Elraglusib

- Near doubling of 1-year overall survival (OS), increased median OS of 4 months (12.5 vs 8.5 months), and 43% reduction in risk of death in patients treated with at least one cycle (4 weeks) of elraglusib plus gemcitabine/nab-paclitaxel (GnP) vs GnP alone - Patients with liver metastases experienced a 2.5x improvement in 1-year OS with a 38% reduction in risk of death when treated with elraglusib plus GnP June 24, 2025 -- 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 highlighted results from a pre-specified subgroup analysis of its Phase 2 (Actuate-1801 Part 3B) trial of elraglusib in combination with gemcitabine/nab-paclitaxel (GnP) in first-line metastatic pancreatic adenocarcinoma (mPDAC). Patients treated for at least one complete cycle (4 weeks) of therapy achieved a median overall survival (mOS) of 12.5 months in the elragusib/GnP arm, compared to 8.5 months in the control arm. The analysis showed a 43% reduction in the risk of death relative to control, highlighting the significant potential impact of early disease control by elraglusib. Improved outcomes were reported in the combination versus control arms, respectively: disease control rate (DCR): 53.4% vs 44.8%, overall response rate (ORR): 37.9% vs 29.3%, and median progression-free survival (PFS): 6.9 vs 5.6 months In patients with liver metastases, treatment with elraglusib led to a 2.5-fold increase in 1-year OS and a 38% reduction in the risk of death compared to control. While the GnP arm showed 0% OS probability at 18 months, patients on elraglusib achieved a survival probability of 13.6% OS at 18 months. Additional efficacy metrics showed improvements as follows: DCR: 36.8% vs 27.9%, ORR: 29.8% vs 19.7%, and PFS: 4.9 vs 3.9. “We are highly encouraged by the significant clinical benefit provided by elraglusib demonstrated in this study,” said Daniel Schmitt, President & Chief Executive Officer of Actuate. “Patients who received at least one cycle – or 4 weeks – of elraglusib showed a rapid and meaningful survival benefit, including a near doubling of the 1-year overall survival and 43% reduction in the risk of death compared to control. Separately, in the subgroup of patients with liver metastases, a population with historically poor prognosis, we observed a more than 2.5-fold improvement in 1-year OS with a 38% reduction in risk of death. These results underscore the potential of elraglusib to generate rapid and durable benefit in high-risk patients, which could be highly impactful in future development and commercial pathways.” Metastatic pancreatic ductal adenocarcinoma (mPDAC) is an advanced stage of pancreatic cancer, the most common type of pancreatic malignancy, originating from the ductal cells of the pancreas. When metastatic, the cancer has spread beyond the pancreas to distant organs, such as the liver, lungs, or peritoneum, and is typically classified as stage IV. mPDAC accounts for approximately 90% of pancreatic cancers; one of the deadliest cancers with a 5-year survival rate of ~3-5% for metastatic cases. 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. The content above comes from the network. if any infringement, please contact us to modify.

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