Targeting RORγt and Th17
IMU-935 has the potential to be a highly potent and selective inverse agonist of a transcription factor called RORgt (retinoic acid receptor-related orphan nuclear receptor gamma) with additional activity on DHODH (dihydroorotate dehydrogenase). Immunic believes that the nuclear receptor RORgt is the main driver for the differentiation of Th17 cells and the expression of cytokines involved in various inflammatory and autoimmune diseases. This target is believed to be an attractive alternative to approved antibodies for targets such as IL-23, IL-17 receptor and IL-17, itself. Immunic has observed strong cytokine inhibition targeting both Th1 and Th17 responses in preclinical testing, as well as indications of activity in animal models for psoriasis and IBD. Preclinical experiments indicated that, while leading to a potent inhibition of Th17 differentiation and cytokine secretion, IMU-935 did not affect thymocyte maturation. Based on these preclinical data, Immunic believes that IMU-935 has potential as a best-in-class therapy for various autoimmune diseases.
A double-blind, placebo-controlled clinical phase 1 trial of IMU-935 is currently ongoing. The current, single ascending dose part in healthy volunteers, being conducted in Australia, is planned to be followed by a multiple ascending dose portion in healthy volunteers and a safety evaluation in patients with mild-to-moderate psoriasis as a third part of this phase 1 trial.