Aprea Therapeutics, Inc. · NASDAQ:APRE

Aprea Therapeutics — Technical Presentation (June 2024)

25 slides from Aprea Therapeutics's technical presentation, Jun 24, 2024

Slide 1: Precision Oncology Through Synthetic Lethality
Precision Oncology Through Synthetic Lethality Aprea Therapeutics KOL Event June 24, 2024
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 the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended, related to our clinical trials, regula
Slide 3: Today’s Speakers
Today’s Speakers Key Opinion Leaders Joseph Vacca, PhD Eric Brown, PhD Aprea Management Team Oren Gilad, PhD Nadeem Mirza, MD, MPH President and CEO Chief Medical Officer 3 © 2024 Aprea Therapeutics, Inc. All Rights Reserved
Slide 4: Today’s Agenda
Today’s Agenda 9:00 – 9:05 Welcome and Introductions Dr. Oren Gilad 9:05 – 9:15 Clinical Overview: Neutropenia and Sepsis of Other WEE1 Inhibitors Dr. Nadeem Mirza 9:15 – 9:25 Aprea’s Medicinal Chemistry Design Approach to APR-1051 Development Dr. Joe Vacca 9:25 – 9:35 APR-1051: Chemistry Design Lea
Slide 5: Who We Are
Who We Are We are a biopharmaceutical company focused on developing and commercializing novel synthetic lethality-based cancer therapeutics targeting DDR pathways Our programs are Outstanding team of designed to address world-class scientific significant unmet leaders medical needs 5 © 2024 Aprea Th
Slide 6: Aprea Therapeutics (NASDAQ: APRE)
Aprea Therapeutics (NASDAQ: APRE) Precision Oncology via Novel Synthetic Lethality Therapeutics All programs address significant unmet medical need, are synergistic with other anticancer therapies, and potentially differentiated in safety and tolerability ATR Inhibitor: ATRN-119 WEE1 Inhibitor: APR-
Slide 7: Today’s Take Home Messages
Today’s Take Home Messages Potential best in class WEE1 inhibitor 01 Same target Structurally different molecule different drug 02 Similar efficacy observed High potency for WEE1 inhibition in vitro in vitro • Limited off-target inhibition of the PLK family of kinases 03 Potential higher safety •
Slide 8: Published Data Showing Other WEE1 Inhibitors Are Potent with Limited Selectivity
Published Data Showing Other WEE1 Inhibitors Are Potent with Limited Selectivity Potentially Implies Off-Target Toxicity On-Target IC50 (nM) Off-Target Inhibition at 1 µM (%) WEE1 PLK1 PLK2 PLK3 Zentalis: Azenosertib (ZN-c3)1 3.2 79 96 92 AstraZeneca: Adavosertib 3.9 70 101 91 (AZD-1775)1,2 Note: He
Slide 9: Clinical Overview: Neutropenia and Sepsis of Other WEE1 Inhibitors
Neutropenia and Sepsis of Clinical Overview: Other WEE1 Inhibitors Dr. Nadeem Mirza 9 © 2024 Aprea Therapeutics, Inc. All Rights Reserved
Slide 10: Azenosertib (ZN-c3) – Partial Clinical Hold on Three Clinical Studies
Azenosertib (ZN-c3) – Partial Clinical Hold on Three Clinical Studies • On June 18, 2024, the FDA placed 3 clinical studies of azenosertib on a partial clinical hold: • ZN-c3-001, a Phase 1 dose-escalation monotherapy study in solid tumors • ZN-c3-004 (TETON), a Phase 2 monotherapy study in USC1 • Z
Slide 11: Sepsis Has Also Been Reported With AstraZeneca’s Adavosertib
Sepsis Has Also Been Reported With Astra Zeneca’s Adavosertib Phase AEs of Interest With Treatment Tumor Type Sepsis Cases (n) Respect to Sepsis Adavosertib Phase 1 Neutropenia 40%, Grade ≥3 16% Solid tumors 1 fatal sepsis Monotherapy (25)1 FN2 4% Recurrent high grade serous Dose reduction was requi
Slide 12: PLK1 Inhibitors Are Associated with Severe Neutropenia/Sepsis in Clinical Studies
PLK1 Inhibitors Are Associated with Severe Neutropenia/Sepsis in Clinical Studies Volasertib (BI6727), a PLK1 Inhibitor, Boehringer Ingelheim Phase 1 trial1: Most common drug-related AE in schedule A2 was neutropenia (56.3%). Gr≥3 neutropenia in 13 of 20 patients (65%) treated with doses (300 and 35
Slide 13: Aprea’s Medicinal Chemistry Design Approach to APR-1051 Development
Aprea’s Medicinal Chemistry Design APR -1051 Approach to APR-1051 Development Dr. Joe Vacca 13 © 2024 Aprea Therapeutics, Inc. All Rights Reserved
Slide 14: AZD1775 and ZN-c3 Inhibit WEE1 and PLK1 Similarly
AZD1775 and ZN-c3 Inhibit WEE1 and PLK1 Similarity Asn 431 active site In WEE1 is similar Asp 194 In PLK1 site Binds to Asn 431 In WEE 1 site Similar Asp in PLK1 Small difference AZD17751 ZN-c32 WEE1 IC50 = 3.9 nM WEE1 IC50 = 3.2 nM PLK1 IC50 = 3.0 nM PLK1 = IC50 92.1 nM • AZD1775 had equal activity
Slide 15: Aprea Design – Eliminate Alcohol to Increase Selectivity and Maintain Efficacy
Aprea Design – Eliminate Alcohol to Increase Selectivity and Maintain Efficacy Compound 36* APR-1051 general scaffold WEE1 IC50 = 0.5 nM WEE1 IC50 = 1.8 nM PLK1 IC50 = 15,900 nM • Aprea decided to use a different design based on potent literature scaffolds • Eliminated the alcohol that bound to PLK1
Slide 16: APR-1051 Chemistry Design Leads to Potential Best in Class WEE1 Inhibitor
Chemistry Design Leads to Potential Best in Class APR -1051 WEE1 Inhibitor Dr. Eric Brown 16 © 2024 Aprea Therapeutics, Inc. All Rights Reserved
Slide 17: WEE1 Inhibitor APR-1051 Mechanism of Action
WEE1 Inhibitor – APR-1051 Mechanism of Action – Prevent CDK1 Phosphorylation by WEE1 Kinase Inactive Mitotic cycle pause phos-CDK1 DNA repair WEE1 Cancer cell survival active APR-1051 WEE1 Active Mitotic catastrophe inactive CDK1 Cancer cell death ATRN-1051 5 Cumulative Cell Doublings 120 4 Activity
Slide 18: APR-1051: Potentially Best-in-Class WEE1 Inhibitor
APR-1051: Potentially Best-in-Class WEE1 Inhibitor APR-1051 is a potent WEE1i that does not substantially inhibit PLK1, PLK2 or PLK3 On-target WEEi activity Off-target inhibition of PLK1, PLK2 and PLK3 WEE1 IC50 Determination PLK1 IC50 Determination PLK2 IC50 Determination PLK3 IC50 Determination 12
Slide 19: Studies Show PLK1 Suppression is Associated with Sepsis-Induced Loss of Intestinal Barrier Function
Studies Show PLK1 Suppression is Associated with Sepsis-Induced Loss of Intestinal Barrier Function 1. PLK1 protects against sepsis-induced intestinal barrier dysfunction, Cao et al, Scientific Reports (2018). 2. PLK1 protects intestinal barrier function in sepsis: A translational research, Cao et a
Slide 20: Studies Indicate That PLK1 Protects the Intestinal Barrier
Studies Indicate That PLK1 Protects the Intestinal Barrier • The intestine plays a crucial role in the pathophysiology of sepsis • Intestinal barrier prevents the entry of bacteria and toxins into the circulation • Maintenance of the intestinal barrier is critical for limiting the effects of sepsis
Slide 21: APR-1051 Suppresses Tumor Growth While Causing Little Effect on Body Weight
APR-1051 Suppresses Tumor Growth While Causing Little Effect on Body Weight OVCAR Xenograft Tumor Model in Female Nude Mice Tumor Volume (mm3) (Mean±SEM) Body Weight (g) (Mean±SEM) 1,800 25 1,600 1,400 20 Tumor Volume (mm³) Body Weight (g) 1,200 15 1,000 800 10 600 400 5 200 0 0 0 5 10 15 20 25 30 0
Slide 23: Summary
Summary Potential best in class WEE1 inhibitor 01 Same target Structurally different molecule different drug 02 Similar efficacy observed High potency for WEE1 inhibition in vitro in vitro • Limited off-target inhibition of the PLK family of kinases 03 Potential higher safety • PLK1 suppression i
Slide 24: ACESOT-1051 Single-agent APR-1051 Dose Escalation Study Schema
ACESOT-1051 Part 1 - Single-agent APR-1051 Dose Escalation Study Schema BOIN design 3-12 patients per dose level Dose level 8 Dose level 7 Dose Select two level 6 doses Up to 39 patients with Dose advanced solid tumors level 5 harboring cancer- Dose associated gene level 4 alterations: Accelerated t

