ACTU

Median overall survival increased by >40% in elraglusib arm compared to the control arm, with a 1-year survival rate of 44% in the elraglusib arm versus 22% in the control arm 18-month survival rate >20% in elraglusib arm compared to 4% in control arm Consistent survival benefit observed across the poorest prognosis patient subgroups, including those with liver metastases and high disease burden 7-40X increases in tumor-infiltrating cytotoxic immune cells and biomarker signals in the elraglusib arm reflect immunomodulatory mechanisms of action CHICAGO and FORT WORTH, Texas, April 14, 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 publication of new data in Nature Medicine from a randomized phase 2 clinical trial (NCT03678883) evaluating elraglusib in combination with the gemcitabine-Nab-paclitaxel (GnP) chemotherapy compared to GnP alone in patients with previously untreated metastatic pancreatic cancer. The peer-reviewed paper (DOI: 10.1038/s41591-026-04327-4), entitled “Elraglusib and Chemotherapy in Metastatic Pancreatic Ductal Adenocarcinoma: A Randomized Controlled Phase 2 Trial” is available here. “These Phase 2 results continue to reinforce elraglusib’s potential as a combination-ready, first-line therapy with the ability to enhance the activity of standard of care chemotherapeutic backbones,” said Daniel Schmitt, Chief Executive Officer of Actuate. “The significant improvement in overall survival with an acceptable safety profile marks an important milestone for patients facing metastatic pancreatic cancer, historically one of the most difficult to treat diseases. The elraglusib containing regimen delivered a 40% improvement in median overall survival, a 38% lower risk of death, and doubled the survival rate at one year compared to the current first-line chemotherapy regimen of GnP alone. By targeting a central signaling node such as GSK-3β, elraglusib may modulate tumor cell survival, reshape tumor microenvironment, and suppress adaptive resistance pathways, enabling a broader biological impact across a broad range of cancers. Importantly, we are also advancing our research focused on exploring the expected synergistic potential of elraglusib in combination with RAS and MEK/RAF inhibitors, with the goal of further enhancing anti-tumor activity and broadening elraglusib’s therapeutic potential for patients. We remain deeply committed to advancing treatments that can improve patients’ lives and are grateful to the investigators and families who made this study possible.” Pancreatic cancer remains one of the deadliest malignancies worldwide. Pancreatic ductal adenocarcinoma (PDAC), which accounts for the majority of cases, is often diagnosed at a metastatic stage, where survival outcomes remain poor. For these patients, GnP is a commonly used first‑line regimen, yet median overall survival typically remains limited to approximately seven to ten months. Despite advances in understanding the molecular drivers of pancreatic cancer, meaningful therapeutic progress has been scarce, and immunotherapies successful in other solid tumors have not delivered similar benefits in PDAC, highlighting the urgent need for novel treatment approaches. Elraglusib (9‑ING‑41), a first‑in‑class GSK‑3β inhibitor, was evaluated in combination with GnP in a global, open‑label, phase 2 study in previously untreated metastatic pancreatic ductal adenocarcinoma. Patients were randomized 2:1 to receive elraglusib plus GnP or GnP alone. The combination improved median overall survival to 10.1 months versus 7.2 months and reduced the risk of death by 38% (HR 0.62; p=0.01), with one‑year survival rates of 44.1% and 22.3%, respectively. Safety was generally manageable in the elraglusib/GnP combination, with the most common Grade ≥3 adverse events including neutropenia, anemia, and fatigue. Exploratory analyses identified cytokine biomarkers and immune‑cell changes consistent with the immunomodulatory effect of elraglusib. Key Highlights and Readouts: Among the 286 patients enrolled across 60 global sites, efficacy analyses focused on 155 patients treated with once‑weekly elraglusib plus GnP and 78 patients receiving GnP alone in the modified intent‑to‑treat population, the study’s prespecified population for efficacy and safety analyses. Median overall survival (OS) was 10.1 months in the elraglusib/GnP arm (95% CI, 7.7–12.5) vs 7.2 months on the GnP arm (95% CI, 5.7–9.0), corresponding to a 2.9‑month improvement and a 38% reduction in risk of death (HR 0.62; p=0.01). A 1-year survival rate of 44.1% was observed in patients receiving elraglusib/GnP compared with 22.3% treated with GnP alone; at 18 and 24 months, landmark survival rates were 20.5% and 13.2% vs 4.4% and 0%, respectively. Survival benefits were consistent across poor prognosis subgroups; in patients with liver metastases, median OS was 8.3 vs 6.6 months (HR 0.62; p=0.008), and 1‑year survival rates were 39.2% vs 15.2%. Exploratory immunophenotyping demonstrated 7–40X increases in intratumoral CD8⁺ T cells, granzyme‑B⁺ cells, and CD56⁺ NK cells following elraglusib/GnP, with no comparable increases observed with GnP alone. High pre‑dose cytokine levels correlated with improved survival only in the elraglusib/GnP arm, indicating emerging predictive biomarker associations. The combination was well tolerated; the most common ≥Grade 3 TEAEs with elraglusib/GnP vs GnP were neutropenia (52.3% vs 30.8%), anemia (25.2% vs 29.5%), and fatigue (16.8% vs 5.1%). The mild to moderate visual changes observed in the elraglusib arm were transient and reversible. “Metastatic pancreatic cancer remains one of the most