Temozolomide

Two Complete Metabolic Responses (CMRs) observed in patients with relapsed/refractory metastatic Ewing sarcoma and one Complete Response (CR) observed in a patient with relapsed/refractory metastatic neuroblastoma Clinical responses and disease control observed in 15 of 40 patients with difficult-to-treat refractory pediatric cancers, including 10 of 19 patients treated with elraglusib plus cyclophosphamide/topotecan Data support advancing clinical development of elraglusib in Ewing sarcoma and potentially neuroblastoma in 2026; Company has been granted Rare Pediatric Designations from the FDA for both indications CHICAGO and FORT WORTH, Texas, Jan. 06, 2026 (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 results from the phase 1 portion of its phase 1/2 clinical study evaluating elraglusib as a monotherapy or in combination with irinotecan, irinotecan plus temozolomide, or with cyclophosphamide plus topotecan in pediatric patients with refractory malignancies (Actuate-1902; NCT 04239092 ). The Actuate-1902 trial was an open-label, multicenter phase 1/2 study evaluating the safety and efficacy of elraglusib in 40 pediatric patients ages 3 – 21 with relapsed (>2 remissions)/refractory cancers, including Ewing sarcoma (EWS), neuroblastoma, Central Nervous System (CNS) tumors, non-EWS sarcomas, and other refractory pediatric malignancies. Importantly, data from the Phase 1 trial showed clinical responses in relapsed/refractory EWS, which is viewed as positive evidence of clinical activity in this difficult-to-treat indication. Following initial responses observed in the Actuate-1902 clinical study, the Company plans to advance clinical development of elraglusib in children, adolescents, and adults with relapsed/refractory EWS, while assessing collaborative development programs in neuroblastoma and other pediatric indications with leading pediatric consortia and Key Opinion Leaders to align future studies with patient needs and regulatory expectations. “Elraglusib continues to exhibit the potential to extend and improve the lives of patients in disease settings where specific treatment options are extremely limited,” said Daniel Schmitt, President & Chief Executive Officer of Actuate. “In the 1902 trial, we observed early signals of significant efficacy in EWS, neuroblastoma and Desmoplastic Small Round Cell Tumor (DSRCT), showing that elraglusib’s unique mechanism of action can play an important role in multiple difficult-to-treat cancers. We plan to initiate additional clinical trials in 2026 that expedite a registration pathway for the program in patients with Ewing sarcoma and potentially advancing elraglusib in neuroblastoma”. Actuate-1902 Key Study Highlights Elraglusib in combination with Cyclophosphamide and Topotecan Regimen: Clinical responses and disease control observed in 10 of 19 patients with relapsed/refractory Ewing sarcoma and neuroblastoma. One patient with six prior treatments for EWS achieved a CMR with Partial Response (PR) (60% reduction in tumor size) of a lung target lesion. The patient completed 30 weeks (Cycle 10) on treatment. Long term treatment with elraglusib monotherapy is continuing without disease progression outside of the study. One patient with four prior treatments for EWS (+EWSR1 translocation) was identified as a CR (BOR) at week 9 (Cycle 3) with CT showing a 100% decrease in piriformis muscle tumor compared to baseline (CMR by PET). One patient with six prior treatments for unfavorable neuroblastoma histology (Indeterminate MYCN, ALK, and ploidy) had a first response at week 9 (Cycle 3) of stable disease (SD), with a best overall response (BOR) of complete bone marrow response identified at week 27 (Cycle 9). One patient with 10 prior treatments for DSRCT achieved a PR (52.6% decrease in liver/lung target lesions compared to baseline). Non-target lesions included multiple lung and liver lesions, which were not present at the end of treatment. Six patients (osteosarcoma, anaplastic ependymoma, glioblastoma multiforme, and four EWS) with prior treatments ranging from 2 to 11, achieved BORs of stable disease. Elraglusib in combination with Irinotecan Regimen: Four patients (neuroblastoma, ganglioneuroblastoma (a high-risk variant with an unfavorable prognosis)) achieved BOR of stable disease. One patient with neuroblastoma achieved a 35% reduction in tumor burden between baseline and week 9 (Cycle 3). One patient with ependymoma experienced stable disease with a prolonged time to progression of 54 weeks. About Actuate-1902 Actuate-1902 was an