Aprea Therapeutics, Inc. · NASDAQ:APRE

Aprea Therapeutics — Corporate Update (May 2024)

35 slides from Aprea Therapeutics's corporate update, May 14, 2024

  1. Slide 1: Precision Oncology Through Synthetic Lethality

    Precision Oncology Through Synthetic Lethality May 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 2024 2025 1Q 2Q 3Q 4Q 1Q 2Q 3Q 4Q ATR ATRN-119 Complete Dose Escalation RP2D Enroll First Patient Additional Open-Label Efficacy Data WEE1 APR-1051 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) • Inhibition of DDR leads to mitotic catastrophe and

  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

    7 © 2024 Aprea Therapeutics, Inc. All Rights Reserved ATR Inhibitor: ATRN-119 A Potentially Differentiated ATRi

  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: Reported Challenges with Other ATR Inhibitors

    9 © 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, A

  10. Slide 10: ATRN-119: Potential Best-in-Class Oral ATR Inhibitor

    10 © 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. Rou

  11. Slide 11: ATRN-119 Daily Dosing Supports Potential Continuous Tumor Suppression

    11 © 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”

  12. Slide 12: ATR Inhibitor: ATRN-119 ABOYA-119: Clinical Proof-of-Concept

    12 © 2024 Aprea Therapeutics, Inc. All Rights Reserved ATR Inhibitor: ATRN-119 ABOYA-119: Clinical Proof-of-Concept

  13. Slide 13: ABOYA-119: Phase 1/2a Study Overview

    13 © 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 Part 1 Up to 30 patients Dose escalation (8 dose levels*) 3+3 design

  14. Slide 14: ABOYA-119: Clinical Study Design

    14 © 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 ABOYA-119: Clinical Study Design MTD/RP2D

  15. Slide 15: ATRN-119 Steady State Plasma Concentrations (Cycle Day 7)

    15 © 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

  16. Slide 16: ABOYA-119: Summary of Duration of Treatment

    16 © 2024 Aprea Therapeutics, Inc. All Rights Reserved CONFIDENTIAL 30 55 112 55 25 46 57 55 188 57 53 22 0 20 40 60 80 100 120 140 160 180 200 001-001 002-002 003-003 003-004 002-005 002-006 003-007 002-008 003-009 003-010 003-011 004-012 003-013 004-014 003-015 003-016 550 mg 350 mg 200 mg 100 mg

  17. Slide 17: ABOYA-119: Summary of Related Adverse Events

    17 © 2024 Aprea Therapeutics, Inc. All Rights Reserved ABOYA-119: Summary of Related Adverse Events Update – March 12, 2024 Diarrhea Grade 1 (001- 001*, 003-003, 004-014) Vomiting Grade 1 (001-001*) Non-cardiac chest pain Grade 1 (001-001) Dehydration Grade 2 (001-001*) Decreased Appetite Grade 1 (0

  18. Slide 18: ATRN-119: Summary

    18 © 2024 Aprea Therapeutics, Inc. All Rights Reserved ATRN-119: Summary First and only macrocyclic ATR inhibitor • Differentiated from other ATR inhibitors in selectivity and toxicity profile, permitting continuous dosing • Strong tumor control observed in vivo, including in challenging genetic bac

  19. Slide 19: WEE1 Inhibitor: APR-1051

    19 © 2024 Aprea Therapeutics, Inc. All Rights Reserved WEE1 Inhibitor: APR-1051 A Potentially Differentiated Wee1i

  20. Slide 20: WEE1 – Clinically Validated Target: An Unmet Medical Need

    20 © 2024 Aprea Therapeutics, Inc. All Rights Reserved WEE1 – Clinically Validated Target: An Unmet Medical Need Phase 2 Study Indication Evaluable Patients N ORR PFS NCT03668340 2 Recurrent uterine serous carcinoma 34 29.4% 1 CR 9 PR mPFS - 6.1 PFS6 – 16 Pt (47.1%) IGNITE 3 Recurrent high-grade, se

  21. Slide 21: WEE1 Inhibitor – APR-1051 Mechanism of Action

    21 © 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

  22. Slide 22: APR-1051 Potentially Best in Class WEE1 Inhibitor

    22 © 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 1.9 APR-1051 Potentially Best in Class WEE1 Inhibitor APR-1051 Potent and Structurally Differentiated, with High Selectivity to L

  23. Slide 23: PLK1 Inhibition Reduces Cytotoxic Effects of WEE1 Inhibitors

    23 © 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 0 nM NT 675 nM 25 nM 225 nM 75 nM Phos– H2AX Control (MCM3) Phos-CDK1 300 nM APR-1051 + increasing GSK-461364 37

  24. Slide 24: APR-1051 Preclinical Data Highlight Potentially Favorable PK Properties

    24 © 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

  25. Slide 25: APR-1051 Shows Negligible Inhibition of hERG Channels

    25 © 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)

  26. Slide 26: APR-1051 Demonstrated Anti-tumor Activity In Pre-clinical Model

    26 © 2024 Aprea Therapeutics, Inc. All Rights Reserved Pre-clinical studies with APR-1051 Data on file N=7 mice per group, APR-1051, exploratory formulation - 30 mg/kg/day APR-1051 Demonstrated Potentially Compelling Anti-tumor Activity In Pre-clinical Model IND Cleared March 2024 Tumor Growth Inhib

  27. Slide 27: APR-1051 Suppresses Tumor Growth While Causing Little Effect on RBCs

    27 © 2024 Aprea Therapeutics, Inc. All Rights Reserved APR-1051 Suppresses Tumor Growth While Causing 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 Tumo

  28. Slide 28: WEE1 Inhibitor: APR-1051 ACESOT-1051: Clinical Proof-of-Concept

    28 © 2024 Aprea Therapeutics, Inc. All Rights Reserved WEE1 Inhibitor: APR-1051 ACESOT-1051: Clinical Proof-of-Concept

  29. Slide 29: ACESOT-1051: Clinical Study Overview

    29 © 2024 Aprea Therapeutics, Inc. All Rights Reserved Patients aged 18 years or older with advanced solid tumor harboring cancer-associated gene alterations CCNE1 or CCNE2 FBXW7 or PPP2R1A KRAS-GLY12 & TP53 Part 2 Dose selection optimization further evaluation of the selected 2 dose levels Up to 40

  30. Slide 30: ACESOT-1051: Clinical Study Design

    30 © 2024 Aprea Therapeutics, Inc. All Rights Reserved Up to 39 patients with advanced solid tumors harboring cancer-associated gene alterations: ACESOT-1051: Clinical Study Design Part 1 - Single-agent APR-1051 Dose Escalation Study Schema BOIN design 3-12 patients per dose level Accelerated titrat

  31. Slide 31: APR-1051: Summary

    31 © 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

  32. Slide 32: Intellectual Property Portfolio, Financial Summary & Capitalization, Investment Highlights

    32 © 2024 Aprea Therapeutics, Inc. All Rights Reserved Aprea Therapeutics (NASDAQ: APRE) Intellectual Property Portfolio Financial Summary & Capitalization Investment Highlights

  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 $32.4M as of March 31, 2024 Closed approximately $16.0M (before deducing placement agent fees and offering costs of approximately $1.3 million) from our p

  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 • 1H 2024 initiate APR-1051 Phase 1; clinical update 4Q 2024 • 2H 2024 potential efficacy ATRN-119; complete d

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