Aprea Therapeutics, Inc. · NASDAQ:APRE

Aprea Therapeutics — Investor Presentation (April 2024)

39 slides from Aprea Therapeutics's investor presentation, Apr 10, 2024

Slide 1: Precision Oncology Through Synthetic Lethality
Precision Oncology Through Synthetic Lethality April 2024
Slide 2: Forward-Looking Statements
2 © 2024 Aprea Therapeutics, Inc. All Rights Reserved 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 19
Slide 3: Aprea Therapeutics (NASDAQ: APRE)
3 © 2024 Aprea Therapeutics, Inc. All Rights Reserved Aprea Therapeutics (NASDAQ: APRE) All programs address significant unmet medical need, are synergistic with other anticancer therapies, and potentially differentiated in safety and tolerability ATR - Ataxia telangiectasia and Rad3‐related DDR – D
Slide 4: Robust DDR Development Pipeline Milestones 2024-2025
4 © 2024 Aprea Therapeutics, Inc. All Rights Reserved Robust DDR Development Pipeline Milestones 2024-2025 Anticipated Clinical Milestones 1. A Multi-Center Evaluation of WEE1 Inhibitor in Patients with Advanced Solid Tumors, APR-1051 2024 2025 1Q 2Q 3Q 4Q 1Q 2Q 3Q 4Q ATR ATRN-119 Complete Dose Esca
Slide 5: Synthetic Lethality
5 © 2024 Aprea Therapeutics, Inc. All Rights Reserved Synthetic Lethality • Cancer cell death only upon the loss of function of two codependent pathways • DNA Damage Response (DDR) allows cells to pause and self repair during replication (mitosis) • Inhibition of DDR leads to mitotic catastrophe and
Slide 6: Leadership with Strong Drug Development and Commercial Expertise
6 © 2024 Aprea Therapeutics, Inc. All Rights Reserved Leadership with Strong Drug Development and Commercial Expertise Pioneers in Synthetic Lethality 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. Directo
Slide 8: ATRN-119: First and Only Macrocyclic ATR Inhibitor
8 © 2024 Aprea Therapeutics, Inc. All Rights Reserved ATRN-119: First and Only Macrocyclic ATR Inhibitor1 Macrocycles: A Well-Evolved Approach for PIK-Related Kinase Inhibition (e.g., rapamycin and mTOR)2-4 1 Based on company knowledge 2 Brown, EJ et al, (1994) Nature 3 Brown, EJ et al, (1995) Natur
Slide 9: AR-276-01: Aprea Phase 1/2a - Study Overview
9 © 2024 Aprea Therapeutics, Inc. All Rights Reserved AR-276-01: Aprea Phase 1/2a - Study Overview A Phase 1/2a, Open-Label, Safety, Pharmacokinetic, and Preliminary Efficacy Study of Oral ATRN-119 in Patients with Advanced Solid Tumors Part 1 Up to 30 patients Dose escalation (8 dose levels*) 3+3 d
Slide 10: 3+3 dose escalation with once-daily dosing
10 © 2024 Aprea Therapeutics, Inc. All Rights Reserved 3+3 dose escalation with once-daily dosing (up to 30* patients) Dose expansion (up to 30 patients) Potential indications Colorectal Prostate Gastric Endometrial Mutations Undisclosed RepliBiom biomarkers Aprea AR-276-01 Study MTD/RP2D *Planned p
Slide 11: AR-276-01 Summary of Duration of Treatment Update
11 © 2024 Aprea Therapeutics, Inc. All Rights Reserved CONFIDENTIAL Site Key 001 - University of Pennsylvania 002 - Mary Crowley Cancer Research 003 - University Hospitals Cleveland Medical Center 004 - Yale Cancer Center 30 55 112 55 25 46 57 55 188 57 53 22 0 20 40 60 80 100 120 140 160 180 200 00
Slide 12: No ATRN-119 Related SAE or Grade Adverse Events Reported
12 © 2024 Aprea Therapeutics, Inc. All Rights Reserved CONFIDENTIAL No ATRN-119 Related SAE or Grade 4 Adverse Events Reported As of March 12, 2024: Ten Of Sixteen Patients Experienced AEs# Possibly/probably Related to ATRN-119 # No grade 4 AEs were observed * Resulted in treatment interruption Not
Slide 13: ATRN-119 2024-2025 Anticipated Clinical Milestones
13 © 2024 Aprea Therapeutics, Inc. All Rights Reserved ATRN-119 2024-2025 Anticipated Clinical Milestones Planned protocol amendment adding cohorts 7 and 8 to monotherapy dose escalation 1Q2024 Milestone Timeline Phase 1/2a – Monotherapy Dose Escalation Potential efficacy data 2H 2024 Complete Dose