open-label, multicenter phase 1/2 study evaluating the safety and efficacy of elraglusib in forty (40) pediatric patients ages 3 to 21 with relapsed (>2 remissions)/refractory cancers, including EWS, neuroblastoma, CNS tumors, non-EWS sarcomas, and other refractory pediatric malignancies. The phase 1 dose escalation portion of the trial was designed primarily to determine the maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D) of elraglusib as a single agent and in combination with chemotherapy. While an MTD was not reached, initial evidence of anti-tumor activity was observed, particularly when elraglusib is administered with a standard cyclophosphamide and topotecan regimen. The phase 1 portion of this study was closed in July 2025. About Ewing Sarcoma Ewing sarcoma (EWS) is a small round blue cell tumor defined by a recurring cytogenetic fusion event involving the Ewing sarcoma breakpoint region 1 gene (EWSR1) and the Erythroblast Transformation Specific (ETS) transcription family. EWS is derived from primordial bone marrow–derived mesenchymal stem cells, which originate in bone and soft tissue and constitute the second most common bone tumor in children and adolescents, most commonly occurring in white adolescents with a median age of 15 years. For patients with metastatic disease up-front, 5-year survival remains low at 13-30%. The risk of relapse is notable, regardless of upfront disease status, at 30-40% with local disease and 60-80% with primary metastatic disease. Post-relapse, survival is approximately 20% and although new therapeutic approaches have been attempted, there has been no improvement in the prognosis of relapsed EWS. The development of novel therapeutics and clinical trials is essential to advance the prognosis of relapsed/refractory EWS. About Neuroblastoma Neuroblastoma is a type of cancer that originates in nerve tissue of the adrenal gland, neck, chest, or spinal cord. This type of cancer often begins in early childhood, usually in children younger than 5 years of age. Sometimes, neuroblastoma forms before birth and is found during a fetal ultrasound. Usually, however, neuroblastoma is diagnosed after it has metastasized. This form of cancer spreads most often to the lymph nodes, bones, bone marrow, liver, and in infants, skin. Approximately 650 children in the United States are diagnosed with neuroblastoma each year, according to estimates from the National Cancer Institute. 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 . Forward-Looking Statements This press release contains forward-looking statements about us, including our and other parties’ 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 preliminary and unpublished data may be subject to change and further interpretation following the availability of more data or following a more comprehensive review of the data and should not be relied upon as a final analysis; clinical and preclinical drug development involves a lengthy and expensive process with uncertain timelines and outcomes; results of prior preclinical studies, early clinical trials and sub-group studies are not necessarily predictive of future results and may not correlate with improved responses, and elraglusib may not achieve positive clinical results or favorable preclinical results 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, including through conversations with the FDA or EMA and the standards such bodies may impose for such 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; our ability to fund development activities, including because our financial condition raises substantial doubt as to our ability to continue as a going concern and we require additional capital to finance our continued operations, and a failure to obtain this necessary capital in the near term on acceptable terms, or at all, could force us to delay, limit, reduce or terminate our development programs, commercialization efforts or other operations. In addition, any forward-looking statements are qualified in their entirety by reference to the factors discussed under the heading “Item 1A. Risk Factors” in our Annual Report on Form 10-K for the year ended December 31, 2024, filed with the SEC on March 13, 2025, and our subsequently filed Quarterly Reports on Form 10-Q, 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 Media Contact Ignacio Guerrero-Ros, Ph.D., or David Schull Russo Partners, LLC Ignacio.guerrero-ros@russopartnersllc.com David.schull@russopartnersllc.com (858) 717-2310 or (646) 942-5604

