Table of Contents UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 FORM 10-Q (Mark One) ý QUARTERLY REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the quarterly period ended June 30, 2025 OR ☐ TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the transition period from _________ to _________ Commission File Number: 001-42139 Actuate Therapeutics, Inc. (Exact name of registrant as specified in its charter) De ...

Core Insights - Actuate Therapeutics has completed the Phase 1 study of elraglusib in pediatric patients, showing promising results in treating refractory Ewing Sarcoma (EWS) [1][2][3] - The company plans to advance to a Phase 2 trial for elraglusib in children, adolescents, and adults with relapsed/refractory EWS due to the observed complete responses [1][3] Company Overview - Actuate Therapeutics is a clinical-stage biopharmaceutical company focused on developing therapies for high-impact, difficult-to-treat cancers, specifically through the inhibition of glycogen synthase kinase-3 beta (GSK-3β) [1][6] - Elraglusib, the company's lead investigational drug, targets molecular pathways involved in tumor growth and resistance to conventional cancer treatments [6] Clinical Study Details - The Phase 1/2 trial (NCT 04239092), known as Actuate-1902, is an open-label, multicenter study evaluating the safety and efficacy of elraglusib in pediatric patients with relapsed/refractory malignancies, including EWS [2][3] - The study enrolled ten patients with relapsed/refractory EWS, with two patients achieving complete responses and two others showing stable disease [3] Future Plans - The company is planning to initiate a Phase 2 trial in 2026, subject to funding availability, and will engage with regulators to discuss the potential registration path for elraglusib [3][1] - Actuate is collaborating with key opinion leaders and consortiums to ensure the upcoming study design meets patient needs and regulatory expectations [3]

Core Insights - Actuate Therapeutics, Inc. reported significant clinical benefits of elraglusib in combination with gemcitabine/nab-paclitaxel (GnP) for patients with first-line metastatic pancreatic adenocarcinoma, showing a near doubling of 1-year overall survival (OS) and a 43% reduction in risk of death compared to GnP alone [1][2][7] Company Overview - Actuate Therapeutics is a clinical-stage biopharmaceutical company focused on developing therapies for difficult-to-treat cancers, with elraglusib as its lead investigational drug targeting GSK-3β to inhibit tumor growth and enhance anti-tumor immunity [9] Clinical Trial Results - In the Phase 2 trial (Actuate-1801 Part 3B), patients receiving elraglusib plus GnP achieved a median overall survival (mOS) of 12.5 months compared to 8.5 months in the control group, with a disease control rate (DCR) of 53.4% versus 44.8% and an overall response rate (ORR) of 37.9% versus 29.3% [2][5] - Patients with liver metastases experienced a 2.5-fold increase in 1-year OS and a 38% reduction in risk of death, with a survival probability of 13.6% at 18 months for those treated with elraglusib [5][7] Efficacy Metrics - Additional efficacy metrics for patients with liver metastases included a DCR of 36.8% versus 27.9%, an ORR of 29.8% versus 19.7%, and a median progression-free survival (PFS) of 4.9 months compared to 3.9 months in the control group [5][7]

Core Insights - Actuate Therapeutics, Inc. announced promising biomarker data from the Phase 2 trial of elraglusib in combination with gemcitabine/nab-paclitaxel for first-line metastatic pancreatic adenocarcinoma, highlighting the potential for improved patient stratification based on pre-dose plasma biomarkers [1][2][3] Group 1: Study Findings - The analysis of 40 cytokines, chemokines, soluble cell receptors, and growth factors identified 7 significant biomarkers predicting favorable survival in the elraglusib-treated cohort, particularly highlighting CXCL2's unique survival trend [2][3] - Univariate analysis showed that elevated levels of CXCL2 and TRAIL were associated with improved overall survival, while lower levels of CCL3, IL-1α, IL-18, TGF-β, and TRAIL R3 were linked to better survival outcomes [3] - Multivariate machine learning models were developed to accurately predict patients likely to survive over one year when treated with elraglusib and GnP [3] Group 2: Company Strategy and Future Plans - The results support the use of non-invasive blood-based markers to identify patients