Aprea Therapeutics, Inc. · NASDAQ:APRE

Aprea Therapeutics — Investor Presentation (October 2023)

34 slides from Aprea Therapeutics's investor presentation, Oct 13, 2023

  1. Slide 1: Precision Oncology Through Synthetic Lethality

    Precision Oncology Through Synthetic Lethality October 2023

  2. Slide 2: Forward-Looking Statements

    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 1934, as amended, related to our clinical trials, regula

  3. Slide 3: Precision Oncology via Synthetic Lethality in Defined Patient Populations

    © 2023 Aprea Therapeutics, Inc. All Rights Reserved. 3 Aprea Therapeutics (NASDAQ: APRE) Precision Oncology via Synthetic Lethality in Defined Patient Populations ▪ Clinical stage precision medicine via novel synthetic lethality (SL) - based therapeutics ▪ All programs addressing significant unmet m

  4. Slide 4: WEE1 Inhibitor ATRN-1051 and DDR Inhibitor Programs

    © 2023 Aprea Therapeutics, Inc. All Rights Reserved. 4 Aprea Therapeutics (NASDAQ: APRE) Precision Oncology via Synthetic Lethality in Defined Patient Populations ▪ WEE1 Inhibitor: ATRN-1051 ◊ IND enabling studies ◊ Anticipate submitting an IND by the end of 2023 ◊ Pre-clinical proof-of-principle ◊

  5. Slide 5: Experienced Leadership

    Experienced Leadership © 2023 Aprea Therapeutics, Inc. All Rights Reserved. 5 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. Director Marc Duey Director Michael Grissinger Director Gabriela Gruia, M.D. Dir

  6. Slide 6: ATR Inhibitor: ATRN-119

    ATR Inhibitor : ATRN-119 © 2023 Aprea Therapeutics, Inc. All Rights Reserved Confidential. 6

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

    Clinical Proof-Of-Concept © 2023 Aprea Therapeutics, Inc. All Rights Reserved. 7 ATR Inhibitor : ATRN-119

  8. Slide 8: Aprea Phase 1/2a AR-276-01 Study Overview

    © 2023 Aprea Therapeutics, Inc. All Rights Reserved. 8 Aprea Phase 1/2a - AR-276-01 - Study Overview AR-276-01: A PHASE 1/2a, OPEN-LABEL, SAFETY, PHARMACOKINETIC, AND PRELIMINARY EFFICACY STUDY OF ORAL ATRN-119 IN PATIENTS WITH ADVANCED SOLID TUMORS Sites: 4 US sites for dose escalation ❖University

  9. Slide 9: AR-276-01 Study Overview, Continued

    © 2023 Aprea Therapeutics, Inc. All Rights Reserved. 9 Aprea AR-276-01 Study Overview, Continued Part 1 (up to 18 patients) Dose escalation (6 dose levels) 3+3 design Part 2 (up to 30 patients) Dose expansion, after MTD / RP2D established Primary objectives: • Safety, MTD, RP2D • Pharmacokinetics (P

  10. Slide 10: AR-276-01 Study Overview, Dose Escalation Levels

    © 2023 Aprea Therapeutics, Inc. All Rights Reserved. 10 Aprea AR-276-01 Study Overview, Continued 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 3+3 dose escalation with once-daily dosing (up to 18 patients) Potential indication

  11. Slide 11: Summary of Duration of Treatment as of Sept 22, 2023

    © 2023 Aprea Therapeutics, Inc. All Rights Reserved. 11 Summary of Duration of Treatment as of Sept 22, 2023 30 55 112 55 25 45 57 46 16 0 20 40 60 80 100 120 001-001 002-002 003-003 003-004 002-005 002-006 003-007 002-008 003-009 200 mg 100 mg 50 mg Site Key 001 – University of Pennsylvania 002 – M

  12. Slide 12: No ATRN-119 Related Grade 3 or 4 Adverse Events Reported

    © 2023 Aprea Therapeutics, Inc. All Rights Reserved. 12 No ATRN-119 Related Grade 3 or 4 Adverse Events Reported Not all data source verified Related AEs Diarrhea, Grade 1 (001-001*, 003-003) Vomiting, Grade 1 (001-001*) Non-cardiac chest pain, Grade 1 (001-001) Dehydration, Grade 2 (001-001*) Decre

