A Novel Glycosaminoglycan-Based Therapeutic for Chronic Rhinosinusitis

PROJECT SUMMARY Chronic rhinosinusitis (CRS) is one of the most prevalent inflammatory diseases in the U.S., affecting up to 12% of the population and substantially diminishing the quality of life and productivity of patients. In four years, the annual U.S. health care expenditure to treat patients with CRS increased from $9B to $64B, with a corresponding rise in surgical treatment for those 20% of patients who fail medical management with the first line of defense – saline nasal irrigation and corticosteroid nasal sprays. Recently approved or emerging technologies for CRS continue to rely on corticosteroid treatment with new delivery methods. However, safety concerns over the long-term use of corticosteroids still remain, and the end result continues to be inadequate control of the disease. GlycoMira Therapeutics’ GM-1111 is a synthetic glycosaminoglycan-based drug candidate that targets innate immunity molecules Toll-like receptor 2 and 4 to reduce downstream inflammatory consequences, such as the production of inflammatory cytokines and influx of inflammatory immune cells into damaged tissues. In models of CRS, intra-nasal administration of GM-1111 outcompetes corticosteroids as an effective treatment for reducing sinonasal inflammation, with significantly decreased inflammatory cytokine production, leukocyte infiltration, mucus accumulation, and air-sinonasal epithelial cell barrier breakdown/impaired mucociliary clearance. Studies have additionally demonstrated that GM-1111 is safe and stable when administered in a wide range of formulations and doses. In this Phase IIB proposal, GM- 1111 will be further developed as a new therapeutic for the effective treatment of CRS. The overall goal is to advance GM-1111 to an Investigational New Drug (IND) application filing and human clinical trials, which will be accomplished through the completion of IND-enabling safety/toxicology studies in two animal species (Aim 1), GM-1111 drug product stability testing for clinical trial use, and IND application submission (Aim 2).