DAS181 inhibits H5N1 Influenza lung virus infection of human lung tissues

Aug 26 2009

NexBio, Inc. announced today the publication "DAS181 Inhibits H5N1 Influenza Lung Virus Infection of Human Lung Tissues" in the September, 2009 issue of the journal Antimicrobial Agents and Chemotherapy (AAC).

DAS181 (Fludase((R))) is an investigational drug candidate in clinical development for Influenza-Like Illness. Unlike neuraminidase inhibitors (e.g. Tamiflu((R))), which target the virus, DAS181 works by inactivating the human host receptor for all influenza and para-influenza viruses tested so far including the current pandemic Novel H1N1 strain ("Swine Flu"). Previous preclinical studies conducted in collaboration with the Centers for Disease Control and Prevention have shown DAS181 to have significant prophylactic and therapeutic activity in an in vivo animal model for a highly virulent H5N1 (A/VN/1203/04) strain of influenza. The current published study, conducted in collaboration with the University of Hong Kong, examined for the first time the effects of DAS181 in human lung tissue and cells. DAS181 strongly inhibited H5N1 (A/VN/3046/2004) infection in human lung tissue and cells. The study also demonstrated that DAS181 effectively removes the two types of sialic acid (Sia) receptors to which influenza virus binds, thereby preventing both the invasion by virus into new cells and further replication where infection already exists.

The human lung tissue and cells described have been critical models for understanding the clinical pathogenesis of influenza, as people contain two types of receptors for influenza. While H5N1 preferentially binds to A2-3-linked Sia, Novel H1N1 preferentially binds to A2-6-linked Sia. DAS181 was shown in these studies to remove both the A2-6-linked and A2-3-linked types found in human respiratory tissue. Most importantly, virus was suppressed by inactivation of the entry receptors by DAS181 treatment.

"DAS181 is a particularly important potential new broad-spectrum drug for influenza because as an entry blocker, it works by a mechanism of action different from all other antiviral drugs either on-market or in development," said John M. Nicholls, M.D., Associate Professor, Department of Pathology, the University of Hong Kong, one of the two corresponding authors on the publication. "Our study clearly shows DAS181's remarkable effectiveness in protecting fresh human tissue from infection by a highly lethal H5N1 strain. Though the world is currently coping with a pandemic caused by a much less virulent H1N1 strain, DAS181 has shown significant inactivation of both types of influenza receptors found in the human airways."

In the "Report To The President On U.S. Preparations For 2009-H1N1 Influenza" by the President's Council of Advisors on Science and Technology (PCAST) announced yesterday, it is recommended that "It will be important to develop new classes of drugs to expand the armamentarium. A particularly promising new approach is to develop drugs that block the virus by acting on a human cellular function ('host target'), rather than a viral protein ('pathogen target'), because such drugs should be less likely to encounter acquired resistance." DAS181 development takes this "promising new approach."

NexBio will be presenting data on DAS181 activity against Novel H1N1 and against seasonal influenza isolates from winter 2008-09 that are resistant to Tamiflu((R)) in in vitro, ex vivo and in vivo models at the upcoming Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) annual meeting in San Francisco, CA on Tuesday, September 15, 2009.