Actuate Therapeutics, Inc. · NASDAQ:ACTU
Actuate Therapeutics — Investor Presentation (November 2025)
29 slides from Actuate Therapeutics's investor presentation, November 2025
Slide 1: Corporate Overview
Corporate Overview November 2025
Slide 2: Forward-Looking Statements
Forward-Looking Statements This presentation contains forward-looking statements about us, including our clinical trials and development plans, and our industry, that are based on management’s beliefs and assumptions and on information currently available to our management. The words “anticipate,” “
Slide 3: Company Highlights
Company Highlights Class-Leading • Highly specific small molecule kinase-inhibitor with excellent drug-like properties GSK-3β Inhibitor • >500 patients treated to date • Statistically significant improvements in overall survival (OS) in global Phase 2 trial in 1L mPDAC Compelling • 40% improvement i
Slide 4: Elraglusib: Multimodal MOA Supported by Clinical Data
Elraglusib: Multimodal MOA Supported by Clinical Data Inhibition of epithelial- T Cells and NK mesenchymal transition (EMT) cells activation ↓ Wnt/β –catenin signaling ↑ MHC-I expression ↓ TGF- β - pathways ↑ IFN-y signaling ↑ TCR signaling ↓ T cell exhaustion markers (PD-1, TIGIT, LAG-3) elraglusib
Slide 5: Strategic Pipeline Growth for IV and Oral Elraglusib
Strategic Pipeline Growth for IV and Oral Elraglusib Elraglusib Injection (IV) Program Preclinical Phase 1 Phase 2 Phase 3 Milestones - Updated Phase 2 data to be presented at ASCO GI in January 2026 Pancreatic Cancer (with Adult Actuate-1801 - FDA meeting request: clarity for In Planning** registra
Slide 6: Elraglusib Advancing Under a Master Protocol 1801
Elraglusib Advancing Under a Master Protocol 1801 Accelerated Study Design from Phase 1 to Phase 2 for Elraglusib Injection (IV) Establishes process for transition from elraglusib monotherapy (Part 1) to evaluation of multiple chemotherapy combinations (Part 2) to Phase 2 efficacy studies (Part 3) u
Slide 7: mPDAC Represents a High Unmet Need With Significant Commercial Potential
mPDAC Represents a High Unmet Need With Significant Commercial Potential Pancreatic Cancer Metastatic pancreatic cancer is highly aggressive and accounts for approximately 80-85% of all pancreatic cancer diagnoses. Projected market growth to >$5 billion by 20301 Survival Rate and Economic Burden The
Slide 8: Phase 2 Clinical Activity with Extended Median Overall Survival
Phase 2 – Clinical Activity with Extended Median Overall Survival Kaplan Meier – Overall Survival (EE) 1801 Part 3A in mPDAC Subjects 29 Survival Probability Event 21 (72%) • Simon Two-Stage trial design - Stage 1 Censored 8 (28%) • Evaluate the combination of elraglusib and GnP Median Survival 15.2
Slide 9: 1801-Part 3B: Phase 2 RCT in First-Line Metastatic PDAC
1801-Part 3B: Phase 2 RCT in First-Line Metastatic PDAC Inclusion Criteria Treatment Endpoints ≥ 18 yrs old with metastatic Primary endpoints: pancreatic adenocarcinoma 1 year OS/mOS 2:1 Elraglusib + GnP Randomization Secondary endpoints: Participants must have Follow Up ORR, DOR, PFS measurable dis
Slide 10: PDAC: A Disease with Urgent Unmet Needs
9 PDAC: A Disease with Urgent Unmet Needs • Most patients with PDAC present with advanced or metastatic disease with poor survival • Median survival remains <1 year, with real world data for mOS ranging from 6-9 months • Apart from PARP inhibitors as maintenance therapy in a subset of patients with
Slide 11: Study 1801 Part 3B RCT Patient Demographics
Study 1801 Part 3B RCT Patient Demographics Demographics GnP (n=78) Elraglusib + GnP (n=155) Demographics GnP (n=78) Elraglusib + GnP (n=155) Sex Eastern Cooperative Oncology Group Performance Status Female 35 (44.9%) 75 (48.4%) 0 31 (39.7%) 64 (41.3%) Male 43 (55.1%) 80 (51.6%) 1 45 (57.7%) 89 (57.
