10-K: Actuate Therapeutics' Elraglusib Shows Strong mPDAC Survival

Actuate Therapeutics' lead drug candidate, elraglusib, demonstrated a statistically significant improvement in median overall survival for metastatic pancreatic cancer in a Phase 2 trial.

Summary

• Actuate Therapeutics is a clinical-stage biopharmaceutical company focused on developing GSK-3 inhibitors for difficult-to-treat cancers, with elraglusib as its sole product candidate.
• The Phase 2 Actuate-1801 Part 3B study of elraglusib plus gemcitabine/nab-paclitaxel (GnP) in first-line metastatic pancreatic ductal adenocarcinoma (mPDAC) met its primary endpoint.
• Elraglusib/GnP achieved a median overall survival (mOS) of 10.1 months compared to 7.2 months for GnP alone (p=0.02, HR=0.62), representing a 38% reduction in the risk of death.
• The trial showed a near doubling of the 12-month survival rate (from 22.3% to 44.4%) and an almost fivefold increase in the 24-month survival rate (from 2.6% to 12.9%) in the elraglusib/GnP arm.
• Treatment-emergent adverse events (TEAEs) and Serious Adverse Events (SAEs) in the elraglusib/GnP arm were similar to GnP alone, with visual disturbance (68.4%, mostly mild/moderate) and fatigue (62.6%) being the most common TEAEs attributed to elraglusib.
• Elraglusib Injection is also being evaluated in pediatric cancer patients (Actuate-1902 study), showing objective responses in Ewing sarcoma and neuroblastoma.
• An oral tablet formulation of elraglusib has been developed, with plans for a Phase 1 study in adult patients with advanced, refractory cancers, subject to future funding.
• The company reported a net loss of $22.2 million for the year ended December 31, 2025, and an accumulated deficit of $154.6 million.
• As of December 31, 2025, cash and cash equivalents were $13.2 million, with working capital of $7.9 million, and existing capital is estimated to last only until July 2026.
• Actuate Therapeutics raised $3.8 million from a Committed Equity Facility, $4.6 million from a private placement, and $15.6 million from a public offering in 2025, and has an At Market Issuance Sales Agreement for up to $100 million.
• The company has Orphan Drug Designations for pancreatic cancer, glioblastomas, neuroblastoma, and soft tissue sarcomas, and Fast Track Designation for pancreatic cancer.
• The independent registered public accounting firm included an explanatory paragraph regarding substantial doubt about the company's ability to continue as a going concern.

Sentiment

Score: 7

Explanation: StockSavvy.ai views this filing positively due to the statistically significant and clinically meaningful Phase 2 results for elraglusib in mPDAC, a high-unmet-need cancer. However, the company's precarious financial position, highlighted by the going concern warning and continuous need for capital raises, tempers the overall sentiment.

Positives

• Elraglusib in combination with GnP demonstrated a statistically significant improvement in median overall survival (mOS) of 10.1 months versus 7.2 months for GnP alone (p=0.02, HR=0.62) in first-line mPDAC.
• The 12-month survival rate nearly doubled (from 22.3% to 44.4%) and the 24-month survival rate increased almost fivefold (from 2.6% to 12.9%) in the elraglusib/GnP arm, indicating potential for long-term clinical benefit.
• The safety profile of elraglusib/GnP was similar to GnP alone, with most common adverse events being mild or moderate and transient, suggesting a favorable risk-benefit profile.
• Promising clinical responses, including Complete Metabolic Responses (CMRs) and Complete Responses (CRs), were observed in pediatric patients with relapsed/refractory Ewing sarcoma and neuroblastoma.
• The company has developed an oral tablet formulation of elraglusib, which showed greater than 95% oral bioavailability in dogs, potentially expanding treatment options and indications.
• Elraglusib has received Orphan Drug Designations (ODD) for pancreatic cancer, glioblastomas, neuroblastoma, and soft tissue sarcomas, and Fast Track Designation (FTD) for pancreatic cancer, which may accelerate development and review.
• Rare Pediatric Disease Designation (RPDD) was granted for Ewing sarcoma, potentially making the company eligible for a Priority Review Voucher upon approval.

