Evaluate in vivo prophylactic and therapeutic efficacy of a RNAi-based drug against highly pathogenic influenza A (HPIA) virus, H5N1 (A/Viet Nam/1203/2004)

The UTMB team will be led by Dr. Chien-Te Kent Tseng who will serve as Pl on this Sponsored Research Agreement. The emerged and t o-be-emerged HPIA viruses, including pandemic swine flu virus arose in Mexico and China and the constant threat of new strains, e.g., HSNl (A/Viet Nam/1203/2004) and H7N9, have highlighted the potential risk to public health worldwide, making the development of novel and effective anti-influenza drugs and improved vaccines critical. UTMB has established mouse and ferret as influenza animal models and has routinely used them in the past for studying viral-host interactions that contribute to transmission and onset of morbidity and mortality caused by HPIA viruses and assessing the efficacy of drug and vaccine candidates developed against HPIA viruses. The goal is to assess the prophylactic or therapeutic efficacy in vivo of a selected RNAi-based novel anti-infl uenza drug, namely TAl. In addition to highly permissive to mouse adapted IAV, mice are naturally permissive (without the need to adaptation in murine) to HPIA HSNl and other zoonotic strains of avian/swine IAV. Because of the highly characterized nature of the murine immune system with huge and complete collection of available immune reagents, mice are particularly attractive as influenza model for identification of pathogenic factors and for analysis of multiple immunological parameters in antiviral and/or vaccine desig n. Thus, UTMB will evaluate the protective efficacy of TAl primarily using the established mouse model. A comprehensive design and strategy of the study and the endpoints to be used for assessing the protective efficacy of the test article, TAl, was provided by the Sponsor of this project (attached Appendix). Study design details are subject to change based on communication between Dr. Tseng and Arrowhead Pharmaceuticals, Inc.