Monte Rosa Therapeutics Presents Preclinical Data at ACR Convergence 2025 on the Potential of MRT-6160, a VAV1-directed Molecular Glue Degrader, to Treat Immune-mediated Diseases

Rhea-AI Summary

Monte Rosa Therapeutics (Nasdaq: GLUE) announced preclinical data for MRT-6160, a VAV1-directed molecular glue degrader, showing broad activity in immune cells and disease reduction in a spontaneous autoimmune MRL-Faslpr mouse model.

Key reported effects include attenuated autoantibody production, reduced proteinuria, lymphadenopathy, skin lesions, organomegaly, and kidney glomerular and interstitial nephritis. The company reported MRT-6160 was equivalent or superior to prednisone and an anti-CD40L antibody across multiple pathology metrics. In vitro, MRT-6160 decreased TfH-mediated B cell activation and immunoglobulin secretion. Monte Rosa said it continues to work with Novartis to advance MRT-6160 toward Phase 2 studies. Poster presentation: October 26, 2025, 10:30–12:30 pm CDT (Poster #0009).

Positive

• Oral MRT-6160 reduced proteinuria in MRL-Faslpr mouse model
• Attenuated autoantibody production and reduced skin lesion formation
• Equivalence or superiority to prednisone and anti-CD40L across pathology metrics
• In vitro reduction of TfH-driven B cell activation and immunoglobulin secretion

Negative

• Data limited to preclinical in vitro and mouse models; no clinical efficacy data yet
• Advancement described toward Phase 2 without binding timelines or human results

Insights

Immunology-drug development expert

Preclinical VAV1 degrader shows broad disease activity in a mouse model and ex vivo human cells; Phase 2 advancement is noted.

MRT-6160, a VAV1-directed molecular glue degrader from Monte Rosa Therapeutics, produced robust preclinical signals: potent VAV1 degradation, reduced T and B cell effector functions in donor-derived PBMCs, decreased TfH-driven B cell activation and immunoglobulin secretion in vitro, and attenuation of multiple disease endpoints in the spontaneous MRL-Faslpr autoimmune mouse model.

These data imply a mechanism that suppresses both cellular and humoral arms of autoimmunity by targeting a signaling node (VAV1) rather than single cytokines; that breadth could explain equivalence or superiority to prednisone and anti-CD40L across reported metrics. Key dependencies and risks include translational gaps from mouse to human biology and the usual uncertainty between ex vivo cellular effects and clinical efficacy; the announcement does not provide safety, PK/PD tolerability data, or quantitative effect sizes that would allow clinical projection.

Concrete items to watch: the planned poster presentation on October 26, 2025 for protocol details and quantitative readouts, disclosed safety/PK in any first-in-human reports, and formal notice of Phase 2 trial starts with Novartis timelines. Expect material next milestones around detailed preclinical datasets at the poster and any regulatory or Phase 2 initiation updates over the coming months.

MRT-6160 inhibited disease pathology, including proteinuria, lymphadenopathy, skin lesion formation, autoantibody production, and organomegaly, in a spontaneous autoimmune disease mouse model 

Data support the potential of MRT-6160 to address multiple rheumatic autoimmune and inflammatory diseases, including Sjögren’s disease, systemic lupus erythematosus, and rheumatoid arthritis

Poster presentation on October 26th at 10:30 am CDT

BOSTON, Oct. 24, 2025 (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 on the potential of MRT-6160, a rationally designed molecular glue degrader (MGD) that selectively degrades VAV1, to treat multiple autoimmune and inflammatory diseases, at ACR Convergence 2025, held October 24-29 in Chicago, IL.

“In a preclinical autoimmune disease model characterized by chronic inflammation, autoantibody production, and multi-organ involvement, administration of MRT-6160 resulted in broad activity across an array of disease markers, including attenuated autoantibody levels and reduced skin and kidney pathology,” said Sharon Townson, Ph.D., Chief Scientific Officer of Monte Rosa Therapeutics. “We believe these findings reinforce the breadth of MRT-6160's potential across multiple immune-mediated diseases, including systemic lupus erythematosus, Sjögren’s disease, rheumatoid arthritis, and others. These data also further highlight the potential capacity of MGDs to potently degrade otherwise ‘undruggable’ proteins, providing an opportunity to treat immune-mediated diseases with a novel, orally dosed modality blocking multiple pathogenic cytokines and secreted autoantibodies. We continue to work with Novartis to advance MRT-6160 towards Phase 2 studies across multiple indications where alternative treatment options are urgently needed.”

The poster, entitled, “MRT-6160, a VAV1-directed molecular glue degrader, attenuates T and B cell effector functions and inhibits disease progression in a spontaneous autoimmune MRL-Fas^lpr mouse model” (Poster Number #0009), will be displayed on Sunday, October 26, from 10:30 am to 12:30 pm CDT in Poster Session A, “B Cell Biology & Targets in Autoimmune & Inflammatory Disease Poster I.” The poster will be presented by Marisa Peluso, Senior Director, Biology, Monte Rosa Therapeutics.