who may benefit from elraglusib, indicating a significant advancement in the company's biomarker strategy [4] - The company plans to prospectively test the identified biomarkers in future trials and focus on optimizing patient stratification and predictive accuracy through refined machine learning models [4] - Actuate aims to apply this biomarker identification approach to guide the development of elraglusib in metastatic pancreatic cancer and other advanced cancer indications [4] Group 3: Company Overview - Actuate Therapeutics is a clinical-stage biopharmaceutical company focused on developing therapies for difficult-to-treat cancers, with elraglusib as its lead investigational drug targeting pathways involved in tumor growth and resistance to conventional therapies [5] - Elraglusib may also enhance anti-tumor immunity by regulating immune checkpoints and immune cell functions, indicating its potential in cancer treatment [5]

Core Insights - Actuate Therapeutics, Inc. will be added to the Russell 3000® Index and automatically included in the Russell 2000® Index effective after the U.S. market close on June 27, 2025, marking a significant milestone for the company [1][3] - The inclusion reflects the company's strong momentum following positive topline Phase 2 data in metastatic pancreatic ductal adenocarcinoma (mPDAC), demonstrating a clinically meaningful increase in median overall survival (mOS) of 10.1 months compared to 7.2 months, with a 37% reduction in the risk of death [3] Company Overview - Actuate is a clinical-stage biopharmaceutical company focused on developing therapies for high-impact, difficult-to-treat cancers, with its lead investigational drug, elraglusib, targeting molecular pathways involved in tumor growth and resistance to conventional cancer treatments [4] - Elraglusib is a novel glycogen synthase kinase-3 beta (GSK-3β) inhibitor that may also mediate anti-tumor immunity through the regulation of immune checkpoints and immune cell function [4] Industry Context - The Russell 3000® Index tracks the performance of the largest 3,000 publicly traded U.S. companies and serves as a broad benchmark for the U.S. equity market, with approximately $10.6 trillion in assets benchmarked against the Russell U.S. Indexes as of May 2025 [2]

Core Insights - Actuate Therapeutics announced positive topline results from the Phase 2 trial of elraglusib in combination with gemcitabine/nab-paclitaxel for treating metastatic pancreatic ductal adenocarcinoma, indicating a significant improvement in overall survival [1][2][5] Study Results - The study achieved its primary endpoint with a median overall survival of 10.1 months for the elraglusib/GnP group compared to 7.2 months for the GnP group, resulting in a 37% reduction in the risk of death (HR = 0.63) [2][8] - The 12-month survival rate was 44.1% in the elraglusib/GnP arm versus 22.3% in the GnP arm, demonstrating a doubling of survival rates [2][8] - Continued survival benefits were observed at 18 and 24 months, with survival rates of 19.7% vs 4.4% and 13.8% vs 0% for elraglusib/GnP compared to GnP alone, respectively [8] - The overall response rate was numerically improved at 29.0% for the elraglusib/GnP arm compared to 21.8% for the GnP arm [8] Safety Profile - The trial met its primary safety endpoint, with treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs) in the elraglusib/GnP arm being similar to those in the GnP arm, indicating a favorable risk-benefit profile [8] - Most treatment-related adverse events (TRAEs) were Grade 1-2, with transient visual impairments being the most common [8] Mechanism of Action - Elraglusib works by inhibiting GSK-3β, which may enhance chemotherapy activity, activate anti-tumor immunity, and regulate gene expression, potentially leading to improved survival outcomes [10][11] Clinical Context - The KOL event highlighted the unmet need in mPDAC and the potential of elraglusib to reshape treatment paradigms, emphasizing the importance of new drugs with unique mechanisms [4][5]