SAN DIEGO, Dec. 16, 2025 /PRNewswire/ -- Inhibrx Biosciences, Inc. (Nasdaq: INBX) ("Inhibrx" or the "Company"), a clinical-stage biopharmaceutical company focused on developing therapeutics for oncology today announced an update on the INBRX-106 Phase 2/3 clinical trial in combination with Keytruda® (pembrolizumab) as a first-line treatment for patients with locally advanced unresectable or metastatic head and neck squamous cell carcinoma (HNSCC) and the Phase 1/2 trial evaluating patients with checkpoint inhibitor refractory or relapsed non-small cell lung cancer (NSCLC) in combination with Keytruda. The Company also provided a brief progress update on the expansion cohorts investigating ozekibart in combination with FOLFIRI in late-line colorectal cancer and in combination with irinotecan and temozolomide in refractory Ewing sarcoma. INBRX-106 Inhibrx has recruited 46 of the 60 patients in the randomized Phase 2 portion of the Phase 2/3 clinical trial evaluating INBRX-106 in combination with Keytruda versus Keytruda as a first-line treatment for patients with unresectable or metastatic HNSCC. Inhibrx expects to complete enrollment in the Phase 2 portion of the trial during the first quarter of 2026. This trial is recruiting patients who have not received prior systemic therapy for unresectable or metastatic HNSCC and have tumor PD-L1 CPS expression equal to or greater than 20. Patients are randomized one to one to either INBRX-106 in combination with Keytruda or Keytruda. The primary endpoint of the Phase 2 portion of this trial is overall response rate, supported by secondary endpoints of duration of response, progression free survival and safety. In November 2025, Inhibrx completed enrollment of the Phase 1/2 trial evaluating 34 patients in checkpoint inhibitor refractory or relapsed NSCLC in combination with Keytruda. Primary endpoints for this cohort are objective response rate, disease control rate, duration of response and safety. The current datasets for both HNSCC and NSCLC lack sufficient maturity to support an interpretation and conclusion on the viability of this program. Inhibrx expects that in the second half of 2026, the data should be mature enough to inform whether INBRX-106, in combination with Keytruda, demonstrates superior efficacy and sustained clinical benefit relative to the current standard of care. KEYTRUDA® is a registered trademark of Merck Sharp & Dohme Corp. Ozekibart (INBRX-109) In late October 2025, Inhibrx completed enrollment of 44 patients in the expansion cohort of the Phase 1/2 trial evaluating ozekibart in combination with FOLFIRI in heavily pretreated (third and fourth line) advanced or metastatic, unresectable colorectal cancer. As previously reported, ozekibart in combination with FOLFIRI was well tolerated, with durable responses and a high rate of disease control. The progression free survival data should be mature in the second quarter of 2026, and we plan to provide an update at that time. Inhibrx expects to complete enrollment in the Phase 1/2 trial of ozekibart in combination with irinotecan and temozolomide (IRI/TMZ) for advanced or metastatic, unresectable, relapsed, or refractory Ewing sarcoma in the second quarter of 2026. If the current response and duration trends observed continue, Inhibrx plans to meet with the FDA in the second half of 2026 to discuss an accelerated approval pathway for this indication. About INBRX-106 INBRX-106 is a precisely engineered hexavalent sdAb-based therapeutic candidate targeting OX40, designed to be an optimized agonist of this co-stimulatory receptor. It is currently being investigated in combination with Keytruda in patients with locally advanced or metastatic solid tumors, specifically HNSCC and NSCLC. About ozekibart (INBRX-109) Ozekibart is a precision-engineered, tetravalent death receptor 5 (DR5) agonist antibody designed to exploit the tumor-biased cell death induced by DR5 activation. Inhibrx read out a successful single agent registration study in chondrosarcoma and a BLA filing is expected in early Q2 of 2026. Additionally, Inhibrx is evaluating ozekibart in patients diagnosed with colorectal cancer and Ewing sarcoma. About Inhibrx Biosciences, Inc. Inhibrx Biosciences is a clinical-stage biopharmaceutical company focused on developing a broad pipeline of novel biologic therapeutic candidates. Inhibrx Biosciences utilizes diverse methods of protein engineering to address the specific requirements of complex target and disease biology, including its proprietary protein engineering platforms. Inhibrx Biosciences was incorporated in January 2024 as a direct, wholly-owned subsidiary