BCX4430

BCX4430 is the lead compound in the BioCryst’s Broad Spectrum Antiviral (BSAV) program. The objective of the BSAV program is to develop broad-spectrum parenteral and oral therapeutics for viruses that pose a threat to health and national security. 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. BioCryst plans to develop these compounds in collaboration with US Government Agencies following the Animal Rule regulatory pathway.

BCX4430 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. 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.

In November 2012, BioCryst announced proof-of-principle data demonstrating that BCX4430 is efficacious and well tolerated in a preclinical disease model for evaluating efficacy against yellow fever virus infection. The study was conducted under the National Institute of Allergy and Infectious Diseases’ (NIAID’s) Animal Models of Infectious Disease Program. More information is available at the links below:

BCX4430 is a small-molecule adenosine analog drug that is chemically synthesized using well-understood synthetic transformations and chemical processes. It displays favorable pharmaceutical characteristics, including aqueous solubility (> 150 mg/mL) and stability under typical laboratory conditions and handling. BCX4430 may be suitable for administration by intravenous (IV), intramuscular (IM), and oral (PO) routes.