Two recent publications by the biotech company Arsanis confirmed that the two human antibodies ASN-1 and ASN-2 that make up Arsanis’ lead compound ASN100 effectively target infections with the bacteria Staphylococcus aureus (S. aureus), one of the most common causes of pneumonia.
S. aureus pneumonia is particularly difficult to treat since the microorganism releases multiple toxins that current antibiotics are unable to neutralize. The toxins damage cells lining the airways and destroy immune cells that are needed to fight the infection, leading to a high mortality rate associated with the disease. ASN100 is designed to neutralize six of the toxins believed to be crucial in pneumonia.
The first study, “Improved protection in a rabbit model of CA-MRSA necrotizing pneumonia upon neutralization of leukocidins in addition to alpha-hemolysin,” published in the journal Antimicrobial Agents and Chemotherapy, focused on the ASN-1 antibody.
Researchers used a rabbit model of S. aureus pneumonia to show that the antibody neutralized five of the six toxins and protected the animal from the negative effects of the infection. The study also demonstrated that mice are unsuitable for the study of these toxins because they are insensitive to them. Rabbits, on the other hand, react to the toxins similarly to humans.
The second study, “Context matters: The importance of dimerization-induced conformation of the LukGH leukocidin of Staphylococcus aureus for the generation of neutralizing antibodies,” published in the journal mAbs, described Arsanis’ path to the discovery of ASN-2, the second antibody that targets the last of the six toxins.
Dr. Eszter Nagy, MD, PhD, co-founder and chief scientific officer at Arsanis, said in a news release that she believes the combined action of the two antibodies position ASN100 as the only antibody product in development that can treat all strains of S. aureus causing serious pneumonia.
“ASN100 has the potential to offer a novel, precision approach to address serious and life-threatening infections in high-risk patients,” Nagy said.
David Mantus, PhD, chief development officer at Arsanis, said the addition of approaches like ASN100 to treat serious infections should be critical given the high mortality and antibiotic resistance of these infections worldwide.
“We are looking forward to initiating our Phase 2 study of ASN100 later this year,” he added.