Aprea Therapeutics, Inc. · NASDAQ:APRE
Aprea Therapeutics — Investor Presentation (May 2022)
29 slides from Aprea Therapeutics's investor presentation, May 17, 2022
Slide 1: Precision Oncology Through Synthetic Lethality
Precision Oncology Through Synthetic Lethality May 2022
Slide 2: Forward-Looking Statements
Forward - Looking Statements Certain information contained in this presentation includes “ forward - looking statements ” , within the meaning of Section 27 A of the Securities Act of 1933 , as amended, and Section 21 E of the Securities Exchange Act of 1934 , as amended, related to our clinical tri
Slide 3: Aprea Acquisition of Atrin
Aprea Acquisition of Atrin 3 • Aprea Therapeutics, Inc. (NASDAQ: APRE) and Atrin Pharmaceuticals, Inc. have completed a business combination • Atrin assets targeting DNA damage repair (DDR) at the core of future development strategy • Aprea shareholders receive non - transferable CVR related to Apre
Slide 4: Corporate Highlights
Corporate Highlights Precision Oncology Via Synthetic Lethality In Defined Patient Populations 4 ▪ Robust synthetic lethality (SL) portfolio built in - house from foundational, proprietary DNA damage repair (DDR) platform ◊ Integrated discovery engine leverages three proprietary technologies to fuel
Slide 5: SL & Inhibitors of the DDR Pathway
SL & Inhibitors of the DDR Pathway 5 © 2022 Aprea Therapeutics, Inc. All Rights Reserved.
Slide 6: DDR: One Critical Pathway, Multiple Targets
Ngoi et al., Trends in Cancer, 2021 DDR: One Critical Pathway, Multiple Targets 6 © 2022 Aprea Therapeutics, Inc. All Rights Reserved. ▪ Within DDR, PARP inhibitors have validated the SL paradigm but are just the tip of the iceberg ◊ Responses to PARPi are rarely durable and resistance is acquired r
Slide 7: Integrated Discovery Engine
Integrated Discovery Engine Three proprietary integrated technologies fueling pipeline growth 7 SCET & ATRIZE: Macrocyclic drug design and rapid screening methods to increase potency, limit off - target binding and improve tolerability Cancer Repli - Biom : Proteomic and genetic methods to identify
Slide 8: Repli-Biom and Combination Approaches
Repli - Biom and Combination Approached An Integrated Platform for Discovery of Novel SL Targets and Biomarkers 8 © 2022 Aprea Therapeutics, Inc. All Rights Reserved. Repli - Biom to Identify Biomarkers and New Targets Drug Combination SL Approach ▪ Repli - Biom platform is designed to identify fact
Slide 9: ATR Inhibitor ATRN-119
ATR Inhibitor ATRN - 119 9 © 2022 Aprea Therapeutics, Inc. All Rights Reserved.
Slide 10: 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
Slide 11: ATRN-119 is Potentially Differentiated from Other ATRi
ATRN - 119 is Potentially Differentiated from Other ATRi ▪ ATRN - 119: Has shown potential to be potent and structurally differentiated, with high selectivity to limit off - target tox © 2022 Aprea Therapeutics, Inc. All Rights Reserved. 11 Note: Head - to - head studies hav e not been conducted ( 1
Slide 12: 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 ▪ Strong tumor control observed in vivo, including challenging genetic backgrounds © 2022 Aprea Therapeutics, I
Slide 13: ATRi In Combination With PARPi
ATRi In Combination With PARPi 13 Surgery Tumor “Avatars” Cell lines, genomics & proteomics Preclinical trial Transplant to mouse ovary Expand & transfer Personalized Treatments Orthotropic Patient - Derived Xenografts (PDXs) ATRN - 119 + PARPi Inhibits Ovarian Tumor Growth Over Time Human Ovarian P
Slide 14: ATR Landscape
ATR Landscape 14 Parameter AstraZeneca AZD6738 (1)(2) Bayer BAY1895344 (3) Repare RP - 3500 (4) 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 160m
Slide 15: ATRN-119: Potential Best-in-Class Oral ATR inhibitor
ATRN - 119: Potential “Best - in - Class” Oral ATR inhibitor 15 Parameter Aprea ATRN - 119 (1) Route Of Administration Oral Clinical Studies Chosen (MTD/RP2D) , Dose Schedule QD (dose TBD in Phase 1) 7 - days - on (1) Hematological toxicities in preclinical studies Pre - Clinical, Toxicology Studies
Slide 16: ATRN-119 Phase 1/2a Clinical Trial
ATRN - 119 Phase 1/2a Clinical Trial ▪ Patients ◊ Advanced solid tumors that have at least 1 DDR mutation ◊ Panel of unique potential biomarkers for increased sensitivity to ATRN - 119 have been characterized in preclinical studies ◊ IHC assay and NGS DDR Panel will be used to determine presence of
Slide 17: ATR Back-up: Second-Generation ATR Inhibitors
ATR Back - up: Second - Generation ATR Inhibitors ▪ Additional SAR improvements may have increased potency and exposure for second generation ATRi ▪ ATR backup is ready to enter IND - enabling studies © 2022 Aprea Therapeutics, Inc. All Rights Reserved. 17 IC 50 = 8.43 nM * NT 125 62 32 16 8 4 2 1 N
Slide 18: WEE1 Inhibitor ATRN-W1051
WEE 1 Inhibitor ATRN - W 1051 18 © 2022 Aprea Therapeutics, Inc. All Rights Reserved.
