Siege Pharmaceuticals, Inc.

Evaluating the Efficacy of a Novel Nash Therapeutic - Project Summary Obesity and Other Characteristics of Metabolic Syndrome Are Key Underlying Factors in the Development of Non- Alcoholic Fatty Liver Disease (nafld). If Left Unchecked, Nafld Can Progress to Non-alcoholic Steatohepatitis (nash), Cirrhosis, and Hepatocellular Carcinoma. Up to 60% of the 80-100 Million Americans With Nafld Will Progress to Nash, Yet There Are No Fda-approved Therapeutics; the Only Treatment Option Currently Available Is Weight Loss. the Overall Objective of This Project Is to Determine Whether the Siege Compound Merits Development as a Nash Therapy. Recently Published Work Demonstrates Improvement of Liver Phenotypes in a Diet-induced Obesity Model Without Toxicity in Normal Tissues and Thus the Potential to Address an As-yet Unmet Need for Nash Patients. Siege Pharmaceuticals Is Taking a New Approach to Treating This Disease: Correcting Ros, Er Stress, and Hyperleptinemia Upstream of Liver Dysfunction, Inflammation, and Fibrosis Instead of Just Targeting the Pheno- Types Without Addressing the Root Cause. Aim 1 Will Evaluate the Efficacy of Siege’s Compound in a Mouse Model That Reproduces the Pathological Features Seen in Patients With Nash While Aim 2 Will Test SGE-893 in a Liver Microtissue Model Derived From Primary Human Cells, Allowing for Dissection of Liver-specific and Weight Loss- Driven Effects and Validation in a Human Model System. These Studies Will Establish Whether Development as a Nash Therapeutic Is Merited and Could Support a Future Phase Ii Program. If the Siege Compound Performs as Expected, Both Improving Nash Phenotypes and Correcting Metabolic Dysfunction, It Could Dramatically Im- Prove the Overall Health of Patients Who Currently Have No Therapeutic Options.