Rapidly boosting innate immunity in the lungs to protect against pneumonia

描述（由申请人提供）：问题：肺炎是全球主要的死亡原因。即使在发达国家，它仍然是感染死亡的主要原因，也是因其他疾病接受治疗的病人的严重并发症。当宿主抵抗力水平降低（例如免疫功能低下的癌症患者）和病原体暴露水平增加（例如流行病，生物恐怖和生物战）时，肺部感染的威胁就会增加。急性白血病患者是目前最危险的患者之一，因为他们面临着癌症治疗导致的显著免疫功能低下。很多时候，这些风险阻止了完整的癌症治疗计划的完成。因此，每年估计有44，700名白血病患者花费超过15亿美元用于一系列治疗以预防肺炎。 Pulmotect的解决方案：Pulmotect已经确定并正在开发一种新技术，以解决吸入微生物的风险。我们的治疗药物（PUL-042）是两种TLR配体的组合，可刺激肺部自身的先天防御机制，为病原体创造一个敌对的环境，减少或预防感染。已经完成了体外和体内实验以验证该技术。重要的是，由于细胞更新率低，肺上皮细胞对化疗药物具有抗性，因此先天免疫反应保持完整。正是在这些风险最高的患者中，可以为其他市场捕获概念验证。该提案的重点是实现关键里程碑，以验证该技术的商业化。该SBIR应用程序专注于解决重要的临床前重要问题。所包含的三个目标旨在验证和扩展已经获得的概念验证数据。目标是将该技术转移到临床。实现这些里程碑将为安全有效的产品的IND申请提供重要数据。该I期提案的积极结果可能会导致II期SBIR申请，以在第二种动物模型中进行深入的治疗研究，包括FDA批准的安全性和毒性研究。此外，通过展示Pulmotect管道中的后续发现，可以更好地从投资者那里获得额外的外部资金，以将这项技术转移到诊所和市场。总的来说，本提案概述的里程碑将建立在以前的工作基础上，增加该平台技术的基础，并帮助将该技术引入临床。) 公共卫生相关性：Pulmotect公司正在开发新的疗法，刺激先天免疫系统，以防止感染性疾病，即使在免疫力严重受损的情况下。概念验证数据表明，该技术有效地防止了广泛的吸入性病原体。该项目将提供重要的数据，以帮助将这项技术从实验室转移到诊所，医生们要求使用这项技术来造福他们的患者。

DESCRIPTION (provided by applicant): Problem: Pneumonia is the leading cause of death worldwide. Even in developed countries, it continues to be the leading cause of death from infection and a serious complication for patients being treated for other diseases. The threat of lung infections is elevated when there is a decreased level of host resistance (e.g. immunocompromised cancer patients) and when there is an increased level of pathogen exposure (e.g. pandemics, bioterror, and biowarfare). Acute leukemia patients are currently some of the most at-risk patients, as they are faced with significant immunocompromise resulting from their cancer treatments. Many times these risks prevent the full cancer treatment plan from being completed. As a result, each year an estimated 44,700 leukemia patients spend more than one-half billion dollars on a range of treatments in an effort to prevent pneumonia. Pulmotect's Solution: Pulmotect has identified and is developing a novel technology to address the risks of inhaled microbes. Our therapeutic (PUL-042) is a combination of two TLR ligands that stimulate the lung's own innate defense mechanisms to create a hostile environment for pathogens and reduce or prevent infection. Both in vitro and in vivo experiments have been completed to validate this technology. Importantly, because of the low cell-turnover rate, the lung epithelium is resistant to chemotherapy drugs so the innate immune response remains intact. It is in these most at-risk patients where proof-of-concept can be captured for additional markets. The focus of this proposal is to accomplish key milestones that will validate this technology for commercialization. This SBIR application is focused on addressing important preclinical important issues. The three Aims included are designed to validate and expand upon the proof-of-concept data already obtained. The Aims are focused for transitioning this technology into the clinic. Achieving these milestones would provide significant data for an IND application for a product that is safe and efficacious. Positive results from this phase I proposal would potentially lead to a phase II SBIR application to perform an in-depth study of the therapy in a second animal model, including FDA approved safety and toxicity studies. Additionally, by demonstrating subsequent discoveries in Pulmotect's pipeline, additional outside funds from investors can better be pursued to transition this technology into the clinic and market place. Overall, the outlined milestones of this proposal would build upon previous work, add to the foundation of this platform technology, and help bring this technology to the clinic. ) PUBLIC HEALTH RELEVANCE: Pulmotect, Inc is developing novel therapeutics that stimulates the innate immune system to protect against infectious diseases, even in cases of severely compromised immunity. Proof-of-concept data has shown that this technology effectively protects against a broad range of inhaled pathogens. This project will provide significant data to help transition this technology from the lab to the clinic, where physicians are asking to use the technology to benefit their patients.