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 elra ...

Core Insights - Actuate Therapeutics has completed the Phase 1 study of elraglusib in pediatric patients, showing promising results in treating refractory Ewing Sarcoma (EWS) [1][2][3] - The company plans to advance to a Phase 2 trial for elraglusib in children, adolescents, and adults with relapsed/refractory EWS due to the observed complete responses [1][3] Company Overview - Actuate Therapeutics is a clinical-stage biopharmaceutical company focused on developing therapies for high-impact, difficult-to-treat cancers, specifically through the inhibition of glycogen synthase kinase-3 beta (GSK-3β) [1][6] - Elraglusib, the company's lead investigational drug, targets molecular pathways involved in tumor growth and resistance to conventional cancer treatments [6] Clinical Study Details - The Phase 1/2 trial (NCT 04239092), known as Actuate-1902, is an open-label, multicenter study evaluating the safety and efficacy of elraglusib in pediatric patients with relapsed/refractory malignancies, including EWS [2][3] - The study enrolled ten patients with relapsed/refractory EWS, with two patients achieving complete responses and two others showing stable disease [3] Future Plans - The company is planning to initiate a Phase 2 trial in 2026, subject to funding availability, and will engage with regulators to discuss the potential registration path for elraglusib [3][1] - Actuate is collaborating with key opinion leaders and consortiums to ensure the upcoming study design meets patient needs and regulatory expectations [3]

Core Insights - Actuate Therapeutics, Inc. reported significant clinical benefits of elraglusib in combination with gemcitabine/nab-paclitaxel (GnP) for patients with first-line metastatic pancreatic adenocarcinoma, showing a near doubling of 1-year overall survival (OS) and a 43% reduction in risk of death compared to GnP alone [1][2][7] Company Overview - Actuate Therapeutics is a clinical-stage biopharmaceutical company focused on developing therapies for difficult-to-treat cancers, with elraglusib as its lead investigational drug targeting GSK-3β to inhibit tumor growth and enhance anti-tumor immunity [9] Clinical Trial Results - In the Phase 2 trial (Actuate-1801 Part 3B), patients receiving elraglusib plus GnP achieved a median overall survival (mOS) of 12.5 months compared to 8.5 months in the control group, with a disease control rate (DCR) of 53.4% versus 44.8% and an overall response rate (ORR) of 37.9% versus 29.3% [2][5] - Patients with liver metastases experienced a 2.5-fold increase in 1-year OS and a 38% reduction in risk of death, with a survival probability of 13.6% at 18 months for those treated with elraglusib [5][7] Efficacy Metrics - Additional efficacy metrics for patients with liver metastases included a DCR of 36.8% versus 27.9%, an ORR of 29.8% versus 19.7%, and a median progression-free survival (PFS) of 4.9 months compared to 3.9 months in the control group [5][7]

Core Insights - Actuate Therapeutics, Inc. announced promising biomarker data from the Phase 2 trial of elraglusib in combination with gemcitabine/nab-paclitaxel for first-line metastatic pancreatic adenocarcinoma, highlighting the potential for improved patient stratification based on pre-dose plasma biomarkers [1][2][3] Group 1: Study Findings - The analysis of 40 cytokines, chemokines, soluble cell receptors, and growth factors identified 7 significant biomarkers predicting favorable survival in the elraglusib-treated cohort, particularly highlighting CXCL2's unique survival trend [2][3] - Univariate analysis showed that elevated levels of CXCL2 and TRAIL were associated with improved overall survival, while lower levels of CCL3, IL-1α, IL-18, TGF-β, and TRAIL R3 were linked to better survival outcomes [3] - Multivariate machine learning models were developed to accurately predict patients likely to survive over one year when treated with elraglusib and GnP [3] Group 2: Company Strategy and Future Plans - The results support the use of non-invasive blood-based markers to identify patients who may benefit from elraglusib, indicating a significant advancement in the company's biomarker strategy [4] - The company plans to prospectively test the identified biomarkers in future trials and focus on optimizing patient stratification and predictive accuracy through refined machine learning models [4] - Actuate aims to apply this biomarker identification approach to guide the development of elraglusib in metastatic pancreatic cancer and other advanced cancer indications [4] Group 3: Company Overview - Actuate Therapeutics is a clinical-stage biopharmaceutical company focused on developing therapies for difficult-to-treat cancers, with elraglusib as its lead investigational drug targeting pathways involved in tumor growth and resistance to conventional therapies [5] - Elraglusib may also enhance anti-tumor immunity by regulating immune checkpoints and immune cell functions, indicating its potential in cancer treatment [5]