Negatives

• The company has a limited operating history, has incurred significant operating losses since inception, and expects to continue incurring substantial losses for the foreseeable future, with an accumulated deficit of $154.6 million as of December 31, 2025.
• Existing cash and cash equivalents of $13.2 million are estimated to not satisfy operational and capital requirements beyond July 2026, raising substantial doubt about the company's ability to continue as a going concern.
• The company is entirely dependent on the success of elraglusib, its only product candidate, making it highly vulnerable to any setbacks in its development or commercialization.
• Reliance on a single drug substance (DS) manufacturer in China introduces geopolitical and supply chain risks, potentially increasing costs or delaying clinical trials and regulatory approval.
• The company relies on third-party manufacturers for drug products and raw materials without long-term supply agreements, posing risks of supply interruptions or unfavorable terms.
• The need for substantial additional capital through equity or debt financings may cause significant dilution to stockholders or impose restrictive covenants.

Risks

• Limited operating history, significant operating losses since inception, and expectation of continued losses for the foreseeable future, with no guarantee of revenue or sustained profitability.
• Requirement for substantial additional capital to finance operations; failure to obtain capital could force delays, reductions, or termination of development programs and operations.
• Raising additional capital through equity or debt may cause dilution to stockholders or restrict operations through lending/licensing arrangements.
• Complete dependence on the success of elraglusib; inability to advance, obtain regulatory approval, or commercialize elraglusib in a timely manner would materially harm the business.
• Uncertainty of clinical and preclinical drug development, with lengthy and expensive processes and results not necessarily predictive of future outcomes.
• Early stage of product development and lack of marketing efforts; no assurance that market testing will validate marketing strategy or that products will be successfully developed or marketed.
• Successful commercialization depends on governmental authorities and health insurers establishing coverage, adequate reimbursement levels, and favorable pricing policies; failure to obtain these could limit marketability and revenue generation.
• Termination of third-party licenses (e.g., UIC, NU) could adversely affect rights to important technologies.
• Reliance on a single drug substance manufacturer in China poses geopolitical and supply chain risks.
• Dependence on third-party manufacturers for drug substances, products, and raw materials without long-term supply agreements, risking delays or increased costs.
• Data provided by collaborators and other parties may be inaccurate, misleading, or incomplete.
• Inability to enforce intellectual property rights globally, especially in countries with weaker protection.
• Risk that intellectual property protection for key rights may not be obtained or preserved, allowing competitors to exploit development efforts.
• Intellectual property disputes could incur significant costs and limit intellectual property rights.
• Patent terms may be inadequate to protect the competitive position of elraglusib or future product candidates for a sufficient duration.
• Claims challenging the inventorship or ownership of patents and other intellectual property.
• Third parties initiating legal proceedings alleging infringement, misappropriation, or violation of their intellectual property rights.
• Intellectual property rights of third parties could adversely affect the ability to commercialize technologies or drug candidates, potentially requiring litigation or licenses on unfavorable terms.
• Claims that employees, consultants, or advisors have wrongfully used or disclosed alleged trade secrets of former employers or claims asserting ownership of the company's intellectual property.
• Subject to various U.S. federal, state, and foreign healthcare laws and regulations, increasing compliance costs and potential for significant fines or liability for non-compliance.
• Potential for substantial changes to fiscal, tax, and other federal policies by the U.S. Congress or any new administration to adversely affect the business.
• Information technology systems, or those of service providers, may fail or suffer security incidents, disrupting development programs or compromising sensitive information.
• Disruptions at the FDA and other government agencies due to funding shortages, personnel changes, or global health concerns could hinder timely development, approval, or commercialization.
• Effective collaboration with the FDA's Center for Drug Evaluation and Research (CDER) is a demanding process that can increase time and expense for approvals.
• Concentration of ownership by principal stockholders limits the ability of others to influence corporate actions and creates potential for conflicts of interest.
• Lack of a sustained active, liquid, and orderly market for common stock, or failure to satisfy Nasdaq listing requirements, could impair ability to resell shares.
• High volatility in the trading price of common stock, regardless of operating performance, potentially leading to substantial losses for purchasers.
• No intention to pay dividends in the foreseeable future, meaning return on investment depends solely on stock price appreciation.
• Delaware law and company bylaws could make mergers, tender offers, or proxy contests difficult, potentially depressing the stock price.
• Unstable market and economic conditions may adversely affect the ability to raise funds, potentially delaying or ceasing operations.
• Failure of securities or industry analysts to publish research or publishing unfavorable reports could cause stock price and trading volume to decline.
• Failure to maintain proper and effective internal control over financial reporting could impair ability to produce accurate and timely financial statements.

