ATRN-119 / Aprea - LARVOL DELTA

ABOYA-119: Study Of ATRN-119 In Patients With Advanced Solid Tumors (clinicaltrials.gov) - P1/2 | N=43 | Completed | Sponsor: Aprea Therapeutics | Active, not recruiting ➔ Completed | N=132 ➔ 43 | Trial completion date: Feb 2028 ➔ Mar 2026 | Trial primary completion date: Feb 2028 ➔ Mar 2026

Enrollment change • Trial completion • Trial completion date • Trial primary completion date • Oncology • Solid Tumor

Combining Neo-adjuvant ATR-inhibition With Nodal SBRT for Early-stage Resectable HPV+ OPSCCs (clinicaltrials.gov) - P1/2 | N=35 | Not yet recruiting | Sponsor: Abramson Cancer Center at Penn Medicine | Trial completion date: May 2030 ➔ Aug 2030 | Initiation date: May 2026 ➔ Aug 2026

Trial completion date • Trial initiation date • Oncology • Oropharyngeal Cancer • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

ATRN-119 in Combination With Decitabine in Patients With TP53-Mutated AML or Higher-Risk MDS (clinicaltrials.gov) - P1 | N=27 | Not yet recruiting | Sponsor: Washington University School of Medicine

New P1 trial • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology • TP53

Combining Neo-adjuvant ATR-inhibition With Nodal SBRT for Early-stage Resectable HPV+ OPSCCs (clinicaltrials.gov) - P1/2 | N=35 | Not yet recruiting | Sponsor: John Lukens

New P1/2 trial • Oncology • Oropharyngeal Cancer • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

A first-in-class series of potent and selective macrocyclic ATR inhibitors [WITHDRAWN] (AACR 2025) - "Overall, Aprea's new class of macrocyclic ATRi represents a new class of ATRi with selectivity for inhibiting ATR over other PIKKs, has cellular activities that match biochemical and cellular inhibition of ATR, and exhibits tumor suppressive effects and a single agent and in combination with PARP inhibition. ATRN-119 is now progressing through Phase I clinical dose escalation studies."

Genito-urinary Cancer • Oncology • Ovarian Cancer • Prostate Cancer • Solid Tumor • BRCA2 • CHEK1 • PRKDC

First-in-human phase 1/2a trial of a macrocyclic ATR inhibitor (ATRN-119) in patients with advanced solid tumors (AACR 2024) - P1/2 | "In these early cohorts, once-daily oral ATRN-119 appears to be well tolerated with a manageable safety profile, exhibits near dose proportionality, and demonstrates disease stabilization warranting further investigation. Further studies to explore a twice-daily schedule are being considered."

Clinical • First-in-human • Metastases • P1/2 data • Oncology • Solid Tumor • CYP3A4 • TP53

Updated data from ABOYA-119: A phase 1/2a trial of ATRN-119, a novel macrocyclic ATR inhibitor, in patients with advanced solid tumors harboring DNA damage repair alterations (AACR-NCI-EORTC 2025) - P1/2 | "Continuous oral administration of ATRN-119 demonstrates manageable safety profile and preliminary indications of clinical activity in this ongoing trial. Updated results will be presented at the congress."

Clinical • Metastases • P1/2 data • Breast Cancer • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Gynecologic Cancers • Lung Cancer • Oncology • Pancreatic Cancer • Prostate Cancer • Solid Tumor

ABOYA-119: Study Of ATRN-119 In Patients With Advanced Solid Tumors (clinicaltrials.gov) - P1/2 | N=132 | Active, not recruiting | Sponsor: Aprea Therapeutics | Recruiting ➔ Active, not recruiting

Enrollment closed • Solid Tumor

Aprea Therapeutics…announced that two abstracts on its clinical programs, APR-1051 amd ATRN-119, have been accepted for poster presentation at the EORTC-NCI-AACR International Conference on Molecular Targets and Cancer Therapeutics… (GlobeNewswire)

Clinical data • Solid Tumor

Key Business Updates and Potential Upcoming Key Milestones (GlobeNewswire) - "Additional safety and efficacy data from ABOYA-119 are expected in the second half of 2025 and the recommended Phase 2 dose is expected to be identified in the first half of 2026."

