Aprea Therapeutics, Inc. · NASDAQ:APRE
Aprea Therapeutics — Investor Presentation (March 2023)
25 slides from Aprea Therapeutics's investor presentation, Mar 30, 2023
Slide 1: Precision Oncology through Synthetic Lethality
Precision Oncology through Synthetic Lethality March 2023
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 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,
Slide 3: Precision Oncology via Synthetic Lethality in Defined Patient Populations
3 © 2023 Aprea Therapeutics, Inc. All Rights Reserved. ▪ Clinical stage precision oncology company developing novel synthetic lethality - based therapeutics in areas of high unmet need ◊ ATRN - 119: ATR Inhibitor ◊ ATRN - 1051: WEE1 Inhibitor ◊ Undisclosed DDR Inhibitor ▪ Synthetic lethality assets
Slide 4: Robust DDR Development Pipeline
Robust DDR Development Pipeline 1 ATRN - 354 timeline and anticipated milestones subject to data from ATRN - 119 clinical trial 4 © 2023 Aprea Therapeutics, Inc. All Rights Reserved.
Slide 5: Repli-Biom Proprietary Platform and Combination Approaches
Repli - Biom Proprietary Platform and Combination Approaches An Integrated Platform for Discovery of Novel SL Targets and Biomarkers 5 Drug response factor identification ▪ Repli - Biom platform is designed to identify factors that respond to drug treatment at the mechanistic site of drug action, th
Slide 6: ATR Inhibitor
ATRN - 119 ATR Inhibitor 6 © 2023 Aprea Therapeutics, Inc. All Rights Reserved.
Slide 7: 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 8: Preclinical Profile
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 backgrounds 8 © 2023 Aprea Therapeutics, Inc. All Rights Reserved. Pre - clinical studi
Slide 9: Combination with Olaparib: Regression of BRCA2-Deficient Ovarian Tumors
ATRN - 119 + Olaparib: Regression of BRCA2 - Deficient Ovarian (HGSOC) Tumors 9 ATRN - 119 + Olaparib Inhibits Ovarian Tumor Growth Over Time ATRN - 119 + Olaparib Shows Negligible Weight Loss Over Time © 2023 Aprea Therapeutics, Inc. All Rights Reserved. Pre - clinical studies with ATRN - 119 N=6 -
Slide 10: Potentially Differentiated from Other ATR Inhibitors
ATRN - 119 is Potentially Differentiated from Other ATR Inhibitors ▪ ATRN - 119 has shown the potential to be highly potent with high selectivity to limit off - target toxicity 10 Note: Head - to - head studies with ATRN - 119 have not been conducted (1) Atrin data reported for HCT116 - Bcl/XL cell
Slide 11: Comparison of ATR Inhibitor Clinical Parameters and 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
Slide 12: Daily Dosing Is Desirable
ATRN - 119 Daily dosing Is Desirable Lack of daily dosing may contribute to formation of resistance 12 © 2023 Aprea Therapeutics, Inc. All Rights Reserved. Cancer cell proliferation Drug “ On ” Drug “ Off ” Drug “ On ” Cancer cell death/ decreased rate of proliferation Continuous dosing Intermittent
Slide 13: Dosing and Preclinical Hematological Toxicity Profile
13 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
Slide 14: Phase 1/2a Clinical Trial
ATRN - 119 Phase 1/2a Clinical Trial 14 Trial Objectives: • Primary: MTD / RP2D; safety; tolerability; PK • Secondary: ORR • Exploratory: PD; PK/PD relationships; bioavailability; predictive value of DDR biomarkers Patients with advanced solid tumors with at least one DDR mutation Part 1 : Dose Esca
Slide 15: ATRN-1051 WEE1 Inhibitor
ATRN - 1051 WEE1 Inhibitor 15 © 2023 Aprea Therapeutics, Inc. All Rights Reserved.
Slide 16: ATRN-1051 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 (CCNE1 - amplified cell line) ATRN - 1051 Has Demonstrated Potentially Compelling Anti - tumor Activity IND filing targeted by the
Slide 17: ATRN-1051 is Potentially Differentiated from Other WEE1 Inhibitors
ATRN - 1051 is Potentially Differentiated from Other WEE1 Inhibitors 17 © 2023 Aprea Therapeutics, Inc. All Rights Reserved. ATRN - 1051 shows potential to be potent and structurally differentiated, with high selectivity to limit off - target toxicity Note: Head - to - head studies have not been con
Slide 18: ATRN-1051 Preclinical Data Highlight Potentially Favorable PK Properties
ATRN - 1051 Preclinical Data Highlight Potentially Favorable PK Properties 18 ATRN - 1051 (1) Zentalis ZN - c3 (2) AstraZeneca AZD - 1775 (2) Dose (mg/kg/d) 10 20 40 80 20 40 80 C max , ng/mL 1460 1167 1997 5100 635 2460 4703 T max , hr 2.7 1 1 1 1 1 1 AUC 0 - 24 , ng*hr/mL 16739 4863 17088 39722 14
Slide 19: Intellectual Property
Intellectual Property 19 © 2023 Aprea Therapeutics, Inc. All Rights Reserved.
Slide 20: Intellectual Property Portfolio of DDR Inhibitors
Intellectual Property Portfolio Of DDR Inhibitors Four issued US patents protecting lead molecule and analogs ▪ 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. 13 th , 2
Slide 21: Corporate Highlights & Milestones
Corporate Highlights & Milestones 21 © 2023 Aprea Therapeutics, Inc. All Rights Reserved.
Slide 22: Robust DDR Development Milestones
Robust DDR Development Milestones © 2022 Aprea Therapeutics, Inc. All Rights Reserved. 22 1 ATRN - 354 timeline and anticipated milestones subject to data from ATRN - 119 clinical trial
Slide 23: Corporate Summary and Recent Highlights
Corporate Summary and Recent Highlights 23 © 2023 Aprea Therapeutics, Inc. All Rights Reserved. Robust synthetic lethality (SL) portfolio built in - house from foundational, proprietary DNA damage repair (DDR) platform ◊ Addressing critical unmet therapeutic needs for patients with genetically defin
Slide 24: Financial Summary & Capitalization
24 © 2023 Aprea Therapeutics, Inc. All Rights Reserved. Aprea Therapeutics (NASDAQ: APRE) Financial Summary & Capitalization - Cash & Equivalents of $28.8 million as of December 31, 2022 - Closed $5.5M (gross) public offering February 2023 - Obtained non - dilutive funding via research grant from Na
Slide 25: Precision Oncology through Synthetic Lethality
Precision Oncology through Synthetic Lethality March 2023
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