Aprea Therapeutics, Inc. · NASDAQ:APRE

Aprea Therapeutics — Corporate Update (August 2025)

36 slides from Aprea Therapeutics's corporate update, Aug 12, 2025

  1. Slide 1: Precision Oncology Through Synthetic Lethality

    Precision Oncology Through Synthetic Lethality August 2025

  2. Slide 2: Aprea Therapeutics Opportunity to Lead SL and DDR

    2 © 2025 Aprea Therapeutics, Inc. All Rights Reserved Aprea Therapeutics Opportunity to Lead SL and DDR WEE1 Inhibitor: APR-1051 • Pre-clinical proof-of-principle: • Highly potent and selective • Minimal off-target effect • Phase 1 study – ongoing • Evidence of activity in early dose cohorts • Promi

  3. Slide 3: Forward-Looking Statements

    3 © 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

  4. Slide 4: Robust DDR Development Pipeline Milestones 2024-2026

    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 Comp

  5. Slide 5: Synthetic Lethality

    5 © 2025 Aprea Therapeutics, Inc. All Rights Reserved Synthetic Lethality • Cancer cell death only upon the loss of function of two codependent pathways • DNA Damage Response (DDR) allows cells to pause and self repair during replication (mitosis) overcoming affected pathway • Inhibition of DDR lead

  6. Slide 6: Strong Drug Development and Commercial Expertise

    6 © 2025 Aprea Therapeutics, Inc. All Rights Reserved Strong Drug Development and Commercial Expertise Leaders 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, M.D. Dir

  7. Slide 7: WEE1 Inhibitor: APR-1051

    7 © 2025 Aprea Therapeutics, Inc. All Rights Reserved WEE1 Inhibitor: APR-1051

  8. Slide 8: WEE1 Inhibitor: APR-1051 ACESOT-1051: Clinical Proof-Of-Concept

    8 © 2025 Aprea Therapeutics, Inc. All Rights Reserved 8 WEE1 Inhibitor: APR-1051 ACESOT-1051: Clinical Proof-Of-Concept

  9. Slide 9: WEE1 – Clinically Validated Target

    9 © 2025 Aprea Therapeutics, Inc. All Rights Reserved WEE1 – Clinically Validated Target Examples for Phase 2 Studies with Adavosertib as monotherapy 1 AZD-1775. AstraZeneca announced in July 2022 the discontinuation of development of AZD-1775 due to its tolerability profile 2 Phase II Study of the

  10. Slide 10: ACESOT-1051: Study Design

    10 © 2025 Aprea Therapeutics, Inc. All Rights Reserved Part 2 Dose selection optimization Up to 40 patients 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

  11. Slide 11: APR-1051 Summary of duration of treatment (n=15)

    11 © 2025 Aprea Therapeutics, Inc. All Rights Reserved 36 54 56 45 57 125 25 43 47 51 55 55 48 36 50 0 20 40 60 80 100 120 140 01-004 01-001 03-007 02-002 03-005 03-002 01-002 02-001 03-003 01-006 01-003 03-004 03-006 02-003 01-005 10 mg 20 mg 30 mg 50 mg 70 mg 100 mg Site Key 01 – MD Anderson Cance

  12. Slide 12: Treatment-related AEs in Patients Treated with APR-1051 (N=15)

    12 © 2025 Aprea Therapeutics, Inc. All Rights Reserved Treatment-related AEs in Patients Treated with APR-1051 (N=15) MedDRA Preferred Term APR-1051 All dose levels Treatment-related AEsa , n All Grades Grade ≥ 3b Alanine aminotransferase increased 3 1 c Anemia 2 1 Aspartate aminotransferase increas

  13. Slide 13: APR-1051: Potentially Differentiated WEE1 Inhibitor Pre-Clinical

    13 © 2025 Aprea Therapeutics, Inc. All Rights Reserved 13 APR-1051: Potentially Differentiated WEE1 Inhibitor Pre-Clinical

  14. Slide 14: APR-1051 Potentially Best in Class WEE1 Inhibitor

    14 © 2025 Aprea Therapeutics, Inc. All Rights Reserved APR-1051 Potentially Best in Class WEE1 Inhibitor Potent and Structurally Differentiated, with High Selectivity to Limit Off-target Toxicity AstraZeneca Adavosertib (AZD-1775) Zentalis Azenosertib (ZN-c3) Aprea APR-1051 Undisclosed