P1 data • Solid Tumor

ABOYA-119: Ongoing Clinical Trial Evaluating ATR inhibitor, ATRN-119 (Aprea Press Release) - P1/2 | N=132 | NCT04905914 | Sponsor: Aprea Therapeutics | "Six patients have demonstrated stable disease to date, with three patients in the 550 mg twice daily cohort showing tumor shrinkage of 7%, 14% and 21%. The individual results include: A female patient with leiomyosarcoma harboring RB1/ATM mutations achieved a 21% tumor reduction at her first follow-up scan after two months of therapy; A male patient with acinar cell carcinoma of the pancreas harboring ATM mutation experienced a 14% tumor reduction at his first follow-up scan; A female patient with ovarian cancer harboring BRIP1 mutation showed a 7% tumor reduction at her first follow-up scan...these results were observed at a dose level that is below the recommended Phase 2 dose, as dose escalation continues in the trial...Preliminary safety and efficacy data from ABOYA-119 are expected in the second half of 2025 and RP2D is expected to be identified in the first half of 2026."

P1/2 data • Trial status • Solid Tumor

Select Financial Results for the Year ended December 31, 2024 (GlobeNewswire) - "R&D expenses were $9.4 million for the year ended December 31, 2024, compared to $7.6 million for the year ended December 31, 2023. The increase in R&D expense was primarily related to the ABOYA-119 clinical trial to evaluate ATRN-119, the initiation of the ACESOT-1051 clinical trial to evaluate APR-1051 and an increase in personnel costs primarily related to new hires and severance."

Commercial • Solid Tumor

ABOYA-119: Ongoing Clinical Trial Evaluating ATR inhibitor, ATRN-119 (GlobeNewswire) - "Twice daily (BID) dosing regimen in ongoing ABOYA-119 trial expected to maximize clinical benefit of ATR inhibitor ATRN-119; plan to complete dose escalation H2 2025...ATRN-119 is being evaluated in the open-label Phase 1/2a clinical trial of ABOYA-119 as monotherapy in patients with advanced solid tumors having at least one mutation in a defined panel of DDR-related genes. Patients are currently being enrolled at Dose Level 7, with both 1100 mg once daily and 550 mg twice daily doses being evaluated independently and in parallel. The addition of twice daily dosing was implemented to potentially optimize ATRN-119’s activity across a 24-hour cycle thereby providing better target coverage and maximal clinical benefit."

Trial status • Solid Tumor

ABOYA-119: Study Of ATRN-119 In Patients With Advanced Solid Tumors (clinicaltrials.gov) - P1/2 | N=132 | Recruiting | Sponsor: Aprea Therapeutics | Trial completion date: Jun 2025 ➔ Feb 2028 | Trial primary completion date: Dec 2024 ➔ Feb 2028

Trial completion date • Trial primary completion date • Oncology • Solid Tumor

Aprea Therapeutics Announces Strategic IP Portfolio Evolution in DNA Damage Response (DDR) Cancer Therapeutics (GlobeNewswire) - "Aprea’s ATR inhibitor program is protected by a strong patent estate, including four granted U.S. patents, one pending U.S. application, and one pending provisional application. There are 19 granted non-U.S. patents and 16 pending non-U.S. patent applications. The granted patents will expire 2035-2037 and the pending applications, if granted, could extend exclusivity into 2044....The Company’s lead ATR inhibitor, ATRN-119, is currently being evaluated in the ABOYA-119 clinical trial as monotherapy in patients with advanced solid tumors having at least one mutation in a defined panel of DNA damage response (DDR)-related genes." "