Core Insights - Actuate Therapeutics, Inc. will be added to the Russell 3000® Index and automatically included in the Russell 2000® Index effective after the U.S. market close on June 27, 2025, marking a significant milestone for the company [1][3] - The inclusion reflects the company's strong momentum following positive topline Phase 2 data in metastatic pancreatic ductal adenocarcinoma (mPDAC), demonstrating a clinically meaningful increase in median overall survival (mOS) of 10.1 months compared to 7.2 months, with a 37% reduction in the risk of death [3] Company Overview - Actuate is a clinical-stage biopharmaceutical company focused on developing therapies for high-impact, difficult-to-treat cancers, with its lead investigational drug, elraglusib, targeting molecular pathways involved in tumor growth and resistance to conventional cancer treatments [4] - Elraglusib is a novel glycogen synthase kinase-3 beta (GSK-3β) inhibitor that may also mediate anti-tumor immunity through the regulation of immune checkpoints and immune cell function [4] Industry Context - 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, with approximately $10.6 trillion in assets benchmarked against the Russell U.S. Indexes as of May 2025 [2]

Core Insights - Actuate Therapeutics announced positive topline results from the Phase 2 trial of elraglusib in combination with gemcitabine/nab-paclitaxel for treating metastatic pancreatic ductal adenocarcinoma, indicating a significant improvement in overall survival [1][2][5] Study Results - The study achieved its primary endpoint with a median overall survival of 10.1 months for the elraglusib/GnP group compared to 7.2 months for the GnP group, resulting in a 37% reduction in the risk of death (HR = 0.63) [2][8] - The 12-month survival rate was 44.1% in the elraglusib/GnP arm versus 22.3% in the GnP arm, demonstrating a doubling of survival rates [2][8] - Continued survival benefits were observed at 18 and 24 months, with survival rates of 19.7% vs 4.4% and 13.8% vs 0% for elraglusib/GnP compared to GnP alone, respectively [8] - The overall response rate was numerically improved at 29.0% for the elraglusib/GnP arm compared to 21.8% for the GnP arm [8] Safety Profile - The trial met its primary safety endpoint, with treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs) in the elraglusib/GnP arm being similar to those in the GnP arm, indicating a favorable risk-benefit profile [8] - Most treatment-related adverse events (TRAEs) were Grade 1-2, with transient visual impairments being the most common [8] Mechanism of Action - Elraglusib works by inhibiting GSK-3β, which may enhance chemotherapy activity, activate anti-tumor immunity, and regulate gene expression, potentially leading to improved survival outcomes [10][11] Clinical Context - The KOL event highlighted the unmet need in mPDAC and the potential of elraglusib to reshape treatment paradigms, emphasizing the importance of new drugs with unique mechanisms [4][5]

Core Insights - Actuate Therapeutics, Inc. presented topline results from the Phase 2 trial of elraglusib in combination with gemcitabine/nab-paclitaxel for treating metastatic pancreatic ductal adenocarcinoma, demonstrating significant improvements in overall survival [1][2][5] Efficacy - The trial met its primary endpoint, showing a median overall survival (mOS) of 10.1 months for the elraglusib combination group compared to 7.2 months for the control group, with a hazard ratio (HR) of 0.63 and a log-rank p-value of 0.01, indicating a 37% reduction in the risk of death [2][4][5] - The 12-month survival rate for patients receiving elraglusib with GnP was 44.1%, which is double that of the GnP alone group at 22.3% [2][5] - Continued survival benefits were observed at 18 and 24 months, with survival rates of 19.7% vs 4.4% and 13.8% vs 0% for the elraglusib/GnP combination versus GnP alone, respectively [10] - The overall response rate was numerically improved at 29.0% for the elraglusib combination compared to 21.8% for GnP alone [10] Safety Profile - The trial met its primary safety endpoint, with treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs) in the elraglusib combination arm being similar to those in the GnP arm, indicating a favorable risk-benefit profile [10] - Most treatment-related adverse events (TRAEs) were Grade 1-2, with transient visual impairments being the most common [10] - Grade 3 or higher neutropenia was observed, but rates of febrile neutropenia and sepsis were similar across both treatment arms [10] Future Plans - Based on the positive clinical results and manageable safety profile, the company plans to engage with the FDA and EMA in the second half of 2025 to discuss a path towards product registration [3][5] - Actuate will host a Key Opinion Leader (KOL) event to discuss the trial results, featuring prominent experts in the field [8]

