Aprea Therapeutics Announces First Patient Dosed in ACESOT-1051 Phase 1 Trial Evaluating Oral WEE1 Inhibitor APR-1051
Aprea Therapeutics has announced the dosing of the first patient in the ACESOT-1051 Phase 1 trial for their oral WEE1 inhibitor, APR-1051. This study is evaluating APR-1051 as a monotherapy for patients with advanced solid tumors who have unmet medical needs. APR-1051, developed by Aprea, targets the WEE1 kinase, an enzyme involved in the DNA damage response pathway. The trial will assess safety, pharmacokinetics, pharmacodynamics, and preliminary efficacy over 28-day cycles. The first part involves dose escalation, while the second part focuses on dose optimization. The trial aims to confirm APR-1051's safety and determine the recommended Phase 2 dose. Updates are expected by year-end 2024 with preliminary efficacy data in 2025.
- First patient dosed in ACESOT-1051 Phase 1 trial for APR-1051.
- APR-1051 targets WEE1 kinase, showing potential for high selectivity and favorable drug exposure.
- Trial to assess key factors like safety, pharmacokinetics, and preliminary efficacy.
- Study aims to confirm APR-1051's safety profile and define its optimal use.
- Initial clinical update expected by year-end 2024.
- Preliminary efficacy data anticipated in 2025.
- Study aligns with addressing unmet medical needs in advanced solid tumor patients.
- Phase 1 trial focused on dose escalation indicates early-stage testing with inherent uncertainties.
- No head-to-head studies conducted with APR-1051 may limit comparative efficacy understanding.
- Potential delay in efficacy data, with initial updates by end of 2024 and preliminary data in 2025.
Insights
The initiation of the ACESOT-1051 Phase 1 trial for the oral WEE1 inhibitor APR-1051 marks a significant step for Aprea Therapeutics. WEE1 kinase has emerged as a promising target in oncology because it plays a critical role in the DNA damage response pathway, essential for cancer cell survival. Patients with tumors harboring specific genetic alterations, like amplification of CCNE1/CCNE2 or KRAS-GLY12 and TP53 co-mutations, often face poor prognoses and lack effective treatment options. By focusing on such high-need populations, Aprea aims to fill a critical gap in cancer therapy.
APR-1051’s unique molecular structure and selectivity for WEE1 over PLK family kinases may translate into a better safety profile and improved pharmacokinetics, reducing the risks of off-target effects and QT prolongation—a common challenge with other WEE1 inhibitors. If successful, this drug could offer a new line of treatment, either as a monotherapy or in combination with other therapies. However, it is important to note that this is still early-stage research and efficacy and safety data are not yet available.
For investors, the beginning of a Phase 1 trial often indicates both potential and risk. Aprea Therapeutics’ advancement with APR-1051 could attract investor interest due to the high unmet need in the target patient population and the specificity of the drug's design. This first dosing milestone shows progress in their clinical pipeline, enhancing the company’s asset portfolio, which is important for long-term growth and valuation.
However, Phase 1 trials are primarily about assessing safety and tolerability and it will take time before efficacy data emerges. Investors should closely monitor upcoming clinical updates by year-end 2024 and preliminary efficacy data expected in 2025. The differentiation of APR-1051 based on its selectivity and pharmacokinetic properties could provide competitive advantages over other WEE1 inhibitors if clinical trials validate these claims.
While promising, the inherent risks of early-stage clinical trials—such as potential adverse effects or failure to demonstrate efficacy—should be considered. Additionally, financial stability and the ability to sustain lengthy and expensive clinical trials are factors that require investor scrutiny.
The enrollment of the first patient in the ACESOT-1051 trial demonstrates Aprea Therapeutics' commitment to advancing precision oncology, specifically targeting solid tumors with significant genetic alterations. The focus on biomarkers like CCNE1/CCNE2 overexpression and KRAS-GLY12 co-mutations highlights the company's strategy to develop tailored therapies that could potentially improve patient outcomes in otherwise difficult-to-treat cancers.
The broader market for oncology therapies is highly competitive but also highly rewarding. A drug that addresses an unmet medical need with a favorable safety and efficacy profile can capture substantial market share. If APR-1051 proves successful, it could position Aprea as a leader in the WEE1 inhibitor space, offering a unique treatment option that may be combined with existing therapies to enhance patient care. The collaboration with prestigious institutions like MD Anderson Cancer Center and NEXT Oncology adds credibility and could accelerate patient recruitment and data collection.
Investors should be aware that while the initial development phase is promising, the competitive landscape in oncology means that continuous innovation and positive clinical outcomes are essential for long-term success. The market potential is substantial, but so are the challenges in achieving market entry and patient adoption.
