Actuate Therapeutics Announces Plans to Expand Clinical Pipeline, Advancing Elraglusib Tablet into a Phase 1/2 Clinical Program in Refractory Cancers

-Initiation of phase 1 portion of the trial planned in 2H 2026

-Phase 2 portion of the trial will initiate development of the elraglusib tablet in specific indications, including refractory melanoma and additional target solid tumor and hematologic cancers

-Program builds on early clinical evidence of monotherapy activity observed in immune checkpoint inhibitor (CPI)-refractory metastatic melanoma in a previously completed trial

CHICAGO and FORT WORTH, Texas, Jan. 21, 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 plans to initiate a Phase 1/2 clinical program evaluating the oral tablet dosage form of elraglusib in patients with advanced cancer.

The phase 1 portion of the planned Phase 1/2 program aims to determine the maximum tolerated dose (MTD) or maximum administered dose (MAD) and dose-limiting toxicities (DLTs) of elraglusib tablets administered once daily and will investigate the pharmacokinetics (PK) of elraglusib tablets as well as the preliminary anti-tumor activity of elraglusib when administered as tablets. The goal of the phase 1 portion of the program will be to establish the recommended dose(s) of elraglusib tablets for expansion (RDE) in subsequent development

The Company then plans to advance the RDE into phase 2 in patients with refractory metastatic melanoma and other potential target indications. Phase 2 trial will build on the early encouraging clinical activity observed with elraglusib monotherapy in CPI-refractory metastatic melanoma. In a Phase 1 study of 67 patients that included 11 patients with advanced relapsed, CPI-refractory, metastatic melanoma treated with escalating doses of elraglusib, 5 of the 10 patients achieved disease control lasting 12 weeks or longer, and 5 patients demonstrated overall survival of 31 weeks or more, with a median overall survival of 9.9 months. Most notably, one patient with BRAFV600E-mutated metastatic melanoma with significant CNS involvement achieved a complete radiographic and metabolic response that remains ongoing with a duration of response currently exceeding 6 years.

"With the promising results we have seen with the IV formulation of elraglusib across an array of difficult-to-treat cancers, we are excited to advance the oral tablet formulation in additional indications, including patients with R/R metastatic melanoma," said Dan Schmitt, Chief Executive Officer of Actuate Therapeutics. "Elraglusib oral tablet will allow us to further explore elraglusib dose using a convenient and easily administered tablet dosage form that will be amenable to evaluation as a single agent. The program builds on encouraging results from our phase 1 monotherapy clinical trial with the IV formulation, including a remarkable complete response lasting more than 6 years from a patient with highly advanced, highly disseminated, refractory BRAFV600E-mutated metastatic melanoma. We believe the elraglusib oral tablet will have the potential to play an important role in addressing a significant unmet need in the treatment of refractory melanoma as well as other advanced cancer indications."



R/R metastatic melanoma is one of the most difficult-to-treat cancers. For patients who exhibit disease progression after CPI therapy or targeted agents, treatment options are limited, with historically low chemotherapy response rates of approximately 4 to 10% and a median overall survival of approximately 4 to 7 months. Elraglusib targets both GSK3α and GSK3β, an important consideration in melanoma, where both isoforms have been implicated in disease progression. Inhibition of GSK3α/β may also provide synergistic potential with BRAF and MEK inhibitors, as well as ICIs, where elraglusib could help restore sensitivity or prolong response duration.

To support the broader development of the oral tablet formulation of elraglusib, Actuate also anticipates including additional targeted histologies in the final design of the Phase 1/2 study, including select hematologic malignancies where GSK3β inhibition has demonstrated activity and the potential for clinical benefit.

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 www.actuatetherapeutics.com or follow us on LinkedIn, X, and Facebook.

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 operations beyond the second quarter of fiscal year 2026, 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 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.

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LifeSci Advisors, LLC

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