A new anti-virulence therapy, RESP-X, treating Pseudomonas aeruginosa (Pa) infections in non-cystic fibrosis bronchiectasis (NCFB) patients has been given to the first subjects in a trial run by Infex Therapeutics.
Infex Therapeutics is an anti-infectives company and announced the first subjects were dosed in the phase 1 study in healthy volunteers evaluating the company’s lead drug candidate RESP-X.
Pa is a critical factor in the chronic and debilitating respiratory disease NCFB, leading to recurring severe episodes of life-threatening infection, for which there are currently no approved preventative treatments.
The phase 1 study is a 32 subject, single center, first-in-human, double-blind, placebo-controlled, single ascending dose study, administered intravenously to cohorts of healthy volunteers. It will evaluate the safety, tolerability, pharmacokinetic, pharmacodynamic and immunogenicity profile of RESP-X in healthy subjects.
Profile of RESP-X in healthy subjects
Top line results from the RESP-X phase 1 study are expected to be available in the first half of 2023 and will be used to inform further clinical trials in NCFB patients to reduce the frequency and severity of Pa-mediated exacerbations.
Peter Jackson, executive director of Infex Therapeutics, said: “The start of the phase 1 study for our RESP-X program is a significant milestone for Infex, marking our transition from a preclinical to a clinical stage biotechnology company.
“The study will assess the safety and tolerability of RESP-X in a cohort of healthy volunteers and will inform the dosing in the subsequent trials with NCFB patients. RESP-X has huge potential to improve the outcomes for millions of patients worldwide who suffer from Pa colonized NCFB, a chronic and debilitating condition for which there are currently no approved preventative treatments.”
The study, which is being conducted at NIHR Liverpool Clinical Research Facility, part of the Liverpool University Hospital, is the culmination of a work program supported by a £2m grant awarded by the Infection Innovation Consortium (iiCON), a center for infection innovation and research and development.
Growing concern for healthcare systems
Richard Fitzgerald, director of the NIHR Liverpool Clinical Research Facility, said: “There is a desperate need for new treatment options in the escalating fight against antimicrobial resistance, which is a serious and growing concern for global healthcare systems.
“We are delighted to be working with Infex to leverage our experience and expertise in early-stage clinical trials to progress the clinical development of RESP-X, a promising and important new treatment option against Pa, a devastating WHO critical-priority infectious disease, which impacts millions of patients around the world.”
In-licensed from Japanese pharma company Shionogi, RESP-X is a novel humanized monoclonal antibody designed to help the body tackle Pa infections, a hard-to-treat, drug-resistant pathogen recognized by the WHO as a critical threat to human health. It does not kill the bacteria directly but deactivates a critical virulence mechanism, enabling the patient’s own immune system to clear the infection. NCFB is a disease defined by an irreversible and progressive dilatation of bronchi due to chronic bronchial inflammation.
RESP-X promising and important
It is characterized by periods of stable disease, with flare-ups, known as “exacerbations,” which 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 colonization. In the U.K., 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 hospitalization and mortality rates. As the disease progresses there are serious economic impacts for patients and healthcare systems.