Core Insights - Actuate Therapeutics, Inc. announced the acceptance of an abstract for an oral presentation at the 2025 ASCO Annual Meeting, focusing on the Phase 2 trial data of elraglusib in combination with GnP for treating metastatic pancreatic ductal adenocarcinoma (mPDAC) [1][2] Group 1: Clinical Trial Results - The topline data from the Actuate-1801 Part 3B trial show clinically meaningful improvements in primary efficacy measures when elraglusib is combined with GnP compared to GnP alone [2] - Preliminary results indicate statistically significant increases in the 1-year survival rate and median overall survival for patients treated with the elraglusib/GnP combination versus those receiving GnP alone [3] - The combination treatment also led to higher Objective Response Rates (ORR) and Disease Control Rates (DCR) compared to the control arm [3] Group 2: Company Statements and Future Outlook - The CEO of Actuate highlighted the significance of achieving statistical significance in increased survival rates in a Phase 2 trial, emphasizing elraglusib's potential as a promising therapy for mPDAC [4] - The company views elraglusib as a highly valuable late-stage asset with substantial regulatory and commercial potential [4] - Actuate plans to host a KOL event on May 31, 2025, to discuss the data presented at ASCO, featuring discussions with key opinion leaders [6][8] Group 3: Study Design and Methodology - The Actuate-1801 Part 3B study is a randomized, controlled Phase 2 trial involving 286 mPDAC patients, comparing elraglusib with GnP to GnP alone [9] - Elraglusib is administered at a dose of 9.3 mg/kg via IV infusion on Day 1 of each week in a 28-day cycle, with median overall survival as the primary endpoint [9] - Secondary endpoints include DCR, ORR, progression-free survival (PFS), and adverse events (AE) [9] Group 4: Mechanism of Action - Elraglusib, a GSK-3β inhibitor, may enhance chemotherapy efficacy, activate anti-tumor immunity, and regulate gene expression, potentially leading to improved survival outcomes [10][11]

Core Insights - Actuate Therapeutics, Inc. is hosting a key opinion leader event at the 2025 ASCO annual meeting to discuss topline clinical data from the randomized Phase 2 study of elraglusib [1][3][7] - The event will feature a discussion moderated by the CEO of Actuate and include four distinguished KOLs from leading medical institutions [2][3] - The focus will be on the clinical relevance and potential impact of the study's findings on treatment paradigms for metastatic pancreatic ductal adenocarcinoma (mPDAC) [3][7] Event Details - The event is scheduled for May 31, 2025, at 6:30 PM CDT, and will be available both in-person and via live webcast [4][7] - Registration details and a replay of the event will be accessible on the Actuate website [4] Featured Speakers - The event will include notable speakers such as Dr. Tanios Bekaii-Saab, Dr. Devalingam Mahalingam, Dr. Rachna Shroff, and Dr. Colin Weekes, all of whom have significant expertise in gastrointestinal cancers [5][6][8][9] ASCO Presentation Details - Actuate will present preliminary results from the randomized Phase 2 study of elraglusib in combination with gemcitabine/nab-paclitaxel versus gemcitabine/nab-paclitaxel alone for previously untreated mPDAC patients [10][11] - The study enrolled 286 patients, randomized in a 2:1 ratio to receive elraglusib or the control treatment [13] - The primary endpoint is the 1-year survival rate, with secondary endpoints including disease control rate, overall response rate, progression-free survival, and adverse events [13] Mechanism of Action - Elraglusib, a GSK-3β inhibitor, may enhance chemotherapy activity, activate anti-tumor immunity, and regulate gene expression, potentially improving survival outcomes [14][15]

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 ...