Preclinical Development of a Therapeutic Agent for COPD

描述（由申请方提供）：粘液分泌过多进入呼吸道，导致阻塞以及发病率和死亡率增加，是几种肺部疾病的主要因素，包括慢性阻塞性肺病（COPD）、哮喘和囊性纤维化。目前没有有效的治疗方法来控制这些疾病中的过度粘液分泌。在先前发表的研究中，我们发现一种称为MARCKS蛋白的特定蛋白质是粘液分泌途径中的关键分子。基于这一发现，发现了一种新的肽，其抑制培养的人气道上皮细胞中的粘液分泌过多。 在SBIR I期资助的财政支持下，BioMarck Pharmaceuticals扩展了这些研究，并证实这种新型肽在三种不同的动物模型中是一种有效的粘液分泌过多抑制剂。这一发现可能会导致一种新的和有效的治疗方法，以抑制各种肺部疾病的过度粘液分泌。 在目前的SBIR II期提案中，我们希望进一步开发这种肽，以支持向FDA提交IND（研究性新药）申请，用于在人类志愿者中进行可能的临床研究。在本提案中，公司希望实现两个主要目标。即，a）开发用于基于喷雾器的靶向肺递送的肽的最佳制剂，和B）确定当通过喷雾器递送至实验室动物时肽的安全性。拟定的一系列安全性研究是IND获批用于后续人体临床研究的先决条件。 BioMarck的目标是开发和商业化一种新型，有效和安全的治疗剂，以满足治疗粘液分泌过多疾病（如COPD）的未满足的医疗需求，COPD是美国和全球的第四大死亡原因。

DESCRIPTION (provided by applicant): Hypersecretion of mucus into the respiratory airways, leading to obstruction and increased morbidity and mortality, is a major factor in several lung diseases, including chronic obstructive pulmonary disease (COPD), asthma, and cystic fibrosis. There are presently no effective therapies to control excessive mucus secretion in these diseases. In previously published studies, we discovered that a specific protein called MARCKS protein is a key molecule in the mucus secretory pathway. Based on this finding, a novel peptide was discovered, which inhibited mucus hypersecretion in human airway epithelial cells in culture. With financial support from SBIR Phase I grant, BioMarck Pharmaceuticals has extended these studies and confirmed that this novel peptide is an effective inhibitor of mucus hypersecretion in three different animal models when instilled intratracheally. This discovery can potentially lead to a novel and effective therapy to inhibit excessive mucus secretion in a variety of pulmonary diseases. In the present SBIR Phase II proposal, we wish to further develop this peptide in order to support an IND (Investigational New Drug) application to the FDA for possible clinical studies in human volunteers. In this proposal, the Company wishes to accomplish two major objectives. Namely, a) to develop an optimum formulation of the peptide for nebulizer-based targeted lung delivery, and b) to establish the safety of the peptide when delivered by nebulizer to laboratory animals. The series of proposed safety studies are prerequisites for approval of an IND for subsequent human clinical studies. BioMarck's goal is to develop and commercialized a novel, effective, and safe therapeutic agent to satisfy the unmet medical needs for the treatment of mucus hypersecretory diseases like COPD, the 4th leading cause of death in the United States and worldwide.