BCX4430 (GALIDESIVIR) is a viral RNA-dependent RNA polymerase (RdRp) inhibitor discovered by BioCryst scientists that has demonstrated broad-spectrum activity in multiple viruses and a favorable preliminary preclinical safety profile. BioCryst is developing BCX4430 in collaboration with the National Institute of Allergy and Infectious Diseases (NIAID). BioCryst’s objective is to develop broad-spectrum parenteral and/or oral therapeutics for viruses that pose a threat to health and national security. In September 2013, NIAID contracted with BioCryst in September 2013 for the development of BCX4430 as a treatment for Marburg virus disease and potentially for other filoviruses, including Ebola virus disease. The total funding from NIAID could be up to $26.3 million over five years, if all contract options are exercised.

In March 2015, BioCryst announced that the Biomedical Advanced Research and Development Authority (BARDA) within the U.S. Department of Health and Human Services’ Office of the Assistant Secretary for Preparedness and Response (ASPR) has awarded BioCryst a contract for the continued development of BCX4430 as a potential treatment for diseases caused by RNA pathogens, including filoviruses. This ASPR/BARDA contract includes a base contract of $12.1 million to support BCX4430 drug manufacturing, as well as $22.9 million in additional development options that can be exercised by the Government, bringing the potential value of the contract to $35.0 million.

BioCryst intends to develop one or more small-molecule antiviral drugs directed against viral ribonucleic acid (RNA) polymerase, a common and essential component of RNA viruses. This approach could allow a single drug to address gaps in the U.S. government’s medical countermeasure plan such as treatments for viral hemorrhagic fevers, and to possibly replace multiple, pathogen-specific drugs for use in response to both natural outbreaks and bioterrorist threats.

RNA polymerase plays a crucial role in viral replication process; transcription and replication of the virus genome. Nucleoside RNA polymerase inhibitors, such as BCX4430, are metabolized to the active triphosphate (nucleotide) form by cellular kinases. The drug nucleotide binds to the viral enzyme active site and becomes incorporated into the growing viral RNA strand, leading to premature chain termination. Interfering with the replication process is a well-established antiviral strategy that has been successfully exploited in developing such life-saving drugs as the nucleoside inhibitors of HIV and acyclovir for herpes simplex complex. BCX4430 may be suitable for administration by intravenous (IV), intramuscular (IM), and oral (PO) routes.