Aprea Therapeutics, Inc. · NASDAQ:APRE

Aprea Therapeutics — DDR Inhibitors Summit 2023

15 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: Understanding DDRi's in the Clinic: Why is Toxicity Such a Big Issue?

    2 Understanding DDRi’s In the Clinic: Why is Toxicity Such a Big Issue? 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: How much inhibition is needed? On Target vs Off Target Toxicological Effects

    How much inhibition is needed? On Target Vs Off Target Toxicological Effects: • Lesson learned from ATR inhibitors © 2023 Aprea Therapeutics, Inc. All Rights Reserved. 4

  5. Slide 5: Target Coverage

    Target Coverage Ngoi et al., Trends in Cancer, 2021

  6. Slide 6: ATR - On Target Toxicological Effects

    ATR - On Target Toxicological Effects E liminatinIgI ATRI inI adultI miceI leadsI toI defectsI inI tissueI homeostasisI andI theI rapidI appearanceI ofI aIge - relatedI phenotypes,I suchI asI hairI IgrayinIg,I alopecia,I kyphosis,I osteoporosis,I thymicI involution,I fibrosis,I andI otherI abnormali

  7. Slide 7: ATR - On Target Toxicological Effects: Hypomorphic Suppression Has Minimal Impact

    ATR - On Target Toxicological Effects ATRI hypomorphic suppressionI hasI aI minimalI impactI onI normalI tissueI homeostasis.I Schoppy et al. J Clin Invest 2012 research article The Journal of Clinical Investigation http://www.jci.org Volume 122 Number 1 January 2012 243 Remarkably, no significant d

  8. Slide 8: ATR - On Target Toxicological Effects: Hypomorphic Suppression Affects Tumor Growth

    ATR - On Target Toxicological Effects ATRI hypomorphic suppressionI affectsI tumorI Igrowth Schoppy et al. J Clin Invest 2012 research article The Journal of Clinical Investigation http://www.jci.org Volume 122 Number 1 January 2012 245 contrast, the appreciable genomic instability induced by comple

  9. Slide 9: Target Coverage: Daily dosing is desirable

    Target Coverage: Daily dosing is desirable 9 © 2023 Aprea Therapeutics, Inc. All Rights Reserved. •I LackI ofI dailyI dosinIgI mayI contributeI toI formationI ofI resistance •I MostI ofI theI druIgsI inI DDRI carryI aI shortI halfI life •I Assumption:I CancerI cellsI proliferateI atI anI estimatedI

  10. Slide 10: Potential Off Target Toxicological Effects

    Potential Off Target Toxicological Effects 10 Note: Hexaxd - to - hexaxd stuxdies with ATRN - 119 hxave not been conxductexd (1) Atrin xdxatxa reportexd for HCT116 - Bcl/XL cell line; (2) Foote et xal (2018), J Mexd Chem; (3) Lücking et xal (2020), J Mexd Chem; (4) Roulston et xal (2022) Mol Cxancer

  11. Slide 11: Comparison of ATR Inhibitors: Dose Schedule and Hematological 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: 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 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

  14. Slide 14: ATRN-119 + Olaparib: Regression of BRCA2-Deficient Ovarian Tumors

    ATRN - 119 + Olaparib (Lynparza®): Regression of BRCA2 - Deficient Ovarian (HGSOC) Tumors 14 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

  15. Slide 15: Summary

    Summary • Multiple DDR inhibitors have been shown to cause hematologic toxicity • However, genetic models of ATR suppression showed tumor can be targeted with limited toxicity • This leads to the hypothesis that selectivity can help limit toxicity for ATR inhibitors • ATRN - 119 shows decrease hemat

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