Aprea Therapeutics, Inc. · NASDAQ:APRE

Aprea Therapeutics — Investor Presentation (February 2023)

24 slides from Aprea Therapeutics's investor presentation, Feb 10, 2023

  1. Slide 1: Precision Oncology through Synthetic Lethality

    Precision Oncology through Synthetic Lethality February 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 t he Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended, related to our clinic al trials,

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

    3 © 2023 Aprea Therapeutics, Inc. All Rights Reserved. ▪ Clinical stage precision oncology company developing novel synthetic lethality - based therapeutics in areas of high unmet need ◊ ATRN - 119: ATR Inhibitor ◊ ATRN - W1051: WEE1 Inhibitor ◊ Undisclosed DDR Inhibitor ▪ Synthetic lethality assets

  4. Slide 4: Robust DDR Development Pipeline

    Program Target Pre - Clinical Development IND Enabling Phase 1 Notes ATRN - 119 Mono ATR Anticipated Ph1 Results by end of 2023 ATRN - 119 Combo ATR Phase 1 initiation planned 2H, 2023 Anticipated Ph1 Results by end of 2024 ATRN - W1051 WEE1 Anticipated IND submission by end of 2023 ATRN - 354 (2 ND

  5. Slide 5: ATR is the Master Regulator of DDR

    ATR is the Master Regulator of DDR ▪ Defects in DDR lead to compromised genomic instability and stalling of the replication fork ▪ ATR is activated by replication stress ▪ ATR Inhibition leads to replication fork collapse and cancer cell death ◊ Cancer cells with dysfunctional and/or dysregulated DD

  6. Slide 6: Repli-Biom Proprietary Platform and Combination Approaches

    Repli - Biom Proprietary Platform and Combination Approaches An Integrated Platform for Discovery of Novel SL Targets and Biomarkers 6 Drug response factor identification ▪ Repli - Biom platform is designed to identify factors that respond to drug treatment at the mechanistic site of drug action, th

  7. Slide 7: ATR Inhibitor

    ATRN - 119 ATR Inhibitor 7 © 2023 Aprea Therapeutics, Inc. All Rights Reserved.

  8. Slide 8: Preclinical Profile

    0 200 400 600 800 0 5 10 15 20 25 30 Tumor Volume (mm 3 ) Time (Days) 100 mg/kg n=8 ATRN - 119 Preclinical Profile ▪ Nanomolar potency in vitro across a broad spectrum of cancer cell lines ▪ Based on pre - clinical studies, strong tumor control observed in vivo , including in challenging genetic bac

  9. Slide 9: Combination with Olaparib: Regression of BRCA2-Deficient Ovarian Tumors

    ATRN - 119 + Olaparib (Lynparza®): Regression of BRCA2 - Deficient Ovarian (HGSOC) Tumors 9 Human Ovarian PDX - PARPi & ATRi Tumor Size Based on pre - clinical results to date, the combination of ATRN - 119 and PARPi has shown potentially compelling tumor growth inhibition ATRN - 119 + PARPi Inhibit

  10. Slide 10: Potentially Differentiated from Other ATR Inhibitors

    ATRN - 119 is Potentially Differentiated from Other ATR Inhibitors ▪ ATRN - 119 has shown the potential to be highly potent with high selectivity to limit off - target toxicity 10 Note: Head - to - head studies with ATRN - 119 have not been conducted (1) Atrin data reported for HCT116 - Bcl/XL cell

  11. Slide 11: Comparison of ATR Inhibitor Clinical Parameters and Toxicities

    11 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

  12. Slide 12: Daily Dosing Is Desirable

    ATRN - 119 Daily dosing Is Desirable Lack of daily dosing may contribute to formation of resistance 12 © 2023 Aprea Therapeutics, Inc. All Rights Reserved. Cancer cell proliferation Drug “On” Drug “Off” Drug “On” Cancer cell death/ decreased rate of proliferation ATRN - 119 Continuous dosing Competi

