BioCryst integrates the necessary disciplines of biology, crystallography, medicinal chemistry and computer modeling to effectively use structure-based drug design to discover and develop small molecule pharmaceuticals.

BioCryst has progressed two novel compounds into late-stage pivotal clinical trials:

• Forodesine, a purine nucleoside phosphorylase (PNP) inhibitor for cutaneous T-cell lymphoma (CTCL)
• Peramivir, an anti-viral for influenza

Purine Nucleoside Phosphorylase (PNP) Inhibitors

Active site of PNP with an inhibitor bound

PNP is an enzyme that plays an important role in T-cell proliferation, because it is necessary to maintain normal DNA synthesis in human T-cells. Selective inhibition of PNP causes certain nucleosides, including deoxyguanosine, to accumulate. As the concentration of deoxyguanosine increases within T-cells, it is converted by specific enzymes to dGTP. A high concentration of dGTP in T-cells causes an imbalance in the intra-cellular trinucleotide pool and thus causes cell death.

In June 2000, BioCryst licensed a series of potent PNP inhibitors from Albert Einstein College of Medicine of Yeshiva University (AECOM) and Industrial Research, Ltd. (IRL), New Zealand. One of BioCryst's most advanced product candidates, forodesine, is a transition-state analog inhibitor of the target enzyme purine nucleoside phosphorylase (PNP). Forodesine is a more potent inhibitor of human lymphocyte proliferation than other previously known PNP inhibitors. Clinical data in past and on-going clinical trials, plus extensive pre-clinical studies indicate that forodesine can modulate T-cell activities. Forodesine is an investigational PNP inhibitor for the potential treatment of T-cell leukemias and lymphomas. In February 2006, BioCryst licensed forodesine to Mundipharma International Holdings Limited to develop and commercialize in markets across Europe, Asia and Australia for use in oncology. An oral formulation of the compound is currently in a pivotal Phase IIb trial for patients with Cutaneous T-cell Lymphoma (CTCL). The trial is being conducted under a special protocol assessment (SPA) negotiated with the United States Food and Drug Administration (FDA).

To learn more about our Forodesine

During 2002, BioCryst added BCX4208, to the series of inhibitors of PNP licensed from AECOM and IRL. Pre-clinical results indicated that BCX4208 was a more potent inhibitor than forodesine.  In September 2009, BioCryst announced the initiation of a Phase 2 study in gout.

To learn more about our BCX4208

Neuraminidase Inhibitor

Influenza Neuraminidase Protein Crystals

Research during the past two decades has seen dramatic advances in understanding the molecular structure and function of the influenza virus. Considerable attention has been focused on the enzyme neuraminidase, which is located on the surface of the virus. Neuraminidase assists in the release and spread of the flu virus by breaking the chemical strands that hold the new viruses to the cell surface, allowing the replicated virus to spread and infect other cells. This process progresses until the host’s immune response can produce enough antibodies to bring the infection under control. Inhibiting the neuraminidase enzyme keeps new viruses attached to the cell surface, thereby preventing the spread of the virus and the further infection of other cells. The subsequent quantities of virus in the bloodstream are not enough to cause disease but are sufficient to induce the body to mount an immune response.

In 1987, scientists at BioCryst and University of Alabama (UAB) began determining the molecular structure of the influenza neuraminidase enzyme from several different strains of influenza, using x-ray crystallography. Subsequently, based on the three-dimensional structure of the active site of the neuraminidase, BioCryst scientists have developed numerous new inhibitors leading to the selection of peramivir for clinical development.  In 2005, BioCryst initiated a program to develop a parenteral formulation of peramivir to address the growing concern for an influenza pandemic. BioCryst received fast track designation from the FDA for intravenous (i.v.) peramivir in January 2006. In June 2006, BioCryst entered into an agreement with Green Cross Corporation to develop and commercialize peramivir in Korea. In March 2007, we announced a separate collaboration with Shionogi & Co., Ltd. for the development and commercialization of peramivir in Japan and Taiwan.

Government Stockpiling

With the concern of H5N1 and H1N1 influenza strains and the possible threat of a pandemic, many governments throughout the world have been stockpiling anti-viral drugs, such as Roche's neuraminidase inhibitor, oseltamivir. There is interest in many of these governments, including the U.S. government to find additional vaccines and anti-virals to address a potential pandemic situation.

To learn more about our peramivir