Elraglusib

Preclinical Study Highlight the Potential of Elraglusib in Overcoming FOLFIRINOX-induced Chemoresistance Through Downregulation of Epithelial to Mesenchymal Transition (EMT)Initial Data Demonstrates Early Evidence of Increased Clinical Activity of Combining FOLFIRINOX with Elraglusib and Losartan in Patients with Untreated Metastatic Pancreatic Ductal Adenocarcinoma (PDAC)Deep, Durable Responses Observed in 3/6 patients with Extensive Liver Metastases CHICAGO and FORT WORTH, Texas, Sept. 16, 2024 (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), announced data from the safety cohort of an ongoing Phase 2 trial of FOLFIRINOX in combination with elraglusib and losartan for untreated metastatic pancreatic adenocarcinoma at the American Association for Cancer Research (AACR) Special Conference on Advances in Pancreatic Cancer Research taking place on September 15-18, 2024, in Boston, Massachusetts. “We are encouraged by the data presentation at this year’s AACR’s Special Conference underscoring elraglusib’s potential in addressing critical challenges in pancreatic cancer treatment,” said Daniel Schmitt, President & Chief Executive Officer of Actuate. “These initial findings provide early clinical evidence that elraglusib may overcome a key chemoresistance mechanism associated with FOLFIRINOX thus enhancing the effectiveness of the combination therapy.” The Phase 2 trial (NCT05077800) is an open-label, multi-arm, non-comparator study of FOLFIRINOX in combination with elraglusib and losartan for the treatment of adult patients with untreated metastatic pancreatic adenocarcinoma. The primary objectives of the trial are to determine the safety, tolerability, and progression-free survival of the combination therapy. The trial will enroll up to 70 treatment-naïve metastatic pancreatic adenocarcinoma patients. Actuate Therapeutics supports this trial by supplying the study drug, elraglusib. The Lustgarten Foundation is providing funding support for this study through a research grant. “We are excited by the promising safety profile and initial evidence of clinical activity demonstrated by the combination of FOLFIRINOX, elraglusib and losartan in this study,” said Colin Weekes, MD, Ph.D., Director of Medical Oncology Research for Pancreatic Cancer, Massachusetts General Hospital, and the study’s Principal Investigator. “The synergy observed with these drugs suggests that this combination could offer a novel and effective therapeutic strategy for patients with metastatic pancreatic cancer.” Poster presentation details Abstract: C073 Title: “FOLFIRINOX with Glycogen Synthase Kinase-3 Beta (GSK-3β) Inhibitor Elraglusib and Transforming Growth Factor- β (TGFβ) Inhibitor Losartan in Untreated Metastatic Pancreatic Ductal Adenocarcinoma (PDAC): Interim analysis of safety cohort.”Presenting Author: Priyadarshini Pathak, MD, Medical Oncologist, Massachusetts General Hospital Session date: Tuesday, September 17, 6:45-9 p.m. ETLocation: Westin Copley Place The abstract is available online and the poster will be available on Actuate’s website after the AACR Meeting. 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 product, 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 including several DDR pathways. Elraglusib is designed to act as a mediator of anti-tumor immunity through the inhibition of NF-kB and regulates multiple immune checkpoints and immune cell function. For additional information, please visit the Company’s website at http://www.actuatetherapeutics.com. About Massachusetts General HospitalMassachusetts General Hospital, founded in 1811, is the original and largest teaching hospital of Harvard Medical School. The Mass General Research Institute conducts the largest hospital-based research program in the nation, with annual research operations of more than $1 billion and comprises more than 9,500 researchers working across more than 30 institutes, centers and departments. MGH is a founding member of the Mass General Brigham healthcare system. Forward-Looking Statements This press release contains forward-looking statements about us, including our 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 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 favorable results in clinical trials or preclinical studies 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; 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; and our ability to fund development activities. . In addition, any forward-looking statements are qualified in their entirety by reference to the factors discussed under the heading “Risk Factors” in our final prospectus filed with the SEC on August 13, 2024 pursuant to Rule 424(b)(4) under the Securities Act with respect to our Registration Statement on Form S-1 (File No. 333-279734) 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 mmoyer@lifesciadvisors.com

Elraglusib is a Class-Leading GSK-3β Inhibitor with a Novel, Multimodal Mechanism of Action in Multiple Refractory Cancer TrialsOrphan Drug Designation in Soft Tissue Sarcomas Expands Company’s Potential to Address Cancers with High Unmet Medical Need CHICAGO and FORT WORTH, Texas, Sept. 11, 2024 (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), announced that the U.S. Food and Drug Administration (FDA) has granted Orphan Drug Designation (ODD) for elraglusib, a novel GSK-3β inhibitor for treatment of soft tissue sarcoma (STS). “We are pleased to receive the ODD from the FDA, which underscores elraglusib’s potential to address the significant yet unmet medical needs for patients with advanced cancers,” said Daniel Schmitt, President & Chief Executive Officer of Actuate. “Elraglusib is a leading GSK-3β inhibitor that has demonstrated a favorable safety profile and antitumor activity across several solid tumors including melanoma, Ewing sarcoma, colorectal and pancreatic cancers. We look forward to the continued development of elraglusib and working closely with regulators to deliver its promise to cancer patients.” According to the American Cancer Society, it is projected that in 2024 alone, approximately 13,590 new cases of soft tissue sarcoma will be diagnosed in the United States. Additionally, an estimated 5,200 individuals are expected to die from this disease1. “Soft tissue sarcomas are a rare but heterogeneous mix of tumors with >70 histological subtypes identified to date making sarcoma difficult to treat. Surgery remains the most effective treatment for localized cancer with median survival approaching 50%. However, patients with metastatic disease have a median overall survival of less than 6-12 months and remain a therapeutic challenge. Doxorubicin, approved almost 50 years ago, remains the recommended 1st line systemic treatment despite exhibiting minimal antitumor activity highlighting the unmet medical need for patients with metastatic STS,” said Dr. Steven D. Reich, Senior VP, Clinical Development and Acting Chief Medical Officer of Actuate. “Preclinical studies have demonstrated that elraglusib induces significant STS cell apoptosis and synergistic effects with chemotherapy providing rationale for the clinical evaluation in metastatic STS.” The FDA’s Orphan Drug Designation FDA Orphan Drug Designation is granted to investigational therapies addressing rare medical diseases or conditions that affect fewer than 200,000 people in the United States. Orphan drug status provides benefits to drug developers, including assistance in the drug development process, tax credits for clinical costs, exemptions from certain FDA fees, and seven years of post-approval marketing exclusivity. 1 American Cancer Society. Cancer Facts & Figures 2024. Atlanta: American Cancer Society; 2024. 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 product, 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 including several DDR pathways. Elraglusib is designed to act as a mediator of anti-tumor immunity through the inhibition of NF-kB and regulates 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 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 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 favorable results in clinical trials or preclinical studies 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; 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; and our ability to fund development activities. In addition, any forward-looking statements are qualified in their entirety by reference to the factors discussed under the heading “Risk Factors” in our final prospectus filed with the SEC on August 13, 2024 pursuant to Rule 424(b)(4) under the Securities Act with respect to our Registration Statement on Form S-1 (File No. 333-279734) 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 mmoyer@lifesciadvisors.com