Slide 15: ATRN-119 Mechanism of Action – Prevent CHK1 Phosphorylation by ATR Kinase
15 © 2024 Aprea Therapeutics, Inc. All Rights Reserved ATR Inhibitor – ATRN-119 Mechanism of Action – Prevent CHK1 Phosphorylation by ATR Kinase pCHK1 – Phosphorylated Checkpoint kinase 1 Data on file No Treatment ATRN-119 Tumor Samples Pharmacodynamics - ɣH2AX (green) -9 -8 -7 -6 -5 0 20 40 60 80 1
Slide 16: ATRN-119 Preclinical Profile
16 © 2024 Aprea Therapeutics, Inc. All Rights Reserved 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 N=4 female mice per group, ATRN-119 - 100 mg/kg/day P.O, ATR
Slide 17: ATRN-119 + Olaparib: Regression of BRCA2-Deficient Ovarian Tumors
17 © 2024 Aprea Therapeutics, Inc. All Rights Reserved ATRN-119 + Olaparib: Regression of BRCA2-Deficient Ovarian (HGSOC) Tumors N=6-8 mice per group, ATRN-119 - 90 mg/kg P.O BID, Olaparib - 50 mg/kg/day P.O, ATRN-119+Olaparib at the same doses and schedules. Pre-clinical studies with ATRN-119. Data
Slide 19: Reported Challenges with Other ATR Inhibitors
19 © 2024 Aprea Therapeutics, Inc. All Rights Reserved Reported Challenges with Other ATR Inhibitors First Generation Compounds Share Similar Core, Backbone, Toxicity, and Intermittent Dosing Schedule Note: Head-to-head studies with ATRN-119 have not been conducted 1 Phase I study of ATR inhibitor,
Slide 20: ATRN-119 Daily Dosing Means Continuous Tumor Reduction
20 © 2024 Aprea Therapeutics, Inc. All Rights Reserved Tumor reduction and regrowth Continuous tumor reduction Drug “On” Drug “Off” Drug “On” ATRN-119 Daily Dosing Means Continuous Tumor Reduction Intermittent Dosing May Lead to Tumor Resistance
Slide 21: Daily Dosing Is Clinically Superior Based on Other ATRi in Development
21 © 2024 Aprea Therapeutics, Inc. All Rights Reserved Daily Dosing Is Clinically Superior Based on Other ATRi in Development Artios ATR Inhibitor: ART0380 Initial Results From Phase 1 Dose Escalation1 1ART0380-ESMO-Poster-2023 Efficacy Among Measurable Patients • Continuous – ORR 29% (2/7). One of
Slide 22: ATRN-119: Potential Best-in-Class Oral ATR Inhibitor
22 © 2024 Aprea Therapeutics, Inc. All Rights Reserved ATRN-119: Potential Best-in-Class Oral ATR Inhibitor with Structurally Differentiated Core, Backbone, and Toxicity Profile Note: ATRN-119 has not yet been tested clinically 1 ATRN-119, Phase 1/2a Clinical Study Protocol 2 Internal pre-clinical h
Slide 23: WEE1 Inhibitor: APR-1051
23 © 2024 Aprea Therapeutics, Inc. All Rights Reserved WEE1 Inhibitor: APR-1051 ACESOT-1051: First-in-human phase 1 study of WEE1 inhibitor APR-1051 in patients with advanced solid tumors harboring cancer-associated gene alterations
Slide 24: APR-1051: Study Design
24 © 2024 Aprea Therapeutics, Inc. All Rights Reserved APR-1051: Study Design Multi-center, open-label Phase 1 single-agent APR-1051 dose escalation and dose selection optimization Assess the safety, pharmacokinetics, pharmacodynamics, and preliminary efficacy of single-agent APR-1051 in advanced so
Slide 25: APR-1051: Study Design – Dose Escalation Schema
25 © 2024 Aprea Therapeutics, Inc. All Rights Reserved APR-1051: Study Design Single-agent APR-1051 dose escalation study schema BOIN design 3-12 patients per dose level Accelerated titration 1-6 patients per dose level Up to 39 patients with advanced solid tumors harboring cancer-associated gene al
Slide 26: APR-1051: Study Design – Dose Selection Optimization
26 © 2024 Aprea Therapeutics, Inc. All Rights Reserved APR-1051: Study Design Single-agent APR-1051 dose selection optimization study schema & key eligibility criteria 1:1 randomization RP2D Selected dose 1 Selected dose 2 Up to 40 patients with advanced solid tumors harboring cancer-associated gene
