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9,700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 大约64%的患者在诊断后的前5年内死亡。从历史上看，OC一直存在于重 吸烟者和饮酒者然而，最近OC也变得更加流行的年轻人，由于增加， 致癌的人乳头瘤病毒（HPV）通过口交传播。患者的当前标准治疗（SOC） 早期疾病是手术干预。然而，这可能导致损害口腔形态的毁容副作用， 例如说话和吞咽的能力。OC的手术治疗也具有极高的复发率， 部分由于肿瘤边缘难以识别或接近。 为了解决这一未满足的需求，Privo Technologies开发了一种局部化疗贴片PRV 111， 直达肿瘤。PRV 111由粘膜粘附聚合物贴剂和包埋的顺铂负载颗粒（CP）组成 以及促进单向药物释放、防止药物损失和掩盖味道的非渗透性背衬。顺铂是 被认为是治疗口腔癌的金标准化疗剂。然而，顺铂的功效往往受到阻碍 由于传统的全身静脉内（IV）给药导致的显著的全身毒性。 CP具有优化的尺寸、电荷和渗透参数，以确保顺铂局部保留在肿瘤内 组织并且不暴露于全身性身体循环。Privo已在5种动物中进行了12组体内研究 以检查PRV 111的安全性和有效性。在所有情况下，PRV 111均显示出稳健的抗肿瘤作用，并且没有局部或局部抑制作用。 全身毒性。该提案的目标是成功完成Privo的临床试验。本研究结果 将发表，与科学和医学界分享其发现。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实现其既定目标。

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.