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Feb 12, 2015
 |  BC Innovations  |  Targets & Mechanisms

High five for Arsanis

Arsanis finds neutralizing antibody against five Staphylococcus aureus toxins

Researchers at Arsanis Inc. and Adimab LLC have identified an antibody that simultaneously neutralizes five Staphylococcus aureus toxins - defying the odds of hitting such diverse structures by fishing out an exposed conserved patch. While Arsanis is moving this compound towards the clinic, Adimab is doubling down on the screening strategy and hopes it will yield cross-neutralizing antibodies for other indications as well.

Eszter Nagy, president and CEO of Arsanis, told BioCentury hitting multiple toxins together could extend protection against S. aureus to antibiotic-resistant strains, while preventing tissue damage caused by all the strains. The antibodies in clinical testing neutralize only one toxin, she said, but blocking the toxins together should produce much greater efficacy because the toxins act on different subsets of cells.

The five toxins include aHL, a hemolysin that is toxic to lung and epithelial cells, and four leukocidins that are cytotoxic to red and white blood cells.

"What is exceptional about this antibody is that it also protects the immune cells which are lysed by the bi-component leukocidins," said Nagy. "We compared the potency of the cross-reactive antibody versus the aHL-specific antibody and we see exceptional potency and a great difference because the other antibody is not able to protect phagocytic cells."

Dane Wittrup, a co-author on the study and co-founder of Adimab, agreed the multi-pronged approach was a real advantage. "Because there are so many homologs if we don't block them all we have nothing," he said.

Wittrup is also a professor of chemical engineering and biological engineering at Massachusetts Institute of Technology and associate director of the Koch Institute for Integrative Cancer Research at MIT.

AstraZeneca plc has MEDI4893, an anti-aHL antibody, in Phase II testing for methicillin-resistant S. aureus(MRSA) infection and hospital-acquired pneumonia (HAP) in mechanically ventilated adult subjects. Aridis Pharmaceuticals LLC has AR-301, a mAb against S. aureus aHL, in Phase I for Staphylococcusinfection.Arsanis was spun out of Adimab in 2010 to develop antibodies against infectious diseases identified using Adimab's yeast-based screening platform. Last June, Arsanis exercised its option to license rights to develop and commercialize antibodies identified by Adimab against multiple undisclosed targets.

You get what you screen for

To select for a widely cross-reactive antibody, the team used Adimab's high diversity IgG libraries displayed on yeast cells, and crafted a screening campaign to find rare antibodies that hit...

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