IMU-935

Izumerogant has potential to be a first-and-best-in-class therapy for various autoimmune diseases.

Izumerogant (proposed International Nonproprietary Name for IMU-935) is a highly potent and selective inverse agonist of a transcription factor called RORγ/RORγt. The nuclear receptor RORγt is believed to be the main driver for the differentiation of Th17 cells and the release of cytokines involved in various inflammatory and autoimmune diseases. Immunic believes this target is an attractive potential alternative to approaches acting on IL-23, the IL-17 receptor and directly on IL-17.

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, graft versus host disease, multiple sclerosis and inflammatory bowel disease. Preclinical experiments indicated that izumerogant leads to a potent inhibition of Th17 differentiation, inhibition of cytokine secretion, and induction of regulatory T cells. Importantly, izumerogant did not affect thymocyte maturation, one of the important physiological functions of RORγt that should be maintained. Based on these preclinical data and the selectivity of the effect maintaining important physiological functions while providing the desired anti-Th17 effect, Immunic believes that izumerogant has potential to be a first-and-best-in-class therapy for various autoimmune diseases.

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 izumerogant in healthy human subjects. The data established a favorable safety and tolerability profile for izumerogant 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 izumerogant. For the third portion of the phase 1 clinical trial, which evaluates izumerogant in patients with moderate-to-severe psoriasis, Immunic plans to provide further updates and guidance on potential next steps towards the end of the first quarter of 2023.

Based on strong preclinical results, highlighting izumerogant’s therapeutic potential in castration-resistant prostate cancer, Immunic has started an open-label phase 1 dose escalation trial of izumerogant designed to establish a recommended phase 2 dose and to assess safety, tolerability, anti-tumor activity, biomarkers and pharmacokinetics of izumerogant in patients with progressive metastatic castration-resistant prostate cancer.