  13. Slide 13: Potential Best-in-Class Oral ATR Inhibitor

    13 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

  14. Slide 14: Phase 1/2a Clinical Trial Design

    ATRN - 119 Phase 1/2a Clinical Trial Design 14 Trial Objectives: • Primary: MTD / RP2D; safety; tolerability; PK • Secondary: ORR • Exploratory: PD; PK/PD relationships; bioavailability; predictive value of DDR biomarker Patients with advanced solid tumors with at least one DDR mutation Part 1 : Dos

  15. Slide 15: ATRN-W1051 WEE1 Inhibitor

    ATRN - W1051 WEE1 Inhibitor 15 © 2023 Aprea Therapeutics, Inc. All Rights Reserved.

  16. Slide 16: ATRN-W1051 Has Demonstrated Potentially Compelling Anti-tumor Activity

    ▪ Nanomolar anti - proliferative potency in vitro against multiple cancer cell lines ▪ Potent anti - tumor activity observed in vivo in an ovarian cancer xenograft model 0.00 200.00 400.00 600.00 800.00 1000.00 1200.00 1400.00 1600.00 1800.00 0 5 10 15 20 25 30 Tumor Volume (mm3) Days Post Treatment

  17. Slide 17: ATRN-W1051 is Potentially Differentiated from Other WEE1 Inhibitors

    ATRN - W1051 is Potentially Differentiated from Other WEE1 Inhibitors 17 © 2023 Aprea Therapeutics, Inc. All Rights Reserved. ATRN - W 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

  18. Slide 18: ATRN-W1051 Preclinical Data Highlight Potentially Favorable PK Properties

    ATRN - W1051 Preclinical Data Highlight Potentially Favorable PK Properties 18 ATRN - W1051 (1) Zentalis ZN - c3 (2) AstraZeneca AZD - 1775 (2) Dose (mg/kg/d) 10 20 40 80 20 40 80 C max , ng/mL 1219 1167 1997 5100 635 2460 4703 T max , hr 2 1 1 1 1 1 1 AUC 0 - 24 , ng*hr/mL 14211 4863 17088 39722 14

  19. Slide 19: Intellectual Property

    Intellectual Property 19 © 2022 Aprea Therapeutics, Inc. All Rights Reserved.

  20. Slide 20: Intellectual Property Portfolio

    Intellectual Property Portfolio Four issued US patents protecting lead molecule and analogs ▪ Family 1 : Ataxia Telengiectasia And Rad 3 - Related (ATR) Protein Kinase Inhibitors ‒ Macrocyclic inhibitors of ATR & methods of using them to treat various cancers, filed on Oct. 13 th , 2015 ‒ Patents gr

  21. Slide 21: Corporate Highlights & Milestones

    Corporate Highlights & Milestones 21 © 2023 Aprea Therapeutics, Inc. All Rights Reserved.

  22. Slide 22: Robust DDR Development Milestones

    2023 2024 2025 ATR ATRN - 119 Monotherapy NCT04905914 PARPi Combination WEE1 ATRN - W1051 ATR* (Second Generation) ATRN - 354 ATRN - DDRi U ndisclosed *ATR = Timeline and capital allocation will be adjusted upon clinical data from lead ATR program. Robust DDR Development Milestones © 2022 Aprea Ther

  23. Slide 23: Precision Oncology via Synthetic Lethality in Defined Patient Populations

    23 © 2023 Aprea Therapeutics, Inc. All Rights Reserved. ▪ Clinical stage precision oncology company developing novel synthetic lethality - based therapeutics in areas of high unmet need ◊ ATRN - 119: ATR Inhibitor ◊ ATRN - W1051: WEE1 Inhibitor ◊ Undisclosed DDR Inhibitor ▪ Synthetic lethality asset

  24. Slide 24: Precision Oncology through Synthetic Lethality

    Precision Oncology through Synthetic Lethality February 2023

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