SBIR Phase I: Clinical-Trials-on-a-Chip

该项目更广泛的影响/商业潜力是一项突破性创新，将彻底改变临床前药物测试，为首个人类临床试验提供有价值的信息，拯救药物，缩短优化治疗的时间，并减少安全风险和不良反应的发生率。芯片临床试验将成为人性化生物疗法体外预测性测试的开创性平台，人性化生物疗法已成为癌症、炎症性疾病、自身免疫疾病、传染性疾病、心血管疾病和神经系统疾病的一线疗法；这是一个价值2000亿美元的市场。该平台还将通过识别人类亚群和疾病亚型的基因组和分子签名来帮助拯救药物，这些药物对这些药物是有效和安全的；因此，在为患者带来安全药物的同时，每种失败的药物为制药业节省超过10亿美元和十年的研究。最后，该平台将服务于价值420亿美元的个性化靶向治疗市场，以比目前通过在小鼠体内植入异种移植实现的成本更低、速度更快的方式优化癌症患者的治疗；从而拯救生命。最终，该项目将降低将安全有效的药物推向市场的成本，并加快一线疗法的开发，造福患者、医疗保健和社会。这个小型企业创新研究(SBIR)第一阶段项目将为人性化生物制药的预测疗效和安全性测试提供临床试验芯片平台；这是一个价值2000亿美元的市场。由于缺乏适当的检测解决方案，靶向治疗和免疫治疗药物在免疫系统受损的动物身上进行测试，从而能够携带这种疾病。例如，癌症免疫疗法在免疫抑制的小鼠身上进行测试，以避免肿瘤移植的排斥反应。其次，动物和人类研究之间的相关性很低，因为这些药物是人性化的，只在人类身上有效。最后，生物制药是大分子，也不能在体外进行适当的测试。在体外平台上，检测小分子、类泰诺、药物清除需要3-4小时，而不是像抗体那样需要1-30天。该项目将通过提供新的体外平台和方法来解决这一问题，用于评估高分子量药物的疗效和安全性。具体地说，片上临床试验将使药物研究人员能够以一种简单易用的研究工具，反映药物分布、半衰期消除和重复剂量测试，以更好地预测疾病器官模型中的抗体特异性和有效性、与正常组织的交叉反应以及目标外器官的责任，如意外的靶外器官毒性。

The broader impact/commercial potential of this project is a breakthrough innovation that will revolutionize preclinical drug testing, provide valuable information for the first-in-human clinical trials, rescue drugs, decrease time to optimize therapies, and reduce the incidence of safety hazards and adverse reactions. Clinical-Trials-on-a-Chip will serve as the pioneering platform for predictive in vitro testing of humanized biotherapeutics that have become first line therapies for cancer, inflammatory, autoimmune, infectious, cardiovascular and neurological diseases; a market worth $200 billion. The platform will also help rescue drugs by identifying genomic and molecular signatures of human sub-populations and disease sub-types for which these drugs are efficacious and safe; thus, saving pharmaceutical industry over $1 billion per failed drug and a decade of research while bringing safe drugs to patients. Lastly, the platform will serve in a $42 billion personalized targeted therapies market to optimize therapies of cancer patients at a lower cost and faster than is currently attainable using xenografts implanted in mice; thus, saving lives. Ultimately, this project will lower cost of bringing safe and efficacious drugs to market and expedite development of frontline therapies for the benefit of patients, health care and society.This Small Business Innovation Research (SBIR) Phase I project will provide Clinical-Trials-on-a-Chip platform for predictive efficacy and safety testing of humanized biopharmaceuticals; a market worth $200 billion. Due to lack of appropriate testing solutions, targeted therapy and immunotherapy drugs are tested in animals which immune system is compromised to be able to carry the disease. For example, cancer immunotherapeutics are tested in immunosupressed mice to avoid rejection of tumor grafts. Next, the correlation between animal and human studies is low because these drugs are humanized and active only in humans. Lastly, biopharmaceuticals are large molecules which cannot be appropriately tested in vitro either. In vitro platforms are made for testing small molecule, Tylenol-like, drugs clearing in 3-4 hours, not in 1-30 days like antibodies do. This project will solve this problem by providing novel in vitro platforms and methods for efficacy and safety assessment of high molecular weight therapeutics. Specifically, Clinical-Trials-on-a-Chip will enable drug researchers to mirror drug distribution, half-life elimination, and conduct repeat dose testing to better predict antibody specificity and efficacy in diseased organ models, cross-reactivity with normal tissues, and off-target organ liabilities such as unexpected off-target organ toxicity in a simple and easy to use research tool.