Reglemers™ are novel therapeutics that result in increased production of anti-inflammatory IL-10 by TREGs, specifically at sites of inflammation. Our lead program is based on a molecule derived from the gram-negative, anaerobic commensal organism, Bacterioides fragilis. B. fragilis produces eight different capsular polysaccharides, which envelope the organism and form its protective capsule. Polysaccharide A (PSA) is one of these polysaccharides and, interestingly, has a unique zwitterionic motif that includes alternating positively and negatively charged sugar residues. PSA consists of a tetrasaccharide repeat unit that forms a polymer of between 50-250 repeats and is the only B. fragilis capsular polysaccharide that imparts anti-inflammatory activity.
Bacterial capsular polysaccharides are well known to industry, and are the basis of polysaccharide conjugate vaccines (such as Pfizer’s Prevnar™) used successfully for decades in millions of people. The mechanism of action for the specific zwitterionic polysaccharide of our focus, PSA, was shown, in a series of landmark papers by our company’s scientific founders that overturned established immunologic paradigms: PSA is processed via the endosomal pathway in antigen-presenting cells, depolymerized by NO-dependent deamination, and presented to CD4+ T-cells by MHC class II molecules.
The elucidation of this mechanism laid to rest conventional wisdom that thought only protein antigens are presented by MHC class II. Upon presentation, such zwitterionic polysaccharides, now referred to as Reglemers™, are able to induce the activation and proliferation of regulatory CD4+ T cells, and control the Th1/Th2 physiologic balance. Our recent published work has demonstrated the capacity of Reglemers™ to protect against experimental models of inflammatory bowel disease (IBD) and multiple sclerosis (MS). Based on the discovery of fundamentally new biology that has been described in over 100 scientific publications, we are advancing development on a new class of therapeutics that modulate the function of regulatory T cells (TREGs) to control immune-mediated diseases.
Our Reglemer™ technology and programs are protected by 29 issued patents, including issued composition-of-matter patents protecting our lead program and issued patents protecting engineered production strains of B. fragilis.