  13. Slide 13: ATRN-119 2023-2025 Anticipated Clinical Milestones

    ATRN-119 2023-2025 Anticipated Clinical Milestones Milestone Timeline Phase 1/2a – Monotherapy Dose Escalation Preliminary clinical data 4Q 2023 Last Patient Enrolled 1Q 2024 Phase 1/2a – Monotherapy Dose Expansion First Patient Enrolled 2Q 2024 Last Patient Enrolled 2Q 2025 Phase 1/2a – Combination

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

    Preclinical Proof-Of-Principal © 2023 Aprea Therapeutics, Inc. All Rights Reserved. 14 ATR Inhibitor : ATRN-119

  15. Slide 15: ATR Inhibitor ATRN-119 Mechanism of Action

    ATR Inhibitor - ATRN-119 Mechanism of Action © 2023 Aprea Therapeutics, Inc. All Rights Reserved. 15 …and triggers replication fork collapse and Double Strand Breaks ATRN-119 binds to ATR …inhibits its biological activity… Replication fork collapse + Double Strand Breaks NT NT 125 62 32 16 8 4 2 1 p

  16. Slide 16: 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 © 2023 Aprea Therapeutics, Inc. All Rights Reserved. 16 Pre-clinical studies with ATRN-119 and ATRN-157 ATRN-119 Preclinical Profile N=4 fem

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

    ATRN-119 + Olaparib: Regression of BRCA2-Deficient Ovarian (HGSOC) Tumors 17 ATRN-119 + Olaparib Inhibits Ovarian Tumor Growth Over Time ATRN-119 + Olaparib Shows Negligible Weight Loss Over Time © 2023 Aprea Therapeutics, Inc. All Rights Reserved. Pre-clinical studies with ATRN-119 N=6-8 mice per g

  18. Slide 18: Potential Differentiation ATR Inhibitor: ATRN-119

    Potential Differentiation © 2023 Aprea Therapeutics, Inc. All Rights Reserved. 18 ATR Inhibitor : ATRN-119

  19. Slide 19: Comparison of ATR Inhibitors: Route, Dosing and Toxicities

    19 Parameter AstraZeneca AZD6738 (1)(2) Bayer BAY1895344 (3) Repare / Roche(4) RP-3500 (5) Route Of Administration Oral Oral Oral Clinical Studies Chosen (MTD/RP2D), Dose Schedule 160mg BID, 2-weeks-on, 2-weeks-off, or: Continuous dosing (1) 40mg BID, 3-days-on/4-days-off 160mg QD, 3-days-on/4-days-

  20. Slide 20: ATRN-119 Daily Dosing Is Advantageous

    ATRN-119 Daily Dosing Is Advantageous Lack of daily dosing may contribute to formation of resistance © 2023 Aprea Therapeutics, Inc. All Rights Reserved. 20 Tumor reduction and regrowth Drug “On” Drug “Off” Drug “On” Continuous tumor reduction

  21. Slide 21: ATRN-119 Dosing Schedule and Preclinical Toxicology

    21 Parameter ATRN-119 (1) Route Of Administration Oral Clinical Studies Chosen (MTD/RP2D), Dose Schedule continuous once-daily dosing (dose TBD in Phase 1) (1) Hematological toxicities in preclinical studies Pre-Clinical, Toxicology Studies: • In 28-day GLP tox study in dogs, hematological changes w

  22. Slide 22: WEE1 Inhibitor: ATRN-1051 Preclinical proof-of-principle

    WEE1 Inhibitor : ATRN-1051 Preclinical proof-of-principle 22 © 2023 Aprea Therapeutics, Inc. All Rights Reserved.

