Core Insights - Actuate Therapeutics, Inc. announced promising results from a Phase II study of elraglusib, showing a median overall survival of 18.6 months and 40% of patients alive at 2 years [1][5][6] 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 [8] Study Details - The Phase II study evaluated elraglusib in combination with platinum chemotherapy in patients with advanced, metastatic salivary gland cancers, including adenoid cystic carcinoma [3][7] - The study enrolled 32 patients, with a median progression-free survival of 6.4 months and 27% of patients progression-free at 1 year [5][11] Key Findings - Nuclear GSK-3β expression was significantly higher in responders (50%) compared to non-responders (2%), suggesting its potential as a biomarker for treatment response [3][11] - Among non-ACC patients receiving immune priming followed by cisplatin plus elraglusib, the response rate was 18%, with all responders showing elevated nuclear GSK-3β expression [4][6] Treatment Efficacy - The median overall survival for non-ACC patients was notably higher at 27.8 months, indicating a potential benefit of elraglusib in this subgroup [5] - The combination treatment was well tolerated, with no treatment-related deaths and a low discontinuation rate due to toxicity [11]

Core Insights - Actuate Therapeutics, Inc. is advancing its investigational drug elraglusib for the treatment of metastatic pancreatic cancer, with a recent public offering raising $17.25 million to support its regulatory path and clinical initiatives [1][5] Regulatory Path and Clinical Trials - The company has amended its IND application with updated clinical data from the Actuate-1801 Part 3B trial, which demonstrated a statistically significant improvement in median overall survival for patients receiving elraglusib in combination with gemcitabine/nab-paclitaxel (GnP) compared to GnP alone [2][5] - The ongoing Phase 2 study has enrolled 286 patients, with 22 patients currently in the elraglusib plus GnP arm showing survival follow-up ranging from 20 to 42 months [3][6] - The trial met its primary endpoint, showing a 37% reduction in the risk of death and a doubling of the 12-month survival rate for the elraglusib combination arm [7] Mechanism of Action and Clinical Collaborations - Elraglusib is a GSK-3β inhibitor that may enhance chemotherapy efficacy and regulate anti-tumor immunity, potentially serving as a backbone therapy in pancreatic cancer treatment [8][10] - The company is collaborating with Incyte and UPMC Hillman Cancer Center to explore elraglusib in combination with modified FOLFIRINOX and retifanlimab for advanced pancreatic cancer [4][8] Financial Position and Future Outlook - The recent financing is expected to provide sufficient capital to support corporate initiatives through the second half of 2026, including anticipated interactions with the FDA and EMA regarding elraglusib's regulatory path [5][8] - The company is optimistic about the survival benefits observed with elraglusib and its potential to be combined with various treatment regimens, addressing the limited options available for pancreatic cancer patients [5][8]

Core Viewpoint - Actuate Therapeutics, Inc. has successfully closed a public offering, raising $17.25 million through the sale of 2,464,286 shares of common stock, with a public offering price of $7.00 per share [1]. Company Overview - Actuate Therapeutics, Inc. is a clinical-stage biopharmaceutical company focused on developing therapies for high-impact, difficult-to-treat cancers by inhibiting glycogen synthase kinase-3 beta (GSK-3β) [5]. - The company's lead investigational drug, elraglusib, targets molecular pathways that promote tumor growth and resistance to conventional cancer treatments, potentially enhancing anti-tumor immunity [5]. Financial Details - The net proceeds from the offering are approximately $15.62 million, which will be used for working capital and general corporate purposes [2]. - The offering was managed by Lucid Capital Markets, with Titan Partners Group acting as a financial advisor [2]. Regulatory Information - The common stock was offered under a shelf registration statement on Form S-3, which has been declared effective by the SEC [3]. - A final prospectus supplement related to the offering has been filed with the SEC and is available on their website [3].

Core Viewpoint - Actuate Therapeutics, Inc. has announced a public offering of 2,142,858 shares of common stock at a price of $7.00 per share, aiming to raise approximately $15.0 million for working capital and general corporate purposes [1][3]. Group 1: Offering Details - The offering includes a 30-day option for underwriters to purchase an additional 321,428 shares at the public offering price [1]. - Lucid Capital Markets is the sole book-running manager, while Titan Partners Group serves as the financial advisor for the offering [2]. Group 2: Financial Information - The gross proceeds from the offering are expected to be around $15.0 million before deducting underwriting discounts and commissions [3]. - The net proceeds will be utilized for working capital and general corporate purposes [3]. Group 3: Company Overview - Actuate Therapeutics is a clinical-stage biopharmaceutical company focused on therapies for high-impact, difficult-to-treat cancers, specifically through the inhibition of glycogen synthase kinase-3 beta (GSK-3β) [6]. - The lead investigational drug, elraglusib, targets molecular pathways that promote tumor growth and resistance to conventional cancer treatments [6].

Core Viewpoint - Actuate Therapeutics has initiated a Phase 1b clinical trial to evaluate the combination of elraglusib, retifanlimab, and modified FOLFIRINOX as a frontline therapy for advanced pancreatic adenocarcinoma, aiming to address unmet medical needs in this challenging cancer type [1][4]. Group 1: Clinical Trial Details - The Phase 1b trial, named RiLEY (NCT06896188), will enroll up to 12 patients initially, with plans for expansion based on interim efficacy results [2]. - The primary objective is to determine the recommended phase 2 dose (RP2D) for the combination regimen, while secondary objectives include evaluating overall response rate (ORR), disease control rate (DCR), median progression-free survival (mPFS), overall survival (OS), and safety [2]. Group 2: Mechanism and Previous Results - The combination therapy is expected to provide a synergistic immune-modulatory approach, enhancing anti-tumor responses by targeting multiple immune checkpoints [3]. - Previous studies indicated that elraglusib combined with gemcitabine/nab-paclitaxel resulted in 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 patients with metastatic pancreatic adenocarcinoma [3]. Group 3: Company Strategy and Future Plans - The collaboration with UPMC Hillman Cancer Center and Incyte aims to explore new synergistic opportunities for patients who have not yet received systemic therapy, enhancing both efficacy and durability of response [4]. - Actuate is also conducting a separate Phase 2 trial (NCT05077800) studying elraglusib in combination with FOLFIRINOX and losartan, with initial data showing promising results in patients with extensive liver metastases [4].

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]