Development of SP-A Derived Peptidomimetics for the Treatment of Asthma - Phase II

目前的哮喘治疗方法，同时通过关注气道， 炎症，不要消除它们。哮喘恶化是发病的重要原因， 死亡率，因为它们可导致气道损伤、肺功能下降和死亡。有病情加重 更严重的哮喘患者尤其令人担忧，因为医疗保健费用和生产力损失占了 210亿美元/年的美国年度医疗保健支出。目前还没有先天免疫调节剂 哮喘的治疗因此，迫切需要开发新的治疗方法，以用于 治疗炎性肺病，包括哮喘。我们发现了一些小分子， 模拟内源性肺蛋白表面活性蛋白A（SP-A）在降低气道阻力中的作用， 与哮喘相关的收缩，导致症状和恶化。SP-A是一种天然 肺中的衬里流体的组分，并作为抵抗吸入性损伤的第一道防线， 病原体许多哮喘患者的SP-A水平非常低，或者由于哮喘发作而导致SP-A受损。 哮喘肺的炎症环境。全长SP-A直接输送到肺部， 由于其规模和结构，这是可行的。 我们公司RaeSedo Inc.是建立在我们可以创建自定义修改的原则， 以小肽模拟物形式递送SP-A的活性区， 药代动力学性质和稳定性。这些SP-A衍生的肽模拟物代表了一类新的多肽。 哮喘治疗学在第一阶段，RaeSedo Inc.和亚利桑那大学合作， 提出的里程碑：设计，合成和优化肽模拟物，并表征 在特定的细胞靶点处的肽模拟物的生物活性以鉴定先导化合物。RaeSedo Inc. S 第二阶段计划的目标是推进气雾剂的开发、药理学和评价 我们的先导化合物（C867和C892）在两个大型动物模型中的毒性 与亚利桑那大学和Lovelace生物医学合作。第二阶段提案的总体目标是 在豚草致敏的哮喘犬模型中证明了安全性和有效性。如果成功， RaeSedo Inc.将有能力提交IND申请， 治疗药物提交给FDA审批

Current treatments for asthma, while reducing exacerbations in a subset of patients by focusing on airway inflammation, do not eliminate them. Asthma exacerbations are a significant cause of morbidity and mortality in asthma as they can lead to airway injury, lung function decline and death. Exacerbations in more severe asthmatics are of particular concern, as health care costs and lost productivity account for $21 billion/year in US annual health care expenditures. There is no current innate immune modulator for the treatment of asthma. Thus, there is a critical need to develop new therapies to be used in the treatment of inflammatory lung diseases including asthma. We have discovered small molecules that mimic the effect of an endogenous lung protein, Surfactant Protein A (SP-A), in reducing airway constriction associated with asthma that causes symptoms and exacerbations. SP-A is a natural component of the lining fluid in the lungs and serves as a first line of defense against inhaled insults and pathogens. Many asthma patients have either very low levels of SP-A or damaged SP-A due to the inflammatory environment of the asthma lung. Full-length SP-A delivered directly to the lungs is not feasible due to its size and structure. Our company, RaeSedo Inc., was founded on the principle that we can create custom modifications of the active region of SP-A that are delivered in small peptidomimetic form that have improved pharmacokinetic properties and stability. These SP-A derived peptidomimetics represent a new class of asthma therapeutics. During Phase I, RaeSedo Inc. and the University of Arizona, worked to meet the milestones proposed: Design, synthesize and optimize peptidomimetics and to characterize the bioactivity of the peptidomimetics at specific cellular targets to identify lead compounds. RaeSedo Inc.’s objectives for the Phase II proposal are to advance aerosol development, pharmacology and evaluation of toxicity of our lead compounds (C867 and C892) in two large animal models through collaborations with the University of Arizona and Lovelace Biomedical. The overall goal of this phase II proposal is to demonstrate safety and efficacy in the ragweed sensitized canine model of asthma. If successful, RaeSedo Inc. will be equipped to submit an IND application bringing a new class of asthma therapeutics to the FDA for approval.