Aprea Therapeutics, Inc. · NASDAQ:APRE

Aprea Therapeutics — DDR Inhibitors Summit 2023

17 slides from Aprea Therapeutics's conference presentation, Jan 26, 2023

  1. Slide 1: DDR Inhibitors Summit, January 24-26, 2023, Boston

    © 2023 Aprea Therapeutics, Inc. All Rights Reserved. 1 January 24 - 26 , 2023 | Boston, MA | ddr - inhibitors - summit.com

  2. Slide 2: Adding On to Monotherapy: Combining DDR Inhibitors

    2 Adding On to Monotherapy: Combining DDR Inhibitors January 2023

  3. Slide 3: 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,

  4. Slide 4: Combinations to combat emerging resistance: identifying combination agents

    Combinations to combat emerging resistance: identifying combination agents © 2023 Aprea Therapeutics, Inc. All Rights Reserved. 4

  5. Slide 5: Potential Benefits For Combination Therapy

    Potential Benefits For Combination Therapy: • Overcome Resistance • Increase Efficacy • Reduce Toxicity • Indication Expansion Drug Target 1 Cancer mutation Drug Target 2 SL SL SL Drug Combination SL Approach

  6. Slide 6: Combining DDR Inhibitors with PARPi: Standard of Care

    Combining DDR Inhibitors with PARPi : Standard of Care

  7. Slide 7: PARP inhibitor-based combination treatment strategies

    PARP inhibitor – based combination treatment strategies Broad categories of PARP inhibitors: combination treatment strategies © 2023 Aprea Therapeutics, Inc. All Rights Reserved. Pilié et al., Clin Cancer Res. 2019;25(13):3759 - 3771

  8. Slide 8: Comparison of PARP inhibitors under clinical development

    Comparison of PARP inhibitors under clinical development Including toxicity profile © 2023 Aprea Therapeutics, Inc. All Rights Reserved. Pilié et al., Clin Cancer Res. 2019 ; 25 ( 13 ): 3759 - 3771

  9. Slide 9: Clinical ATR inhibitors: dosing and hematological toxicity

    9 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 Q

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

    10 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

  11. Slide 11: ATRN-119 + Olaparib: Regression of BRCA2-Deficient Ovarian Tumors

    ATRN - 119 + PARPi Shows Negligible Weight Loss Over Time ATRN - 119 + PARPi Inhibits Ovarian Tumor Growth Over Time ATRN - 119 + Olaparib (Lynparza®): Regression of BRCA2 - Deficient Ovarian (HGSOC) Tumors © 2023 Aprea Therapeutics, Inc. All Rights Reserved. 11 Pre - clinical studies with ATRN - 11

  12. Slide 12: Leading WEE1i are potent but off-target PLK1, PLK2 and PLK3

    12 Leading WEE1i are potent but off - target PLK1, PLK2 and PLK3 © 2023 Aprea Therapeutics, Inc. All Rights Reserved. AZD - 1775 (1) ZN - c3 Leading WEE 1 i are potent but off - target PLK 1 , PLK 2 and PLK 3 On - Target IC 50 ( nM ) Off - Target Inhibition at 1 m M (%) WEE1 PLK1 PLK2 PLK3 ZN - c3 (

  13. Slide 13: ATRN-W1051 is potentially differentiated from other WEE1 inhibitors

    ATRN - W1051 is potentially differentiated from other WEE1 inhibitors © 2023 Aprea Therapeutics, Inc. All Rights Reserved. 13 (1) Head - to - head studies have not been conducted. (2) Huang et al, J Med Chem, 2021 On - Target IC 50 (nM) Off - Target Inhibition at 1 m M (%) WEE1 PLK1 PLK2 PLK3 ATRN -

  14. Slide 14: ATRN-W1051 inhibits OvCa cell proliferation alone and in combination

    ATRN - W1051 potently inhibits OvCa cell proliferation both alone and in combination © 2023 Aprea Therapeutics, Inc. All Rights Reserved. 14 -3 -2 -1 0 1 2 3 4 5 6 0 2 4 6 Days Post Initial Treatment ATRN - W1051 (125nM) + low - dose ATRN - 119 ( ATRi ) in OVCAR8 Vehicle ATRN - 119 ATRN - W1051 Comb

  15. Slide 15: ATRN-W1051 has potentially compelling PK and anti-tumor activity

    ATRN - W1051 has potentially compelling PK and anti - tumor activity © 2023 Aprea Therapeutics, Inc. All Rights Reserved. 15 1. Head - to - head studies have not been conducted. 2. Data from study in normal mice 3. Data from study in A - 427 NSCLC xenograft model as reported in Zentalis Corporate Ov

  16. Slide 16: Summary

    Summary • Numerous ongoing trials investigating inhibitors in Synthetic Lethality and DDR as monotherapy or in combination • PARP inhibitors are approved as standard of care • Toxicity remains a major challenge in the development of new therapies as single agents and in combination • ATRN - 119 ’ s

  17. Slide 17: ATRN-119 causes recruitment of factors shown to be SL with ATRi

    ATRN - 119 causes recruitment of factors previously shown to be SL with ATRi In collaboration with Aprea Therapeutics Yap et al .. , Cancer Discov ery, 2021 Ngoi et al .. , Trends Cancer , 2021 Chen et al .. , Molecular Cancer , 2009 Wang et al .. , Oncogene , 2019 Zimmerman et al .. , Cell Report,

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