HZ-W084

HZ-W084 is an orally bioavailable, highly selective, and potent molecular glue degrader of VAV1, a guanine nucleotide exchange factor downstream of the T-cell receptor (TCR) and B-cell receptor (BCR). Developed by HealZen Therapeutics, HZ-W084 is designed to target VAV1, which is historically considered an undruggable protein but is overexpressed or associated with polymorphisms in multiple autoimmune conditions, including inflammatory bowel disease (IBD), multiple sclerosis, systemic lupus erythematosus, and rheumatoid arthritis. In preclinical studies, HZ-W084 demonstrated robust VAV1 degradation potency, strong immunomodulatory activity (including suppression of Th1, Th2, and Th17 differentiation), and significant efficacy in preventing disease progression and reducing colon inflammation in a murine colitis model. The drug is currently in IND-enabling studies.