Monte Rosa Therapeutics Announces FDA Clearance of IND Application for MRT-8102, a NEK7-Directed Molecular Glue Degrader for the Treatment of Multiple Inflammatory Diseases
- FDA clearance received for IND application of MRT-8102, allowing clinical trials to begin
- Preclinical studies show strong safety profile with 200-fold exposure margin over projected human efficacious dose
- Demonstrated nanomolar-level degradation of NEK7 with no off-target activity
- Company retains full worldwide rights to MRT-8102 and second-generation CNS-optimized NEK7 MGDs
- Second-generation NEK7 program with enhanced CNS penetration in development for 2026 IND submission
- Clinical results not expected until first half of 2026
- Early-stage development with no proven efficacy in humans yet
Insights
FDA clearance for Monte Rosa's NEK7-targeting molecular glue degrader is a significant milestone advancing their inflammation pipeline with promising preclinical data.
Monte Rosa Therapeutics has achieved a crucial regulatory milestone with FDA clearance of their IND application for MRT-8102, a NEK7-directed molecular glue degrader (MGD). This represents their second clinical program for inflammatory conditions, expanding their immunology and inflammation (I&I) portfolio beyond their previous VAV1-directed MGD.
The scientific approach here is noteworthy. By targeting NEK7, Monte Rosa aims to disrupt the NLRP3 inflammasome pathway - a critical mediator of inflammatory response implicated in numerous conditions. This mechanism differs from conventional approaches like IL-1 antibodies by targeting an upstream regulatory protein. The preclinical data shows nanomolar potency with high selectivity (no off-target effects on related NEK proteins) and near-complete inhibition of downstream inflammatory markers in non-human primates.
The clinical development plan includes initiating a Phase 1 study shortly with results expected in H1 2026. Importantly, the company has incorporated an early proof-of-concept assessment by including subjects with elevated C-reactive protein levels to evaluate inflammatory marker changes. This smart trial design could provide early efficacy signals beyond just safety data.
The preclinical toxicology data revealing a 200-fold safety margin between efficacious and toxic doses in both rats and non-human primates suggests a potentially favorable safety profile. Additionally, the company is already developing a second-generation NEK7 program optimized for CNS penetration, indicating their commitment to expanding this mechanism across different disease areas.
MRT-8102, a highly selective NEK7-directed molecular glue degrader (MGD) developed to treat inflammatory conditions linked to NLRP3, IL-1β, and IL-6 dysregulation, expands Monte Rosa’s clinical I&I portfolio
Potency, selectivity, and long-lasting pharmacodynamics of MRT-8102 observed in preclinical studies create potential for clinical differentiation from competitive approaches for inflammatory diseases
MRT-8102 Phase 1 clinical results, including data on safety, pharmacokinetics, NEK7 protein degradation, and key downstream pharmacodynamic markers, expected in H1 2026
BOSTON, June 10, 2025 (GLOBE NEWSWIRE) -- Monte Rosa Therapeutics, Inc. (Nasdaq: GLUE), a clinical-stage biotechnology company developing novel molecular glue degrader (MGD)-based medicines, today announced U.S. Food and Drug Administration (FDA) clearance of an Investigational New Drug (IND) application for MRT-8102, a NEK7-directed MGD being developed for the treatment of inflammatory diseases driven by the NLRP3 inflammasome and IL-1β. The Company plans to initiate a Phase 1 study of MRT-8102 in the coming weeks and anticipates sharing initial results in H1 2026.
“The IND clearance of MRT-8102 is another important milestone in our quest to broadly establish MGDs as a modality in immunology and inflammatory (I&I) indications. MRT-8102, following on the heels of our VAV1-directed MGD MRT-6160, is our second IND specifically for I&I indications, and represents the only clinical-stage MGD that selectively targets NEK7, with potential to address multiple inflammatory diseases, including cardio-immunology, rheumatology, and respiratory indications,” said Markus Warmuth, M.D., Chief Executive Officer of Monte Rosa Therapeutics. “We believe MRT-8102 could provide a highly differentiated clinical profile compared to IL-1 antibodies and NLRP3 inhibitors in development based on its potency, selectivity, and long-lasting pharmacodynamics. We look forward to initiating a Phase 1 healthy volunteer study in the coming weeks, with clinical results expected in H1 2026, including data on safety, pharmacokinetics, NEK7 protein degradation, and downstream pharmacodynamic markers. As part of the Phase 1 study, we plan to establish initial proof-of-concept (POC) for cardio-immunology indications by evaluating changes in C-reactive protein (CRP) and other key inflammatory markers in a cohort of subjects with high CRP levels.”
Monte Rosa believes its preclinical studies support MRT-8102’s potential to address multiple inflammatory diseases driven by the NLRP3 inflammasome, IL-1β and IL-6. MRT-8102 has demonstrated nanomolar-level degradation of NEK7 in vitro with no off-target activity observed, including related NEK family proteins. In non-human primates (NHPs), oral administration of MRT-8102 resulted in near-complete inhibition of downstream inflammatory markers in ex vivo stimulation assays, as well as improvements in pathological measures in inflammatory disease models. Furthermore, in a rabbit gout model, daily oral dosing of MRT-8102 was observed to reduce pathogenic effects, including a reduction in joint swelling and histopathology scores. Preclinical GLP toxicology studies suggest a considerable safety margin for MRT-8102, with a greater than 200-fold exposure margin over the projected human efficacious dose in both rats and NHPs.
In addition to MRT-8102, Monte Rosa is also working to advance a second-generation NEK7 program with enhanced CNS penetration with an IND submission expected in 2026. Monte Rosa retains full worldwide rights to MRT-8102 and its second-generation CNS-optimized NEK7 MGDs.
About MRT-8102
MRT-8102 is a potent, highly selective, and orally bioavailable investigational molecular glue degrader (MGD) that targets NEK7 for the treatment of inflammatory diseases linked to NLRP3, IL-1β, and IL-6 dysregulation. NEK7 has been shown to be required for NLRP3 inflammasome assembly, activation and IL-1β release both in vitro and in vivo. Aberrant NLRP3 inflammasome activation and the subsequent release of active IL-1β and interleukin-18 (IL-18) has been implicated in multiple inflammatory disorders, including cardiovascular disease, gout, osteoarthritis, neurologic disorders including Parkinson’s disease and Alzheimer’s disease, and metabolic disorders. In a non-human primate model, MRT-8102 was shown to potently, selectively, and durably degrade NEK7, and resulted in near-complete reductions of IL-1β and caspase-1 following ex vivo stimulation of whole blood. MRT-8102 has demonstrated a considerable safety margin (>200-fold exposure margin over projected human efficacious dose) in GLP toxicology studies.
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. Monte Rosa has a global license agreement with Novartis to advance VAV1-directed molecular glue degraders and 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
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