APR-1051 / Aprea - LARVOL DELTA

Aprea Therapeutics Announces Dosing of Patient with HPV+ Head and Neck Squamous Cell Carcinoma (HNSCC) in Ongoing ACESOT-1051 Trial (GlobeNewswire) - "Aprea Therapeutics, Inc...today announced that a patient with HPV+ head and neck squamous cell carcinoma (HNSCC) has been dosed in the ongoing ACESOT-1051 clinical trial evaluating APR-1051. This is the first patient to be dosed in Cohort 5 (70 mg once daily) of the study. Open label data from the study are expected in the second half of 2025....We look forward to continuing the study as we work toward identifying the optimal dose for future studies....The latest patient in ACESOT-1051 was enrolled at MD Anderson Cancer Center."

P1 data • Trial status • Squamous Cell Carcinoma of Head and Neck

Aprea Therapeutics Reports Fourth Quarter and Full Year 2024 Financial Results and Provides a Business Update (GlobeNewswire) - "ACESOT-1051 trial evaluating WEE1 kinase inhibitor APR-1051 now enrolling patients in Cohort 5; open label safety and efficacy data expected H2 2025; 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."

P1 data • Trial status • Oncology • 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

ACESOT-1051: A Biomarkers Focused, Phase 1 Trial of Oral WEE1 inhibitor, APR-1051 (GlobeNewswire) - "Patients are now being enrolled in Cohort 5 (70 mg dose) of the ACESOT-1051 (A Multi-Center Evaluation of WEE1 Inhibitor in Patients with Advanced Solid Tumors, APR-1051) trial. This Phase 1 clinical trial is evaluating single-agent APR-1051 in advanced solid tumors harboring cancer-associated gene alterations. No hematological toxicities have been observed to date....Preliminary efficacy data from ACESOT-1051 are expected in the second half of 2025."

P1 data • Trial status • Solid Tumor

Aprea Therapeutics Announces Agreement with MD Anderson Cancer Center to Explore APR-1051 as a Potential Treatment for Head and Neck Squamous Cell Carcinoma (HNSCC) (GlobeNewswire) - "Aprea Therapeutics, Inc...announced today that it has entered into a Material Transfer Agreement (MTA) with MD Anderson Cancer Center. Under the agreement, Aprea will supply its proprietary WEE1 kinase inhibitor, APR-1051, to support preclinical research aimed at exploring its potential in treating HPV+ and HPV- head and neck squamous cell carcinoma (HNSCC) expressing genomic markers of replication stress....The agreement will enable the research group at MD Anderson to conduct a series of pre-clinical experiments designed to generate preliminary efficacy and mechanistic data to support future clinical trials and treatment regimens."

Licensing / partnership • Squamous Cell Carcinoma of Head and Neck

Aprea Therapeutics Announces Strategic IP Portfolio Evolution in DNA Damage Response (DDR) Cancer Therapeutics (GlobeNewswire) - "The intellectual property covering Aprea’s WEE1 kinase inhibitor program includes one pending U.S. patent application and 12 pending non-U.S. patent applications. The WEE1 family of applications, if granted, will expire in 2043, not including any regulatory exclusivities that may be awarded. The WEE1-portfolio covers key aspects of the program, including proprietary compounds, pharmaceutical compositions, and methods of use. The Company’s lead WEE1 inhibitor, APR-1051, is currently being evaluated in the ACESOT-1051 Phase 1 clinical trial in advanced/metastatic solid tumors harboring certain cancer-associated gene alterations."

Patent • 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

The novel WEE1i, APR-1051, does not substantially off-target PLK1, PLK2, or PLK3 and exhibits favorable in vivo characteristics for treating CCNE1-overexpressing cancers (EORTC-NCI-AACR 2024) - "For comparison, similar assays were performed with a previously developed WEE1i (ZN-c3). However, APR-1051 had little impact on body weight, the loss of which is a well-known characteristic of sepsis and intestinal distress. These data imply that APR-1051's potency for WEE1 inhibition and its substantially reduced off-targeting of PLK1, PLK2, and PLK3 may decrease the risk of sepsis-related deaths and other adverse effects associated with other WEE1 inhibitors."

Preclinical • Oncology • CCNE1 • PLK1 • PLK2

Safety and Preliminary Efficacy of APR-1051, a WEE1 Inhibitor, in a Phase 1 Study of Patients with Cancer-Associated Gene Alterations (ACESOT-1051) (EORTC-NCI-AACR 2024) - P1 | "Conclusion. The study is continuing to enroll up to 79 patients at 3 sites in the United States."