Summary of key findings:

• MRT-6160, a first-in-class VAV1-directed MGD, potently degraded VAV1 and attenuated T and B cell effector functions in both healthy and rheumatic disease patient donor-derived peripheral blood mononuclear cells (PBMCs).
• In vitro data demonstrated that MRT-6160 decreased TfH cell-mediated B cell activation, differentiation, and immunoglobulin secretion.
• In the spontaneous autoimmune disease MRL-Fas^lpr mouse model, oral administration of MRT-6160 resulted in attenuated proteinuria, lymphadenopathy, skin lesion formation, autoantibody production, organomegaly, and kidney glomerular and interstitial nephritis. MRT-6160 was equivalent or superior to prednisone or anti-CD40L monoclonal antibody treatments across multiple metrics of disease pathology.
  
  

About MRT-6160
MRT-6160 is a potent, highly selective, and orally bioavailable investigational molecular glue degrader of VAV1, which in preclinical studies has shown deep degradation of its target with no detectable effects on other proteins. VAV1 is a key signaling protein downstream of both the T- and B-cell receptors. VAV1 expression is restricted to immune cells, including T and B cells. MRT-6160 has shown promising activity in preclinical models of multiple immune-mediated conditions. In a Phase 1, single ascending dose / multiple ascending dose (SAD/MAD) study in healthy subjects (clinicaltrials.gov identifier NCT06597799), MRT-6160 demonstrated sustained, dose-dependent VAV1 degradation in peripheral blood T and B cells after single and multiple dose administration. MRT-6160 also substantially inhibited secretion of inflammatory cytokines from whole blood derived T and B cells following ex vivo stimulation. Under the terms of an agreement announced in October 2024, Novartis has exclusive worldwide rights to develop, manufacture and commercialize MRT-6160 and other VAV1 MGDs. Monte Rosa is eligible to receive up to $2.1 billion in development, regulatory, and sales milestones, beginning upon initiation of Phase 2 studies. Monte Rosa will co-fund any Phase 3 clinical development and will share any profits and losses associated with the manufacturing and commercialization of MRT-6160 in the U.S., and is also eligible for tiered royalties on ex-U.S. net sales.

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 rationally design MGDs with unprecedented selectivity. Monte Rosa has developed the industry’s leading pipeline of MGDs, which spans autoimmune and inflammatory diseases, oncology, and beyond. 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 therapeutic potential of VAV1 degradation, including using the VAV1-directed MGD MRT-6160, including the breadth of MRT-6160's potential across multiple immune-mediated diseases, including systemic lupus erythematosus, Sjögren’s disease, rheumatoid arthritis, and others, the capacity of MGDs to potently degrade otherwise ‘undruggable’ proteins and the therapeutic opportunities for such MGDs to treat immune-mediated diseases with a novel, orally dosed modality blocking multiple pathogenic cytokines and secreted autoantibodies, work being performed with Novartis to advance MRT-6160 into Phase 2 studies across multiple indications, including the scope and timing of any such Phase 2 studies, about preclinical data presented at the ACR Convergence 2025 supporting the potential of MRT-6160 to address multiple autoimmune and inflammatory diseases including Sjögren’s disease, systemic lupus erythematosus, and rheumatoid arthritis, 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, 2024, filed with the U.S. Securities and Exchange Commission on March 20, 2025, 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

FAQ

When and where will Monte Rosa present MRT-6160 data at ACR Convergence 2025?

Poster #0009 will be displayed on October 26, 2025, 10:30–12:30 pm CDT in Poster Session A.

What effects did MRT-6160 show in the MRL-Faslpr mouse model reported by Monte Rosa (GLUE)?

Reported effects include reduced proteinuria, lymphadenopathy, skin lesions, autoantibodies, organomegaly, and kidney nephritis.

How did MRT-6160 compare to prednisone and anti-CD40L in the preclinical results for GLUE?

Monte Rosa reported MRT-6160 was equivalent or superior to prednisone and anti-CD40L across multiple disease pathology metrics.

What is the molecular target and proposed mechanism of MRT-6160 (GLUE)?

MRT-6160 is a VAV1-directed molecular glue degrader designed to selectively degrade VAV1 and attenuate T and B cell effector functions.

Do the Monte Rosa (GLUE) data include human clinical trial results for MRT-6160?

No; the announcement describes in vitro PBMC data and preclinical mouse model results, not clinical trial outcomes.

Is Monte Rosa advancing MRT-6160 to clinical studies with a partner?

Monte Rosa stated it is continuing to work with Novartis to advance MRT-6160 toward Phase 2 studies.