Highly focused loco-regional chemotherapy for oral cancer - IND 132234 - October 01 2017

项目摘要 根据美国国家癌症研究所的数据，美国约有5万人将被新诊断为口腔癌(OC) 2018年，造成9700多人死亡。OC是一种严重被忽视的孤儿疾病，缺乏显著的治疗进展。 在40年内，约有%的患者在确诊后的头5年内死亡。从历史上看，OC一直存在于重型 烟民和酒鬼。然而，最近，由于 致癌的人类乳头瘤病毒(HPV)通过口交传播。当前的护理标准(SOC)适用于患有 早期疾病是外科手术治疗。然而，这可能会导致损害口腔形态和美观的副作用 功能，如说话和吞咽的能力。手术治疗OC的复发率也非常高， 部分原因是肿瘤边缘难以识别或接触到。 为了解决这一未得到满足的需求，Privo Technologies开发了一种局部化疗贴片PRV111 直接进入肿瘤。PRV111由嵌入顺铂颗粒(CP)的粘附性聚合物贴片组成 以及便于单向药物释放、防止药物流失并掩盖味道的非渗透性衬垫。顺铂是 被公认为治疗口腔癌的金标准化疗药物。然而，顺铂的疗效经常受到阻碍 由传统的全身静脉(IV)给药引起的严重的全身毒性。 CP具有优化的大小、电荷和渗透参数以确保顺铂被局部保留在肿瘤内 组织，不暴露在全身的身体循环中。Privo已经在5种动物身上进行了12组体内研究 目的：研究PRV111的安全性和有效性。在所有病例中，PRV111都显示出强大的抗肿瘤作用，并且没有局部或 全身毒性。这项提议的目标是成功完成Privo的临床试验。这项研究的结果 将出版，与科学界和医学界分享其研究结果。Privo相信其专家团队 科学家、商业领袖和合作者可以通过里程碑和交付成果来执行其定义的目标。

Project Summary According to the National Cancer Institute, about 50,000 people in the US will be newly diagnosed with oral cancer (OC) in 2018, causing over 9,700 deaths. OC is a severely neglected orphan disease with a lack of significant treatment advances in 4 decades and about 64% of patients die within the first 5 years of diagnosis. Historically, OC has been present in heavy smokers and drinkers. However, more recently OC has also become more prevalent in younger people due to an increase in cancer-causing human papillomavirus (HPV) spread through oral sex. The current standard of care (SOC) for patients with early stage disease is surgical intervention. However, this can result in disfiguring side effects that impair oral form and function such as the ability to speak and swallow. Surgical treatment of OC also has an exceptionally high rate of recurrence, due in part to tumor margins which are difficult to identify or access. To address this unmet need, Privo Technologies has developed a topical chemotherapy patch, PRV111 that is applied directly to the tumor. PRV111 consists of a mucoadhesive polymeric patch with embedded cisplatin-loaded particles (CPs) and a non-permeable backing that facilitates unidirectional drug release, prevents drug loss, and masks taste. Cisplatin is recognized as the gold standard chemotherapeutic for treating oral cancer. However, cisplatin’s efficacy is often hindered by significant systemic toxicity resulting from traditional systemic intravenous (IV) administration. CP’s have optimized size, charge, and permeation parameters to ensure that cisplatin is locally retained within the tumor tissue and not exposed to systemic bodily circulation. Privo has performed 12 sets of in vivo studies in 5 species of animals to examine the safety and efficacy of PRV111. In all cases, PRV111 has shown robust antitumor effect and no local or systemic toxicities. The goal of this proposal is the successful completion of Privo’s clinical trial. The results of this study will be published to share its findings with the scientific and medical community. Privo is confident that its team of expert scientists, business leaders, and collaborators can execute its defined aims with milestones and deliverables.