Targeting RORγt and Th17
IMU-935 is 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. IMU-935 shows 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.
IMU-935 is currently in late preclinical development. The company expects to begin phase 1 single and multiple ascending dose trials during September 2019. Immunic also plans to extend these studies in the first half of 2020 to assess safety and mechanism-related biomarkers in patients with psoriasis.