Broadly Neutralizing Cross-Reactive Antibody Targets Five Staphylococcus aureus Cytotoxins


Arsanis, Inc. scientists and their collaborators at Adimab, LLC have described a unique monoclonal antibody with the potential to treat Staphylococcus aureus (S. aureus) infections through the simultaneous neutralization of multiple key toxins produced by S. aureus, including alpha-hemolysin and four additional leukocidins. The findings are published online this week in the journal mAbs and demonstrate superior in vitro potency compared to antibodies targeting alpha-hemolysin alone. The mAb also shows high protective efficacy from lethal S. aureus infections in several animal models.

Arsanis also noted the recent online publication in the American Journal of Respiratory and Critical Care Medicine describing alpha-hemolysin expression as a novel predictive biomarker for S. aureus ventilator-associated pneumonia (VAP) enabling the possibility to identify at risk patients and use prophylactic approaches to prevent the disease.

"The growing problem of S. aureus antibiotic resistance and the inability of antibiotics to counteract cytotoxins involved in the bacterium's pathogenesis of disease call for novel therapeutic approaches," says Eszter Nagy, MD, PhD, president and chief scientific officer of Arsanis, lead author of the new publications. "We believe that targeted therapies such as passive immunization with mAbs, which are much less likely to cause resistance, are the way of the future."

Efforts by others have focused on neutralizing alpha-hemolysin, a major virulence factor that damages several types of human cells. However, recent findings suggest that the concerted actions of several cytotoxins, including the bi-component leukocidins, also play important roles in staphylococcal pathogenesis. Arsanis' research team has drawn on its extensive infectious disease experience and the company's partnership with Adimab LLC to develop this unique cross reactive antibody which is incorporated in Arsanis' lead product candidate, ASN100.

"VAP contributes to prolonged ventilation and stay in the intensive care unit, increased healthcare costs, and unacceptably high patient mortality," says Nagy. "Early detection of these at-risk patients, potentially through novel point-of-care diagnostics, will lead to better clinical management of VAP, and the use of prophylactic approaches such as Arsanis' pioneering ASN100 antibody product."

ASN100 is currently in preclinical development for GMP manufacture with a leading contract research organization, and Arsanis expects to begin human clinical trials with ASN100 in 2015. Further preclinical programs in Arsanis' pipeline target multidrug-resistant Gram-negative nosocomial infections and severe community-acquired infections.

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