Core Insights - Actuate Therapeutics, Inc. presented topline results from the Phase 2 trial of elraglusib in combination with gemcitabine/nab-paclitaxel for treating metastatic pancreatic ductal adenocarcinoma, demonstrating significant improvements in overall survival [1][2][5] Efficacy - The trial met its primary endpoint, showing a median overall survival (mOS) of 10.1 months for the elraglusib combination group compared to 7.2 months for the control group, with a hazard ratio (HR) of 0.63 and a log-rank p-value of 0.01, indicating a 37% reduction in the risk of death [2][4][5] - The 12-month survival rate for patients receiving elraglusib with GnP was 44.1%, which is double that of the GnP alone group at 22.3% [2][5] - Continued survival benefits were observed at 18 and 24 months, with survival rates of 19.7% vs 4.4% and 13.8% vs 0% for the elraglusib/GnP combination versus GnP alone, respectively [10] - The overall response rate was numerically improved at 29.0% for the elraglusib combination compared to 21.8% for GnP alone [10] Safety Profile - The trial met its primary safety endpoint, with treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs) in the elraglusib combination arm being similar to those in the GnP arm, indicating a favorable risk-benefit profile [10] - Most treatment-related adverse events (TRAEs) were Grade 1-2, with transient visual impairments being the most common [10] - Grade 3 or higher neutropenia was observed, but rates of febrile neutropenia and sepsis were similar across both treatment arms [10] Future Plans - Based on the positive clinical results and manageable safety profile, the company plans to engage with the FDA and EMA in the second half of 2025 to discuss a path towards product registration [3][5] - Actuate will host a Key Opinion Leader (KOL) event to discuss the trial results, featuring prominent experts in the field [8]

Core Insights - Actuate Therapeutics, Inc. announced the acceptance of an abstract for an oral presentation at the 2025 ASCO Annual Meeting, focusing on the Phase 2 trial data of elraglusib in combination with GnP for treating metastatic pancreatic ductal adenocarcinoma (mPDAC) [1][2] Group 1: Clinical Trial Results - The topline data from the Actuate-1801 Part 3B trial show clinically meaningful improvements in primary efficacy measures when elraglusib is combined with GnP compared to GnP alone [2] - Preliminary results indicate statistically significant increases in the 1-year survival rate and median overall survival for patients treated with the elraglusib/GnP combination versus those receiving GnP alone [3] - The combination treatment also led to higher Objective Response Rates (ORR) and Disease Control Rates (DCR) compared to the control arm [3] Group 2: Company Statements and Future Outlook - The CEO of Actuate highlighted the significance of achieving statistical significance in increased survival rates in a Phase 2 trial, emphasizing elraglusib's potential as a promising therapy for mPDAC [4] - The company views elraglusib as a highly valuable late-stage asset with substantial regulatory and commercial potential [4] - Actuate plans to host a KOL event on May 31, 2025, to discuss the data presented at ASCO, featuring discussions with key opinion leaders [6][8] Group 3: Study Design and Methodology - The Actuate-1801 Part 3B study is a randomized, controlled Phase 2 trial involving 286 mPDAC patients, comparing elraglusib with GnP to GnP alone [9] - Elraglusib is administered at a dose of 9.3 mg/kg via IV infusion on Day 1 of each week in a 28-day cycle, with median overall survival as the primary endpoint [9] - Secondary endpoints include DCR, ORR, progression-free survival (PFS), and adverse events (AE) [9] Group 4: Mechanism of Action - Elraglusib, a GSK-3β inhibitor, may enhance chemotherapy efficacy, activate anti-tumor immunity, and regulate gene expression, potentially leading to improved survival outcomes [10][11]

PART I. FINANCIAL INFORMATION [Item 1. Financial Statements](index=8&type=section&id=Item%201.%20Financial%20Statements) The company reported a net loss of **$6.3 million** for the quarter ended March 31, 2025, a decrease from the **$8.3 million** loss in the prior year period, with cash and cash equivalents significantly decreasing to **$3.9 million** from **$8.6 million** at the end of 2024, leading to a working capital deficit of **$4.9 million** Condensed Consolidated Balance Sheet Highlights (Unaudited) | Account | March 31, 2025 | December 31, 2024 | | :--- | :--- | :--- | | Cash and cash equivalents | $3,889,405 | $8,641,622 | | Total current assets | $4,248,564 | $9,207,900 | | Total assets | $4,483,039 | $9,318,448 | | Total current liabilities | $9,153,954 | $8,802,503 | | Total liabilities | $9,570,776 | $9,214,262 | | Total stockholders' equity (deficit) | $(5,087,737) | $104,186 | Condensed Consolidated Statements of Operations (Unaudited) | Account | Three Months Ended March 31, 2025 | Three Months Ended March 31, 2024 | | :--- | :--- | :--- | | Research and development | $3,220,319 | $6,860,430 | | General and administrative | $3,145,265 | $912,824 | | Total operating expenses | $6,365,584 | $7,773,254 | | Loss from operations | $(6,365,584) | $(7,773,254) | | Net loss | $(6,317,024) | $(8,296,059) | | Net loss per share, basic and diluted | $(0.32) | $(5.40) | Condensed Consolidated Statements of Cash Flows (Unaudited) | Activity | Three Months Ended March 31, 2025 | Three Months Ended March 31, 2024 | | :--- | :--- | :--- | | Net cash used in operating activities | $(4,618,740) | $(5,247,582) | | Net cash provided by (used in) financing activities | $(133,477) | $4,357,230 | | Net change in cash and cash equivalents | $(4,752,217) | $(890,352) | | Cash and cash equivalents, end of period | $3,889,405 | $2,068,307 | [Notes to Financial Statements](index=12&type=section&id=Notes%20to%20Financial%20Statements) The notes detail the company's critical financial situation, emphasizing the 'going concern' issue due to recurring losses and insufficient cash reserves - The company is a clinical-stage biopharmaceutical firm focused on developing elraglusib, a GSK-3 inhibitor for cancer treatment[33](index=33&type=chunk) - There is substantial doubt about the Company's ability to continue as a going concern, with cash and cash equivalents of **$3.9 million** as of March 31, 2025, not expected to satisfy operational requirements beyond the second quarter of fiscal year 2025[37](index=37&type=chunk)[38](index=38&type=chunk) - On March 27, 2025, the Company entered into a Committed Equity Facility with B. Riley, allowing it to sell up to **$50 million** of its common stock over 36 months, subject to conditions[39](index=39&type=chunk)[63](index=63&type=chunk) - Subsequent to March 31, 2025, the company issued **72,082 shares** to B. Riley under the Committed Equity Facility for net proceeds of approximately **$597,000**[89](index=89&type=chunk) [Item 2. Management's Discussion and Analysis of Financial Condition and Results of Operations](index=24&type=section&id=Item%202.%20Management's%20Discussion%20and%20Analysis%20of%20Financial%20Condition%20and%20Results%20of%20Operations) Management discusses the company's focus on developing its sole product candidate, elraglusib, for cancer treatment, highlighting a significant decrease in R&D expenses and a sharp increase in G&A expenses, while addressing critical liquidity issues and the **$50 million** Committed Equity Facility as a primary means to address near-term capital requirements [Business Overview](index=24&type=section&id=Business%20Overview) Actuate is a clinical-stage biopharmaceutical company developing elraglusib, a GSK-3β inhibitor, for difficult-to-treat cancers, with its lead program, Actuate-1801, in a Phase 2 trial for metastatic pancreatic cancer (mPDAC) - The company's lead investigational product is elraglusib, a small molecule GSK-3β inhibitor for cancer treatment[92](index=92&type=chunk) - The most advanced clinical program is a Phase 2 trial (Actuate-1801) evaluating elraglusib for metastatic pancreatic ductal adenocarcinoma (mPDAC)[93](index=93&type=chunk)[95](index=95&type=chunk) - The company has incurred significant operating losses since inception, with a net loss of **$6.3 million** for Q1 2025 and an accumulated deficit of **$138.7 million** as of March 31, 2025[98](index=98&type=chunk) [Results of Operations](index=28&type=section&id=Results%20of%20Operations) For Q1 2025, total operating expenses decreased to **$6.4 million** from **$7.8 million** in Q1 2024, driven by a **$3.6 million** reduction in R&D expenses, offset by a **$2.2 million** rise in G&A expenses Comparison of Results of Operations (in thousands) | | Three Months Ended March 31, 2025 | Three Months Ended March 31, 2024 | Change | | :--- | :--- | :--- | :--- | | Research and development | $3,220 | $6,860 | $(3,640) | | General and administrative | $3,145 | $913 | $2,232 | | **Total operating expenses** | **$6,366** | **$7,773** | **$(1,407)** | | **Net loss** | **$(6,317)** | **$(8,296)** | **$1,979** | - R&D expenses decreased by **$3.6 million**, mainly due to a **$3.3 million** reduction in external clinical trial expenses related to fewer patients on study in the randomized Phase 2 mPDAC trial (Actuate-1801 Part 3B)[116](index=116&type=chunk) - G&A expenses increased by **$2.2 million**, primarily due to a **$1.2 