izumerogant (IMU-935)

This differential effect arose because different concentrations of IMU-935 were required to disrupt the interaction in Th17 cells versus thymocytes, due to varying levels of RUNX1 that compete with RORγt for CBFβ binding. This study reveals an unreported mechanism for RORγt regulation and a selective RORγt inhibitor that prevents Th17-driven autoimmunity without the risk of lethal lymphoma from thymocyte disruption.

P1, N=18, Terminated, Immunic AG | N=42 --> 18 | Trial completion date: Dec 2023 --> May 2023 | Recruiting --> Terminated | Trial primary completion date: Mar 2023 --> May 2023; Lack of Efficacy

The main reasons were lack of efficacy (topical) or safety signals (oral) as well as, amongst other things, thymic lymphomas as seen with BMS-986251 in a preclinical study and liver enzyme elevations in humans with VTP-43742. Possibilities to mitigate these risks could be the use of RORγt inverse agonists with different chemical structures not interfering with thymocytes maturation and no liver tox inducing properties. With few new frontrunners (e.g. ABBV-157 (cedirogant), BI 730357 or IMU-935) this is still an exciting time for this novel treatment approach.