Infex Therapeutics announces positive phase IIa study results for RESP-X in NCFB patients colonised with Pseudomonas aeruginosa

Infex Therapeutics, a leader in critical-priority infectious diseases, with a broad and diverse pipeline of innovative best-in-class and first-in-class drug candidates to address the urgent global shortage of novel anti-infective treatments, has announced positive results from its phase IIa dose-ranging study evaluating RESP-X, a first-in-class anti-virulence monoclonal antibody, in non-cystic fibrosis bronchiectasis (NCFB) patients colonised with Pseudomonas aeruginosa (Pa).

The phase IIa study was designed to evaluate the safety, pharmacokinetics, immunogenicity, lung deposition and exploratory efficacy endpoints of RESP-X. The study met its primary and secondary objectives, demonstrating that RESP-X was safe and well tolerated in NCFB patients colonised with Pa. RESP-X demonstrated favourable pharmacokinetics and lack of immunogenicity supporting quarterly dosing. The study also showed encouraging early efficacy signals, including reduced exacerbation rates in Pa-positive patients and complete target coverage. These results build on the previously reported phase I, 32 healthy volunteer study and support the advancement of RESP-X into the next phase efficacy study.

“These highly encouraging phase IIa results continue to demonstrate that RESP-X is safe and well tolerated while showing promising efficacy signals in NCFB patients colonised with Pseudomonas aeruginosa,” said Dr Peter Jackson, CEO of Infex Therapeutics. “The excellent safety profile, favorable pharmacokinetics supporting quarterly dosing, complete target coverage, and reduced exacerbation rates provide strong support for advancing RESP-X into the next phase of clinical development. These results represent an important milestone for Infex and offer hope for NCFB patients colonised with Pa, a population with significant unmet medical need and no approved preventative treatment options.”

Prof Colm Leonard, chief clinical officer at Infex, commented: “I was delighted to share this exciting data on our novel anti-Pseudomonal therapy with the clinical and scientific community at the ATS. There is a lot of interest in RESP-X as a new approach to make a real difference to Pa-colonised patients with bronchiectasis.”

The randomised, double-blinded, placebo-controlled phase IIa study was conducted at the Liverpool University Hospitals NHS Foundation Trust Clinical Research Facility, UK, and evaluated two dose levels of RESP-X 6 mg/kg and 10 mg/kg across two cohorts in NCFB patients colonised with Pa.

RESP-X demonstrated an excellent safety profile across both dose levels tested in the phase IIa study. There were no severe or life-threatening treatment-emergent adverse events (TEAEs) related to the study drug, and no adverse events led to patient withdrawal from the study. All TEAEs potentially related to the study intervention were mild to moderate in nature, and the incidence of these events was not dose-responsive. Importantly, no infusion reactions, either systemic or at the infusion site, were observed after dosing with RESP-X.

The study confirmed favourable pharmacokinetic properties that support convenient quarterly dosing intervals. Pharmacokinetic profiles in NCFB patients aligned with healthy volunteer data from the phase I study, demonstrating dose-proportional increases in exposure across the dosing range. RESP-X exhibited a long half-life of 28.8 days, with the 10 mg/kg dose providing serum coverage over the PK/PD target necessary to support 3-monthly dosing intervals. Exposure in lung epithelial lining fluid (ELF) was confirmed by bronchoscopy and bronchoalveolar lavage at 48 hours post-dose in all RESP-X-treated patients, demonstrating good lung deposition. Additionally, no anti-drug antibodies (ADAs) were detected in blood samples from NCFB patients at any timepoint.

The study demonstrated complete target coverage and encouraging efficacy signals across multiple measures. All Pa isolates collected from patient sputum throughout the study encoded the RESP-X target (PcrV), and all target sequences identified were known to bind RESP-X. Pa-positive NCFB patients experienced fewer exacerbations from day 1 until the final study visit on day 180 compared with the previous 12 months before dosing, with a reduced exacerbation rate observed for Pa-positive patients.

The company plans to engage with regulatory authorities to pursue a next phase efficacy study evaluating the efficacy of RESP-X in NCFB patients colonised with Pseudomonas aeruginosa.

RESP-X is a first-in-class anti-virulence humanized IgG4 monoclonal antibody in-licensed from Japanese pharmaceutical company Shionogi. RESP-X targets Pseudomonas aeruginosa’s Type 3 Secretion System (T3SS), specifically the PcrV protein, a critical virulence mechanism by which Pa causes organ injury, evades the immune system and gains a foothold in humans.

RESP-X is initially being developed as a long-term treatment to reduce disease flares and exacerbations in NCFB patients colonised with Pseudomonas aeruginosa. The programme has potential for expansion into additional indications, including cystic fibrosis, COPD, asthma, and acute settings such as hospital and ventilator-acquired pneumonia, in addition to complicated urinary tract infection, burns, diabetic foot ulcers, and bloodstream infections due to Pa.

NCFB is a chronic and debilitating respiratory disease defined by irreversible and progressive dilatation of bronchi due to chronic bronchial inflammation. The disease is characterised by periods of stable disease punctuated by flare-ups, known as exacerbations, that increase in frequency and severity over the patient’s lifetime.

There are currently up to six million NCFB patients in major global markets, of which up to 30% have chronic Pa colonisation. Colonisation with Pa increases the severity of NCFB, leading to recurring episodes of debilitating and life-threatening infection. NCFB exacerbations are closely associated with acute bacterial infections, with Pa being one of the leading causes. In the most severe cases, patients have multiple exacerbations per year, resulting in high hospitalisation and mortality rates.

Despite its prevalence and severity, there are currently no licensed treatments for the prevention of infective exacerbations due to Pa colonisation in NCFB patients, representing a significant unmet medical need.

Pseudomonas aeruginosa is a difficult-to-treat, drug-resistant pathogen recognised by the WHO as a significant threat to human health. Pa is a leading cause of healthcare-associated infections and is particularly problematic in patients with chronic respiratory diseases, where it can establish persistent colonisation leading to recurrent, severe infections.

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