Koli: A non-surgical solution for gallstone disease

症状性胆结石疾病影响美国近500万人， 每年6.3亿美元。并发症发生时，胆结石从广泛的胆囊体，并进入 连接胆囊和小肠的狭窄的管道系统。胆结石的发病率增加 随着年龄的增长，女性和肥胖者的发病率更高。其他风险因素包括怀孕，激素替代 治疗，快速减肥，糖尿病，克罗恩病，家族史，老年和长期禁食。作为 随着西式饮食在地球仪上的普及，全球胆结石发病率在快速上升， 手术治疗并不总是可用的区域。 目前，最常见和有效的胆石病治疗方法是手术切除胆结石。 胆囊或胆囊切除术。不幸的是，手术并不总是一种选择。患者可能无法 由于合并症（如无法控制的心脏或肺部疾病）导致全身麻醉， 不可能或他们有暂时的条件，延迟手术，例如最近的心脏病发作，中风，或 败血症复发性胆石相关并发症的风险随着等待时间的增加而增加， 手术禁忌症或时间安排延迟会增加发生胆结石相关疾病的风险 并发症急性胆囊炎可以迫使决定进行紧急手术，这些患者非常 高死亡率和发病率风险。 Kōli开发了一种治疗胆结石疾病的非手术替代方案。一种小型植入式过滤器， 在胆囊中展开，以防止与阻塞胆囊出口的胆结石相关的并发症。 器官. Kōli以微创门诊手术取代手术，旨在确保高风险患者的安全 患者，包括老年人、孕妇和近期MI、卒中或手术患者。Kōli适合于 现有的转诊和报销模式，将利用传统的超声和荧光技术， 并将通过介入放射学、胃肠病学或普通外科进行。 该公司的技术是在NSF SBIR奖（#1248295）和私人 投资在过去的5年里，Kōli已经从概念验证， 实验室测试，GLP样大型动物研究，最近完成了成功的首次人体临床试验， 在菲律宾进行可行性研究。 Kōli系统的当前迭代依赖于尖锐的倒钩锚钉穿透血管腔壁。 并将自膨胀过滤器固定到位。穿透锚具有与以下相关的风险： 穿孔疤痕和机械故障一旦展开，锚定装置不能被移除， 手术为了解决这些风险，Kōli与Hoowaki，LLC合作，整合了一种新颖的反移民微 表面进入我们的过滤系统，而不是倒钩锚。这种方法将消除与以下方面有关的风险： 目前的锚和过滤系统将更容易制造，更容易部署， 可在放置后数月内取出。该项目代表了第一次微表面植入物将 用于胆道系统，是胃肠病学中许多创新应用的起点。 这一直接到第二阶段的奖励将资助过滤系统的先进发展，包括 结合创新的微表面纹理涂层以取代当前的带倒钩的金属锚， 集成不透射线钽标记，并在实验室和大型动物中确认更新后的系统 这些活动的完成将使公司能够开始与FDA进行提交前讨论， 初步可行性研究，作为第二B期申请的基础。

Symptomatic gallstone disease affects nearly 5 million people in the United States and consumes over $6.3B annually. Complications occur when gallstones move from the wide body of the gallbladder and enter the narrow system of ducts connecting the gallbladder to the small intestine. The incidence of gallstones increases with age and is higher in women and obese people. Other risk factors include pregnancy, hormone replacement therapy, rapid weight loss, diabetes, Crohn's disease, family history, older age, and prolonged fasting. As Western-style diets gain traction across the globe, the worldwide rate of gallstone disease is rising quickly in areas where surgical treatment is not always available. The most common and effective treatment for gallstone disease today is surgical removal of the gallbladder, or cholecystectomy. Unfortunately, surgery is not always an option. Patients may be unable to tolerate surgery due to comorbidities such as uncontrolled heart or lung diseases which make general anesthesia impossible or they have temporary conditions which delay surgery, for example a recent heart attack, stroke, or sepsis. The risk of a recurrent gallstone-related complication increases with waiting time and patients with a surgical contraindication or scheduling delays are subject to increasing risk of developing gallstone-related complications. Acute cholecystitis can force a decision to perform emergency surgery in these patients with very high mortality and morbidity risks. Kōli has developed a non-surgical alternative to treat gallstone disease. A small implantable filter is deployed in the gallbladder to prevent complications associated with gallstones obstructing the outlet of the organ. Kōli replaces surgery with a minimally invasive outpatient procedure designed to be safe in high risk patients, including the elderly, pregnant women, and patients with recent MI, stroke, or surgery. Kōli fits into existing referral and reimbursement patterns, would utilize conventional ultrasound and fluoroscopic techniques, and will be performed by interventional radiology, gastroenterology, or general surgery. The company’s technology was developed with support from an NSF SBIR award (#1248295) and private investment. Over the past 5 years, Kōli has advanced their novel gallstone filtering system from proof-of-concept bench testing, GLP-like large animal studies, and recently completed a successful first-in-human clinical feasibility study in the Philippines. The current iteration of the Kōli system relies on sharp barbed anchors to penetrate the luminal wall of the gallbladder and hold the self-expanding filter in place. Penetrating anchors carry risks associated with perforation, scarring, and mechanical failure. Once deployed, the anchored device cannot be removed without surgery. To address these risks, Kōli has partnered with Hoowaki, LLC to integrate a novel anti-migration micro surface into our filtering system in place of barbed anchors. This approach will eliminate risks associated with the current anchors and the filtering system will be easier to manufacture, easier to deploy, and completely removable up to months after placement. This project represents the first time a micro surfaced implant will be used in the biliary system and a starting point for a number of innovative applications in gastroenterology. This Direct to Phase II award will fund advanced development of the filtering system, including incorporation of an innovative micro surface textured coating to replace the current barbed metal anchors, integration of radiopaque tantalum markers, and validation of the updated system in bench and large animal studies Completion of these activities will allow the company to begin pre-submission discussions with FDA for an early feasibility study that will form the basis of a Phase IIB application.