Development of heparan sulfate-based therapeutics to treat inflammatory diseases

Glycan Therapeutics Corporation, Raleigh NC

Investigators

Linked publications, trials & patents

Abstract

Abstract More than 60 million Americans consume acetaminophen (APAP) on a weekly basis. Unfortunately, an overdose of APAP causes liver toxicity and is responsible for over half of acute liver failure cases in the US. N-acetyl cysteine is the only antidote for APAP overdose and is effective if given within 10 hours after APAP ingestion. However, many patients don’t seek out treatment during the therapeutic window for N-acetyl cystine. Currently, a liver transplant is the only available treatment option for these late-presenting patients. APAP toxicity is a leading cause for liver transplantation in the US and worldwide. The goal of this SBIR phase II project is to develop an anti-inflammatory synthetic heparan sulfate oligosaccharide, GLY-202, for APAP overdose patients specifically late-presenting patients. GLY- 202 was selected after compound optimization studies in efforts to identify a smaller, easier to synthesize oligosaccharide with in vivo efficacy compared to 18-mer in the APAP overdose model. Unlike 18-mer, the synthesis of GLY-202 can be achieved in a shorter synthetic route, substantially decreasing the production cost and reducing a significant commercialization barrier. This application for TABA funding is to support consulting work to progress GLY-202 for a Type B (pre-IND meeting) which will heavily influence our IND. The success of this project will provide a new approach to treat drug induced liver toxicity by targeting to HMGB1-mediated inflammation with a first-in-class therapeutic.