Monte Rosa Therapeutics Announces Initiation of IND Enabling Studies for First-in-Class NEK7 Directed Molecular Glue Degrader & NLRP3/IL-1β Pathway Inhibitor

Monte Rosa Therapeutics, Inc. recently announced a novel development candidate, MRT-8102, a potent, highly selective and orally bioavailable NIMA related kinase 7 (NEK7)-directed MGD. MRT-8102 is expected to be developed for the treatment of inflammatory diseases driven by interleukin-1β (IL-1β) and the NLRP3 inflammasome, which are critical elements of the inflammatory process. This is the first development candidate to be declared from the company’s NEK7 development program.

“NEK7 is an essential component of the NLRP3 inflammasome pathway that has been implicated in many serious diseases, and we are excited to advance MRT-8102 toward clinical development,” said Markus Warmuth, MD, Chief Executive Officer of Monte Rosa Therapeutics. “In preclinical non-human primate studies, MRT-8102 has demonstrated potent and selective degradation of NEK7, reducing downstream IL-1β. We believe MRT-8102 has the potential to be developed in multiple inflammatory diseases, including gout, pericarditis and other cardiovascular diseases. We are also evaluating opportunities for the program in CNS disorders such as Parkinson’s disease as well as in obesity and other metabolic disorders in light of the ability of our NEK7-directed MGDs to penetrate the blood brain barrier. IND-enabling studies are underway, and we plan to file our first IND for the program in the first quarter of 2025. The advancement of MRT-8102, along with our VAV1-directed MGD MRT-6160, which is progressing toward an IND filing in the first half of this year, demonstrates the continued growth of our immunology and inflammation portfolio and the power and versatility of our QuEEN discovery engine.”

The NLRP3 inflammasome is a multiprotein complex that regulates the innate immune system and inflammatory signaling. 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 gout, cardiovascular disease, neurological disorders including Parkinson’s disease and Alzheimer’s disease, ocular disease, diabetes, obesity, and liver disease. NEK7 has been shown to be required for NLRP3 inflammasome assembly, activation and IL-1β release both in vitro and in vivo, and Monte Rosa’s own in vitro and in vivo work has shown that NEK7 degradation leads to blockade of the pathway leading to inhibition of the production of IL-1β.

MRT-8102 is a potent, highly selective, and orally bioavailable investigational molecular glue degrader (MGD) that targets NEK7 for the treatment of inflammatory diseases driven by IL-1β and the NRLP3 inflammasome. 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 gout, cardiovascular disease, neurological disorders including Parkinson’s disease and Alzheimer’s disease, ocular disease, diabetes, obesity, and liver disease. In non-human primate models, MRT-8102 potently, selectively, and durably degrades NEK7 and results in near-complete reductions of IL-1β. MRT-8102 has shown a favorable safety profile in non-GLP toxicology studies.

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.