Slide 12: Study 1801 Part 3B Meets Primary Endpoint of Improved Survival
Study 1801 Part 3B Meets Primary Endpoint of Improved Survival Doubling of 1 year OS and 37% Reduction in Risk of Death vs GnP GnP Elraglusib/GnP (n=78) (n=155) Primary Endpoint: mOS (months) 7.2 10.1 HR=0.63; log-rank p=0.01 12-month OS (%) 22.3 44.1 p=0.0005 Kaplan- Meier Estimate Events (% events
Slide 13: Durable and Sustained Responses Observed Relative to GnP
Durable and Sustained Responses Observed Relative to GnP GnP + weekly elraglusib: n=155 (8 on treatment, 114 events) GnP : n= 78 (0 on treatment, 70 events) Predefined Safety Population Draft unaudited data as of March 27, 2025 12 The final data and results may change as the study continues through
Slide 14: Elraglusib Arm Demonstrated Strong Improvement in ORR and Depth of Response vs. GnP
Elraglusib Arm Demonstrated Strong Improvement in ORR and Depth of Response vs. GnP GnP Best Overall Response Elraglusib + GnP Best Overall Response N=59 N=111 * ** *Patient had a partial response on treatment, then was referred for a Whipple procedure and subsequently came off treatment **Patient h
Slide 15: Clinical Benefit Observed For Elraglusib + GnP Across All Subgroups Evaluated
Clinical Benefit Observed For Elraglusib + GnP Across All Subgroups Evaluated GnP, Elraglusib + GnP, Subgroup event/patients event/patients HR (95% CI) Elraglusib + GnP Better GnP Better Predefined Safety Population Draft unaudited data as of April 27, 2025 14 The final data and results may change a
Slide 16: Subgroup of Patients Treated for One Cycle - Significant Benefit in OS
Subgroup of Patients Treated for One Cycle (4 weeks) - Significant Benefit in OS Near Doubling of 1 year OS and 43% Reduction in Risk of Death vs GnP GnP Elraglusib/GnP (n=58) (n=116) Primary Endpoint: mOS (months) 8.5 12.5 HR=0.57; log-rank p=0.018 12-month OS (%) 28.3 52.5 Kaplan- Meier Estimate E
Slide 17: Patients with Liver Metastases - Significant Benefit in mOS and mPFS
Patients with Liver Metastases - Significant Benefit in mOS and mPFS 2.5X Increase in 1 Year Survival and a 38% Reduction in Risk of Death GnP Elraglusib/GnP (n=61) (n=114) Primary Endpoint: mOS (months) 6.6 8.3 HR=0.62; log-rank p=0.008 12-month OS (%) 15.2 39.2 p=0.0003* Kaplan- Meier Estimate Eve
Slide 18: Subsequent Anti-Cancer Therapy Is Balanced Between Both Arms
17 Subsequent Anti-Cancer Therapy Is Balanced Between Both Arms GnP Elraglusib/GnP (n=78) (n=155) Subsequent anti-cancer therapy (%) 37 (47.4%) 78 (50%) Systemic anti-neoplastic therapy 36 (46%) 78 (50%) FOLFIRINOX 13 (35%) 23 (28%) FOLFOX 1 (3%) 0 (0%) FOLFIRI 3 (8%) 7 (9%) GnP 3 (8%) 10 (13%) 5-FU
Slide 19: Safety Profile of Elraglusib in Combination with GnP
Safety Profile of Elraglusib in Combination with GnP Actuate 1801 Part 3B (ongoing) TEAEs of Any Grade Reported in 20% of Patients Treated with elraglusib Key Takeaways • Overall rate of a TEAE and/or an SAE observed were similar in the elraglusib + GnP-treated patients as compared to GnP-treated p
Slide 20: mPDAC Future Development and Registration Plans
