The 'Dan Crozier Building,' USAMRIID, Fort Detrick, MD, USA (Photo credit: Granted public domain status by U.S. Army)
BioCryst Pharmaceuticals, Inc. announced this morning that their small-molecule, nucleoside analogue, BCX-4430, would be entering safety trials in non-human primates within the next few weeks.
The company, based in Research Triangle Park, North Carolina, is developing agents first identified in the laboratory of Yarligadda S. Babu, Ph.D., previously with the University of Alabama at Birmingham.
In a March, 2014 paper published in the journal Nature, where Dr. Babu is a co-author, the majority of the other co-authors were from the Division of Molecular and Translational Sciences, Therapeutic Discovery Center, United States Army Medical Research Institute of Infectious Diseases (USAMRIID). The team was led by the well-regarded virologist, Dr. Sina Bavari. Previous inquiries have been made to interview Dr. Bavari but are being denied by communications staff.
The Nature paper demonstrated that BCX-4430 could prevent Ebola and related Marburg infections in rodents. Most notably, BCX-4430 affords complete protection in cynmologous monkeys from Marburg infection when given 48 hours after viral exposure.
USARMIID personnel are essential to these drug development efforts because of thie tremendous institutional expertise, particularly in rodent and non-human primate studies with biosafety level-4 viruses.
The National Institute of Allergy and Infectious Diseases (NIAID) had already committed $22 million over five years to the Biocryst project, when all operations are exercised. An recent infusion of an additional $2.4 million brings that commitment up to $24.4 million.
Much of the press regarding Ebola treatment has focused on passive immunotherapy agents, such as Mapp Biopharmaceutical's ZMapp, vaccines from private and public entities, and small RNA drugs from companies such as Tekmira and Sarepta.
Biocryst's BCX-4430 is a much smaller molecule intended for broad spectrum anti-viral use, described by the company as 'an RNA dependent-RNA polymerase inhibitor that has demonstrated broad-spectrum activity against more than 20 RNA viruses in nine different families, including filoviruses, togaviruses, bunyaviruses, arenaviruses, paramyxoviruses, coronaviruses and flaviviruses.'
Their goal is to develop the drug under FDA's Animal Rule that permits non-human primate efficacy and safety studies for conditional approval as phase I human trials proceed.
The only other company widely publicized as a player in the small-miolecule Ebola space is Toyoma, a subsidiary of Fujifilm. Their drug, favipiravir, or T-705, has been approved in Japan to treat influenza, a virus that, like Ebola, has a genome made of RNA.
For those readers with medicinal chemistry interests, the supplementary material for the Nature paper contains the synthetic procedure and a more detailed description of the assays. A rudimentary description of BCX-4430 would be to say that it's an adenosine analogue where ribose is replaced by a pyrrolidine.
