Actuate Therapeutics Inc 2025年度报告

Dear Stockholders, 2025 was a pivotal year for Actuate Therapeutics as we advanced our clinical programs andcontinued building a foundation for long-term value creation. At the center of that progress iselraglusib, a novel small molecule with a differentiated, multi-layered mechanism of action. In metastatic pancreatic ductal adenocarcinoma (mPDAC), one of the most aggressive anddifficult-to-treat cancers, we achieved what we believe is a meaningful clinical breakthrough. Ourrandomized Phase 2 trial met its primary endpoint, demonstrating a statistically significantimprovementin overall survival when elraglusib was added to the standard of caregemcitabine/nab-paclitaxel. The combination reduced the risk of death by 38%, increased themedian overall survival to 10.1 months versus 7.2 months, and importantly demonstrateddurable survival. We saw 12-month survival rates double and 24-month survival increase fivefold.In a disease where historical survival is often less than one year, these results truly matter. What excites us most is not just the magnitude of benefit but the pattern - increased durability,patients living longer than expected, and signals, both genomic and immunologic, that suggestelraglusib is not simply adding incremental benefit but may be reshaping the tumor environmentand enhancing anti-tumor response. With that, we increasingly believe elraglusib has thepotential to serve as a backbone therapy in pancreatic cancer, capable of combining acrossmultiple treatment regimens. Our strategy has always extended beyond a single indication. Elraglusib, originally developed asa GSK-3 inhibitor, modulates key tumor survival and resistance pathways. This positions itdifferently from therapies that focus solely on driver mutations – it allows us to potentiallyenhance the effectiveness of existing treatments across multiple cancers. In 2025 and recently,we expanded this vision by: -Advancingcombination strategies,including ongoing and planned studies withchemotherapy, immunotherapy, and RAS / RAF pathway-inhibitors;-Updating our clinical data package to support planned regulatory submissions with theFDA and EMA in 2026; and-Continuing to build clinical and scientific evidence supporting elraglusib’s role acrossadditional tumor types. We are particularly encouraged by early signals of efficacy in pediatric cancers, where unmetneed is especially high. In a Phase 1 study in heavily pretreated patients, we observed clinicalresponsesand disease control,including complete responses in Ewing sarcoma andneuroblastoma patients. These data, along with Rare Pediatric Disease Designations from theFDA, support advancing elraglusib in these indications in 2026. We are also expanding potential use of elraglusib with an oral tablet formulation, with a plannedPhase 1/2 program in advanced cancers. This approach enables broader use and builds on earlyencouraging activity in refractory metastatic melanoma, including a durable complete responselasting more than six years using elraglusib as a monotherapy. Importantly, the oral formulationhas the potential to expand patient access, improve convenience, and ultimately drive betteroutcomes,while also enabling more flexible and efficient development across multipleindications. We believe that the new oral formulation will play an important role in extendingelraglusib across additional indications and treatment settings. As we enter 2026, our priorities are clear:-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., and with the EMA todiscuss regulatory and clinical trial requirements for potential conditional approval inEurope for the treatment of first-line mPDAC;-Advance development of elraglusib in pediatric cancers and other high-need indications;-Initiate the oral tablet program;-Expand combination strategies across tumor types, including combinations with RAS /RAF pathway-inhibitors; and-Continue to strengthen our balance sheet with additional capital with which to fund ourgoals. The data we generated to date reinforce our belief that elraglusib has the potential to become afoundational therapy across multiple oncology settings. We are energized by the data, theopportunities ahead, and the potential to deliver meaningful impact for patients. Thank you for your continued support. Yours sincerely, Daniel M. Schmitt, President & Chief Executive OfficerActuate Therapeutics, Inc. UNITED STATESSECURITIES AND EXCHANGE COMMISSIONWashington, D.C. 20549FORM 10-K Indicate by check mark if the registrant is a well-known seasoned issuer, as defined in Rule 405 of the Securities Act. YesտNoց Indicate by check mark if the registrant is not required to file reports pursuant to Section 13 or Section 15(d) of the Act. YesտNoց Indicate by check mark whether the registrant (1) has filed all reports required to be filed by Section 13 or 15(d) of the Securities Exchange A