Monte Rosa Therapeutics, Inc. 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-1b (IL-1b) 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.

The NLRP3 inflammasome is a multiprotein complex that regulates the innate immune system and inflammatory signaling. Aberrant NLRP3 inflammaome activation and the subsequent release of active IL-1b 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-1ß 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-1ß.

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-1ß and the NRLP3 inflammasome. NEK7 has been shown to be required for NLRP3 inflammasome assembly, activation and IL-1ß release both in vitro and in vivo. Aberrant NLRP3 inflammasome activation and the subsequent release of active IL-1ß 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-1ß. MRT-8102 has shown a favorable safety profile in non-GLP toxicology studies.