Complement Inhibitors for Macular Degeneration

描述（由申请人提供）：在美国，视网膜相关性黄斑变性（AMD）影响着近1000万人（预防失明研究基金会）。最近批准的抗VEGF疗法是迄今为止治疗湿性AMD的唯一方法。最近的研究已经证明了替代途径（AP）在AMD中的作用。最终导致失明的视力逐渐丧失是成年人群中AMD的主要症状。使用小鼠AMD模型，Bora等人证明了旁路途径的补体因子B在该疾病中起重要作用。通过使用siRNA技术，Bora博士证明了因子B基因的沉默可以防止AMD的诱导和持续。受这些结果的鼓舞，我们决定评估我们的阻断性抗B因子单克隆抗体（Bikaciomab）在抑制AMD发生和进展中的作用。Bikaciomab结合人血液中的因子B蛋白，并阻断其在AP介导的补体激活中的功能。Bikaciomab可预防旁路途径介导的C3 a、C5 a和C5 b-9（负责炎症反应的关键过敏毒素）形成。我们将检测这种阻断性抗B因子抗体在预防和建立疾病模型中的作用，以提供受试药物的直接临床相关性。公共卫生相关性：视网膜相关性黄斑变性（AMD）影响着美国近1000万人（预防失明研究基金会）。最近批准的抗VEGF疗法是迄今为止治疗湿性AMD的唯一方法。在黄斑变性领域存在未满足的医疗需求。NovelMed目前的方法主要集中在中和因子B的功能和提供疾病的好处。使用先前开发的AMD动物模型，NovelMed打算测试其用于治疗AMD的铅补体抑制剂。Bikaciomab在体外、离体和体内的有效活性使得该药物不仅可以作为AMD的潜在治疗药物，还可以作为替代途径在疾病病理学中起重要作用的几种疾病的潜在治疗药物。

DESCRIPTION (provided by applicant): Age-related macular degeneration (AMD) affects nearly 10 million people in the U.S (Research to Prevent Blindness Foundation). Recently approved anti-VEGF therapy is the only cure for wet AMD as of today. Recent studies have demonstrated the role of the alternative pathway (AP) in AMD. Gradual loss of vision eventually resulting in blindness is the key symptom of AMD in the adult population. Using the mouse AMD model, Bora et al demonstrated that complement factor B of the alternative pathway plays an important role in the disease. With the use of siRNA techniques, Dr. Bora demonstrated that silencing of the factor B gene prevents the induction and persistence of AMD. Encouraged by these results, we decided to evaluate the effect of our blocking anti-factor B monoclonal antibody (Bikaciomab) in inhibiting the development and progression of AMD. Bikaciomab binds factor B protein in human blood and blocks its function in AP mediated complement activation. Bikaciomab prevents alternative pathway mediated formation of C3a, C5a, and C5b-9, the key anaphylatoxins responsible for the inflammatory responses. We will test the effect of this blocking anti-factor B antibody in prophylaxis and established models of the disease to provide direct clinical relevance of the drug under testing. PUBLIC HEALTH RELEVANCE: Age-related macular degeneration (AMD) affects nearly 10 million people in the U.S (Research to Prevent Blindness Foundation). Recently approved anti-VEGF therapy is the only cure for wet AMD as of today. There is an unmet medical need in the area of macular degeneration. NovelMed's current approach focuses on neutralizing factor B function and providing disease benefit. Using the previously developed animal models of AMD, NovelMed intends to test its lead complement inhibitor for the treatment of AMD. Potent activity of Bikaciomab in vitro, ex vivo and in vivo makes the drug as a potential therapeutic for not only AMD but also for several diseases where alternative pathway plays an important role in disease pathology.