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Data presented support broad potential therapeutic applications of MRT-6160 in a variety of autoimmune and inflammatory disorders driven by underlying dysregulation of T- and B-cells, including rheumatoid arthritis
Investigational New Drug filing for MRT-6160 expected in 1H 2024
Data will be presented during Poster Session A on Sunday, November 12, 2023 from 9:00-11:00 am PT
BOSTON, Nov. 07, 2023 (GLOBE NEWSWIRE) -- Monte Rosa Therapeutics, Inc. (NASDAQ:GLUE), a clinical-stage biotechnology company developing novel molecular glue degrader (MGD)-based medicines, today announced the company will present preclinical data at the American College of Rheumatology (ACR) Convergence Annual Meeting held November 10-15 in San Diego, CA. The data demonstrate that MRT-6160, a novel, highly selective MGD targeting VAV1, attenuated disease progression in a murine collagen-induced arthritis (CIA) model.
In vitro, MRT-6160 induced selective degradation of VAV1, and attenuated TCR- and BCR-mediated activation and function of primary human T- and B-cells. In the CIA model, oral dosing of MRT-6160 elicited rapid VAV1 degradation across multiple tissues in a dose-dependent manner. Over the course of 20 days, MRT-6160 significantly decreased disease progression and endpoint functional scores compared to vehicle and showed a trend towards superior activity compared to an anti-TNF antibody.
"We are highly encouraged by these preclinical data, which we believe further establish the importance of VAV1 as a potential therapeutic target in T- and B-cell mediated autoimmunity, as well as MRT-6160's potential to broadly treat autoimmune and inflammatory diseases including rheumatoid arthritis, multiple sclerosis, inflammatory bowel disease, psoriasis and other autoimmune diseases," said Owen Wallace, Ph.D., Chief Scientific Officer of Monte Rosa Therapeutics. "Together with extensive preclinical data in other models of autoimmunity, these promising results further support MRT-6160 as it advances to the clinic, and we look forward to our anticipated IND filing in the first half of next year."
Poster presentation details:
Poster Presentation: A VAV1-Directed Molecular Glue Degrader, MRT-6160, Reduces Joint Inflammation in the Collagen-Induced Arthritis Autoimmune Disease Model (abstract #0082)
Session: Poster Session A: T Cell Biology & Targets in Autoimmune & Inflammatory Disease
Date: Sunday, November 12, 2023
Time: 9:00-11:00 am PT
Presenter: Marisa Peluso, Director, Target and Discovery Biology
Location: Poster Hall
About VAV1 and MRT-6160
VAV1, a Rho-family guanine nucleotide exchange factor, is a key signaling protein downstream of both the T-and B-cell receptors. VAV1 expression is restricted to blood and immune cells, including T and B cells. Preclinical studies have shown that targeted degradation of VAV1 protein via an MGD modulates both T- and B-cell receptor-mediated activity. This modulation is evident both in vitro and in vivo, demonstrated by a significant decrease in cytokine secretion, proteins vital for maintaining autoimmune diseases. Moreover, VAV1-directed MGDs have shown promising activity in preclinical models of autoimmune diseases and thus have the potential to provide therapeutic benefits in multiple indications, such as multiple sclerosis, rheumatoid arthritis, and dermatological disorders.
MRT-6160 is a potent, highly selective, and orally bioavailable degrader of VAV1, which has shown deep degradation of its target with no detectable effects on other proteins. Preclinical studies demonstrate MRT-6160 inhibits disease progression in in vivo autoimmunity models.
Posted In: GLUE
