10-Q: Actuate Therapeutics Reports Q3 2025, Elraglusib Trial Success

Actuate Therapeutics reported its Q3 2025 results, showcasing positive topline data from its Phase 2 mPDAC trial for elraglusib and detailing recent capital raises to fund ongoing operations.

Summary

• Net loss for the three months ended September 30, 2025, was $(5,407,470), an improvement from $(5,970,961) for the same period in 2024.
• Net loss for the nine months ended September 30, 2025, was $(17,673,899), an improvement from $(20,839,239) for the same period in 2024.
• Cash and cash equivalents totaled $16,924,763 as of September 30, 2025, up from $8,641,622 at December 31, 2024.
• Working capital as of September 30, 2025, was $11,071,338.
• The Phase 2 mPDAC trial (Actuate-1801) for elraglusib met its primary endpoint, demonstrating statistically significant increases in 1-year survival rate (44.1% vs 22.3%, p=0.0005) and median overall survival (10.1 months vs 7.2 months, HR=0.63, log-rank p=0.01) with a 37% reduction in the risk of death versus treatment with GnP alone.
• Topline data also showed numerically improved overall response rates (29.0% vs 21.8%), median progression-free survival (5.6 months vs 5.1 months), and disease control rate (61.3% vs 56.4%) in the elraglusib/GnP combination arm.
• Treatment-emergent adverse events (TEAEs) and Serious Adverse Events (SAEs) in the elraglusib/GnP arm were similar to the GnP arm, indicating a favorable risk-benefit profile.
• The FDA notified the company that for Breakthrough Therapy Designation (BTD) in mPDAC, a new therapy must demonstrate substantial improvement over all existing standard of care therapies, including irinotecan-containing regimens.
• A Phase 1/2 clinical trial (Actuate-1902) in refractory pediatric malignancies was completed in July 2025, identifying Ewing sarcoma (EWS) as a potential second indication for further development.
• The company selected an oral dosage form (Elraglusib Oral Tablet) for further development and plans a Phase 1 study (Actuate-2401) to identify the maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D) in advanced, refractory adult cancers, subject to future funding.
• Recent capital raises include $15,573,966 net from a September 2025 Public Offering, $4,592,462 net from a June 2025 Private Placement, and $3,800,465 net from a Committed Equity Facility with B. Riley during the nine months ended September 30, 2025.
• Management concluded there is substantial doubt regarding the company's ability to continue as a going concern beyond the second quarter of fiscal year 2026 without raising additional capital.

Sentiment

Score: 7

Explanation: The positive topline results from the Phase 2 mPDAC trial for elraglusib are a significant positive development, demonstrating improved overall survival and a favorable safety profile. This clinical success is crucial for a biopharmaceutical company. The company also successfully raised substantial capital, improving its liquidity position. However, the persistent 'going concern' doubt, the high bar set by the FDA for BTD, and the increasing general and administrative expenses remain notable concerns. The future development of other indications and oral formulations is contingent on further funding.

Positives

• The Phase 2 mPDAC trial (Actuate-1801) for elraglusib met its primary endpoint, demonstrating statistically significant improvement in median overall survival (10.1 months vs 7.2 months) and 1-year survival rate (44.1% vs 22.3%) for elraglusib/GnP compared to GnP alone.
• The elraglusib/GnP combination showed a 37% reduction in the risk of death.
• A favorable risk-benefit profile for elraglusib/GnP was observed, with TEAEs and SAEs similar to the control arm.
• The company successfully raised significant capital, including $15,573,966 net from a public offering, $4,592,462 net from a private placement, and $3,800,465 net from a committed equity facility, substantially increasing cash reserves to $16,924,763.
• Ewing sarcoma was identified as a potential second indication for elraglusib following the completion of a Phase 1/2 pediatric trial.
• Development of an oral dosage form (Elraglusib Oral Tablet) is underway, which could expand target indications and improve patient convenience.

Negatives

• The company has a limited operating history, has not generated any revenue from product sales since inception, and has an accumulated deficit of $150,053,748 as of September 30, 2025.
• Management concluded there is substantial doubt regarding the company's ability to continue as a going concern beyond the second quarter of fiscal year 2026 without raising additional capital.
• The FDA requires a 'substantial improvement over all existing standard of care therapies, including irinotecan-containing regimens' for Breakthrough Therapy Designation (BTD) for mPDAC, setting a high bar for elraglusib.
• Future clinical trials and development plans, such as the Phase 2 EWS study and Phase 1 oral tablet study, are explicitly stated as 'subject to available funding'.
• Research and development expenses decreased by $1,579,180 for Q3 2025 and $6,827,291 for the nine months ended September 30, 2025, primarily due to lower patient fees and CRO costs associated with fewer patients on study and timing of drug product manufacturing, which may indicate a slowdown in trial activity.
• General and administrative expenses increased significantly by $1,658,655 for Q3 2025 and $6,032,524 for the nine months ended September 30, 2025, largely due to increased personnel-related expenses (including stock-based compensation) and public company costs.

