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
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
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
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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.
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Forward-Looking Statements
This communication includes express and implied “forward-looking statements,” including forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Forward-looking statements include all statements that are not historical facts, and in some cases, can be identified by terms such as “may,” “might,” “will,” “could,” “would,” “should,” “expect,” “intend,” “plan,” “objective,” “anticipate,” “believe,” “estimate,” “predict,” “potential,” “continue,” “ongoing,” or the negative of these terms, or other comparable terminology intended to identify statements about the future. Forward-looking statements contained in herein include, but are not limited to, statements about our product development activities, including our expectations around the potential of molecular glue degraders, the potential of our pipeline of molecular glue degraders, including our molecular glue degrader for VAV1, known as MRT-6160, , our expectation of the relevance of our pre-clinical data for VAV1 and/or MRT-6160 and the potential relevance of such with respect to potential therapeutic utility in immunological and/or inflammatory disorders, our expectations regarding the advancement and timing of ongoing pre-clinical and clinical development of MRT-6160, including our estimated timing for filing of an investigational new drug application therefor, our ability to initiate clinical studies for MRT-6160, our expectations regarding potential therapeutic opportunities for VAV1 as a target and specifically for MRT-6160, our expectations regarding medical needs and potential therapeutic opportunities for MRT-6160. By their nature, these statements are subject to numerous risks and uncertainties, including those risks and uncertainties set forth in our most recent Annual Report on Form 10-K for the year ended
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