Patent • Solid Tumor

Aprea Therapeutics Announces Twice Daily (BID) Dosing of Patients in ABOYA-119 Clinical Trial of ATRN-119 to Potentially Optimize Clinical Outcomes and Strengthen Clinical Path Forward (GlobeNewswire) - "Aprea Therapeutics, Inc...announced today that the first patient has been dosed at Dose Level 7, evaluating ATRN-119 550 mg twice daily, in the ongoing ABOYA-119 Phase 1/2a clinical trial....A protocol amendment allows for twice daily dosing, beginning with 550 mg twice daily (for a total daily dose of 1,100 mg). This strategic dose adjustment is driven by robust scientific evidence suggesting that more frequent dosing of ATRN-119 will maintain optimal therapeutic levels and potentially enhance the drug’s efficacy....Twice daily dosing is expected to optimize ATRN-119’s activity across a 24-hour cycle thereby providing better target coverage and maximal benefit....Under the current updated protocol, Aprea anticipates the Phase 1 readout in the second half of 2025."

P1 data • Trial status • Solid Tumor

Aprea Therapeutics Reports Third Quarter 2024 Financial Results and Provides Business Update (GlobeNewswire) - "Enrollment is ongoing in the ACESOT-1051...Cohort 3 has been cleared ahead of schedule, with no safety concerns noted. Accelerated titration is complete and, in November 2024, the trial begun enrolling at Cohort 4 (50 mg) within the BOIN (Bayesian Optimal Interval) design...Preliminary efficacy data from ACESOT-1051 are expected in the first half of 2025; Under the current updated protocol, the Company anticipates the ABOYA-119 Phase 1 readout to be available in the second half of 2025; Research and development expenses for the three months ended September 30, 2024 were approximately $2.8 million, compared to approximately $2.1 million for the three months ended September 30, 2023. The overall increase was primarily due to an increase in costs related to the ABOYA-119 clinical trial to evaluate ATRN-119 and personnel costs. These were offset in part by a decrease in costs related to IND enabling studies for ATRN-1051."

Clinical data • Commercial • Trial status • Oncology • Solid Tumor

ABOYA-119: Study of ATRN-119 in Patients with Advanced Solid Tumors (clinicaltrials.gov) - P1/2 | N=132 | Recruiting | Sponsor: Aprea Therapeutics | N=45 ➔ 132

Enrollment change • Metastases • Oncology • Solid Tumor

Development and testing of a first-in-class series of macrocyclic ATR inhibitors for cancer treatment (EORTC-NCI-AACR 2024) - "Finally, in vivo studies demonstrate that ATRN-119 has broad-spectrum single-agent activity in xenografted tumors from colon and prostate cancer cell lines and suppresses the growth of BRCA2-deficient ovarian cancer PDX tumors both alone and in combination with PARP inhibition. In Conclusion, macrocyclic ATRi represent a promising new class of potent and selective ATRi with the potential to treat a wide range of cancers."

Colon Cancer • Colorectal Cancer • Genito-urinary Cancer • Oncology • Ovarian Cancer • Prostate Cancer • Solid Tumor • BRCA2 • CHEK1

ATRN-119, a Novel Macrocyclic ATR Inhibitor, in Patients with Advanced Solid Malignancies: A Phase 1/2a Trial (ABOYA-119) (EORTC-NCI-AACR 2024) - P1/2 | "Safety, PK, and efficacy data will be presented at the congress.Table 1. Genomic alterations of currently enrolled patients (n=18)Study patientCancerQualifying genomic alteration1EndometrialTP53, RB12AdrenocorticalCDK12, CDKN2A, RAD51D3ColorectalTP53, CDKN2A4PancreaticTP53, CDKN2A5AppendicealTP53, ATM6Unknown PrimaryTP53, CDKN2A7Fallopian tubeTP538ColorectalTP539DuodenalARID1A10ColonTP5311RectalTP53, CHEK212BreastCHEK213Non-small cell lung cancerTP5314ProstateCDK12, CHEK2, PALB215BreastTP53, MYC16PancreaticTP5317Neuroendocrine lungATM18OvarianARID1A"

Clinical • Metastases • P1/2 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Prostate Cancer • Solid Tumor • ARID1A • CDKN2A • CHEK2 • PALB2

Aprea Therapeutics Announces Presentations at EORTC-NCI-AACR International Conference on Molecular Targets and Therapeutics (GlobeNewswire) - "Aprea Therapeutics, Inc...today announced that four abstracts have been accepted for poster presentation at the EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics, to take place in Barcelona, Spain, October 23 - 25, 2024. Details on the posters are below."

