Production of a Hydrogel-based Mucosal Sealant for Gastrointestinal Bleeding Prevention - ABSTRACT Gastrointestinal (GI) bleeding is a life-threatening condition that affects millions of American citizens every year, resulting in 500,000 hospitalizations, more than 2 million hospital days, and over $5 billion in direct costs. GI bleeding often originate from lacerations created following surgical interventions, such as after polypectomies. The established method to prevent GI bleeding involves the use of endoscopic clips, which was invented in 1975. However, clips are unable to provide wound shielding, are technically challenging to apply, and are limited to small lesions only. Novel powder-based hemostatic products have been suggested; Yet, they lack proper adhesion to mucosal tissues being quickly dissolved post application, and can only work in actively bleeding lesions which is not often the case for GI lacerations that bleed days post-surgical intervention. To address this need, BioDevek has been focusing on the research and development of GastroShield - a sprayable biocompatible adhesive biomaterial for endoscopic management of GI lesions. GastroShield is formed by cross-linking of biodegradable polymer solutions (amine-terminated Poloxamer and oxidized Dextran), designed to be easy-to-use, fast, and also less dependent on operator skill. Prior to this direct-to-Phase II application, Biodevek obtained critical de-risking milestones of the technology, including the (1) Identification of the optimal formulation for gastrointestinal mucosal adhesion, (2) Performing mechanical studies of the technology ensuring its conformability to the GI features and the catheter spraying application (3) Confirming wound protection of GastroShield against acid and catabolic agents (4) Conducting preliminary in vitro and In vivo biocompatibility studies (5) Confirming the acute homeostatic effect and (6) the chronic protection of gastrointestinal submucosal in a pilot porcine in vivo model. The direct-to-Phase II project will focus on achieving critical pre-clinical results and quality control levels to support the regulatory submission. Also, the performance of a pre-submission meeting with the FDA to confirm the regulatory pathway and design of preclinical studies. Aligned with this goal, we aim at the completion of key Go/no-Go milestones: I) Scale-up manufacturing of the product and the development of quality control methods, II) Conducting complete safety studies under GLP conditions, III) executing an FDA pre-submission meeting to validate the selected in-vivo pre-clinical model and predicate device for 510(k) submission IV) Conducting efficacy studies comparing GastroShield to FDA-validated predicate device. Successful execution of these aims will allow Biodevek to initiate the regulatory approval of GastroShield.
