Preclinical Test of Biodefense Drug for SEB Toxin

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DESCRIPTION (provided by applicant): Staphylococcal enterotoxin B (SEB), a primary cause of food poisoning, is also a superantigen that can cause toxic shock after traumatic or surgical Staphylococcal wound infections. In addition to being a major public health threat, SEB is regarded as one of 10 most dangerous BW agents. SEB is believed to be a part of the biological weapons arsenals of certain countries, and to pose a real bioterrorism threat. At the present there are no licensed drugs or vaccines available to protect humans against the toxic effects of SEB. Our Hypothesis is that the properties of Vpr protein suggest that it may have efficacy in controlling toxin-induced cytokine storm thus preventing the lethal effects of SEB toxemia. Our company's approach shuts down cytokine storm post-SEB toxin binding. There is a significant need to develop agents, which may benefit exposed individuals post-toxin binding. We have developed VGX-750 (recombinant Vpr protein), as a potential novel therapy for SEB Toxin Exposure. We believe VGX-750 has important therapeutic qualities relevant to the pathogenesis of SEB toxemia. Our company has a diverse and proprietary patent position on the use of recombinant Vpr protein to treat toxemia and other inflammatory diseases. In addition, many recombinant protein based drugs have been approved and have become some of the most important drugs in modern medicine. Successful completion of these Phase I studies will result in the demonstration of feasibility for using recombinant Vpr protein as a novel drug to treat post-toxin binding SEB exposure. We propose to test this important hypothesis through the following three specific aims: Aim 1: Establish a scale-up manufacturing process for VGX-750 (recombinant Vpr protein), a potential novel therapy for SEB toxin exposure. Aim 2: Perform GLP preclinical toxicity and pharmacokinetics testing of VGX-750 in rodents. Aim 3: Test the protective effects of VGX-750 in a lethal SEB toxin challenge model in rhesus macaques. This project will test the hypothesis that VGX-750 will be effective at preventing morbidity and mortality from toxin induced cytokine storm and sepsis in a rhesus macaque challenge system. Our plan is to use the proposed IV macaque studies to support our plan to conduct rhesus inhalation studies (in collaborations with R. Ulrich and the US Army) in the Phase II portion of this SBIR application. Furthermore, in anticipation of carrying the Vpr protein into clinical evaluation, we will perform GLP pre-clinical toxicity and pharmacokinetics studies in mice as a part of the Phase I SBIR studies. With successful characterization of the protective effects of VGX-750 in Phase I, we plan to focus on bringing this product to clinical evaluation as expediently as possible during the Phase II funding portion of the SBIR application. In the long run, we also feel that VGX-750 could also be a novel treatment for toxic shock due to SEB and other pyrogenic superantigen bacterial toxins. It is also possible that VGX-750 could be effective against other inflammatory diseases. Such a broad potential applicability of this drug candidate increases the likelihood that VGXO-50 could have a considerable value for both a population subject to bioterrorism and the general population.