Aprea Therapeutics, Inc. · NASDAQ:APRE

Aprea Therapeutics — Investor Presentation (March 2025)

34 slides from Aprea Therapeutics's investor presentation, Mar 25, 2025

  1. Slide 1: Precision Oncology Through Synthetic Lethality

    Precision Oncology Through Synthetic Lethality March 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: Aprea Therapeutics: Precision Oncology via Novel Synthetic Lethality Therapeutics

    3 © 2025 Aprea Therapeutics, Inc. All Rights Reserved Aprea Therapeutics (NASDAQ: APRE) All programs are designed to address significant unmet medical need, are potentially synergistic with other anticancer therapies, and potentially differentiated in safety and tolerability ATR – Ataxia telangiecta

  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 Complete Dose Escalation RP2D Enroll First Patient ACESOT-1051 : Phase 1 – Monothera

  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 ACESOT-1051: Clinical Proof-of-Concept

  8. Slide 8: WEE1 – Clinically Validated Target

    8 © 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

  9. Slide 9: APR-1051 Demonstrated Potentially Compelling Anti-tumor Activity

    9 © 2025 Aprea Therapeutics, Inc. All Rights Reserved APR-1051 Demonstrated Potentially Compelling Anti-tumor Activity Pre-clinical studies with APR-1051 Data on file N=7 mice per group, APR-1051, 30 mg/kg/day Preclinical Tumor Growth Inhibition OVCAR-3

  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 & TP53 USC regardless biomarker status. HPV+

  11. Slide 11: ACESOT-1051: Treatment Related Adverse Events

    11 © 2025 Aprea Therapeutics, Inc. All Rights Reserved MedDRA Preferred Term APR-1051 All dose levels N=9 Treatment related AEsa , n All Grades Grade ≥ 3b Alanine aminotransferase increased 2 1 Aspartate aminotransferase increased 2 1 Dyspepsia 1 0 Gastroesophageal reflux disease 1 0 Lymphocyte coun

  12. Slide 12: WEE1 Inhibitor: APR-1051 Potentially Differentiated Clinical Stage WEE1i

    12 © 2025 Aprea Therapeutics, Inc. All Rights Reserved WEE1 Inhibitor: APR-1051 Potentially Differentiated Clinical Stage WEE1i

  13. Slide 13: APR-1051 Potentially Best in Class WEE1 Inhibitor

    13 © 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

  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 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

  15. Slide 15: PLK1 Suppression and Sepsis-Induced Loss of Intestinal Barrier Function

    15 © 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

  16. Slide 16: PLK1 Inhibition Reduces Cytotoxic Effects of WEE1 Inhibitors

    16 © 2025 Aprea Therapeutics, Inc. All Rights Reserved PLK1 Inhibition Reduces Cytotoxic Effects of WEE1 Inhibitors 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-461

  17. Slide 17: APR-1051 Preclinical Data Highlight Potentially Favorable PK Properties

    17 © 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

  18. Slide 18: APR-1051 Shows Negligible Inhibition of hERG Channels

    18 © 2025 Aprea Therapeutics, Inc. All Rights Reserved APR-1051 Shows Negligible Inhibition of hERG Channels 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)

  19. Slide 19: APR-1051: Summary

    19 © 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

  20. Slide 20: ATR Inhibitor: ATRN-119

    20 © 2025 Aprea Therapeutics, Inc. All Rights Reserved ATR Inhibitor: ATRN-119 ABOYA-119: Clinical Proof-of-Concept

  21. Slide 21: ABOYA-119: Phase 1/2a Study Overview

    21 © 2025 Aprea Therapeutics, Inc. All Rights Reserved ABOYA-119: Phase 1/2a - Study Overview A Phase 1/2a, Open-Label, Safety, Pharmacokinetic, and Preliminary Efficacy Study of Oral ATRN-119 in Patients with Advanced Solid Tumors Objectives: Primary • Safety, MTD, RP2D • Pharmacokinetics Secondary