Future Outlook

Actuate Therapeutics plans to meet with the FDA and EMA in the first half of 2026 to discuss the design and execution of a Phase 3 global registration study for elraglusib in mPDAC. The company also intends to advance the development of elraglusib in pediatric cancers, including Ewing sarcoma and neuroblastoma, and plans a Phase 1 study for the Elraglusib Oral Tablet in adult patients with advanced, refractory cancers, all subject to future funding. Strategic partnerships and investigator-initiated trials are also being explored to expand elraglusib's development and leverage non-dilutive funding.

Management Comments

• Daniel Schmitt, President, Chief Executive Officer and founder, and Dr. Andrew Mazar, scientific co-founder and Chief Operating Officer, bring over 60 years of combined experience in biotechnology management and healthcare investing, leading the company's vision to build a sustainable oncology company.
• Management believes elraglusib represents a pipeline in a molecule with broad opportunity for multiple drug development programs based on its multimodal mechanisms of action and emerging data.
• Management believes the ability to extend survival by even a few months would be considered meaningful in the mPDAC patient population, given the high unmet need.
• Management believes elraglusib may improve outcomes in first-line mPDAC regardless of the chemotherapy backbone used, due to its ability to enhance chemotherapy activity even in resistant tumors.

Industry Context

StockSavvy.ai notes that Actuate Therapeutics is operating in the highly competitive and rapidly evolving oncology sector, particularly targeting pancreatic cancer, which represents a significant unmet medical need with a 5-year survival rate of less than 5% for Stage IV disease. Current first-line mPDAC treatments like FOLFIRINOX (mOS 11.1 months) and GnP (mOS 8.5 months in MPACT trial, unweighted mOS 6.9 months in a review) offer modest survival benefits. Elraglusib's Phase 2 results showing an mOS of 10.1 months in combination with GnP, along with a near doubling of 1-year survival and a fivefold increase in 2-year survival, position it as a potentially significant advancement in this challenging disease, approaching the efficacy of FOLFIRINOX while potentially offering a favorable safety profile. The development of an oral formulation and pursuit of pediatric indications (Ewing sarcoma, neuroblastoma) further diversifies its potential market, addressing other rare, high-unmet-need cancers. The company's strategy to combine elraglusib with existing standard-of-care chemotherapies is a common approach to enhance efficacy and accelerate market entry, as seen with other agents in development.

Comparison to Industry Standards

• Elraglusib/GnP achieved a median overall survival (mOS) of 10.1 months in first-line mPDAC, which is a statistically significant improvement over GnP alone (7.2 months). This compares favorably to the 8.5 months mOS for GnP in the MPACT Phase 3 trial and an unweighted mOS of 6.9 months in a recent review of real-world clinical trials for GnP.
• The 10.1 months mOS for elraglusib/GnP approaches the 11.1 months mOS achieved by FOLFIRINOX, which is considered a standard of care for advanced or mPDAC.
• The near doubling of the 12-month survival rate (22.3% to 44.4%) and almost fivefold increase in 24-month survival rate (2.6% to 12.9%) with elraglusib/GnP are notable improvements compared to historical data for GnP alone, suggesting a more durable benefit.
• In comparison to other agents in development for first-line mPDAC: Onivyde (Ipsen Pharma) as part of NALIRIFOX showed an mOS of 11.1 months vs. GnP's 9.2 months, an improvement of 1.9 months. Elraglusib's 2.9-month improvement over GnP alone is competitive.
• Other competitors like Revolution Medicines' daraxonrasib (panRAS inhibitor) and Arcus Biosciences' quemliclustat (CD73 inhibitor) are in Phase 3 trials for previously untreated mPDAC, but specific comparative efficacy data are not yet available.
• The company's strategy to combine elraglusib with existing chemotherapy backbones (GnP, FOLFIRINOX, NALIRIFOX) is a common industry approach to enhance efficacy and expand market reach, similar to how other targeted agents are being explored in combination with standard chemotherapies.

