The challenges of developing an effective vaccine against S. aureus due to the different strains and evasion mechanisms have been well documented. Clinical results with vaccines and therapeutic IgG antibodies suggest failure is a result of S. aureus’ evasion of humoral immunity.
The Company has completed its Phase I/II study evaluating dosing, safety and efficacy of its novel antibody, 514G3. 514G3 was developed from a healthy human donor with natural antibodies effective at neutralizing Methicillin-resistant Staphylococcus aureus (MRSA) and non-MRSA forms of Staphylococcus aureus (S. aureus). Patients with infections due to S. aureus typically have severe complications, extended hospital stays, and a 30-day mortality of approximately 20 percent.
514G3 works to eliminate the principle immune evasion mechanism of the bacteria, allowing white blood cells to detect and destroy the bacteria. 514G3 has potential to treat all strains of MRSA and can be used without consideration for strain-specific resistance to various antibiotics. As a True Human monoclonal antibody, 514G3 is expected to be well tolerated without the side effects or risks of antibiotics, including the lack of risk of antibiotic resistance. This proprietary antibody received Fast Track Designation by the FDA for the treatment of all forms of S. aureus infections, including Methicillin-resistant S. aureus (MRSA). Top line results from the Phase I/II study were announced in April 2017 and reported a reduction in adverse events and shorter hospitalization associated with the 514G3 therapy, even with 514G3-treated subjects tending to be sicker than those receiving placebo. Research involving 514G3 was published in January 2018 in the journal PLOS ONE in a manuscript titled, “A Natural Human Monoclonal Antibody Targeting Staphylococcus Protein A Protects Against Staphylococcus aureus (S. aureus) Bacteremia.”
The Company is now planning further clinical development of the 514G3 antibody. XBiotech plans to evaluate 514G3 as a prophylaxis to reduce the risk of S. aureus infections in patients being treated with hemodialysis for kidney failure. Patients undergoing hemodialysis are at significant risk for life-threatening S. aureus bacteremia. About one-half million patients currently receive over 50 million dialysis treatments annually in the U.S. Patients on hemodialysis have about a 20% one-year mortality risk while being treated. Infections are the second leading cause of death in these patients, and S. aureus infections are the main cause of infectious morbidity and mortality. The Company is currently planning to use 514G3 as a prophylaxis to reduce S. aureus risk in hemodialysis patients, with a planned clinical study launch in 2019.