Expanding the Market and Success Rates for Myeloablative Cancer Treatments Using PUL-042, an Innate Immune Stimulant

使用先天免疫兴奋剂 PUL-042 扩大清髓性癌症治疗的市场和成功率

• 批准号: 9061821
• 负责人: Brenton Scott
• 金额: $ 99.88万
• 依托单位: PULMOTECT, INC
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-02-01 至 2018-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9061821
• 关键词: Achievement; Address; Agonist; Agreement; Aspergillus fumigatus; Asthma; Bacteria; Basic Science; Biotechnology; Breathing; Cancer Patient; Clinical; Clinical Research; Clinical Trials; Collaborations; Communicable Diseases; Cyclic GMP; Data; Development; Dose; Double-blind trial; Enrollment; Epithelium; Evaluation; Funding; Goals; Hematologic Neoplasms; Hematology; Human; Immune; Immune system; Immunity; Immunocompromised Host; Incidence; Infection; Lead; Lower Respiratory Tract Infection; Lung; Marketing; Methods; Mus; Myeloablative Chemotherapy; Nasal Lavage Fluid; Parainfluenza; Patients; Pharmaceutical Preparations; Phase; Phase II Clinical Trials; Placebos; Pneumonia; Positioning Attribute; Prevention; Process; Pulmonology; Randomized; Recruitment Activity; Research; Resistance; Safety; Secure; Seeds; Sendai virus; Severities; Site; Staging; Survival Rate; TLR2 gene; Technology; Testing; Therapeutic; Time; Toll-like receptors; Translating; United States National Institutes of Health; University of Texas M D Anderson Cancer Center; Vaccines; Viral; Virus; Virus Diseases; aerosolized; base; cancer therapy; clinical research site; design; disease transmission; follow-up; fungus; healthy volunteer; immune resistance; immunosuppressed; individual patient; influenzavirus; man; microbial; microbiome; neutralizing antibody; novel therapeutics; oncology; outreach; pandemic influenza; pathogen; phase I trial; phase II trial; prevent; resistance mechanism; respiratory; response; study population; success; technology development; virome

Pulmotect, Inc. was founded in 2007 to translate discoveries that induce innate immune resistance in the lung into therapeutics that will provide protection from inhaled pathogens. Our technology platform is a direct result of basic research by our founders on the mechanisms of microbial resistance in the lung epithelium. We have developed an inhaled therapeutic, PUL-042, that provides immediate protection against a broad spectrum of respiratory pathogens. PUL-042 is a clinical stage, specific combination of two well-characterized synthetic molecules, a lipopeptide (Pam2CSK4) and an oligodeoxynucleotide (ODN M362) that act as agonists of the Toll-like Receptors TLR2/6 and TLR9, respectively. This unique, proprietary combination of molecules synergizes to rapidly and powerfully stimulate the body’s natural defenses. The response is localized and specific to the site of administration. In mice, treatment before and after exposure with aerosolized PUL-042 results in increased survival rates to pathogens including multiple Gram+ and Gram– bacteria (three of which are Class A bioterror agents), the fungus Aspergillus fumigatus, and the Sendai and influenza viruses. In each case, increased survival is associated with a reduction of lung pathogen burden, not simply increased tolerance to the pathogen by the host, which indicates a resistance mechanism of action. Pulmotect's long-term strategy is to leverage its technology across a wide array of important threats from inhaled pathogens by limiting the pathogen burden and transmission of disease. The range of applications for PUL-042 currently in development includes use in immunosuppressed patients, pandemic influenza, asthma exacerbations associated with viral infections and manmade bioterror threats as well as naturally emerging viruses. While this broad spectrum technology is not envisioned to replace traditional vaccine approaches, its value and differentiation reside in the ability to confer immediate host-based protection that is not limited by the identity of the pathogen. The potential indications that lie outside the scope of this proposal are synergistic, building on experimental methods that we established since our earliest research in this field. The scientific basis of boosting the innate immune system in the lungs is rapidly expanding as we better understand the underlying mechanism of action. The primary goal of this proposal is to complete a Phase II clinical trial in immunosuppressed cancer patients. This will be a multi-center randomized double-blind trial that will compare PUL-042 against placebo on the overall incidence and severity of pneumonia, specifically on those who have been screened to have a parainfluenza infection prior to enrollment. The three objectives of the trial are described below. • Primary objective: to determine the safety and tolerability of PUL-042 inhalation solution in patients with documented parainfluenza infection. • Secondary objective: to determine the efficacy of PUL-042 inhalation solution to prevent the progression of documented parainfluenza infection to clinically documented lower respiratory tract infection. • Exploratory objectives: 1) evaluate the effect of PUL-042 on parainfluenza viral titers and neutralizing antibodies; 2) evaluate the effect of PUL-042 over time on the microbiome and virome in nasal washes in the study population; and 3) determine whether PUL-042 induces neutralizing antibodies against PUL-042 components. The successful achievement of these objectives will demonstrate proof-of-concept in man and further validate the technology for market use. With secured matching funds already in place, this NIH proposal is designed to help move the project to the end goal, rather than provide the initial seed funds to start the process. The Company would be well positioned to advance existing collaborations, partnerships and discussions with leading large pharma and biotechnology organizations, accelerating the path to the market to address the serious unmet needs that many patients are currently facing.

