FDA Clears Monte Rosa's IND for NEK7-Targeting MRT-8102 for Inflammatory Diseases

Monte Rosa Therapeutics is advancing its clinical-stage portfolio with the FDA's recent approval of an Investigational New Drug (IND) application for MRT-8102, a promising NEK7-directed molecular glue degrader (MGD) aimed at treating inflammatory diseases. This advancement marks a significant milestone for the biotechnology company, which specializes in developing novel MGD-based therapies. MRT-8102 is designed to address inflammatory conditions associated with dysregulation of the NLRP3 inflammasome, IL-1β, and IL-6.

Monte Rosa plans to start a Phase 1 clinical trial in a few weeks, targeting participants with high levels of C-reactive protein (CRP) to evaluate safety and pharmacokinetics. The trial will also assess NEK7 protein degradation and key pharmacodynamic markers. The company expects to unveil initial results, including proof-of-concept data for cardio-immunology, in the first half of 2026.

MRT-8102 stands out due to its potency, selectivity, and durable pharmacodynamics, distinguishing it from existing therapies like IL-1 antibodies and NLRP3 inhibitors. Preclinical studies have illustrated the compound's potential. In vitro tests showed MRT-8102's ability to degrade NEK7 at nanomolar concentrations without affecting related NEK family proteins. Experiments in non-human primates showed that oral administration of MRT-8102 led to significant inhibition of inflammatory markers, as well as improvements in pathological measures in models of inflammatory diseases. Additionally, studies in a rabbit model of gout demonstrated its efficacy in reducing joint swelling and other pathogenic effects.

Preclinical toxicology studies indicate MRT-8102 has a significant safety margin, with a more than 200-fold exposure margin compared to the projected human efficacious dose. This suggests the potential for safe use in humans, reinforcing the compound’s promising profile for treating various inflammatory diseases.

Monte Rosa is not just stopping at MRT-8102. The company is working on enhancing the potential of its NEK7-targeting treatments. A second-generation NEK7 program, designed to improve central nervous system (CNS) penetration, is in the works, with plans to submit an IND application in 2026.

MRT-8102 targets NEK7, a protein integral to the assembly and activation of the NLRP3 inflammasome, a key player in the inflammatory process. Aberrant activation of the NLRP3 inflammasome is linked to numerous inflammatory disorders, such as cardiovascular diseases, gout, osteoarthritis, and certain neurological and metabolic conditions. MRT-8102's ability to effectively degrade NEK7 could open new therapeutic avenues for these diseases.

The development of MRT-8102 is part of Monte Rosa's broader strategy to expand its pipeline of molecular glue degraders, which are small molecules that promote the degradation of specific proteins. These degraders hold promise for treating diseases that are challenging to address with traditional therapies. Monte Rosa's QuEEN™ discovery engine is instrumental in this effort, employing advanced technologies like AI-guided chemistry and structural biology to create MGDs with high selectivity.

The company's strategic collaborations, like its global license agreement with Novartis and its partnership with Roche, underscore its commitment to advancing the frontier of drug discovery. These collaborations focus on developing MGDs for cancer and neurological diseases, further highlighting Monte Rosa's versatile and innovative approach.

Monte Rosa Therapeutics continues to build momentum in its quest to deliver cutting-edge therapies for complex diseases, with MRT-8102 representing a significant step forward in the treatment of inflammatory conditions.