Rapidly boosting innate immunity in the lungs to protect against pneumonia

描述(申请人提供)：肺炎可由包括细菌、真菌和病毒在内的各种病原体引起，是全球主要的死亡原因。即使在发达国家，肺炎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。许多时候，感染性并发症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。尽管有这样的支出，15%-20%的急性白血病患者仍会发生肺炎。普尔莫特的解决方案：普尔莫特已经确定并正在开发一种新的专利技术，以解决吸入微生物的风险。我们的治疗性药物(PUL-042)是两种Toll样受体(TLR)激动剂配体的组合，刺激肺自身的固有防御机制，创建对入侵病原体的广泛保护，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的临床前概念验证实验，以验证这项技术并进一步将其推向临床。正是在风险最高的癌症患者中，可以获得临床概念验证，并支持更多患者群体的发展(移植、重症监护病房、生物恐怖、大流行)。这项提议的重点是完成关键里程碑，这些里程碑将进一步推动这项技术走向商业化，并为已经为第一阶段和第二阶段临床试验争取到的资金铺平道路。该项目被组织成四个具体的目标，以解决所需的数据、药物制造和批准，将这项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.