Elraglusib Demonstrated Anti-Tumor Activity with Two Ongoing Durable Complete Responses and ~62% Disease Control Rate in First 8 Patients with Relapsed/Refractory Ewing and Ewing-related SarcomasEnrollment Ongoing with Topline Data Anticipated in 1H 2025 CHICAGO and FORT WORTH, Texas, Sept. 09, 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), provided an update on its Phase 1/2 trial of elraglusib in relapsed/refractory Ewing Sarcoma (r/r EWS). “Ewing sarcoma is a highly metastatic form of sarcoma and the second most prevalent primary malignant tumor in children and adolescents. There are currently no standardized second-line treatments for r/r EWS and the prognosis for these patients remains poor. There is an urgent need for new therapeutic strategies that combine novel targeted therapies with new mechanisms of action and existing chemotherapy regimens of established but limited efficacy,” said Daniel Schmitt, President & Chief Executive Officer of Actuate. “Elraglusib is one of the few novel targeted agents being pursued for the refractory EWS population and continues to show promise as a viable therapeutic option. Early clinical data suggest that the enhanced antitumor activity of chemotherapy observed in multiple preclinical refractory cancer models is translating well into clinical responses.” The ongoing Phase 1/2 Trial (NCT 04239092) is an open-label, multicenter study evaluating the safety and efficacy of elraglusib in pediatric patients with relapsed/refractory malignancies, including EWS and EWS-related pediatric small round cell sarcomas. To date, the study has enrolled 6 patients with relapsed/refractory EWS (>1 remission); one patient with a desmoplastic small round cell tumor (DSRCT), an ultra-rare, highly aggressive pediatric sarcoma; and one patient with a CIC rearrangement. All patients were treated with elraglusib in combination with cyclophosphamide/topotecan. Two patients with recurrent /refractory EWS are experiencing ongoing complete responses (CR), two patients achieved stable disease (SD), and two patients withdrew from the study before their tumor response could be assessed (Table 1). The patient with Desmoplastic Small-Round-Cell Tumor (DSRCT) achieved a partial response (PR) with a 52% reduction in tumor size but withdrew from the study and is now being followed for survival. Table 1. Summary of EWS and other small round cell sarcomas treated in Clinical Study 1902. PatientTumor TypeBest Overall ResponseOS (days)11EWSCR (CT and CMR by PET)Alive OS = 933 days2EWSCR (CMR by PET)Alive OS = 284 days3DSRCTPRAlive OS = 329 days4EWSSDOS = 177 days5EWSSDOS = 272 days6EWSNot Determined.Patient withdrew from the StudyAlive OS = 318 (LTFU)7EWSNot Determined.Patient withdrew from the StudyOS = 89 days8CIC-rearrangementNot Determined.Patient withdrew from the StudyN/A 1 As of most recent follow-up visits May – August 2024 “We are pleased to share our continued, promising progress with elraglusib in r/r EWS,” said Dr. Andrew Mazar, Actuate’s Scientific Co-Founder and Chief Operating Officer. “Although the sample size is small, we are encouraged by the disease stabilization and two ongoing complete responses observed, including one patient with an overall survival of over 2.5 years. These results are considered promising by clinical experts in pediatric oncology, particularly given the significant unmet medical need and lack of therapeutic alternatives in recurrent EWS, and support the continued development of elraglusib in this rare cancer patient population.” The 1902 study remains open only to patients with recurrent EWS, who will be treated with the combination of elraglusib with cyclophosphamide/topotecan. The study will enroll up to 12 total EWS patients to provide additional rationale for moving the elraglusib/cyclophosphamide/topotecan combination into a phase 2 study in patients with recurrent EWS. Actuate plans to meet with the FDA to discuss the design of a phase 2 study and options for accelerating the development path for elraglusib to commercial registration for the treatment of EWS. About Ewing Sarcoma Ewing sarcoma (EWS) is a highly metastatic form of sarcoma that ranks as the second most prevalent primary malignant tumor of childhood and adolescence originating in bone with a peak incidence at the age of 15 years. Approximately 25% of new EWS patients have metastatic disease when first diagnosed, which is the most significant predictor of poor survival. Treatment options for relapsed/refractory metastatic EWS are limited. Despite intensive therapy, recurrent EWS, whether local or with distant metastases, is almost always fatal. While the use of chemotherapy regimens in conjunction with surgery has resulted in the 5-year survival rate increasing from 59 to 78% in children and young adolescents, and from 20 to 60% in adults, to date, no standard treatment has been defined in the relapsed/refractory setting. 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-3 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. For more information on the 1902 Study, please visit ClinicalTrial.gov and reference Identifier NCT04239092. 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, and 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 phase 2 or other 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. You should assume that the information appearing in this press release is accurate as of its date only. 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 MoyerManaging DirectorLifeSci Advisors, LLCmmoyer@lifesciadvisors.com
