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.
The current, single ascending dose part of the ongoing phase 1 trial of IMU-935 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. Unblinded safety data from the single and multiple ascending dose parts in healthy volunteers is expected to be available in the first half of 2021. Initiation of the third portion in patients with mild-to-moderate psoriasis is expected in the first half of 2021 and is expected to last approximately 12 months.
Upon completion of the single and multiple ascending dose portions of the ongoing phase 1 trial, Immunic anticipates that it may also begin a phase 2 proof-of-concept clinical trial of IMU-935 in an orphan autoimmune indication. This orphan approach may allow for an accelerated path to approval, in parallel to IMU-935’s previously planned development in psoriasis. The company has targeted IMU-935 for further development in Guillain-Barré syndrome, an acute neurological disorder in which the body’s immune system attacks its peripheral nervous system, and for which very few therapies exist. The company plans to announce additional details as soon as design and timing of the envisaged trial are defined.