Actuate Therapeutics, Inc.

Company at a glance

• Name: Actuate Therapeutics, Inc. (Delaware); previously Apotheca Therapeutics, Inc.
• Focus: Clinical-stage biopharmaceutical company developing therapies for hard-to-treat cancers by inhibiting glycogen synthase kinase-3 beta (GSK-3β).
• Lead asset: elraglusib (formerly 9-ING-41), an ATP-competitive GSK-3β inhibitor designed to enter cancer cells and disrupt multiple signaling pathways that drive tumor survival, growth, migration, and invasion. Elraglusib is being developed in multiple forms and indications.
• IP and collaborations: Exclusive licenses with Northwestern University (NU) and University of Illinois‑Chicago (UIC) related to elraglusib; owned and in‑licensed patent families cover elraglusib polymorphs and oral forms; collaboration with Lantern Pharma for AI-driven biomarker work.

Business focus

• Develop elraglusib as a “pipeline in a molecule” with a multimodal mechanism of action in oncology, intended for combination with standard or novel therapies across multiple tumor types.
• Two primary drug formats:
  • Elraglusib Injection (IV)
  • Elraglusib Oral Tablet (oral solid dosage form)
• Plans to advance additional indications (for example, pediatric cancers, metastatic melanoma, colorectal and lung cancers) and to pursue strategic collaborations to fund and expand development.

Lead product and mechanism of action

• Elraglusib: GSK-3β inhibitor.
  • Target: GSK-3β, a regulator of signaling pathways involved in oncogenesis and tumor immunity.
  • Proposed effects: immune modulation; inhibition of tumor cell proliferation; reduction of tumor fibrosis; decreased immune evasion; enhanced apoptosis and DNA damage response; and inhibition of epithelial-to-mesenchymal transition.
  • Competitive position: Company asserts elraglusib is among the most advanced high-affinity GSK-3β inhibitors in clinical development; there are no approved high-affinity GSK-3β inhibitors.

Product candidates and dosage forms

• Elraglusib Injection

  • Lead clinical program in first-line metastatic pancreatic ductal adenocarcinoma (mPDAC).
  • Phase 2 Actuate-1801 Part 3B: randomized trial of elraglusib plus gemcitabine/nab-paclitaxel (GnP) versus GnP alone; 286 patients enrolled.
  • Updated January 2026 data (cutoff November 22, 2025):
    • Median overall survival (mOS): 10.1 months (elraglusib/GnP) vs 7.2 months (GnP) in safety population; hazard ratio 0.62; p = 0.02.
    • 12-month survival: 44.4% vs 22.3%; 24-month survival: 12.9% vs 2.6%.
    • Objective response rate (ORR): 28.4% vs 21.8%; median progression-free survival (mPFS): 5.6 vs 5.1 months; disease control rate (DCR): 39.4% vs 29.5%.
    • Treatment-emergent adverse events (Grade 1–2) frequently observed: visual disturbance and fatigue; most events were mild/moderate and reversible.
  • Program status: planning a Phase 3 global registration study; FDA and EMA discussions anticipated in 2026.

• Elraglusib Oral Tablet

  • Oral dosage form selected for expanded indications and convenience.
  • Pharmacokinetics: preclinical data showed >95% oral bioavailability with food.
  • Planned Phase 1/2 dose-escalation to identify MTD and RP2D for adults with advanced, refractory cancers.
  • Potential Phase 2 indications (based on prior data): refractory/metastatic melanoma, refractory/metastatic colorectal cancer, and non-small cell lung cancer.

Clinical experience

• Over 500 patients treated with elraglusib across Phase 1 and Phase 2 studies (Elraglusib Injection).
• Pediatric signal: Actuate-1902 (Phase 1/2) includes Ewing sarcoma and neuroblastoma; several objective responses observed, including complete metabolic responses and partial/complete responses in combination regimens.
• Pediatric regulatory designations: FDA Orphan Drug Designation (ODD) for sarcoma (EWS and others) and Rare Pediatric Disease Designation (RPDD) for Ewing sarcoma; EMA designation for sarcoma; potential priority review voucher (PRV) opportunity under certain conditions.

Investigator-initiated trials and collaborations

• Phase 1b IIT at UPMC Hillman Cancer Center evaluating elraglusib with retifanlimab (PD-1 inhibitor) and mFOLFIRINOX as frontline therapy in advanced pancreatic cancer (RiLEY trial). Open-label; up to 12 patients; four enrolled as of February 2026.
• Phase 2 IIT at Massachusetts General Hospital evaluating elraglusib with FOLFIRINOX and losartan in untreated metastatic pancreatic cancer; 49 patients enrolled as of 2026; exploratory data expected.
• Collaboration with Lantern Pharma to apply AI-derived biomarker signatures to identify patient subtypes more likely to respond to GSK-3 inhibition.

