Infex Therapeutics has announced the dosing of the first patient in a Phase IIa clinical trial for RESP-X, a novel anti-virulence therapy targeting Pseudomonas aeruginosa (Pa) infections in non-cystic fibrosis bronchiectasis (NCFB) patients. This study marks a significant step forward in addressing a critical unmet need for preventative treatments in this patient population.
The Phase IIa trial is designed as a single-center, double-blinded, placebo-controlled, dose-ranging study involving 12 patients. Conducted at the NIHR Clinical Research Facility in Liverpool University NHS Foundation Trust, the trial will evaluate the safety, initial efficacy, and optimal dosing of RESP-X. Two doses of RESP-X, 6mg/kg and 10mg/kg, will be assessed.
RESP-X: A Novel Approach to Targeting Pa Infections
RESP-X represents a first-in-class anti-virulence antibody developed to combat chronic Pa bacterial infections in respiratory diseases. Initially, it is being developed as a long-term treatment to reduce disease flares and exacerbations in NCFB patients colonized with Pa. Colonization with Pa exacerbates the severity of NCFB, leading to recurring episodes of debilitating and life-threatening infections. Currently, there are no licensed treatments specifically designed to prevent or reduce infective exacerbations caused by Pa colonization in NCFB patients.
According to Infex Therapeutics, there are up to six million NCFB patients in major global markets, with up to 30% having chronic Pa colonization. The potential exists to expand the development of RESP-X into cystic fibrosis and COPD, as well as acute settings such as hospital and ventilator-acquired pneumonia and bloodstream infections caused by Pa.
Mechanism of Action
In-licensed from Shionogi, a Japanese pharmaceutical company, RESP-X is a humanized monoclonal antibody engineered to assist the body in combating Pa infections. Pa is a difficult-to-treat, drug-resistant pathogen recognized by the WHO as a critical threat to human health. RESP-X functions by deactivating a critical virulence mechanism, enabling the patient's immune system to more effectively combat the infection. It achieves this by blocking Pa exotoxin delivery via the Pa type III secretion system (T3SS). The T3SS is a crucial mechanism by which Pa causes organ injury, evades the immune system, and establishes itself in humans. By blocking this virulence system, RESP-X reduces the ability of Pa to attack human tissues and restores the ability of immune cells to control Pa.
NCFB Disease Burden
NCFB is characterized by irreversible and progressive dilatation of the bronchi due to chronic bronchial inflammation. The disease is marked by periods of stability interspersed with flare-ups, known as exacerbations, which increase in frequency and severity over time. There are at least eight million NCFB patients in major markets, with approximately 30% chronically colonized with Pa. In the UK, the British Lung Foundation estimates there are over 30,000 NCFB patients.
NCFB exacerbations are closely linked to acute bacterial infections, with Pa being a leading cause. In severe cases, patients may experience multiple exacerbations per year, leading to high rates of hospitalization and mortality. As the disease progresses, it places a significant economic burden on patients and healthcare systems.
Dr. Peter Jackson, CEO of Infex Therapeutics, stated, "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."
