HPP has discovered a novel role for 11βHSD1 inhibition in POAG. An animal study has demonstrated lowering of IOP after subconjunctival injection of an cortisol antagonist. Furthermore several studies have described the presence of 11βHSD1 in the epithelium of the ciliary body, and studies have demonstrated a 14:1 ratio of cortisol to cortisone in the aqueous humor of the eye, a ratio much higher than seen in plasma, thus supporting an active role of 11βHSD1 in the eye.
Exploratory clinical study with carbenoxalone (a model compound inhibiting both 11βHSD1 and 11βHSD2) has demonstrated a decrease in intraocular pressure in healthy people as well as in patients with ocular hypertension.
HPP851, HPP’s novel 11βHSD1 inhibitor, inhibited cortisone from increasing intraocular pressure when compared to the anterior segment that received only cortisone, by 17-20% in cultured human anterior segments.
HPP851 is currently being evaluated in a phase 1b/2a study in patients with elevated IOP or POAG.