IMU-935: Targeting RORγt and Th17
IMU-935 has potential to be a best-in-class therapy for various autoimmune diseases and beyond.
The recent success of antibodies targeting the IL-17 pathway to treat IL-17 mediated diseases, including psoriasis, have spurred global efforts to identify oral drugs targeting this important molecular pathway. Interestingly, IMU-935 has shown a potent suppression of IL-17A and IL-17F. As a highly potent and selective inverse agonist of a transcription factor called RORγt with additional activity on DHODH, IMU-935 has the potential to serve as an oral alternative for injectables. 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 of IMU-935 is currently ongoing. Unblinded safety, pharmacodynamic and pharmacokinetic data from the single and multiple ascending dose parts in healthy volunteers is expected to be available in the fourth quarter of 2021. Initial human data from the third portion of the phase 1 trial in patients with moderate-to-severe psoriasis, which evaluates the safety and tolerability of IMU-935 in this patient population, is expected to be available in the second quarter of 2022.
Based on strong preclinical results, highlighting IMU-935’s therapeutic potential in castration-resistant prostate cancer, Immunic is currently preparing an open-label phase 1 dose escalation trial designed to establish a recommended phase 2 dose and to assess safety, tolerability, anti-tumor activity, biomarkers and pharmacokinetics of IMU-935 in patients with progressive metastatic castration-resistant prostate cancer. The trial was approved by the relevant authorities in the United Kingdom and is expected to commence in the fourth quarter of 2021.
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.