Bipolar and Related Disorders

Company to initiate Phase 2 trial of ABX-002 for bipolar depression by yearend 2024 ABX-002 also being evaluated as an adjunctive treatment for major depressive disorder in the ongoing AMPLIFY Phase 2 trial SAN DIEGO--(BUSINESS WIRE)--Autobahn Therapeutics, a biotechnology company developing restorative treatments for people affected by neuropsychiatric and neuroimmunologic disorders, today announced the clearance of an investigational new drug (IND) application by the U.S. Food and Drug Administration (FDA) to support initiation of a Phase 2 trial of ABX-002 as an adjunctive treatment for patients with bipolar depression. ABX-002 is a highly potent, oral, thyroid hormone beta receptor (TRβ) selective agonist designed to enhance the CNS benefits of thyroid hormone biology and drug concentrations directly in the brain. “We are thrilled to expand our depression treatment program with ABX-002 and evaluate its potential to safely address the debilitating symptoms of bipolar depression, a highly prevalent and potentially life-threatening disorder,” said Kevin Finney, Autobahn’s President and CEO. “In the U.S. alone, seven million patients suffer from bipolar disorder and there are limited safe and effective therapies that focus specifically on the depressive symptoms that patients face. Our planned Phase 2 trial is designed to provide proof-of-concept for ABX-002 and inform further clinical development in bipolar depression. With this regulatory clearance, we are excited to advance ABX-002 into a second clinical development program later this year alongside our recently initiated Phase 2 study in major depressive disorder.” The Phase 2 trial will evaluate ABX-002 as adjunctive therapy in adult patients with depressive episodes associated with bipolar I or bipolar II disorder. Autobahn will evaluate the biological and clinical proof-of-concept for ABX-002 across multiple endpoints in the trial, including changes in energy metabolism in the brain as determined by phosphorus magnetic resonance spectroscopy ( 31 P-MRS) and changes in patients’ depressive symptoms as measured by the Hamilton Depression Rating Scale (HAMD). ABX-002 is also being evaluated in the company’s ongoing AMPLIFY Phase 2 trial as an adjunctive treatment for patients with major depressive disorder (MDD), with topline data expected in the second half of 2025. About Autobahn Therapeutics Autobahn Therapeutics is a biotechnology company developing a portfolio of neuropsychiatric and neuroimmunologic clinical candidates leveraging its brain-targeting chemistry platform. Autobahn aims to unlock new therapeutic opportunities through precision tuning of CNS exposure, pursuing validated clinical and biologic targets, and guiding development with biomarkers. The company’s pipeline is led by ABX-002, a thyroid hormone receptor beta (TRβ) agonist being developed as a potential adjunctive treatment for people with major depressive disorder and bipolar disorder depression. Autobahn Therapeutics is based in San Diego. For more information, visit . About ABX-002 ABX-002 is an orally administered, potent and selective thyroid hormone beta receptor (TRβ) agonist designed to enhance the CNS benefits of thyroid hormone biology while also reducing the peripheral liabilities of synthetic thyroid hormone (e.g., triiodothyronine, T3), a treatment which has shown efficacy in numerous placebo-controlled human studies across MDD and bipolar depression. Thyroid hormone agonism has demonstrated activity on cellular energy metabolism pathways, which play an important role on the regulation of brain bioenergetics and may be uniquely suited to address symptoms of atypical depression, a highly prevalent and underserved sub-population of MDD. In nonclinical and clinical studies, ABX-002 has demonstrated optimized PK properties, target engagement in brain regions associated with depression, and an attractive safety and tolerability profile. Contacts Investors: Alex Straus THRUST Strategic Communications alex@thrustsc.com Media: Ryan Flinn In Like Flinn Communications ryan@inlikeflinncommunications.com

