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)

通过经肺递送工程甲型流感病毒 (eIAV) 治疗晚期肺癌和其他转移至肺部的癌症的临床前和 IND 研究

• 批准号: 10822598
• 负责人: mallikarjun srivatsan
• 金额: $ 40万
• 依托单位: ACCURIUS THERAPEUTICS, INC.
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-21 至 2024-06-01
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10822598
• 关键词: Address; Agreement; Animal Model; Animals; Body Weight decreased; Breathing; Cancer Model; Cancer Patient; Cell Culture Techniques; Cells; Cessation of life; Clinic; Clinical Research; Collaborations; Combination Drug Therapy; Data; Development; Diagnostic; Disseminated Malignant Neoplasm; Distant; Dose; Drug Targeting; Engineering; Face; Formulation; Goals; Human; Immune; Immune response; Immunity; Immunologic Markers; Immunotherapy; Influenza A virus; Infusion procedures; Injections; Injury; Intellectual Property; Intravenous; Joints; Lead; Licensing; Lung; Lung Neoplasms; Malignant neoplasm of lung; Marketing; Mediating; Metastatic Neoplasm to the Lung; Metastatic to; Mus; Nebulizer; Neoplasm Metastasis; Non-Small-Cell Lung Carcinoma; Oncology; Oncolytic viruses; Overdose; Patients; Persons; Phase; Primary Neoplasm; Process; Production; Safety; Small Business Innovation Research Grant; Survival Rate; T cell infiltration; Testing; Therapeutic; Therapeutic Effect; Time; Toxic effect; Treatment Efficacy; United States; Up-Regulation; anti-tumor immune response; arm; cancer cell; chemotherapy; commercial application; commercialization; effective therapy; experimental study; follow-up; immune activation; immune checkpoint blockers; immune-related adverse events; improved; manufacture; manufacturing process; medical schools; mouse model; new technology; novel; novel therapeutics; patient population; pre-clinical; preclinical efficacy; research clinical testing; response; success; tumor

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.

项目摘要 /摘要 每年有超过230,000例新的肺癌病例和130,000多人死亡 在美国，每年约有12万人将出现转移性非小细胞肺癌 （MNSCLC）第一次，这些患者中只有7％的生存五年或更长时间。 Accureius正在开发一种可吸入剂的第一个，它将是一种安全且高效的治疗方法 MNSCLC和其他癌症转移到肺部。代理是一种基于 流感病毒（EIAV），该病毒将在保留健康细胞和 诱导人体自己的抗肿瘤免疫反应。这种治疗将大大改善总体生存 每年有50,000名患者的转移性NSCLC患者群体的发生率 癌症转移到肺部的类型。 精确项目的第一阶段将确定精确管道中的前两个EIAV候选者 与动物模型中的控制组相比，它必须将中位生存时间提高超过50％，而 显示出显着引起对肿瘤存在的自然免疫反应的能力。后续 测试将确定任何一个或两个候选人是否可以额外提高中位生存时间25％ 结合免疫检查点阻滞剂。 第二阶段将最终确定通过两种测试的候选人的基于细胞培养的制造过程 在第一阶段，还优化了它们的吸入形式。然后，吸入形式将必须通过相同的效率 和自然免疫响应刺激测试，如第一阶段以及在动物模型中证明安全性 没有肿瘤以进行人类进一步的临床测试。 精确安全，可吸入，有效的EIAV的潜在可实现市场超过100,000个转移性肺 仅在美国，癌症患者每年都在美国，其中绝大多数不会回应当前可用的 治疗和面临惨淡的生存前景。