MRT-6160, a VAV1-directed molecular glue degrader (MGD), inhibits disease progression, pro-inflammatory cytokines and autoantibody production in a model of rheumatoid arthritis
Initiation of MRT-6160 Phase 1 SAD/MAD study anticipated in mid-year 2024 with initial clinical data expected in Q1 2025
Poster presentation today at 14:45 CET / 8:45 a.m. ET
BOSTON, June 14, 2024 (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 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.
“We believe these preclinical data support our hypothesis that targeting VAV1 has strong therapeutic potential for rheumatoid arthritis,” said Sharon Townson, Ph.D., Chief Scientific Officer of Monte Rosa Therapeutics. “The data being presented at EULAR showed that oral dosing of MRT-6160 led to decreased TCR- and BCR-mediated immune activation and reduced levels of clinically relevant pro-inflammatory cytokines and autoantibodies, as well as statistically significant reductions in clinical scores of disease activity, in the CIA murine model. Today’s data combined with data from other autoimmune disease models and our GLP toxicology data reinforce our belief in the therapeutic potential of VAV1 across multiple autoimmune and inflammatory diseases. We look forward to initiating our Phase 1 single ascending dose/multiple ascending dose (SAD/MAD) study of MRT-6160 this summer and sharing initial clinical data from that study in Q1 2025.”
The poster, entitled “MRT-6160, a VAV1-Directed Molecular Glue Degrader, Reduces Joint Inflammation and Autoantibody Production in a Collagen-Induced Arthritis Autoimmune Disease Model” (Poster Number 1200), will be presented today by Adam Cartwright, Ph.D., Senior Scientist II at Monte Rosa Therapeutics, at 14:45 CET / 8:45 a.m. ET.
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-1β, 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.
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 systemic and neurological autoimmune indications, such as inflammatory bowel disease, rheumatoid arthritis, multiple sclerosis, 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.
About Monte Rosa
Monte Rosa Therapeutics is a clinical-stage biotechnology company developing highly selective molecular glue degrader (MGD) medicines for patients living with serious diseases in the areas of oncology, autoimmune and inflammatory diseases, and more. MGDs are small molecule protein degraders that have the potential to treat many diseases that other modalities, including other degraders, cannot. Monte Rosa’s QuEEN™ (Quantitative and Engineered Elimination of Neosubstrates) discovery engine combines AI-guided chemistry, diverse chemical libraries, structural biology and proteomics to identify degradable protein targets and rationally design MGDs with unprecedented selectivity. The QuEEN discovery engine enables access to a wide-ranging and differentiated target space of well-validated biology across multiple therapeutic areas. Monte Rosa has developed the industry’s leading pipeline of MGDs, which spans oncology, autoimmune and inflammatory disease and beyond, and has a strategic collaboration with Roche to discover and develop MGDs against targets in cancer and neurological diseases previously considered impossible to drug. For more information, visit www.monterosatx.com.
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 herein include, but are not limited to, statements about the advancement and timeline of our preclinical and clinical programs, including the ongoing development of MRT-6160, and the planned submission of an IND to the FDA for MRT-6160 in the second quarter of 2024, our expectations of timing for initiation of a Phase 1 SAD/MAD study mid-2024 and the timing for our disclosure of Phase 1 clinical data of MRT-6160 in the first quarter of 2025, as well as our expectation to present additional preclinical data in models of autoimmune and inflammatory diseases at the upcoming medical meetings and our expectation to initiate POC studies for MRT-6160 in autoimmune/inflammatory diseases including ulcerative colitis and rheumatoid arthritis, with additional potential POC studies, dermatology, rheumatology, and neurology indications in mid-2025, our expectations of success for our programs, among others. 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 December 31, 2023, filed with the U.S. Securities and Exchange Commission on March 14, 2024, and any subsequent filings, that could cause actual results, performance or achievement to differ materially and adversely from those anticipated or implied in the statements. You should not rely upon forward-looking statements as predictions of future events. Although our management believes that the expectations reflected in our statements are reasonable, we cannot guarantee that the future results, performance, or events and circumstances described in the forward-looking statements will be achieved or occur. Recipients are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date such statements are made and should not be construed as statements of fact. We undertake no obligation to publicly update any forward-looking statements, whether as a result of new information, any future presentations, or otherwise, except as required by applicable law. Certain information contained in these materials and any statements made orally during any presentation of these materials that relate to the materials or are based on studies, publications, surveys and other data obtained from third-party sources and our own internal estimates and research. While we believe these third-party studies, publications, surveys and other data to be reliable as of the date of these materials, we have not independently verified, and make no representations as to the adequacy, fairness, accuracy or completeness of, any information obtained from third-party sources. In addition, no independent source has evaluated the reasonableness or accuracy of our internal estimates or research and no reliance should be made on any information or statements made in these materials relating to or based on such internal estimates and research.
Investors
Andrew Funderburk
ir@monterosatx.com
Media
Cory Tromblee, Scient PR
media@monterosatx.com
