PROJECT SUMMARY Gastroesophageal reflux disease (GERD) affects 8-33% of the global population. GERD can lead to esophagitis, strictures, ulcerations and Barrett's esophagus (BE). Patients with BE have up to an 125-fold increased risk of developing esophageal adenocarcinoma—a devastating outcome which is fatal in roughly 80-90% of cases. Currently, the gold standard treatment for GERD remains long-term proton pump inhibitors, i.e. PPI therapy, or laparoscopic Nissen fundoplication (LNF). However, PPI therapy fails to control GERD symptoms in 25%-42% of patients, and the chronic use of PPIs is associated with serious adverse effects. Moreover, LNF is technically exacting, and currently fewer than 1% of the eligible GERD population pursue surgery due to concerns of postoperative complications and surgical failure. Thus, an alternative surgical treatment is needed to close the “therapy gap”. Re cently, LINX magnetic sphincter augmentation surgery (MSA) has become an alternative surgical option to address the therapy gap (FDA-approved, January, 2012; Torax Medical, MN), The LINX device is a ring of magnets permanently placed laparoscopically around the gastroesophageal junction (GEJ). Although the side-effect profile of MSA is somewhat superior to LNF, unfortunately, high rates of postoperative dysphagia are routinely seen after LINX placement along with low rates of device erosion. To address these issues and improve GERD therapy, we have developed an entirely new class of GERD treatment: a novel biodegradable device. Our device is called the Eschara suture collar and consists of a dense, tubular matrix of bioabsorbable suture material that will create a ring of collagen around the lower esophageal sphincter, in the region of the GEJ. As the material biodegrades within a matter of days, it loses tensile strength, thus avoiding any dysphagia. Within a matter of weeks, the suture collar material totally absorbs and, via a foreign body reaction, leaves behind a collar of collagen that supplies the appropriate amount of LES augmentation to demonstrably improve LES effacement characteristics, increase yield pressure, decrease compliance at the GEJ, and increase functional LES length, thereby preventing pathologic acid reflux. We developed the Eschara device in order to provide an ideal GERD solution with the following advantages over LNF and LINX: 1) Correct GERD pathophysiology, 2) preserve natural physiological swallowing, belching, and vomiting, minimize dysphagia, 3) cause minimal risk to the vagus nerve, 4) no risk of erosion, 5) MRI, and all imaging, compatible, 6) simple manufacturing, 7) Enable simplified Hiatal Hernia repair, and 8) eliminate the need for continued PPI use. To ensure adequate performance of the Eschara suture collar prototype, we will 1) fabricate and develop the design; then 2) test and validate it in an in vivo swine model. Based on the results of initial experiments, we will: 3) Fabricate and develop the second round of design iteration; 4) perform second swine experiment. This Phase 1 SBIR proposal prepares us for an SBIR Phase II grant aimed at achieving design freeze, regulatory preparation, and commercialization. Also, we will critically evaluate our suture model to determine whether the Eschara technology could efficiently meet the needs of the GERD market and be a successful alternative to current surgical techniques, leading to improved care for GERD patients.

PROJECT NARRATIVE There is currently no ideal minimally invasive surgery for patients with gastroesophageal reflux failing medical management, and current surgical approaches are either physiologically and anatomically disruptive (Nissen fundoplication) or require a permanent foreign body implant around the gastroesophageal junction (LINX magnetic augmentation). In this Phase 1 SBIR program, we will develop and validate a novel biodegradable suture collar device (Eschara Medical) to be positioned around the gastroesophageal junction, ultimately resulting in uniform collagen deposition that will augment the lower esophageal sphincter, and favorably affect yield pressure and compliance dynamics at the gastroesophageal junction. This will provide the GERD therapy community a safe and effective tool to enhance the GERD treatment armamentarium.