Financial Condition and Operating Losses - The company has incurred significant operating losses since its inception in January 2015, with an accumulated deficit of approximately $132.4 million as of December 31, 2024[243]. - As of December 31, 2024, the company had approximately $8.6 million in cash and cash equivalents and working capital of approximately $0.4 million, raising substantial doubt about its ability to continue as a going concern[247]. - The company expects to continue incurring substantial operating losses for the foreseeable future as it develops its sole drug candidate, elraglusib[243]. - The company has not generated any revenue from product sales and does not expect to do so in the near future, if ever[244]. - The development of elraglusib and any future product candidates is highly capital-intensive, and the company will require substantial additional capital to finance its operations[249]. - The company plans to address its financial conditions by raising funds from public or private offerings of equity or debt securities, but there is no assurance that such funding will be available on favorable terms[248]. - The company intends to seek additional financing to achieve business objectives, but adequate financing may not be available on acceptable terms[254]. - There is no assurance that the company will be able to secure additional financing in sufficient quantities or at all, which may delay or limit product development[256]. Clinical Development and Regulatory Approval - The company may face delays or difficulties in clinical trials, which could adversely affect its ability to obtain regulatory approvals and commercialize its product candidates[237]. - The company relies on third parties for conducting non-clinical studies and clinical trials, and any failure on their part could adversely impact the company's financial condition[241]. - The company’s future capital requirements will depend on the success of clinical trials and the ability to obtain regulatory approvals, which are uncertain and time-consuming processes[253]. - Regulatory approvals are critical for the commercialization of elraglusib, and the process is expensive and time-consuming[258]. - The company may encounter delays in clinical trials that could preclude regulatory approval and commercialization of its products[259]. - The company has no experience in successfully obtaining regulatory approval, which may hinder its ability to manage related risks[268]. - The success of elraglusib depends on various factors, including successful clinical trials and regulatory submissions[266]. - The company has not yet completed a Phase 2 clinical trial, which is critical for obtaining regulatory approval and commercializing elraglusib[289]. - Safety concerns in clinical trials could adversely affect the prospects for regulatory approval of elraglusib, impacting the company's financial condition[291]. - The company anticipates developing product candidates for use in combination with other oncology drugs, which may complicate clinical trial designs and regulatory approval processes[298]. Manufacturing and Supply Chain Risks - The company relies on third-party manufacturers for the production of elraglusib, which poses risks related to quality control and regulatory compliance[305]. - The company does not control the manufacturing process and is dependent on third-party manufacturers for compliance with cGMP requirements[305]. - The company relies on third-party manufacturers for drug substances and products, with no long-term supply agreements in place, which may delay clinical trials if supplies are not sourced timely[308]. - The current manufacturer for elraglusib's drug substance is located in China, and geopolitical relationships may impact costs and regulatory approvals[317]. - Establishing new suppliers could take up to two years for regulatory approval, potentially delaying clinical development and increasing costs[318]. - The company may face higher than expected costs in manufacturing elraglusib due to inflation, supply chain issues, or component shortages[255]. - The company has not experienced significant supply chain disruptions but acknowledges the risk of future interruptions[309]. Intellectual Property and Legal Risks - The company may face challenges in obtaining licenses from third parties, which could adversely affect its ability to develop and commercialize products[375]. - The company may not have control over the prosecution and maintenance of licensed patents, which could jeopardize its rights to develop and commercialize products[376]. - The company may face claims regarding the inventorship or ownership of its patents and intellectual property, which could lead to litigation and substantial costs, adversely affecting its business and financial condition[378]. - The company may lose valuable intellectual property rights if it is unsuccessful in interference proceedings or other disputes regarding patent validity, which could impact its ability to commercialize drug candidates[380]. - The company may need to litigate or obtain licenses from third parties to develop or market its technologies, which may not be available on commercially reasonable terms[381]. - The company faces significant risks regarding its intellectual property, as patents may be challenged, invalidated, or circumvented, potentially impacting competitive advantage[363]. - The biopharmaceutical industry is characterized by extensive litigation, which could lead to costly and time-consuming legal disputes that may adversely affect the company's business[365]. Market and Competitive Risks - The company faces significant competition in establishing strategic partnerships, which can be time-consuming and costly[325]. - The company is exposed to risks from competitors who may develop superior products or obtain regulatory approvals more quickly[394]. - The commercial success of elraglusib and future product candidates depends significantly on market acceptance among physicians, patients, and healthcare payors, with no assurance of achieving adequate revenue if acceptance is low[342]. - The company currently lacks a marketing and