Actuate Announces Promising Preclinical Data Showing Synergistic Activity of Elraglusib in Combination with RAS Inhibitors Zoldonrasib and Daraxonrasib

• Independent studies conducted at Northwestern University and Mayo Clinic demonstrate synergistic activity of elraglusib in combination with RAS-targeted agents across multiple murine and human pancreatic cancer models
• Data further support the potential for combination therapy strategies across other RAS-driven cancers
• Additional studies are ongoing with results to be presented at upcoming medical conferences
  

CHICAGO and FORT WORTH, Texas, Sept. 09, 2026 (GLOBE NEWSWIRE) -- Actuate Therapeutics, Inc. (NASDAQ: ACTU) (“Actuate” or the “Company”), a clinical-stage biopharmaceutical company, focused on developing novel therapies for high-impact, difficult-to-treat cancers, today announced new preclinical data evaluating elraglusib in combination with zoldonrasib (RMC-9805), an investigational RAS(ON) G12D-selective inhibitor, and daraxonrasib (RMC-6236), a RAS(ON) multi-selective inhibitor, in pancreatic ductal adenocarcinoma (PDAC), including models resistant to FOLFIRINOX chemotherapy. The studies were conducted in collaboration with investigators at Northwestern University and the Mayo Clinic.

Across a panel of murine KPC pancreatic cancer cell lines, the addition of elraglusib to zoldonrasib resulted in greater inhibition of tumor-cell growth compared with zoldonrasib alone. Synergistic combination activity was also observed across human patient-derived xenograft (PDX)-derived pancreatic cancer cell lines, demonstrating the effect across multiple independent pancreatic cancer models. Studies of elraglusib in combination with daraxonrasib were also conducted, demonstrating synergistic anti-cancer activity compared with either agent alone. Together, the findings with two distinct RAS-targeted agents provide evidence that the combination effect of elraglusib extends beyond a single RAS inhibitor.

“The emergence of direct RAS inhibitors represents a major advance in pancreatic cancer and creates an opportunity to identify combinations capable of further enhancing RAS-directed activity,” said Tanios “Tony” Bekaii-Saab, MD, FASCO - Chair for the Division of Hematology/Medical Oncology, Mayo Clinic in Arizona. “Importantly, the enhanced activity observed when elraglusib was combined with either zoldonrasib or daraxonrasib, two distinct RAS-targeted agents, highlights the potential for elraglusib to synergize with diverse RAS-directed therapies. Based on the unique and complementary mechanisms of action of elraglusib with these new RAS inhibition therapies, we are eager to evaluate the potential of combining elraglusib with RAS inhibition therapies in a clinical setting to expand treatment opportunities across RAS-driven diseases, including pancreatic cancer.”

Separate studies evaluated the combination of elraglusib with zoldonrasib in FOLFIRINOX-resistant murine and human pancreatic cancer models. Both murine and human models demonstrated that the combination of elraglusib with zoldonrasib in vitro resulted in enhanced anti-tumor activity of the combination and greater reductions in tumor cell viability compared with either agent alone.

“Resistance to frontline chemotherapy remains a major challenge in pancreatic cancer, underscoring the need for new therapeutic strategies to be used after patients progress on FOLFIRINOX,” said Dr. Deva Mahalingam, Professor of Medicine, Robert H. Lurie Comprehensive Cancer Center, Northwestern University. “Across multiple FOLFIRINOX-resistant pancreatic cancer models, we observed greater antitumor activity when elraglusib was combined with zoldonrasib than with either agent alone, with quantitative analysis supporting enhanced anti-tumor activity and potential synergistic interactions of the combination in the models evaluated. These findings provide a compelling rationale to further investigate whether combining GSK-3β (elraglusib) and RAS G12D inhibition can enhance therapeutic activity in treatment-resistant pancreatic cancer. We look forward to participating in advancing the development of elraglusib in upcoming clinical trials, including combination trials with these most promising RAS inhibitors.”

Key preclinical findings

• Across murine KPC and human PDX-derived pancreatic cancer cell lines, the addition of elraglusib to zoldonrasib reduced cell growth beyond that observed with zoldonrasib alone across all models tested.
• Elraglusib in combination with daraxonrasib demonstrated enhanced activity across multiple murine/human PDAC models compared with daraxonrasib alone.
• In independent cell line models of FOLFIRINOX-resistant PDAC, both murine and human models of elraglusib plus zoldonrasib produced greater reductions in tumor-cell viability than either agent alone
  

Additional studies are ongoing, with results planned for presentation at upcoming medical conferences.

“RAS-targeted therapies are rapidly reshaping the treatment landscape for pancreatic cancer, highlighted by the recent FDA approval of daraxonrasib, the first broad RAS-targeted therapy approved for metastatic pancreatic cancer,” said Daniel Schmitt, President and Chief Executive Officer of Actuate Therapeutics. “What is particularly compelling about the synergy data with elraglusib is the breadth and consistency of these findings. Elraglusib enhanced RAS-targeted activity across multiple murine and human models, with two distinct RAS inhibitors, and in models resistant to FOLFIRINOX. We believe these independent findings strengthen the potential for elraglusib to work synergistically with RAS-directed therapies and establish an important new combination approach in pancreatic and potentially other 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 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’ preclinical and 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, including statements concerning the potential for elraglusib to synergize with diverse RAS-directed therapies, our intention to advance the development of elraglusib in upcoming clinical trials in combination with RAS inhibitors and the potential for elraglusib in combination with RAS-directed therapies to establish an important new combination approach in pancreatic and potentially other RAS-driven cancers. 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 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 October 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; and those other factors discussed under the heading “Item 1A. Risk Factors” in our Annual Report on Form 10-K for the year ended December 31, 2025, filed with the SEC on March 26, 2026, and in our subsequent filed 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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LifeSci Advisors, LLC
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