MRT-6160, a potent and highly selective VAV1-directed molecular glue degrader, represents a potential novel therapeutic approach for systemic and neurological autoimmune and inflammatory diseases
Initial Phase 1 clinical results, including biomarker data to demonstrate pharmacodynamic effects, anticipated in Q1 2025
BOSTON, MA, USA I August 19, 2024 I Monte Rosa Therapeutics, Inc. (Nasdaq: GLUE), a clinical-stage biotechnology company developing novel molecular glue degrader (MGD)-based medicines, today announced that the first participants have been dosed in a Phase 1, single ascending dose / multiple ascending dose (SAD/MAD), healthy volunteer study evaluating MRT-6160, a VAV1-directed MGD being developed for systemic and neurological autoimmune diseases. The Company expects to obtain initial data from the Phase 1 study in Q1 2025.
“We are very pleased to initiate our Phase 1 clinical study of MRT-6160, a potent, highly selective, and orally bioavailable VAV1-directed MGD, which we believe is the first rationally designed MGD in clinical development for a non-oncology indication,” said Markus Warmuth, M.D., Chief Executive Officer of Monte Rosa Therapeutics. “Our MGD-based therapeutic approach is well suited to degrade proteins that have been challenging to address with conventional modalities, and we believe we have opportunities to apply our technology to well-characterized targets like VAV1 that were previously considered undruggable. By degrading VAV1, a key regulator of T- and B-cell receptor activity, MRT-6160 could offer a differentiated approach to treat multiple autoimmune and inflammatory diseases. The Phase 1 study of MRT-6160 is designed to provide early insights into safety, pharmacokinetics, VAV1 protein degradation, and key downstream pharmacodynamic markers including CD69, IL-2, IL-6, and IL-17, helping to further inform our clinical strategy. We look forward to sharing initial clinical data from the study in Q1 2025, and subsequently initiating anticipated proof-of-concept studies in ulcerative colitis, rheumatoid arthritis, and potentially other indications.”
The development of MRT-6160 is supported by preclinical data in multiple models of autoimmune/inflammatory diseases and preclinical GLP toxicology data that suggest the potential for a differentiated therapeutic profile in T-cell, T/B-cell, and Th17-mediated systemic and neurologic autoimmune diseases. MRT-6160 has been shown to potently and selectively degrade VAV1 in vitro in human T and B cells and has demonstrated encouraging results in multiple preclinical studies of autoimmune disease, including in models of inflammatory bowel disease, rheumatoid arthritis, and multiple sclerosis.
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, 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. Preclinical studies have demonstrated that MRT-6160 can inhibit disease progression in several 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.
SOURCE: Monte Rosa Therapeutics
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MRT-6160, a potent and highly selective VAV1-directed molecular glue degrader, represents a potential novel therapeutic approach for systemic and neurological autoimmune and inflammatory diseases
Initial Phase 1 clinical results, including biomarker data to demonstrate pharmacodynamic effects, anticipated in Q1 2025
BOSTON, MA, USA I August 19, 2024 I Monte Rosa Therapeutics, Inc. (Nasdaq: GLUE), a clinical-stage biotechnology company developing novel molecular glue degrader (MGD)-based medicines, today announced that the first participants have been dosed in a Phase 1, single ascending dose / multiple ascending dose (SAD/MAD), healthy volunteer study evaluating MRT-6160, a VAV1-directed MGD being developed for systemic and neurological autoimmune diseases. The Company expects to obtain initial data from the Phase 1 study in Q1 2025.
“We are very pleased to initiate our Phase 1 clinical study of MRT-6160, a potent, highly selective, and orally bioavailable VAV1-directed MGD, which we believe is the first rationally designed MGD in clinical development for a non-oncology indication,” said Markus Warmuth, M.D., Chief Executive Officer of Monte Rosa Therapeutics. “Our MGD-based therapeutic approach is well suited to degrade proteins that have been challenging to address with conventional modalities, and we believe we have opportunities to apply our technology to well-characterized targets like VAV1 that were previously considered undruggable. By degrading VAV1, a key regulator of T- and B-cell receptor activity, MRT-6160 could offer a differentiated approach to treat multiple autoimmune and inflammatory diseases. The Phase 1 study of MRT-6160 is designed to provide early insights into safety, pharmacokinetics, VAV1 protein degradation, and key downstream pharmacodynamic markers including CD69, IL-2, IL-6, and IL-17, helping to further inform our clinical strategy. We look forward to sharing initial clinical data from the study in Q1 2025, and subsequently initiating anticipated proof-of-concept studies in ulcerative colitis, rheumatoid arthritis, and potentially other indications.”
The development of MRT-6160 is supported by preclinical data in multiple models of autoimmune/inflammatory diseases and preclinical GLP toxicology data that suggest the potential for a differentiated therapeutic profile in T-cell, T/B-cell, and Th17-mediated systemic and neurologic autoimmune diseases. MRT-6160 has been shown to potently and selectively degrade VAV1 in vitro in human T and B cells and has demonstrated encouraging results in multiple preclinical studies of autoimmune disease, including in models of inflammatory bowel disease, rheumatoid arthritis, and multiple sclerosis.
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, 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. Preclinical studies have demonstrated that MRT-6160 can inhibit disease progression in several 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.
SOURCE: Monte Rosa Therapeutics
Post Views: 3,743
