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BLOOD SUGAR LEVEL BLOOD SUGAR LEVEL Targeted Approach to Inhibit Effects of Excessive GLP-1 in PBH to Mitigate Hypoglycemia GLP-1 levels observed to be more than 10-fold Avexitide inhibits GLP-1 receptor activity and higher in PBH than in Nonsurgical Controls, decreases the insulin response to glucose in rat resulting in dysregulated secretion of insulin and 1,2, 3 pancreatic islet cells subsequent hypoglycemia 300 4 Gastric Bypass + PBH (GB + PBH) 16.7 G +/- GLP-1 +/- Avexitide Gastric Bypass (GB) Overweight (OW) Morbidly Overweight (Mob) 200 Glucose Glucose + GLP-1 Glucose + GLP-1 + Avexitide 100 Glucose + GLP-1 + Avexitide 0 0 20 40 60 80 100 120 Time (min) Time (min) GLP-1=glucagon-like peptide-1

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Approximately 95% of 5-HT is synthesized in the gut, and gut microbes regulate its production by modulating the activity of tryptophan hydroxylase 1 (TPH1), the rate-limiting enzyme for 5-HT synthesis