Actuate Therapeutics Launches Strategic Research Initiative to Combine Elraglusib with RAS Inhibitors

• Inform future clinical development plans, further establishing elraglusib as a potential backbone therapy in difficult-to-treat cancers
• Mechanisms of action support enhanced activity of GSK-3β plus RAS inhibition
• Preclinical combination results expected in 2H2026
  
  

CHICAGO and FORT WORTH, Texas, March 09, 2026 (GLOBE NEWSWIRE) -- Actuate Therapeutics, Inc. (NASDAQ: ACTU) (“Actuate” or the “Company”), a clinical-stage biopharmaceutical company focused on developing therapies for the treatment of high-impact, difficult-to-treat cancers through the inhibition of glycogen synthase kinase-3 beta (GSK-3β), today announced the launch of an expanded research initiative evaluating combinations of its clinical-stage GSK-3β inhibitor elraglusib with emerging RAS-targeted therapies.

Despite recent advances in RAS-targeted therapies, adaptive resistance mechanisms and pathway reactivation remain some of the key barriers to achieving durable responses in patients.

Based on the mechanisms of action, GSK-3 inhibition may represent a critical complementary strategy capable of enhancing RAS-targeted therapies by suppressing downstream survival signaling and resistance pathways, including

• NF-κB–mediated survival signaling
• MYC-driven transcriptional programs
• metabolic adaptation and oxidative stress buffering
• tumor microenvironment immune suppression

In addition, RAS-mutant tumors — particularly pancreatic cancer — are widely considered immunologically resistant. Preclinical research suggests that GSK-3β inhibition may enhance antigen presentation, activate T cells and NK cells, and reduce exhausted T-cells. By simultaneously targeting tumor intrinsic survival pathways and modulating the tumor immune microenvironment, the combination of elraglusib and RAS inhibitors has the potential to create a multi-modal therapeutic strategy designed to overcome resistance and expand clinical benefit in RAS-driven cancers.

Expanding the Strategic Opportunity for Elraglusib

Elraglusib is a best-in-class, highly selective GSK-3β inhibitor with broad potential across multiple oncology indications, including pancreatic cancer, melanoma, colorectal cancer, and sarcoma. The investigational product has been administered to more than 500 patients and is currently being evaluated in a Phase 2 trial in metastatic pancreatic cancer (mPDAC).

The combination strategy is designed to simultaneously block proliferative signaling through RAS inhibition and disrupt tumor survival pathways via elraglusib’s GSK-3β inhibition, potentially enhancing apoptotic signaling beyond the threshold achieved with RAS inhibition alone.

The combination program is expected to include in-vitro studies of elraglusib with select RAS inhibitors using tumor models of RAS resistance, in-vivo tumor regression and survival studies, and translational biomarker analysis. Initial data from the program are expected in Q2 2026, with additional results in 2H26.

While next-generation RAS inhibitors are making meaningful progress, the emerging data suggest that combination strategies will be required to maximize clinical benefit. By targeting GSK-3 – a central regulator of tumor survival – the Company believes that elraglusib has the potential to enhance depth and durability of RAS-targeted therapies. Actuate is advancing this work with leading academic collaborators and potential industry partners, further positioning elraglusib as a potential foundational component of next-generation treatment paradigms for RAS-driven cancers.

About Actuate Therapeutics, Inc.

Actuate is a clinical-stage biopharmaceutical company focused on developing therapies for the treatment of high-impact, difficult-to-treat cancers. Actuate’s lead investigational drug, elraglusib (a novel GSK-3β inhibitor), targets molecular pathways in cancer that are involved in promoting tumor growth and resistance to conventional cancer drugs such as chemotherapy through the inhibition of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB) and DNA Damage Response (DDR). Elraglusib may also mediate anti-tumor immunity through the regulation of multiple immune checkpoints and immune cell function.

For additional information, please visit the Company’s website at or follow us on LinkedIn, X, and Facebook.