Management Changes

Corporate Governance

Legal Proceedings

• The company is not aware of any ongoing or pending material legal proceedings as of the date of this report.

Related Party Transactions

• Bios Clinical Opportunity Fund, LP, an affiliate of Bios Partners (co-founded by Chairman Aaron G.L. Fletcher), is a majority shareholder and was issued convertible promissory notes totaling $5,500,000 in February, March, and May 2024, which converted into 884,427 shares of common stock upon the IPO.
• Bios Clinical Opportunity Fund, LP was issued a promissory note of $200,000 in August 2024, which was paid in full on August 14, 2024.
• Bios 2024 Co-Invest, LP, another affiliate of Bios Partners, participated in the June 2025 Private Placement, providing $499,996 in exchange for 71,428 shares of common stock and warrants.
• Certain affiliates of the Bios Equity Affiliated Funds beneficially owned greater than 10% of Lantern Pharma Inc.'s common stock as of December 31, 2025, with whom Actuate has a collaboration agreement.

Stakeholder Impact

• **Shareholders:** Potential for significant value appreciation if elraglusib achieves regulatory approval and commercial success, especially given strong Phase 2 mPDAC data. However, face substantial dilution risk from ongoing capital raises and the 'going concern' warning indicates high financial risk.
• **Employees:** Continued employment and potential for equity-based compensation, but job security is tied to the company's ability to secure future funding and achieve product commercialization.
• **Customers (future patients/healthcare providers):** Potential for a new, effective treatment option for mPDAC and pediatric cancers, addressing high unmet medical needs. The favorable safety profile and oral formulation development could improve patient convenience and outcomes.
• **Suppliers/Creditors:** Risk due to the company's 'going concern' status and reliance on short-term purchase orders for manufacturing. The company's ability to meet future obligations depends on successful capital raises and product development.

Next Steps

• Meet with the U.S. Food and Drug Administration (FDA) and European Medicines Agency (EMA) in the first half of 2026 to discuss the design and execution of a Phase 3 global registration study of elraglusib for mPDAC.
• Advance the development of elraglusib in pediatric cancers, including Ewing sarcoma and neuroblastoma, pending additional internal or external funding support.
• Plan a Phase 1 study to identify the maximum tolerated dose and recommended Phase 2 dose (RP2D) for Elraglusib Oral Tablet in adult patients with advanced, refractory cancers, subject to future funding.
• Identify several Phase 2 studies for further clinical development of Elraglusib Oral Tablet, including for refractory, metastatic melanoma, refractory, metastatic colorectal cancer, and non-small cell lung cancer, subject to additional funding.
• Continue to explore strategically identified investigator-initiated trials (IITs) to identify additional indications and standard of care products to combine with elraglusib.
• Leverage academic and research partnerships, including the collaboration with Lantern Pharma Inc. to utilize their artificial intelligence platform.
• Evaluate potential strategic partnering opportunities with pharmaceutical companies to accelerate development and expand the pipeline.
• Consider potentially out-licensing certain geographic rights to elraglusib or other product candidates.
• Continue to seek additional financing through equity offerings, debt financings, or other capital sources to fund operations beyond July 2026.

Key Dates

Recommendation

Actuate Therapeutics' Phase 2 results for elraglusib in metastatic pancreatic cancer are highly encouraging, demonstrating statistically significant improvements in overall survival in a disease with very limited treatment options. This strong clinical data is a significant positive and could drive future value. However, the company's financial position is precarious, with a 'going concern' warning and a stated need for substantial additional capital beyond July 2026. While the clinical upside is considerable, the financial risk is equally high. A seasoned investor would likely 'hold' to monitor the company's progress in securing necessary funding and advancing to Phase 3, as well as the outcome of regulatory discussions, before committing further capital. The potential for dilution from future capital raises also warrants caution.

Keywords

Elraglusib, GSK-3 inhibitor, Pancreatic cancer, mPDAC, Ewing sarcoma, Neuroblastoma, Oncology, Clinical stage biopharmaceutical, Phase 2 clinical trial, Overall survival, Orphan Drug Designation, Fast Track Designation, Rare Pediatric Disease Designation, Cancer therapy, Biotechnology, SEC filing, 10-K