Disease Modifying Biologics for Rheumatoid Arthritis

描述（由申请人提供）： 在美国有近7000万人患有关节炎相关疾病[1，2]。其中，类风湿性关节炎（RA）病例约占300万例。RA是一种慢性全身性炎症性疾病，主要导致关节的侵蚀性破坏，并伴有其他可变的关节外效应。不断增长的老年人口加上RA在老年人群中的患病率（高达三分之一的病例），突出了开发有效治疗方案以减轻美国未来几十年医疗保健负担的迫切需要。 NovelMed开发了一种有效的抗关节炎药物YalcioMab，可特异性阻断补体旁路途径的激活。该化合物可防止单核细胞产生TNF-1（肿瘤坏死因子1）;有效抑制RA动物模型中的炎症和关节破坏;并在初步研究中表现出良好的安全性。该快速通道申请提出通过1）评估其在抗原诱导的关节炎（AIA）的兔模型的预防和治疗模型中的功效; 2）表征和体内测试其嵌合形式c-YalcioMab;和3）生产、表征、体内和毒理学评估其人源化形式h-YalcioMab来进一步开发YalcioMab作为有效的抗关节炎剂。 NovelMed预计，在这项重要的研究之后，h-YalcioMab将准备作为临床前IND（研究性新药）工作的产品。根据迄今为止获得的初步结果，NovelMed预计h-YalcioMab治疗将比目前的药物英夫利昔单抗（RemicadeTM）和Enbrel更具特异性，后者也针对人体中TNF-1的基础水平。NovelMed已经提交了保护YalcioMab及其类似物的专利申请，并拥有新生物制剂的专有权。NovelMed由NIH和几个投资者的资金支持，是一家设备齐全的药物发现公司，专注于生物制剂。总的来说，所提出的工作是在通过调节特异性补体介导的炎症反应来预防RA患者关节破坏的成本有效、有效和安全的治疗剂的方向上。 公共卫生相关性： 风湿性关节炎（RA）影响了美国近300万人，但没有有效和安全的治疗方法。目前主要针对炎症的类风湿性关节炎（RA）疗法并不是对所有患者都有效。NovelMed开发了一种有效的抗关节炎药物，在有限的动物模型研究中显示出优异的结果。NovelMed的治疗剂可防止中性粒细胞、单核细胞和血小板的激活，这些细胞共同驱动与RA相关的炎症和关节破坏。本申请拟通过体外和体内研究开发该药剂，以便在不久的将来向FDA提交IND申请。

DESCRIPTION (provided by applicant): Nearly 70 million people in the US suffer from arthritis related conditions[1, 2]. Of these, rheumatoid arthritis (RA) cases constitute approximately 3 million. RA is a chronic systemic inflammatory disease that primarily results in erosive destruction of articular joints with additional variable extra-articular effects. The growing elderly population coupled with the prevalence of RA in the elderly age group (up to a third of cases) highlights the critical need to develop effective treatment options to reduce the health care burden of the US in the coming couple of decades. NovelMed has developed a potent anti-arthritic pharmaceutical agent YalcioMab that specifically blocks the activation of the alternative complement pathway. This compound prevents TNF-1 (tumor necrosis factor 1) production by monocytes; effectively inhibits inflammation and joint destruction in an animal model of RA; and exhibits a good safety profile in initial studies. This Fast Track application proposes to further develop YalcioMab as a potent anti-arthritic agent through 1) evaluation of its efficacy in prophylactic and therapeutic models of rabbit models of antigen-induced arthritis (AIA); 2) characterization and in vivo testing of its chimeric version c-YalcioMab; and 3) production, characterization, in vivo and toxicological evaluation of its humanized version h-YalcioMab. NovelMed expects that following this important research, h-YalcioMab will be ready as a product for pre-clinical IND (investigational new drug) work. Based on the preliminary results obtained so far, NovelMed projects that h-YalcioMab treatment will be more specific than current drugs, infliximab (RemicadeTM) and Enbrel, which also target basal levels of TNF-1 in the human body. NovelMed has filed patent applications protecting YalcioMab and its analogs and has exclusive rights on the new biologic. NovelMed is supported by funds from the NIH and a couple of investors, and is a fully equipped drug discovery company focusing on biological agents. Overall, the proposed work is in the direction of a cost-effective, efficacious and safe therapeutic agent for preventing joint destruction in RA patients through regulation of a specific complement- mediated inflammatory response. PUBLIC HEALTH RELEVANCE: Rheumatoid arthritis (RA) affects nearly 3 million individuals in the US, yet no effective and safe treatment is available. Current therapies for rheumatoid arthritis (RA), which primarily target inflammation, are not effective in all patients. NovelMed has developed a potent anti-arthritic pharmaceutical agent that shows excellent results in limited animal model studies. NovelMed's therapeutic agent prevents activation of neutrophils, monocytes and platelets, which together drive inflammation and joint destruction associated with RA. This application proposes to develop the pharmaceutical agent through in vitro and in vivo studies so as to file an IND application with the FDA in the near future.