  23. Slide 23: WEE1 Inhibitor ATRN-1051 Mechanism of Action

    WEE1 Inhibitor - ATRN-1051 Mechanism of Action © 2023 Aprea Therapeutics, Inc. All Rights Reserved. 23 …and triggers mitotic catastrophe and cancer cell death ATRN-1051 binds to WEE1 …inhibits its biological activity… Mitotic catastrophe + cancer cell death WEE1 active ATRN-1051 WEE1 inactive Active

  24. Slide 24: ATRN-1051 Has Demonstrated Anti-tumor Activity

    ATRN-1051 Has Demonstrated Potentially Compelling Anti-tumor Activity IND filing targeted by the end of 2023 © 2023 Aprea Therapeutics, Inc. All Rights Reserved. 24 Pre-clinical studies with ATRN-1051 N=7 mice per group, ATRN-1051, exploratory formulation - 30 mg/kg/day Data on file

  25. Slide 25: Potential Differentiation WEE1 Inhibitor: ATRN-1051

    Potential Differentiation © 2023 Aprea Therapeutics, Inc. All Rights Reserved. 25 WEE1 Inhibitor : ATRN-1051

  26. Slide 26: ATRN-1051 Potentially Differentiated from Other WEE1 Inhibitors

    ATRN-1051 is Potentially Differentiated from Other WEE1 Inhibitors © 2023 Aprea Therapeutics, Inc. All Rights Reserved. 26 ATRN-1051 shows potential to be potent and structurally differentiated, with high selectivity to limit off-target toxicity Note: Head-to-head studies have not been conducted (1)

  27. Slide 27: PLK1 Inhibition Limits Genotoxic Effects of WEE1i

    © 2023 Aprea Therapeutics, Inc. All Rights Reserved. 27 PLK1 Inhibition Limits The Genotoxic Effects of WEE1i 37 nM 111 nM 333 nM 1 µM 37 nM 111 nM 333 nM NT 1 µM 400nM BI-2536 ATRN-1051 0 nM NT 675 nM 25 nM 225 nM 75 nM pH2AX MCM3 pCDK1 300 nM ATRN-1051 + increasing GSK-461364 pH2AX MCM3 37 nM 111

  28. Slide 28: ATRN-1051 Preclinical Data Highlight Favorable PK Properties

    © 2023 Aprea Therapeutics, Inc. All Rights Reserved. 28 ATRN-1051 Preclinical Data Highlight Potentially Favorable PK Properties Note: Head-to-head studies have not been conducted (1) Data from an exploratory formulation of ATRN-1051 administered to fasted Balb/c mice (2) Data from study in A-427 NS

  29. Slide 29: ATRN-1051 Suppresses Tumor Growth With Little Effect on RBCs

    © 2023 Aprea Therapeutics, Inc. All Rights Reserved. 29 ATRN-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 (1

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

    © 2023 Aprea Therapeutics, Inc. All Rights Reserved. 30 ATRN-1051 Shows Negligible Inhibition of hERG Channels In vitro kinase assays Average WEE1 kinase IC50 hERG inhibition Average hERG IC50 Fold difference between kinase and hERG inhibition LanthaScreen (Thermo) Hotspot (Reaction Biology) 21.8 nM

  31. Slide 31: ATRN-1051 2023-2025 Anticipated Preclinical and Clinical Milestones

    ATRN-1051 2023-2025 Anticipated Preclinical and Clinical Milestones Milestone Timeline Preclinical proof-of-principle Additional differentiation data 4Q 2023 IND Submission Clearance 4Q 2023 1Q 2024 Phase 1/2a – Monotherapy Dose Escalation First Patient Enrolled 1H 2024 Last Patient Enrolled 2H 2025

  32. Slide 32: Summary

    Summary © 2023 Aprea Therapeutics, Inc. All Rights Reserved. 32

  33. Slide 33: Financial Summary & Capitalization

    ▪ Cash & Equivalents of $27.7 million as of June 30, 2023 ▪ Closed $4.9M (net) public offering in February 2023 ▪ Obtained $2.0 million non-dilutive funding via research grant from National Cancer Institute (NCI) © 2023 Aprea Therapeutics, Inc. All Rights Reserved. 33 Aprea Therapeutics (NASDAQ: APR

  34. Slide 34: Summary

    © 2023 Aprea Therapeutics, Inc. All Rights Reserved. 34 Summary ▪ Diversified portfolio with de-risked clinical and preclinical plans underway ▪ Opportunities in ovarian, CRC, prostate and breast cancers ◊ Single agent and combination therapies ▪ Supportive follow-on strategy ◊ IND submission by end

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