Risks

• The company has a limited operating history, has incurred significant operating losses, and expects to incur significant operating losses for the foreseeable future, with a high risk of never generating revenue or becoming profitable.
• The company's financial condition raises substantial doubt as to its ability to continue as a going concern.
• Substantial additional capital is required in the near term to finance operations; failure to obtain this capital could force delays, reductions, or termination of development programs or commercialization efforts.
• Raising additional capital may cause dilution to stockholders, restrict operations, or require relinquishing rights to technologies or product candidates.
• The actual number of shares sold to B. Riley under the Committed Equity Facility or the actual gross proceeds from those sales are unpredictable.
• The company does not have, and may never have, any approved products on the market, and its business is highly dependent upon receiving approvals from various governmental agencies.
• The company depends entirely on the success of elraglusib; failure to advance, obtain regulatory approval, or commercialize elraglusib in a timely manner will materially harm the business.
• There is no guarantee that the U.S. Food and Drug Administration (FDA) will accept a New Drug Application (NDA) even if all planned clinical trials, including a Phase 3 trial, are completed.
• Clinical and preclinical drug development is a lengthy and expensive process with uncertain timelines and outcomes, and results of prior studies are not necessarily predictive of future results.
• Elraglusib or any future product candidates may not achieve favorable results or receive regulatory approval on a timely basis, if at all.
• The company may not be successful in advancing elraglusib in additional indications and may expend limited resources on less profitable alternatives.
• Use of elraglusib or any future product candidates could be associated with side effects, adverse events, or other safety risks, which could delay or preclude regulatory approval or harm the business.
• Delays or difficulties in the enrollment of subjects to clinical trials could delay or adversely affect regulatory approvals.
• Interim, topline, and preliminary data from clinical trials may change as more patient data become available and are subject to audit and verification.
• Termination of third-party licenses could adversely affect rights to important technologies.
• Reliance on a China-based drug substance (DS) manufacturer poses risks related to geopolitical relationships, increased costs, and potential delays in clinical trials and regulatory approval.
• Unfavorable tariffs could increase the cost of elraglusib DS.
• Reliance on third parties to conduct non-clinical studies and clinical trials means failure by these parties could prevent regulatory approval or commercialization.
• Data provided by collaborators and other parties have not been independently verified and could be inaccurate, misleading, or incomplete.
• The company may not be able to enforce its intellectual property rights throughout the world.
• Failure to obtain and preserve protection for key intellectual property rights could allow competitors to take advantage of development efforts.
• Failure to comply with license, collaboration, or other intellectual property-related agreements may incur damages or loss of necessary rights.
• Loss of key management, leadership, and/or scientific personnel, or inability to recruit qualified employees, may cause program delays and increased compensation costs.
• Competition and technological change may make product candidates less competitive or obsolete.
• Anticipated operating expenses and capital expenditures are based on management's estimates, and actual amounts could differ materially.
• Concentration of ownership by principal stockholders limits the ability of others to influence director elections and other transactions, creates potential for conflicts of interest, and may negatively impact stock price or deter acquisitions.
• Current and new investors will experience dilution due to future sales or issuances of common stock.
• The trading price of common stock could be highly volatile.
• Substantial sales of shares into the open market upon expiry of the IPO lock-up in February 2025, or through the underwritten public offering, Committed Equity Facility, or private placement resale registration, could cause the stock price to decline.
• An agreement not to sell capital stock for 75 days from September 11, 2025, limits immediate financing options.

Future Outlook

The company expects to incur significant expenses and operating losses for the foreseeable future, anticipating these losses will increase substantially as it continues development, seeks regulatory approval, and potentially commercializes elraglusib and other product candidates. Management estimates that existing cash and cash equivalents will not satisfy operational and capital requirements beyond the second quarter of fiscal year 2026 without raising additional capital. The company plans to request meetings with the FDA for regulatory clarity on future clinical trial design for mPDAC registration in the U.S. and with the European Medicines Agency (EMA) for potential conditional approval in Europe. Plans are also in place to advance a Phase 2 study in Ewing sarcoma in 2026 and a Phase 1 study for an oral tablet formulation of elraglusib, both subject to future funding.

Management Comments

• Management anticipates, based on currently proposed plans and assumptions, that our cash and cash equivalents on hand will not satisfy the Company’s operational and capital requirements beyond the second quarter of fiscal year 2026 without raising additional capital.
• We have concluded that there is substantial doubt regarding the Company’s ability to continue as a going concern.

Industry Context

Actuate Therapeutics operates in the highly competitive and capital-intensive clinical-stage biopharmaceutical sector, focusing on novel cancer therapies. Its lead candidate, elraglusib, targets GSK-3 inhibition, a mechanism with broad potential across various cancers, including pancreatic cancer and Ewing sarcoma, which are areas of high unmet medical need. The positive Phase 2 mPDAC data is a significant step in a challenging indication, but the FDA's high bar for Breakthrough Therapy Designation (requiring comparison to all existing standard of care, including irinotecan-containing regimens) highlights the intense regulatory scrutiny and competitive landscape for new cancer treatments. The development of an oral dosage form aligns with industry trends towards more convenient patient administration. The need for continuous capital raises is typical for clinical-stage biotech companies, especially those without approved products or revenue streams.

