IMU-935: Targeting RORγt and Th17

IMU-935 has potential to be a best-in-class therapy for various autoimmune diseases and beyond.

The 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, 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.

In December 2021, Immunic announced positive unblinded safety, tolerability and pharmacokinetic results from Part A (single ascending doses, or SAD) and Part B (multiple ascending doses, or MAD) of its phase 1 clinical trial of IMU-935 in healthy human subjects. The data established a favorable safety and tolerability profile for IMU-935 in single dose and 14-day multiple dose assessments. Single daily dosing up to 400 mg and multiple daily dosing of 300 mg were found to be safe and well-tolerated in healthy human subjects, with no maximum tolerated dose established, and the investigated doses are believed to be well within the potential therapeutic window of IMU-935. The third portion of the phase 1 clinical trial, which evaluates the safety, tolerability, pharmacodynamics, pharmacokinetics and exploratory efficacy of IMU-935 in patients with moderate-to-severe psoriasis, is currently ongoing. Immunic plans to provide further updates and guidance on potential next steps in the first quarter of 2023.

Based on strong preclinical results, highlighting IMU-935’s therapeutic potential in castration-resistant prostate cancer, Immunic has started an open-label phase 1 dose escalation trial of IMU-935 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.