Aprea Therapeutics, Inc. · NASDAQ:APRE

Aprea Therapeutics — Corporate Update (March 2024)

35 slides from Aprea Therapeutics's corporate update, Mar 26, 2024

  1. Slide 1: Precision Oncology Through Synthetic Lethality

    Precision Oncology Through Synthetic Lethality March 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 2024-2025

    4 © 2024 Aprea Therapeutics, Inc. All Rights Reserved Robust DDR Development Pipeline Milestones 2024-2025 Anticipated Clinical Milestones 1. A Multi-Center Evaluation of WEE1 Inhibitor in Patients with Advanced Solid Tumors, APR-1051 2024 2025 1Q 2Q 3Q 4Q 1Q 2Q 3Q 4Q ATR ATRN-119 Complete Dose Esca

  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 • Single pathway loss of function is inconsequential • DNA Damage Response (DDR) allows cells to pause and self repair during replication (mitosis)

  6. Slide 6: Leadership with Strong Drug Development and Commercial Expertise

    6 © 2024 Aprea Therapeutics, Inc. All Rights Reserved Leadership with Strong Drug Development and Commercial Expertise Pioneers in Synthetic Lethality 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. Directo

  7. Slide 7: ATR Inhibitor: ATRN-119 Clinical Proof-of-Concept

    7 © 2024 Aprea Therapeutics, Inc. All Rights Reserved ATR Inhibitor: ATRN-119 Clinical Proof-of-Concept

  8. Slide 8: ATRN-119: First and Only Macrocyclic ATR Inhibitor

    8 © 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) Natur

  9. Slide 9: AR-276-01: Aprea Phase 1/2a Study Overview

    9 © 2024 Aprea Therapeutics, Inc. All Rights Reserved AR-276-01: Aprea 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 Part 1 Up to 30 patients Dose escalation (8 dose levels*) 3+3 d

  10. Slide 10: 3+3 dose escalation with once-daily dosing

    10 © 2024 Aprea Therapeutics, Inc. All Rights Reserved 3+3 dose escalation with once-daily dosing (up to 30* patients) Dose expansion (up to 30 patients) Potential indications Colorectal Prostate Gastric Endometrial Mutations Undisclosed RepliBiom biomarkers Aprea AR-276-01 Study MTD/RP2D *Planned p

  11. Slide 11: AR-276-01 Summary of Duration of Treatment Update

    11 © 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 55 112 55 25 45 57 55 175 57 52 28 0 20 40 60 80 100 120 140 160 180 200 001-001 002-002

  12. Slide 12: No ATRN-119 Related SAE or Grade 4 Adverse Events Reported

    12 © 2024 Aprea Therapeutics, Inc. All Rights Reserved No ATRN-119 Related SAE or Grade 4 Adverse Events Reported As of February 23, 2024: Seven Of Fifteen Patients Experienced AEs# Possibly/probably Related to ATRN-119 # No grade 4 AEs were observed * Resulted in treatment interruption Not all data

  13. Slide 13: ATRN-119 2024-2025 Anticipated Clinical Milestones

    13 © 2024 Aprea Therapeutics, Inc. All Rights Reserved ATRN-119 2024-2025 Anticipated Clinical Milestones Planned protocol amendment adding cohorts 7 and 8 to monotherapy dose escalation 1Q2024 Milestone Timeline Phase 1/2a – Monotherapy Dose Escalation Potential efficacy data 2H 2024 Complete Dose

  14. Slide 14: ATR Inhibitor: ATRN-119 Preclinical Proof-of-Principle

    14 © 2024 Aprea Therapeutics, Inc. All Rights Reserved ATR Inhibitor: ATRN-119 Preclinical Proof-of-Principal

  15. Slide 15: ATRN-119 Mechanism of Action

    15 © 2024 Aprea Therapeutics, Inc. All Rights Reserved ATR Inhibitor – ATRN-119 Mechanism of Action – Prevent CHK1 Phosphorylation by ATR Kinase pCHK1 – Phosphorylated Checkpoint kinase 1 Data on file No Treatment ATRN-119 Tumor Samples Pharmacodynamics - ɣH2AX (green) -9 -8 -7 -6 -5 0 20 40 60 80 1