Aprea Therapeutics — Technical Presentation (June 2024) on 6ix

Aprea Therapeutics — Technical Presentation (June 2024)

Slide 1: Precision Oncology Through Synthetic Lethality

Slide 2: Forward-Looking Statements

Slide 3: Today’s Speakers

Slide 4: Today’s Agenda

Slide 5: Who We Are

Slide 6: Aprea Therapeutics (NASDAQ: APRE)

Slide 7: Today’s Take Home Messages

Slide 8: Published Data Showing Other WEE1 Inhibitors Are Potent with Limited Selectivity

Slide 9: Clinical Overview: Neutropenia and Sepsis of Other WEE1 Inhibitors

Slide 10: Azenosertib (ZN-c3) – Partial Clinical Hold on Three Clinical Studies

Slide 11: Sepsis Has Also Been Reported With AstraZeneca’s Adavosertib

Slide 12: PLK1 Inhibitors Are Associated with Severe Neutropenia/Sepsis in Clinical Studies

Slide 13: Aprea’s Medicinal Chemistry Design Approach to APR-1051 Development

Slide 14: AZD1775 and ZN-c3 Inhibit WEE1 and PLK1 Similarly

Slide 15: Aprea Design – Eliminate Alcohol to Increase Selectivity and Maintain Efficacy

Slide 16: APR-1051 Chemistry Design Leads to Potential Best in Class WEE1 Inhibitor

Slide 17: WEE1 Inhibitor APR-1051 Mechanism of Action

Slide 18: APR-1051: Potentially Best-in-Class WEE1 Inhibitor

Slide 19: Studies Show PLK1 Suppression is Associated with Sepsis-Induced Loss of Intestinal Barrier Function

Slide 20: Studies Indicate That PLK1 Protects the Intestinal Barrier

Slide 21: APR-1051 Suppresses Tumor Growth While Causing Little Effect on Body Weight

Slide 22: Summary

Slide 23: Summary

Slide 24: ACESOT-1051 Single-agent APR-1051 Dose Escalation Study Schema

Slide 25: Questions? Answers.