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)

项目摘要/摘要 每年新增的肺癌病例超过23万例，死于肺癌的病例超过13万例 在美国，每年大约有12万人患有转移性非小细胞肺癌 (MNSCLC)，这些患者中只有7%能存活五年或更长时间。 Accurius正在开发第一种吸入剂，这种吸入剂将是一种安全高效的治疗方法 MNSCLC和其他癌症转移到肺部。该制剂是一种工程设计的溶瘤病毒，基于 甲型流感病毒(EIAV)将选择性地感染和摧毁癌细胞，同时保留健康的细胞和 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存活率。 每年50,000名不同肿瘤患者的非小细胞肺癌转移率 癌症转移到肺部的类型。 精确度项目的第一阶段将确定精确度管道中排名前两位的eIAV候选对象，每个 在动物模型中，与对照组相比，它必须将中位存活时间提高50%以上，而 对肿瘤的存在表现出显著的诱导自然免疫反应的能力。跟进 测试将确定两名候选人中的一人或两人是否可以将中位生存时间额外提高25% 与免疫检查点阻滞剂结合使用。 第二阶段将最终确定通过两项测试的候选人(S)的基于细胞培养的制造工艺 在第一阶段，并优化其可吸入形式。然后，可吸入形式必须通过相同的效果 和第一阶段的自然免疫反应刺激试验一样，在动物模型中证明是安全的 没有肿瘤，以便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10万个转移性肺 仅在美国每年就有癌症患者，其中绝大多数人对目前可用的 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.