Preclinical Innovation

临床前创新

基本信息

批准号：
8940135
负责人：
John McKew
金额：
$ 3071.36万
依托单位：
NATIONAL CENTER FOR ADVANCING TRANSLATIONAL SCIENCES
依托单位国家：
美国
项目类别：
财政年份：
资助国家：
美国
起止时间：
至
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/8940135
关键词：
Academia Acute Acute Brain Injuries Adopted Adoption Alzheimer&apos s Disease Anemia due to Chronic Disorder Area Aromatic-L-Amino-Acid Decarboxylases Atherosclerosis Auranofin Award Biological Products Biotechnology Businesses Chronic Chronic Lymphocytic Leukemia Clinical Clinical Trials Collaborations Combined Modality Therapy Congenital herpes simplex Contractor Core-Binding Factor Cryptococcal Meningitis Cyclodextrins Data Defect Degenerative polyarthritis Development Disease Dose Drug Formulations Drug Kinetics Duchenne muscular dystrophy Epilepsy Failure Fragile X Syndrome Funding Future Giardiasis Goals Government Grant Hemoglobinopathies Human Hyperinsulinism Hypoparathyroidism Inclusion Bodies Induced Heart Arrest Inherited Investigational Drugs Investigational New Drug Application Joints LEOPARD Syndrome Lassa Fever Malaria Marketing Metabolic Diseases Modeling Multiple Sclerosis Myopathy Nonprofit Organizations Patients Peptides Pharmaceutical Chemistry Pharmacodynamics Pharmacologic Substance Phase Pilot Projects Pulmonary Alveolar Proteinosis Radiation Syndromes Rare Diseases Recombinant Proteins Reporting Research Research Infrastructure Research Personnel Research Project Grants Resources Retinitis Pigmentosa Rheumatoid Arthritis Risk Schistosomiasis Science Scientist Services Sickle Cell Anemia Simplexvirus Speed Spinal cord injury Staging Therapeutic Therapeutic Agents Therapeutics for Rare and Neglected Diseases TimeLine Toxicology Translational Research Traumatic Brain Injury United States Food and Drug Administration United States National Institutes of Health Work base beta Thalassemia chronic pain cost creatine transporter eye dryness improved innovation leukemia meetings mimetics neglect new technology novel therapeutics peritoneal cancer pre-clinical preclinical study programs progressive myositis ossificans public-private partnership research clinical testing small molecule therapeutic development