million** increase in personnel-related expenses (including **$920,917** in non-cash stock-based compensation) and higher costs for D&O insurance, board fees, and legal fees from operating as a public company[117](index=117&type=chunk) [Liquidity and Capital Resources](index=30&type=section&id=Liquidity%20and%20Capital%20Resources) The company's financial position is critical, with only **$3.9 million** in cash and cash equivalents as of March 31, 2025, insufficient to support operations beyond the second quarter of 2025, necessitating substantial additional capital - As of March 31, 2025, the company had cash and cash equivalents of **$3,889,405**[119](index=119&type=chunk) - Existing cash and cash equivalents are not sufficient to fund operations beyond the second quarter of fiscal year 2025[121](index=121&type=chunk)[100](index=100&type=chunk) - The company entered into a Committed Equity Facility with B. Riley, providing the right to sell up to **$50 million** in common stock over 36 months to raise capital[124](index=124&type=chunk) - Failure to raise additional funds may require the company to delay, limit, reduce, or terminate its product development programs or even cease operations[123](index=123&type=chunk) [Item 3. Quantitative and Qualitative Disclosures About Market Risk](index=34&type=section&id=Item%203.%20Quantitative%20and%20Qualitative%20Disclosures%20About%20Market%20Risk) As a "smaller reporting company," Actuate Therapeutics, Inc. is not required to provide the information for this item - The company is not required to provide quantitative and qualitative disclosures about market risk because it qualifies as a "smaller reporting company" under SEC rules[144](index=144&type=chunk) [Item 4. Controls and Procedures](index=34&type=section&id=Item%204.%20Controls%20and%20Procedures) Management, including the CEO and CFO, evaluated the company's disclosure controls and procedures as of March 31, 2025, concluding they were effective at a reasonable assurance level - Based on an evaluation as of March 31, 2025, the company's management, including the CEO and CFO, concluded that disclosure controls and procedures were effective at a reasonable assurance level[146](index=146&type=chunk) PART II. OTHER INFORMATION [Item 1. Legal Proceedings](index=35&type=section&id=Item%201.%20Legal%20Proceedings) The company is not currently subject to any pending legal proceedings that are considered significant - To the company's knowledge, it is not subject to any pending legal proceedings[57](index=57&type=chunk)[148](index=148&type=chunk) [Item 1A. Risk Factors](index=35&type=section&id=Item%201A.%20Risk%20Factors) This section reiterates and expands upon the significant risks facing the company, including its critical financial condition, reliance on a single drug substance manufacturer in China, and uncertainties associated with the Committed Equity Facility [Risks Related to Our Financial Condition and Capital Requirements](index=35&type=section&id=Risks%20Related%20to%20Our%20Financial%20Condition%20and%20Capital%20Requirements) The company's financial condition raises substantial doubt about its ability to continue as a going concern, requiring immediate and substantial additional capital to finance operations beyond Q2 2025 - The company's financial condition raises substantial doubt about its ability to continue as a going concern, a conclusion also noted by its independent registered public accounting firm[152](index=152&type=chunk)[154](index=154&type=chunk) - Existing cash and cash equivalents are not sufficient to fund operations beyond the second quarter of fiscal year 2025[157](index=157&type=chunk) - The company requires substantial additional capital in the near term to finance operations, and failure to obtain it could force a delay, reduction, or termination of development programs or a cessation of operations[156](index=156&type=chunk)[162](index=162&type=chunk) [Risks Related to Our Reliance on Third Parties](index=37&type=section&id=Risks%20Related%20to%20Our%20Reliance%20on%20Third%20Parties) The company faces risks due to its reliance on a single manufacturer located in China for the drug substance (DS) of its sole product candidate, elraglusib, exposing it to geopolitical and trade policy vulnerabilities - The company relies on a single manufacturer in China for the drug substance (DS) of elraglusib, making it vulnerable to geopolitical and trade policy changes[163](index=163&type=chunk) - Unfavorable