Targeting RORγt and Th17
IMU-935 has the potential to be a highly potent and selective inverse agonist of a transcription factor called RORγt with additional activity on DHODH. Immunic believes that the nuclear receptor RORγt is the main driver for the differentiation of Th17 cells and the expression of various cytokines involved in various inflammatory and autoimmune diseases. Immunic believes this target is an attractive alternative to approved antibodies for targets such as IL-23, IL-17 receptor and IL-17A as well as IL-17F cytokine directly. 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, one of the physiological functions of RORγt, and therefore reduces the risk for thymoma development in patients. Based on these preclinical data, Immunic believes that IMU-935 has potential to be a best-in-class therapy for various autoimmune diseases and beyond.
A clinical phase 1 trial exploring safety, pharmacodynamics and pharmacokinetics of IMU-935 is currently ongoing and progressing. Subsequent to the ongoing single and multiple ascending dose parts in healthy volunteers, Immunic plans to extend this trial to assess safety and exploratory disease endpoints in patients with psoriasis. Unblinded safety data from the single and multiple ascending dose parts in healthy volunteers is expected to be available in the second half of 2021. Initiation of the third portion of the phase 1 trial in patients with mild-to-moderate psoriasis is expected around mid-2021 and is expected to last approximately 12 months.
Upon completion of at least the first two cohorts of the multiple ascending dose portion in healthy volunteers, Immunic anticipates that it may also begin a phase 2a proof-of-concept clinical trial of IMU-935 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. This orphan approach may allow for an accelerated path to approval, in parallel to IMU-935’s previously planned development in psoriasis. The company plans to announce additional details as soon as design and timing of the envisaged trial are defined.