Actuate Therapeutics To Collaborate with Incyte Corporation and the University of Pittsburgh on Clinical Trial of Elraglusib in Combination with Retifanlimab and mFOLFIRINOX in Patients with Advanced Pancreatic Cancer

• Clinical Trial Study to be Conducted at UPMC Hillman Cancer to Evaluate Novel Combination as Frontline Therapy

CHICAGO and FORT WORTH, Texas, Aug. 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 the initiation of the Phase 1b trial of elraglusib in combination with Incyte’s PD-1 inhibitor, retifanlimab, and modified FOLFIRINOX (mFOLFIRINOX) as frontline therapy in advanced pancreatic adenocarcinoma. The trial is being conducted in collaboration with UPMC Hillman Cancer Center and Incyte Corporation.

The Investigator-Initiated Phase 1b open-label, single-arm RiLEY (NCT06896188) trial, led by Anwaar Saeed, MD, Associate Professor of Medicine, and Chief of the Gastrointestinal Medical Oncology at UPMC Hillman Cancer Center, will initially enroll up to 12 patients with advanced pancreatic adenocarcinoma with an expansion plan based on interim efficacy results. The primary objective of the trial is to determine the recommended phase 2 dose (RP2D) for the combination regimen, while the secondary objectives include evaluation of overall response rate (ORR), disease control rate (DCR), median progression-free survival (mPFS), overall survival (OS), and assessment of safety and tolerability.

“We are very excited to launch this study of elraglusib combined with retifanlimab and mFOLFIRINOX as a potentially synergistic, immune-modulatory approach for patients with advanced pancreatic cancer,” said Anwaar Saeed, MD, study principal investigator. “While the first generation of immune checkpoint (PD-1, PDL-1, CTLA-4) inhibitors, including retifanlimab, has been transformative by targeting key immune pathways and restoring anti-cancer effector cells activity, this study explores complementary mechanisms – particularly those evoked by elraglusib – that may modulate additional checkpoints and work synergistically with existing inhibitors to deepen and broaden anti-tumor responses. A growing body of preclinical and clinical data suggests that elraglusib can stimulate NK/T-cell anticancer effector functions, enhance antigen presentation, and reduce myeloid-derived suppressor cells in the tumor. These effects have been observed in the context of emerging clinical activity in metastatic pancreatic cancer.”

In a recent Phase 2 study, elraglusib in combination with gemcitabine/nab-paclitaxel (GnP) in first-line metastatic pancreatic adenocarcinoma (mPDAC) met its primary endpoint, showing a significant increase in median overall survival, a 37% reduction in the risk of death, and a doubling of the 12-month survival rate. In addition, increased CD8-positive and granzyme B-positive T cells, increased NK cells, and decreased myeloid-derived suppressor cells were observed in tumor biopsies only from elraglusib-treated patients, demonstrating elraglusib’s proposed immune modulating mechanism of action in patients with mPDAC.

“We believe the combination of elraglusib with retifanlimab and mFOLFIRINOX represents a novel and mechanistically compelling strategy to address unmet needs in advanced pancreatic adenocarcinoma,” said Daniel Schmitt, President & Chief Executive Officer of Actuate. “The collaboration with UPMC Hillman Cancer Center and Incyte enables us to explore new synergistic opportunities for patients who have not yet received systemic therapy and builds on the momentum of our ongoing clinical programs. The study further allows us to assess ways to optimize elraglusib’s potential through a complementary multi-agent approach designed to enhance both efficacy and durability of response.”  

In addition, elraglusib is being studied in a separate investigator initiated Phase 2 (NCT05077800) trial in combination with FOLFIRINOX and losartan in treatment-naïve mPDAC patients. Initial data from this Phase 2 trial, which were presented at the American Association for Cancer Research (“AACR”) Special Conference on Advances in Pancreatic Cancer Research last September, showed patients with extensive liver metastases experienced deep, durable responses to the novel combination treatment. Additional results from that study are expected in 2026.

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, 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 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.

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