Nimbus Therapeutics Presents New Mechanistic Data Highlighting Differentiated Biology of Selective SIK2 Inhibitors at IMMUNOLOGY2026™

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Nimbus Therapeutics, LLC (“Nimbus Therapeutics” or “Nimbus”), a drug discovery company developing breakthrough medicines through AI-enhanced computational chemistry, today announced that it is presenting new mechanistic data on its novel salt-inducible kinase 2 (SIK2) inhibitor program at IMMUNOLOGY2026™, the 109^th annual meeting of the American Association of Immunologists (AAI), taking place April 15–19, 2026, in Boston, Massachusetts.

Salt-inducible kinases (SIKs) comprise three closely related isoforms (SIK1, SIK2, and SIK3) that function as key signaling nodes in myeloid cells, integrating pathogen- and damage-associated cues to drive inflammation. Among these, SIK2 plays a critical role in regulating proinflammatory gene expression. Using structure-based drug design, Nimbus has developed highly selective SIK2 inhibitors with greater than 300-fold selectivity over the SIK1 and SIK3 isoforms. Preclinical data demonstrate that selective inhibition of SIK2 drives a dual pharmacological profile in myeloid cells and mice, suppressing proinflammatory cytokines while simultaneously promoting pro-resolution and tissue repair signals, a mechanistic profile distinct from SIK3 and JAK1 inhibition.

Presentation Details:

Abstract Title: Selective SIK2 Inhibitors Suppress Proinflammatory Responses While Upregulating Pro-Resolution Signals in Stimulated Myeloid Cells and Mice

Session: Therapeutics for Autoimmune Diseases I

Date: Thursday, April 16, 2026

Time: 2:30 p.m. – 3:30 p.m. ET

Poster Board Number: 556

Session Location: Exhibit Hall

Presenter: Leon Collis, Ph.D.

The poster will be available on the Nimbus website here.

These findings build on data presented earlier this year at the 21^st Congress of the European Crohn’s and Colitis Organisation (ECCO), where Nimbus reported robust efficacy and protection of the mucosal barrier in mouse colitis models, and anti-inflammatory and tissue repair activity in human ex vivo systems. The IMMUNOLOGY2026 presentation extends that work with a deeper mechanistic characterization, demonstrating that Nimbus’ highly selective SIK2 inhibitors simultaneously downregulate multiple proinflammatory cytokines, including TNFα, IL-23, and IL-6, while upregulating pro-resolution and tissue repair factors, including IL-10. Importantly, this dual effect was not observed with SIK3 inhibition, which instead elevates IL-23 and IL-12, key drivers of inflammatory disease, further highlighting the critical importance of isoform selectivity.

“These data continue to strengthen our conviction that SIK2-selective inhibition is required for this dual mechanism of dampening inflammation and promoting tissue repair,” said Peter Tummino, Ph.D., President of Research and Development at Nimbus. “This distinct profile supports SIK2 inhibition as a differentiated oral therapeutic approach for inflammatory bowel disease and other chronic inflammatory diseases.”

Nimbus’ SIK2 program is advancing through investigational new drug (IND)-enabling studies toward first-in-human evaluation in inflammatory and autoimmune diseases.

About Nimbus Therapeutics

Nimbus Therapeutics is a structure-based drug discovery company developing breakthrough small molecule medicines through AI-enhanced computational chemistry. Nimbus pursues well-validated but difficult-to-drug targets with high potential to transform patients’ lives. The company advances promising research based on a unique strategy that combines leading-edge computational technologies with a tailored array of machine learning-based predictive modeling approaches.

Nimbus’ pipeline includes NDI-219216, a Werner syndrome helicase (WRN) inhibitor in Phase 1/2 clinical development for microsatellite instability high (MSI-H) tumors, a salt-inducible kinase 2 (SIK2) inhibitor program advancing toward first-in-human studies for inflammatory and autoimmune diseases, and multiple preclinical programs across oncology, immunology, and metabolic diseases. The company is headquartered in Boston, Mass. To learn more about Nimbus, please visit www.nimbustx.com.