of Inhibrx, Inc. Prior to the sale of Inhibrx, Inc. and the INBRX-101 program to Sanofi S.A., Inhibrx Biosciences acquired certain corporate infrastructure and other assets and liabilities through a series of internal restructuring transactions effected by Inhibrx, Inc. Inhibrx, Inc. also completed a distribution to holders of its shares of common stock of 92% of the issued and outstanding shares of Inhibrx Biosciences. Following such transactions, Inhibrx Biosciences' current clinical pipeline of therapeutic candidates includes ozekibart and INBRX-106, both of which utilize multivalent formats where the precise valency can be optimized in a target-centric way to mediate what we believe to be the most appropriate agonist function. For more information, please visit . Forward-Looking Statements Inhibrx cautions you that statements contained in this press release regarding matters that are not historical facts are forward-looking statements. These statements are based on Inhibrx's current beliefs and expectations. These forward-looking statements include, but are not limited to, statements regarding: Inhibrx's judgments and beliefs regarding the strength of Inhibrx's pipeline; statements regarding the safety and efficacy of its therapeutic candidatesbased on topline and interim results; the potential for its therapeutic candidates to be used for certain indications; the clinical development of its therapeutic candidates, including expected enrollment, data readouts, regulatory submissions and interactions, and the timing thereof; and any presumption that topline, interim or preliminary data will be representative of final data or data in later clinical trials. Actual results may differ from those set forth in this press release due to the risks and uncertainties inherent in Inhibrx's business, including, without limitation, risks and uncertainties regarding: topline data may not accurately reflect the complete results of a particular study or trial and remain subject to audit, and final data may differ materially from topline data; the initiation, timing, progress and results of its preclinical studies and clinical trials, and its research and development programs; its ability to advance therapeutic candidates into, and successfully complete, clinical trials; its interpretation of topline, interim or preliminary data from its clinical trials, including interpretations regarding disease control and disease response; results from preclinical studies or early clinical trials not necessarily being predictive of future results; unexpected adverse side effects or inadequate efficacy of its therapeutic candidates that may limit their development, regulatory approval and/or commercialization; the potential for its programs and prospects to be negatively impacted by developments relating to its competitors, including the results of studies or regulatory determinations relating to its competitors; the timing or likelihood of regulatory filings and approvals and regulatory developments in the U.S. and foreign countries; the successful commercialization of its therapeutic candidates, if approved; an accelerated development or approval pathway may not be available for its therapeutic candidates and any such pathway may not lead to a faster development process; it may not realize the benefits associated with orphan drug designation, including that orphan drug exclusivity may not effectively protect a product from competition and that such exclusivity may not be maintained; the pricing, coverage and reimbursement of its therapeutic candidates, if approved; its ability to utilize its technology platform to generate and advance additional therapeutic candidates; and other risks described from time to time in the "Risk Factors" section of its filings with the U.S. Securities and Exchange Commission, including those described in its Annual Report on Form 10-K, its Quarterly Reports on Form 10-Q, and supplemented from time to time by its Current Reports on Form 8-K as filed from time to time. You are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date hereof, and Inhibrx undertakes no obligation to update these statements to reflect events that occur or circumstances that exist after the date hereof. All forward-looking statements are qualified in their entirety by this cautionary statement, which is made under the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. Investor and Media Contact: Kelly Deck, CFO [email protected] 858-795-4260 SOURCE Inhibrx Biosciences, Inc. 21% more press release views with Request a Demo