Aprea Therapeutics, Inc. · NASDAQ:APRE

Aprea Therapeutics — Investor Presentation (October 2025)

21 slides from Aprea Therapeutics's investor presentation, Oct 15, 2025

1. Slide 1: Precision Oncology Through Synthetic Lethality

   1 © 2025 Aprea Therapeutics, Inc. All Rights Reserved Precision Oncology Through Synthetic Lethality Transforming DDR Inhibition into Patient Benefit October 2025

2. Slide 2: Forward-Looking Statements

   2 © 2025 Aprea Therapeutics, Inc. All Rights Reserved Forward-Looking Statements Certain information contained in this presentation includes “forward-looking statements”, within the meaning of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 19

3. Slide 3: One Critical Pathway, Multiple Targets

   3 © 2025 Aprea Therapeutics, Inc. All Rights Reserved One Critical Pathway, Multiple Targets Li et al., Nucleic Acids Research, 2024 Undisclosed Target Precision Medicine Synthetic Lethality Aprea

4. Slide 4: Robust DDR Development Pipeline

   4 © 2025 Aprea Therapeutics, Inc. All Rights Reserved Robust DDR Development Pipeline Milestones 2024-2026 Accomplished And Anticipated Clinical Milestones 2024 2025 2026 H1 H2 H1 H2 H1 H2 ATR ATRN-119 WEE1 APR-1051 RP2D ACESOT-1051: Phase 1 – Monotherapy Dose Escalation Enrolled First Patient Compl

5. Slide 5: Strong Drug Development and Commercial Expertise

   5 © 2025 Aprea Therapeutics, Inc. All Rights Reserved Strong Drug Development and Commercial Expertise Experienced Team in Synthetic Lethality and Targeted Therapy Management Board of Directors Richard Peters, M.D., Ph.D. Chairman of the Board Oren Gilad, Ph.D. President and CEO Jean-Pierre Bizzari,

6. Slide 6: WEE1 Inhibitor: APR-1051

   6 © 2025 Aprea Therapeutics, Inc. All Rights Reserved 6 WEE1 Inhibitor: APR-1051 ACESOT-1051: Clinical Proof-Of-Concept

7. Slide 7: ACESOT-1051: Phase 1 Study Design

   7 © 2025 Aprea Therapeutics, Inc. All Rights Reserved Eligible patients ≥ 18 yo with advanced solid tumor harboring cancer-associated gene alterations CCNE1 or CCNE2 FBXW7 or PPP2R1A, KRAS-GLY12/GLY13 & TP531 USC2 regardless biomarker status. HPV+ oropharyngeal squamous cell carcinoma, HPV+ cervical

8. Slide 8: ACESOT-1051: Summary of Duration of Treatment

   8 © 2025 Aprea Therapeutics, Inc. All Rights Reserved 0 20 40 60 80 100 120 140 160 10 mg 20 mg 30 mg 50 mg 70 mg 100 mg Site Key 01 – MD Anderson Cancer Center 02 – NEXT Oncology, San Antonio 03 – NEXT Oncology, Dallas Days on treatment ACESOT-1051: Summary of Duration of Treatment (n=15) Consent w

9. Slide 9: ACESOT-1051: Early Signals of Clinical Activity

   9 © 2025 Aprea Therapeutics, Inc. All Rights Reserved ACESOT-1051: WEE1 Inhibitor, Single Agent Early Signals of Clinical Activity in Dose Escalation Study Cohort/Dose Patients with SD Tumor Shrinkage 70 mg 1 (Two Scans) (-5%, +7%) 100 mg 2 -5%; +15% Total 3 Initial clinical activity at dose levels

10. Slide 10: From Bench to Bedside #1

    10 © 2025 Aprea Therapeutics, Inc. All Rights Reserved From Bench to Bedside #1: Preclinical Activity Observed in Early Patient Outcomes Pre-clinical studies with APR-1051 Data on file APR-1051 shows single agent activity in cancer cells overexpressing Cyclin E N=7 mice per group, APR-1051, 30 mg/kg

