Development of Fludase as an Anti-Influenza Agent

描述（由申请人提供）：流感是一种高度传染性的急性呼吸道病毒性疾病，其特点是每年复发性流行和周期性的全球大流行。疫情是由高度多样化和可变的流感病毒A和B （IFV A和IFV B）感染引起的。迫切需要新的广谱预防和治疗方法，以应对每年的流感流行和不断升级的大流行性流感威胁。NexBio开发了一种新的重组融合蛋白抗ifv试剂，称为Fludase(r)。与传统疫苗和抗病毒药物不同，Fludase(r)通过消除气道表面的流感病毒受体起作用。它可能提供针对所有流感病毒亚型和毒株的广谱保护，而无需每年更新。Fludase(r)也有几个内置的特性，使药物在气道表面长期保留，并且在人体中被设计成非免疫原性的。在过去的两年中，NexBio已经确定了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。这些成就为进一步开展fluudase (r)的发育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，并指出作为一类首个候选药物，彻底了解Fludase(r)的安全性问题和作用机制是必要的。这项挑战拨款提案的主要焦点是解决FDA的具体要求。此外，该拨款提案解决了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.