Comparison to Industry Standards

• The median overall survival (mOS) of 10.1 months for elraglusib/GnP in first-line mPDAC compares favorably to historical data for gemcitabine/nab-paclitaxel (GnP) alone, which typically shows mOS in the range of 7-9 months in similar patient populations (e.g., the MPACT trial showed 8.5 months). The 7.2 months mOS for the GnP arm in this trial is consistent with historical ranges.
• The 1-year overall survival rate of 44.1% for elraglusib/GnP is a notable improvement over historical GnP data, which is often in the 30-35% range.
• The FDA's requirement for Breakthrough Therapy Designation (BTD) to demonstrate substantial improvement over all existing standard of care, including irinotecan-containing regimens (e.g., FOLFIRINOX, which has shown mOS of 11.1 months in some trials for mPDAC), sets a high bar. While elraglusib/GnP's 10.1 months mOS is promising against GnP, it may not yet clearly surpass FOLFIRINOX, indicating further clinical development or specific patient population targeting might be needed for BTD.
• The company's financial position, with substantial doubt about its ability to continue as a going concern, is common for early-stage biotechs but underscores the high burn rate and reliance on external funding typical in this industry.

Corporate Governance

Legal Proceedings

• To the company's knowledge, the company is not subject to any pending legal proceedings.

Related Party Transactions

• In the June 2025 Private Placement, Bios 2024 Co-Invest, LP, an affiliate of Bios Partners (where Dr. Aaron G.L. Fletcher, Chairman of the Board, is a Managing Partner), purchased 71,428 shares of common stock and warrants to purchase 71,428 shares of common stock for $499,996.
• The company incurred $450,197 in services from Pacific BioPharma Logistics, Inc. (PBL) during the nine months ended September 30, 2025. Richard Kenley, Vice President of Manufacturing (not an executive officer), is an unpaid advisor for PBL, and his spouse is a shareholder in PBL. An outstanding balance of $29,776 was owed to PBL as of September 30, 2025.

Stakeholder Impact

• Shareholders: Positive clinical trial results offer potential for future value, but significant dilution from recent and future capital raises, along with the 'going concern' warning, introduce considerable risk and potential stock price volatility.
• Patients: Positive Phase 2 data for elraglusib in mPDAC provides hope for a new treatment option in a difficult-to-treat cancer, with potential for new indications (EWS) and oral formulations to expand access and convenience.
• Employees: Continued development programs and capital raises offer job security, but the 'going concern' risk could create uncertainty. Stock-based compensation is a significant part of their remuneration.
• Creditors/Suppliers: The 'going concern' warning indicates potential risk, though recent capital raises improve short-term liquidity.
• Regulatory Bodies: The FDA's feedback on Breakthrough Therapy Designation highlights rigorous standards for approval, influencing the company's strategic regulatory path.

Next Steps

• Request meetings with the FDA to gain regulatory clarity on the design of a future clinical trial required to support potential product registration in the U.S. for mPDAC.
• Discuss regulatory and clinical trial requirements with the European Medicines Agency (EMA) for potential conditional approval in Europe for first-line mPDAC.
• Advance the clinical program towards a Phase 2 study in children, adolescents, and adults with relapsed/refractory Ewing sarcoma (EWS) in 2026, subject to available funding.
• Plan a Phase 1 study (Actuate-2401) to identify the maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D) for Elraglusib Oral Tablet in patients with advanced, refractory adult cancers, subject to future funding.
• Seek additional financing through equity offerings, debt financings, or other capital sources beyond Q2 2026.

Key Dates

Recommendation

While the positive Phase 2 clinical data for elraglusib in metastatic pancreatic ductal adenocarcinoma is a significant and encouraging development, demonstrating improved overall survival and a favorable safety profile, the company faces substantial financial challenges. The 'going concern' warning, coupled with the need for continuous capital raises and the high bar set by the FDA for Breakthrough Therapy Designation, introduces considerable risk. The recent capital raises provide short-term liquidity but also result in dilution. Investors should hold to monitor the company's progress in securing additional funding, navigating regulatory pathways, and advancing its clinical pipeline, particularly the planned FDA and EMA meetings and the EWS study. The long-term viability remains highly dependent on successful clinical development and commercialization, which are still years away and subject to significant uncertainties.

Keywords

Actuate Therapeutics, elraglusib, pancreatic cancer, mPDAC, GSK-3 inhibitor, clinical trial, Phase 2, overall survival, Ewing sarcoma, biopharmaceutical, oncology, capital raise, SEC filing, 10-Q, drug development, regulatory approval, Breakthrough Therapy Designation, stock offering, private placement