent infections. Up to six million patients are affected across major global markets, with approximately one‑third chronically colonised by P. aeruginosa. Colonisation is associated with more frequent exacerbations, increased hospitalisation, and higher mortality rates. Despite the burden of disease, there are currently no approved therapies specifically indicated to prevent P. aeruginosa‑related exacerbations in this population.
In addition to NCFB, Infex is exploring RESP‑X’s potential across a range of other indications, including cystic fibrosis, chronic obstructive pulmonary disease, asthma, and acute infections such as ventilator‑associated pneumonia.
