Aprea Therapeutics, Inc. · NASDAQ:APRE

Aprea Therapeutics — Investor Presentation (November 2024)

37 slides from Aprea Therapeutics's investor presentation, Nov 7, 2024

  1. Slide 1: Precision Oncology Through Synthetic Lethality

    Precision Oncology Through Synthetic Lethality November 2024

  2. Slide 2: Forward-Looking Statements

    2 © 2024 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 © 2024 Aprea Therapeutics, Inc. All Rights Reserved Aprea Therapeutics (NASDAQ: APRE) All programs address significant unmet medical need, are synergistic with other anticancer therapies, and potentially differentiated in safety and tolerability ATR – Ataxia telangiectasia and Rad3‐related DDR – D

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

    4 © 2024 Aprea Therapeutics, Inc. All Rights Reserved Robust DDR Development Pipeline Milestones 2024-2026 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 Additional Open-Label Efficacy Data ACESOT-1051 :

  5. Slide 5: Synthetic Lethality

    5 © 2024 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 © 2024 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 © 2024 Aprea Therapeutics, Inc. All Rights Reserved WEE1 Inhibitor: APR-1051 Potentially Differentiated Clinical Stage WEE1i

  8. Slide 8: WEE1 – Clinically Validated Target: An Unmet Medical Need

    8 © 2024 Aprea Therapeutics, Inc. All Rights Reserved WEE1 – Clinically Validated Target: An Unmet Medical Need 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

  9. Slide 9: APR-1051 Potentially Best in Class WEE1 Inhibitor

    9 © 2024 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

  10. Slide 10: APR-1051: Does Not Substantially Inhibit PLK1, PLK2 or PLK3

    10 © 2024 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

  11. Slide 11: PLK1 Suppression and Sepsis-Induced Loss of Intestinal Barrier Function

    11 © 2024 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

  12. Slide 12: PLK1 Inhibition Reduces Cytotoxic Effects of WEE1 Inhibitors

    12 © 2024 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

  13. Slide 13: APR-1051 Preclinical Data Highlight Potentially Favorable PK Properties

    13 © 2024 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

  14. Slide 14: APR-1051 Shows Negligible Inhibition of hERG Channels

    14 © 2024 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)

  15. Slide 15: APR-1051 Demonstrated Potentially Compelling Anti-tumor Activity

    15 © 2024 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

  16. Slide 16: APR-1051 Suppresses Tumor Growth with Little Effect on RBCs and Body Weight

    16 © 2024 Aprea Therapeutics, Inc. All Rights Reserved APR-1051 Suppresses Tumor Growth with Little Effect on RBCs and Body Weight Tumor Volume (mm3 ) (Mean±SEM) Body Weight (g) (Mean±SEM) APR-1051 15mg/kg, PO, BID, 5 on/2 off x 28 days Vehicle 10mL/kg, PO, QD x 28 days OVCAR Xenograft Tumor Model i

  17. Slide 17: ACESOT-1051: Clinical Proof-of-Concept

    17 © 2024 Aprea Therapeutics, Inc. All Rights Reserved WEE1 Inhibitor: APR-1051 ACESOT-1051: Clinical Proof-of-Concept

  18. Slide 18: ACESOT-1051: Clinical Study Overview

    18 © 2024 Aprea Therapeutics, Inc. All Rights Reserved ACESOT-1051: Clinical Study Overview Multi-center, Open-Label Phase1 Single-Agent Dose Escalation and Dose Selection Optimization 1 Colorectal cancer patients 2 Uterine serous carcinoma patients Patients aged 18 years or older with advanced soli

  19. Slide 19: ACESOT-1051: Study Design

    19 © 2024 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 ACESOT-1051: Study Design Part 1 Dose escalation up to 39 patients Select 2 dose levels RP2D Or

  20. Slide 20: ACESOT-1051: Summary of all-cause AEs

    20 © 2024 Aprea Therapeutics, Inc. All Rights Reserved ACESOT-1051: Summary of all-cause AEs Update - October 7, 2024 *One AE possibly related to APR-1051 AACR-NCI-EORTC Meeting, Poster B065, 2024

  21. Slide 21: APR-1051: Summary

    21 © 2024 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 PLK family of kinases​ • Suppresses growth of CCNE1-amplified HGSOC xenografted tumors and relatively well-t

