Next generation drugs for bipolar depression and maintenance

蓝橡树制药公司正在开发治疗急性双相情感障碍的下一代药物 抑郁症和长期维持(BPD)，这是一种影响约600万美国成年人的精神障碍。现有 药物类别相对无效，在过去的40多年里很少有新的作用模式被开发出来 好几年了。这在一定程度上是由于生物制药行业专注于单分子靶标的药物，而缺乏 双相情感障碍的预测动物模型。为了克服这些重大障碍，蓝橡树的药物 发现范式将定制设计的特权化学类型与经过验证的深度行为分析相结合 方法。成功的第一阶段研究使用了这种新颖的、但之前经过验证的方法，导致了这一发现 以及治疗BPD的新型先导化合物的优化。候选药物的治疗作用 已通过分子靶标分析、BPD和BPD所涉及的前脑回路的体外成像得到证实 预测性转化医学生物标记物。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)启用研究，FDA审查和批准的必要下一步 人类研究的一部分。目标包括：(1)量化铅的临床前治疗(安全)边际，或 高级支持分子，包括抗抑郁活性的分析；(2)确认增强的脑电 在非人类灵长类动物中，伽马带是BPD药物活性和疗效的可靠翻译生物标志物；(3) 适合IND研究的cGLP药物产品的制造和资格；及(4)完成 向FDA提交IND文件所需的临床前研究，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 在第一次人类临床研究之前是必要的。这些目标的成功实现将导致B类 召开会议以获得FDA的指导，并提交IND包。蓝橡树制药团队 包括经验丰富的“药物猎人”，具有系统神经生物学、药物化学和 信息学，以及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、开发和验证翻译方面得到值得信赖的合作伙伴的支持 药物生物标记物、临床场地管理和临床开发。如果成功，该计划将提供 一种治疗双相抑郁的新药候选药物，将改善患者及其家人的生活质量。

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.