Clinical data • Preclinical • Oncology • Solid Tumor

Aprea Therapeutics Reports Second Quarter 2024 Financial Results and Provides Business Update (GlobeNewswire) - "ATRN-119 is currently being evaluated in the open-label Phase 1/2a clinical trial of ABOYA-119 (study AR-276-01) as monotherapy in patients with advanced solid tumors having at least one mutation in a defined panel of DDR-related genes. The first five dose cohorts (50mg to 550mg once daily) have been completed, and patients continue to enroll in additional cohorts in the dose escalation part of the trial. The primary endpoint of this Phase 1 trial is the tolerability and pharmacokinetics of ATRN-119 when administered orally on a continuous, once-daily schedule. Aprea is planning to amend the study protocol to add a group of patients who will receive ATRN-119 twice a day and to investigate the effect of food on ATRN-119 absorption and drug exposure in blood. Under the current protocol, the Company anticipates the ABOYA-119 Phase 1 readout to be available in the first half of 2025."

Clinical protocol • P1 data • Trial status • Solid Tumor

Aprea Therapeutics Announces that Safety Review Committee (SRC) Endorses Dosing of Patients with ATRN-119 at 800 mg Once Daily in Ongoing ABOYA-119 Clinical Trial (GlobeNewswire) - "Aprea Therapeutics...today announced that the Safety Review Committee (SRC) overseeing the ongoing ABOYA-119 clinical trial has determined that dosing of patients with ATRN-119 at 800 mg once daily (Cohort 6) can commence and that Cohort 6 is open for enrollment. This decision follows review of the safety and pharmacokinetic data from patients treated at 550 mg once daily (Cohort 5)....ABOYA-119 is a Phase 1/2a multi-center, open-label, dose-escalation and expansion clinical trial designed to test ATRN-119 monotherapy in patients with advanced solid tumors harboring defined mutations in DDR pathways."

DSMB • Oncology • Solid Tumor

Aprea Therapeutics Reports First quarter 2024 Financial Results and Provides a Business Update (GlobeNewswire) - "ABOYA-119: ATR inhibitor, ATRN-119, on track to complete monotherapy dose escalation end of the year...Initial efficacy data from Part 1 of the study may potentially be announced in 2H 2024. At completion of Part 1, the company anticipates identification of a recommended Phase 2 dose (RP2D) that will be used in a Phase 2a cohort expansion (Part 2) to test the tolerability and potential efficacy of ATRN-119 monotherapy in approximately 30 additional patients. The Phase 1 dose escalation is expected to be completed in 4Q 2024, and RP2D is to be determined in 1Q 2025. Enrollment in the Phase 2a cohort is expected to begin in 1Q 2025 with additional efficacy data expected in 3Q 2025."

Enrollment status • P1 data • Trial status • Oncology • Solid Tumor

Aprea Therapeutics Announces Presentations on its Next Generation WEE1 Inhibitor, APR-1051, and A Novel Macrocyclic ATR Inhibitor, ATRN-119, at AACR Annual Meeting 2024 (GlobeNewswire) - P1/2a | N=45 | NCT04905914 | Sponsor: Aprea Therapeutics | "Abstract Number: CT195: This poster reports on the ongoing first-in-human Phase 1 study of ATRN-119 in patients with advanced solid tumors harboring specific DDR mutations (NCT04905914). As of March 12, 2024, 16 patients were enrolled in the first five cohorts of the dose escalation stage (50 mg/day, 100 mg/daily, 200 mg/daily, 350 mg/daily, and 550 mg/daily). ATRN-119 is being administered daily on a continuous schedule. ATRN-119 has been found to be safe and well tolerated. No reported DLTs and no treatment-related Grade 4 or higher AEs have been reported....Preliminary signs of clinical benefit have been observed. Two patients have achieved stable disease (SD) - one each in the 50 mg and 200 mg cohorts."

P1 data • Solid Tumor