Slide 28: APR-1051 Mechanism of Action – Prevent CDK1 Phosphorylation by WEE1 Kinase
28 © 2024 Aprea Therapeutics, Inc. All Rights Reserved WEE1 Inhibitor – APR-1051 Mechanism of Action – Prevent CDK1 Phosphorylation by WEE1 Kinase pCDK1- Phosphorylated Cyclin Dependent Kinase 1 Data on file -10 -9 -8 -7 -6 0 20 40 60 80 100 120 ATRN-1051 Log10 [ATRN1051] (M) Activity (% Displacemen
Slide 29: Pre-clinical studies with APR-1051
29 © 2024 Aprea Therapeutics, Inc. All Rights Reserved Pre-clinical studies with APR-1051 Data on file Tumor Growth Inhibition OVCAR-3 N=7 mice per group, APR-1051, exploratory formulation - 30 mg/kg/day APR-1051 Demonstrated Potentially Compelling Anti-tumor Activity IND Cleared March 2024 Vehicle
Slide 31: APR-1051 Potentially Differentiated from Other WEE1 Inhibitors
31 © 2024 Aprea Therapeutics, Inc. All Rights Reserved AstraZeneca Adavosertib (AZD-1775)1,2 Zentalis Azenosetrib (ZN-c3)1 Aprea APR-1051 On-Target IC50 (nM) WEE1 3.8 3.8 1.9 APR-1051 Potentially Differentiated from Other WEE1 Inhibitors APR-1051 Potent and Structurally Differentiated, with High Sel
Slide 32: PLK1 Inhibition Reduces Cytotoxic Effects of WEE1 Inhibitors
32 © 2024 Aprea Therapeutics, Inc. All Rights Reserved PLK1 Inhibition Reduces Cytotoxic Effects of WEE1 Inhibitors Minimal PLK1 Co-inhibition Enables Full Therapeutic Potential APR-1051 AACR-NCI-EORTC Meeting, Poster C147, 2023 0 nM NT 675 nM 25 nM 225 nM 75 nM Phos– H2AX Control (MCM3) Phos-CDK1 3
Slide 33: APR-1051 Preclinical Data Highlight Potentially Favorable PK Properties
33 © 2024 Aprea Therapeutics, Inc. All Rights Reserved APR-1051 Preclinical Data Highlight Potentially Favorable PK Properties Note: Head-to-head studies have not been conducted 1 Data from an exploratory formulation of APR-1051 administered to fasted Balb/c mice 2 Data from study in A-427 NSCLC xen
Slide 34: APR-1051 Shows Negligible Inhibition of hERG Channels
34 © 2024 Aprea Therapeutics, Inc. All Rights Reserved APR-1051 Shows Negligible Inhibition of hERG Channels AACR-NCI-EORTC Meeting, Poster C147, 2023 In vitro kinase assays IC50 Average WEE1 kinase IC50 hERG inhibition IC50 Average hERG IC50 Fold difference between kinase IC50 and hERG IC50 LanthaS
Slide 35: APR-1051 Suppresses Tumor Growth While Causing Little Effect on RBCs and Body Weight
35 © 2024 Aprea Therapeutics, Inc. All Rights Reserved APR-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 (10
Slide 36: APR-1051 2024-2025 Anticipated Clinical Milestones
36 © 2024 Aprea Therapeutics, Inc. All Rights Reserved APR-1051 2024-2025 Anticipated Clinical Milestones Milestone Timeline Phase 1 – Monotherapy Dose Escalation Enroll first patient 1H 2024 Clinical Update 4Q 2024 Open-Label Efficacy Data 2Q 2025 RP2D 2H 2025
Slide 37: Strong Intellectual Property Portfolio
37 © 2024 Aprea Therapeutics, Inc. All Rights Reserved Strong Intellectual Property Portfolio Family 1: Ataxia Telengiectasia and Rad3-Related (ATR) Protein Kinase Inhibitors • Macrocyclic inhibitors of ATR & methods of using them to treat various cancers, filed on Oct. 13th, 2015 • Patents granted
Slide 38: Financial Summary & Capitalization
38 © 2024 Aprea Therapeutics, Inc. All Rights Reserved Aprea Therapeutics (NASDAQ: APRE) Financial Summary & Capitalization Cash & Equivalents of $21.6M as of December 31, 2023 Closed approximately $16.0M (before deducing placement agent fees and offering costs of approximately $1.4 million) from ou
Slide 39: Investment Highlights
39 © 2024 Aprea Therapeutics, Inc. All Rights Reserved Financed into 3Q 2025 • Reach short term inflection points and catalysts • Evaluate optimal strategic partnerships Near term catalysts • Phase 1/2a ATRN-119 potential efficacy 2H 2024; complete dose escalation 4Q 2024 • Initiate Phase 1 for APR-