项目摘要

The TRND program was initiated in May 2009, establishing infrastructure and six pilot projects. Through subsequent rounds of public solicitation for new collaborative proposals, a robust portfolio of projects has been developed. Collaborators represent academia, non-profit organizations, small and large biotechnology businesses, and government labs. Upon adoption into the TRND portfolio, a joint project team develops a research project plan and agrees to critical milestones and timelines that must be reached. A project that successfully meets these milestones will be supported scientifically and financially until it can be adopted by an outside organization to complete development and approval by the FDA for marketing. As TRND is a data-driven and milestone-dependent program, projects that fail to meet agreed-upon milestones in a timely fashion are discontinued. Projects adopted for collaboration (in order of solicitation / adoption) include: Pilot Phase: 1. Niemann-Pick Type C1 Disease, a rare disease 2. Hereditary Inclusion Body Myopathy, a rare disease 3. Giardiasis, a neglected disease (project completed) 4. Schistosomiasis, a neglected disease (project discontinued) 5. Sickle Cell Disease, a rare disease (project completed) 6. Chronic Lymphocytic Leukemia, a rare disease (project discontinued) Two solicitations in FY 2011: 1. Duchenne Muscular Dystrophy, a rare disease (2 different projects; one discontinued) 2. Fragile X Syndrome, a rare disease (project discontinued) 3. Cryptococcal Meningitis, a neglected disease 4. CBF Leukemia, a rare disease 5. Neonatal Herpes Simplex Virus, a rare disease 6. Pulmonary Alveolar Proteinosis, a rare disease 7. Fibrodysplasia Ossificans Progressiva, a rare disease 8. Schistosomiasis, a neglected disease 9. Creatine Transporter Defect, a rare disease One solicitation in FY 2012: 1. Retinitis Pigmentosa, a rare disease (2 different projects; one completed) 2. Hypoparathyroidism, a rare disease 3. LEOPARD Syndrome, a rare disease One solicitation in FY 2013: 1. Hemoglobinopathies, a rare disease 2. Lassa Fever, a neglected disease 3. Malaria, a neglected disease Within two years of initiation, four projects (Aes-103 for Sickle Cell Disease; Auranofin for Chronic Lymphocytic Leukemia; Cyclodextrin for Niemann-Pick Type C; and DEX-M74 for Hereditary Inclusion Body Myopathy) yielded successful IND applications to the FDA, and first in-human clinical trials were initiated in all four. One pilot project (Giardiasis) successfully completed its project milestones, while another pilot project (Schistosomiasis) was discontinued for failure to meet preclinical milestones. A third pilot (Chronic Lymphocytic Leukemia) was discontinued for failure to meet clinical milestones. Two projects adopted in FY 2011 (Duchenne Muscular Dystrophy; Fragile X Syndrome) were discontinued from the TRND portfolio. The Duchenne Muscular Dystrophy partner is now able to carry out future steps without further TRND support, whereas the Fragile X Syndrome project was discontinued due to realignment of the collaborators business strategy. Two projects have been successfully de-risked and adopted by outside biopharmaceutical partners (Aes-103 for Sickle Cell Disease; a small molecule for Retinitis Pigmentosa). The development of therapeutics for these rare or neglected indications continues to involve resources in the following areas, performed and/or provided by TRND: 1. Medicinal Chemistry Optimization 2. Pharmacokinetics / Pharmacodynamics 3. Toxicology 4. Dosing 5. Formulation 6. Regulatory Support 7. Project Management In FY 2014, three new BrIDGs projects were initiated. These projects include a small molecule combination therapy for cardiac arrest-induced acute brain injury, a peptide mimetic therapy for beta thalassemia, and a recombinant protein therapeutic for Acute Radiation Syndrome. Other ongoing BrIDGs projects support the development of potential therapies for Aromatic L-Amino Acid Decarboxylase Deficiency, Alzheimers Disease, Anemia of Inflammation, Atherosclerosis, Chronic Pain, Epilepsy, Fibrodysplasia Ossificans Progressiva, Hyperinsulinism, Hypoparathyroidism, Peritoneal Cancer, Niemann-Pick C Disease, Metabolic Disorder, Multiple Sclerosis, Osteoarthritis, Spinal Cord Injury and Traumatic Brain Injury. Upon completion of agreed upon in-kind studies, projects related to therapies for Chronic Dry Eye and Rheumatoid Arthritis were discontinued. The Chronic Dry Eye project led to an IND filing by the BrIDGs collaborator, Parion Sciences. In January 2014, BrIDGs solicited applications for new projects. Over seventy pre-application calls were held and awards are expected in September 2014.