  15. Slide 15: APR-1051: Potentially Best-in-Class WEE1 Inhibitor

    15 © 2025 Aprea Therapeutics, Inc. All Rights Reserved APR-1051: Potentially Best-in-Class WEE1 Inhibitor Potent WEE1i that Does Not Substantially Inhibit PLK1, PLK2 or PLK3 -10 -9 -8 -7 -6 -5 -4 0 25 50 75 100 125 PLK1 IC50 Determination Log10 [conc] (M) % Activity ZN-c3 APR-1051 -10 -9 -8 -7 -6 -5

  16. Slide 16: Studies Show PLK1 Suppression is Associated with Sepsis-Induced Loss of Intestinal Barrier Function

    16 © 2025 Aprea Therapeutics, Inc. All Rights Reserved Studies Show PLK1 Suppression is Associated with Sepsis-Induced Loss of Intestinal Barrier Function 1 PLK1 protects against sepsis-induced intestinal barrier dysfunction, Cao et al, Scientific Reports (2018). 2 PLK1 protects intestinal barrier f

  17. Slide 17: PLK1 Inhibition Reduces Cytotoxic Effects of WEE1 Inhibitors

    17 © 2025 Aprea Therapeutics, Inc. All Rights Reserved PLK1 Inhibition Reduces Cytotoxic Effects of WEE1 Inhibitors1 Minimal PLK1 Co-inhibition Enables Full Therapeutic Potential Of APR-1051 37 nM 111 nM 333 nM 1 µM 37 nM 111 nM 333 nM 1 µM Phos-H2AX Control (MCM3) NT Phos-CDK1 APR-1051 75 nM GSK-46

  18. Slide 18: APR-1051 Preclinical Data Highlight Potentially Favorable PK Properties

    18 © 2025 Aprea Therapeutics, Inc. All Rights Reserved APR-1051 Preclinical Data Highlight Potentially Favorable PK Properties Note: Head-to-head studies have not been conducted 1 Data from an exploratory formulation of APR-1051 administered to fasted Balb/c mice 2 Data from study in A-427 NSCLC xen

  19. Slide 19: APR-1051 Shows Negligible Inhibition of hERG Channels

    19 © 2025 Aprea Therapeutics, Inc. All Rights Reserved APR-1051 Shows Negligible Inhibition of hERG Channels1 In vitro kinase assays IC50 Average WEE1 kinase IC50 hERG inhibition IC50 Average hERG IC50 Fold difference between kinase IC50 and hERG IC50 LanthaScreen (Thermo) Hotspot (Reaction Biology)

  20. Slide 20: APR-1051 Demonstrates Anti-Proliferative Results in HPV+ HNSCC

    20 © 2025 Aprea Therapeutics, Inc. All Rights Reserved APR-1051 Demonstrates Anti-Proliferative Results in HPV+ Head and Neck Squamous Cell Carcinoma (HNSCC) Under Collaboration with MD Anderson Cancer Center • Potent single-agent activity: APR-1051 demonstrated robust antiproliferative effects acro

  21. Slide 21: APR-1051: Summary

    21 © 2025 Aprea Therapeutics, Inc. All Rights Reserved APR-1051: Summary Potential best in class WEE1 inhibitor • High potency for WEE1 inhibition in vitro​ • Low off-target inhibition of the LK family of kinases​ • Suppresses growth of CCNE1-amplified HGSOC xenografted tumors and relatively well-to

  22. Slide 22: ATR Inhibitor: ATRN-119

    22 © 2025 Aprea Therapeutics, Inc. All Rights Reserved ATR Inhibitor: ATRN- 119

  23. Slide 23: ATR Inhibitor: ATRN-119 ABOYA-119: Clinical Proof-Of-Concept

    23 © 2025 Aprea Therapeutics, Inc. All Rights Reserved 23 ATR Inhibitor: ATRN-119 ABOYA-119: Clinical Proof-Of-Concept

  24. Slide 24: ABOYA-119: Study Overview

    24 © 2025 Aprea Therapeutics, Inc. All Rights Reserved ABOYA-119: Study Overview A Phase 1/2a, Open-Label, Safety, Pharmacokinetic, and Preliminary Efficacy Study of Oral ATRN-119 in Patients with Advanced Solid Tumors Part 1 Up to patients​ Dose escalation ​ ( dose levels)​ 3+3 design​ Primary obje