Aprea Therapeutics — Investor Presentation (April 2024) on 6ix

Aprea Therapeutics — Investor Presentation (April 2024)

Slide 1: Precision Oncology Through Synthetic Lethality

Slide 2: Forward-Looking Statements

Slide 3: Aprea Therapeutics (NASDAQ: APRE)

Slide 4: Robust DDR Development Pipeline Milestones 2024-2025

Slide 5: Synthetic Lethality

Slide 6: Leadership with Strong Drug Development and Commercial Expertise

Slide 7: ATR Inhibitor: ATRN-119 Clinical Proof-of-Concept

Slide 8: ATRN-119: First and Only Macrocyclic ATR Inhibitor

Slide 9: AR-276-01: Aprea Phase 1/2a - Study Overview

Slide 10: 3+3 dose escalation with once-daily dosing

Slide 11: AR-276-01 Summary of Duration of Treatment Update

Slide 12: No ATRN-119 Related SAE or Grade Adverse Events Reported

Slide 13: ATRN-119 2024-2025 Anticipated Clinical Milestones

Slide 14: ATR Inhibitor: ATRN-119 Preclinical Proof-of-Principal

Slide 15: ATRN-119 Mechanism of Action – Prevent CHK1 Phosphorylation by ATR Kinase

Slide 16: ATRN-119 Preclinical Profile

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

Slide 18: ATR Inhibitor: ATRN-119 A Potentially Differentiated ATRi

Slide 19: Reported Challenges with Other ATR Inhibitors

Slide 20: ATRN-119 Daily Dosing Means Continuous Tumor Reduction

Slide 21: Daily Dosing Is Clinically Superior Based on Other ATRi in Development

Slide 22: ATRN-119: Potential Best-in-Class Oral ATR Inhibitor

Slide 23: WEE1 Inhibitor: APR-1051

Slide 24: APR-1051: Study Design

Slide 25: APR-1051: Study Design – Dose Escalation Schema

Slide 26: APR-1051: Study Design – Dose Selection Optimization

Slide 27: WEE1 Inhibitor: APR-1051 Preclinical Proof-of-Principle

Slide 28: APR-1051 Mechanism of Action – Prevent CDK1 Phosphorylation by WEE1 Kinase

Slide 29: Pre-clinical studies with APR-1051

Slide 30: WEE1 Inhibitor: APR-1051 A Potentially Differentiated Wee1i

Slide 31: APR-1051 Potentially Differentiated from Other WEE1 Inhibitors

Slide 32: PLK1 Inhibition Reduces Cytotoxic Effects of WEE1 Inhibitors

Slide 33: APR-1051 Preclinical Data Highlight Potentially Favorable PK Properties

Slide 34: APR-1051 Shows Negligible Inhibition of hERG Channels

Slide 35: APR-1051 Suppresses Tumor Growth While Causing Little Effect on RBCs and Body Weight

Slide 36: APR-1051 2024-2025 Anticipated Clinical Milestones

Slide 37: Strong Intellectual Property Portfolio

Slide 38: Financial Summary & Capitalization

Slide 39: Investment Highlights