Intellectual property and licenses

• Northwestern University (NU) license:
  • Exclusive rights to elraglusib and related compounds.
  • NU equity: 5% of common stock issued to NU.
  • Milestone payments up to $1.25 million (including up to $0.25M on clinical milestones and $1.0M on initiation of commercial sales).
  • Royalties in the low single digits and sublicense revenue sharing.
• University of Illinois‑Chicago (UIC) license:
  • Exclusive rights to GSK-3β inhibitor technology for cancer.
  • Equity: 5% of capital stock issued to UIC.
  • Milestone and royalty structure, including potential Deferred Amount obligations adjusted by events such as change in control or large partnerships; obligations extend through last‑to‑expire market exclusivity and for a defined post‑approval period in certain jurisdictions.
• Patent portfolio (as of 12/31/2025):
  • 119 issued patents and pending applications worldwide.
  • Elraglusib-specific patents: two polymorph-based composition-of-matter families (Polymorph I and Polymorph II) with U.S., Europe, Australia, Japan, and other family coverage; U.S. patents expiring around 2038 (subject to extensions); European and other national patents with various expiration dates around 2038.
  • Oral dosage forms: patent family covering elraglusib oral dosage forms (PCT/US2023/069158) with filings in multiple jurisdictions.
• Lantern Pharma collaboration includes biomarker-derived work; investor affiliates held >10% of Lantern as of 12/31/2025.

Manufacturing and supply

• Drug substance manufactured by a non-exclusive supplier in China.
• Finished drug product largely manufactured in the United States.
• Third-party manufacturers used for clinical supply; no current long-term supply agreements.
• No in-house manufacturing facilities; plan to rely on contract manufacturers for clinical and potential commercial production.

Regulatory strategy and incentives

• Fast Track and Breakthrough Therapy designations may be sought depending on indication and data.
• Orphan Drug Designations for pancreatic cancer and other indications; EU orphan designation for sarcoma; potential PRV path if an NDA for a designated orphan indication is approved.
• EU pathway: centralized authorization via EMA for pivotal approvals; data exclusivity protections in the EU (8 years data exclusivity + 2 years market exclusivity; up to 11 years with new indications); potential PRIME and other accelerated routes.
• UK considerations: MHRA framework changes, ILAP/IRP frameworks discussed.
• U.S. FDA pathway: INDs, potential SPA for Phase 3 design, and NDA submission for marketing approval; post‑approval covenants and pharmacovigilance obligations apply.

Market focus and opportunity

• Primary target: first-line metastatic pancreatic cancer (mPDAC) in patients with no prior systemic therapy.
• Market context: mPDAC has limited survival with current chemotherapies; standard regimens include GnP or FOLFIRINOX; NALIRIFOX approval has shown some survival gains. Elraglusib aims to extend survival and enhance chemotherapy activity.
• Additional indications under development: pediatric sarcomas (Ewing sarcoma, neuroblastoma) and other solid tumors (melanoma, colorectal, NSCLC) based on prior signals.

Financials and corporate status (as of 12/31/2025)

• Cash and cash equivalents: approximately $13.2 million.
• Working capital: approximately $7.9 million.
• Accumulated deficit: about $154.6 million.
• Revenue: no product revenue to date.
• Operating losses: ongoing and expected while development continues.
• Employees: 12 full-time employees; additional contract workers; nine employees in R&D.
• Going concern: management has noted substantial doubt about continuing as a going concern and plans to raise capital through equity, debt, collaborations, or licensing arrangements.
• Ownership concentration: Bios Equity Affiliated Funds held about 43% of common stock as of 12/31/2025.

Operations and facilities

• Headquarters: Fort Worth, Texas; office space on a month-to-month basis since December 1, 2024.
• Prior to December 2024, space was provided by a major investor at no cost.
• All R&D conducted via CROs and academic collaborators; no internal manufacturing facilities.

Key risks

• Dependence on a single lead asset (elraglusib) with clinical and regulatory risk.
• No current revenue and ongoing need for substantial external financing.
• Reliance on third-party manufacturers and CROs, which creates supply and operational risk.
• Regulatory timing uncertainties for Phase 3 and international approvals.
• Intellectual property protection challenges and dependence on license agreements.
• Market and payer dynamics, including pricing, reimbursement, and competition.
• Concentrated ownership could influence strategic decisions and financing.

Summary

Actuate Therapeutics is a clinical-stage oncology company focused on elraglusib, a GSK-3β inhibitor being developed in IV and oral forms for metastatic pancreatic cancer and additional cancers, including pediatric sarcomas. The company has completed and ongoing Phase 1/2 programs with promising signals, is preparing for a Phase 3 registration study, and relies on NU and UIC licenses, a growing patent portfolio, and partnerships (including Lantern Pharma and IITs) to advance development. As of end‑2025, the company had 12 full-time employees, over 500 patients treated in clinical settings, approximately $13.2 million in cash, and an accumulated deficit of about $154.6 million.