  16. Slide 16: ATRN-119 Preclinical Profile

    16 © 2024 Aprea Therapeutics, Inc. All Rights Reserved ATRN-119 Preclinical Profile Nanomolar potency in vitro across a broad spectrum of cancer cell lines Strong tumor control observed in vivo, including in challenging genetic backgrounds N=4 female mice per group, ATRN-119 - 100 mg/kg/day P.O, ATR

  17. Slide 17: ATRN-119 + Olaparib: Regression of BRCA2-Deficient Ovarian Tumors

    17 © 2024 Aprea Therapeutics, Inc. All Rights Reserved ATRN-119 + Olaparib: Regression of BRCA2-Deficient Ovarian (HGSOC) Tumors N=6-8 mice per group, ATRN-119 - 90 mg/kg P.O BID, Olaparib - 50 mg/kg/day P.O, ATRN-119+Olaparib at the same doses and schedules. Pre-clinical studies with ATRN-119. Data

  18. Slide 18: ATR Inhibitor: ATRN-119 A Potentially Differentiated ATRi

    18 © 2024 Aprea Therapeutics, Inc. All Rights Reserved ATR Inhibitor: ATRN-119 A Potentially Differentiated ATRi

  19. Slide 19: Reported Challenges with Other ATR Inhibitors

    19 © 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,

  20. Slide 20: ATRN-119 Daily Dosing Means Continuous Tumor Reduction

    20 © 2024 Aprea Therapeutics, Inc. All Rights Reserved Tumor reduction and regrowth Continuous tumor reduction Drug “On” Drug “Off” Drug “On” ATRN-119 Daily Dosing Means Continuous Tumor Reduction Intermittent Dosing May Lead to Tumor Resistance

  21. Slide 21: Daily Dosing Is Clinically Superior Based on Other ATRi in Development

    21 © 2024 Aprea Therapeutics, Inc. All Rights Reserved Daily Dosing Is Clinically Superior Based on Other ATRi in Development Artios ATR Inhibitor: ART0380 Initial Results From Phase 1 Dose Escalation1 1ART0380-ESMO-Poster-2023 Efficacy Among Measurable Patients • Continuous – ORR 29% (2/7). One of

  22. Slide 22: ATRN-119: Potential Best-in-Class Oral ATR Inhibitor

    22 © 2024 Aprea Therapeutics, Inc. All Rights Reserved ATRN-119: Potential Best-in-Class Oral ATR Inhibitor with Structurally Differentiated Core, Backbone, and Toxicity Profile Note: ATRN-119 has not yet been tested clinically 1 ATRN-119, Phase 1/2a Clinical Study Protocol 2 Internal pre-clinical h

  23. Slide 23: WEE1 Inhibitor: APR-1051 Preclinical Proof-of-Principle

    23 © 2024 Aprea Therapeutics, Inc. All Rights Reserved WEE1 Inhibitor: APR-1051 Preclinical Proof-of-Principle

  24. Slide 24: APR-1051 Mechanism of Action

    24 © 2024 Aprea Therapeutics, Inc. All Rights Reserved WEE1 Inhibitor – APR-1051 Mechanism of Action – Prevent CDK1 Phosphorylation by WEE1 Kinase pCDK1- Phosphorylated Cyclin Dependent Kinase 1 Data on file -10 -9 -8 -7 -6 0 20 40 60 80 100 120 ATRN-1051 Log10 [ATRN1051] (M) Activity (% Displacemen

  25. Slide 25: Pre-clinical studies with APR-1051

    25 © 2024 Aprea Therapeutics, Inc. All Rights Reserved Pre-clinical studies with APR-1051 Data on file Tumor Growth Inhibition OVCAR-3 N=7 mice per group, APR-1051, exploratory formulation - 30 mg/kg/day APR-1051 Demonstrated Potentially Compelling Anti-tumor Activity IND Cleared March 2024 Vehicle

