Rapidly boosting innate immunity in the lungs to protect against pneumonia

描述（由申请人提供）：肺炎可由多种病原体引起，包括细菌、真菌和病毒，是全球主要的死亡原因。即使在发达国家，肺炎仍然是感染导致死亡的主要原因，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，感染性并发症会阻止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。尽管如此，肺炎仍继续发生在15-20%的急性白血病患者中。Pulmotect的解决方案：Pulmotect已经确定并正在开发一种新颖的专有技术，以解决吸入微生物的风险。我们的治疗药物（PUL-042）是两种Toll样受体（TLR）激动剂配体的组合，可刺激肺部自身的先天防御机制，以产生广泛的保护作用，抵御入侵病原体，从而减少和预防感染。在成功的I期SBIR的部分支持下，已经完成了体外和体内临床前概念验证实验，以验证该技术并将其进一步推向临床。在风险最高的癌症患者中，可以捕获临床概念验证并支持其他患者人群的开发（移植，ICU，生物恐怖，大流行）。该提案的重点是实现关键里程碑，进一步推动该技术走向商业化，并为I期和II期临床试验提供资金。该项目分为四个具体目标，解决所需的数据，药物制造和批准，以将该技术与临床联系起来。

DESCRIPTION (provided by applicant): Pneumonia can be caused by a variety of pathogenic organisms including bacteria, fungi and viruses and is the leading cause of death worldwide. Even in developed countries, pneumonia 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 infectious complications 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. Despite this expenditure, pneumonia continues to occur in 15-20% of acute leukemia patients. Pulmotect's Solution: Pulmotect has identified and is developing a novel, proprietary technology to address the risks of inhaled microbes. Our therapeutic (PUL-042) is a combination of two Toll-like receptor (TLR) agonist ligands that stimulate the lung's own innate defense mechanisms to create a broad protection against invading pathogens thereby reducing and preventing infection. Supported in part by a successful Phase I SBIR, both in vitro and in vivo preclinical proof-of-concept experiments have been completed to validate this technology and further advance it to the clinic. It is in the most at-risk cancer patients where clinical proof-of- concept can be captured and support development for additional patient populations (transplant, ICU, bioterror, pandemic). The focus of this proposal is to accomplish key milestones that will advance this technology further towards commercialization and bridge to funding already secured for Phase I and Phase II clinical trials. The project is organized into four Specific Aims that address the needed data, drug manufacturing, and approvals to bridge this technology to the clinic.