Actuate Therapeutics Highlights Significant and Sustained Survival Benefit in Key Metastatic Pancreatic Cancer Patient Populations in Phase 2 Elraglusib Trial

Rhea-AI Summary

Actuate Therapeutics (NASDAQ: ACTU) reported significant results from its Phase 2 trial of elraglusib combined with gemcitabine/nab-paclitaxel (GnP) for metastatic pancreatic cancer treatment. Patients receiving at least one cycle showed improved median overall survival of 12.5 months vs 8.5 months in the control group, with a 43% reduction in death risk.

The trial demonstrated enhanced outcomes with elraglusib/GnP combination, including disease control rate of 53.4% vs 44.8% and overall response rate of 37.9% vs 29.3%. Notably, patients with liver metastases experienced a 2.5-fold increase in 1-year overall survival and 38% reduced death risk compared to control, with 13.6% survival probability at 18 months versus 0% in the control group.

Positive

• Significant 4-month improvement in median overall survival (12.5 vs 8.5 months)
• 43% reduction in risk of death for patients treated with at least one cycle
• Higher disease control rate (53.4% vs 44.8%) and overall response rate (37.9% vs 29.3%)
• 2.5-fold increase in 1-year overall survival for liver metastasis patients
• 13.6% survival probability at 18 months for liver metastasis patients vs 0% in control group

Negative

• None.

- Near doubling of 1-year overall survival (OS), increased median OS of 4 months (12.5 vs 8.5 months), and 43% reduction in risk of death in patients treated with at least one cycle (4 weeks) of elraglusib plus gemcitabine/nab-paclitaxel (GnP) vs GnP alone

- Patients with liver metastases experienced a 2.5x improvement in 1-year OS with a 38% reduction in risk of death when treated with elraglusib plus GnP

CHICAGO and FORT WORTH, Texas, June 24, 2025 (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 highlighted results from a pre-specified subgroup analysis of its Phase 2 (Actuate-1801 Part 3B) trial of elraglusib in combination with gemcitabine/nab-paclitaxel (GnP) in first-line metastatic pancreatic adenocarcinoma (mPDAC).

Patients treated for at least one complete cycle (4 weeks) of therapy achieved a median overall survival (mOS) of 12.5 months in the elragusib/GnP arm, compared to 8.5 months in the control arm. The analysis showed a 43% reduction in the risk of death relative to control, highlighting the significant potential impact of early disease control by elraglusib. Improved outcomes were reported in the combination versus control arms, respectively: disease control rate (DCR): 53.4% vs 44.8%, overall response rate (ORR): 37.9% vs 29.3%, and median progression-free survival (PFS): 6.9 vs 5.6 months.

Figure 1: Actuate-1801 Part 3B: Kaplan-Meier Estimate for mOS of Patients Receiving At Least One Complete Cycle of Treatment

In patients with liver metastases, treatment with elraglusib led to a 2.5-fold increase in 1-year OS and a 38% reduction in the risk of death compared to control. While the GnP arm showed 0% OS probability at 18 months, patients on elraglusib achieved a survival probability of 13.6% OS at 18 months. Additional efficacy metrics showed improvements as follows: DCR: 36.8% vs 27.9%, ORR: 29.8% vs 19.7%, and PFS: 4.9 vs 3.9.

Additional clinical benefit was observed across other subgroups:

Figure 2: Elraglusib + GnP Data Show OS Benefit Across Key Subgroups

“We are highly encouraged by the significant clinical benefit provided by elraglusib demonstrated in this study,” said Daniel Schmitt, President & Chief Executive Officer of Actuate. “Patients who received at least one cycle – or 4 weeks – of elraglusib showed a rapid and meaningful survival benefit, including a near doubling of the 1-year overall survival and 43% reduction in the risk of death compared to control. Separately, in the subgroup of patients with liver metastases, a population with historically poor prognosis, we observed a more than 2.5-fold improvement in 1-year OS with a 38% reduction in risk of death. These results underscore the potential of elraglusib to generate rapid and durable benefit in high-risk patients, which could be highly impactful in future development and commercial pathways.”

About Metastatic Pancreatic Cancer

Metastatic pancreatic ductal adenocarcinoma (mPDAC) is an advanced stage of pancreatic cancer, the most common type of pancreatic malignancy, originating from the ductal cells of the pancreas. When metastatic, the cancer has spread beyond the pancreas to distant organs, such as the liver, lungs, or peritoneum, and is typically classified as stage IV. mPDAC accounts for approximately 90% of pancreatic cancers; one of the deadliest cancers with a 5-year survival rate of ~3-5% for metastatic cases.

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 http://www.actuatetherapeutics.com.

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 2025, 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 Report on Form 10-Q for the quarter ended March 31, 2025, filed with the SEC on May 15, 2025, 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

Photos accompanying this announcement are available at:
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https://www.globenewswire.com/NewsRoom/AttachmentNg/7c9dc33e-cd62-4cc5-b3a0-e8660eefc9a8

FAQ

What were the key results of Actuate Therapeutics (ACTU) Phase 2 elraglusib trial in pancreatic cancer?

The trial showed a 4-month improvement in median overall survival (12.5 vs 8.5 months) and 43% reduction in death risk for patients treated with elraglusib plus GnP compared to GnP alone.

How did elraglusib affect liver metastasis patients in ACTU's Phase 2 trial?

Patients with liver metastases showed a 2.5-fold increase in 1-year overall survival, 38% reduction in death risk, and 13.6% survival probability at 18 months compared to 0% in the control group.

What were the disease control and response rates for ACTU's elraglusib in the Phase 2 trial?

The elraglusib/GnP combination achieved a disease control rate of 53.4% vs 44.8% and overall response rate of 37.9% vs 29.3% compared to the control arm.

What is the mechanism of action for Actuate Therapeutics' elraglusib?

Elraglusib works through the inhibition of glycogen synthase kinase-3 beta (GSK-3β) for treating high-impact, difficult-to-treat cancers.

How long did patients need to be treated with elraglusib to show survival benefits?

Patients needed to complete at least one complete cycle (4 weeks) of therapy to demonstrate significant survival benefits.