Preclinical and IND enabling studies for treatment of advanced lung cancer and other cancers metastatic to lung by pulmonary delivery of engineered Influenza A Virus (eIAV)

项目总结/摘要 每年有超过230，000例肺癌新发病例和超过130，000例因肺癌死亡 在美国，每年约有120，000人患有转移性非小细胞肺癌。 （mNSCLC），这些患者中只有7%将存活五年或更长时间。 accurius正在开发第一种可吸入剂，这将是一种安全和高效的治疗方法， mNSCLC和其他转移到肺的癌症。所述试剂是一种工程化的溶瘤病毒， 甲型流感病毒（eIAV）将选择性地感染和破坏癌细胞，同时保留健康细胞， 诱导人体自身的抗肿瘤免疫反应。这种治疗将显著提高总体生存率 转移性NSCLC患者人群以及每年50，000例不同肿瘤患者的发生率 癌症转移到肺部的类型。 Accurius项目的第一阶段将确定Accurius管道中的前两名候选eIAV， 在动物模型中，与对照组相比， 显示出对肿瘤的存在引发天然免疫应答的显著能力。后续行动 测试将确定候选人中的一个或两个是否可以将中位生存时间延长25% 与免疫检查点阻断剂组合。 第II阶段将最终确定通过两项检测的候选产品的基于细胞培养的生产工艺 并优化其可吸入形式。然后，可吸入形式必须通过相同的功效 和天然免疫应答刺激试验，如I期试验，并在动物模型中证明安全性 没有肿瘤，以便在人类中进行进一步的临床试验。 Accurius安全、可吸入、有效的eIAV的潜在可实现市场超过10万例转移性肺 癌症患者每年仅在美国，其中绝大多数将不会响应目前可用的 治疗和面临惨淡的生存前景。

PROJECT SUMMARY / ABSTRACT There are more than 230,000 new cases of lung cancer and over 130,000 deaths due to lung cancer each year in the U.S. Approximately 120,000 people each year will present with metastatic Non-Small Cell Lung Cancer (mNSCLC) for the first time, and only 7% of these patients will survive five years or more. accurius is developing the first of a kind inhalable agent that will be a safe and highly effective treatment for mNSCLC and other cancers metastatic to the lung. The agent is an engineered oncolytic virus based on the Influenza A virus (eIAV) which will selectively infect and destroy cancer cells while sparing healthy cells and induce the body’s own anti-tumor immune response. This treatment will dramatically improve overall survival rates for the metastatic NSCLC patient population as well for the 50,000 patients each year with different tumor types that have their cancer metastasize to the lung. Phase I of the accurius project will determine the top two eIAV candidates in the accurius pipeline, each of which must improve median survival time by more than 50% versus the control arm in animal models while showing significant ability to elicit the natural immune response to the presence of the tumors. Follow-up testing will determine if either or both of the candidates can improve median survival time by an additional 25% in combination with an immune checkpoint blocker. Phase II will finalize the cell culture-based manufacturing process for the candidate(s) which passed both tests in phase I and also optimize their inhalable form. The inhalable forms will then have to pass the same efficacy and natural immune response stimulation tests as in Phase I as well as demonstrating safety in animal models without tumors in order to proceed to further clinical testing in humans. The potential realizable market for accurius’s safe, inhalable, effective eIAV is over 100,000 metastatic lung cancer patients annually in the US alone, the vast majority of whom will not respond to currently available treatments and face dismal survival prospects.