Monte Rosa Therapeutics Showcases MRT-6160 Preclinical Data for Rheumatoid Arthritis at EULAR 2024

Monte Rosa Therapeutics, Inc., a biotechnology company focused on developing molecular glue degrader (MGD)-based medicines, announced the presentation of promising preclinical data on their novel drug candidate, MRT-6160, at the European Alliance of Associations for Rheumatology (EULAR) 2024 Congress in Vienna, Austria. The presentation highlighted MRT-6160's ability to inhibit disease progression in a murine model of rheumatoid arthritis.

MRT-6160 targets VAV1, a signaling protein involved in the activation of T- and B-cells, which are critical to the immune response. By degrading VAV1, MRT-6160 aims to modulate immune cell activity and reduce inflammation. The preclinical data demonstrated that oral administration of MRT-6160 in a collagen-induced arthritis (CIA) murine model significantly inhibited disease progression compared to both control and anti-TNF treatments. Additionally, MRT-6160 reduced serum levels of pro-inflammatory cytokines and autoantibodies, which are markers of rheumatoid arthritis.

In vitro studies showed that MRT-6160-mediated degradation of human VAV1 dose-dependently reduced T-cell receptor (TCR) and B-cell receptor (BCR) activation, proliferation, and function. This included a decrease in cytokine and immunoglobulin G (IgG) secretion. These findings suggest that targeting VAV1 could be a promising strategy for treating various autoimmune and inflammatory diseases.

Sharon Townson, Ph.D., Chief Scientific Officer of Monte Rosa Therapeutics, expressed confidence in the therapeutic potential of MRT-6160, stating that the preclinical data support the hypothesis that VAV1 degradation can effectively treat rheumatoid arthritis. She highlighted that the data presented at EULAR demonstrated reduced TCR- and BCR-mediated immune activation and lower levels of pro-inflammatory cytokines and autoantibodies. Townson also noted that these results, combined with data from other autoimmune disease models and GLP toxicology studies, reinforce the belief in VAV1's potential across multiple autoimmune and inflammatory diseases.

Monte Rosa Therapeutics plans to initiate a Phase 1 single ascending dose/multiple ascending dose (SAD/MAD) study for MRT-6160 in mid-2024, with initial clinical data expected in the first quarter of 2025. This study will be crucial in determining the safety and efficacy of MRT-6160 in humans.

Adam Cartwright, Ph.D., Senior Scientist II at Monte Rosa Therapeutics, presented a poster titled "MRT-6160, a VAV1-Directed Molecular Glue Degrader, Reduces Joint Inflammation and Autoantibody Production in a Collagen-Induced Arthritis Autoimmune Disease Model" at EULAR 2024. The poster (Number 1200) detailed the significant reduction in clinical scores and inhibition of disease progression in mice treated with MRT-6160, as well as the reduced production of key pro-inflammatory cytokines and autoantibodies in the CIA murine model.

VAV1, a Rho-family guanine nucleotide exchange factor, plays a vital role in signaling pathways downstream of T- and B-cell receptors. The expression of VAV1 is restricted to blood and immune cells, making it an attractive target for autoimmune and inflammatory diseases. Preclinical studies have shown that MRT-6160, a potent and selective degrader of VAV1, effectively inhibits disease progression in in vivo models. This suggests that MRT-6160 and similar VAV1-directed MGDs could have therapeutic benefits for conditions such as inflammatory bowel disease, multiple sclerosis, and dermatological disorders.

Monte Rosa Therapeutics continues to leverage their QuEEN™ discovery engine, which uses AI-guided chemistry, structural biology, and proteomics to identify and design highly selective MGDs. Their growing pipeline includes candidates for oncology, autoimmune, and inflammatory diseases, supported by a strategic collaboration with Roche to develop treatments for previously undruggable targets in cancer and neurological diseases.