Next generation drugs for bipolar depression and maintenance

用于双相抑郁症和维持治疗的下一代药物

• 批准号: 10588254
• 负责人: Thomas H Large
• 金额: $ 33万
• 依托单位: BLUE OAK PHARMACEUTICALS, INC.
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-01 至 2024-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10588254
• 关键词: Acute; Adult; Adverse effects; Affect; American; Animal Model; Anticonvulsants; Antidepressive Agents; Antipsychotic Agents; Behavioral; Biological Markers; Bipolar Depression; Bipolar Disorder; Businesses; Chemistry; Clinical Research; Cognition; Custom; Development; Dose; Drug Kinetics; Drug Packaging; Drug Prescriptions; Economic Burden; Electroencephalography; Excretory function; Exhibits; Family; Fingerprint; Formulation; Future; Gender; Human; Industry; Informatics; Investigational Drugs; Investigational New Drug Application; Ketamine; Lead; Legal patent; Libraries; Macaca fascicularis; Maintenance; Medical; Mental Health; Mental disorders; Metabolism; Methods; Modeling; Molecular; Molecular Target; Monkeys; Morbidity - disease rate; Mus; N-Methylaspartate; National Institute of Mental Health; Neurobiology; Oral; Patient Noncompliance; Patients; Pharmaceutical Chemistry; Pharmaceutical Preparations; Pharmacodynamics; Pharmacologic Substance; Pharmacotherapy; Phase; Phase I Clinical Trials; Primates; Property; Prosencephalon; Qualifying; Quality of life; Race; Rattus; Records; Recurrence; Regulation; Research; Rodent; Safety; Schedule; Societies; Structure; Substance abuse problem; System; Technology; Therapeutic; Toxicology; Trust; Validation; absorption; bioactive scaffold; bipolar mania; clinical candidate; clinical development; clinical research site; commercialization; design; drug candidate; drug development; drug discovery; drug maintenance; ex vivo imaging; experience; first-in-human; forced swim test; good laboratory practice; improved; lead optimization; machine learning algorithm; manufacture; meetings; next generation; nonhuman primate; novel; novel drug class; novel lead compound; novel therapeutics; object recognition; phase 1 study; phase 2 study; pre-clinical; pre-clinical research; preclinical development; preclinical study; preclinical toxicity; programs; response; safety assessment; scale up; small molecule; social; suicide rate; symptom treatment; therapeutic development; translational medicine

Blue Oak Pharmaceuticals is developing the next generation of drugs for the treatment of acute bipolar depression and long-term maintenance (BPD), a mental disorder that affects ~6 million adult Americans. Existing drug classes are relatively ineffective and very few new modes-of-action have been developed in the past 40+ years. This is due, in part, to the biopharma industry’s focus on drugging single molecular targets, and the lack of predictive animal models for bipolar disorder. To overcome these significant hurdles, Blue Oak’s drug discovery paradigm combines custom-designed privileged chemotypes with a proven deep behavioral profiling method. Successful Phase I studies using this novel, but previously validated, approach resulted in the discovery and optimization of a novel lead compound for the treatment of BPD. The therapeutic utility of drug candidates was confirmed using molecular target profiling, ex vivo imaging of the forebrain circuits implicated in BPD and predictive translational medicine biomarkers. Phase II studies are focused on advancing the lead compound through Investigational New Drug (IND)-enabling studies, the necessary next step for FDA review and approval of human studies. Aims include: (1) quantification of the preclinical therapeutic (safety) margin for the lead, or superior back-up molecule, including analyses of antidepressant activity; (2) confirmation of an enhanced EEG gamma band as a reliable translational biomarker of BPD drug activity and efficacy in non-human primates; (3) manufacture and qualification of cGLP drug product suitable for IND-enabling studies; and (4) completion of preclinical studies necessary for an IND filing with the FDA, including standard absorption, distribution, metabolism, excretion, and toxicity (ADME/TOX) preclinical studies and preclinical dose escalation studies necessary prior to first-in-human clinical studies. The successful completion of these aims will result in a Type B meeting to obtain guidance from the FDA and the filing of an IND package. The Blue Oak Pharmaceuticals team includes experienced “drug hunters” with expertise in systems neurobiology, medicinal chemistry and informatics, and advisors with proven track records in drug development and commercialization. The internal team is supported by trusted partners in preclinical research, development and validation of translational medicine biomarkers, clinical site management, and clinical development. If successful, this program will deliver a new drug candidate for bipolar depression that will improve the quality of life of patients and their families.

Blue Oak Pharmaceuticals正在开发下一代治疗急性双相情感障碍的药物 抑郁症和长期维持（BPD），一种影响约600万成年美国人的精神障碍。现有 药物类别相对无效，在过去的40多年中几乎没有开发出新的作用方式 年这在一定程度上是由于生物制药行业专注于单一分子靶点的药物， 双相情感障碍的预测动物模型。为了克服这些重大障碍，Blue Oak的药物 发现范式结合了定制设计的特权化学型和经过验证的深度行为分析 法使用这种新颖但之前经过验证的方法进行的成功的第一阶段研究导致了这一发现 以及用于治疗BPD的新型先导化合物的优化。候选药物的治疗效用 使用分子靶点分析、涉及BPD的前脑回路的离体成像和 预测性转化医学生物标志物。第二阶段研究的重点是推进先导化合物 通过研究性新药（IND）-使能研究，FDA审查和批准的必要下一步 人类研究。目的包括：（1）电极导线临床前治疗（安全）裕度的量化，或 上级备用分子，包括抗抑郁活性分析;（2）确认增强EEG γ带作为非人灵长类动物中BPD药物活性和疗效的可靠翻译生物标志物;（3） 适用于IND使能研究的cGLP制剂的生产和确认;以及（4）完成 向FDA提交IND申请所需的临床前研究，包括标准吸收、分布， 代谢、排泄和毒性（ADME/TOX）临床前研究和临床前剂量递增研究 在首次人体临床研究之前，这些目标的成功完成将导致B型 会议，以获得FDA的指导和IND包装的备案。Blue Oak制药公司 包括经验丰富的“药物猎人”，在系统神经生物学，药物化学和 在药物开发和商业化方面有良好记录的顾问。内部 团队在临床前研究、开发和转化验证方面得到值得信赖的合作伙伴的支持。 医学生物标志物、临床研究中心管理和临床开发。如果成功，该计划将提供 一种治疗双相抑郁症的新药候选药物，将改善患者及其家人的生活质量。