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-3- 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-3ß), today announced the launch of an expanded research initiative evaluating combinations of its clinical-stage GSK-3ß 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 (Dilly et al., Cancer Discov 2024).

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-?B-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-3ß 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-3ß 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-3ß 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 (Long et al., Cancer Res 2026). 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-3ß 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 www.actuatetherapeutics.com or follow us on LinkedIn, X, and Facebook.

Forward Looking Statements

This press release contains forward-looking statements about us, including our and other parties' clinical trials and development plans, and our industry. The words "anticipate," "believe," "continue," "could," "estimate," "expect," "intend," "may," "might," "ongoing," "plan," "potential," "predict," "project," "should," "target," "will," "would," or the negative of these terms or other comparable terminology are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. All statements, other than statements related to present facts or current conditions or of historical facts, contained in this press release are forward-looking statements. Accordingly, these statements involve estimates, assumptions, substantial risks and uncertainties which could cause actual results to differ materially from those expressed in them, including but not limited to that we may not successfully conduct our preclinical study of GSK-3ß in combination with RAS-targeted therapies; we may not be able to report preclinical combination results by the second half of 2026 or, if we are able to do so, the results may not be favorable; preliminary and unpublished data may be subject to change and further interpretation following the availability of more data or following a more comprehensive review of the data and should not be relied upon as a final analysis; clinical and preclinical drug development involves a lengthy and expensive process with uncertain timelines and outcomes, results of prior preclinical studies, early clinical trials and sub-group studies are not necessarily predictive of future results and may not correlate with improved responses, and elraglusib may not achieve positive clinical results or favorable preclinical results or receive regulatory approval on a timely basis, if at all; that we may not successfully enroll additional patients or establish or advance plans for further development, including through conversations with the FDA or EMA and the standards such bodies may impose for such development; that elraglusib could be associated with side effects, adverse events or other properties or safety risks, which could delay or preclude regulatory approval, cause us to suspend or discontinue clinical trials or result in other negative consequences; our reliance on third parties to conduct our non-clinical studies and our clinical trials; our reliance on third-party licensors and ability to preserve and protect our intellectual property rights; that we face significant competition from other biotechnology and pharmaceutical companies; our ability to fund development activities, including because our financial condition raises substantial doubt as to our ability to continue as a going concern and we require additional capital to finance our operations beyond the second quarter of fiscal year 2026, and a failure to obtain this necessary capital in the near term on acceptable terms, or at all, could force us to delay, limit, reduce or terminate our development programs, commercialization efforts or other operations. In addition, any forward-looking statements are qualified in their entirety by reference to the factors discussed under the heading "Item 1A. Risk Factors" in our Annual Report on Form 10-K for the year ended December 31, 2024, filed with the SEC on March 13, 2025, and our Quarterly Reports on Form 10-Q, and other filings with the SEC. Because the risk factors referred to above could cause actual results or outcomes to differ materially from those expressed in any forward-looking statements made by us or on our behalf, you should not place undue reliance on any forward-looking statements. Further, any forward-looking statement speaks only as of the date on which it is made. New factors emerge from time to time, and it is not possible for us to predict which factors will arise. In addition, we cannot assess the impact of each factor on our business or the extent to which any factor, or combination of factors, may cause actual results to differ materially from those contained in any forward-looking statements. Unless legally required, we do not undertake any obligation to release publicly any revisions to such forward-looking statements to reflect events or circumstances after the date of this press release or to reflect the occurrence of unanticipated events.

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