权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Production and quality analysis of clinical drug for a novel CNS protein kinase inhibitor therapeutic candidate

新型中枢神经系统蛋白激酶抑制剂治疗候选药物的生产和临床质量分析

基本信息

批准号：
9902252
负责人：
Daniel Martin Watterson
金额：
$ 201.87万
依托单位：
NEUROKINE THERAPEUTICS, LLC
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-09-30 至 2021-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9902252
关键词：
Address Alzheimer&apos s Disease Alzheimer&apos s disease related dementia Amyloid Animal Model Arts Attenuated Canis familiaris Central Nervous System Diseases Clinical Clinical Research Clinical Trials Cognition Disorders Complex Development Disease Disease Progression Drug Targeting Drug effect disorder Foundations Frontotemporal Dementia Functional disorder Funding GMP lots Gelatin Generations Goals Heat shock proteins Impaired cognition Investigation Investigational Drugs Neurodegenerative Disorders Neuroglia Neurons Outcome Parkinson Disease Pathway interactions Patients Pharmaceutical Preparations Pharmacology Phase Phase II Clinical Trials Preparation Production Progressive Disease Protein Isoforms Protein-Serine-Threonine Kinases Rattus Scheme Specificity Stress Synapses Testing Therapeutic Toxicology Treatment Efficacy Validation Work capsule clinical development drug candidate drug production drug quality first-in-human improved insight large scale production lot production neglect neuroinflammation novel novel therapeutic intervention prevent protein kinase inhibitor therapeutic candidate therapeutic development virtual

项目摘要

ABSTRACT Alzheimer’s disease (AD) and related dementias are increasing rapidly yet, remarkably, there are no approved disease modifying drugs. Virtually all trials targeting amyloid related pathways have failed over the last 10 years. Regrettably, few alternative targets or pathways have been explored. Therefore, there is an urgent need to explore alternative pathways as monotherapies or as constituents of a multi-drug armamentarium for a complex disease. An alternative view of progressive neurodegenerative disorders such as AD, frontotemporal dementia, and Parkinson’s disease is diseases of progressive synaptic dysfunction. Protein kinase inhibitors (PKI) are logical candidates to explore as potential attenuators of such progressive synaptic dysfunction and cognitive decline. However, PKI drug candidates are under explored as a foundation for CNS disease- modifying therapeutic development and there are currently no approved CNS PKI drugs for any indication. This proposal is a discrete component of a clinical development campaign for a novel stress PKI drug candidate, MW01-18-150SRM (= MW150) that represents a paradigm change for CNS targeted diseases such as AD. MW150 is distinct from past or current drug candidates in AD clinical trials. MW150 ameliorates cognitive dysfunction in discrete AD-relevant animal models. MW150 has a unique profile of target recognition, pharmacological features, and efficacy outcomes. A GMP production scheme was developed and provided the first released clinical drug supply for first-in-human (FIH) trials. This prior art provides a firm foundation for a commercial scale production of GMP drug substance (API) and drug product (drug-in-capsule). There is an immediate need for multi-Kg scale production of drug substance and validation of commercial drug product in order to move into first-in-patient (FIP) status without untoward delays. In this regard, our specific aims are: aim 1, develop and validate a large-scale production lot for GMP clinical drug substance (API); aim 2, generate a pilot lot of. Completion of aim 1 is required immediately for the extended toxicology studies. Completion of aims 1 and 2 allows immediate generation of the phase 2 IND quality (CMC) section and initiation of planning for phase 2 FIP trials. The FIP trials will provide alternative therapeutic approaches to AD and related dementia. The clinical campaign is directly testing the hypothesis that an isoform selective PKI drug can address the synaptic dysfunction and injurious neuroinflammation that characterize diverse neurodegenerative diseases. Further, attenuating the disease relevant pathways associated with increased p38aMAPK activity in both neurons and glia tests the hypothesis that improved efficacy can be obtained with a single target drug that works via pleiotropic drug action.

摘要