EULAR 2025 – Targeting NLRP3 Inflammasome Activation and Inflammation in Gout with NEK7 Molecular Glue Degraders: A Novel Therapeutic Strategy

Published: 2025-06-16 07:41:07 ET GLUE

Published on 06/16/2025 at 07:41

Targeting NLRP3 Inflammasome Activation and Inflammation in Gout with NEK7 Molecular Glue Degraders: A Novel Therapeutic Strategy

Arvin Iracheta-Vellve, PhD

Associate Director, Biology

EULAR 2025

Targeting NLRP3 Inflammasome Activation and Inflammation in Gout with NEK7 Molecular Glue Degraders

NEK7 as a Critical Component of NLRP3 Inflammasome-driven Gout

Utilizing a Molecular Glue Degrader, MRT-8102, to Target NEK7/NLRP3 inflammasome

PKPD of MRT-8102, a NEK7 MGD

Confidential and Proprietary

2

Gout as a Clinical Opportunity

NEK7 is a Key Regulator of NLRP3 Inflammasomes, IL-1 and IL-18

Inactive

NLRP3

+

Active NLRP3

Wheel-like oligomerization

pro-IL-1 pro-IL-18

NLRP3 NEK7

IL-1 IL-18

Cytokine secretion

Pyroptosis

Activated NLRP3 complex

Activation of the NLRP3 inflammasome critically

depends on NEK7

NEK7 licenses NLRP3 assembly in a kinase-independent manner

NEK7-deficient macrophages are severely impaired in IL-1β and IL-18 secretion

Consequently, NEK7 degradation has the potential to become an important treatment modality for a variety of inflammatory diseases

Diseases driven by IL-1 and the NLRP3 inflammasome including gout, pericarditis and other cardiovascular disease, neurodegenerative disease, and obesity

3

Pericarditis

Confidential and Proprietary

Gout

Parkinson

Obesity Atherosclerosis

Our Novel Approach To Targeting the NLRP3 Inflammasome Through NEK7 Degradation With Molecular Glue Degraders (MGDs)

Ubiquitin chain

Ternary complex

4

Neosubstrate (NEK7)

Proteasome-mediated degradation of neosubstrate

Confidential and Proprietary

Targeting NLRP3 Inflammasome Activation and Inflammation in Gout with NEK7 Molecular Glue Degraders

NEK7 as a Critical Component of NLRP3 Inflammasome-driven Gout

Utilizing a Molecular Glue Degrader, MRT-8102, to Target NEK7/NLRP3 inflammasome

PKPD of MRT-8102, a NEK7 MGD

Confidential and Proprietary

5

Gout as a Clinical Opportunity

Disclaimer

Monte Rosa Therapeutics Inc. published this content on June 16, 2025, and is solely responsible for the information contained herein. Distributed via Public Technologies (PUBT), unedited and unaltered, on June 16, 2025 at 11:40 UTC.