Monte Rosa Therapeutics, Inc. announced the company will present preclinical data at the European Alliance of Associations for Rheumatology (EULAR) 2024 Congress, being held June 12-15 in Vienna, Austria. The data demonstrated that in a collagen-induced arthritis (CIA) murine model, oral dosing of MRT-6160 inhibited disease progression as compared to vehicle and anti-TNF, concomitant with reduced serum pro-inflammatory cytokines and anti-collagen II autoantibodies. In vitro, MRT-6160-mediated degradation of human VAV1 dose-dependently reduced T-cell receptor (TCR)- and B-cell receptor (BCR)-mediated activation, proliferation, and function in T- and B-cells, including cytokine and IgG secretion.

VAV1 is a key signaling protein downstream of both the T-and B-cell receptors, and its degradation has potential to treat multiple T-cell, T/B-cell, and Th17-mediated autoimmune and inflammatory diseases. Summary of findings: In a CIA murine model, MRT-6160-mediated mouse VAV1 (mVAV1) degradation was associated with significantly reduced clinical scores and inhibition of disease progression in mice, with observable impact on signs of arthritis compared to control and anti-TNF-treated mice. Analysis of murine serum samples from the CIA model showed that degradation of mVAV1 was associated with significantly reduced production of key pro-inflammatory cytokines, including IL-1ß, IL-6, TNF, and IL-17A, and autoantibody production, including anti-collagen II IgG1.

Primary human T- and B-cells treated with MRT-6160 in vitro resulted in dose-dependent attenuation of TCR- and BCR-mediated activation (CD69 expression) and effector function in T- and B-cells, including cytokine and IgG secretion.