Elraglusib

Phase 2 highlights robust biomarker identification and survival correlations in first-line metastatic pancreatic cancer (mPDAC) treated with elraglusib CHICAGO, IL and FORT WORTH, TX, USA I June 20, 2025 I 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 biomarker data from a recent poster presentation at the American Society of Clinical Oncology (ASCO) annual meeting from the Phase 2 (Actuate-1801 Part 3B) trial of elraglusib in combination with gemcitabine/nab-paclitaxel (GnP) in first-line metastatic pancreatic adenocarcinoma (mPDAC). The study demonstrated the use of machine learning and statistical models to predict overall survival (OS) based on pre-dose plasma biomarkers. The poster described an analysis of 40 cytokines, chemokines, soluble cell receptors, and growth factors (CCSGs) from plasma samples obtained prior to treatment from all patients enrolled in Actuate-1801 Part 3B. The analysis identified 7 biomarkers as uniquely significant predictors of favorable survival in the elraglusib-treated cohort, including one, CXCL2, with an inverse survival trend compared to the GnP control arm. This indicates that in patients not treated with elraglusib, high CXCL2 was unfavorable, but this trend is reversed with elraglusib treatment, highlighting the potential of elraglusib to favorably affect the immune microenvironment. Univariate analysis revealed strong predictive performance with CXCL2 emerging as a consistently reliable biomarker for survival across multiple cross-validation analyses. Elevated levels of CXCL2 and TRAIL were associated with improved OS, while lower levels of CCL3, IL-1α, IL-18, TGF-β, and TRAIL R3 were similarly linked to better survival. These signatures were combined into multivariate machine learning models that accurately predicted patients who would survive for greater than one year if treated with elraglusib and GnP. “These results represent an important advance in our biomarker strategy,” said Daniel Schmitt, President & Chief Executive Officer of Actuate. “They support the ability to use simple, non-invasive blood-based markers to potentially identify patients more likely to benefit from elraglusib. The pre-dose biomarker signatures identified in the 1801 Part 3B study, particularly involving high CXCL2 and low TGF-β, CCL3, and IL-18, which were all associated with a survival benefit, suggests that elraglusib may exert pleiotropic immunomodulatory effects regulating cytotoxic T cells, NK cells and cells of the myeloid lineage including macrophages and neutrophils. Crosstalk between components of the immune system support the growing body of evidence that elraglusib enhances immune response mechanisms critical to its antitumor efficacy.” “The application of unbiased mathematical and machine learning models allowed us to pinpoint the strongest biomarker signals free from pre-conceived notions of elraglusib’s mechanisms. What is so exciting about this project is that the unbiased approach aligns with prior mechanistic studies. The congruence of our clinical data analytics and the preclinical research combined with the strength of our predictive models gives us confidence that these biomarkers could be extremely beneficial in identifying the right patients at the right time,” said Taylor Weiskittel, MD, Ph.D., the lead author on this study. “We look forward to applying this approach to guide the development of elraglusib in mPDAC as well as other advanced cancer indications in the future.” The company plans to test the identified biomarkers prospectively in future trials. Additional efforts will focus on optimizing sequential univariate combinations for patient stratification, refining multivariate machine learning models for predictive accuracy, and comparing these approaches head-to-head. 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 http://www.actuatetherapeutics.com. SOURCE: Actuate Therapeutics

Inclusion reflects continued growth and momentum in the company’s mission to transform the treatment of metastatic pancreatic ductal adenocarcinoma (mPDAC) CHICAGO and FORT WORTH, Texas, June 16, 2025 (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), announced today that the Company will be added to the Russell 3000® Index, with automatic inclusion in the Russell 2000® Index, effective after the U.S. market close on June 27, as part of the 2025 Russell indexes annual reconstitution. The inclusion follows the initial announcement on Friday, May 23, and the latest update on Friday, June 13, 2025, in connection with the annual reconstitution of the Russell U.S. Indexes. The Russell 3000® Index tracks the performance of the largest 3,000 publicly traded U.S. companies and serves as a broad benchmark for the U.S. equity market. The Russell 2000® Index, a subset of the Russell 3000®, measures the performance of the small-cap stocks and represents approximately 10% of the total market capitalization of the U.S. equity market. Membership in the Russell Index lasts for one year and results in automatic inclusion in appropriate growth and value style indexes. The Russell indexes are used by investment managers and institutional investors for index funds and as benchmarks for active investment strategies. As of May 2025, approximately $10.6 trillion in assets are benchmarked against the Russell U.S. Indexes. “Inclusion in the Russell 3000® and 2000® Indexes represents a significant milestone for Actuate and reflects the company’s strong momentum since our IPO last year,” said Daniel Schmitt, President & Chief Executive Officer of Actuate. ”It comes on the heels of very positive topline Phase 2 data in mPDAC, which showed that the trial met its primary endpoint, demonstrating a clinically meaningful increase in median overall survival (mOS) of 10.1 months compared to 7.2 months (p = 0.01), with a 37% reduction in the risk of death (HR = 0.63), reinforcing the therapeutic potential of our lead candidate, elraglusib. This recognition not only elevates our visibility within the investment community but also validates our platform and strategic direction. As we advanced the development of elraglusib, we believe this is a pivotal moment that further positions Actuate for long-term growth and value creation.” For more information on the Russell 2000® Index and Russell 3000® Index and the annual reconstitution, go to the “Russell Reconstitution” section on the FTSE Russell website. 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 http://www.actuatetherapeutics.com. 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 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 and early clinical trials are not necessarily predictive of future results, 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 2025, 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 Report on Form 10-Q for the quarter ended March 31, 2025, filed with the SEC on May 15, 2025, 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. Investor Contact Mike MoyerManaging DirectorLifeSci Advisors, LLCmmoyer@lifesciadvisors.com Media Contact Ignacio Guerrero-Ros, Ph.D., or David SchullRusso Partners, LLCIgnacio.guerrero-ros@russopartnersllc.com David.schull@russopartnersllc.com (858) 717-2310 or (646) 942-5604