Novel Immunoregulatory Therapeutics for Bacterial Gastritis

About This Grant

Novel Immunoregulatory Therapeutics for Bacterial Gastritis Biotherapeutics Inc (BTI) is an emerging biotech company that synergistically combines the power of advanced computational modeling and A.I. with translational experimentation to accelerate the development of novel products for precision immunology. The goal of this project is to develop the next wave of oral therapeutics for the treatment of bacterial gastritis targeting inflammation. Helicobacter pylori colonizes the stomach of more than 50% of the population worldwide causing chronic gastritis, peptic ulcer and gastric cancer. Despite the induction of strong mucosal immune responses, H. pylori can persist chronically in the gastric niche. While the infection is asymptomatic in 80% of the cases, 10 to 15% of H. pylori-infected individuals develop gastroduodenal ulcers, and H. pylori infection is associated with a two- fold increased risk of developing gastric cancer. Additionally, H. pylori infection induces a low-grade systemic inflammation that has been postulated to contribute to the development of multiple diseases, including cardiovascular disorders, eczema and Alzheimer’s disease. Eradication of H. pylori is the main strategy to prevent chronic gastritis and the development of gastric cancer. However, this antimicrobial-based standard of care therapy is associated with significant concerns, including failure to successfully eradicate the bacteria, the emergence of antimicrobial resistance or the negative effects of antibiotic treatment in the wider gut microbiome. Managing excessive inflammatory responses associated with bacterial gastritis and subclinical systemic inflammation via host-centered therapeutics is a promising novel approach. This SBIR Phase I application will evaluate the therapeutic efficacy in regulating local and systemic inflammation and the translational potential of a novel host-centered product candidate in H. pylori-induced gastritis. The Specific Aims of this SBIR Phase I application are to: AIM 1. Characterize the therapeutic efficacy of the novel product candidate for the treatment of H. pylori- induced gastritis. We will conduct dose-ranging studies in a mouse model of H. pylori infection. Mice will be infected with the H. pylori strain Pre-Mouse Sydney Strain 1 (PM-SS1). Gastric infiltration of immune subsets, histological lesions, bacterial loads and ex vivo stimulation with H. pylori antigen of gastric lymph node cells will be assessed. AIM 2. Evaluate the translational potential of the novel product candidate in an ex vivo H. pylori infection system with human gastric primary cells. We will utilize an ex vivo culture system of human polarized monolayers of gastric cells. Cells will be infected with H. pylori PM-SS1, J99 and J68 strains. Cytokine inflammatory profile, cell permeability, production of reactive oxygen species and cell viability will be evaluated. Commercial Application: This proposal will launch the development of a novel, oral, host-centered therapeutic for the treatment of bacterial gastritis with the potential to disrupt a global market of $1.3 billion by 2033.