Slide 19: WEE1 is a Key Regulator of Mitotic Entry in the DDR Pathway
WEE1 is a Key Regulator of Mitotic Entry in the DDR Pathway WEE1 ▪ Regulates the G2 - M cell cycle checkpoint and prevents entry into mitosis in response to DNA damage ▪ About 50% of HGSOCs overexpress Cyclin E through amplification, copy number gain or transcriptional means ▪ Inhibition of WEE1 lea
Slide 20: ATRN-W1051 is Potentially Differentiated from Other WEE1 Inhibitors
ATRN - W1051 is Potentially Differentiated from Other WEE1 Inhibitors ▪ ATRN - W1051 : shows potential to be potent and structurally differentiated, with high selectivity to limit off - target tox ▪ Preclinical data highlight potentially favorable PK properties of ATRN - W1051 © 2022 Aprea Therapeut
Slide 21: 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
Slide 22: Integrated Discovery Engine
Integrated Discovery Engine Three proprietary integrated technologies fueling pipeline growth 22 SCET & ATRIZE: Macrocyclic drug design and rapid screening methods to increase potency, limit off - target binding and improve tolerability Cancer Repli - Biom : Proteomic and genetic methods to identify
Slide 23: Intellectual Property
Intellectual Property 23 © 2022 Aprea Therapeutics, Inc. All Rights Reserved.
Slide 24: Intellectual Property Portfolio
Intellectual Property Portfolio Four issued US patents protecting lead molecule and close analogs ▪ Family 1 : Ataxia Telengiectasia And Rad 3 - Related (ATR) Protein Kinase Inhibitors ‒ Macrocyclic inhibitors of ATR & methods of using them to treat various cancers, filed on Oct. 13 th , 2015 ‒ Nati
Slide 25: p53 Reactivator Eprenetapopt (APR-246)
p53 Reactivator Eprenetapopt (APR - 246) 25 © 2022 Aprea Therapeutics, Inc. All Rights Reserved.
Slide 26: Future Development Opportunity for p53 Reactivator Eprenetapopt
Future Development Opportunity for p53 Reactivator Eprenetapopt ▪ Lymphoid malignancies ◊ Lymphoid cancer cell lines are among the most sensitive to treatment with eprenetapopt ◊ Open IND and FDA accepted protocol for clinical trial evaluating eprenetapopt in late - line NHL ◊ Introduce new oral for
Slide 27: Corporate Milestones
Corporate Milestones 27 © 2022 Aprea Therapeutics, Inc. All Rights Reserved.
Slide 28: Robust DDR Development Pipeline Milestones
Robust DDR Development Pipeline Milestones 28 2021 2022 2023 2024 1Q 2Q 3Q 4Q 1Q 2Q 3Q 4Q 1Q 2Q 3Q 4Q 1Q 2Q 3Q 4Q Key Development Milestones ATR ATRN - 119 Phase 1 / 2 a Dose Escalation Phase 1 / 2 a Dose Expansion Monotherapy, NCT04905914 Phase 1/2a Dose Escalation Phase 1/2a Dose Expansion PARPi C
Slide 29: Precision Oncology Through Synthetic Lethality
Precision Oncology Through Synthetic Lethality May 2022
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