To develop FLUNET(tm), a novel neuraminidase inhibitor (NAI) for use in treatment and prevention of influenza in the event of a pandemic or bioterrorist attack. This grant aims to develop a novel influenza neuraminidase inhibitor (NAI) for treatment and protection in a pandemic situation occurring as a result of deliberate release of highly pathogenic strain or though natural circumstances. The antiviral drug would have complementary value in the event of a natural pandemic particularly when vaccine supply is limited or mismatched to the circulating strain. Biota Holdings Ltd developed FLUNET as a second generation NAI, following the launch of Relenza, the first in class NAI, which was developed by Biota and GlaxoSmithKline PLC (GSK). While Relenza is considered safe and effective for treatment of all existing influenza A and B infections, it and other antiinfluenza drugs have features which are not ideal for mass treatment and prophylaxis. In particular, multiple dose administration of these drugs are required during the period of exposure or treatment, which presents challenges for stockpiling, supply, and compliance in the event of an epidemic, pandemic or bioterrorist attack. Biota and Sankyo Co Ltd are currently developing an NAI pro-drug named LANI(tm) (long-acting neuraminidase inhibitor), which has displayed a long residency time in the lung and increased potency against some viruses. FLUNET is not a pro-drug approach. FLUNET achieves long residency and outstanding antiviral activity through a novel mode of action. The program has progressed to a stage where a preclinical candidate and two backup candidates have been selected. Further studies, as outlined in this application, are required to progress the candidate through preclinical development to ultimately gain approval for clinical studies. Preliminary studies have shown that the lead candidate chosen for FLUNET demonstrates outstanding in vitro and in vivo efficacy, and long retention time in the lung. These properties potentially allow for development of a once only treatment and once weekly prophylaxis, and make FLUNET ideal for stockpiling and treatment as much less compound will be required compared to current treatment options and could potential have low resistance. This grant application proposes to progress FLUNET through the preclinical regulatory studies required prior to FLUNET being progressed into clinical trials in humans. As part of the project we also aim to study the resistance profile of FLUNET and its antiviral activity against strains resistant to other NAI's.
