Nimbus Therapeutics Advances Novel SIK2 Inhibitors for Inflammatory Bowel Disease with Dual Anti-Inflammatory and Mucosal Healing Mechanism
核心洞察
Nimbus Therapeutics (搜索) will present preclinical data on highly selective SIK2 (搜索) inhibitors at the 21st ECCO Congress, demonstrating dual mechanisms of suppressing inflammation and promoting mucosal healing.
The company's SIK2 (搜索) inhibitors show greater than 300-fold selectivity over other SIK isoforms, potentially avoiding cardiovascular and bone toxicities associated with broader SIK inhibition.
Data from preclinical models and human ex vivo systems support selective SIK2 (搜索) inhibition as a differentiated oral therapeutic approach for inflammatory bowel disease.
Nimbus Therapeutics (搜索) will present promising preclinical data on its novel salt-inducible kinase 2 (SIK2 (搜索)) inhibitor program at the 21st Congress of the European Crohn's and Colitis Organisation (ECCO), taking place February 18-21, 2026, in Stockholm, Sweden. The company's highly selective SIK2 inhibitors demonstrate a dual mechanism of suppressing inflammation and promoting mucosal healing in both preclinical models and human ex vivo systems.
Targeting SIK2 for Enhanced Selectivity and Safety
Salt-inducible kinases comprise three closely related isoforms (SIK1 (搜索), SIK2 (搜索), and SIK3 (搜索)) that function as downstream signaling nodes integrating pathogen- and damage-associated cues. Among these isoforms, SIK2 serves as a key regulator in myeloid cells that amplifies pro-inflammatory gene expression. Studies have shown that selective inhibition of SIK2 reduces pro-inflammatory cytokines and uniquely upregulates tissue repair factors such as interleukin-10 (IL-10), an effect not observed with SIK1 or SIK3 inhibition.
Nimbus' therapeutic approach to selectively targeting SIK2 (搜索) is positioned to avoid potential toxicities associated with inhibition of other SIK isoforms, including cardiovascular effects linked to SIK1 (搜索) inhibition and bone defects observed with SIK3 (搜索) loss-of-function. Using structure-based drug design, the company has developed highly selective SIK2 inhibitors with greater than 300-fold selectivity over SIK1 and SIK3.
ECCO Congress Data Presentations
The company will present two poster presentations at ECCO on Friday, February 20, 2026, from 12:40 p.m. to 1:40 p.m. CET in Poster Exhibition Hall A. The first presentation, titled "Selective SIK2 (搜索) Inhibition Suppresses Intestinal Inflammation and Promotes Mucosal Healing in Models of Colitis" (Poster P0115), will be presented by Yanbo Zhang, Ph.D. The second presentation, "SIK2 Selective Inhibitors Demonstrate Dual Anti-inflammatory and Mucosal Repair Profiles in Human ex vivo Models of Ulcerative Colitis" (Poster P0156), will be presented by Scott Daigle.
Clinical Development Path Forward
"This body of data validates that highly selective SIK2 (搜索) inhibition achieves robust efficacy across preclinical and human ex vivo models through a dual mechanism of suppressing inflammation and promoting mucosal healing," said Peter Tummino, Ph.D., President of Research and Development at Nimbus. "The data support selective SIK2 inhibition as a differentiated oral therapeutic approach for inflammatory bowel disease and other chronic inflammatory diseases, with a potentially improved safety profile compared to therapies that target broader SIK inhibition."
Tummino added that the company looks forward to advancing its novel SIK2 (搜索) program toward first-in-human studies for inflammatory and autoimmune diseases in the months ahead. This development represents part of Nimbus Therapeutics (搜索)' broader pipeline, which includes NDI-219216 (搜索), a Werner syndrome helicase (WRN (搜索)) inhibitor currently in Phase 1/2 clinical development for microsatellite instability high (MSI-H) tumors, along with multiple preclinical programs in oncology, immunology, and metabolic diseases.
AI-Enhanced Drug Discovery Platform
Nimbus Therapeutics (搜索) operates as a structure-based drug discovery company developing breakthrough small molecule medicines through AI-enhanced computational chemistry. The company pursues well-validated but difficult-to-drug targets with high potential to transform patients' lives, combining leading-edge computational technologies with a tailored array of machine learning-based predictive modeling approaches.