  26. Slide 26: WEE1 Inhibitor: APR-1051 A Potentially Differentiated Wee1i

    26 © 2024 Aprea Therapeutics, Inc. All Rights Reserved WEE1 Inhibitor: APR-1051 A Potentially Differentiated Wee1i

  27. Slide 27: APR-1051 Potentially Differentiated from Other WEE1 Inhibitors

    27 © 2024 Aprea Therapeutics, Inc. All Rights Reserved AstraZeneca Adavosertib (AZD-1775)1,2 Zentalis Azenosetrib (ZN-c3)1 Aprea APR-1051 On-Target IC50 (nM) WEE1 3.8 3.8 2.2 Off-Target Inhibition at 1 µM (%) PLK1 70 79 17 PLK2 101 96 33 PLK3 91 92 12 APR-1051 Potentially Differentiated from Other W

  28. Slide 28: PLK1 Inhibition Reduces Cytotoxic Effects of WEE1 Inhibitors

    28 © 2024 Aprea Therapeutics, Inc. All Rights Reserved PLK1 Inhibition Reduces Cytotoxic Effects of WEE1 Inhibitors Minimal PLK1 Co-inhibition Enables Full Therapeutic Potential APR-1051 AACR-NCI-EORTC Meeting, Poster C147, 2023 0 nM NT 675 nM 25 nM 225 nM 75 nM Phos– H2AX Control (MCM3) Phos-CDK1 3

  29. Slide 29: APR-1051 Preclinical Data Highlight Potentially Favorable PK Properties

    29 © 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

  30. Slide 30: APR-1051 Shows Negligible Inhibition of hERG Channels

    30 © 2024 Aprea Therapeutics, Inc. All Rights Reserved APR-1051 Shows Negligible Inhibition of hERG Channels AACR-NCI-EORTC Meeting, Poster C147, 2023 In vitro kinase assays IC50 Average WEE1 kinase IC50 hERG inhibition IC50 Average hERG IC50 Fold difference between kinase IC50 and hERG IC50 LanthaS

  31. Slide 31: APR-1051 Suppresses Tumor Growth While Causing Little Effect on RBCs

    31 © 2024 Aprea Therapeutics, Inc. All Rights Reserved APR-1051 Suppresses Tumor Growth While Causing Little Effect on RBCs and Body Weight Vehicle ATRN-1051, 15mg/kg PO, BID, 5 on/ 2 of 0 5 10 15 RBC (10 12 /L) Vehicle ATRN-1051, 15mg/kg PO, BID, 5 on/ 2 of 0 200 400 600 800 Retiuclocyte Count (10

  32. Slide 32: APR-1051 2024-2025 Anticipated Clinical Milestones

    32 © 2024 Aprea Therapeutics, Inc. All Rights Reserved APR-1051 2024-2025 Anticipated Clinical Milestones Milestone Timeline Phase 1 – Monotherapy Dose Escalation Enroll first patient 1H 2024 Clinical Update 4Q 2024 Open-Label Efficacy Data 2Q 2025 RP2D 2H 2025

  33. Slide 33: Strong Intellectual Property Portfolio

    33 © 2024 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

  34. Slide 34: Financial Summary & Capitalization

    34 © 2024 Aprea Therapeutics, Inc. All Rights Reserved Aprea Therapeutics (NASDAQ: APRE) Financial Summary & Capitalization Cash & Equivalents of $21.6M as of December 31, 2023 Closed approximately $16.0M (before deducing placement agent fees and offering costs of approximately $1.4 million) from ou

  35. Slide 35: Investment Highlights

    35 © 2024 Aprea Therapeutics, Inc. All Rights Reserved Financed into 3Q 2025 • Reach short term inflection points and catalysts • Evaluate optimal strategic partnerships Near term catalysts • Phase 1/2a ATRN-119 potential efficacy 2H 2024; complete dose escalation 4Q 2024 • Initiate Phase 1 for APR-

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