AR-105: Broadly Active Human Monoclonal Antibody (mAb) Against Pseudomonas aeruginosa
The Gram negative bacterium Pseudomonas aeruginosa is one of the most important public health pathogens and is associated with a number of difficult-to-treat infections such as pneumonia, bacteremia, and cystic fibrosis lung infection. AR-105 (Aerucin®) is a broadly active, fully human IgG1 monoclonal antibody targeted against P. aeruginosa alginate, a widely distributed cell surface polysaccharide involved in surface adhesion, biofilm formation, and protection against the human immune system. AR-105 exhibits a broad recognition to diverse, unrelated P. aeruginosa clinical isolates due to the ubiquitous nature of the alginate surface polysaccharide. AR-105’s mechanism of action is different from mechanisms of antibiotic resistance, and is effective against a broad collection of P. aeruginosa clinical isolates tested.
AR-105 effectively protected against lethal challenges of a variety of P. aeruginosa strains in mouse models of acute pneumonia and bacteremia. AR-105 is also shown to be effective when used in combination with standard of care antibiotics in P. aeruginosa infection models. This mAb candidate is being developed as first-line adjunctive therapy to standard of care antibiotics, and has been granted Fast-Track designation by the FDA. AR-105 has successfully completed a Phase 1 clinical trial in 16 healthy volunteers, demonstrating safety up to doses of 20 mg/kg. A worldwide Phase 2 trial of AR-105 in ventilator associated pneumonia patients infected with P. aeruginosa was initiated in the second quarter of 2017 and is actively enrolling patients. This clinical study is expected to be completed in mid-2019.