mPDAC Future Development and Registration Plans • Regulatory discussions planned with FDA and EMA on registration pathway • Registration trial design to be harmonized to support approval in both the US and EU Inclusion Criteria Treatment Endpoints ≥ 18 yrs old with mPDAC Primary endpoints: mOS Parti
Slide 21: Elraglusib Has Potential in Multiple Indications with High Unmet Need
Elraglusib Has Potential in Multiple Indications with High Unmet Need MRI on prior MRI during MRI after 2 MRI after 4 therapy washout (growth) cycles (PR) cycles (CR) Actuate 1801 Part 1 evaluated elraglusib as a single agent • First objective response reported in patient treated with 5 mg/kg elragl
Slide 22: Elraglusib Oral Tablet Demonstrates Positive PK Profile
Elraglusib Oral Tablet Demonstrates Positive PK Profile Target Dose Half-life Tmax Cmax AUClast Dose-limiting Route Potency (mg/kg) (hr) (hr) (ng/mL) (hr*ng/mL) Toxicity IV N/A 10 2.63 0.0830 6,560 22,300 No Oral 250 mg 25 3.01 4.50 6,090 77,000 No (MTD) Oral 500 mg 50 7.63 6.00 9,230 137,000 Yes •
Slide 23: Elraglusib Oral Tablet Development Plan
Elraglusib Oral Tablet Development Plan Benefits Development Plan – Phase 1/2 Study in Cancer Patients • Preclinical studies show Oral Solid >95% bioavailability • Elraglusib oral dosage forms may allow potential expansion Phase 1 Daily Dose Escalation Study into pediatric and adult cancer indicatio
Slide 24: Ewing Sarcoma: Pediatric Trial Demonstrates Clinical Responses in Multiple Patients
Ewing Sarcoma: Pediatric Trial Demonstrates Clinical Responses in Multiple Patients Trial Update • Twelve patients were enrolled in Actuate-1902 and appear to have Phase 1/2 study (Actuate-1902) in pediatric metastatic, refractory Ewing and Ewing-like sarcoma and had disease cancer patients with rec
Slide 25: Elraglusib Ewing Sarcoma Development Plan
Elraglusib Ewing Sarcoma Development Plan • Actuate has been engaging with KOLs and patient advocacy groups in US and EU on Phase 2 study • Pre-IND meeting with FDA planned to discuss registration pathway • Discussions initiated and ongoing with US, EU, and UK patient advocacy groups regarding clini
Slide 26: Key Near Term Anticipated Development Plans and Milestones
Key Near Term Anticipated Development Plans and Milestones 2025 2026 mPDAC: mPDAC: mPDAC: mPDAC: FDA Meeting on FDA and EMA Meeting Initiate Global Global Registration Clinical & Registration Minutes Available Registration Trial Trial - FPFD Pathway Dec Jan Mar Jun Sep Dec EWS: mPDAC: CCR mPDAC: Ini
Slide 27: Seasoned and Successful Leadership
Seasoned and Successful Leadership Experienced leadership team with demonstrated ability to develop and commercialize cancer drugs Daniel M. Schmitt – Chief Executive Officer and Founder • 30+ years of biotechnology and pharmaceutical experience across senior executive roles • Led and contributed to
Slide 28: Investment Highlights
Investment Highlights Compelling Survival Data in mPDAC Broad Therapeutic Potential in Multiple Oncology Indications Significant Commercial Potential in Major Markets Extended IP Protection Seasoned Leadership Team 27
Slide 29: Ticker: ACTU
ACTUATE THERAPEUTICS Ticker: ACTU
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