7月2日，中国国家药监局药品审评中心（CDE）官网公示，纽欧申医药申报的1类新药NS-136片获批临床，拟开发治疗精神分裂症。根据纽欧申医药公开资料，这是一款新型选择性毒蕈碱型乙酰胆碱M4受体正向变构调节剂（M4 PAM），此前该药已经在澳大利亚启动1期临床研究。 精神分裂症是一种高致残率的精神疾病，至少困扰世界上约1%的人口。其临床特征为阳性症状（幻觉、妄想）、阴性症状（情绪扁平、社交失能）和认知障碍。阳性症状目前已有临床药物进行治疗，而长期影响患者社会功能和生活质量的阴性症状和认知障碍仍缺乏有效的治疗手段。 根据纽欧申医药此前新闻稿介绍，对M4受体进行正向调节是治疗精神分裂症的新作用机制，尤其是对阴性症状和认知功能损伤的改善被认为是精神分裂症治疗重要的进步，受到广泛的关注。该靶点还显示在治疗阿尔茨海默病或帕金森病伴随的精神症状有很大的潜力。 NS-136是纽欧申医药公司自有的小分子药物研发平台上研发出的新型高选择性M4 PAM，其在临床前各项研究中表现出良好的体外活性，在疾病动物模型上对阳性症状和阴性症状都展现出良好的治疗效果，成药性也具有差异化优势。 今年4月，纽欧申医药宣布NS-136于澳大利亚正式启动1期临床试验，并已完成首例受试者给药。该1期临床试验是一项随机、双盲、安慰剂对照研究，旨在评估候选药物在健康受试者中的安全性和耐受性，支持后续在精神分裂症等病人上的进一步临床研究。本次该药在中国获批临床，意味着该产品也将在中国开展临床研究。 公开资料显示，纽欧申医药是一家临床阶段的国际化生物技术公司，采用小分子发现和基于AAV的基因治疗的双平台策略，专注于神经和精神疾病的创新药物和疗法的研发。除了本次获批临床的NS-136，该公司还有另一款小分子候选药物NS-041正在开展1期临床，这是一款高选择性KCNQ2/3激活剂，潜在适应症包括癫痫、重度抑郁症、双极情感障碍等疾病。 参考资料： [1]中国国家药监局药品审评中心（CDE）官网. Retrieved July 2，2024. From https://www.cde.org.cn/main/xxgk/listpage/9f9c74c73e0f8f56a8bfbc646055026d [2]纽欧申医药 (NeuShen Therapeutics) 启动新一代精神分裂症候选药物NS-136的首次人体试验. Retrieved Apr 30，2024. From https://mp.weixin.qq.com/s/ATN029dApLsRh5ljRxTbEg 内容来源于网络，如有侵权，请联系删除。

Intra-Cellular Therapies今天宣布在研疗法lumateperone作为抗抑郁药物的辅助治疗，在治疗抑郁症（MDD）的3期临床试验502中获得积极顶线结果。该公司预计将在2024年下半年向美国FDA提交lumateperone的补充新药申请（sNDA），作为辅助疗法治疗MDD。 在502研究中，作为抗抑郁药物的辅助治疗，每日一次服用的lumateperone达到了主要终点，在第6周时与安慰剂相比，显示出在蒙哥马利-阿斯伯格抑郁评分表（MADRS）总评分上的统计学显著和具有临床意义的减少。在调整后的意向治疗（mITT）研究人群中，lumateperone组MADRS总分比基线减少14.7分，而安慰剂为10.2分（平均差异为-4.5分；p<0.0001）。值得一提的是，在第1周就观察到与安慰剂相比在MADRS总分上的数值改善（p=0.0504），并在第2周开始出现统计学显著差异，并在整个研究期间保持。 Lumateperone还达到了研究的关键性次要终点，在第6周时显示出在临床总体印象严重程度（CGI-S）评分上与安慰剂相比统计学显著和具有临床意义的减少（p<0.0001）。从第3周开始在CGI-S评分上与安慰剂相比显示出统计学显著差异，并在整个研究期间保持。 在这项研究中，通过快速抑郁症状自评量表（QIDS-SR-16）测量，lumateperone显著改善了患者报告的抑郁症状（p<0.0001）。QIDS-SR-16是一种由患者评定的16项量表，用于评估抑郁症症状的严重程度。它评估了抑郁症的多个关键症状：包括失眠/嗜睡、情绪低落、食欲/体重变化、自我认知障碍、注意力困难、兴趣/愉快感丧失、自杀意念、精神运动性激越和疲劳。 Lumateperone总体安全性和耐受性良好。最常见的不良事件（≥5%且超过安慰剂两倍）是头晕、嗜睡、口干、恶心、腹泻和疲劳。不良事件大多为轻至中度，并在研究过程中自行缓解。 Lumateperone是一种口服、每日一次的非典型抗精神病药。它已经获得FDA的批准用于治疗精神分裂症以及辅助治疗成人1型或2型双相情感障碍相关的精神分裂症和抑郁发作。虽然其作用机制尚未得到完全澄清，但已知其疗效可通过中枢5-羟色胺受体2A（5-HT2A）的拮抗活性和中枢多巴胺D2受体的突触后拮抗活性联合介导。 参考资料： [1] Intra-Cellular Therapies Announces Positive Topline Results in Second Phase 3 Trial Evaluating Lumateperone as Adjunctive Therapy in Patients with Major Depressive Disorder. Retrieved June 18, 2024, from https://www.globenewswire.com/news-release/2024/06/18/2900311/30597/en/Intra-Cellular-Therapies-Announces-Positive-Topline-Results-in-Second-Phase-3-Trial-Evaluating-Lumateperone-as-Adjunctive-Therapy-in-Patients-with-Major-Depressive-Disorder.html 内容来源于网络，如有侵权，请联系删除。