Pulmotect，Inc。成立于2007年，以翻译诱导肺部先天免疫力的发现 进入可以保护遗传病原体的治疗。我们的技术平台是直接结果 我们的创始人关于肺上皮中微生物抗性机制的基础研究。我们有 开发了一种遗传疗法PUL-042，可立即保护，以防止 呼吸道病原体。 PUL-042是一个临床阶段，是两个特征良好的合成的特异性组合 分子，脂肽（PAM2CSK4）和寡脱氧核苷酸（ODN M362），它们充当激动剂 Toll样受体TLR2/6和TLR9分别。这种独特的专有分子组合 协同迅速，有力地刺激人体的自然防御能力。响应是本地化的， 特定于管理部位。在小鼠中，用雾化PUL-042接触前后的治疗 导致病原体的存活率提高，包括多个克+和革兰氏细菌（其中三个 是A类BiotError剂），真菌曲霉的烟气和仙台并影响病毒。每个 情况，生存率增加与肺病病原体的减少有关，而不是仅仅增加 宿主对病原体的耐受性，这表明作用的抗性机理。 PulMotect的长期策略是利用其技术在各种重要威胁中。 通过限制病原体伯嫩和疾病的传播来遗传病原体。申请的范围 当前正在开发的PUL-042包括用于免疫抑制的患者，大流行的影响，哮喘 与病毒感染和人造生物侵蚀威胁以及自然出现的加剧 病毒。尽管没有设想这种广泛的技术来取代传统的疫苗方法，但它 价值和差异化存在于提供不受受宿主的立即保护的能力而不受受限制的限制 病原体的身份。本提案范围之外的潜在迹象是协同作用的， 自从我们在该领域最早的研究以来就建立了实验方法。科学 提高肺部先天免疫系统的基础正在迅速扩大，因为我们更好地了解 基本的作用机理。 该提案的主要目标是完成免疫抑制癌症患者的II期临床试验。 这将是一项多中心随机双盲试验，将在 肺炎的总体事件和严重性，特别是那些被筛选的人 入学前的副氟藻感染。试验的三个目标如下所述。 •主要目的：确定PUL-042吸入溶液的安全性和耐受性 记录的副磷氟氮蛋白酶感染。 •次要目标：确定PUL-042吸入解决方案的效率以防止 记录在临床记录的下呼吸道感染中，记录了Parainfluenza感染。 •探索性目标：1）评估PUL-042对parainfluenza病毒滴度的影响并中和 抗体； 2）评估PUL-042随时间的影响对鼻洗的微生物组和病毒蛋白的影响 研究人群； 3）确定PUL-042是否诱导对PUL-042的中和抗体 成分。 这些目标的成功实现将证明人的概念证明，并进一步验证 市场使用技术。有了安全的匹配资金，该NIH提案旨在 帮助将项目移至最终目标，而不是提供初始种子资金来开始过程。这 公司将有能力提高现有的合作，合作伙伴关系和讨论 领导大型药物和生物技术组织，加速了通往市场的道路，以解决 许多患者目前面临的严重未满足需求。