AKDS001 MSs, administered at a dose at least 10 times greater than the effective dose, were well tolerated with no systemic effects, including diarrhea, vomiting, injection site erythema, or abnormalities in biochemistry and hematology, which are reported in clinical trials of systemic EP4 agonists for ulcerative colitis or heart failure (Nakase et al., 2010; Ward et al., 2016). Here, PTGER4 is linked to heart failure.