Nov. 10 at 11:05 AM
$GLUE $12.31
https://stocktwits.com/G101SPM/message/633550151
today announced the company will present preclinical data on the potential of MRT-8102, a first-in-class, NEK7-directed MGD for inflammatory diseases driven by the NLRP3 inflammasome, at the American Heart Association’s Scientific Sessions 2025, held November 7-10 in New Orleans, LA.
“These promising findings reinforce our belief in the highly differentiated profile of MRT-8102, the only clinical-stage degrader targeting NEK7, as a potential treatment for cardiovascular and cardiometabolic diseases such as pericarditis, atherosclerosis, and others,” said Sharon Townson, Ph.D., Chief Scientific Officer of Monte Rosa Therapeutics. “By modulating the NLRP3/IL-1/IL-6 pathway upstream of other approaches, MRT-8102 potently inhibited pyroptotic cell death and inhibited the release of multiple inflammatory cytokines. Furthermore, MRT-8102 has the potential to block cholesterol crystal-induced cardiovascular inflammation characterized by pyroptosis and cytokine release that leads to atherosclerotic plaque pathogenesis. We are encouraged by the growing interest in targeting the NLRP3/NEK7 inflammasome to treat cardiovascular disease, and we believe we have a unique approach to achieve this. We continue to enroll our Phase 1 study of MRT-8102 and look forward to presenting initial data in healthy volunteers and elevated CVD-risk subjects in the first half of 2026.”
The poster, entitled, “Selective Degradation of NIMA-related kinase 7 (NEK7) via a Molecular Glue Degrader Inhibits IL-1 Downstream of NLRP3 Inflammasome Activation: A Novel Therapeutic Approach for Cardiovascular Inflammation” (Poster Number #Sa4063), will be displayed on Saturday, November 8, 2025 from 10:30 to 11:30 a.m. CST in a poster session entitled, “Novel Cellular Stress Sensors in Cardiovascular Pathology: Metabolic, Mechanical, and Immune Interactions.” The poster will be presented by Daric Wible, Ph.D., Senior Scientist II, Biology, Monte Rosa Therapeutics.
Summary of key findings:
MRT-8102 is a selective, potent, and durable NEK7 degrader. Activation of the NLRP3 inflammasome critically depends on NEK7.
Administration of MRT-8102 led to inhibition of NLRP3 inflammasome in vitro and in vivo and subsequently inhibited production of multiple inflammatory cytokines.
In in vitro assays, MRT-8102 inhibited pyroptotic membrane permeabilization in stimulated human monocyte-derived macrophages (hMDM), unlike anti-IL-1 and anti-IL-6 therapies. Additionally, only MRT-8102 inhibited release of multiple cytokines from stimulated hMDM.
In vitro, NEK7 degradation inhibited cholesterol crystal-induced NLRP3 inflammasome activation, a key driver of atherosclerotic plaque pathogenesis, more potently than selnoflast, an NLRP3 inhibitor currently in development.
In a mouse peritonitis model, MRT-8102 led to potent inhibition of the cytokines IL-1β, IL-1α, IL-6, and TNF in peritoneal lavage.
MRT-8102 demonstrated near-complete suppression of IL-1β and Caspase-1 activity in ex vivo-stimulated whole blood from orally dosed cynomolgus monkeys.
Degrading NEK7 to modulate the inflammasome represents a novel and differentiated approach with potential therapeutic application in multiple cardiovascular and cardiometabolic diseases, including pericarditis and atherosclerosis.