APR-1051 is a highly selective and potentially best-in-class oral WEE1 inhibitor
Phase 1 ACESOT-1051 clinical trial is evaluating APR-1051 as monotherapy treatment in patients with significant unmet medical need
Dosing of the first patient in the ACESOT-1051 study represents a key advancement in Aprea’s clinical pipeline
DOYLESTOWN, Pa., June 17, 2024 (GLOBE NEWSWIRE) -- Aprea Therapeutics, Inc. (Nasdaq: APRE) (“Aprea”, or the “Company”), a clinical-stage biopharmaceutical company focused on precision oncology through synthetic lethality, 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.
APR-1051 was discovered and preclinically evaluated by Aprea’s team of chemists and scientists. APR-1051 is a potent and highly selective small molecule designed to limit off-target toxicity that may provide good safety and tolerability and has shown a potentially favorable drug exposure in pre-clinical models.
APR-1051 targets WEE1 kinase, an enzyme involved in the DNA damage response pathway. Based on preclinical studies, we believe APR-1051 may solve liabilities associated with other WEE1 inhibitors and is differentiated based on: 1) molecular structure; 2) selectivity for WEE1 versus off-target inhibition of the polo-like kinase, or PLK, family of kinases; 3) potentially improved pharmacokinetic (PK) properties; and 4) potential absence of QT prolongation at doses that significantly inhibit WEE1. No head-to-head studies with APR-1051 have been conducted.
ACESOT-1051 is a focused biomarker-driven study with advanced/metastatic solid tumors harboring the following cancer-associated gene alterations:
- Amplification/overexpression of CCNE1 or CCNE2 regardless of tumor type, or
- Deleterious mutations in FBXW7 or PPP2R1A regardless of tumor type, or
- Colorectal cancer with KRAS-GLY12 and TP53 co-mutation, or
- Uterine serous carcinoma regardless of biomarker status
“Dosing of the first patient in the ACESOT-1051 study is an important milestone in our APR-1051 development program and represents a key advancement of our clinical pipeline,” said Oren Gilad, Ph.D., President and Chief Executive Officer of Aprea. “Adding a second clinical program enriches our asset portfolio. We are initially evaluating single agent activity of APR-1051 to provide the basis for future rational combination treatments. We hope to confirm APR-1051’s safety profile in this Phase 1 study and generate the necessary data that will help us understand how it can be best utilized to treat patients. We plan to provide a clinical update by year-end 2024 and generate preliminary efficacy data during 2025.”
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.
Anthony Tolcher M.D., Founder of Next Oncology commented, “NEXT Oncology is committed to exploring new treatment options for cancer patients and we are pleased to begin this important clinical trial. Cancers that over express Cyclin E (CCNE1 and CCNE2) represent a high unmet medical need, and patients with Cyclin E over expression have poor prognosis and no effective therapies. WEE1 kinase is a validated oncology target and we look forward to the results of this study.”
ACESOT-1051 Study Design
ACESOT-1051 (A Multi-Center Evaluation of WEE1 Inhibitor in Patients with Advanced Solid Tumors, APR-1051) is designed to assess the safety, pharmacokinetics, pharmacodynamics, and preliminary efficacy of single-agent APR-1051 in advanced solid tumors harboring cancer-associated gene alterations. Oral APR-1051 will be administered once daily for 28-day cycles. The study consists of two parts: Part 1 is dose escalation and is expected to enroll up to 39 patients with advanced solid tumors. The first three dose levels will use accelerated titration followed by Bayesian Optimal Interval (BOIN) design for the remaining dose levels; Part 2 (up to 40 patients) is designed for dose optimization, with the goal of selecting the Recommended Phase 2 Dose (RP2D).
The primary objectives of the study are to measure safety, dose-limiting toxicities (DLTs), maximum tolerated dose or maximum administered dose (MTD/MAD), and RP2D; secondary objectives are to evaluate pharmacokinetics, preliminary efficacy according to RECIST or PCWG3 criteria; pharmacodynamics is an exploratory objective. The University of Texas MD Anderson Cancer Center is the lead site, and the study will be performed at between 3 and 10 sites in the U.S.
The ACESOT-1051 design was featured in a poster at the American Association of Cancer Research (AACR) annual meeting which took place in April 2024 in San Diego. A copy of the poster can be found here. For more information, refer to ClinicalTrials.gov NCT06260514.
About Aprea
Aprea Therapeutics, Inc. is a clinical-stage biopharmaceutical company headquartered in Doylestown, Pennsylvania, focused on precision oncology through synthetic lethality. The Company’s lead program is ATRN-119, a clinical-stage small molecule ATR inhibitor in development for solid tumor indications. APR-1051, an oral, small molecule WEE1 inhibitor, recently entered the clinic. For more information, please visit the company website at www.aprea.com.
The Company may use, and intends to use, its investor relations website at https://ir.aprea.com/ as a means of disclosing material nonpublic information and for complying with its disclosure obligations under Regulation FD.
Forward-Looking Statement
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Investor Contact:
Mike Moyer
LifeSci Advisors
mmoyer@lifesciadvisors.com
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