A potential drug to combat a complication of severe infections known as a cytokine storm will advance in development under an agreement announced today by the U.S. Department of Health and Human Services (HHS). A cytokine storm can complicate recovery and in extreme cases can drive the body’s organs to shut down, causing death.
Cytokines, chemicals produced by the body, modulate the inflammatory and immune responses to infection. In severe infections, such as skin and soft tissue infections caused by Streptococcus pyogenes, cells can over-react and create an overwhelming surge of cytokines – the cytokine storm. This can result in tissue and organ damage and cause a severe systemic inflammatory response associated with a high likelihood that the patient could die.
Sepsis, with or without an associated cytokine storm, is a life-threatening complication of infection with many pathogens, including bioterrorism threats such as tularemia and plague, viral diseases such as avian influenza, bacteria causing pneumonia, and multi-drug resistant bacteria.
Advanced development of the potential drug, AB103, to combat cytokine storm will be supported under a one and one-half year, $4.4 million contract with the Israeli biotechnology company Atox Bio. If options are fully exercised, the contract could be extended up to an additional three years and could total $23.9 million. The Biomedical Advanced Research and Development Authority (BARDA), within the HHS Office of the Assistant Secretary for Preparedness and Response (ASPR), will oversee the project.
AB103 acts by modulating the body’s cytokine response without repressing the normal immune response, and could be used to reduce excessive inflammation. The drug provides protection against lethal infections in experimental models of a wide range of bacterial pathogens. Because it works by targeting the host’s immune system rather than attacking bacteria directly, it should not be subject to the development of resistance.
“Novel, host directed therapies like AB103 that target the immune system can help us address unmet medical needs such as necrotizing fasciitis, a severe skin and soft tissue infection,” says BARDA director Robin Robinson, PhD. “AB103 illustrates one of several approaches that BARDA is supporting as part of President Obama’s new initiative to combat antimicrobial resistance.”
Under the agreement with BARDA, Atox Bio will prepare and conduct clinical trials to prove the drug’s effectiveness in improving outcomes in patients with severe skin or soft tissue infections like flesh-eating bacteria. Because of the drug’s mechanism of action, BARDA is also interested in evaluating the product against a number of agents that could pose a national health security threat. As part of the agreement, Atox Bio will supply AB103 to BARDA for testing in animal models against plague, tularemia, and other bioterrorism threats.