TRND计划于2009年5月启动，建立了基础设施和六个试点项目。通过随后对新合作提案的公共招标，已经开发了强大的项目组合。合作者代表学术界，非营利组织，小型和大型生物技术业务以及政府实验室。通过收养TRND投资组合后，一个联合项目团队制定了研究项目计划，并同意必须达到的关键里程碑和时间表。成功符合这些里程碑的项目将得到科学和财务的支持，直到外部组织可以通过FDA来完成开发和批准以进行营销。由于TRND是一个数据驱动和里程碑依赖的计划，因此停止了及时达到同意的里程碑的项目。通过合作的项目（按照征求 /采用的顺序）包括：飞行员阶段： 1。Niemann-Pick型C1疾病，一种罕见疾病 2。遗传性包容体肌病，一种罕见的疾病 3。贾第鞭毛疾病，一种被忽视的疾病（项目完成） 4。血吸虫病，一种被忽视的疾病（已终止的项目） 5。镰状细胞疾病，一种罕见疾病（项目完成） 6。慢性淋巴细胞性白血病，一种罕见疾病（已终止项目） 2011财年的两项招标： 1。Duchenne肌肉营养不良，一种罕见疾病（2个不同的项目；一个停产） 2。脆弱的X综合征，一种罕见的疾病（已停用的项目） 3。隐球菌脑膜炎，一种被忽视的疾病 4。CBF白血病，一种罕见疾病 5。新生儿单纯疱疹病毒，一种罕见的疾病 6。肺肺泡蛋白质病，一种罕见的疾病 7。纤维状发育异常，一种罕见的疾病 8。血吸虫病，一种被忽视的疾病 9。肌酸转运蛋白缺陷，一种罕见的疾病 2012财年的一次招标： 1。色素性视网膜炎，一种罕见疾病（2个不同的项目；一个完成） 2。甲状腺功能减退症，一种罕见疾病 3。豹综合症，一种罕见的疾病 2013财年的一次招标： 1。血红蛋白病，一种罕见的疾病 2。拉萨发烧，一种被忽视的疾病 3.疟疾，一种被忽视的疾病在开始的两年内，四个项目（镰状细胞疾病的AES-103；慢性淋巴细胞性白血病的Auranofin；用于Niemann-Pick type c; cyclodextrin cyclodextrin c;和遗传性包含体的DEX-M74）为FDA提供了成功的IND应用程序，并获得了FDA的成功应用程序，并在Human In-Human Clunical Intial Intial Inter Intial Inder In All Firical Inders In in All Firsiped Siped Shiss in Your Firs中启动了四个四周的临床。一个试点项目（Giardiasis）成功完成了其项目里程碑，而另一个试点项目（Schistosomisis）因未能达到临床前里程碑而停产。第三个试点（慢性淋巴细胞性白血病）因未能达到临床里程碑而停产。 2011财年通过的两个项目（Duchenne肌肉营养不良；脆弱的X综合征）与TRND投资组合停产。 Duchenne肌肉营养不良伴侣现在能够在没有进一步支持的情况下执行未来的步骤，而由于协作者业务策略的重组，脆弱的X综合征项目被停止了。两个项目已被外部生物药物伴侣（用于镰状细胞疾病的AES-103；色素性视网膜炎的小分子）成功地脱离风险和采用。这些罕见或被忽视的指示的治疗剂的开发继续涉及以下领域的资源，该领域由TRND执行和/或提供： 1。药物化学优化 2。药代动力学 /药效学 3。毒理学 4。给药 5。配方 6。监管支持 7。项目管理在2014财年，启动了三个新的Bridgs项目。这些项目包括用于心脏骤停引起的急性脑损伤的小分子组合疗法，用于β地中海贫血的肽模拟疗法以及用于急性辐射综合征的重组蛋白质治疗。 Other ongoing BrIDGs projects support the development of potential therapies for Aromatic L-Amino Acid Decarboxylase Deficiency, Alzheimers Disease, Anemia of Inflammation, Atherosclerosis, Chronic Pain, Epilepsy, Fibrodysplasia Ossificans Progressiva, Hyperinsulinism, Hypoparathyroidism, Peritoneal Cancer, Niemann-Pick C Disease, Metabolic Disorder, Multiple Sclerosis,骨关节炎，脊髓损伤和创伤性脑损伤。完成商定的实物研究后，停止了与慢性干眼症和类风湿关节炎有关的项目。慢性干眼项目导致Bridgs合作者Parion Sciences提交了IND申请。 2014年1月，Bridgs征求了新项目的申请。举行了超过70次预定的电话，预计将于2014年9月奖励。