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: 10080262
• 负责人: Thomas H Large
• 金额: $ 142.59万
• 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/10080262
• 关键词: Acute; Adult; Adverse effects; Affect; American; Animal Model; Anticonvulsants; Antidepressive Agents; Antipsychotic Agents; Back; Behavioral; Biological; Biological Markers; Bipolar Depression; Bipolar Disorder; Businesses; Chemistry; Clinical; Clinical Research; Cognition; Custom; Development; Dose; Drug Combinations; Drug Kinetics; 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; Psyche structure; Quality of life; Race; Rattus; Records; Recurrence; Regulation; Research; Rivers; Rodent; Safety; Schedule; Structure; Substance abuse problem; System; Therapeutic; Toxic effect; Toxicology; Trust; Validation; absorption; base; bipolar mania; clinical candidate; clinical development; clinical research site; commercialization; design; drug candidate; drug development; drug discovery; ex vivo imaging; experience; first-in-human; forced swim test; good laboratory practice; improved; lead optimization; machine learning algorithm; 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; programs; research and development; response; scaffold; scale up; small molecule; social; 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.

蓝橡树制药正在开发下一代药物以治疗急性双极 抑郁和长期维护（BPD），一种精神障碍，影响约600万成年美国人。现存的 药物类相对无效，在过去的40多个中，很少有新的行动方式 年。这部分是由于生物制药行业专注于吸毒单分子靶标的，而缺乏 躁郁症的预测动物模型。为了克服这些重大障碍，蓝橡树的毒品 发现范式结合了定制设计的特权化学型和经过验证的深层行为概况 方法。成功使用这部小说但先前验证的方法进行了I阶段研究，导致了发现 并优化了用于治疗BPD的新型铅化合物。候选毒品的治疗效用 使用分子靶分析，在BPD和 预测转化医学生物标志物。第二阶段研究的重点是推进铅化合物 通过调查新药（IND）增强研究，这是FDA审查和批准的必要下一步 人类研究。目的包括：（1）铅的临床前疗法（安全）范围的数量，或 较高的备份分子，包括抗抑郁活性的分析； （2）确认增强的脑电图 伽马频段是BPD药物活性和非人类隐私效率的可靠翻译生物标志物； （3） CGLP药物的制造和资格适用于辅助研究； （4）完成 与FDA提交IND所必需的临床前研究，包括标准滥用，分布， 代谢，极端和毒性（ADME/TOX）临床前研究和临床前剂量升级研究 在人类第一临床研究之前必不可少。这些目标的成功完成将导致B类 开会以获取FDA和提交IND包的指导。蓝橡树制药团队 包括具有系统神经生物学，医学化学和 信息和顾问具有验证的药物开发和商业化记录。内部 团队得到了临床前研究，开发和验证的信任合作伙伴的支持 医学生物标志物，临床现场管理和临床开发。如果成功，该计划将提供 躁郁症抑郁症的新药候选者，将改善患者及其家人的生活质量。