Development of Fludase as an Anti-Influenza Agent

描述（由申请方提供）：流感是一种高度传染性的急性呼吸道病毒性疾病，其特征是每年反复发生流行病和周期性全球大流行病。暴发是由高度多样化和变异的流感病毒A和B（IFV A和IFV B）感染引起的。迫切需要新型广谱预防和治疗药物来应对每年的流感流行和大流行性流感的不断升级的威胁。NexBio已经创建了一种新的基于重组融合蛋白的抗IFV剂，称为Fludase（r）。与传统的疫苗和抗病毒药不同，Fludase（r）通过消除气道表面的流感病毒受体起作用。它有可能提供针对所有亚型和流感病毒株的广谱保护，而无需每年更新。Fludase（r）也有几个内置的功能，使药物能够在气道表面长时间保留，并被设计成在人类中无免疫原性。在过去的两年中，NexBio已经完成了Fludase（r）的分子序列，并在组织培养和两种动物模型中证明了其广泛而有效的抗IFV功效。这些成就为Fludase（r）的进一步开发研究提供了强有力的理由。在最近的IND前会议上，FDA提出了几个临床前问题，并表示作为一流的候选药物，有必要彻底了解Fludase（r）的安全性问题和作用机制。这项挑战补助金提案的主要重点是解决FDA的具体要求。此外，该拨款提案还解决了Fludase（r）分析和制造开发中出现的新的重要问题。

DESCRIPTION (provided by applicant): Influenza is a highly infectious acute respiratory viral disease that is characterized by recurrent annual epidemics and periodic major worldwide pandemics. Outbreaks are caused by infection of the highly diverse and mutable influenza viruses A and B (IFV A & IFV B). Novel broad-spectrum prophylaxis and therapeutics are critically needed to address the annual influenza epidemics and the escalating threat of pandemic influenza. NexBio has created a novel recombinant fusion protein-based anti-IFV agent, referred to as Fludase(r). Distinct from conventional vaccines and antivirals, Fludase(r) works by eliminating influenza virus receptors on the airway surface. It potentially confers broad-spectrum protection against all subtypes and strains of influenza viruses without the need for annual updates. Fludase(r) also has several built-in features to enable long drug retention on the airway surface and was engineered to be nonimmunogenic in humans. In the last 2 years, NexBio has finalized the molecular sequence of Fludase(r) and demonstrated its broad and potent anti-IFV efficacy in tissue culture and in two animal models. These accomplishments have provided strong justification for further developmental studies of Fludase(r). During the recent pre-IND meeting, the FDA raised several preclinical questions and indicated that as a first-in-class drug candidate, a thorough understanding of the Fludase(r) safety issues and mechanism of action is necessary. The main focus of this Challenge Grant proposal is to address the FDA's specific requests. Additionally, this grant proposal addresses new and important issues arising from Fludase(r) analytical and manufacture development.