  25. Slide 25: ABOYA-119: Current Dose Escalation

    25 © 2025 Aprea Therapeutics, Inc. All Rights Reserved ABOYA-119: Current Dose Escalation 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). ❖ Single agent ATRN-119 after MTD/RP2D is determined ❖ Poten

  26. Slide 26: ABOYA-119: ATR Inhibitor, Single Agent Key Highlights

    26 © 2025 Aprea Therapeutics, Inc. All Rights Reserved ABOYA-119: ATR Inhibitor, Single Agent Key Highlights Encouraging Early Signals of Clinical Activity in Dose Escalation Study Optimized Twice-Daily (BID) Regimen: • Aprea has introduced a BID dosing schedule for ATRN-119 to maximize its activity

  27. Slide 27: ABOYA-119: Treatment-related AEs

    27 © 2025 Aprea Therapeutics, Inc. All Rights Reserved ABOYA-119: Treatment-related AEs (in ≥ 2 patients and/or any Grade ≥ 3) MedDRA Preferred Term ATRN-119, All dose levels N=38 Treatment related AEsa , n All Grades Grade ≥ 3b Diarrhea 22 2 Nausea 14 0 Fatigue 12 2 Vomiting 7 0 Transaminases incre

  28. Slide 28: ATRN-119: Potentially Differentiated ATR Inhibitor

    28 © 2025 Aprea Therapeutics, Inc. All Rights Reserved 28 ATRN-119: Potentially Differentiated ATR Inhibitor

  29. Slide 29: ATRN-119: First and Only Macrocyclic ATR Inhibitor

    29 © 2025 Aprea Therapeutics, Inc. All Rights Reserved ATRN-119: First and Only Macrocyclic ATR Inhibitor1 Macrocycles: A Well-Evolved Approach for PIK-Related Kinase Inhibition (e.g., rapamycin and mTOR)2-4 1 Based on company knowledge 2 Brown, EJ et al, (1994) Nature 3 Brown, EJ et al, (1995) Natu

  30. Slide 30: Reported Challenges with Other ATR Inhibitors

    30 © 2025 Aprea Therapeutics, Inc. All Rights Reserved Reported Challenges with Other ATR Inhibitors First Generation Compounds Share Similar Core, Backbone and Associated Toxicity Note: Head-to-head studies with ATRN-119 have not been conducted 1 Phase I study of ATR inhibitor, AZD6738, as monother

  31. Slide 31: ATRN-119: Summary

    31 © 2025 Aprea Therapeutics, Inc. All Rights Reserved ATRN-119: Summary First and only macrocyclic ATR inhibitor • Potentially differentiated from other ATR inhibitors in selectivity and toxicity profile • Strong tumor control observed in vivo, including in challenging genetic backgrounds ABOYA-119

  32. Slide 32: Aprea Therapeutics

    32 © 2025 Aprea Therapeutics, Inc. All Rights Reserved Aprea Therapeutics (NASDAQ: APRE)

  33. Slide 33: Intellectual Property Portfolio, Financial Summary & Capitalization, Investment Highlights

    33 © 2025 Aprea Therapeutics, Inc. All Rights Reserved 33 Intellectual Property Portfolio Financial Summary & Capitalization Investment Highlights

  34. Slide 34: Strong Intellectual Property Portfolio

    34 © 2025 Aprea Therapeutics, Inc. All Rights Reserved Strong Intellectual Property Portfolio 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 granted

  35. Slide 35: Aprea Therapeutics Financial Summary & Capitalization

    35 © 2025 Aprea Therapeutics, Inc. All Rights Reserved Aprea Therapeutics (NASDAQ: APRE) Financial Summary & Capitalization 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,

  36. Slide 36: Investment Highlights

    36 © 2025 Aprea Therapeutics, Inc. All Rights Reserved Financed into Q2 2026 • Achieve short term inflection points and catalysts • Evaluate optimal strategic partnerships Near term catalysts • APR-1051: H2 2025 Safety/efficacy data ; H1 2026 Complete dose escalation • ATRN-119: H2 2025 Safety/effic

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