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

该项目的广泛影响/商业潜力是一项突破性创新，将彻底改变临床前药物测试，为首次人体临床试验提供有价值的信息，挽救药物，缩短优化治疗的时间，并减少安全隐患和不良反应的发生率。临床试验芯片将作为人类生物治疗药物预测性体外测试的开创性平台，这些药物已成为癌症、炎症、自身免疫、感染性、心血管和神经系统疾病的一线治疗方法；价值2000亿美元的市场。该平台还将通过识别这些药物有效和安全的人类亚群和疾病亚型的基因组和分子特征来帮助拯救药物；因此，每个失败的药物为制药业节省了超过10亿美元和十年的研究时间，同时为患者带来了安全的药物。最后，该平台将服务于420亿美元的个性化靶向治疗市场，以更低的成本和更快的速度优化癌症患者的治疗方法，而不是目前使用植入小鼠的异种移植物。因此，挽救生命。最终，该项目将降低将安全有效药物推向市场的成本，加快一线疗法的开发，造福患者、医疗保健和社会。这个小企业创新研究（SBIR）一期项目将为人源化生物制药的预测疗效和安全性测试提供芯片临床试验平台；价值2000亿美元的市场。由于缺乏适当的测试方案，靶向治疗和免疫治疗药物在免疫系统受损而无法携带疾病的动物身上进行测试。例如，癌症免疫疗法在免疫抑制的小鼠中进行测试，以避免肿瘤移植物的排斥反应。其次，动物和人类研究之间的相关性很低，因为这些药物是人源化的，只对人类有效。最后，生物制药是大分子，也不能在体外进行适当的测试。体外平台用于测试小分子，类似泰诺的药物，在3-4小时内清除，而不是像抗体那样在1-30天内清除。本项目将通过为高分子量治疗药物的疗效和安全性评估提供新的体外平台和方法来解决这一问题。具体来说，clinal - trials -on-a- chip将使药物研究人员能够通过一个简单易用的研究工具来反映药物分布、半衰期消除、进行重复剂量测试，从而更好地预测抗体在病变器官模型中的特异性和有效性、与正常组织的交叉反应性以及意外脱靶器官毒性等脱靶器官负荷。

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.