dWIZ-2

dWIZ-2 is a small-molecule molecular glue degrader that targets the transcription factor WIZ for proteasomal degradation. Developed by Novartis, it acts as a cereblon (CRBN)-dependent degrader, specifically designed to induce fetal hemoglobin (HbF) expression by de-repressing the gamma-globin gene. WIZ was identified as a repressor of HbF, and its targeted degradation provides a potential oral therapeutic approach for sickle cell disease (SCD) and beta-thalassemia. In preclinical studies, dWIZ-2 demonstrated robust, dose-dependent WIZ degradation and significant increases in HbF levels in humanized mouse models and non-human primates, while maintaining a favorable safety profile without myelosuppression.