11. Slide 11: From Bench to Bedside #2

    11 © 2025 Aprea Therapeutics, Inc. All Rights Reserved s si e s e e 100 80 0 40 20 0 0 10 20 30 HPV+ HNSCC Mouse Model Clinical Data – 70 mg Cohort From Bench to Bedside #2: Preclinical Activity Observed in Early Patient Outcomes Patient: 52-year-old Male Site: MDACC Diagnosis: HPV+ Oropharyngeal Sq

12. Slide 12: HPV+ Cancer – Collaboration with MD Anderson

    12 © 2025 Aprea Therapeutics, Inc. All Rights Reserved HPV+ Cancer – Collaboration with MD Anderson Ovarian Cancer* UMSCC47 tumor cells OVCAR3 tumor xenograft Tumor Volume (mm3 ) Vehicle Aprea ATRi 30 mg/kg QD Aprea WEE1i 30 mg/kg QD Combination – half dose, 15mg/kg each Days Post Treatment Tumor Vo

13. Slide 13: ATR Inhibitor: ATRN-119

    13 © 2025 Aprea Therapeutics, Inc. All Rights Reserved 13 ATR Inhibitor: ATRN-119 ABOYA-119: Clinical Proof-Of-Concept

14. Slide 14: ABOYA-119: Phase 1/2a Trial Design and Status

    14 © 2025 Aprea Therapeutics, Inc. All Rights Reserved ABOYA-119: Phase 1/2a Trial Design and Status Patient Population: Male or female subjects 12 years of age or older with solid tumors harboring any DDR mutation per NGS (or Merkel Cell Carcinoma). Potential Combinations • Radiation therapy • Anti

15. Slide 15: ABOYA-119: Early Signals of Clinical Activity

    15 © 2025 Aprea Therapeutics, Inc. All Rights Reserved ABOYA-119: ATR Inhibitor, Single Agent Early Signals of Clinical Activity in Dose Escalation Study Initial clinical activity: Cohort/Dose Patients with SD Tumor Shrinkage QD 50mg 1 QD 200mg 1 QD 1100mg 1 QD 1300mg 1 -10% Total 4 Cohort/Dose Pati

16. Slide 16: From Bench to Bedside: Preclinical Activity Reflected in Patient Outcomes

    16 © 2025 Aprea Therapeutics, Inc. All Rights Reserved From Bench to Bedside: Preclinical Activity Reflected in Early Patient Outcomes ATRN-119 shows single agent activity in cancer cells with ARID1A mutation 200mg Cohort -3.0 -2.5 -2.0 -1.5 -1.0 -0.5 0.0 0 20 40 60 80 100 Log10 [ATRN119] (μM) % Act

17. Slide 17: Aprea Therapeutics

    17 © 2025 Aprea Therapeutics, Inc. All Rights Reserved Aprea Therapeutics (NASDAQ: APRE)

18. Slide 18: Intellectual Property, Financial Summary & Capitalization, Investment Highlights

    18 © 2025 Aprea Therapeutics, Inc. All Rights Reserved 18 Intellectual Property Portfolio Financial Summary & Capitalization Investment Highlights

19. Slide 19: Robust Global Intellectual Property Protection

    19 © 2025 Aprea Therapeutics, Inc. All Rights Reserved Robust Global Intellectual Property Protection Family 1: Ataxia Telengiectasia and Rad3-Related (ATR) Protein Kinase Inhibitors • Macrocyclic inhibitors of ATR & methods of using them to treat various cancers, filed on Oct. 13th, 2015 • Patents

20. Slide 20: Financial Summary & Capitalization

    20 © 2025 Aprea Therapeutics, Inc. All Rights Reserved Securities Common Equivalents as of August 12, 2025 Preferred Stock (as converted) 15,596 Common Stock 1 5,825,261 Warrants: Pre-Funded Tranche A Tranche B Total 507,076 1,097,394 1,097,394 2,701,864 Options 815,723 Restricted Stock Units 31,008

21. Slide 21: Investment Highlights

    21 © 2025 Aprea Therapeutics, Inc. All Rights Reserved Financed into Q2 2026 • Achieve near term inflection points and catalysts • Evaluate optimal strategic partnerships Near term catalysts • APR-1051: Q4 2025 Safety/efficacy data; H1 2026 Complete dose escalation • ATRN-119: October 2025 RP2D ✓ Q4

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