Aprea Therapeutics, Inc. · NASDAQ:APRE

Aprea Therapeutics — Investor Presentation (January 2023)

24 slides from Aprea Therapeutics's investor presentation, Jan 9, 2023

  1. Slide 1: Precision Oncology through Synthetic Lethality

    Precision Oncology through Synthetic Lethality January 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: Aprea Therapeutics: Precision Oncology via Synthetic Lethality

    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: 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 4 Repli - Biom to Identify Biomarkers and New Targets Drug Combination SL Approach ▪ Repli - Biom platform is designed to identify factors that respond to drug treatme

  5. Slide 5: Robust DDR Development Pipeline

    Program Target Pre - Clinical Development IND Enabling Phase 1 ATRN - 119 Mono ATR ATRN - 119 Combo ATR Phase 1 initiation planned 2H, 2023 ATRN - W1051 WEE1 ATRN - 354 (2 ND Gen) ATR* ATRN - DDRi Undisclosed *ATR = Timeline and capital allocation will be adjusted upon clinical data from lead ATR pr

  6. Slide 6: ATRN-119 ATR Inhibitor

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

  7. Slide 7: 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

  8. Slide 8: ATRN-119 is 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 8 Note: Head - to - head studies with ATRN - 119 have not been conducted (1) Atrin data reported for HCT116 - Bcl/XL cell l

  9. Slide 9: ATRN-119 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

  10. Slide 10: ATRN-119 + Olaparib: Regression of BRCA2-Deficient Ovarian Tumors

    ATRN - 119 + Olaparib (Lynparza®): Regression of BRCA2 - Deficient Ovarian (HGSOC) Tumors 10 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 Inhibi

  11. Slide 11: Clinical toxicity of other ATR inhibitors

    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: ATRN-119: Potential Best-in-Class Oral ATR Inhibitor

    12 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

  13. Slide 13: ATRN-119 Phase 1/2a Clinical Trial Design

    ATRN - 119 Phase 1/2a Clinical Trial Design 13 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

  14. Slide 14: ATRN-W1051 WEE1 Inhibitor

    ATRN - W1051 WEE1 Inhibitor 14 © 2023 Aprea Therapeutics, Inc. All Rights Reserved.

  15. Slide 15: 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

  16. Slide 16: ATRN-W1051 is Potentially Differentiated from Other WEE1 Inhibitors

    16 ATRN - W 1051 is Potentially Differentiated from Other WEE 1 Inhibitors 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 conducted ( 1 ) Huang et al, ( 2021 ) J Med Chem On

  17. Slide 17: ATRN-W1051 Preclinical Data Highlight Potentially Favorable PK Properties

    ATRN - W1051 Preclinical Data Highlight Potentially Favorable PK Properties 17 ATRN - W1051 (1) ZN - c3 (2) 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 1494 6313 13408 Tumor c

  18. Slide 18: Eprenetapopt (APR-246) p53 Reactivator

    Eprenetapopt (APR - 246) p53 Reactivator 18 © 2023 Aprea Therapeutics, Inc. All Rights Reserved.

  19. Slide 19: Eprenetapopt (APR-246) - Future Development Opportunities

    Eprenetapopt (APR - 246 ) - Future Development Opportunities ◊ Myeloid Malignancies ◊ Supportive Clinical Data: encouraging Phase 2 overall survival (OS) and relapse - free survival (RFS) data for Eprenetapopt + Azacitidine in TP 53 mutant acute myeloid leukemia (AML) and myelodysplastic syndrome (M

  20. Slide 20: Corporate Highlights & Milestones

    Corporate Highlights & Milestones 20 © 2023 Aprea Therapeutics, Inc. All Rights Reserved.

  21. Slide 21: Atrin Pharmaceuticals Acquisition

    Atrin Pharmaceuticals Acquisition ◊ Acquisition of Atrin Pharmaceuticals on May 16 , 2022 ◊ Cash and cash equivalents as of September 30 , 2022 is sufficient to fund Aprea ’ s operations through the end of 2023 ◊ Multiple assets and innovative platform technologies ◊ Primary focus on: ◊ The ATR inhi

  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: Aprea Therapeutics: Precision Oncology via Synthetic Lethality

    23 ▪ 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 potentially differentiated from competitors ▪ Innov

  24. Slide 24: Precision Oncology through Synthetic Lethality

    Precision Oncology through Synthetic Lethality January 2023

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