Alaxia has joined the European consortium iABC to accelerate the development of ALX-009, an investigational inhaled antibiotic for multi-drug resistant lung infections in people with cystic fibrosis (CF).
Under the partnership, Alaxia will have support for setting up clinical trials and recruiting patients, and will gain access to expertise on antimicrobial agents from iABC members.
The iABC project (inhaled Antibiotics in Bronchiectasis and Cystic Fibrosis) joins together academic, industrial, public, and non-profit organizations in Europe, and is advancing the development of two inhaled antibiotics for patients with CF and bronchiectasis, a population at higher risk of respiratory infections.
Frequently, these infections are caused by antibiotic-resistant bacteria and are life-threatening, being the main cause of disease and death among patients with CF and bronchiectasis.
“Alaxia is honored to have been selected to join the iABC project on fighting antimicrobial resistance in patients with lung diseases,” Philippe Bordeau, Alaxia’s vice president of innovation and business development, said in a press release.
“Our ALX-009 candidate has demonstrated strong potential as a therapy against antibiotic resistant lung infections in cystic fibrosis. We look forward to collaborating with iABC members on advancing this drug candidate, and discussing this therapeutic opportunity with new financial partners,” Bordeau said.
ALX-009 is a first-in-class investigational therapy that contains two antimicrobials, hypothiocyanite (OSCN–) and lactoferrin (LF), which are naturally present in the airway liquid of healthy people, as part of the body’s first line of defense against microbes — the innate immune system. This defense system is defective in people with CF, contributing to their greater susceptibility to bacterial infections.
By providing both molecules, ALX-009 will help restore the natural capacity of the lung to fight infections. It works on multiple targets, a mode of action particularly effective against multi-drug resistant gram-negative bacteria, known as “super bugs,” for which no treatments are available.
Tests done in cell and animal models showed that multi-drug resistant bacteria isolated from the airways of CF patients are fully sensitive to ALX-009, including Burkholderia species, Pseudomonas aeruginosa, Achromobacter xylosoxidans, and Stenotrophomonas maltophilia.
The lungs of CF and bronchiectasis patients have large amounts of sticky mucus that cover the surface of the airways (epithelium). In this environment, bacteria get together to form biofilms that facilitate their survival. Both sticky mucus and biofilms are complex mixtures that reduce the effectiveness of antibiotics.
In contrast, ALX-009 efficacy is not altered by biofilms or thick mucus, and no increase in dose is required to maintain its bacteria-killing activity. So far, tests indicate that bacteria are unable to become resistant to ALX-009.
ALX-009 is being tested as an inhalable solution administered through nebulization, to be used as a standalone therapy or as an add-on treatment to antibiotics.
The safety, tolerability, and pharmacokinetics (uptake, distribution, and elimination in the body) of ALX-009 and each of its compounds, OSCN and LF, are under evaluation in a Phase 1 dose-escalation study (NCT02598999). The first and second part of the study, which have been completed, tested different doses of OSCN or LF alone, or in combination with ALX-009, versus placebo in healthy male volunteers.
The study is in its final parts evaluating multiple doses of each of the active substances or ALX-009 in patients with CF or non-CF bronchiectasis, compared to placebo.
According to Alaxia, patient enrollment in Phase 2a trials testing ALX-009’s effectiveness is planned to start in 2020.