  22. Slide 22: ATR Inhibitor: ATRN-119

    22 © 2024 Aprea Therapeutics, Inc. All Rights Reserved ATR Inhibitor: ATRN-119 Potentially Differentiated Clinical Stage ATRi

  23. Slide 23: ATRN-119: First and Only Macrocyclic ATR Inhibitor

    23 © 2024 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

  24. Slide 24: Reported Challenges with Other ATR Inhibitors

    24 © 2024 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,

  25. Slide 25: ATRN-119: Potential Best-in-Class Oral ATR Inhibitor

    25 © 2024 Aprea Therapeutics, Inc. All Rights Reserved ATRN-119: Potential Best-in-Class Oral ATR Inhibitor Structurally Differentiated Core, Backbone and Toxicity Profile 1 ATRN-119, Phase 1/2a Clinical Study Protocol 2 Internal pre-clinical head-to-head tolerability study in male beagle dogs Route

  26. Slide 26: ATRN-119 Daily Dosing Supports Potential Continuous Tumor Suppression

    26 © 2024 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”

  27. Slide 27: ABOYA-119: Clinical Proof-of-Concept

    27 © 2024 Aprea Therapeutics, Inc. All Rights Reserved ATR Inhibitor: ATRN-119 ABOYA-119: Clinical Proof-of-Concept

  28. Slide 28: ABOYA-119: Phase 1/2a - Study Overview

    28 © 2024 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

  29. Slide 29: ABOYA-119: Clinical Study Design

    29 © 2024 Aprea Therapeutics, Inc. All Rights Reserved ABOYA-119: Clinical Study Design 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 pa

  30. Slide 30: ATRN-119 Steady State Plasma Concentrations

    30 © 2024 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

  31. Slide 31: ABOYA-119 Summary of Duration of Treatment

    31 © 2024 Aprea Therapeutics, Inc. All Rights Reserved Site Key 001 - University of Pennsylvania 002 - Mary Crowley Cancer Research 003 - University Hospitals Cleveland Medical Center 004 - Yale Cancer Center 30 56 112 55 22 46 57 55 224 57 53 22 0 50 100 150 200 250 001-001 002-002 003-003 003-004

  32. Slide 32: ABOYA-119: Summary of Related Adverse Events

    32 © 2024 Aprea Therapeutics, Inc. All Rights Reserved ABOYA-119: Summary of Related Adverse Events Update – October 2, 2024 Not all data source verified Gastrointestinal General Metabolism Vascular No ATRN-119 Related SAE or Grade 4 Adverse Events Reported AACR-NCI-EORTC Meeting, Poster, B336 2024

  33. Slide 33: ATRN-119: Summary

    33 © 2024 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, permitting continuous dosing • Strong tumor control observed in vivo, including in challenging

  34. Slide 34: Intellectual Property Portfolio, Financial Summary & Capitalization, Investment Highlights

    34 © 2024 Aprea Therapeutics, Inc. All Rights Reserved Aprea Therapeutics (NASDAQ: APRE) Intellectual Property Portfolio Financial Summary & Capitalization Investment Highlights

  35. Slide 35: Strong Intellectual Property Portfolio

    35 © 2024 Aprea Therapeutics, Inc. All Rights Reserved Strong Intellectual Property Portfolio Four issued US patents protecting lead molecule and analogs Family 1: Ataxia Telengiectasia and Rad3-Related (ATR) Protein Kinase Inhibitors • Macrocyclic inhibitors of ATR & methods of using them to treat

  36. Slide 36: Financial Summary & Capitalization

    36 © 2024 Aprea Therapeutics, Inc. All Rights Reserved Aprea Therapeutics (NASDAQ: APRE) Financial Summary & Capitalization Securities Common Equivalents as of November 7, 2024 Preferred Stock (as converted) 28,112 Common Stock 5,434,903 Warrants: Pre-Funded Tranche A Tranche B Total 507,076 1,097,3

  37. Slide 37: Investment Highlights

    37 © 2024 Aprea Therapeutics, Inc. All Rights Reserved Financed into Q4 2025 • Achieve short term inflection points and catalysts • Evaluate optimal strategic partnerships Near term catalysts • H1 2025 open label data APR-1051; Complete dose escalation H2 2025 • H1 2025 open label data ATRN-119; Com

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