sales organization and must invest significant resources to develop these capabilities, which may delay revenue generation[343]. - Establishing effective marketing, sales, and distribution relationships with third parties is critical, as failure to do so could hinder product commercialization and revenue generation[345]. Compliance and Regulatory Environment - Compliance with cGMP and regulatory requirements is critical, and failure to meet these could delay product approvals and revenue generation[307]. - The company may face increased compliance costs due to various healthcare laws and regulations, which could adversely affect its business operations[399]. - The company is subject to significant risks related to product liability lawsuits, which could lead to substantial costs and reduced demand for its products[410]. - The company is classified as an emerging growth company, allowing it to take advantage of reduced disclosure requirements, which may affect investor attractiveness[404]. Data Privacy and Security Risks - The company relies on third-party vendors for manufacturing and IT infrastructure, which increases vulnerability to disruptions and unauthorized access[415]. - Compliance with health privacy and data protection laws is critical, as violations could lead to government enforcement actions and significant costs[416]. - The company is subject to various state and federal data privacy laws, including the California Consumer Privacy Act, which allows penalties of up to $7,500 per violation[418]. - International data protection laws, including the EU General Data Protection Regulation, impose strict requirements and potential fines of up to 4% of annual worldwide turnover[422]. - The evolving legal framework around privacy could impose significant limitations on data collection and usage practices[424]. Legislative and Pricing Pressures - Current healthcare reform legislation may increase difficulty and costs for the company to obtain coverage and commercialize elraglusib or future product candidates[427]. - The Inflation Reduction Act of 2022 allows HHS to negotiate prices for certain high-expenditure drugs under Medicare, which could significantly impact the pharmaceutical industry[431]. - The American Rescue Plan Act of 2021 eliminates the statutory cap on Medicaid drug rebates starting January 1, 2024, which was previously capped at 100% of a drug's average manufacturer price[430]. - Legislative changes have resulted in reduced Medicare payments to providers, which will remain in effect until 2032 unless further Congressional action is taken[430]. - Increased scrutiny of pharmaceutical pricing practices has led to congressional inquiries and proposed legislation aimed at enhancing transparency and reforming reimbursement methodologies[430]. - The company faces potential pressure on product pricing due to bidding procedures used by regional healthcare authorities and hospitals[432]. - The company anticipates that future legislative changes may further impact drug pricing and reimbursement practices[431].

Core Insights - Actuate Therapeutics, Inc. has completed patient enrollment in a Phase 2 trial for elraglusib in combination with FOLFIRINOX and losartan for untreated metastatic pancreatic adenocarcinoma (mPDAC) [1][2][3] - The trial enrolled 56 treatment-naïve mPDAC patients, focusing on safety, tolerability, and progression-free survival [2] - Initial data from the trial indicates enhanced clinical activity of elraglusib when combined with FOLFIRINOX and losartan [3][7] - The final results from the trial are anticipated in 2026 [3][7] Company Overview - Actuate Therapeutics is a clinical-stage biopharmaceutical company focused on therapies for high-impact, difficult-to-treat cancers [4] - The lead investigational drug, elraglusib, is a novel GSK-3β inhibitor targeting pathways that promote tumor growth and resistance to conventional therapies [4] - Elraglusib is designed to enhance anti-tumor immunity by inhibiting NF-kB and regulating immune checkpoints [4] Research Collaboration - The trial is led by Dr. Colin Weekes at Massachusetts General Hospital, with support from the Lustgarten Foundation and participation from other institutions [1][3] - Massachusetts General Hospital is noted for conducting the largest hospital-based research program in the U.S., with over $1 billion in annual research operations [5]

Core Insights - Actuate Therapeutics, Inc. is a clinical-stage biopharmaceutical company focused on developing therapies for high-impact, difficult-to-treat cancers through the inhibition of glycogen synthase kinase-3 beta (GSK-3β) [1][4] - The company's lead investigational drug, elraglusib, targets molecular pathways involved in tumor growth and resistance to conventional cancer treatments, aiming to enhance anti-tumor immunity [4] Upcoming Investor Conferences - Actuate's President & CEO, Daniel Schmitt, will participate in the BIO CEO & Investor Conference on February 10, 2025, in New York, NY, which includes one-on-one meetings [2] - The company will also be present at the B. Riley Precision Oncology & Radiopharma Conference on February 28, 2025, in New York, NY, featuring a fireside chat and one-on-one meetings [3] Company Overview - Actuate Therapeutics is dedicated to developing therapies for challenging cancers, with elraglusib being a novel GSK-3β inhibitor that mediates anti-tumor immunity by inhibiting NF-kB and regulating immune checkpoints [4]

Core Insights - Actuate Therapeutics announced positive interim data from its Phase 2 trial of elraglusib combined with gemcitabine/nab-paclitaxel (GnP) for treating metastatic pancreatic ductal adenocarcinoma (mPDAC) [1][2][3] Summary by Sections Trial Results - The trial met its primary endpoint with a 1-year survival rate of 43.6% in the elraglusib-GnP combination arm compared to 22.5% in the GnP control arm (p=0.002) [4] - Median overall survival (mOS) was 9.3 months for the elraglusib-GnP arm versus 7.2 months for the GnP arm, indicating a 37% reduction in risk of death (HR=0.63, p=0.016) [4] - Objective Response Rates (ORR) were 27.7% in the elraglusib-GnP arm compared to 20.5% in the GnP arm, while Disease Control Rates (DCR) were 42.6% versus 33.3% respectively [4] Patient Outcomes - As of the data cutoff on November 15, 2024, 38% of patients in the elraglusib-GnP arm were still alive compared to 19% in the control arm [4] - Notable patient outcomes included two patients with previously inoperable metastatic lesions showing significant reductions in target lesions, with one achieving a 100% reduction in total tumor burden after surgery [4] 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 [4][5] Future Plans - The company plans to engage with the FDA in the first half of 2025 to share topline data and discuss next steps, including a proposed Phase 3 registration trial [3][5]

