GB004 is a small molecule prolyl hydroxylase inhibitor (PHDi) that stabilizes hypoxia inducible factors (HIF1-α), key transcription factors involved in the protective cellular responses at the intersection of hypoxia and inflammation. GB004 was selected based on its gut-targeted profile to limit systemic on-target effects associated with HIF1-α stabilization. Consistent with this, orally administered GB004 in a healthy non-human primate model engaged HIF-related genes in the gut, and, in animal models of colitis, demonstrated a significant reduction in disease activity, improvements in histologic measures, and greater exposure in GI tissue relative to plasma.