Clinical • P1 data • Colorectal Cancer • Endometrial Serous Adenocarcinoma • Gastrointestinal Cancer • Genito-urinary Cancer • Oncology • Pancreatic Cancer • Prostate Cancer • Solid Tumor • Uterine Cancer • CCNE1 • CCNE2 • CTCs • FBXW7 • KRAS • PPP2R1A • TP53

Aprea Therapeutics Presents Preliminary Findings on Oral WEE1 Inhibitor APR-1051 at EORTC-NCI-AACR International Conference on Molecular Targets and Therapeutics (GlobeNewswire) - P1| N=79 | ACESOT-1051 (NCT06260514) | Sponsor: Aprea Therapeutics | "Preliminary results demonstrate that APR-1051 is safe and well-tolerated with no hematologic toxicity. Hemoglobin, hematocrit, and platelet counts were stable or increased slightly during the first treatment cycle. There were no signs of neutropenia, with white blood cells and neutrophils trending up for both patients during the first treatment cycle. All adverse events (AEs) recorded were Grade 1 and 2, with one Grade 1 AE (abdominal distention) possibly related to APR-1051. No QT prolongation has been observed....We are excited to explore the full therapeutic benefits of APR-1051, which has best in class potential, and hope to generate preliminary efficacy data from the study during 2025."

P1 data • Oncology • Solid Tumor

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) - "ACESOT-1051: A Biomarkers Focused, Phase 1 Trial of Oral WEE1 inhibitor, APR-1051, initiated:...A second patient has been enrolled at The University of Texas MD Anderson Cancer Center and has commenced treatment in the second dose cohort. The primary objectives of the Phase 1 study are to measure safety, dose-limiting toxicities (DLTs), maximum tolerated dose or maximum administered dose (MTD/MAD), and recommended Phase 2 dose (RP2D); secondary objectives are to evaluate pharmacokinetics, preliminary efficacy according to RECIST or PCWG3 criteria; pharmacodynamics is an exploratory objective. The Company will provide an update on the progress of this clinical study by year end. Open-label safety/efficacy data are expected in the first half of 2025."

P1 data • Trial status • Solid Tumor

Aprea Therapeutics to Host Virtual KOL Event on APR-1051, a Highly Selective and Potentially Best-in-Class Oral WEE1 Inhibitor, on Monday, June 24, 2024 (GlobeNewswire) - "Aprea Therapeutics, Inc...announced that it will host a virtual KOL event to discuss APR-1051, a highly selective and potentially best-in-class oral WEE1 inhibitor, on Monday, June 24, 2024 at 9:00 AM ET....The webinar will feature...the medicinal chemistry history, highly selective drug design, and preclinical findings of APR-1051. It will also feature Eric J. Brown, PhD (University of Pennsylvania) who will discuss preclinical findings across the WEE1 inhibitor class."

Preclinical • Oncology

Aprea Therapeutics Announces First Patient Dosed in ACESOT-1051 Phase 1 Trial Evaluating Oral WEE1 Inhibitor APR-1051 (GlobeNewswire) - "Aprea Therapeutics, Inc...today announced that the first patient has been dosed in the ACESOT-1051 Phase 1 study evaluating daily oral WEE1 inhibitor APR-1051 as monotherapy in advanced solid tumor patients with unmet medical need....The first patient was enrolled at NEXT Oncology, San Antonio, Texas. Additional centers, including The University of Texas MD Anderson Cancer Center, are expected to participate."

Trial status • Oncology • Solid Tumor

APR-1051-001: Study of APR-1051 in Patients With Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=79 | Recruiting | Sponsor: Aprea Therapeutics | Not yet recruiting ➔ Recruiting

Enrollment open • Oncology • Solid Tumor

Aprea Therapeutics Reports First quarter 2024 Financial Results and Provides a Business Update (GlobeNewswire) - "ACESOT-1051: Oral WEE1 inhibitor, APR-1051, expected to enter Phase 1 clinical trial in June, 2024...This dose escalation trial will evaluate the safety, tolerability, and preliminary efficacy of APR-1051. Enrollment of the first patient is expected in 2Q 2024 with an update expected in 4Q 2024...A lead molecule is expected to be declared in 3Q 2024. This program may provide clinically meaningful differences for cancer patients that currently have limited therapies....Research and Development (R&D) expenses were $1.6 million for the quarter ended March 31, 2024, compared to $1.3 million for the comparable period in 2023. The increase in R&D expense was primarily related to IND enabling studies for APR-1051, the Company’s small molecule WEE1 inhibitor, in preparation for enrollment of first patient into Phase 1 dose-escalation in the second quarter of 2024."

Commercial • Enrollment status • New molecule • Trial status • Oncology • Solid Tumor

The novel WEE1i, APR-1051, is a potentially well tolerated and effective treatment for cyclin E-overexpressing cancers (AACR 2024) - "One challenge for two of the leading WEE1i, AZD1775 and ZN-c3, has been the observed off-targeting of PLK family members, namely, PLK1, PLK2 and PLK3. APR-1051 is now progressing through IND-enabling studies. Together, these findings underscore the potential of APR-1051 as a novel WEE1i for the treatment of Cyclin E-overexpressing cancers."

Oncology • Ovarian Cancer • Solid Tumor • CCNE1 • PLK2

First-in-human phase 1 study of WEE1 inhibitor APR-1051 in patients with advanced solid tumors harboring cancer-associated gene alterations (AACR 2024) - "Key exclusion criteria are cancer therapy within 3 weeks or at least 5 half-lives, prior radiation therapy at the target lesion except if evidence of disease progression, unresolved therapy-related AEs, investigational agent within 5 half-lives or 30 days of study drug, prior WEE1 inhibitor, CNS metastases or unstable involvement, secondary malignancies that are active and/or require therapy, and concomitant moderate/strong inhibitors/inducers of CYP3A4/5, MDR1, or BCRP. Up to 79 patients will be enrolled at 3 to 5 sites in the United States."