  22. Slide 22: ABOYA-119: Clinical Study Design

    22 © 2025 Aprea Therapeutics, Inc. All Rights Reserved Dose level 1 50 mg Dose level 2 100 mg Dose level 3 200 mg Dose level 4 350 mg Dose level 5 550 mg Dose level 6 800 mg Dose level 7 1100 mg Dose level 8 1300 mg Dose level 9 1500 mg Once-daily dosing (up to 54 patients) Twice-daily dosing (up to

  23. Slide 23: ATRN-119 Steady State Plasma Concentrations

    23 © 2025 Aprea Therapeutics, Inc. All Rights Reserved ATRN-119 Steady State Plasma Concentrations (Cycle 1 Day 7) ATRN-119 Exhibits Near-dose Proportional Exposure Following Oral Administration Dose Level mg, once daily N AUC 0-24hr (ng*h/mL) Cmax (ng/mL) Half-life (hours) Mean (SD) Mean (SD) Mean

  24. Slide 24: ABOYA-119 Summary of Duration of Treatment

    24 © 2025 Aprea Therapeutics, Inc. All Rights Reserved ABOYA-119 Summary of Duration of Treatment Data Cutoff: March 4, 2025

  25. Slide 25: ABOYA-119: Treatment Related AEs

    25 © 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=30 Treatment related AEsa , n All Grades Grade ≥ 3b Diarrhea 11 1 Fatigue 10 2 Nausea 11 0 Decreased appetite 2 0 Dehydratio

  26. Slide 26: ATR Inhibitor: ATRN-119 Potentially Differentiated Clinical Stage ATRi

    26 © 2025 Aprea Therapeutics, Inc. All Rights Reserved ATR Inhibitor: ATRN-119 Potentially Differentiated Clinical Stage ATRi

  27. Slide 27: ATRN-119: First and Only Macrocyclic ATR Inhibitor

    27 © 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

  28. Slide 28: Reported Challenges with Other ATR Inhibitors

    28 © 2025 Aprea Therapeutics, Inc. All Rights Reserved Reported Challenges with Other ATR Inhibitors First Generation Compounds Share Similar Core, Backbone, Toxicity, and Intermittent Dosing Schedule Note: Head-to-head studies with ATRN-119 have not been conducted 1 Phase I study of ATR inhibitor,

  29. Slide 29: ATRN-119 Daily Dosing Supports Potential Continuous Tumor Suppression

    29 © 2025 Aprea Therapeutics, Inc. All Rights Reserved ATRN-119 Daily Dosing Supports Potential Continuous Tumor Suppression Intermittent Dosing May Lead to Tumor Resistance Tumor reduction and regrowth Continuous tumor reduction Drug “On” Drug “Off” Drug “On”

  30. Slide 30: ATRN-119: Summary

    30 © 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 • Continuous dosing provides increased drug exposure • Strong tumor control observed in vivo, i

  31. Slide 31: Intellectual Property Portfolio, Financial Summary & Capitalization, Investment Highlights

    31 © 2025 Aprea Therapeutics, Inc. All Rights Reserved Aprea Therapeutics (NASDAQ: APRE) Intellectual Property Portfolio Financial Summary & Capitalization Investment Highlights

  32. Slide 32: Strong Intellectual Property Portfolio

    32 © 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

  33. Slide 33: Financial Summary & Capitalization

    33 © 2025 Aprea Therapeutics, Inc. All Rights Reserved Aprea Therapeutics (NASDAQ: APRE) Financial Summary & Capitalization Securities Common Equivalents as of March 25, 2025 Preferred Stock (as converted) 28,112 Common Stock 5,491,953 Warrants: Pre-Funded Tranche A Tranche B Total 507,076 1,097,394

  34. Slide 34: Investment Highlights

    34 © 2025 Aprea Therapeutics, Inc. All Rights Reserved Financed into Q1 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 Complete dos

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