MRT-6160

MRT-6160 is a first-in-class, orally bioavailable small molecule molecular glue degrader that selectively targets VAV1 (vav guanine nucleotide exchange factor 1) for proteasomal degradation. Developed by Monte Rosa Therapeutics, it represents a novel therapeutic approach for systemic and neurological autoimmune and inflammatory diseases. VAV1 is a Rho-family guanine nucleotide exchange factor critical for T-cell receptor (TCR) and B-cell receptor (BCR) signaling, with expression restricted to blood and immune cells such as T and B lymphocytes. By inducing deep degradation of VAV1, MRT-6160 modulates both T-cell and B-cell activity, leading to significant inhibition of cytokine release (including IL-2, IL-6, IL-17A, IFNγ), suppression of immune cell activation markers like CD69, and reduction in disease progression in preclinical models of multiple sclerosis, rheumatoid arthritis, ulcerative colitis/IBD, and other Th17-mediated autoimmune conditions. The drug has demonstrated >90% target degradation in human peripheral blood cells with favorable safety/tolerability in Phase 1 studies[2][5][6][7][8][9].