Clinical • Metastases • P1 data • Oncology • Solid Tumor • ABCB1 • CCNE1 • CCNE2 • CDK1 • CYP3A4 • FBXW7 • PPP2R1A

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) - "Abstract Number: CT196:...This poster summarizes the strategy for the upcoming clinical trial of APR-1051. The aim of this first-in-human Phase 1 study (ACESOT-1051: A Multi-Center Evaluation of WEE1 Inhibitor in Patients with Advanced Solid Tumors, APR-1051) is to assess the safety, pharmacokinetics, pharmacodynamics, and preliminary efficacy of single-agent APR-1051 in advanced solid tumors harboring cancer-associated gene alterations (NCT06260514)....The primary objectives are to measure safety, dose-limiting toxicities (DLTs), maximum tolerated dose or maximum administered dose (MTD/MAD), RP2D; Secondary objectives are to evaluate pharmacokinetics, preliminary efficacy according to RECIST or PCWG3 criteria; Pharmacodynamics is an exploratory objective. Enrollment is anticipated to begin in Q2 2024."

Trial status • 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) - "Aprea Therapeutics...released details about four poster presentations at the ongoing American Association of Cancer Research (AACR) Annual Meeting....Abstract Number: 7121: This poster summarizes the pre-clinical data of APR-1051....APR-1051 demonstrated effectiveness in suppressing the growth of Cyclin E-overexpressing breast and ovarian cancer cell lines. The dose and scheduling of APR-1051 that causes significant suppression of CCNE1-amplified high-grade serous ovarian cancer tumors in mice is well tolerated....APR-1051 received U.S. FDA clearance for a clinical trial, now with plans to dose the first patient in June 2024."

Preclinical • Trial status • Breast Cancer • Ovarian Cancer

Aprea Therapeutics Reports Fourth Quarter and Full Year 2023 Financial Results and Provides a Business Update (GlobeNewswire) - "ATR inhibitor, ATRN-119, on track to complete monotherapy dose escalation end of the year; initial efficacy data expected in second half of 2024; Oral WEE1 inhibitor, APR-1051, expected to enter Phase 1 clinical trial in the first half of 2024."

New P1 trial • P1/2 data • Trial status • Oncology • Solid Tumor

Aprea Therapeutics Announces Acceptance of Abstracts at American Association of Cancer Research Annual Meeting 2024 (GlobeNewswire) - "Aprea Therapeutics, Inc...today announced four poster presentations at the American Association of Cancer Research (AACR) Annual Meeting, to take place April 5 to 10, 2024 in San Diego, CA. The posters will cover ATRN-119, Aprea’s novel macrocyclic ATR inhibitor, and APR-1051, its next generation inhibitor of WEE1 kinase."

P1 data • P1/2 data • Preclinical • Glioblastoma • Oncology • Solid Tumor

Aprea Therapeutics Announces FDA Clearance of IND for APR-1051, its Next Generation WEE1 Kinase Inhibitor for Cyclin E Overexpressing Cancers (GlobeNewswire) - "Aprea Therapeutics, Inc...announced that the U.S. Food and Drug Administration (FDA) has cleared its Investigational New Drug (IND) application (IND 169359) for APR-1051....Clearance of the IND application will allow Aprea to initiate the Phase 1 ACESOT-1051 dose escalation trial to evaluate the safety, tolerability, and preliminary efficacy of APR-1051. Enrollment of the first patient in this study is expected in the first half of 2024 with an update expected in the fourth quarter of the year."

IND • P1 data • Breast Cancer • Gynecologic Cancers • Oncology • Ovarian Cancer • Solid Tumor

Aprea Therapeutics Announces Private Placement Financing of up to $34.0 Million (GlobeNewswire) - "Aprea Therapeutics, Inc...announced that it has entered into a securities purchase agreement with new and existing healthcare focused institutional investors and certain Company insiders to raise up to $34.0 million in gross proceeds, including initial upfront funding of $16.0 million and up to an additional $18.0 million upon cash exercise of accompanying warrants at the election of the investors....'It will provide the capital to fund our Phase 1 ACESOT-1051 clinical trial evaluating a highly potent, oral WEE1 inhibitor for Cyclin E over-expressing cancers including breast and ovarian cancers as well as continuation of patient enrollment in the dose expansion portion of the Phase 1/2a clinical trial (AR-276-01) evaluating ATR inhibitor, ATRN-119, in patients with advanced solid tumors having mutations in defined DDR-related genes'."

Financing • Breast Cancer • Gynecologic Cancers • Oncology • Ovarian Cancer • Solid Tumor

Study of APR-1051 in Patients With Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=79 | Not yet recruiting | Sponsor: Aprea Therapeutics

New P1 trial • Oncology • Solid Tumor