tariffs or other trade actions could increase the cost of the drug substance, adversely affecting the company's financial condition and results of operations[163](index=163&type=chunk)[165](index=165&type=chunk) [Risks Related to the Committed Equity Facility](index=38&type=section&id=Risks%20Related%20to%20the%20Committed%20Equity%20Facility) The company cannot predict the actual number of shares it will sell or the proceeds it will receive from the Committed Equity Facility, and sales under this facility could cause substantial dilution to existing stockholders and depress the market price of the common stock - It is not possible to predict the actual number of shares that will be sold or the gross proceeds that will be received under the **$50 million** Committed Equity Facility with B. Riley[166](index=166&type=chunk)[168](index=168&type=chunk) - Sales of a substantial number of shares to B. Riley could depress the market price of the company's common stock and cause significant dilution to other stockholders[172](index=172&type=chunk) - Management will have broad discretion over the use of any net proceeds from the facility, and investors will be relying on their judgment[171](index=171&type=chunk) [Item 2. Unregistered Sales of Equity Securities and Use of Proceeds](index=39&type=section&id=Item%202.%20Unregistered%20Sales%20of%20Equity%20Securities%20and%20Use%20of%20Proceeds) The company completed its Initial Public Offering (IPO) on August 14, 2024, raising net proceeds of approximately **$22 million**, with no material change in the planned use of these proceeds - On August 14, 2024, the company completed its IPO, receiving net proceeds of approximately **$22 million** after expenses[173](index=173&type=chunk) - There has been no material change in the planned use of proceeds from the IPO[173](index=173&type=chunk) [Item 5. Other Information](index=39&type=section&id=Item%205.%20Other%20Information) During the quarter ended March 31, 2025, no director or officer of the company adopted or terminated any Rule 10b5-1 trading arrangement or non-Rule 10b5-1 trading arrangement - No director or officer adopted or terminated a Rule 10b5-1 trading plan during the first quarter of 2025[176](index=176&type=chunk) [Item 6. Exhibits](index=40&type=section&id=Item%206.%20Exhibits) This section lists the exhibits filed with the quarterly report, including the Securities Purchase Agreement and Registration Rights Agreement with B. Riley, amendments to employment agreements, and standard SEC certification filings - Exhibits filed include agreements related to the B. Riley Committed Equity Facility, amendments to executive employment agreements, and CEO/CFO certifications[178](index=178&type=chunk)

Core Insights - Actuate Therapeutics, Inc. is hosting a key opinion leader event at the 2025 ASCO annual meeting to discuss topline clinical data from the randomized Phase 2 study of elraglusib [1][3][7] - The event will feature a discussion moderated by the CEO of Actuate and include four distinguished KOLs from leading medical institutions [2][3] - The focus will be on the clinical relevance and potential impact of the study's findings on treatment paradigms for metastatic pancreatic ductal adenocarcinoma (mPDAC) [3][7] Event Details - The event is scheduled for May 31, 2025, at 6:30 PM CDT, and will be available both in-person and via live webcast [4][7] - Registration details and a replay of the event will be accessible on the Actuate website [4] Featured Speakers - The event will include notable speakers such as Dr. Tanios Bekaii-Saab, Dr. Devalingam Mahalingam, Dr. Rachna Shroff, and Dr. Colin Weekes, all of whom have significant expertise in gastrointestinal cancers [5][6][8][9] ASCO Presentation Details - Actuate will present preliminary results from the randomized Phase 2 study of elraglusib in combination with gemcitabine/nab-paclitaxel versus gemcitabine/nab-paclitaxel alone for previously untreated mPDAC patients [10][11] - The study enrolled 286 patients, randomized in a 2:1 ratio to receive elraglusib or the control treatment [13] - The primary endpoint is the 1-year survival rate, with secondary endpoints including disease control rate, overall response rate, progression-free survival, and adverse events [13] Mechanism of Action - Elraglusib, a GSK-3β inhibitor, may enhance chemotherapy activity, activate anti-tumor immunity, and regulate gene expression, potentially improving survival outcomes [14][15]