Rapidly boosting innate immunity in the lungs to protect against pneumonia

描述(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，也是正在接受其他疾病治疗的患者的严重并发症。当宿主抵抗力水平降低(例如，免疫受损的癌症患者)和病原体暴露水平增加(例如，流行病、生物恐怖和生物武器)时，肺部感染的威胁就会增加。急性白血病患者目前是风险最高的患者之一，因为他们面临着癌症治疗导致的重大免疫损害。很多时候，这些风险阻碍了完整的癌症治疗计划的完成。因此，据估计，每年有44700名白血病患者在一系列治疗上花费超过15亿美元，以努力预防肺炎。 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。我们的治疗性药物(PUL-042)是两种TLR配体的组合，它们刺激肺自身的固有防御机制，为病原体创造一个敌对的环境，减少或防止感染。为了验证这项技术，已经完成了体外和体内实验。重要的是，由于细胞周转率低，肺上皮对化疗药物具有抵抗力，因此先天免疫反应保持完好。正是在这些风险最高的患者中，概念验证可以被捕获到更多的市场。这项提案的重点是完成关键里程碑，从而验证这项技术的商业化。这项SBIR应用专注于解决重要的临床前重要问题。其中包含的三个目标旨在验证和扩展已获得的概念验证数据。目标是将这项技术转移到临床上。达到这些里程碑将为安全有效的产品的IND应用提供重要数据。这一第一阶段提案的积极结果可能导致第二阶段SBIR应用，以在第二个动物模型中对该疗法进行深入研究，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更多外部资金，将这项技术转化为临床和市场。总体而言，该提案概述的里程碑将建立在以前工作的基础上，增加该平台技术的基础，并帮助将该技术带入临床。) 与公共卫生相关：Pulmotect公司正在开发新的疗法，这种疗法可以刺激先天免疫系统，以预防传染病，即使在免疫严重受损的情况下也是如此。概念验证数据表明，这项技术有效地预防了广泛的吸入病原体。该项目将提供重要的数据，帮助将这项技术从实验室转移到临床，在那里，医生们正在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.