PML antiviral for AIDS

描述（由申请人提供）：Inhibikase Therapeutics是一家早期生物制药公司，开发一种治疗艾滋病患者感染疾病的新策略。该公司寻求创造一种抗感染产品，用于治疗导致进行性多灶性脑白质病（PML）的JC病毒感染，这是一种艾滋病定义疾病。PML由上述患者的JC病毒再激活引起，在中枢神经系统诱发炎症性疾病，已证明其致死率为70%。由于这种疾病发生在各种各样的患者身上，已经迫使Tysabri（治疗多发性硬化症）和Raptiva（治疗牛皮癣）等基准药物由于疾病的零星发生而退出市场，因此Inhibikase有机会帮助目前处于PML风险中的非常大的患者群体。虽然拟议开发的产品可以帮助艾滋病患者群体之外的人，但艾滋病患者中PML的发生代表了开发治疗PML产品的最佳患者群体。艾滋病患者是积极分子，他们在很大程度上得到统一的治疗，因此，这些患者的反应率可能较少受到健康状况、免疫状况等变化的影响。PML的病原体多瘤病毒（polyomavirus JC）是人类病原体的一个小家族，可导致生殖泌尿道和中枢神经系统的衰弱或致命疾病。每年受多瘤病毒疾病影响的患者总数超过15万，因此，该公司开发的抗jc抗病毒药物可能具有为许多致命疾病提供新的治疗范例的额外好处。该公司已经确定了一个小分子家族，其中一些可以重新利用，并已被证明对人类使用是安全的，能够在细胞培养和小鼠中干扰小鼠多瘤病毒感染。由于这些小分子靶向细菌和病毒病原体所依赖的宿主途径，这些小分子代表了对当前传染病治疗范式的巨大背离，因此该公司的治疗策略有可能同时应用于单个患者的多种传染病。在本案例中，该公司已经筛选了其针对结核病、流感（H5N1）、痘、小鼠多瘤和疱疹病毒的化合物组合，并观察了其体外抗病毒活性。小鼠多瘤病毒与JC属于同一多瘤病毒家族，这表明该公司的先导化合物可能对JC病毒有活性。公司建议评估其化合物组合在培养中对JC病毒的抗病毒功效，并确定其化合物组合作为可进入临床的药物的效用。目前尚无动物模型对复方抗jc的体内疗效进行评价。因此，在提交初始新药申请之前，将进一步评估培养中具有抗jc疗效的化合物的安全性和可药性，以便在临床环境中试验有效的抗PML化合物。

DESCRIPTION (provided by applicant): Inhibikase Therapeutics is an early stage biopharmaceutical company developing a novel strategy for treating infectious disease that occurs in AIDS patients. The Company seeks to create an anti-infective product for treatment of JC viral infection, which leads to progressive multifocal leukoencephalopathy (PML), an AIDS- defining disease. PML results from JC virus reactivation in the aforementioned patients, inducing an inflammatory disease in the central nervous system that has proven to be >70% fatal. Because the disorder occurs in a wide variety of patients, has forced such benchmark drugs as Tysabri (for MS) and Raptiva (for psoriasis) off the market due to the sporadic occurrence of the disease, Inhibikase has the opportunity to help a very large patient population now at risk for PML. While the proposed product to be developed could help people outside of the AIDS patient population, the occurrence of PML in AIDS patients represents the best patient population for which to develop a product to treat PML. AIDS patients are activist and they are largely treated in a uniform fashion, therefore, the response rate in these patients is likely to be less affected by variations in health, in immunity status, etc. The causative agent for PML, the polyomavirus JC, is one of a small family of human pathogens that can lead to debilitating or fatal diseases of the genitourinary tract and the central nervous system. The total patient population affected by polyomaviral diseases is well in excess of 150,000 patients annually, thus, the Company's development of an anti-JC antiviral could have the added benefit of providing a new therapeutic paradigm for a number of fatal diseases. The Company has identified a family of small molecules, several which could be re-purposed and have been shown to be safe-for-human use, that are capable of interfering with mouse polyoma virus infection in cell culture and in the mouse. These small molecules represent a dramatic departure from current treatment paradigms for infectious disease, because these molecules target host pathways upon which bacterial and viral pathogens depend, the Company's treatment strategy has the potential to be applied to multiple infectious diseases simultaneously in a single patient. In the present case, the Company has screened its compound portfolio against TB, flu (H5N1), pox, mouse polyoma and herpes viruses and seen in vitro antiviral activity. Mouse polyoma is of the same family of polyomaviruses that JC belongs to, suggesting that the Company's lead compounds could be active against JC virus. The Company proposes to assess the antiviral efficacy of its compound portfolio against JC virus in culture and to establish the utility of its compound portfolio as drugs that could enter the clinic. No animal models exist for the evaluation of anti-JC compound efficacy in vivo. Thus, compounds with anti-JC efficacy in culture will be further evaluated for safety and drugability prior to filing Initial New Drug applications to trial the effective compounds against PML in the clinical setting. PUBLIC HEALTH RELEVANCE: Inhibikase Therapeutics is an early stage biopharmaceutical company developing a novel strategy for treating a fatal infectious disease, progressive multifocal leukoencephalopathy, that occurs in AIDS patients. The Company's products will treat this viral infection and save up to 150,000 lives and protect more than 500,000 patients from becoming at risk for this fatal disorder.