Financial Performance - The company reported net losses of approximately $24.7 million and $20.2 million for the years ended December 31, 2023 and 2022, respectively, and $20.8 million and $17.1 million for the nine months ended September 30, 2024 and 2023, respectively [137]. - The company has incurred significant operating losses and negative cash flows from operations since inception, with expectations that these losses will continue to increase as development efforts progress [137]. - The net loss for the three months ended September 30, 2024, was $5,970,961, an improvement of $366,964 compared to a net loss of $6,337,925 in the same period of 2023 [161]. - For the nine months ended September 30, 2024, total operating expenses were $18,601,606, an increase of $1,242,958 compared to $17,358,648 in the same period of 2023 [172]. - The net cash used in operating activities for the nine months ended September 30, 2024, was $20,839,239, compared to a net loss of $17,132,466 for the same period in 2023 [192]. Funding and Capital Structure - The company completed its IPO on August 14, 2024, raising net proceeds of approximately $22 million from the issuance of 3,220,000 shares of common stock at an initial offering price of $8.00 per share [142]. - The Company issued 884,427 shares of common stock upon the conversion of Related Party Convertible Notes Payable at a conversion price of $6.40 per share, representing 80% of the IPO price of $8.00 per share [159]. - Net cash provided by financing activities for the nine months ended September 30, 2024, was $27,635,023, significantly higher than $4,134,516 for the same period in 2023 [194]. Cash Position - The company has cash and cash equivalents of approximately $13.5 million as of September 30, 2024, which is not expected to satisfy operational and capital requirements for the next twelve months [140]. - The company estimates that its existing cash and cash equivalents will not satisfy operational and capital requirements through twelve months from the issuance date of the financial statements [188]. Clinical Development - The company plans to conduct a Phase 1 study for the Elraglusib Oral Tablet to identify the maximum tolerated dose and recommended Phase 2 dose in patients with advanced, refractory adult cancers [135]. - The company is advancing a Phase 2 clinical trial for the treatment of metastatic pancreatic ductal adenocarcinoma and a Phase 1/2 clinical trial in refractory pediatric malignancies, including Ewing sarcoma [134]. - The company expects to incur significant expenses related to developing its commercialization capability to support product sales, marketing, and distribution if regulatory approval for elraglusib is obtained [137]. - The company expects to incur significant expenses and operating losses in the foreseeable future as it advances the clinical development of elraglusib [186]. Operating Expenses - Total operating expenses for the three months ended September 30, 2024, were $5,392,903, a decrease of $1,082,770 compared to $6,475,673 in the same period of 2023 [161]. - Research and development expenses decreased by approximately $2.0 million to $3,757,102 for the three months ended September 30, 2024, primarily due to fewer contracted studies and a decrease in external clinical trial expenses [163]. - General and administrative expenses increased by approximately $0.9 million to $1,635,801 for the three months ended September 30, 2024, mainly due to higher personnel-related expenses and increased professional fees [164]. - General and administrative expenses increased by approximately $1.3 million to $3,611,269 for the nine months ended September 30, 2024, compared to $2,296,143 for the same period in 2023 [176]. - Personnel-related expenses rose by approximately $0.4 million, primarily due to an increase in non-cash stock-based compensation [176]. - Professional and consulting fees increased by approximately $0.7 million, mainly due to search firm fees for adding new board members and increased legal fees [176]. Valuation and Fair Value - The fair value of common stock prior to the IPO was determined by the board of directors based on third-party valuations and various subjective factors [206]. - The company utilized the Black-Scholes valuation model for stock options, requiring inputs such as expected volatility and risk-free rate [204]. - The estimated fair value of Related Party Convertible Notes Payable was determined using valuation models with significant unobservable inputs, classified as Level 3 measurements [216]. - A loss of $400,000 was recorded on the issuance of Related Party Convertible Notes Payable during the nine months ended September 30, 2024, reflecting the difference between estimated fair value and gross proceeds [217]. - The fair value of financial instruments approximates their carrying amounts due to their short-term nature [211]. Company Classification - The company is classified as an emerging growth company, allowing it to take advantage of an extended transition period for new accounting standards [221]. - The company is also a smaller reporting company, which permits scaled disclosures as long as certain revenue and market capitalization thresholds are met [222]. Miscellaneous - The company has no off-balance sheet arrangements during the periods presented [219]. - The fair value of Redeemable Convertible Preferred Stock Warrants was subject to remeasurement until the earlier of exercise, conversion, or expiration [212].