therapeutically challenging solid tumors, with few interventions demonstrating meaningful improvements in survival,” said Dr. Devalingam Mahalingam, MD, PhD, lead author of the manuscript. “The 2.9-month improvement in median overall survival observed with elraglusib plus gemcitabine and nab-paclitaxel, together with early and sustained signals of benefit across poor-prognosis subgroups, is encouraging and supports further clinical evaluation. The observed increases in tumor-infiltrating cytotoxic immune cells provide preliminary biologic context for the clinical findings and raise the possibility of an immunomodulatory effect, although these exploratory observations will require confirmation in future studies. Collectively, these results provide a rationale for continued investigation of elraglusib-based combinations in pancreatic cancer and potentially other difficult-to-treat malignancies.” 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’ 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, 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; 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; 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; 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 July 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, 2025, filed with the Securities and Exchange Commission (the “SEC”) on March 26, 2026, 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. Investor Contact Mike Moyer Managing Director LifeSci Advisors, LLC [email protected] Media Contact Ignacio Guerrero-Ros, Ph.D. Russo Partners, LLC [email protected] (858) 717-2310

Topline data shows statistically significant improvement in overall survival in elraglusib plus GnP combination arm versus GnP control arm Elraglusib/GnP combination arm demonstrated substantial improvement in median overall survival since the last data analysis Clinical trial meets primary endpoint for overall survival and confirms significant 1-year survival rate Elraglusib/GnP combination arm demonstrated a favorable risk-benefit profile Topline dataset to be presented in an oral presentation at the upcoming ASCO Annual Meeting Company plans to work with regulators to expeditiously bring elraglusib to commercialization CHICAGO and FORT WORTH, Texas, May 06, 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), today announced that elraglusib in combination with gemcitabine/nab-paclitaxel (GnP) met the primary endpoints and achieved statistical significance in topline results from its ongoing Phase 2 (Actuate-1801 Part 3B) trial in first-line treatment of metastatic pancreatic ductal adenocarcinoma (mPDAC). The topline results, which demonstrate a substantial improvement in median overall survival benefit in the elraglusib/GnP combination arm compared to the results announced in December 2024, will be presented on May 31, 2025, at the Annual Meeting of the American Society of Clinical Oncology (ASCO). “Pancreatic cancer is one of the most aggressive and difficult-to-treat malignancies, where patients urgently need new therapeutic options,” said Daniel Schmitt, President & Chief Executive Officer of Actuate. “There have been no major advances in improving survival in first-line treatment of metastatic pancreatic cancer in over a decade. Demonstrating statistically significant increases in both median overall survival and percent of patients reaching one-year survival and beyond, along with a favorable risk-benefit profile in this Phase 2 trial, further demonstrates elraglusib’s potential to shift the treatment paradigm in mPDAC. We are incredibly excited to present the topline data at ASCO. Based on the significant improvement in survival we have seen to date in the combination arm, we look forward to working with US and EU regulators in the second half of this year to map out the path to advancing elraglusib to NDA and registration and making the drug available to patients as expeditiously as possible.” ASCO Presentation Details: Abstract Title: Preliminary results from the randomized phase 2 study (1801 part 3B) of elraglusib in combination with gemcitabine/nab-paclitaxel (GnP) versus GnP alone in patients (pts) with previously untreated metastatic pancreatic ductal adenocarcinoma (mPDAC).Abstract Number: 4006Session Title: Gastrointestinal Cancer—Gastroesophageal, Pancreatic, and HepatobiliaryPresenter: Devalingam Mahalingam, MD, PhDOral Presentation Date and Time: Saturday, May 31, 2025, 4:48 PM CDT About Actuate-1801 Part 3B StudyThe Actuate-1801 Part 3B study (NCT03678883) is a randomized, controlled Phase 2 trial of elraglusib with GnP versus GnP alone in first-line mPDAC. The trial enrolled 286 mPDAC patients with no prior systemic treatment for metastatic disease, who were randomized 2:1 to the elraglusib treatment arm (elraglusib + GnP) or the control arm (GnP alone). Elraglusib is administered at a dose of 9.3 mg/kg by IV infusion on Day 1 of each week of a 28-day cycle. The primary endpoint for this study is median overall survival, with OS summarized throughout the study by estimates of 1-year survival. Secondary endpoints are DCR, ORR, PFS, and AE. About GSK-3βInhibition of GSK-3β may inhibit tumor growth and improve survival through several complimentary mechanisms that include enhancement of chemotherapy activity, activation of innate anti-tumor immunity, and regulation of gene expression, leading to alterations in tumor metabolism and Epithelial-to-Mesenchymal Transition (EMT). 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 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 Moyer Managing Director LifeSci Advisors, LLC [email protected]